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Moore KN, Liu JF, Lorusso D. State of the Art: Therapies Now and Around the Corner for Gynecologic Cancers. Am Soc Clin Oncol Educ Book 2025; 45:e473114. [PMID: 40489723 DOI: 10.1200/edbk-25-473114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2025]
Abstract
Therapeutic advances across the gynecologic cancer continuum have resulted in improvements in patient care and outcomes over the past decade, yet challenges remain. In ovarian cancer, the evolution of poly (ADP-ribose) polymerase (PARP) inhibitor therapy has resulted in marked benefit for patients with BRCA-mutated cancers but has also unmasked the need for new therapies in patients whose cancers are proficient in homologous recombination and lack vulnerability to PARP inhibitors, as well as for those patients whose cancers progress on PARP inhibitors. In endometrial cancer, immune checkpoint inhibitors (ICIs) have improved outcomes for patients receiving first-line therapy for advanced or recurrent disease when combined with standard-of-care chemotherapy. However, there remains uncertainty around which patients are most likely to benefit from the addition of immunotherapy, and treatment beyond first-line therapy remains an area of high unmet need. Similarly, ICIs added to chemotherapy for recurrent or metastatic cervical cancer or to chemoradiation for high-risk locally advanced cervical cancers has resulted in improved outcomes, but treatment options beyond this remain limited. Across gynecologic cancers, antibody-drug conjugates (ADCs) hold the promise for further improvement in patient outcomes. A prime example is the demonstrated benefit of mirvetuximab soravtansine over other standard chemotherapy options in folate receptor alpha-high platinum-resistant ovarian cancer. Maximizing such potential will require developing a deeper understanding of relationships between ADC target expression and activity, mechanisms of resistance, and potential approaches to sequencing. Beyond ADCs, additional therapies, including those targeting DNA damage response, remain in development.
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Affiliation(s)
- Kathleen N Moore
- Stephenson Cancer Center at OU Health, University of Oklahoma, Oklahoma City, OK
| | | | - Domenica Lorusso
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Humanitas San Pio X, Milan, Italy
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Najjari-Jamal D, Juarez M, Cordoba S, Celada F, Stefanovic M, Gutierrez C. The Crucial Role of Advanced Image-Guided Brachytherapy for Locally Advanced Cervical Cancer in the Era of Systemic Treatment Intensification. Cancers (Basel) 2025; 17:1809. [PMID: 40507290 PMCID: PMC12153526 DOI: 10.3390/cancers17111809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2025] [Revised: 05/26/2025] [Accepted: 05/27/2025] [Indexed: 06/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Recent advancements in the treatment of LACC have focused on improving outcomes through systemic treatment intensification. Therefore, this review aims to analyze the brachytherapy (BT) techniques employed in recent studies that are likely to change upcoming clinical guidelines, and to discuss the evolving role of IGABT in optimizing patient outcomes. METHODS This review focuses on BT practices reported across main phase III trials-OUTBACK, INTERLACE, CALLA, and KEYNOTE A18-compared with the EMBRACE I study. Analyzed parameters include BT modality, dose prescription techniques, imaging guidance, and overall treatment time (OTT). RESULTS In EMBRACE I, MRI-based IGABT was mandatory, with 43% of patients receiving an intracavitary/interstitial (IC/IS) applicator; cumulative EQD2 D90 HR-CTV was 90 Gy with a median OTT of 46 days. The OUTBACK trial relied predominantly on point A-based BT, with limited use of volume-based BT (28%). The INTERLACE trial reported mixed BT approaches: 70% point A-based, 30% volume-based, and 20% 2D BT. A median cervical dose of 79.4 Gy was reported. CALLA maintained strong protocol adherence, with 60% volume-based BT and a median tumor EQD2 dose of 83 Gy, although lower in the Japan cohort. In the KEYNOTE A 18 cohort, volume-based BT was performed in 88% of patients, with a median D90 HR-CTV dose of 87 Gy; IC/IS applicators were used in 23% of cases. CONCLUSIONS Across these major studies, the following consistent pattern emerges: the quality and technique of BT impact survival outcomes and toxicity profile in LACC. MRI-based IGABT-with the use of IC/IS applicators when needed-is essential.
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Affiliation(s)
- Dina Najjari-Jamal
- Department of Radiation Oncology, Catalan Institute of Oncology, University of Barcelona, Hospitalet de Llobregat, 08908 Barcelona, Spain; (M.J.); (M.S.); or (C.G.)
| | - Marc Juarez
- Department of Radiation Oncology, Catalan Institute of Oncology, University of Barcelona, Hospitalet de Llobregat, 08908 Barcelona, Spain; (M.J.); (M.S.); or (C.G.)
| | - Sofia Cordoba
- Department of Radiation Oncology, Puerta de Hierro University Hospital, 28222 Majadahonda, Spain;
| | - Francisco Celada
- Department of Radiation Oncology, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain;
| | - Milica Stefanovic
- Department of Radiation Oncology, Catalan Institute of Oncology, University of Barcelona, Hospitalet de Llobregat, 08908 Barcelona, Spain; (M.J.); (M.S.); or (C.G.)
| | - Cristina Gutierrez
- Department of Radiation Oncology, Catalan Institute of Oncology, University of Barcelona, Hospitalet de Llobregat, 08908 Barcelona, Spain; (M.J.); (M.S.); or (C.G.)
- Department of Radiation Oncology, Hospital del Mar, 08003 Barcelona, Spain
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Jääskeläinen E, Kärkkäinen H, Palmgren JE, Haataja M, Hinkula M, Anttila M. Implementing treatment according to the guidelines is of paramount importance in locally advanced cervical cancer: a real-world study. Front Oncol 2025; 15:1562067. [PMID: 40406263 PMCID: PMC12094941 DOI: 10.3389/fonc.2025.1562067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 04/10/2025] [Indexed: 05/26/2025] Open
Abstract
Background External beam radiotherapy with concomitant chemotherapy and image-guided brachytherapy is the standard treatment for locally advanced cervical cancer. This retrospective study compared real-world outcomes with those reported in the literature and evaluated the impact of treatment implementation on the outcomes. Methods Medical records of consecutive patients receiving radiotherapy for cervical cancer at Kuopio University Hospital from 2009-2018 were examined. We identified 112 patients with a median age of 53 (27-88) years. The International Federation of Gynecology and Obstetrics 2009 classification stages were IB-IVB, 86% had at least stage IIB disease, and 60% had lymph node metastases. External beam radiotherapy was conducted using intensity-modulated radiotherapy or volumetric modulated arc therapy. Concomitant chemotherapy was administered in 90% of cases. All patients received brachytherapy in magnetic resonance imaging guidance. Seventeen patients received neoadjuvant chemotherapy, deviating from the guidelines, while thirteen patients received adjuvant chemotherapy. The patients were divided into two groups according to how precisely the guidelines were followed, considering the delivery of concomitant chemotherapy, the treatment of lymph node metastases, the radiation dose to the primary tumor, and the overall treatment time. The median follow-up time was 58 months (IQR 35-87), and the primary endpoint was 5-year overall survival. Results The mean delivered biological dose to the high-risk clinical target volume was 93.7 Gy. The median overall treatment time was 49 days. Overall survival, disease-free survival, and local control at five years were 60.1%, 57.0%, and 85.7%, respectively. Receiving less than three cycles of concomitant chemotherapy was a negative prognostic factor for overall and disease-free survival. The guidelines were adequately followed in 76.8% (Group 1) and substantially deviated from in 23.2% of cases (Group 2). Differences were observed between the groups in 5-year overall survival (67% vs 39%, p=0.016), disease-free survival (62% vs 42%, p=0.040), and lymph node control (84% vs 61%, p=0.007). Neither neoadjuvant chemotherapy nor adjuvant chemotherapy improved the outcome. Conclusions The outcomes in this real-world setting were inferior to those reported in the literature. Implementing chemoradiotherapy and brachytherapy according to the guidelines is essential; deviations from the guidelines could worsen the outcome.
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Affiliation(s)
- Ester Jääskeläinen
- Department of Gynecology and Obstetrics, Kuopio University Hospital, Kuopio, Finland
- Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Henna Kärkkäinen
- Department of Gynecology and Obstetrics, Kuopio University Hospital, Kuopio, Finland
| | - Jan-Erik Palmgren
- Department of Radiotherapy, Kuopio University Hospital, Kuopio, Finland
- Department of Brachytherapy, Maastro Clinic, Maastricht, Netherlands
| | - Marjut Haataja
- Department of Gynecology and Obstetrics, Turku University Hospital, Turku, Finland
- Faculty of Medicine, University of Turku, Turku, Finland
| | - Marianne Hinkula
- Department of Gynecology and Obstetrics, Medical Research Center Oulu, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Maarit Anttila
- Department of Gynecology and Obstetrics, Kuopio University Hospital, Kuopio, Finland
- Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
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Eminowicz G, Vaja S, Gallardo D, Kent C, Panades M, Mathew T, Anand A, Forrest J, Adusumalli M, Chan A, Hacker AM, Hackshaw A, Ledermann JA, McCormack M. Induction chemotherapy followed by chemoradiation in locally advanced cervical cancer: Quality of life outcomes of the GCIG INTERLACE trial. Eur J Cancer 2025; 220:115375. [PMID: 40139003 DOI: 10.1016/j.ejca.2025.115375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/03/2025] [Accepted: 03/16/2025] [Indexed: 03/29/2025]
Abstract
AIM Induction chemotherapy (IC) added to chemoradiation (CRT) in locally advanced cervical cancer (LACC) improves survival at the expense of adverse events (AEs), 99 % with IC/CRT vs 95 % CRT alone, 59 % vs 48 % G3/4 AEs. We investigated the impact of this on quality of life (QoL). METHODS 500 women with FIGO 2008 stage IB1 node positive, IB2, II, IIIB and IVA cervical carcinoma were randomised to CRT alone or IC (6 weeks carboplatin AUC2 paclitaxel 80mg/m2) followed by CRT. QoL questionnaires (EORTC QLQ-C30 v3, QLQ-CX24) were completed at baseline, D1 week 4 IC, D1 CRT, D1 week 3 CRT, 4 weeks post CRT and all follow up visits. Mixed modelling for repeated measures was used to compare the groups during trial treatment to 2 years follow up (adjusting for baseline). RESULTS QoL (global health status, physical and social functioning) slightly worsened during IC and symptom experience slightly improved. Emotional functioning improved during IC. Peripheral neuropathy was slightly worse with IC/CRT. Fatigue and nausea/vomiting worsened from baseline to week 4 IC whilst pain and diarrhoea improved, consistent with reported AEs. Over the whole period, mean differences for these symptoms between the treatment groups was small and not clinically significant and resolved by 12-18 months. In all cases, mean score differences during trial treatment until 2 years post CRT showed only small differences (<5 units) not meeting the threshold for clinical relevance. CONCLUSION IC added to CRT does not adversely impact QoL compared to CRT, either during IC, during CRT or later.
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Affiliation(s)
- G Eminowicz
- University College Hospital NHS Trust, London, UK.
| | - S Vaja
- Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
| | - D Gallardo
- Instituto Nacional de Cancerlogia, Mexico City, Mexico
| | - C Kent
- University of Leicester NHS Trust, UK
| | - M Panades
- United Lincolnshire Hospitals NHS Trust, UK
| | - T Mathew
- Sheffield Teaching Hospitals NHS Trust, UK
| | - A Anand
- Nottingham University NHS Trust, UK
| | - J Forrest
- Royal Devon University Hospitals NHS Foundation Trust, UK
| | | | - A Chan
- Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
| | - A M Hacker
- Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
| | - A Hackshaw
- Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
| | - J A Ledermann
- Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
| | - M McCormack
- University College Hospital NHS Trust, London, UK
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Butler S, Niedermayr T, Kidd EA. 3D-printed needle guides for cervical cancer brachytherapy: Optimized dosimetry and improved local control outcomes. Brachytherapy 2025; 24:379-388. [PMID: 39955171 DOI: 10.1016/j.brachy.2025.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 12/21/2024] [Accepted: 01/08/2025] [Indexed: 02/17/2025]
Abstract
PURPOSE We previously designed three-dimensionally-printed needle guides (3D-NG) for cervical cancer brachytherapy, which improved procedure efficiency and tumor coverage while achieving similar organs at risk (OAR) sparing compared to non-3D-printed techniques (non-3D). The subject of this study was whether 3D-NG can help improve local control and other brachytherapy outcomes. METHODS This single institution cohort study includes 130 patients who underwent definitive external-beam radiotherapy and high-dose-rate intracavitary +/- interstitial brachytherapy from February 2017 to July 2023. 3D-NG were implemented for all cases after December 2019 (N = 77). Non-3D included applicator-only/no-needles (N = 28) or freehand-placed needles (N = 25). RESULTS Median follow-up was 24 months. 3D-NG, versus non-3D, achieved higher mean D90 (+5.2 Gy, p < 0.001), D98 (+4.3 Gy, p < 0.001), and V100average (+5.9%, p < 0.001)-with greater improvement for larger tumors (high-risk[HR]-CTV>30 cubic-centimeters[cc]) (Pinteraction<0.10 for all). Maximum D2cc for all OAR were comparable between 3D-NG and non-3D (p > 0.05). 2-year LF was lower with 3D-NG compared to non-3D (8.2% vs. 22.0%; aHR 0.31, p = 0.036)-and compared to freehand-needles alone (8.2% vs. 20.6%, p < 0.001 [log-rank])-particularly among cases with higher cumulative HR-CTV dose (D90 >85 Gy; pinteraction = 0.013) and lower HR-CTV volume (≤30 cc; pinteraction = 0.048). 2-year LF was also lower with concurrent cisplatin (aHR 0.20, p = 0.001) and ≥40% decrease in tumor diameter after EBRT (aHR 0.16, p = 0.010); but higher among minority race (aHR 4.21, p = 0.06). CONCLUSIONS 3D-NG for cervix brachytherapy were associated with improved 2-year LF compared to non-3D/freehand-needles, with higher achievement of EMBRACE II goals for D90 and D98, with similar OAR doses. This study highlights the potential for 3D-NG to simplify needle insertion while simultaneously improving needle position, dosimetry, and disease control outcomes.
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Affiliation(s)
- Santino Butler
- Stanford University School of Medicine, Department of Radiation Oncology, Palo Alto, CA
| | - Thomas Niedermayr
- Stanford University School of Medicine, Department of Radiation Oncology, Palo Alto, CA
| | - Elizabeth A Kidd
- Stanford University School of Medicine, Department of Radiation Oncology, Palo Alto, CA.
