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Roth O'Brien DA, Hristidis VC, Chakrani Z, McCann P, Damato A, Williams V, Cote N, Reyngold M, Rosen R, Connell L, Pappou E, Hajj C, Paty PB, Horvat N, Pernicka JSG, Fiasconaro M, Shia J, Lisanti J, Wu AJ, Gollub MJ, Zhang Z, Yaeger R, Zinovoy M, Weiser MR, Saltz L, Cuaron J, Boe L, Cercek A, Garcia-Aguilar J, Smith JJ, Crane CH, Romesser PB. Clinical Outcomes, Patterns of Failure, and Salvage Therapies of a Large Modern Cohort of Patients With Anal Squamous Cell Carcinoma Treated With Definitive-Intent Intensity-Modulated Radiation Therapy. Int J Radiat Oncol Biol Phys 2025; 121:951-962. [PMID: 39536799 DOI: 10.1016/j.ijrobp.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 09/17/2024] [Accepted: 10/06/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE Patterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy are not well described. METHODS AND MATERIALS We identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure [LRF], distant failure, progression-free survival, colostomy-free survival, and overall survival [OS]), patterns of failure, and salvage therapies were collected. Failures were analyzed using competing risk methods, whereas survival endpoints were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months of completing IMRT. RESULTS A total of 375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for the American Joint Committee on Cancer stages 0 to I, II, and III, respectively. Six-year rates of LRF, distant failure, progression-free survival, colostomy-free survival, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse 6-year OS than patients without LRF (44% vs 86%, P < .0001). Approximately 30% of patients who underwent salvage therapy were alive to 10 years after recurrence, compared with none of the patients who were managed with chemotherapy alone or the best supportive care. CONCLUSIONS This large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment.
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Affiliation(s)
- Diana A Roth O'Brien
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vasilis C Hristidis
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Zakaria Chakrani
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Patrick McCann
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Antonio Damato
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vonetta Williams
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Nicolas Cote
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marsha Reyngold
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Roni Rosen
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Louise Connell
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Emmanouil Pappou
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Carla Hajj
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Philip B Paty
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Megan Fiasconaro
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jeanine Lisanti
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Abraham J Wu
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marc J Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Zhigang Zhang
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Rona Yaeger
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Melissa Zinovoy
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Martin R Weiser
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Len Saltz
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - John Cuaron
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Lillian Boe
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Andrea Cercek
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Julio Garcia-Aguilar
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - J Joshua Smith
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Christopher H Crane
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Paul B Romesser
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, New York.
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Mineur L, Vazquez L, Belkacemi M, Toullec C, Bentaleb N, Boustany R, Plat F. Capecitabine/Mitomycin versus 5-Fluorouracil/Mitomycin in Combination with Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy for Anal Cancer. Curr Oncol 2023; 30:8563-8574. [PMID: 37754536 PMCID: PMC10528380 DOI: 10.3390/curroncol30090621] [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: 07/31/2023] [Revised: 09/15/2023] [Accepted: 09/15/2023] [Indexed: 09/28/2023] Open
Abstract
Since EXTRA, a non-randomized phase II trial with 31 patients, explored the use of capecitabine, mitomycin and radiation therapy (RT) in the treatment of localized squamous cell carcinoma of the anal canal (SCCAC), this treatment has been considered as an acceptable alternative to infusional 5-FU. However, the differences in efficacy between capecitabine and 5-FU in chemoradiation therapy (CRT) with simultaneous integrated boost (SIB) radiation therapy (SIB-IMRT) for local SCCAC are not well documented. Patients included in this prospective monocentric cohort study were treated with SIB-RapidArc (a unique RT method treatment for all patients: identical technique, volume and constraints for at-risk organs), mitomycin C and 5-FU each day of RT for 7 weeks (group 1) or capecitabine each day of RT (group 2). Patients treated between July 2009 and August 2017 (group 1) and between November 2012 and April 2018 (group 2) for local SCCAC T2-4 classified as N, M0 or T, N1-3, M0 were included. Primary endpoints were progression-free survival (PFS) and acute toxicities. Results: One hundred forty-seven patients were included, 91 in group 1 and 56 in group 2. The two groups were statistically comparable in terms of sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and TNM. With a median duration of follow-up of 53.5 months, the PFS rate at 3 years was 80% for group 1 and 75% for group 2 (p = 0.32). The 3-year colostomy-free survival rate was 92% for group 1 and 85% for group 2 (p = 0.11). The rate of patients with at least one grade 3 or higher acute toxicity was 35.5% in group 1 and 21.4% in group 2 (p = 0.10), with a trend of fewer acute toxicities with capecitabine. Conclusion: Capecitabine/mitomycin in combination with SIB RapidArc radiation therapy for anal cancer seems as effective as 5-FU-based chemotherapy and is well tolerated with minimal toxicity.
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Affiliation(s)
- Laurent Mineur
- Oncodigestive and Clinical Research Department, Sainte Catherine Institut du Cancer Avignon-Provence, 84918 Avignon, France
| | - Léa Vazquez
- Oncodigestive and Clinical Research Department, Sainte Catherine Institut du Cancer Avignon-Provence, 84918 Avignon, France
| | - Mohamed Belkacemi
- Statistics Department, PRECIS, Nouvelles Technologies, Languedoc Mutualité, 34000 Montpellier, France
| | - Clémence Toullec
- Oncodigestive and Clinical Research Department, Sainte Catherine Institut du Cancer Avignon-Provence, 84918 Avignon, France
| | - Newfel Bentaleb
- Oncodigestive and Clinical Research Department, Sainte Catherine Institut du Cancer Avignon-Provence, 84918 Avignon, France
| | - Rania Boustany
- Oncodigestive and Clinical Research Department, Sainte Catherine Institut du Cancer Avignon-Provence, 84918 Avignon, France
| | - Frederi Plat
- Oncodigestive and Clinical Research Department, Sainte Catherine Institut du Cancer Avignon-Provence, 84918 Avignon, France
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Untiedt S, Rolf D, Scobioala S, Wolters H, Elsayad K, Oertel M, Kittel C, Pascher A, Rijcken E, Ullerich H, Glasbrenner B, Eich HT. Impact of dose escalation on colostomy-free survival and treatment outcome in squamous cell anal carcinoma. Strahlenther Onkol 2023; 199:749-760. [PMID: 36862155 PMCID: PMC10361861 DOI: 10.1007/s00066-023-02056-y] [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: 09/09/2022] [Accepted: 01/29/2023] [Indexed: 03/03/2023]
Abstract
PURPOSE Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer. METHODS Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). RESULTS The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3‑year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3‑year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3‑year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3‑year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067). CONCLUSION Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.