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Végváry Z, Kószó R, Együd Z, Varga L, Paczona VR, Cserháti A, Gal V, Varga Z, Nagy Z, Deák B, Borzák F, Bontovics J, Fodor E, Oláh J, Kahán Z. MRI-based image-guided adaptive brachytherapy for locally advanced cervical cancer in clinical routine: a single-institution experience. Pathol Oncol Res 2025; 31:1612077. [PMID: 40376012 PMCID: PMC12078146 DOI: 10.3389/pore.2025.1612077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 04/02/2025] [Indexed: 05/18/2025]
Abstract
Background MRI-based image-guided adaptive brachytherapy (IGABT) is a new approach for individual dose escalation and control of organ at risk (OAR) doses and toxicities in the treatment of locally advanced cervical cancer. Methods Various radiotherapy-related parameters and the feasibility of the treatment based on acute toxicity were analyzed in a total of 50 cases in two cohorts who received a brachytherapy (BT) boost after definitive chemoradiotherapy with either an MRI-based IGABT technique (24 patients) or CT-only image guidance (26 patients). For target volume, OAR delineation, and dose prescription, the EMBRACE II protocol was followed. Results The features of the target volumes and dose coverage did not differ between the two groups regarding teletherapy. At BT, however, while the High-Risk Clinical Target Volumes (CTVHR) did not differ the D90 dose coverage was significantly higher in the MRI-based IGABT group than in the non-MRI-based group (7.37 ± 0.55 Gy vs. 6.87 ± 0.84 Gy, p = 0.015). The CTVHR D98 doses showed a strong trend in favor of the MRI-based technique (6.16 ± 0.59 Gy, vs. 5.72 ± 0.95 Gy, p = 0.051). Cumulative doses to the CTVHR by means of both D90 and D98 were significantly higher in the MRI-based treatment group than the other group (86.64 ± 4.76 Gy vs. 81.56 ± 8.29 Gy, p = 0.011 and 77.23 ± 4.39 Gy vs. 73.40 ± 7.80 Gy, p = 0.037, respectively). Regarding OAR exposure, doses to the bladder, rectum, and sigmoid did not differ between the two cohorts. Conclusion Our first clinical results support the implementation of IGABT as a key component of image-guided adaptive radiotherapy (IGART) aiming at tumor dose-escalation and OAR protection.
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Affiliation(s)
| | | | | | | | | | | | | | - Zoltán Varga
- Department of Oncotherapy, University of Szeged, Szeged, Hungary
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Cai Z, Wu Q, Yang X, Qin Q, Zhang Y, Li Z, Li M. Application value of personalized 3D printing vaginal model for the Image-guided adaptive brachytherapy of cervical cancer. J Gynecol Oncol 2025; 36:e48. [PMID: 39727413 PMCID: PMC12099039 DOI: 10.3802/jgo.2025.36.e48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 07/06/2024] [Accepted: 10/30/2024] [Indexed: 12/28/2024] Open
Abstract
OBJECTIVE To explore the application value of using 3-dimensional (3D) printing (3DP) technology to create individualized vaginal molds for brachytherapy (BT) in high-dose-rate 3D cervical cancer through reverse engineering of needle placement. METHODS Prospectively, 11 patients with cervical cancer were treated with 3DP-intracavitary/interstitial (IC/IS) BT using 3DP to create individualized vaginal molds. All patients were performed BT after completion of external beam radiotherapy (EBRT). Each patient was treated with BT 5 times, the prescription dose was 600 cGy/F, which was performed once or twice a week, 2 of them were freehand IC/IS BT, and 3 were 3DP-IC/IS BT. The relevant planning parameters (bladder, rectum, sigmoid colon, and small intestine) and target conformity index (CI) for high-risk clinical target volume (HR-CTV) and organs at risk (OARs) were compared between the groups. RESULTS There were significant advantages in the 3DP-IC/IS BT group compared with the freehand IC/IS BT group: HR-CTV D90 (629.40±19.34 vs. 613.03±15.93 cGy, p=0.002), D95 (580.74±18.31 vs. 567.44±23.94 cGy, p=0.032), bladder D2cc (431.11±23.27 vs. 458.07±23.27 cGy, p<0.001), bladder D1cc and bladder D0.1cc. There was no statistically significant difference (p>0.05) between the 2 groups in rectal D2cc (352.30±42.42 vs. 361.29±42.42 cGy, p=0.470), sigmoid colon D2cc (236.73±78.95 vs. 246.50±58.17 cGy, p=0.621), CI (0.79±0.04 vs. 0.79±0.039 p=0.773), HR-CTV V100, V200, D98, D100 and other OARs parameters (p>0.05). CONCLUSION Compared with IC/IS BT, 3DP-IC/IS BT has apparent advantages with simple operation and high safety. In addition, individualized mold helps to improve the tumor target area's radiation dose while meeting the dose-limiting requirements for organs at risk and reduces the clinical proficiency requirements for operating physicians.
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Affiliation(s)
- Zhantuo Cai
- The 3th Ward of Radiotherapy Department, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qiuyan Wu
- The 3th Ward of Radiotherapy Department, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xinglong Yang
- The 3th Ward of Radiotherapy Department, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qinghua Qin
- The 3th Ward of Radiotherapy Department, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yiqian Zhang
- The 3th Ward of Radiotherapy Department, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Zhouyu Li
- The 3th Ward of Radiotherapy Department, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Mingyi Li
- The 3th Ward of Radiotherapy Department, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China.
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Yadagiri U, Shaik R, Kolure R, Fatima T, Khan H. Immunotherapeutics in Clinical Trials for Cervical Cancer. Cancer Biother Radiopharm 2025. [PMID: 40265298 DOI: 10.1089/cbr.2025.0031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025] Open
Abstract
The fourth most common cause of cancer-related deaths in women is cervical cancer (CC) in the worldwide. Although there are differences in the accessibility of therapies across developed and developing nations, an improvement in survival rate has been observed in patients with precancerous lesions, thanks to the development of precancerous lesion identification and preventative human papillomavirus vaccination programs. Surgery can cure early-stage CC, but patients who experience a recurrence have a poor prognosis and few therapy alternatives. Recently, it has been demonstrated that the drug bevacizumab increases overall survival in this latter context when combined with chemotherapy as opposed to chemotherapy administered alone. Beyond this therapy regimen, there are no established treatments. Therefore, in this situation, new, effective treatments are desperately needed. Immunotherapy has been a revolutionary treatment.
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Affiliation(s)
- Umarani Yadagiri
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad, India
| | - Rahaman Shaik
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Rajini Kolure
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad, India
| | - Tatheer Fatima
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad, India
| | - Huda Khan
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad, India
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Jesus EF, Luchi WM, Castro PC, Martins FL, Caetano MV, Kung VL, Seguro AC, McCormick JA, Girardi ACC. SGLT2 Inhibitors Blunt Kidney Magnesium Wasting in Acute Cisplatin-Induced Hypomagnesemia with Effects on the Thick Ascending Limb and Distal Convoluted Tubule. J Am Soc Nephrol 2025:00001751-990000000-00609. [PMID: 40172993 DOI: 10.1681/asn.0000000700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 03/27/2025] [Indexed: 04/04/2025] Open
Abstract
Key Points
Sodium-glucose cotransporter 2 inhibitors restored magnesium serum levels in cisplatin-treated rats.Empagliflozin reversed cisplatin-induced Na+-K+-Cl− cotransporter 2 inhibition and claudin-16 downregulation in the thick ascending limb.Empagliflozin mitigated distal convoluted tubule area reduction, normalized NaCl cotransporter function, and restored transient receptor potential melastatin 6 expression.
Background
Cisplatin, a chemotherapeutic agent, induces kidney magnesium wasting and hypomagnesemia. Recent studies suggest that sodium-glucose cotransporter 2 inhibitors elevate serum magnesium concentration in patients with or without diabetes. We hypothesized that the sodium-glucose cotransporter 2 inhibitor empagliflozin attenuates acute cisplatin-induced hypomagnesemia by acting on the thick ascending limb (TAL) and distal convoluted tubule (DCT), key sites of magnesium reabsorption.
Methods
Adult male Wistar rats received weekly treatments of cisplatin (2.5 mg/kg) or saline (vehicle) for 5 weeks. After 3 weeks, rats were randomized to receive empagliflozin (10 mg/kg per day) or water (vehicle) for the next 15 days.
Results
Cisplatin-treated rats developed significant hypomagnesemia with increased fractional excretion of magnesium. Empagliflozin treatment reduced fractional excretion of magnesium and restored serum magnesium levels. In the TAL, cisplatin-treated rats had higher Na+-K+-Cl− cotransporter 2 (NKCC2) abundance but lower phosphorylated NKCC2 and claudin-16 levels than empagliflozin-treated cisplatin rats, whose protein levels were similar to controls. By contrast, claudin-19 abundance in the TAL was higher in cisplatin-treated rats than in controls and unaffected by empagliflozin treatment. In the DCT, cisplatin-treated rats displayed reduced abundance of the NaCl cotransporter (NCC), the magnesium channel transient receptor potential melastatin 6, and NCC phosphorylation, all of which were rescued by empagliflozin. Unexpectedly, cisplatin-treated rats exhibited higher mRNA expression and protein abundance of TRPM7 compared with empagliflozin-treated cisplatin rats, whose levels were similar to controls. Diuretic challenge tests with furosemide or hydrochlorothiazide confirmed reduced NKCC2 and NCC activity in cisplatin-treated rats. However, the natriuretic response to furosemide or hydrochlorothiazide did not differ between control and empagliflozin-treated cisplatin rats. Immunohistochemistry suggested that empagliflozin reversed cisplatin-induced DCT remodeling.
Conclusions
Empagliflozin reduces kidney magnesium wasting and restores serum magnesium in cisplatin-treated rats, likely through reversing NKCC2 inhibition and claudin-16 downregulation in the TAL while normalizing NCC function and restoring transient receptor potential melastatin 6 expression in the DCT.
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Affiliation(s)
- Erika F Jesus
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Weverton M Luchi
- Hospital Universitário Cassiano Antonio Moraes, Universidade Federal do Espírito Santo (HUCAM-UFES), Vitoria, Brazil
| | - Paulo C Castro
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Flavia L Martins
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Marcos V Caetano
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Vanderlene L Kung
- Department of Pathology and Laboratory of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Antonio C Seguro
- Laboratório de Investigação Médica 12 (LIM12), Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - James A McCormick
- Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Adriana C C Girardi
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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Parfenov AI, Indejkina LK, Sabelnikova EA, Leontiev AV, Makarova AA. [Radiation-induced intestinal injury]. TERAPEVT ARKH 2025; 97:101-108. [PMID: 40237744 DOI: 10.26442/00403660.2025.02.203116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 02/19/2025] [Indexed: 04/18/2025]
Abstract
This article addresses theoretical and clinical aspects of radiation-induced intestinal injuries, which complicate radiation therapy for malignant neoplasms of the abdominal and pelvic organs. Many clinical aspects of this issue remain unknown due to the lack of awareness among doctors and patients. Further study of radiation-induced intestinal injuries and the development of personalized approaches to their prevention and treatment represent a relevant direction in internal medicine.
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Affiliation(s)
| | - L K Indejkina
- Loginov Moscow Clinical Scientific Center
- Research Institute for Healthcare and Medical Management
| | - E A Sabelnikova
- Loginov Moscow Clinical Scientific Center
- Russian University of Medicine
| | - A V Leontiev
- Loginov Moscow Clinical Scientific Center
- Moscow University for Industry and Finance "Synergy"
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11
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Maina J, Lichter KE, Benishay ET, George J, Henry M, Fakie N, Grover S. Patterns of Care and Outcomes Among Women With Locally Advanced Cervical Cancer Treated With Curative Intent at a Tertiary Center in South Africa. Cancer Med 2025; 14:e70712. [PMID: 40083112 PMCID: PMC11906364 DOI: 10.1002/cam4.70712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 02/04/2025] [Accepted: 02/12/2025] [Indexed: 03/16/2025] Open
Abstract
OBJECTIVE Cervical cancer is the leading cause of cancer-related deaths for women in South Africa. The standard of care treatment for locally advanced cervical cancer (LACC) is external beam radiation followed by brachytherapy with concurrent platinum-based chemotherapy. There exists a paucity of data regarding the treatment regimens received by women with LACC in South Africa. The aim of this study is to assess the patterns of care and survival for patients with LACC treated with curative intent at a tertiary care center in South Africa. MATERIALS AND METHODS This is a retrospective review of cervical cancer patients with histologically confirmed LACC (stage IB2-IVA) who underwent radiation with curative intent at Groote Schuur Hospital in Cape Town, South Africa between July 2013 and July 2018. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method. Cox proportional hazards modeling analyzed patient and treatment factor associations with survival. Logistic regression modeling was performed to assess factors associated with the receipt of chemotherapy and baseline hemoglobin. RESULTS Among 278 patients, 28.4% (n = 79) of women had co-infection with HIV, and 64.8% (n = 180) received chemoradiation. Regardless of HIV status, patients who received chemoradiation had improved 2-year OS (87.4% vs. 52.8%, p < 0.001) and DFS (80.2% vs. 58.3%, p < 0.001) compared to those receiving radiation alone. Factors associated with improved OS were receipt of chemotherapy (HR 0.32, p = 0.005) and higher baseline hemoglobin (HR 0.86, p = 0.018). Upon multivariate logistic regression, adjusting for age, stage, and HIV status, patients with stage III/IV disease were less likely to receive chemotherapy (HR 48.17, p < 0.001) and were less likely to have hemoglobin ≥ 10 g/dL (HR 0.20, p < 0.001). CONCLUSIONS Addition of chemotherapy to standard radiation improved OS in women with LACC, regardless of HIV status. Our findings add to a body of literature highlighting the importance of providing concurrent chemoradiotherapy to all patients with LACC, including persons living with HIV and those with stage III/IV disease.
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Affiliation(s)
- Juliet Maina
- Department of Radiation OncologyUniversity of Cape Town, Groote Schuur HospitalCape TownSouth Africa
| | - Katie E. Lichter
- Department of Radiation OncologyUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Elana T. Benishay
- Feinberg School of MedicineNorthwestern UniversityChicagoIllinoisUSA
| | - Jessica George
- Donald Bren School of Information and Computer SciencesUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Michelle Henry
- Centre for Higher EducationUniversity of Cape TownCape TownSouth Africa
| | - Nazia Fakie
- Department of Radiation OncologyUniversity of Cape TownCape TownSouth Africa
| | - Surbhi Grover
- Botswana‐UPenn PartnershipUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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12
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Soni S, Pruthi DS. Exploring a conundrum: Evaluating the role of neoadjuvant chemotherapy preceding chemo-radiotherapy in locally advanced cervical cancer: A review article. Taiwan J Obstet Gynecol 2025; 64:219-229. [PMID: 40049805 DOI: 10.1016/j.tjog.2024.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2024] [Indexed: 05/13/2025] Open
Abstract
In India, majority of women's with cervical cancer have locally advanced disease. The chemo-radiotherapy (CRT) followed by brachytherapy is the standard treatment for patients with locally advanced cervical cancer (LACC) disease for almost decades. But in developing countries like India with higher incidence and limited radiotherapy facilities, this may result in a delay in treatment initiation. These factors may further contribute to detrimental outcomes. Several researchers have tried to study role of neo-adjuvant chemotherapy (NACT) in LACC with the aim that neo-adjuvant chemotherapy may arrest the disease progression, prevent distant metastasis and therefore improve overall and disease-free survival. However, there is only limited literature so far, comparing NACT followed by CRT with the standard treatment arm alone. Therefore the review article aims to evaluate role of neo-adjuvant chemotherapy (NACT) followed by chemo-radiotherapy in LACC.
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Affiliation(s)
- Sweta Soni
- Department of Radiation Oncology, All India Institute of Medical Sciences, Rajkot, Gujarat, India.
| | - Deep Shankar Pruthi
- Department of Radiation Oncology, Action Cancer Hospital, Paschim Vihar, New Delhi, India
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13
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Francoeur AA, Monk BJ, Tewari KS. Treatment advances across the cervical cancer spectrum. Nat Rev Clin Oncol 2025; 22:182-199. [PMID: 39753753 DOI: 10.1038/s41571-024-00977-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/02/2024] [Indexed: 02/26/2025]
Abstract
Cervical cancer is preventable with screening and vaccination approaches; however, access to these preventative measures is limited both nationally and globally and thus many women will still develop cervical cancer. Novel treatments and practice-changing research have improved cervical cancer outcomes over the past few decades. In this Review, we discuss clinical trials that have refined or redefined the treatment of cervical cancers across the early stage, locally advanced, persistent, recurrent and/or metastatic disease settings. Advances for patients with early stage disease have been achieved through trials evaluating less extensive and fertility-preserving surgeries, different surgical approaches (open versus minimally invasive), and sentinel versus full pelvic lymph node dissection. We also discuss results from trials testing the use of neoadjuvant, induction and adjuvant chemotherapy as well as immune-checkpoint inhibitors in patients with locally advanced disease. Finally, we review the progress made with systemic chemotherapy and novel therapeutics, including anti-angiogenic agents, immune-checkpoint inhibitors and antibody-drug conjugates, in the setting of metastatic and/or recurrent cervical cancer. The advances highlighted in this manuscript have reduced morbidity and improved overall survival for patients with this challenging-to-treat disease, while also inspiring additional research and trials in the field.
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Affiliation(s)
- Alex A Francoeur
- Department of Obstetrics and Gynecology, University of California, Irvine, Irvine, CA, USA.
| | - Bradley J Monk
- Florida Cancer Specialists and Research Institute, West Palm Beach, FL, USA
| | - Krishnansu S Tewari
- Department of Obstetrics and Gynecology, University of California, Irvine, Irvine, CA, USA
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14
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Abutaha S, Alzibdeh A, Mohamad I, Wahbeh L, Salah S, Abuhijlih R, Abuhijla F. Turning the tide: From cervical cancer's grip to complete response: A case report. World J Clin Oncol 2025; 16:98219. [PMID: 39995565 PMCID: PMC11686556 DOI: 10.5306/wjco.v16.i2.98219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 09/24/2024] [Accepted: 10/25/2024] [Indexed: 12/11/2024] Open
Abstract
BACKGROUND Cervical cancer is a formidable global health issue, particularly affecting women in lower-middle-income countries with little or no access to preventative vaccines, screening programs, and treatment modalities. The case report presents a unique case of a large cervical cancer achieving complete response (CR) with concurrent chemoradiotherapy (CCRT), highlighting the effectiveness of this treatment approach even in advanced stages and underscoring the importance of adaptive radiotherapy (RT) in optimizing patient outcomes. CASE SUMMARY We present the case of a 53-year-old woman who presented with four years of abnormal vaginal bleeding and was found to have p16-positive, moderately differentiated cervical squamous cell carcinoma. The tumor measured 14 cm × 12 cm × 8 cm, the largest size reported in the literature to achieve CR with CCRT. Despite this monumental feat, the patient remained disease-free and is currently on follow-up for 2 years; however, she continued to suffer from substantial morbidity caused by a vesicovaginal fistula and hydronephrosis, underscoring the continuing impact of cervical cancer on quality of life. CONCLUSION In this case report, we highlight the effectiveness of CCRT in achieving CR, even in cases of bulky cervical cancer, with adaptive RT offering a customized strategy to improve patient outcomes. We also emphasize the necessity for multidisciplinary team discussions and highlight the need for strategies to mitigate treatment-related toxicities and long-term complications.
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Affiliation(s)
- Shatha Abutaha
- Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan
| | - Abdulla Alzibdeh
- Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan
| | - Issa Mohamad
- Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan
| | - Lina Wahbeh
- Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan
| | - Samer Salah
- Department of Medical Oncology, King Fahad Specialist Hospital, Dammam 32210, Saudi Arabia
| | - Ramiz Abuhijlih
- Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan
| | - Fawzi Abuhijla
- Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan
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Włoszek E, Krupa K, Skrok E, Budzik MP, Deptała A, Badowska-Kozakiewicz A. HPV and Cervical Cancer-Biology, Prevention, and Treatment Updates. Curr Oncol 2025; 32:122. [PMID: 40136326 PMCID: PMC11941113 DOI: 10.3390/curroncol32030122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/13/2025] [Accepted: 02/20/2025] [Indexed: 03/27/2025] Open
Abstract
One of the most significant breakthroughs in cancer research has been the identification of persistent infection with certain human papillomaviruses (HPV) genotypes as the cause of cervical cancer. Since then, a range of diagnostic and therapeutic methods has been developed based on this discovery. This article aims to describe the latest updates in the biology, prevention, and treatment of HPV-related cervical cancer. The current state of knowledge regarding vaccinations, diagnostic tests, and cervical cancer therapies is presented. The latest WHO guidelines on vaccinations are presented, as well as announcements of upcoming changes. The final part of the article summarizes promising new diagnostic and treatment methods, as well as perspectives and the latest research findings on self-administered diagnostic tests, the use of therapeutic vaccines, and circulating cell-free DNA in diagnosis. Despite the significant progress made in recent years, the strategy based on vaccination and testing remains the cornerstone in the fight against HPV-related cervical cancer.
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Affiliation(s)
- Emilia Włoszek
- Students’ Scientific Organization of Cancer Cell Biology, Department of Oncology Propaedeutics, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (E.S.)
| | - Kamila Krupa
- Students’ Scientific Organization of Cancer Cell Biology, Department of Oncology Propaedeutics, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (E.S.)
| | - Eliza Skrok
- Students’ Scientific Organization of Cancer Cell Biology, Department of Oncology Propaedeutics, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (E.S.)
| | - Michał Piotr Budzik
- Department of Oncology Propaedeutics, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.P.B.); (A.D.); (A.B.-K.)
| | - Andrzej Deptała
- Department of Oncology Propaedeutics, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.P.B.); (A.D.); (A.B.-K.)
| | - Anna Badowska-Kozakiewicz
- Department of Oncology Propaedeutics, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.P.B.); (A.D.); (A.B.-K.)
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16
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Alonso-Espías M, Pérez F, Gracia M, Zapardiel I. Management of Bulky Tumors in Cervical Cancer: Limits of the Surgical Approach. J Clin Med 2025; 14:1142. [PMID: 40004673 PMCID: PMC11856161 DOI: 10.3390/jcm14041142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/04/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
The standard treatment for cervical tumors larger than 4 cm, known as bulky tumors, currently involves concurrent chemoradiotherapy followed by vaginal brachytherapy. However, radical surgery is an alternative option in some cases, particularly for those in which a combination of risk factors is not anticipated. Recent studies show that neoadjuvant chemotherapy may help reduce tumor size in these bulky tumors, enabling subsequent surgical intervention reducing the adverse effects derived from radiotherapy. Evidence about fertility sparing surgery in patients with bulky tumors is limited, although some retrospective studies reported good oncological outcomes when adequate tumor reduction is achieved through neoadjuvant chemotherapy. Moreover, the administration of adjuvant radiotherapy after radical surgery in patients with tumor sizes ≥ 4 cm in the final pathological report, combined with other intermediate risk factors for recurrence, remains a topic of debate. Current evidence indicates no significant differences in overall survival or disease-free survival between follow-up alone and the use of adjuvant radiotherapy in these cases, although further research is needed to refine treatment strategies for these patients. This narrative review aims to summarize the available evidence on the comprehensive management of bulky cervical tumors, addressing relevant issues and controversies in the field.
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Affiliation(s)
- María Alonso-Espías
- Gynecologic Oncology Unit, La Paz University Hospital, Paseo de la Castellana 261, 28046 Madrid, Spain
| | - Fátima Pérez
- Gynecology and Obstetrics, Rafael Méndez University Hospital, Ctra N-340, 30813 Lorca, Spain
| | - Myriam Gracia
- Gynecologic Oncology Unit, La Paz University Hospital, Paseo de la Castellana 261, 28046 Madrid, Spain
| | - Ignacio Zapardiel
- Gynecologic Oncology Unit, La Paz University Hospital, Paseo de la Castellana 261, 28046 Madrid, Spain
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18
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DeCesaris C, Bedell S, Kelley K, Gaffney D, Suneja G, Burt L, Jarboe E, Brower J. Use of Radiation Therapy in the Management of Vulvar Cancers-Identification and Management of Acute and Late Toxicities. Pract Radiat Oncol 2025; 15:e57-e62. [PMID: 39303777 DOI: 10.1016/j.prro.2024.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 08/08/2024] [Indexed: 09/22/2024]
Abstract
Radiation therapy plays a critical role in the management of locally advanced vulvar cancers but can lead to a unique spectrum of side effects, with >25% of patients experiencing high-grade toxicities. The treatment phase requires meticulous perineal skincare and may require pharmacologic management of dysuria and cystitis, diarrhea, nausea, and dermatitis/mucositis. The addition of chemotherapy warrants close laboratory monitoring for hematologic and metabolic derangements.
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Affiliation(s)
- Cristina DeCesaris
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
| | - Sabrina Bedell
- Department of Gynecologic Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Kristen Kelley
- Department of Internal Medicine, Division of Hematology and Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - David Gaffney
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Gita Suneja
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Lindsay Burt
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Elke Jarboe
- Department of Pathology, Division of Gynecologic Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
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19
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Feng T, Zhang Y, Zheng G, Lv X, Yan D, Feng Y, Lou H. Efficacy and safety of cisplatin combined with paclitaxel concurrent radiotherapy in patients with locally advanced cervical squamous cell carcinoma. J Gynecol Oncol 2025; 36:e10. [PMID: 39900342 PMCID: PMC11790991 DOI: 10.3802/jgo.2025.36.e10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 05/08/2024] [Accepted: 06/11/2024] [Indexed: 02/05/2025] Open
Abstract
OBJECTIVE This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dual-agent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. METHODS This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. RESULTS Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3-4 acute haematological toxicities was different between the two groups (p<0.05). CONCLUSION Cisplatin combined with paclitaxel CCRT couldn't improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.
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Affiliation(s)
- Tao Feng
- Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gynecological Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Yuxin Zhang
- Department of Oncology Radiotherapy, Hangzhou Cancer Hospital, Hangzhou, China
| | - Guanghao Zheng
- Department of Oncology Radiotherapy, The First Hospital of Akesu Area, Xinjiang, China
| | - Xiaojuan Lv
- Department of Gynecological Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Dingding Yan
- Department of Gynecological Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Yue Feng
- Department of Gynecological Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Hanmei Lou
- Department of Gynecological Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
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Caruso G, Wagar MK, Hsu HC, Hoegl J, Rey Valzacchi GM, Fernandes A, Cucinella G, Sahin Aker S, Jayraj AS, Mauro J, Pareja R, Ramirez PT. Cervical cancer: a new era. Int J Gynecol Cancer 2024; 34:1946-1970. [PMID: 39117381 DOI: 10.1136/ijgc-2024-005579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024] Open
Abstract
Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer.
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Affiliation(s)
- Giuseppe Caruso
- Division of Gynecologic Oncology, European Institute of Oncology (IEO), IRCCS, Milan, Italy
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Matthew K Wagar
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Heng-Cheng Hsu
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Surgery, National Taiwan University Cancer Center, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jorge Hoegl
- Obstetrics and Gynecology, Division of Gynecological Oncology, Clínica Maternidad Santa Ana, IVSS, Caracas, Venezuela, Bolivarian Republic of
| | | | - Andreina Fernandes
- Laboratorio de Genética Molecular, Instituto de Oncología y Hematología, Caracas, Venezuela, Bolivarian Republic of
| | - Giuseppe Cucinella
- Gynecologic Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy
| | - Seda Sahin Aker
- Gynecologic Oncology, Kayseri City Education and Research Hospital, Kayseri, Turkey
- Clinical Anatomy, Ankara University, Ankara, Turkey
| | - Aarthi S Jayraj
- South Tees NHS Foundation Trust, James Cook University, Middlesbrough, UK
| | - Jessica Mauro
- Department of Gynecologic Oncology, Ospedale Michele e Pietro Ferrero, Verduno, Italy
| | - Rene Pareja
- Gynecology, Gynecologic Oncology, Clinica ASTORGA, Medellin, and Instituto Nacional de Cancerología, Bogotá, Colombia
| | - Pedro T Ramirez
- Department of Obstetrics and Gynecology, Houston Methodist Hospital, Houston, Texas, USA
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21
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Predarska I, Kaluđerović GN, Hey-Hawkins E. Nanostructured mesoporous silica carriers for platinum-based conjugates with anti-inflammatory agents. BIOMATERIALS ADVANCES 2024; 165:213998. [PMID: 39236581 DOI: 10.1016/j.bioadv.2024.213998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 08/09/2024] [Accepted: 08/17/2024] [Indexed: 09/07/2024]
Abstract
This review discusses the relationship between inflammation and cancer initiation and progression, which has prompted research into anti-inflammatory approaches for cancer prevention and treatment. Specifically, it focuses on the use of inflammation-reducing agents to enhance the effectiveness of tumor treatment methods. These agents are combined with platinum(II)-based antitumor drugs to create multifunctional platinum(IV) prodrugs, allowing for simultaneous delivery to tumor cells in a specific ratio. Once inside the cells and subjected to intracellular reduction, both components can act in parallel through distinct pathways. Motivated by the objective of reducing the systemic toxicity associated with contemporary chemotherapy, and with the aim of leveraging the passive enhanced permeability and retention effect exhibited by nanostructured materials to improve their accumulation within tumor tissues, the platinum(IV) complexes have been efficiently loaded into mesoporous silica SBA-15 material. The resulting nanostructured materials are capable of providing controlled release of the conjugates when subjected to simulated plasma conditions. This feature suggests the potential for extended circulation within the body in vivo, with minimal premature release of the drug before reaching the intended target site. The primary emphasis of this review is on research that integrates these two approaches to develop chemotherapeutic treatments that are both more efficient and less harmful.