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Affiliation(s)
- Sebastian Untiedt
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany.
| | - Daniel Rolf
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany
| | - Sergiu Scobioala
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany
| | - Heidi Wolters
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany
| | - Khaled Elsayad
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany
| | - Michael Oertel
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany
| | - Christopher Kittel
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany
| | - Andreas Pascher
- Department for General, Visceral and Transplant Surgery, University Hospital Muenster, 48149, Muenster, Germany
| | - Emile Rijcken
- Department for General, Visceral and Transplant Surgery, University Hospital Muenster, 48149, Muenster, Germany
| | - Hansjörg Ullerich
- Department of Medicine B, Gastroenterology, University Hospital Muenster, 48149, Muenster, Germany
| | - Bernhard Glasbrenner
- Department of Medicine B, Gastroenterology, St. Franziskus-Hospital Muenster, 48145, Muenster, Germany
| | - Hans Theodor Eich
- Department of Radiation Oncology, University Hospital Muenster, 48149, Muenster, Germany
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Vendrely V, Lemanski C, Pommier P, LE Malicot K, Saint A, Rivin Del Campo E, Regnault P, Baba-Hamed N, Ronchin P, Crehange G, Tougeron D, Menager-Tabourel E, Diaz O, Hummelsberger M, Minsat M, Drouet F, Larrouy A, Peiffert D, Lievre A, Zasadny X, Hautefeuille V, Mornex F, Lepage C, Quero L. Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE. Radiother Oncol 2023; 183:109542. [PMID: 36813175 DOI: 10.1016/j.radonc.2023.109542] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/02/2023] [Accepted: 02/11/2023] [Indexed: 02/24/2023]
Abstract
INTRODUCTION International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients. METHODS This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. RESULTS Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group. CONCLUSION Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.
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Affiliation(s)
- Véronique Vendrely
- Department of Radiation Oncology, CHU Bordeaux, Bordeaux, France; BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, F-33000, Bordeaux, France.
| | - Claire Lemanski
- Department of Radiation Oncology, Montpellier Cancer Institute (ICM), Montpellier, France
| | | | - Karine LE Malicot
- Fédération Francophone de Cancérologie Digestive, university of Burgundy, Biostatistics, Dijon, France; EPICAD INSERM LNC-UMR 1231, University of Burgundy, Dijon, France
| | - Angélique Saint
- Department of Radiation Oncology, Antoine Lacassagne Cancer Center, Oncology, Nice, France
| | - Eleonor Rivin Del Campo
- Department of Radiation Oncology, Tenon University Hospital, APHP, Sorbonne University, Paris, France
| | | | | | | | - Gilles Crehange
- Radiotherapy department, Georges François Leclerc cancer center, Dijon, France
| | - David Tougeron
- Hepatology and Gastroenterology department, Poitiers University hospital, Poitiers, France
| | | | - Olivia Diaz
- Radiotherapy department, Daniel Hollard Institute, Grenoble, France
| | | | | | | | - Anne Larrouy
- Médical Oncology, Cancer institute, North Paris, France
| | - Didier Peiffert
- Department of radiaton oncology, Lorraine cancer center, Vandoeuvre-Les-Nancy, France
| | - Astrid Lievre
- Gastroenterology Department, Rennes University Hospital, Rennes 1 University, Inserm U1242 COSS (Chemistry Oncogenesis Stress Signaling, Rennes, France
| | - Xavier Zasadny
- Oncology radiotherapy department, Limoges polyclinic François Chenieux, Limoges, France
| | | | | | - Côme Lepage
- Department of hepato-gastroenterology, University hospital of Dijon, Dijon, France
| | - Laurent Quero
- INSERM U1160, Université Paris Cité, Paris, France; Radiotherapy Saint Louis Hospital, APHP, Paris, France
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Theophanous S, Lønne PI, Choudhury A, Berbee M, Dekker A, Dennis K, Dewdney A, Gambacorta MA, Gilbert A, Guren MG, Holloway L, Jadon R, Kochhar R, Mohamed AA, Muirhead R, Parés O, Raszewski L, Roy R, Scarsbrook A, Sebag-Montefiore D, Spezi E, Spindler KLG, van Triest B, Vassiliou V, Malinen E, Wee L, Appelt AL. Development and validation of prognostic models for anal cancer outcomes using distributed learning: protocol for the international multi-centre atomCAT2 study. Diagn Progn Res 2022; 6:14. [PMID: 35922837 PMCID: PMC9351222 DOI: 10.1186/s41512-022-00128-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 06/09/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Anal cancer is a rare cancer with rising incidence. Despite the relatively good outcomes conferred by state-of-the-art chemoradiotherapy, further improving disease control and reducing toxicity has proven challenging. Developing and validating prognostic models using routinely collected data may provide new insights for treatment development and selection. However, due to the rarity of the cancer, it can be difficult to obtain sufficient data, especially from single centres, to develop and validate robust models. Moreover, multi-centre model development is hampered by ethical barriers and data protection regulations that often limit accessibility to patient data. Distributed (or federated) learning allows models to be developed using data from multiple centres without any individual-level patient data leaving the originating centre, therefore preserving patient data privacy. This work builds on the proof-of-concept three-centre atomCAT1 study and describes the protocol for the multi-centre atomCAT2 study, which aims to develop and validate robust prognostic models for three clinically important outcomes in anal cancer following chemoradiotherapy. METHODS This is a retrospective multi-centre cohort study, investigating overall survival, locoregional control and freedom from distant metastasis after primary chemoradiotherapy for anal squamous cell carcinoma. Patient data will be extracted and organised at each participating radiotherapy centre (n = 18). Candidate prognostic factors have been identified through literature review and expert opinion. Summary statistics will be calculated and exchanged between centres prior to modelling. The primary analysis will involve developing and validating Cox proportional hazards models across centres for each outcome through distributed learning. Outcomes at specific timepoints of interest and factor effect estimates will be reported, allowing for outcome prediction for future patients. DISCUSSION The atomCAT2 study will analyse one of the largest available cross-institutional cohorts of patients with anal cancer treated with chemoradiotherapy. The analysis aims to provide information on current international clinical practice outcomes and may aid the personalisation and design of future anal cancer clinical trials through contributing to a better understanding of patient risk stratification.