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Affiliation(s)
- Ivana Predarska
- Leipzig University, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), Institute of Bioanalytical Chemistry, Deutscher Platz 5, 04103 Leipzig, Germany; Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Str. 2, 06217 Merseburg, Germany
| | - Goran N Kaluđerović
- Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Str. 2, 06217 Merseburg, Germany.
| | - Evamarie Hey-Hawkins
- Leipzig University, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), Institute of Bioanalytical Chemistry, Deutscher Platz 5, 04103 Leipzig, Germany.
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22
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Namugga J, Wong J, Nakisige C, Okoth A, Ajeani J, Najjemba JI, Ueda S, Lee PS. Feasibility of neoadjuvant chemotherapy for bulky early stage to stage IIIB cervical cancer in Uganda. Gynecol Oncol Rep 2024; 56:101533. [PMID: 39512271 PMCID: PMC11541667 DOI: 10.1016/j.gore.2024.101533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/14/2024] [Accepted: 10/18/2024] [Indexed: 11/15/2024] Open
Abstract
Introduction External beam radiotherapy (EBRT) became unavailable in Uganda from February 2016 to November 2017. Following resource stratification guidelines, an alternative treatment strategy was developed. Methods Bulky early stage to Stage IIIB patients received at least 3 cycles of neoadjuvant chemotherapy (NAC). Surgery was performed if adequate response was achieved and adjuvant therapy given for high risk factors. Chemotherapy versus supportive care was advised in unresectable disease. NAC protocol completion was defined as receiving at least 3 cycles of NAC followed by either surgery, chemotherapy and/or radiation, or best supportive care. The purpose of this study was to determine the completion rate of NAC and assess the adverse events associated with treatment. Data were collected through retrospective chart review. Results From February 2016 to November 2018, 53 evaluable patients were identified. 86.8% (46/53) of patients presented in Stage IIB or higher. The completion rate of the NAC protocol was 75.5% (40/53). 94.3% (50/53) received platinum-taxane combination. 7.6% (4/52) grade 3 adverse events occurred related to chemotherapy, all hematologic. 18.8% (10/53) patients underwent surgery with 2 aborted cases due to metastatic or inoperable disease. No adverse events related to surgery were reported. 5 patients underwent adjuvant therapy after surgery due to high risk factors or incomplete pathology findings. 26 patients received adjuvant radiation (3 brachytherapy, 23 EBRT after it became available). Reported side effects related to radiation included vaginal fibrosis and skin reactions. Conclusion In this limited-resource setting, majority of patients completed a NAC treatment strategy for cervical cancer with acceptable toxicities.
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Affiliation(s)
- Jane Namugga
- Mulago Specialised Women and Neonatal Hospital, Owen Road, Mulago P.O. Box 22081, Kampala, Uganda
| | - Janice Wong
- Duke University Hospital, DUMC 3084, 203 Baker House, Durham, NC 27710, United States
| | - Carolyn Nakisige
- Uganda Cancer Institute, Upper Mulago Hill Road PO Box 3935, Kampala, Uganda
| | - Anthony Okoth
- Uganda Cancer Institute, Upper Mulago Hill Road PO Box 3935, Kampala, Uganda
| | - Judith Ajeani
- Mulago Specialised Women and Neonatal Hospital, Owen Road, Mulago P.O. Box 22081, Kampala, Uganda
| | | | - Stefanie Ueda
- University of California, San Francisco, UCSF Mission Hall, 550 16th Street, 7th Floor Box 0132, San Francisco, CA 94158, United States
| | - Paula S. Lee
- Duke University Hospital, DUMC 3079, Durham, NC 27710, United States
- University of Hawaii at Manao, 1319 Punahou St Suite 824, Honolulu, HI 96826, United States
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23
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Desravines N, Tran C, Wethington S, Williams-Brown MY. Contemporary Review of Adenocarcinoma of the Cervix. Curr Treat Options Oncol 2024; 25:1538-1549. [PMID: 39535688 DOI: 10.1007/s11864-024-01254-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2024] [Indexed: 11/16/2024]
Abstract
OPINION STATEMENT Among cervical cancers, adenocarcinoma is less common than squamous cell carcinoma of the cervix; however, the incidence of these cancers is rising. The incidence has changed largely due to a shift in risk factors as well as the evolution of the diagnosis and classification of adenocarcinoma. Adenocarcinoma of the cervix is composed of a diverse group of neoplasms that can be classified by various factors. In this review article, preinvasive disease, updated classifications of adenocarcinoma, and treatment options for cervical adenocarcinoma are discussed with a focus on current and future therapies. Advances in antibody-drug conjugates (ADC) and immunotherapy have increased the treatment options available for usual-type adenocarcinoma but there is still a lack of variety of treatment options for the remaining 25% of non-usual-type adenocarcinomas.
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Affiliation(s)
- N Desravines
- Division of Gynecologic Oncology, Department of Women's Health, University of Texas at Austin Dell Medical School, Austin, TX, USA.
| | - C Tran
- Department of Women's Health, University of Texas at Austin Dell Medical School, Austin, TX, USA
| | - S Wethington
- Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - M Y Williams-Brown
- Division of Gynecologic Oncology, Department of Women's Health, University of Texas at Austin Dell Medical School, Austin, TX, USA
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24
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Newton C, Graham R, Liberale V, Burnell M, Menon U, Mould T, Olaitan A, Macdonald N, Widschwendter M, Doufekas K, McCormack M, Mitra A, Arora R, Manchanda R. Outcomes of minimal access retroperitoneal para-aortic lymphadenectomy in patients with locally advanced cervical cancer. J OBSTET GYNAECOL 2024; 44:2344529. [PMID: 38708782 DOI: 10.1080/01443615.2024.2344529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 05/20/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer. METHODS Pathology databases searched for all para-aortic lymphadenectomy cases 2005-2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15). RESULTS 191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively.Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn't (31.27 (SD 32.5) months). CONCLUSION Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.
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Affiliation(s)
- Claire Newton
- Gynaecology Oncology, University Hospitals Bristol NHS Foundation trust, Bristol, UK
- University of Bristol, Bristol, UK
- University College London Hospital NHS Foundation Trust, London, UK
| | - Radha Graham
- University College London Hospital NHS Foundation Trust, London, UK
| | - Viola Liberale
- University College London Hospital NHS Foundation Trust, London, UK
| | - Matthew Burnell
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Usha Menon
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Tim Mould
- University College London Hospital NHS Foundation Trust, London, UK
| | - Adeola Olaitan
- University College London Hospital NHS Foundation Trust, London, UK
| | - Nicola Macdonald
- University College London Hospital NHS Foundation Trust, London, UK
| | - Martin Widschwendter
- University College London Hospital NHS Foundation Trust, London, UK
- European Translational Oncology Prevention and Screening Institute, Leopold-Franzens-University of Innsbruck, Austria
| | - Kostas Doufekas
- University College London Hospital NHS Foundation Trust, London, UK
| | - Mary McCormack
- University College London Hospital NHS Foundation Trust, London, UK
| | - Anita Mitra
- University College London Hospital NHS Foundation Trust, London, UK
| | - Rupali Arora
- University College London Hospital NHS Foundation Trust, London, UK
| | - Ranjit Manchanda
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
- Wolfson Institute of Population Health, Queen Mary University of London, London, UK
- The Royal London hospital, Barts Health NHS trust, London, UK
- Distinguished Infosys Chair in Oncology, All India institute of medical sciences (AIIMS), New Delhi, India
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25
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Versuti Del Cioppo Vasques P, Bakkum-Gamez JN, Dean PG, Molligan JF, Garda AE. Novel use of adjuvant proton beam therapy in patient with pelvic renal transplant diagnosed with stage IB3 cervical adenocarcinoma. Gynecol Oncol Rep 2024; 56:101520. [PMID: 39421440 PMCID: PMC11483286 DOI: 10.1016/j.gore.2024.101520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/26/2024] [Accepted: 09/28/2024] [Indexed: 10/19/2024] Open
Abstract
Cervical adenocarcinoma is the second most common histology of cervical cancer and treatment can involve surgery, radiotherapy, systemic therapy, and any combination of the three. Photon external beam radiation therapy and brachytherapy have been the mainstay of radiation treatment options for cervical cancer. Here, we report a case of a 41-year-old patient who had a prior renal transplant and was diagnosed with early-stage, intermediate-risk adenocarcinoma treated with modified radical hysterectomy plus adjuvant proton-beam therapy and vaginal brachytherapy. Treatment was well tolerated with a disease-free interval of 14-months and preserved renal function.
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Affiliation(s)
| | - Jamie N. Bakkum-Gamez
- Division of Gynecologic Oncology Surgery, Mayo Clinic, Rochester, MN, United States of America
| | - Patrick G. Dean
- Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, United States of America
| | - Jeremy F. Molligan
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America
| | - Allison E. Garda
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States of America
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26
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Cepero A, Yang Y, Young L, Huang J, Ji X, Yang F. Longitudinal FDG-PET Radiomics for Early Prediction of Treatment Response to Chemoradiation in Locally Advanced Cervical Cancer: A Pilot Study. Cancers (Basel) 2024; 16:3813. [PMID: 39594768 PMCID: PMC11592998 DOI: 10.3390/cancers16223813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/06/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
Objectives: This study aimed to assess the capacity of longitudinal FDG-PET radiomics for early distinguishing between locally advanced cervical cancer (LACC) patients who responded to treatment and those who did not. Methods: FDG-PET scans were obtained before and midway through concurrent chemoradiation for a study cohort of patients with LACC. Radiomics features related to image textures were extracted from the primary tumor volumes and stratified for relevance to treatment response status with the aid of random forest recursive feature elimination. Predictive models based on the k-nearest neighbors time series classifier were developed using the top-selected features to differentiate between responders and non-responders. The performance of the developed models was evaluated using receiver operating characteristic (ROC) curve analysis and n-fold cross-validation. Results: The top radiomics features extracted from scans taken midway through treatment showed significant differences between the two responder groups (p-values < 0.0005). In contrast, those from pretreatment scans did not exhibit significant differences. The AUC of the mean ROC curve for the predictive model based on the top features from pretreatment scans was 0.8529, while it reached 0.9420 for those derived midway through treatment scans. Conclusions: The study highlights the potential of longitudinal FDG-PET radiomics extracted midway through treatment for predicting response to chemoradiation in LACC patients and emphasizes that interim PET scans could be crucial in personalized medicine, ultimately enhancing therapeutic outcomes for LACC.
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Affiliation(s)
- Alejandro Cepero
- Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33146, USA
| | - Yidong Yang
- The First Affiliated Hospital of the University of Science and Technology of China, Hefei 230001, China
| | - Lori Young
- Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA
| | - Jianfeng Huang
- Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China
| | - Xuemei Ji
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Fei Yang
- Department of Radiation Oncology, University of Miami School of Medicine, Miami, FL 33136, USA
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27
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Camprodon G, Gabro A, El Ayachi Z, Chopra S, Nout R, Maingon P, Chargari C. Personalized strategies for brachytherapy of cervix cancer. Cancer Radiother 2024; 28:610-617. [PMID: 39395842 DOI: 10.1016/j.canrad.2024.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 10/14/2024]
Abstract
Among most tailored approaches in radiation oncology, the development of brachytherapy for the treatment of cervical cancer patients has benefited from various technological innovations. The development of 3D image-guided treatments was the first step for treatment personalization. This breakthrough preceded practice homogenization and validation of predictive dose and volume parameters and prognostic factors. We review some of the most significant strategies that emerged from the ongoing research in order to increase personalization in uterovaginal brachytherapy. A better stratification based on patients and tumors characteristics may lead to better discriminate candidates for intensification or de-escalation strategies, in order to still improve patient outcome while minimizing the risk of treatment-related side effects.
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Affiliation(s)
- Guillaume Camprodon
- Department of Radiation Oncology, hôpital Pitié Salpêtrière, Assistance publique-hôpitaux de Paris, Sorbonne université, Paris, France
| | - Alexandra Gabro
- Department of Radiation Oncology, hôpital Pitié Salpêtrière, Assistance publique-hôpitaux de Paris, Sorbonne université, Paris, France
| | - Zineb El Ayachi
- Department of Radiation Oncology, hôpital Pitié Salpêtrière, Assistance publique-hôpitaux de Paris, Sorbonne université, Paris, France
| | - Supriya Chopra
- Department of Radiation Oncology and Medical Physics, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Remi Nout
- Department of Radiation Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Philippe Maingon
- Department of Radiation Oncology, hôpital Pitié Salpêtrière, Assistance publique-hôpitaux de Paris, Sorbonne université, Paris, France
| | - Cyrus Chargari
- Department of Radiation Oncology, hôpital Pitié Salpêtrière, Assistance publique-hôpitaux de Paris, Sorbonne université, Paris, France.
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28
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McCormack M, Eminowicz G, Gallardo D, Diez P, Farrelly L, Kent C, Hudson E, Panades M, Mathew T, Anand A, Persic M, Forrest J, Bhana R, Reed N, Drake A, Adusumalli M, Mukhopadhyay A, King M, Whitmarsh K, McGrane J, Colombo N, Mak C, Mandal R, Chowdhury RR, Alamilla-Garcia G, Chávez-Blanco A, Stobart H, Feeney A, Vaja S, Hacker AM, Hackshaw A, Ledermann JA. Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial. Lancet 2024; 404:1525-1535. [PMID: 39419054 DOI: 10.1016/s0140-6736(24)01438-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
BACKGROUND Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. METHODS The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35. FINDINGS Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. INTERPRETATION Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer. FUNDING Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.
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Affiliation(s)
| | | | | | | | - Laura Farrelly
- Cancer Research UK and UCL Cancer Trials Centre, University College London, London, UK
| | | | | | | | - Tony Mathew
- Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
| | | | - Mojca Persic
- University of Derby and Burton NHS Foundation Trust, Derby, UK
| | - Jennifer Forrest
- Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
| | - Rajanee Bhana
- University Hospital of North Midlands NHS Trust, Stoke-on-Trent, UK
| | | | - Anne Drake
- Belfast Health and Social Care Trust, Belfast, UK
| | | | - Asima Mukhopadhyay
- Kolkata Gynaecological Oncology Trials and Translational Research Group, Kolkata, India
| | - Margaret King
- The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Karen Whitmarsh
- The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK
| | | | | | - Choi Mak
- Northampton General Hospital NHS Trust, Northampton, UK
| | | | | | | | | | | | - Amanda Feeney
- Cancer Research UK and UCL Cancer Trials Centre, University College London, London, UK
| | - Simran Vaja
- Cancer Research UK and UCL Cancer Trials Centre, University College London, London, UK
| | - Anne-Marie Hacker
- Cancer Research UK and UCL Cancer Trials Centre, University College London, London, UK
| | - Allan Hackshaw
- Cancer Research UK and UCL Cancer Trials Centre, University College London, London, UK
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29
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Tozzi R, Bigardi S, Spagnol G, Ferrari F, Saccardi C, Noventa M, Marchetti M. Nerve-Sparing Laparoscopic Radical Hysterectomy (nsLRH) without Adjuvant Therapy in FIGO Stage IB3 Cervical Cancer Patients: Surgical Technique and Survival Outcomes. Cancers (Basel) 2024; 16:3355. [PMID: 39409974 PMCID: PMC11475574 DOI: 10.3390/cancers16193355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 09/16/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
(1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4-5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment.
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Affiliation(s)
- Roberto Tozzi
- Department of Gynecology and Obstetrics, Division of Women and Children’s Health, University of Padua, 35128 Padua, Italy (G.S.); (C.S.); (M.N.); (M.M.)
| | - Sofia Bigardi
- Department of Gynecology and Obstetrics, Division of Women and Children’s Health, University of Padua, 35128 Padua, Italy (G.S.); (C.S.); (M.N.); (M.M.)
| | - Giulia Spagnol
- Department of Gynecology and Obstetrics, Division of Women and Children’s Health, University of Padua, 35128 Padua, Italy (G.S.); (C.S.); (M.N.); (M.M.)
| | - Federico Ferrari
- Department of Clinical and Experimental Sciences, University of Brescia, 35122 Brescia, Italy
| | - Carlo Saccardi
- Department of Gynecology and Obstetrics, Division of Women and Children’s Health, University of Padua, 35128 Padua, Italy (G.S.); (C.S.); (M.N.); (M.M.)
| | - Marco Noventa
- Department of Gynecology and Obstetrics, Division of Women and Children’s Health, University of Padua, 35128 Padua, Italy (G.S.); (C.S.); (M.N.); (M.M.)
| | - Matteo Marchetti
- Department of Gynecology and Obstetrics, Division of Women and Children’s Health, University of Padua, 35128 Padua, Italy (G.S.); (C.S.); (M.N.); (M.M.)
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30
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Kunos CA, Miller RW, Fabian D. Cisplatin-Containing Combinations Associate with Survival in Women from Appalachian Kentucky with Metastatic, Persistent, or Recurrent Uterine Cervix Cancer. Cancers (Basel) 2024; 16:3319. [PMID: 39409939 PMCID: PMC11475045 DOI: 10.3390/cancers16193319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/18/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Prior preclinical studies showed promising antitumor activity and an acceptable safety profile associated with radiopharmaceuticals for patients with metastatic, persistent, or recurrent uterine cervix cancers. Whether the addition of a radiopharmaceutical to chemotherapy would significantly increase progression-free survival in such patients is untested. Our retrospective study sought to associate the line of treatment and progression-free survival as benchmarks for next-generation radiopharmaceutical development. Methods: We grouped metastatic, persistent, or recurrent uterine cervix cancer patients not amenable to curable surgery or radiotherapy between 2002 and 2023 by the line of doublet, triplet, and quadruplet chemotherapy or another intervention. After the first-line treatment, patients were monitored for radiographic progression every three months for up to three years. The primary endpoints were the first and any second or third progression-free survival intervals. Results: A total of 127 patients contributed demographic, tumor, line of treatment, and outcome data with a median follow-up of 18 months (25-75% interquartile range: 9 to 37 months). After the first-line treatment, 113 patients had local or distant progression or died from any cause, most often death from the disease (67%). Median progression-free survivals were 5.5 months (95% confidence interval: 4.8-6.0 months), 5.3 months (95% confidence interval: 4.5-6.3 months), and 3.0 months (95% confidence interval: 2.1-3.7 months) for the first-, second-, and third-line treatments, respectively. For a first-line cisplatin-containing regimen, the median progression-free survival was 6.5 months (95% confidence interval: 5.5-7.7 months). Conclusions: This study highlights the limited efficacy of current treatments for metastatic, persistent, or recurrent uterine cancer patients. A five-month progression-free survival might serve as a benchmark for the development of novel therapies in clinical efficacy trials, such as radiopharmaceuticals.
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Affiliation(s)
- Charles A. Kunos
- Department of Radiation Medicine, University of Kentucky, Lexington, KY 40508, USA
| | - Rachel W. Miller
- Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, University of Kentucky, Lexington, KY 40508, USA
| | - Denise Fabian
- Department of Radiation Medicine, University of Kentucky, Lexington, KY 40508, USA
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31
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Xue X, Sun L, Liang D, Zhu J, Liu L, Sun Q, Liu H, Gao J, Fu X, Ding J, Dai X, Tao L, Cheng J, Li T, Zhou F. Deep learning-based segmentation for high-dose-rate brachytherapy in cervical cancer using 3D Prompt-ResUNet. Phys Med Biol 2024; 69:195008. [PMID: 39270708 DOI: 10.1088/1361-6560/ad7ad1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 09/13/2024] [Indexed: 09/15/2024]
Abstract
Objective.To develop and evaluate a 3D Prompt-ResUNet module that utilized the prompt-based model combined with 3D nnUNet for rapid and consistent autosegmentation of high-risk clinical target volume (HRCTV) and organ at risk (OAR) in high-dose-rate brachytherapy for cervical cancer patients.Approach.We used 73 computed tomography scans and 62 magnetic resonance imaging scans from 135 (103 for training, 16 for validation, and 16 for testing) cervical cancer patients across two hospitals for HRCTV and OAR segmentation. A novel comparison of the deep learning neural networks 3D Prompt-ResUNet, nnUNet, and segment anything model-Med3D was applied for the segmentation. Evaluation was conducted in two parts: geometric and clinical assessments. Quantitative metrics included the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95%), Jaccard index (JI), and Matthews correlation coefficient (MCC). Clinical evaluation involved interobserver comparison, 4-grade expert scoring, and a double-blinded Turing test.Main results.The Prompt-ResUNet model performed most similarly to experienced radiation oncologists, outperforming less experienced ones. During testing, the DSC, HD95% (mm), JI, and MCC value (mean ± SD) for HRCTV were 0.92 ± 0.03, 2.91 ± 0.69, 0.85 ± 0.04, and 0.92 ± 0.02, respectively. For the bladder, these values were 0.93 ± 0.05, 3.07 ± 1.05, 0.87 ± 0.08, and 0.93 ± 0.05, respectively. For the rectum, they were 0.87 ± 0.03, 3.54 ± 1.46, 0.78 ± 0.05, and 0.87 ± 0.03, respectively. For the sigmoid, they were 0.76 ± 0.11, 7.54 ± 5.54, 0.63 ± 0.14, and 0.78 ± 0.09, respectively. The Prompt-ResUNet achieved a clinical viability score of at least 2 in all evaluation cases (100%) for both HRCTV and bladder and exceeded the 30% positive rate benchmark for all evaluated structures in the Turing test.Significance.The Prompt-ResUNet architecture demonstrated high consistency with ground truth in autosegmentation of HRCTV and OARs, reducing interobserver variability and shortening treatment times.
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Affiliation(s)
- Xian Xue
- Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention (CDC), Beijing 100088, People's Republic of China
| | - Lining Sun
- Department of radiation oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People's Republic of China
| | - Dazhu Liang
- Digital Health China Technologies Co., LTD, Beijing 100089, People's Republic of China
| | - Jingyang Zhu
- Department of radiation oncology, Zhongcheng Cancer center, Beijing 100160, People's Republic of China
| | - Lele Liu
- Department of radiation oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Quanfu Sun
- Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention (CDC), Beijing 100088, People's Republic of China
| | - Hefeng Liu
- Digital Health China Technologies Co., LTD, Beijing 100089, People's Republic of China
| | - Jianwei Gao
- Digital Health China Technologies Co., LTD, Beijing 100089, People's Republic of China
| | - Xiaosha Fu
- Biomedical Research Centre, Sheffield Hallam University, Sheffield S11WB, United Kingdom
| | - Jingjing Ding
- Department of radiation oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, People's Republic of China
| | - Xiangkun Dai
- Department of radiation oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, People's Republic of China
| | - Laiyuan Tao
- Digital Health China Technologies Co., LTD, Beijing 100089, People's Republic of China
| | - Jinsheng Cheng
- Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention (CDC), Beijing 100088, People's Republic of China
| | - Tengxiang Li
- Department of Nuclear Science and Engineering, Nanhua University, Hunan 421001, People's Republic of China
| | - Fugen Zhou
- Department of Aero-space Information Engineering, Beihang University, Beijing 100191, People's Republic of China
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Restaino S, Pellecchia G, Arcieri M, Bogani G, Taliento C, Greco P, Driul L, Chiantera V, Ercoli A, Fanfani F, Fagotti A, Ciavattini A, Scambia G, Vizzielli G, Gynecologic Oncology Group. Management for Cervical Cancer Patients: A Comparison of the Guidelines from the International Scientific Societies (ESGO-NCCN-ASCO-AIOM-FIGO-BGCS-SEOM-ESMO-JSGO). Cancers (Basel) 2024; 16:2541. [PMID: 39061181 PMCID: PMC11274772 DOI: 10.3390/cancers16142541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/11/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Cervical cancer continues to have a significant incidence, despite global efforts in HPV vaccination campaigns. Managing this condition involves a diverse team of healthcare professionals. Research in this field is undergoing a period of great revolution in multiple areas, and international guidelines will soon have to adapt to new scientific evidence. This could be true mainly in locally advanced stages, and it could also be true for minimal invasive surgery. This paper aims to summarize and compare the most recent recommendations published by international gynecological oncological societies for patients with cervical cancer. From their comparison, common aspects and disagreements emerged, especially in the diagnostic pathway and follow-up strategies. Several issues that remain to be debated in the literature were addressed and compared, highlighting similarities and differences, from the role of the sentinel lymph node in early stages to that of the adjuvant hysterectomy in locally advanced tumors. On the surgical side, for this last subset of patients, currently, a laparotomic approach is recommended. At the same time, the advent of immunotherapy has just opened up new and promising scenarios in systemic treatment for locally advanced cervical cancer, and international guidelines will soon introduce it into their algorithms.
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Affiliation(s)
- Stefano Restaino
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- PhD School in Biomedical Sciences, Gender Medicine, Child and Women Health, University of Sassari, 07100 Sassari, Italy
| | - Giulia Pellecchia
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Martina Arcieri
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
| | - Giorgio Bogani
- Gynaecological Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy;
| | - Cristina Taliento
- Department of Medical Sciences, Obstetrics and Gynecology Unit, University of Ferrara, 44121 Ferrara, Italy; (C.T.); (P.G.)
- Department of Development and Regeneration, Woman and Child, KU Leuven, 3000 Leuven, Belgium
| | - Pantaleo Greco
- Department of Medical Sciences, Obstetrics and Gynecology Unit, University of Ferrara, 44121 Ferrara, Italy; (C.T.); (P.G.)
| | - Lorenza Driul
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Vito Chiantera
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy;
- Unit of Gynecologic Oncology, National Cancer Institute, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
| | - Alfredo Ercoli
- Department of Human Pathology in Adult and Childhood “G. Barresi”, University of Messina, 98122 Messina, Italy;
| | - Francesco Fanfani
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.F.); (G.S.)
| | - Anna Fagotti
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.F.); (G.S.)
| | - Andrea Ciavattini
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, 60121 Ancona, Italy;
| | - Giovanni Scambia
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.F.); (G.S.)
| | - Giuseppe Vizzielli
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
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Ronsini C, Solazzo MC, Braca E, Andreoli G, Vastarella MG, Cianci S, Capozzi VA, Torella M, Cobellis L, De Franciscis P. Locally Advanced Cervical Cancer: Neoadjuvant Treatment versus Standard Radio-Chemotherapy-An Updated Meta-Analysis. Cancers (Basel) 2024; 16:2542. [PMID: 39061182 PMCID: PMC11275180 DOI: 10.3390/cancers16142542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/10/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The treatment of choice for patients with locally advanced cervical cancer (LACC) is definitive concurrent radio chemotherapy which consists of external beam radiotherapy (EBRT) and concurrent platinum-based chemotherapy (CCRT), with the possible addition of brachytherapy (BT). However, the benefits of adjuvant surgery after neoadjuvant treatments remain a debated issue and a still open question in the literature. This meta-analysis aims to provide an updated view on the controversial topic, focusing on comparing surgery after any adjuvant treatment and standard treatment. METHODS Following the recommendations in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, the PubMed and Embase databases were systematically searched in April 2023 for early publications. No limitations on the country were applied. Only English articles were considered. The comparative studies containing data about disease-free survival (DFS) and/or overall survival (OS) were included in the meta-analysis. RESULTS The CCRT + surgery group showed a significantly better DFS than CCRT (RR 0.69 [95% CI 0.58-0.81] p < 0.01) and a better OS (RR 0.70 [95% CI 0.55-0.89] p < 0.01). Nine studies comparing neoadjuvant chemotherapy (NACT) plus surgery and CCRT were also enrolled. The NACT + surgery group showed a significantly better DFS than CCRT (RR 0.66 [95% CI 0.45-0.97] p < 0.01) and a better OS (RR 0.56 [95% CI 0.38-0.83] p < 0.01). In the sub-analysis of three randomized control trials, the surgery group documented a non-significantly better DFS and OS than CCRT (OR 1.10 [95% CI 0.67-1.80] p = 0.72; I2 = 69% p = 0.72; OR 1.09 [95% CI 0.63-1.91] p = 0.75; I2 = 13% p = 0.32). CONCLUSION The results provide updated findings about the efficacy of neoadjuvant treatments, indicating significantly improved DFS and OS in patients undergoing hysterectomy after CCRT or NACT compared with patients undergoing standard treatments.
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Affiliation(s)
- Carlo Ronsini
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
| | - Maria Cristina Solazzo
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
| | - Eleonora Braca
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
| | - Giada Andreoli
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
| | - Maria Giovanna Vastarella
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
| | - Stefano Cianci
- Department of Woman and Child Health, IRCCS, Fondazione Policlinico Gemelli, 00136 Rome, Italy; (S.C.); (V.A.C.)
| | - Vito Andrea Capozzi
- Department of Woman and Child Health, IRCCS, Fondazione Policlinico Gemelli, 00136 Rome, Italy; (S.C.); (V.A.C.)
| | - Marco Torella
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
| | - Luigi Cobellis
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
| | - Pasquale De Franciscis
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.S.); (E.B.); (G.A.); (M.G.V.); (M.T.); (L.C.); (P.D.F.)