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Affiliation(s)
- Stelios Theophanous
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
| | - Per-Ivar Lønne
- Department of Medical Physics, Oslo University Hospital, Oslo, Norway
| | - Ananya Choudhury
- MAASTRO (Dept of Radiotherapy), GROW School of Oncology and Developmental Biology, Maastricht University and Maastricht University Medical Centre+, P. Debyelaan 25, 6229, Maastricht, Netherlands
| | - Maaike Berbee
- MAASTRO (Dept of Radiotherapy), GROW School of Oncology and Developmental Biology, Maastricht University and Maastricht University Medical Centre+, P. Debyelaan 25, 6229, Maastricht, Netherlands
| | - Andre Dekker
- MAASTRO (Dept of Radiotherapy), GROW School of Oncology and Developmental Biology, Maastricht University and Maastricht University Medical Centre+, P. Debyelaan 25, 6229, Maastricht, Netherlands
| | | | | | | | - Alexandra Gilbert
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Marianne Grønlie Guren
- Department of Oncology, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Lois Holloway
- Ingham Research Institute and Liverpool Hospital, Liverpool, New South Wales, Australia
| | | | | | | | | | | | | | - Rajarshi Roy
- Hull University Teaching Hospitals NHS Trust, Hull, UK
| | - Andrew Scarsbrook
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | | | | | - Baukelien van Triest
- The Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, The Netherlands
| | | | - Eirik Malinen
- Department of Medical Physics, Oslo University Hospital, Oslo, Norway
| | - Leonard Wee
- MAASTRO (Dept of Radiotherapy), GROW School of Oncology and Developmental Biology, Maastricht University and Maastricht University Medical Centre+, P. Debyelaan 25, 6229, Maastricht, Netherlands
| | - Ane L Appelt
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Mahmood A, Bhuva N, Fokas E, Glynne-Jones R. Compliance to chemoradiation in squamous cell carcinoma of the anus. Cancer Treat Rev 2022; 106:102381. [DOI: 10.1016/j.ctrv.2022.102381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 11/02/2022]
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Peiffert D, Huguet F, Vendrely V, Moureau-Zabotto L, Rivin Del Campo E, Créhange G, Dietmann AS, Moignier A. Radiotherapy of anal canal cancer. Cancer Radiother 2021; 26:279-285. [PMID: 34955416 DOI: 10.1016/j.canrad.2021.11.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
We present the update of the recommendations of the French society for radiation oncology on external radiotherapy and brachytherapy of anal canal carcinoma. The following guidelines are presented: indications, treatment procedure, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up.
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Affiliation(s)
- D Peiffert
- Département de radiothérapie, Institut de cancérologie de Lorraine Alexis-Vautrin, avenue de Bourgogne, 54511 Vandœuvre-lès-Nancy, France.
| | - F Huguet
- Service de radiothérapie, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France
| | - V Vendrely
- Service d'oncologie-radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, avenue de Magellan, 33600 Pessac, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France
| | - L Moureau-Zabotto
- Service de radiothérapie, institut Paoli-Calmettes, 13000 Marseille, France
| | - E Rivin Del Campo
- Service de radiothérapie, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France
| | - G Créhange
- Département d'oncologie radiothérapie, institut Curie, 25, rue d'Ulm, 75005 Paris, France
| | - A-S Dietmann
- Département de radiothérapie, Institut de cancérologie de Lorraine Alexis-Vautrin, avenue de Bourgogne, 54511 Vandœuvre-lès-Nancy, France
| | - A Moignier
- Service de physique médicale, Institut de cancérologie de l'Ouest centre René-Gauducheau, 44805 Saint-Herblain, France
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Miller ED, Nalin AP, Diaz Pardo DA, Arnett AL, Huang E, Gasior AC, Malalur P, Chen HZ, Williams TM, Bazan JG. Disparate Use of Chemoradiation in Elderly Patients With Localized Anal Cancer. J Natl Compr Canc Netw 2021; 20:644-652.e2. [PMID: 34111839 DOI: 10.6004/jnccn.2020.7691] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 11/30/2020] [Indexed: 01/20/2023]
Abstract
BACKGROUND The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly among the elderly (age ≥65 years). We sought to compare patterns of care for the treatment of SCCA in elderly versus nonelderly patients. METHODS Data for patients with stages I-III SCCA diagnosed from 2004 through 2015 were obtained from the National Cancer Database. Patients were categorized as having received standard-of-care (SOC) chemoradiation (CRT) with multiagent chemotherapy, non-SOC therapy, palliative therapy, or no treatment. Differences in treatment groups were tested using the chi-square test. We used logistic regression to identify predictors of SOC CRT and multiagent versus single-agent chemotherapy in patients receiving CRT. Propensity score matching was used to compare overall survival (OS) in elderly patients receiving multiagent versus single-agent chemotherapy for those receiving CRT. RESULTS We identified 9,156 elderly and 17,640 nonelderly patients. A lower proportion of elderly versus nonelderly patients (54.5% vs 65.0%; P<.0001) received SOC CRT than other treatments or no treatment. In multivariate analysis, elderly patients were 38% less likely than nonelderly patients to receive SOC CRT (odds ratio, 0.62; 95% CI, 0.58-0.65; P<.0001). A higher proportion of the elderly were treated with single-agent versus multiagent chemotherapy (16.9% vs 11.8%; P<.0001), which resulted in a >1.5-fold increase in the likelihood of elderly patients receiving single-agent chemotherapy (odds ratio, 1.52; 95% CI, 1.39-1.66) in multivariate analysis. After propensity score matching, 3-year OS was higher in elderly patients who received CRT with multiagent versus single-agent chemotherapy (77.1% vs 67.5%; hazard ratio, 0.78; 95% CI, 0.68-0.89; P=.0002). CONCLUSIONS In this comprehensive study of patients with stages I-III SCCA, elderly patients were less likely than nonelderly patients to receive SOC CRT. The low proportion of elderly patients receiving SOC CRT with multiagent chemotherapy for localized anal cancer suggests that the optimal treatment approach for this vulnerable population remains undefined.
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Affiliation(s)
| | | | | | | | - Emily Huang
- 2Department of Colon and Rectal Surgery, and
| | | | - Pannaga Malalur
- 3Department of Internal Medicine, Division of Medical Oncology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Hui-Zi Chen
- 3Department of Internal Medicine, Division of Medical Oncology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
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Talwar G, Daniel R, McKechnie T, Levine O, Eskicioglu C. Radiotherapy alone versus chemoradiotherapy for stage I anal squamous cell carcinoma: a systematic review and meta-analysis. Int J Colorectal Dis 2021; 36:1111-1122. [PMID: 33486535 DOI: 10.1007/s00384-021-03846-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/13/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Patients with stage I anal squamous cell carcinoma (SCC) have been underrepresented in landmark trials showing superiority of chemoradiotherapy over radiotherapy for definitive treatment. This review aims to elucidate whether definitive treatment with radiotherapy versus chemoradiotherapy is associated with differences in survival and treatment-related toxicity outcomes in patients with stage I anal SCC. METHODS Medline, EMBASE, and CENTRAL were searched as of November 2020 to identify studies comparing outcomes of radiotherapy versus chemoradiotherapy for non-operative treatment of patients with stage I anal SCC. The primary outcomes were 5-year overall survival and 5-year disease-free survival. The secondary outcome was treatment-related toxicities. A pairwise meta-analysis was performed using an inverse-variance random-effects model. RESULTS From 2174 citations, 5 retrospective studies with 415 patients treated with radiotherapy and 3784 patients treated with chemoradiotherapy were included. Patients treated with chemoradiotherapy had an increased 5-year overall survival (RR 1.18, 95% CI 1.10-1.26, p < 0.00001, I2 = 0%) but no significant difference in 5-year disease-free survival (RR 1.01, 95% CI 0.92-1.11, p = 0.87, I2 = 0%). Treatment-related toxicities could not be meta-analyzed due to heterogeneity. Limited data from individual studies suggested an increased frequency of select toxicities with chemoradiotherapy. CONCLUSION Radiotherapy may be an appropriate alternative to chemoradiotherapy for patients with stage I anal SCC who may be unable to tolerate chemotherapy-related toxicity; however, chemoradiotherapy remains the gold standard. Larger prospective studies comparing strategies for this select patient population are needed to clarify whether treatment can be de-escalated.