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Uke A, Dahake SB, Luharia A, Luharia M, Mishra GV, Mahakalkar C. Investigating and Analyzing Prognostic Factors and Their Impact on Recurrent Cervical Cancers. Cureus 2024; 16:e65361. [PMID: 39184727 PMCID: PMC11344604 DOI: 10.7759/cureus.65361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 07/25/2024] [Indexed: 08/27/2024] Open
Abstract
The incidence of cervical cancer in India is significantly high, and the average recurrence age is much less. The standard line of treatment consists of concurrent chemoradiotherapy. If a recurrence occurs, the treatment options or set of interventions are limited and suboptimal. Through this review, we have analyzed and classified the possible prognostic factors for cervical cancer into three broad categories, viz., (a) disease-related factors, (b) patient-related factors, and (c) treatment-related factors. Disease-related factors include tumor histology, tumor size, stage, parametrial involvement (PMI), Prognostic Nutritional Index (PNI), lymphovascular space invasion (LVSI), and nodal status. Patient-related factors include overall treatment time (OTT), nutritional status, hemoglobin level, comorbidities, and age. Treatment-related factors include addition of chemotherapy, techniques of external beam radiotherapy (EBRT), techniques of brachytherapy, and quality assurance for radiation therapy delivery. Out of these, extremely significant prognostic factors were tumor size and stage, nodal status, PMI, nutritional status, and addition of chemotherapy. Impactful factors include younger age, histology, LVSI, associated comorbidities, hemoglobin level, OTT, and patient-specific quality assurance. The factor that is not related or significant is the technique used for EBRT and brachytherapy delivery.
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Affiliation(s)
- Ashish Uke
- Radiation Oncology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Shweta B Dahake
- Medical Physics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Anurag Luharia
- Medical Physics and Radiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Monika Luharia
- Ayurveda, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Gaurav V Mishra
- Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Chanrashekhar Mahakalkar
- General Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Wang G, Wang Z, Zhang Y, Sun X, Sun Y, Guo Y, Zeng Z, Zhou B, Hu K, Qiu J, Yan J, Zhang F. Daily Online Adaptive Radiation Therapy of Postoperative Endometrial and Cervical Cancer With PTV Margin Reduction to 5 mm: Dosimetric Outcomes, Acute Toxicity, and First Clinical Experience. Adv Radiat Oncol 2024; 9:101510. [PMID: 38826155 PMCID: PMC11140188 DOI: 10.1016/j.adro.2024.101510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 04/02/2024] [Indexed: 06/04/2024] Open
Abstract
PURPOSE This study evaluated the first clinical implementation of daily iterative cone beam computed tomography (iCBCT)-guided online adaptive radiation therapy (oART) in the postoperative treatment of endometrial and cervical cancer. METHODS AND MATERIALS Seventeen consecutive patients treated with daily iCBCT-guided oART were enrolled in this prospective study, with a reduced uniform 3-dimensional PTV margin of 5 mm. Treatment plans were designed to deliver 45 or 50.4 Gy in 1.8 Gy daily fractions to PTV. Pre- and posttreatment ultrasound and iCBCT scans were performed to record intrafractional bladder and rectal volume changes. The accuracy of contouring, oART procedure time, dosimetric outcomes, and acute toxicity were evaluated. RESULTS The average time from first iCBCT acquisition to completion of treatment was 22 minutes and 26 seconds. During this period, bladder volume increased by 44 cm3 using iCBCT contouring, whereas rectal volume remained stable (62.9 cm3 pretreatment vs 61.9 cm3 posttreatment). A total of 91.6% of influencers and 88.1% of CTVs required no or minor edits. The adapted plan was selected in all (434) fractions and significantly improved the dosimetry coverage for CTV and PTV, especially the vaginal PTV coverage by nearly 7% (P < .05). The adapted bladder Dmean was 104.61 cGy, and the rectum Dmean was 123.67 cGy, significantly lower than the scheduled plan of 108.24 and 128.19 cGy, respectively. The bone marrow and femur head left and right dosimetry were also improved with adaptation. Grade 2 acute gastrointestinal and genitourinary toxicities were 24% and 0, respectively. There was a grade 3 acute toxicity of decreased white blood cell count in 1 patient. CONCLUSIONS Daily oART was associated with favorable dosimetry improvement and low acute toxicity, supporting its safety and efficacy for postoperative treatment of endometrial and cervical cancer. These results need to be validated in a larger prospective randomized controlled cohort.
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Affiliation(s)
- Guangyu Wang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Zhiqun Wang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yu Zhang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xiansong Sun
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yuliang Sun
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yuping Guo
- Tumor Hospital affiliated to Xinjiang Medical University, Urumqi, China
| | - Zheng Zeng
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Bing Zhou
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ke Hu
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jie Qiu
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Junfang Yan
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Fuquan Zhang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- Department of Radiation Oncology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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Lawless M, Byrns K, Bednarz BP, Meudt J, Shanmuganayagam D, Shah J, McMillan A, Li K, Pirasteh A, Miller J. Feasibility of identifying proliferative active bone marrow with fat fraction MRI and multi-energy CT. Phys Med Biol 2024; 69:135007. [PMID: 38876111 DOI: 10.1088/1361-6560/ad58a0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 06/14/2024] [Indexed: 06/16/2024]
Abstract
Objective.Active bone marrow (ABM) can serve as both an organ at risk and a target in external beam radiotherapy.18F-fluorothymidine (FLT) PET is the current gold standard for identifying proliferative ABM but it is not approved for human use, and PET scanners are not always available to radiotherapy clinics. Identifying ABM through other, more accessible imaging modalities will allow more patients to receive treatment specific to their ABM distribution. Multi-energy CT (MECT) and fat-fraction MRI (FFMRI) show promise in their ability to characterize bone marrow adiposity, but these methods require validation for identifying proliferative ABM.Approach.Six swine subjects were imaged using FFMRI, fast-kVp switching (FKS) MECT and sequential-scanning (SS) MECT to identify ABM volumes relative to FLT PET-derived ABM volumes. ABM was contoured on FLT PET images as the region within the bone marrow with a SUV above the mean. Bone marrow was then contoured on the FFMRI and MECT images, and thresholds were applied within these contours to determine which threshold produced the best agreement with the FLT PET determined ABM contour. Agreement between contours was measured using the Dice similarity coefficient (DSC).Main results.FFMRI produced the best estimate of the PET ABM contour. Compared to FLT PET ABM volumes, the FFMRI, SS MECT and FKS MECT ABM contours produced average peak DSC of 0.722 ± 0.080, 0.619 ± 0.070, and 0.464 ± 0.080, respectively. The ABM volume was overestimated by 40.51%, 97.63%, and 140.13% by FFMRI, SS MECT and FKS MECT, respectively.Significance.This study explored the ability of FFMRI and MECT to identify the proliferative relative to ABM defined by FLT PET. Of the methods investigated, FFMRI emerged as the most accurate approximation to FLT PET-derived active marrow contour, demonstrating superior performance by both DSC and volume comparison metrics. Both FFMRI and SS MECT show promise for providing patient-specific ABM treatments.
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Affiliation(s)
- M Lawless
- Department of Human Oncology, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI 53792, United States of America
| | - K Byrns
- St. Lukes Radiation Oncology Associates, 915 E 1st St, Duluth, MN 55805, United States of America
| | - B P Bednarz
- Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, United States of America
| | - J Meudt
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI 53706, United States of America
| | - D Shanmuganayagam
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI 53706, United States of America
| | - J Shah
- Siemens Healthineers, 221 Gregson Dr, Cary, NC 27511, United States of America
| | - A McMillan
- Department of Radiology, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI 53792, United States of America
| | - K Li
- Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, United States of America
| | - A Pirasteh
- Department of Radiology, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI 53792, United States of America
| | - J Miller
- Department of Human Oncology, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI 53792, United States of America
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Kumar M, Baruah U, Begum D, Barmon D, Nath J, Khanikar D, Bassetty KC. To study the survival outcomes of uncommon recurrences among patients with cervical cancer compared with loco-regional and nodal recurrences at a tertiary care center in North East India - Bridging the knowledge gap in the existing literature. Eur J Obstet Gynecol Reprod Biol X 2024; 22:100314. [PMID: 38770162 PMCID: PMC11103416 DOI: 10.1016/j.eurox.2024.100314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 01/08/2024] [Accepted: 05/05/2024] [Indexed: 05/22/2024] Open
Abstract
Background Recurrence rates of FIGO stage IB-IIA and IIB-IVA cervical cancer 28-64 respectively. There is a scarcity of data on the recurrence recurrence pattern for unusual sites and theirrecurrence pattern for unusual sites and its association with survival and prognosis. Objective To study overall survival in patients with distant metastasis compared to local and regional nodal metastasis. Methods A retrospective study was done from 1/1/2017 to 30/12/22. Cervical cancer patients post primary treatments were included. Survival was analyzed with respect to 3 groups local, regional nodalconducted from 1/1/2017 to 30/12/22. Cervical cancer patients who had received primary post-primary treatments were included. Survival was analyzed with respect to three groups: local, regional nodal, and distant metastasis. Results 225 patients had recurrences post-completion of primary treatment, of which 105 (46.6%)(46.6 %) had local, 46 (20.4%)(20.4 %) had regional nodal, and 74 (33.3 %) had distant recurrences. The median time for recurrence in local, regional nodal, and atypical recurrences were 9, 9, and 13 months (p value - <0.05), respectively. Treatment included systemic chemotherapy 122 (54.2 %), metronomic therapy 19 (8.4 %), palliative radiotherapy 44 (19.5 %), palliative surgery 8 (3.5 %) and best supportive care 30 (13.3 %) patients. Median Time to treatment-death of patients after recurrence in local, nodal and distant recurrences was 17.0 months, 18.0 months and 10.0 months respectively (p value - < 0.05). Overall Survival of patients after primary treatment with local, nodal and distant recurrences was 35.0 months, 47.0 months and 50.0 months respectively (p value <0.05). Conclusion Local recurrence is most common, followed by regional, nodal, and distant recurrences. Overall survival post recurrence was lowest for distant recurrences and highest for local recurrences however overall survival after primary treatment completion was highest for distant recurrence due to the late presen; however, tation of distant recurrences.
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Affiliation(s)
- Mahendra Kumar
- Department of gynaecological oncology, Dr B Borooah cancer Institute, Guwahati, Assam, India
| | - Upasana Baruah
- Department of gynaecological oncology, Dr B Borooah cancer Institute, Guwahati, Assam, India
| | - Dimpy Begum
- Department of gynaecological oncology, Dr B Borooah cancer Institute, Guwahati, Assam, India
| | - Debabrata Barmon
- Department of gynaecological oncology, Dr B Borooah cancer Institute, Guwahati, Assam, India
| | - Jyotiman Nath
- Department of Radiation oncology, Dr. Bhubaneswar Borooah cancer institute, Guwahati, Assam, India
| | - Duncan Khanikar
- Department of Medical oncology, Dr. Bhubaneswar Borooah cancer institute, Guwahati, Assam, India
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Zhao N, Li Y, Chen X, Ma J, Luo W, Li Y. Evaluating the clinical efficacy and safety of concurrent chemoradiotherapy with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer. J Cancer Res Clin Oncol 2024; 150:233. [PMID: 38709400 PMCID: PMC11074032 DOI: 10.1007/s00432-024-05764-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 04/23/2024] [Indexed: 05/07/2024]
Abstract
OBJECTIVE A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis. METHODS Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted. RESULTS A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions. CONCLUSION The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.
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Affiliation(s)
- Ning Zhao
- Department of Radiation Oncology, Minhang Branch Hospital, Fudan University Shanghai Cancer Center, Shanghai 200240, China
| | - Yunhai Li
- Department of Radiation Oncology, Minhang Branch Hospital, Fudan University Shanghai Cancer Center, Shanghai 200240, China.
| | - Xue Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
| | - Jinli Ma
- Department of Radiation Oncology, Minhang Branch Hospital, Fudan University Shanghai Cancer Center, Shanghai 200240, China
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
| | - Weiming Luo
- Department of Radiation Oncology, Minhang Branch Hospital, Fudan University Shanghai Cancer Center, Shanghai 200240, China
| | - Yunhai Li
- Department of Radiation Oncology, Minhang Branch Hospital, Fudan University Shanghai Cancer Center, Shanghai 200240, China
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Bacorro W, Short M, Baldivia K, Mariano J, Bautista A, Amparo G, Tagayuna I, Jainar CJ, Antonio L, Dancel E, Ortin TS, Gonzalez G, Canlas R. Shared Decision Making in Oncology and Its Implementation in Cervical Cancer Management in the Philippines: A Narrative Review. JCO Glob Oncol 2024; 10:e2300486. [PMID: 38754049 DOI: 10.1200/go.23.00486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 02/21/2024] [Accepted: 03/12/2024] [Indexed: 05/18/2024] Open
Abstract
PURPOSE Shared decision making (SDM) is an approach where clinicians and patients make decisions together using the best available evidence. Although much studied, recognized to be ethically imperative, and recommended in international health policies, it remains poorly implemented. In the Philippines, there are limited studies on patient decision making preferences and SDM. Practical guidance on the implementation of SDM or use of patient decision aids (PtDAs) is often not detailed in existing national clinical practice guidelines in oncology. METHODS We performed a systematic search of Philippine literature on SDM in oncology and an iterative review of international literature on the philosophy and methods of SDM, the utility and effectiveness of PtDAs, and the facilitators and barriers to implementation or usage. We contextualized our review to the cervical cancer management and health service delivery in the Philippines. RESULTS Local literature is limited to five scientific publications and two registered studies. International literature encompasses patient decisional preferences, the role of PtDAs and the standards for their development and evaluation, their effectiveness, and barriers and facilitators to their use in cancer-related decision making. We discussed the implications on the management of cervical cancer in the Philippines, challenges in health service delivery and standards, and SDM research. CONCLUSION Local SDM research is limited. Our preliminary experience in a multicenter clinical trial in Manila on PtDA use in the framework of SDM in cervical cancer suggest good patient and clinician acceptability. Challenges to implementation such as unfavorable financial situations, urgency of clinical decisions, low patient or caregiver educational attainment, and poor integration of multidisciplinary and SDM in organizational workflows will be important when implementing SDM in different settings.
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Affiliation(s)
- Warren Bacorro
- Graduate School, University of Santo Tomas, Manila, Philippines
- Department of Clinical Epidemiology, University of Santo Tomas-Faculty of Medicine and Surgery, Manila, Philippines
- Department of Radiation Oncology, University of Santo Tomas Hospital-Benavides Cancer Institute, Manila, Philippines
| | - Michala Short
- UniSA Allied Health and Human Performance, University of South Australia, Adelaide, Australia
| | - Kathleen Baldivia
- Department of Radiation Oncology, University of Santo Tomas Hospital-Benavides Cancer Institute, Manila, Philippines
| | - Jocelyn Mariano
- Department of Obstetrics and Gynecology, University of Santo Tomas-Faculty of Medicine and Surgery, Manila, Philippines
- Department of Obstetrics and Gynecology, University of Santo Tomas Hospital, Manila, Philippines
| | - Aida Bautista
- Department of Obstetrics and Gynecology, Manila Doctors Hospital, Manila, Philippines
| | - Genalin Amparo
- Department of Obstetrics and Gynecology, Our Lady of Lourdes Hospital, Manila, Philippines
| | - Irene Tagayuna
- Department of Obstetrics and Gynecology, De Los Santos Medical Center, Quezon City, Philippines
| | - Carl Jay Jainar
- Department of Radiation Oncology, University of Santo Tomas Hospital-Benavides Cancer Institute, Manila, Philippines
| | - Linda Antonio
- Department of Radiation Oncology, University of Santo Tomas Hospital-Benavides Cancer Institute, Manila, Philippines
| | - Evelyn Dancel
- Department of Radiation Oncology, University of Santo Tomas Hospital-Benavides Cancer Institute, Manila, Philippines
| | - Teresa Sy Ortin
- Department of Radiation Oncology, University of Santo Tomas Hospital-Benavides Cancer Institute, Manila, Philippines
| | - Gil Gonzalez
- Department of Obstetrics and Gynecology, University of Santo Tomas-Faculty of Medicine and Surgery, Manila, Philippines
- Department of Obstetrics and Gynecology, University of Santo Tomas Hospital, Manila, Philippines
| | - Rodel Canlas
- Graduate School, University of Santo Tomas, Manila, Philippines
- Department of Psychology, University of Santo Tomas-College of Science, Manila, Philippines
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Carobeli LR, Santos ABC, Martins LBM, Damke E, Consolaro MEL. Recent advances in photodynamic therapy combined with chemotherapy for cervical cancer: a systematic review. Expert Rev Anticancer Ther 2024; 24:263-282. [PMID: 38549400 DOI: 10.1080/14737140.2024.2337259] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 03/26/2024] [Indexed: 04/04/2024]
Abstract
INTRODUCTION Despite the evidence that photodynamic therapy (PDT) associated with chemotherapy presents great potential to overcome the limitations of monotherapy, little is known about the current status of this combination against cervical cancer. This systematic review aimed to address the currently available advances in combining PDT and chemotherapy in different research models and clinical trials of cervical cancer. METHODS We conducted a systematic review based on PRISMA Statement and Open Science Framework review protocol using PubMed, Web of Science, Embase, Scopus, LILACS, and Cochrane databases. We selected original articles focusing on 'Uterine Cervical Neoplasms' and 'Photochemotherapy and Chemotherapy' published in the last 10 years. The risk of bias in the studies was assessed using the CONSORT and SYRCLE tools. RESULTS Twenty-three original articles were included, focusing on HeLa cells, derived from endocervical adenocarcinoma and on combinations of several chemotherapeutics. Most of the combinations used modern drug delivery systems for improved simultaneous delivery and presented promising results with increased cytotoxicity compared to monotherapy. CONCLUSION Despite the scarcity of animal studies and the absence of clinical studies, the combination of chemotherapy with PDT presents a potential option for cervical cancer therapy requiring additional studies. OSF REGISTRATION https://doi.org/10.17605/OSF.IO/WPHN5 [Figure: see text].
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Affiliation(s)
- Lucimara Rodrigues Carobeli
- Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil
- Graduate Program in Biosciences and Physiopathology, State University of Maringá, Maringá, Paraná, Brazil
| | - Ana Beatriz Camillo Santos
- Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil
- Graduate Program in Biosciences and Physiopathology, State University of Maringá, Maringá, Paraná, Brazil
| | | | - Edilson Damke
- Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil
| | - Marcia Edilaine Lopes Consolaro
- Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil
- Graduate Program in Biosciences and Physiopathology, State University of Maringá, Maringá, Paraná, Brazil
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Verrelle P, Gestraud P, Poyer F, Soria A, Tessier S, Lescure A, Anthony E, Corbé M, Heinrich S, Beauvineau C, Chaput L, Granzhan A, Piguel S, Perez F, Teulade-Fichou MP, Megnin-Chanet F, Del Nery E. Integrated High-Throughput Screening and Large-Scale Isobolographic Analysis to Accelerate the Discovery of Radiosensitizers With Greater Selectivity for Cancer Cells. Int J Radiat Oncol Biol Phys 2024; 118:1294-1307. [PMID: 37778425 DOI: 10.1016/j.ijrobp.2023.09.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/03/2023]
Abstract
PURPOSE High-throughput screening (HTS) platforms have been widely used to identify candidate anticancer drugs and drug-drug combinations; however, HTS-based identification of new drug-ionizing radiation (IR) combinations has rarely been reported. Herein, we developed an integrated approach including cell-based HTS and computational large-scale isobolographic analysis to accelerate the identification of radiosensitizing compounds acting strongly and more specifically on cancer cells. METHODS AND MATERIALS In a 384-well plate format, 160 compounds likely to interfere with the cell response to radiation were screened on human glioblastoma (U251-MG) and cervix carcinoma (ME-180) cell lines, as well as on normal fibroblasts (CCD-19Lu). After drug exposure, cells were irradiated or not and short-term cell survival was assessed by high-throughput cell microscopy. Computational large-scale dose-response and isobolographic approach were used to identify promising synergistic drugs radiosensitizing cancer cells rather than normal cells. Synergy of a promising compound was confirmed on ME-180 cells by an independent 96-well assay protocol, and finally, by the gold-standard colony forming assay. RESULTS We retained 4 compounds synergistic at 2 isoeffects in U251-MG and ME-180 cell lines and 11 compounds synergistically effective in only one cancer cell line. Among these 15 promising radiosensitizers, 5 compounds showed limited toxicity combined or not with IR on normal fibroblasts. CONCLUSIONS Overall, this study demonstrated that HTS chemoradiation screening together with large-scale computational analysis is an efficient tool to identify synergistic drug-IR combinations, with concomitant assessment of unwanted toxicity on normal fibroblasts. It sparks expectations to accelerate the discovery of highly desired agents improving the therapeutic index of radiation therapy.
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Affiliation(s)
- Pierre Verrelle
- Radiation Oncology Department, Institut Curie Hospital, Paris, France; Chemistry and Modelisation for the Biology of Cancer, CNRS UMR9187, INSERM U1196, Institut Curie, Université Paris Saclay, 91405 Orsay, France.
| | - Pierre Gestraud
- Chemistry and Modelisation for the Biology of Cancer, CNRS UMR9187, INSERM U1196, Institut Curie, Université Paris Saclay, 91405 Orsay, France
| | - Florent Poyer
- Chemistry and Modelisation for the Biology of Cancer, CNRS UMR9187, INSERM U1196, Institut Curie, Université Paris Saclay, 91405 Orsay, France
| | - Adèle Soria
- Biophenics High-Content Screening Laboratory, Department of Translational Research, PSL Research University, PICT-IBiSa, Institut Curie Research Center, Paris, France
| | - Sarah Tessier
- Biophenics High-Content Screening Laboratory, Department of Translational Research, PSL Research University, PICT-IBiSa, Institut Curie Research Center, Paris, France
| | - Aurianne Lescure
- Biophenics High-Content Screening Laboratory, Department of Translational Research, PSL Research University, PICT-IBiSa, Institut Curie Research Center, Paris, France
| | - Elodie Anthony
- Biophenics High-Content Screening Laboratory, Department of Translational Research, PSL Research University, PICT-IBiSa, Institut Curie Research Center, Paris, France
| | - Maxime Corbé
- Biophenics High-Content Screening Laboratory, Department of Translational Research, PSL Research University, PICT-IBiSa, Institut Curie Research Center, Paris, France
| | - Sophie Heinrich
- Experimental Radiotherapy Platform (RadeXp), Translational Research Department, Institut Curie, Orsay, France; Inserm U1021-CNRS UMR 3347, Institut Curie, Paris Saclay University
| | - Claire Beauvineau
- Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, Paris, France
| | - Ludovic Chaput
- Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, Paris, France
| | - Anton Granzhan
- Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, Paris, France
| | - Sandrine Piguel
- Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, Paris, France; BioCIS UMR8076, Université Paris-Saclay, Faculté de Pharmacie, Orsay, France
| | - Franck Perez
- Biophenics High-Content Screening Laboratory, Department of Translational Research, PSL Research University, PICT-IBiSa, Institut Curie Research Center, Paris, France; Cell Biology and Cancer UMR144, Institut Curie, PSL Research University, Paris, France
| | - Marie-Paule Teulade-Fichou
- Chemistry and Modelisation for the Biology of Cancer, CNRS UMR9187, INSERM U1196, Institut Curie, Université Paris Saclay, 91405 Orsay, France
| | - Frédérique Megnin-Chanet
- Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, Paris, France
| | - Elaine Del Nery
- Biophenics High-Content Screening Laboratory, Department of Translational Research, PSL Research University, PICT-IBiSa, Institut Curie Research Center, Paris, France.
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Dou A, Bouchard-Fortier G, Han K, Milosevic M, Lukovic J, L’heureux S, Li X, Doherty MC, Croke J. Utilization and Impact of a Radiation Nursing Clinic to Address Acute Care Needs for Patients with Gynecologic Cancers. Curr Oncol 2024; 31:1645-1655. [PMID: 38534958 PMCID: PMC10969712 DOI: 10.3390/curroncol31030125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 03/14/2024] [Accepted: 03/19/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre's acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT). METHODS This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher's exact test were used for comparisons of continuous and categorical variables, respectively. RESULTS RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre. CONCLUSIONS The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed.
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Affiliation(s)
- Aaron Dou
- Radiation Medicine Program, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
| | - Genevieve Bouchard-Fortier
- Department of Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
| | - Kathy Han
- Radiation Medicine Program, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Michael Milosevic
- Radiation Medicine Program, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Jelena Lukovic
- Radiation Medicine Program, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Stephanie L’heureux
- Department of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
| | - Xuan Li
- Department of Biostatistics, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
| | - Mary C. Doherty
- Radiation Medicine Program, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
| | - Jennifer Croke
- Radiation Medicine Program, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
- Department of Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2M9, Canada
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Dong EE, Xu J, Kim JW, Bryan J, Appleton J, Hamstra DA, Ludwig MS, Hanania AN. Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer. Radiat Oncol 2024; 19:35. [PMID: 38481285 PMCID: PMC10936078 DOI: 10.1186/s13014-024-02425-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 02/27/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. METHODS Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. RESULTS Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10- 3 mm2/s were 5.33 (95% CI, 1.35-24.4) times more likely to achieve CMR. CONCLUSIONS Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.
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Affiliation(s)
- Elizabeth E Dong
- Department of Radiation Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Junqian Xu
- Department of Radiology, Baylor College of Medicine, Houston, TX, USA
- Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA
| | - Joo-Won Kim
- Department of Radiology, Baylor College of Medicine, Houston, TX, USA
- Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA
| | - Jason Bryan
- Smith Clinic Attwell Radiation Therapy Center, Harris Health System, Houston, TX, USA
| | - Jewel Appleton
- Department of Radiology, Baylor College of Medicine, Houston, TX, USA
- Department of Radiology, Texas Children's Hospital, 7200 Cambridge St, 77030, Houston, TX, USA
| | - Daniel A Hamstra
- Department of Radiation Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Michelle S Ludwig
- Department of Radiation Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Alexander N Hanania
- Department of Radiation Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
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Ang DJM, Chan JJ. Evolving standards and future directions for systemic therapies in cervical cancer. J Gynecol Oncol 2024; 35:e65. [PMID: 38282261 PMCID: PMC10948986 DOI: 10.3802/jgo.2024.35.e65] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 01/05/2024] [Indexed: 01/30/2024] Open
Abstract
Several groundbreaking clinical trials with the potential to transform the management paradigm of both locally advanced and persistent, recurrent, or metastatic cervical cancers have been presented in 2023. This review describes the reported data from INTERLACE and KEYNOTE-A18 in the locally advanced setting, as well as BEATcc, innovaTV 301 and DESTINY-PanTumor02 for advanced disease. The practice implications of their positive results are interpreted in the context of global health considerations, and updated treatment algorithms are proposed. Furthermore, emerging trends in drug development for cervical cancer are discussed. As the routine use of immune checkpoint inhibitors (ICIs) for curative and palliative indications increases in the foreseeable future, patients whose cervical cancers which persist, relapse or progress after prior ICI exposure will represent an area of unmet clinical need and form the key target population for next-generation trials. Future research will help shape oncologists' approaches in the optimal selection, sequencing and re-treatment or rechallenge of immuno-oncology agents and/or antibody-drug conjugates in women with cervical cancer.
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Affiliation(s)
| | - Jack Junjie Chan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore
- Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore.
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Tewari KS, Colombo N, Monk BJ, Dubot C, Cáceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Toker S, Keefe SM, Lorusso D. Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial. JAMA Oncol 2024; 10:185-192. [PMID: 38095881 PMCID: PMC10722390 DOI: 10.1001/jamaoncol.2023.5410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 08/22/2023] [Indexed: 12/17/2023]
Abstract
Importance The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown. Objective To assess efficacy outcomes in patient subgroups of KEYNOTE-826. Design, Setting, and Participants Exploratory subgroup analyses were conducted in a global, phase 3, randomized, double-blind, placebo-controlled clinical trial. Participants included women with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment. This subanalysis was conducted from November 20, 2018, to May 3, 2021. Interventions Pembrolizumab, 200 mg, every 3 weeks or placebo for up to 35 cycles plus chemotherapy (paclitaxel, 175 mg/m2, plus cisplatin, 50 mg/m2, or carboplatin AUC 5 [area under the free carboplatin plasma concentration vs time curve]) with or without bevacizumab, 15 mg/kg. Main Outcomes and Measures Overall survival (OS) and progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 in subgroups defined by use of bevacizumab (yes or no), choice of platinum (carboplatin or cisplatin), prior chemoradiotherapy (CRT) exposure only (yes or no), and histologic type (squamous or nonsquamous) in patients with programmed cell death ligand 1-positive tumors (defined as a combined positive score [CPS] ≥1) and in the intention-to-treat population. Results A total of 617 patients (median age, 51 years; range, 22-82 years) were enrolled in the trial. In the CPS greater than or equal to 1 population, hazard ratios (HRs) for OS favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.62; 95% CI, 0.45-0.87) and without bevacizumab (HR, 0.67; 95% CI, 0.47-0.96), use of carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and cisplatin (HR, 0.53; 95% CI, 0.27-1.04), with prior CRT only (HR, 0.56; 95% CI, 0.39-0.81) and without prior CRT only (HR, 0.72; 95% CI, 0.52-1.00), and squamous (HR, 0.60; 95% CI, 0.46-0.79) and nonsquamous (HR, 0.70; 95% CI, 0.41-1.20) histologic type. In the intention-to-treat population, HRs for OS also favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.63; 95% CI, 0.47-0.87) and without bevacizumab (HR, 0.74; 95% CI, 0.53-1.04), use of carboplatin (HR, 0.69; 95% CI, 0.54-0.89) or cisplatin (HR, 0.59; 95% CI, 0.32-1.09), with prior CRT only (HR, 0.64; 95% CI, 0.45-0.91) and without prior CRT only (HR, 0.71; 95% CI, 0.53-0.97), and squamous (HR, 0.61; 95% CI, 0.47-0.80) and nonsquamous (HR, 0.76; 95% CI, 0.47-1.23) histologic type. Similar to OS, the addition of pembrolizumab prolonged PFS across all subgroups in the CPS greater than or equal to 1 and intention-to-treat populations. Conclusions and Relevance The findings of this trial suggest that adding pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer. Trial Registration ClinicalTrials.gov Identifier: NCT03635567.