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Affiliation(s)
- Gaurav Talwar
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Ryan Daniel
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Tyler McKechnie
- Department of Surgery, Division of General Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Oren Levine
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Oncology, Division of Medical Oncology, McMaster University, Hamilton, Ontario, Canada
| | - Cagla Eskicioglu
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. .,Department of Surgery, Division of General Surgery, McMaster University, Hamilton, Ontario, Canada. .,Department of Surgery, Division of General Surgery, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario, Canada.
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10
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Possiel J, Ammon HE, Guhlich M, Conradi LC, Ghadimi M, Wolff HA, Schirmer MA, Samel S, Mügge M, Rieken S, Leu M, Dröge LH. Volumetric Modulated Arc Therapy Improves Outcomes in Definitive Radiochemotherapy for Anal Cancer Whilst Reducing Acute Toxicities and Increasing Treatment Compliance. Cancers (Basel) 2021; 13:cancers13112533. [PMID: 34064061 PMCID: PMC8196749 DOI: 10.3390/cancers13112533] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/16/2021] [Accepted: 05/19/2021] [Indexed: 01/13/2023] Open
Abstract
Simple Summary Intensity-modulated radiotherapy (IMRT) is the standard of care in definitive chemoradiotherapy (CRT) for anal cancer. Only a limited number of studies have analyzed the clinical results with VMAT (volumetric modulated arc therapy, the advanced form of IMRT). We conducted a retrospective study on patients treated at our institution. We compared the outcomes of VMAT-treated and 3DCRT (3D conformal radiotherapy)-treated patients. VMAT reduced acute toxicities (i.e., primarily dermatitis and enteritis) to a great extent. Additionally, VMAT relevantly improved treatment compliance (i.e., less CRT interruptions/delays, shorter overall treatment time, and higher absolute 5-fluorouracil dose applied). Finally, we found improved cancer-specific survival and distant control in VMAT-treated patients. The present study underlines the great progress that has been achieved with IMRT/VMAT in the CRT of anal cancer. Our study is the first to demonstrate an improvement in treatment compliance and outcomes with VMAT. Future studies could address whether VMAT is advantageous when compared to conventional IMRT. Abstract Background: Intensity-modulated radiotherapy (IMRT) is the standard of care in chemoradiotherapy (CRT) for anal cancer. Until now, only a limited number of studies have analyzed the results with VMAT (volumetric modulated arc therapy). We conducted a retrospective study on patients treated at our institution. Patients and Methods: We included patients who received curative CRT for anal cancer. We compared VMAT-treated and 3DCRT (3D conformal radiotherapy)-treated patients. We analyzed toxicities (acute: CTCAE criteria; late: LENT/SOMA criteria), treatment compliance, overall survival, cancer-specific survival (CSS), distant control (DC), and locoregional control. Results: A total of 149 patients (3DCRT: n = 87, VMAT: n = 62) were included. The median follow-up was longer in 3DCRT-treated patients (3DCRT: 61.3 months; VMAT: 39.1 months; p < 0.05). VMAT-treated patients had more G3 tumors (3DCRT: 12/87 (13.8%); VMAT: 18/62 (29.0%), p < 0.001). VMAT reduced acute toxicities ≥grade 3 (3DCRT: n = 48/87 (55.2%); VMAT: n = 11/62 (17.7%), p < 0.001). VMAT improved treatment compliance (less interruptions/delays) (3DCRT: 37/87, 42.5%; VMAT: 4/62, 6.5%; p < 0.001), provided a shorter median overall treatment time (3DCRT: 41 days; VMAT: 38 days; p = 0.02), and gave a higher median absolute 5-fluorouracil dose (3DCRT: 13,700 mg; VMAT: 14,400 mg; p = 0.001). Finally, we found improved CSS (p = 0.02; 3DCRT: 81.9% at 3 years; VMAT: 94.1% at 3 years) and DC (p = 0.01; 3DCRT: 89.4% at 3 years; VMAT: 100.0% at 3 years) with VMAT. Summary: Our study is the first to demonstrate improved treatment compliance and outcomes with VMAT for anal cancer. Previous studies have indicated that organs at risk sparing might be more improved with the use of VMAT vs. with conventional IMRT. Future studies should address whether these advantages lead to a further reduction in CRT-associated morbidity.
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Affiliation(s)
- Jacqueline Possiel
- Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; (J.P.); (H.E.A.); (M.G.); (M.A.S.); (S.R.); (M.L.)
| | - Hanne Elisabeth Ammon
- Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; (J.P.); (H.E.A.); (M.G.); (M.A.S.); (S.R.); (M.L.)
| | - Manuel Guhlich
- Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; (J.P.); (H.E.A.); (M.G.); (M.A.S.); (S.R.); (M.L.)
| | - Lena-Christin Conradi
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany; (L.-C.C.); (M.G.)
| | - Michael Ghadimi
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany; (L.-C.C.); (M.G.)
| | - Hendrik Andreas Wolff
- University Medical Center Göttingen, 37075 Göttingen, Germany;
- Department of Radiology, Nuclear Medicine and Radiotherapy, Radiology Munich, 80333 Munich, Germany
- Department of Radiotherapy and Radiation Oncology, University Medical Center Regensburg, 93053 Regensburg, Germany
| | - Markus Anton Schirmer
- Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; (J.P.); (H.E.A.); (M.G.); (M.A.S.); (S.R.); (M.L.)
| | - Stephan Samel
- Praxis für Koloproktologie und chirurgische Endoskopie, Waldweg 1, 37073 Göttingen, Germany; (S.S.); (M.M.)
| | - Michael Mügge
- Praxis für Koloproktologie und chirurgische Endoskopie, Waldweg 1, 37073 Göttingen, Germany; (S.S.); (M.M.)
| | - Stefan Rieken
- Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; (J.P.); (H.E.A.); (M.G.); (M.A.S.); (S.R.); (M.L.)
| | - Martin Leu
- Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; (J.P.); (H.E.A.); (M.G.); (M.A.S.); (S.R.); (M.L.)
| | - Leif Hendrik Dröge
- Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; (J.P.); (H.E.A.); (M.G.); (M.A.S.); (S.R.); (M.L.)
- Correspondence: ; Tel.: +49-551-398-866
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11
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De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus. Cancers (Basel) 2021; 13:cancers13092099. [PMID: 33925282 PMCID: PMC8123637 DOI: 10.3390/cancers13092099] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 04/22/2021] [Accepted: 04/25/2021] [Indexed: 12/25/2022] Open
Abstract
Simple Summary Management of early-stage squamous cell carcinoma of the anus (SCCA) remains controversial. The current standard of care treatment of chemotherapy combined with radiation therapy can result in both acute and late toxicity. Alternative therapies, including radiation therapy alone or local excision, may be less toxic, but the role of these therapies in early-stage SCCA remains unclear. Additional options for reducing the intensity of therapy for early-stage SCCA include reduction of radiation dose, altering treatment volumes, modifying chemotherapy type and dosage, and using intensity-modulated radiation therapy to reduce the radiation dose to adjacent normal tissues. Multiple prospective studies are actively investigating the role of de-escalation of therapy in patients with early-stage SCCA. Abstract The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.
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Dee EC, Byrne JD, Wo JY. Evolution of the Role of Radiotherapy for Anal Cancer. Cancers (Basel) 2021; 13:1208. [PMID: 33801992 PMCID: PMC8001637 DOI: 10.3390/cancers13061208] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/05/2021] [Accepted: 03/06/2021] [Indexed: 12/11/2022] Open
Abstract
Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy's role in locally persistent or recurrent anal cancer.
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Affiliation(s)
| | - James D. Byrne
- Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA 02115, USA;
| | - Jennifer Y. Wo
- Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA;
- Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom St., Boston, MA 02114, USA
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13
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Susko MS, Lazar AA, Wang CCJ, Van Loon K, Feng M, Hope TA, Behr S, Anwar M. Use of advanced PET-volume metrics predicts risk of local recurrence and overall survival in anal cancer. PLoS One 2021; 16:e0246535. [PMID: 33539412 PMCID: PMC7861457 DOI: 10.1371/journal.pone.0246535] [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: 11/11/2020] [Accepted: 01/20/2021] [Indexed: 11/24/2022] Open
Abstract
Objective Anal cancer is an uncommon malignancy with the primary treatment for localized disease being concurrent radiation and chemotherapy. Pre-treatment PET/CT is useful for target delineation, with minimal exploration of its use in prognostication. In the post-treatment setting there is growing evidence for advanced PET metrics in assessment of treatment response, and early identification of recurrence essential for successful salvage, however this data is limited to small series. Methods Patient with non-metastatic anal cancer from a single institution were retrospectively reviewed for receipt of pre- and post-treatment PET/CTs. PET data was co-registered with radiation therapy planning CT scans for precise longitudinal assessment of advanced PET metrics including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), for assessment with treatment outcomes. Treatment outcomes included local recurrence (LR), progression free survival (PFS), and overall survival (OS), as defined from the completed radiation therapy to the time of the event. Cox proportional hazard modeling with inverse probability weighting (IPW) using the propensity score based on age, BMI, T-stage, and radiation therapy dose were utilized for assessment of these metrics. Results From 2008 to 2017 there were 72 patients who had pre-treatment PET/CT, 61 (85%) had a single follow up PET/CT, and 35 (49%) had two follow up PET/CTs. The median clinical follow-up time was 25 months (IQR: 13–52) with a median imaging follow up time of 16 months (IQR: 7–29). On pre-treatment PET/CT higher MTV2.5 and TLG were significantly associated with higher risk of local recurrence (HR 1.11, 95% CI: 1.06–1.16, p<0.001; and HR 1.12, 95% CI: 1.05–1.19, p<0.001), and worse PFS (HR 1.09, 95% CI: 1.04–1.13, p<0.001; and HR 1.09, 95% CI: 1.03–1.12, p = 0.003) and OS (HR 1.09, 95% CI: 1.04–1.16, p = 0.001; and HR 1.11, 95% CI: 1.04–1.20, p = 0.004). IPW-adjusted pre-treatment PET/CT showed higher MTV2.5 (HR 1.09, 95% CI: 1.02–1.17, p = 0.012) and TLG (HR 1.10, 95% CI: 1.00–1.20, p = 0.048) were significantly associated with worse PFS, and post-treatment MTV2.5 was borderline significant (HR 1.16, 95% CI: 1.00–1.35, p = 0.052). Conclusion Advanced PET metrics, including higher MTV2.5 and TLG, in the pre-treatment and post-treatment setting are significantly associated with elevated rates of local recurrence, and worse PFS and OS. This adds to the growing body of literature that PET/CT for patient with ASCC should be considered for prognostication, and additionally is a useful tool for consideration of early salvage or clinical trial of adjuvant therapies.
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Affiliation(s)
- Matthew S. Susko
- Department of Radiation Oncology, University of California, San Francisco, California, United States of America
- * E-mail:
| | - Ann A. Lazar
- Department of Radiation Oncology, University of California, San Francisco, California, United States of America
| | - Chia-Ching Jackie Wang
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, United States of America
- Zuckerberg San Francisco General Hospital–Medical Oncology, University of California, San Francisco, California, United States of America
| | - Katherine Van Loon
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, United States of America
| | - Mary Feng
- Department of Radiation Oncology, University of California, San Francisco, California, United States of America
| | - Tom A. Hope
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America
| | - Spencer Behr
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America
| | - Mekhail Anwar
- Department of Radiation Oncology, University of California, San Francisco, California, United States of America
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Slim N, Passoni P, Incerti E, Tummineri R, Gumina C, Cattaneo GM, De Nardi P, Canevari C, Fiorino C, Ronzoni M, Tamburini AM, Burgio V, Gianolli L, Di Muzio N. Impact of sentinel lymph-node biopsy and FDG-PET in staging and radiation treatment of anal cancer patients. Sci Rep 2020; 10:14613. [PMID: 32884036 PMCID: PMC7471696 DOI: 10.1038/s41598-020-71577-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 07/23/2020] [Indexed: 11/09/2022] Open
Abstract
To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39-89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6-136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1-G2: 50% vs. 12%; G3-G4: 17% vs. 0%, p < 0.05). For patients treated on groin, G3-G4 inguinal dermatitis, stomatitis and neutropenia were significantly reduced with IMRT against 3DCRT techniques (13% vs. 36%, p = 0.10; 3% vs. 36%, p = 0.003; 8% vs. 29%, p = 0.02, respectively). SLNB improves the FDG-PET inguinal LNs staging in guiding the decision to treat inguinal nodes. IMRT technique significantly reduced G3-G4 toxicities when patients are treated on groin.
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Affiliation(s)
- Najla Slim
- Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Passoni
- Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Elena Incerti
- Unit of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Calogero Gumina
- Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Paola De Nardi
- Unit of Gastroenterology Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carla Canevari
- Unit of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Fiorino
- Unit of Medical Physics, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Monica Ronzoni
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Valentina Burgio
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luigi Gianolli
- Unit of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Nadia Di Muzio
- Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Dell'Acqua V, Surgo A, Arculeo S, Zerella MA, Bagnardi V, Frassoni S, Zampino MG, Ravenda PS, Rotundo MS, Kraja F, Kobiela J, Spychalski P, Fodor C, Gerardi MA, Cattani F, Bazani A, Petz W, Glynne-Jones R, Orecchia R, Leonardi MC, Jereczek-Fossa BA. Intensity-modulated radiotherapy (IMRT) in the treatment of squamous cell anal canal cancer: acute and early-late toxicity, outcome, and efficacy. Int J Colorectal Dis 2020; 35:685-694. [PMID: 32036405 DOI: 10.1007/s00384-020-03517-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/26/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12 months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response. METHODS Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1. RESULTS Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89-99) at 6 months and 92% (95% CI 83-96) at 12 months. At 6 months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12 months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD. CONCLUSION Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11.