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Affiliation(s)
| | - Nicoletta Colombo
- Gynecologic Oncology, European Institute of Oncology IRCCS and Università degli Studi di Milano Bicocca, Milan, Italy
| | - Bradley J. Monk
- HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix
| | - Coraline Dubot
- Oncologie Médicale, Institut Curie Saint Cloud, and GINECO, Paris, France
| | - M. Valeria Cáceres
- Medical Oncology, Instituto de Oncologia Angel H. Roffo, Buenos Aires, Argentina
| | - Kosei Hasegawa
- Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan
| | | | - Pamela Salman
- Medical Oncology, Oncovida Cancer Center, Providencia, Santiago, Chile
| | - Eduardo Yañez
- Medical Oncology, Universidad de la Frontera, Temuco, Chile
| | - Mahmut Gümüş
- Medical Oncology, Istanbul Medeniyet University Hospital, Istanbul, Turkey
| | | | - Vanessa Samouëlian
- Gynecologic Oncology, Centre Hospitalier de l’Université de Montréal, Centre de Recherche de l’Université de Montréal, Université de Montréal, Montreal, Quebec, Canada
| | - Vincent Castonguay
- Medical Oncology, Centre Hospitalier Universitaire de Québec, Université Laval, Quebec City, Quebec, Canada
| | - Alexander Arkhipov
- Oncology and Chemical Therapy, Medical Rehabilitation Center Under the Ministry of Health of Russian Federation, Moscow, Russian Federation
| | | | - Kan Li
- Oncology, Merck & Co, Inc, Rahway, New Jersey
| | | | | | - Domenica Lorusso
- Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy
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Zhang Y, Wang G, Chang Y, Wang Z, Sun X, Sun Y, Zeng Z, Chen Y, Hu K, Qiu J, Yan J, Zhang F. Prospects for daily online adaptive radiotherapy for cervical cancer: Auto-contouring evaluation and dosimetric outcomes. Radiat Oncol 2024; 19:6. [PMID: 38212767 PMCID: PMC10785518 DOI: 10.1186/s13014-024-02398-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 01/03/2024] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Training senior radiation therapists as "adapters" to manage influencers and target editing is critical in daily online adaptive radiotherapy (oART) for cervical cancer. The purpose of this study was to evaluate the accuracy and dosimetric outcomes of automatic contouring and identify the key areas for modification. METHODS A total of 125 oART fractions from five postoperative cervical cancer patients and 140 oART fractions from five uterine cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective study. The same adaptive treatments were replanned using the Ethos automatic contours workflow without manual contouring edits. The clinical target volume (CTV) was subdivided into several separate regions, and the average surface distance dice (ASD), centroid deviation, dice similarity coefficient (DSC), and 95% Hausdorff distance (95% HD) were used to evaluate contouring for the above portions. Dosimetric results from automatic oART plans were compared to supervised oART plans to evaluate target volumes and organs at risk (OARs) dose changes. RESULTS Overall, the paired CTV had high overlap rates, with an average DSC value greater than 0.75. The uterus had the largest consistency differences, with ASD, centroid deviation, and 95% HD being 2.67 ± 1.79 mm, 17.17 ± 12 mm, and 10.45 ± 5.68 mm, respectively. The consistency differences of the lower nodal CTVleft and nodal CTVright were relatively large, with ASD, centroid deviation, and 95% HD being 0.59 ± 0.53 mm, 3.6 ± 2.67 mm, and 5.41 ± 4.08 mm, and 0.59 ± 0.51 mm, 3.6 ± 2.54 mm, and 4.7 ± 1.57 mm, respectively. The automatic online-adapted plan met the clinical requirements of dosimetric coverage for the target volume and improved the OAR dosimetry. CONCLUSIONS The accuracy of automatic contouring from the Ethos adaptive platform is considered clinically acceptable for cervical cancer, and the uterus, upper vaginal cuff, and lower nodal CTV are the areas that need to be focused on in training.
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Affiliation(s)
- Yu Zhang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Guangyu Wang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Yankui Chang
- School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, China
| | - Zhiqun Wang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Xiansong Sun
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Yuliang Sun
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Zheng Zeng
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Yining Chen
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Ke Hu
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Jie Qiu
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Junfang Yan
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
| | - Fuquan Zhang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
- Department of Radiation Oncology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
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Yariv O, Camphausen K, Krauze AV. Small Bowel Dose Constraints in Radiation Therapy—Where Omics-Driven Biomarkers and Bioinformatics Can Take Us in the Future. BIOMEDINFORMATICS 2024; 4:158-172. [DOI: 10.3390/biomedinformatics4010011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Radiation-induced gastrointestinal (GI) dose constraints are still a matter of concern with the ongoing evolution of patient outcomes and treatment-related toxicity in the era of image-guided intensity-modulated radiation therapy (IMRT), stereotactic ablative radiotherapy (SABR), and novel systemic agents. Small bowel (SB) dose constraints in pelvic radiotherapy (RT) are a critical aspect of treatment planning, and prospective data to support them are scarce. Previous and current guidelines are based on retrospective data and experts’ opinions. Patient-related factors, including genetic, biological, and clinical features and systemic management, modulate toxicity. Omic and microbiome alterations between patients receiving RT to the SB may aid in the identification of patients at risk and real-time identification of acute and late toxicity. Actionable biomarkers may represent a pragmatic approach to translating findings into personalized treatment with biologically optimized dose escalation, given the mitigation of the understood risk. Biomarkers grounded in the genome, transcriptome, proteome, and microbiome should undergo analysis in trials that employ, R.T. Bioinformatic templates will be needed to help advance data collection, aggregation, and analysis, and eventually, decision making with respect to dose constraints in the modern RT era.
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Affiliation(s)
- Orly Yariv
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Bethesda, MD 20892, USA
| | - Kevin Camphausen
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Bethesda, MD 20892, USA
| | - Andra V. Krauze
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Bethesda, MD 20892, USA
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Li F, Mei F, Yin S, Du Y, Hu L, Hong W, Li J. Improving the efficacy and safety of concurrent chemoradiotherapy by neoadjuvant chemotherapy: a randomized controlled study of locally advanced cervical cancer with a large tumor. J Gynecol Oncol 2024; 35:e10. [PMID: 37857565 PMCID: PMC10792203 DOI: 10.3802/jgo.2024.35.e10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/05/2023] [Accepted: 09/04/2023] [Indexed: 10/21/2023] Open
Abstract
OBJECTIVE To compare the efficacy and safety of neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (NACT+CCRT) vs. concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC) patients with large tumor masses. METHODS LACC patients with localized tumor diameter >4 cm, were randomly allocated in an unblinded 1:1 ratio to NACT+CCRT or CCRT groups. Patients in the NACT+CCRT group were given paclitaxel combined with cisplatin (TP) NACT every 3 weeks for 2 cycles, followed by CCRT, with the chemotherapy regimen the same as for NACT. CCRT group were given CCRT with the same as for NACT. RESULTS From March 1, 2019, to June 30, 2021, 146 patients were included in the final analysis. Sixty-eight (93.2%) patients in the NACT+CCRT group and 66 (90.4%) patients in the CCRT group completed the expected treatment course. The complete response (CR) rate in the NACT+CCRT group was significantly higher than in the CCRT group (87.7% vs. 67.6%, χ²=54.540, p=0.000). In the NACT+CCRT group, the 1- and 2-year overall survival (OS) rates were significantly higher than those in the CCRT group (96% vs. 89% and 89% vs. 79%, χ²=5.737, p=0.017). Additionally, the rate of recurrences and distant metastases was significantly lower in the NACT+CCRT group than in the CCRT group (4.11% vs. 7.35%, χ²=4.059, p=0.021). Most treatment-related adverse events in both groups were grade 3. CONCLUSION Compared to CCRT, NACT+CCRT might improve the treatment completion rate, increase CR rate and 1- and 2-year OS rates, and reduce distant metastases rate for LACC patients with large tumor masses.
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Affiliation(s)
- Fenghu Li
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
| | - Fan Mei
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
| | - Shuishui Yin
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
| | - Yanjun Du
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
| | - Lili Hu
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
| | - Wei Hong
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
| | - Jiehui Li
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China.
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Chen H, Zhong Q, Liu Y, Li J, Deng W, Wang J, Zhou S, Yu Z, Huang X, Huang Y, Zhen B, Wei J, Zhang W, Ruan X, Xiao L. A prospective single-arm study on the relationship between dose-volume parameters of pelvic functional bone marrow and acute hematological toxicities during intensity-modulated radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer. Radiat Oncol 2023; 18:193. [PMID: 38012675 PMCID: PMC10683159 DOI: 10.1186/s13014-023-02380-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 11/17/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM1 (strongest hemopoietic ability region)and FBM2 (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer. METHODS From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM1/2. RESULTS The incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia in patients during radiotherapy was 63.9%, 45.4%, 19.6% and 38.8% respectively, and the median occurrence time was the 29th, 42th, 35th and 31th day, respectively. Multivariate regression analysis showed that the Dmax of FBM1 was significantly related to grade ≥ 2 leukopenia (OR = 1.277 95% CI 1.067-1.528, P = 0.008), Dmean of FBM2 was significantly related to grade ≥ 2 thrombocytopenia (OR = 1.262 95% CI 1.066-1.494, P = 0.007), and V10 of FBM1 was significantly related to grade ≥ 2 anemia (OR = 1.198 95% CI 1.003-1.431, P = 0.046). The incidence of grade ≥ 2 leukopenia for patients with FBM1 Dmax < 53 Gy was lower than that for patients with FBM1 Dmax ≥ 53 Gy (53.4% vs. 95.8%, P < 0.001). The incidence of grade ≥ 2 thrombocytopenia in patients with FBM2 Dmean < 33 Gy was lower than that in patients with FBM2 Dmean ≥ 33 Gy (0 vs. 28.4%, P < 0.001). The incidence of grade ≥ 2 anemia for patients with FBM1 V10 < 95% was lower than that in patients with FBM1 V10 ≥ 95% (24.4% vs. 57.1%, P = 0.003). CONCLUSIONS Grade ≥ 2 HT usually occurs in the 4th week of radiotherapy for patients with uterine cervical/endometrial cancer. The Dmax and V10 of FBM1 and the Dmean of FBM2 were significantly associated with the occurrence of grade ≥ 2 HT. The recommended optimal dose constraints were FBM1 Dmax < 53 Gy, V10 < 95%, and FBM2 Dmean <33 Gy.
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Affiliation(s)
- Hongbo Chen
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Qian Zhong
- Department of Gynecology, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Yujie Liu
- Department of Oncology Unit II, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Jinyan Li
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Wenjing Deng
- Department of Oncology Unit III, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Jie Wang
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Shuquan Zhou
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Zengrong Yu
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Xianzhan Huang
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
- Department of Oncology, The First People's Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan Province, China
| | - Yuanqiong Huang
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Bo Zhen
- Department of Gynecology, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Jihong Wei
- Department of Gynecology, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Weijian Zhang
- Department of Gynecology, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China
| | - Xiaohong Ruan
- Department of Gynecology, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China.
| | - Lin Xiao
- Department of Radiotherapy Center, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China.
- Department of Oncology Unit II, Jiangmen Central Hospital, Jiangmen, Guangdong Province, China.
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Padhi S, Mahapatra BR, Pati KC, Sahoo B, Kanungo S, Mishra T, Muraleedharan A. Comparison of Acute Gastrointestinal Toxicity of Intensity-Modulated Radiotherapy Versus Three-Dimensional Conformal Radiotherapy in Patients of Carcinoma Cervix. Cureus 2023; 15:e48876. [PMID: 38106724 PMCID: PMC10724709 DOI: 10.7759/cureus.48876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/15/2023] [Indexed: 12/19/2023] Open
Abstract
Introduction Cervical cancer is the most common gynaecological malignancy worldwide, with a higher prevalence in middle- and low-income countries. Chemoradiotherapy, followed by intracavitary brachytherapy, is the treatment of choice in locally advanced cervical cancer. The most common acute side effect of external beam radiotherapy (EBRT) is bowel toxicity in the form of diarrhoea and abdominal cramps. The treatment techniques of EBRT were revolutionised with the advent of intensity modulation. This study aims to prospectively analyse whether the dosimetric advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3DCRT) is translated clinically into a decrease in acute toxicity. Method Twenty-four patients were randomised into two groups: the 3DCRT and the IMRT. Acute gastrointestinal (GI) toxicity was assessed during treatment using radiation therapy oncology group grading. The factors under consideration were age, stage of the disease, treatment technique, chemotherapy, and the intention of therapy (radical or adjuvant). The mean bowel bag dose of the two techniques was analysed. Result Among the factors under consideration, it was found that the treatment technique was the only factor that had a significant association with acute bowel toxicity in both univariate (p = 0.036) and multivariate analyses (p = 0.028). The mean V25 (the volume receiving 25 Gy), V45, and V50 of the bowel bag in the IMRT arm were significantly less than the 3DCRT arm. Grades 2 and 3 acute bowel toxicities were also higher in the 3DCRT arm. Conclusion The treatment technique is essential to determining acute GI toxicity during pelvic radiotherapy. With IMRT, the dose to the bowel bag and, in turn, the acute bowel toxicity can be reduced.
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Affiliation(s)
- Sanjukta Padhi
- Radiation Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, IND
| | | | | | - Bijayalaxmi Sahoo
- Radiation Oncology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Satyabrata Kanungo
- Radiation Oncology, Postgraduate Institute of Medical Education & Research (PGIMER) and Capital Hospital, Bhubaneswar, IND
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