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Affiliation(s)
- Veronica Dell'Acqua
- Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | - Alessia Surgo
- Radiation Oncology Department, General Regional Hospital "F. Miulli", Acquaviva delle Fonti, Italy
| | - Simona Arculeo
- Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy
| | - Maria Alessia Zerella
- Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy.
- Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy.
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
| | - Samuele Frassoni
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
| | - Maria Giulia Zampino
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy
| | - Paola Simona Ravenda
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy
| | - Maria Saveria Rotundo
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy
| | - Fatjona Kraja
- Division of Oncology, University Hospital Centre "Mother Theresa", Rruga e Dibrës 372, 1000, Tirana, AL, Albania
| | - Jarek Kobiela
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, 80-210, Gdańsk, Poland
| | - Piotr Spychalski
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, 80-210, Gdańsk, Poland
| | - Cristiana Fodor
- Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | | | - Federica Cattani
- Unit of Medical Physics, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | - Alessia Bazani
- Unit of Medical Physics, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | - Wanda Petz
- Division of Gastrointestinal Surgery, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | | | - Roberto Orecchia
- Scientific Directorate, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | - Maria Cristina Leonardi
- Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | - Barbara Alicja Jereczek-Fossa
- Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy
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Farris MK, Helis CA, Hughes RT, LeCompte MC, Borg AM, Nieto K, Munley MT, Willey JS. Bench to Bedside: Animal Models of Radiation Induced Musculoskeletal Toxicity. Cancers (Basel) 2020; 12:cancers12020427. [PMID: 32059447 PMCID: PMC7073177 DOI: 10.3390/cancers12020427] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 02/04/2020] [Accepted: 02/05/2020] [Indexed: 12/29/2022] Open
Abstract
Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. Radiation therapy (RT)-induced bone loss leading to fracture is a source of substantial morbidity. The mechanisms of RT likely involve multiple pathways, including changes in angiogenesis and bone vasculature, osteoblast damage/suppression, and increased osteoclast activity. The majority of bone loss appears to occur rapidly after exposure to ionizing RT, with significant changes in cortical thickness being detectable on computed tomography (CT) within three to four months. Additionally, there is a dose–response relationship. Cortical thinning is especially notable in areas of bone that receive >40 gray (Gy). Methods to mitigate toxicity due to RT-induced bone loss is an area of active investigation. There is an accruing clinical trial investigating the use of risderonate, a bisphosphonate, to prevent rib bone loss in patients undergoing lung stereotactic body radiation therapy (SBRT). Additionally, several other promising therapeutic/preventative approaches are being explored in preclinical studies, including parathyroid hormone (PTH), amifostine, and mechanical loading of irradiated bones.
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Hunter AJ, Hendrikse AS. Estimation of the effects of radiotherapy treatment delays on tumour responses: A review. SOUTH AFRICAN JOURNAL OF ONCOLOGY 2020. [DOI: 10.4102/sajo.v4i0.91] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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18
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Sauter M, Lombriser N, Bütikofer S, Keilholz G, Kranzbühler H, Heinrich H, Rogler G, Vavricka SR, Misselwitz B. Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer. Strahlenther Onkol 2020; 196:356-367. [PMID: 31980834 DOI: 10.1007/s00066-019-01534-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 10/17/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Radiochemotherapy is the standard treatment for anal carcinoma (ACa). Intensity-modulated radiotherapy (IMRT) has been introduced, allowing focused irradiation of the tumor area. Whether physical benefits of IMRT translate to clinical benefits has not been sufficiently demonstrated. METHODS We retrospectively reviewed data from 82 patients with newly diagnosed ACa. Patients treated with IMRT were compared with previous patients treated with conventional three-dimensional computational radiotherapy (3D-CRT). The influence of IMRT on complete remission and acute and chronic side effects was analyzed in univariate and multivariate analyses. RESULTS 39/40 patients treated with IMRT were in complete remission after 1 year compared to 31/39 patients treated with 3D-CRT (p = 0.014). Multivariate analysis confirmed tumor T stage as well as lack of IMRT treatment as risk factors for persistent tumor at 6 months. No significant benefits of IMRT were apparent at later timepoints (median follow up 52 months, IQR: 31.5-71.8 months). Patients treated with IMRT had a significantly lower degree of skin toxicity (median 2 vs. 3 in a scale ranging from 0 to 3, p = 0.00092). Rates of hematological toxicity/proctitis were not reduced and rates of acute diarrhea increased (p = 0.034). Median length of hospitalization tended to be shorter in patients treated with IMRT (n. s.). CONCLUSION We present a real-world experience of shifting radiation technique from conventional 3D-CRT to IMRT. IMRT patients had better tumor control at 1 year and lower degrees of skin toxicity. Our data indicate that IMRT can enable therapies with lower side effects with equal or better oncological results for patients with ACa.
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Affiliation(s)
- Matthias Sauter
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland. .,University Center for Gastrointestinal and Liver Diseases, Clarunis, Basel, Switzerland. .,Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland.
| | | | - Simon Bütikofer
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland
| | - Georg Keilholz
- Division of Radio-Oncology, Triemli Hospital, Zurich, Switzerland
| | | | - Henriette Heinrich
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.,Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland
| | - Stephan R Vavricka
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.,University Center for Gastrointestinal and Liver Diseases, Clarunis, Basel, Switzerland
| | - Benjamin Misselwitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.,Department of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland
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19
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de Meric de Bellefon M, Lemanski C, Castan F, Samalin E, Mazard T, Lenglet A, Demontoy S, Riou O, Llacer-Moscardo C, Fenoglietto P, Aillères N, Thezenas S, Debrigode C, Vieillot S, Gourgou S, Azria D. Long-term follow-up experience in anal canal cancer treated with Intensity-Modulated Radiation Therapy: Clinical outcomes, patterns of relapse and predictors of failure. Radiother Oncol 2019; 144:141-147. [PMID: 31809980 DOI: 10.1016/j.radonc.2019.11.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 11/02/2019] [Accepted: 11/14/2019] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND PURPOSE To assess the long-term outcomes of patients with squamous cell carcinoma of the anal canal (SCCAC) treated with Intensity-Modulated Radiation Therapy (IMRT). MATERIAL AND METHODS From 2007 to 2015, 193 patients were treated by IMRT for SCCAC. Radiotherapy delivered 45 Gy in 1.8 Gy daily-fractions to the primary tumor and elective nodal areas, immediately followed by a boost of 14.4-20 Gy to the primary tumor and involved nodes. Concurrent chemotherapy with 5-FU-mitomycin (MMC) or cisplatin was added for locally advanced tumors. Survivals were estimated by Kaplan-Meier method. Locoregional (LR) relapses were precisely assessed. Prognostic factors were evaluated by uni- and multivariate analyses. Late toxicity was scored according to the Common Toxicity Criteria for Adverse Events v4.0. RESULTS Median follow-up was 70 months (range, 1-131). Forty-nine men (25%) and 144 women (75%) were analyzed. Median age was 62 years. Tumor stages were I, II, III and IV in 7%, 24%, 63% and 6% of cases, respectively. Chemotherapy was delivered in 167 patients (87%), mainly MMC (80%). Five-year OS, DFS, CFS and LR control rates were 74%, 68%, 66% and 85%, respectively. Forty-one patients (21%) had a relapse: 22 were LR, mostly in-field (68%). Predictors for LR failure were exclusive radiotherapy, chemotherapy lacking MMC and treatment breaks >3 days. Overall late toxicity ≥grade 2 occurred in 43% of patients, with 24% grade 3 and one case of grade 4 (hematuria). CONCLUSION CRT with IMRT assures excellent local control in locally advanced SCCAC with manageable long-term toxicity. Multicentric prospective trials are required to reinforce those results.
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Affiliation(s)
- Maïlys de Meric de Bellefon
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France.
| | - Claire Lemanski
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Florence Castan
- Biometrics Unit ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Emmanuelle Samalin
- Department of Medical Oncology, ICM, Montpellier Cancer Institute - University of Montpellier, INSERM U1194, IRCM, France
| | - Thibault Mazard
- Department of Medical Oncology, ICM, Montpellier Cancer Institute - University of Montpellier, INSERM U1194, IRCM, France
| | - Alexis Lenglet
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Sylvain Demontoy
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Olivier Riou
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Carmen Llacer-Moscardo
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Pascal Fenoglietto
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Norbert Aillères
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Simon Thezenas
- Biometrics Unit ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - Charles Debrigode
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, CHU Nîmes, France
| | - Sabine Vieillot
- Department of Radiation Oncology, Catalan Oncology Center, Perpignan, France
| | - Sophie Gourgou
- Biometrics Unit ICM, Montpellier Cancer Institute - University of Montpellier, France
| | - David Azria
- Department of Radiation Oncology, University Federation of Radiation Oncology Montpellier-Nîmes, ICM, Montpellier Cancer Institute - University of Montpellier, France
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20
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Russo S, Anker CJ, Abdel-Wahab M, Azad N, Bianchi N, Das P, Dragovic J, Goodman KA, Jones W, Kennedy T, Kumar R, Lee P, Sharma N, Small W, Suh WW, Jabbour SK. Executive Summary of the American Radium Society Appropriate Use Criteria for Treatment of Anal Cancer. Int J Radiat Oncol Biol Phys 2019; 105:591-605. [PMID: 31288054 PMCID: PMC11101015 DOI: 10.1016/j.ijrobp.2019.06.2544] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 06/10/2019] [Accepted: 06/11/2019] [Indexed: 10/26/2022]
Affiliation(s)
- Suzanne Russo
- Case Western Reserve University School of Medicine and University Hospitals, Cleveland Ohio
| | | | - May Abdel-Wahab
- International Atomic Energy Agency, Division of Human Health, New York City, New York
| | - Nilofer Azad
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nancy Bianchi
- University of Vermont Cancer Center, Burlington, Vermont
| | - Prajnan Das
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | | | - William Jones
- UT Health Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | | | - Rachit Kumar
- Banner MD Anderson Cancer Center, Gilbert, Arizona
| | - Percy Lee
- University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California
| | - Navesh Sharma
- Milton S. Hershey Cancer Institute, Hershey, Pennsylvania
| | | | - W Warren Suh
- Ridley-Tree Cancer Center, Sansum Clinic, Santa Barbara, California
| | - Salma K Jabbour
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
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21
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Rivin Del Campo E, Matzinger O, Haustermans K, Peiffert D, Glynne-Jones R, Winter KA, Konski AA, Ajani JA, Bosset JF, Hannoun-Levi JM, Puyraveau M, Chakravarthy AB, Meadows H, Northover J, Collette L, Christiaens M, Maingon P. Pooled Analysis of external-beam RADiotherapy parameters in phase II and phase III trials in radiochemotherapy in Anal Cancer (PARADAC). Eur J Cancer 2019; 121:130-143. [PMID: 31574418 PMCID: PMC6924923 DOI: 10.1016/j.ejca.2019.08.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 08/16/2019] [Accepted: 08/24/2019] [Indexed: 10/25/2022]
Abstract
PURPOSE Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer. MATERIALS AND METHODS Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up). RESULTS After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p < 0.001) and male gender (p = 0.045). Although significant differences were not observed, subset analyses for LRF (dose range: 50.4-59 Gy) seemed to favour lower doses (p = 0.412), and when comparing a 2-week gap versus 3 (dose: 59.4 Gy), results suggested 3 weeks might be detrimental (p = 0.245). For a 2-week gap versus none (dose range: 55-59.4 Gy), no difference was observed (p = 0.89). Five-year PFS was 65.7% (95% CI: 62.8-68.5%). Higher PFS rates were observed in women (p < 0.001), smaller tumour sizes (p < 0.001) and shorter OTT (p = 0.025). Five-year overall survival [76.7% (95% CI: 73.9%-79.3%)] correlated positively with female gender (p < 0.001), small tumour size (p = 0.027) and short OTT (p = 0.026). Descriptive toxicity data are presented. CONCLUSION For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome. Further trials involving modern techniques may better define optimal OTT and total dose.
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Affiliation(s)
- Eleonor Rivin Del Campo
- Department of Radiation Oncology, Tenon University Hospital, Sorbonne University, Paris, France.
| | - Oscar Matzinger
- Department of Radiation Oncology, Genolier Clinic, Genolier, Switzerland
| | - Karin Haustermans
- Department of Radiation Oncology, UZ Leuven University Hospital, Leuven, Belgium
| | - Didier Peiffert
- Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy, France
| | - Robert Glynne-Jones
- Department of Radiation Oncology, Mount Vernon Cancer Centre, Northwood, United Kingdom
| | - Kathryn A Winter
- NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA, USA
| | - Andre A Konski
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Leonard Davis Institute of Health Economics, West Chester, PA, USA; Department of Radiation Oncology, The Chester County Hospital, West Chester, PA, USA
| | - Jaffer A Ajani
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-François Bosset
- Department of Radiation Oncology, Jean Minjoz University Hospital, Besançon, France
| | | | - Marc Puyraveau
- Department of Statistics, Jean Minjoz University Hospital, Besançon, France
| | - A Bapsi Chakravarthy
- Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Helen Meadows
- Cancer Research UK & UCL Cancer Trials Centre, London, United Kingdom
| | - John Northover
- Department of Surgery, The London Clinic and St Marks Hospital, London, United Kingdom
| | | | - Melissa Christiaens
- Department of Radiation Oncology, UZ Leuven University Hospital, Leuven, Belgium
| | - Philippe Maingon
- Department of Radiation Oncology, La Pitié Salpêtrière - Charles Foix University Hospital, Sorbonne University, Paris, France
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22
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Peiffert D. [Anal channel cancer: customization of dose, volume and breaching]. Cancer Radiother 2019; 23:773-777. [PMID: 31471250 DOI: 10.1016/j.canrad.2019.07.138] [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: 07/04/2019] [Accepted: 07/16/2019] [Indexed: 10/26/2022]
Abstract
The conservative treatment of squamous cell carcinoma of anal canal by irradiation is recommended as first indication. Despite its rarity, significant improvements were obtained by retrospective or prospective clinical studies these 20 past years, evaluating concomitant chemotherapy and IMRT. Nevertheless, the individualisation of the treatment, over dose distribution, has poor data available. Fractionation remains classic (1.8-2.0Gy/Fr), but the optimal dose level remains under discussion. The strategy concerning the volumes and doses for the prophylactic volumes remains under discussion. This paper will describe the data published, and the recommendations of working Groups, and the main options under evaluation. To conclude, today only the absence of gap is recommended, the benefit of a one-step schedule reducing the treatment time, then increasing local control and survival, but personalised schedules remain under investigation.
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Affiliation(s)
- D Peiffert
- Département de radiothérapie, institut de cancérologie de Lorraine Alexis-Vautrin, avenue de Bourgogne, 54511 Vandoeuvre-les-Nancy, France.
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23
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Lee A, Albert A, Sheth N, Adedoyin P, Rowley J, Schreiber D. Patterns of care and outcomes of intensity modulated radiation therapy versus three-dimensional conformal radiation therapy for anal cancer. J Gastrointest Oncol 2019; 10:623-631. [PMID: 31392042 DOI: 10.21037/jgo.2019.02.12] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Definitive chemoradiation is the standard of care for anal squamous cell carcinoma. Compared to three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) is increasingly becoming the preferred technique in order to reduce treatment related toxicity. The objective of this study is to evaluate practice patterns and total radiation treatment times of two radiation modalities. Methods A total of 6,966 patients with non-metastatic squamous cell carcinoma of the anus who received definitive chemoradiation were queried from the National Cancer Database (NCDB) from 2004-2013. Logistic regression was performed to assess for predictors of IMRT receipt. The Kaplan-Meier method and multivariable Cox regression analysis was used to assess overall survival (OS). Results In total, 3,868 (55.5%) received 3DCRT and 3,098 (44.5%) received IMRT. Total radiation treatment time was <7 weeks for 54.3% of patients treated with 3DCRT versus 63.8% of patients treated with IMRT. On multivariable logistic regression, positive clinical nodes (OR =1.20, P=0.001) and treatment at an academic facility (OR =1.23, P<0.001) were associated with increased likelihood of receiving IMRT. The 5-year OS was 73.0% for 3DCRT and 73.9% for IMRT (P=0.315). On multivariable analysis, total radiation treatment time ≥7 weeks (HR =1.33, P<0.001) was associated with worse survival while radiation modality (3DCRT vs. IMRT) did not impact survival (HR =0.98, P=0.763). Conclusions IMRT has dramatically increased in utilization from 2% to 65% during the study time period. IMRT was less likely than 3DCRT to have prolonged radiation treatment times, which was associated with worse survival.
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Affiliation(s)
- Anna Lee
- Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA.,Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY, USA
| | - Ashley Albert
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Niki Sheth
- Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA.,Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY, USA
| | - Paul Adedoyin
- Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA.,Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY, USA
| | - Jared Rowley
- Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA.,Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY, USA
| | - David Schreiber
- Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA.,Summit Medical Group MD Anderson Cancer Center, Berkeley Heights, NJ, USA
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24
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David JM, Yue Y, Blas K, Hendifar A, Kabolizadeh P, Tuli R. 18F-FDG PET Predicts Hematologic Toxicity in Patients with Locally Advanced Anal Cancer Treated With Chemoradiation. Adv Radiat Oncol 2019; 4:613-622. [PMID: 31681863 PMCID: PMC6817719 DOI: 10.1016/j.adro.2019.06.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 06/10/2019] [Accepted: 06/19/2019] [Indexed: 01/26/2023] Open
Abstract
Purpose Hematologic toxicity (HT) during chemoradiation therapy (CRT) for anal cancer can lead to treatment breaks that compromise efficacy. We hypothesized that CRT-induced HT correlates with changes in active bone marrow (ABM) characterized by pre-/post-CRT positron emission tomography (PET)/computed tomography. Methods and materials Data from 36 patients with anal cancer who were treated with 18F-fluorodeoxyglucose PET/computed tomography scans 2 weeks before and 6 to 16 weeks after CRT were analyzed. Complete blood counts with differential within 2 weeks from, weekly during, and 2 week after treatment were obtained. HT was defined as baseline complete blood count change to nadir and posttreatment recovery. Total bone marrow was segmented into 2 subregions: lumbosacral (LS) pelvis (L5 vertebrae, sacrum, and coccyx) and lower pelvis (LP) (ilium, femoral head/neck, and greater and lesser trochanter). PET ABM was characterized as the volume having standard uptake value (SUV) greater than the mean uptake of unirradiated extrapelvic bone marrow. PET variables of pre-/post-CRT and HT predictors were analyzed by linear regression. Results Average pelvic ABM was significantly reduced from 52% to 41% in pre- to post-CRT PET scans for all patients (P = .0012). Regional analysis indicated significant post-CRT reduction of LS-ABM (P < .0001) and LP-ABM (P = .006). Linear regression analysis identified post-CRT SUVmean, differential ΔSUVmean, and ΔABM as correlating significantly with pre- and posttreatment HT. ΔWBC linearly correlated with ΔABM of LS and LP pelvis (P = .033 and P = .028, respectively). Dosimetrically, ABM was sensitive to higher radiation doses (>50 Gy) in terms of acute hematologic ΔWBC (P = .021) and ΔANC(P = .028). HT increased with increasing volume of ABM receiving 40 Gy. The results also suggest that ABM V40 Gy ≤ 20% to 25% may significantly reduce the risk of HT. Conclusions HT was significantly associated with ΔABM in patients with anal cancer who were treated with CRT. LS-ABM was a robust surrogate for evaluating CRT-induced HT. Our results suggest implementation of ABM dosimetric constraints, V40 Gy ≤ 20-25%, may significantly reduce HT and lead to decreased treatment delays associated with clinical outcomes.
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Affiliation(s)
- John M David
- Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Yong Yue
- Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Kevin Blas
- Department of Radiation Oncology, Beaumont Hospital, Royal Oak, Michigan
| | - Andrew Hendifar
- Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Peyman Kabolizadeh
- Department of Radiation Oncology, Beaumont Hospital, Royal Oak, Michigan
| | - Richard Tuli
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
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Ahsen OO, Liang K, Lee HC, Wang Z, Fujimoto JG, Mashimo H. Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study. World J Gastroenterol 2019; 25:1997-2009. [PMID: 31086467 PMCID: PMC6487379 DOI: 10.3748/wjg.v25.i16.1997] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 02/12/2019] [Accepted: 02/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic radiation proctopathy (CRP) occurs as a result of pelvic radiation therapy and is associated with formation of abnormal vasculature that may lead to persistent rectal bleeding. While incidence is declining due to refinement of radiation delivery techniques, CRP remains one of the major complications of pelvic radiation therapy and significantly affects patient quality of life. Radiofrequency ablation (RFA) is an emerging treatment modality for eradicating abnormal vasculature associated with CRP. However, questions remain regarding CRP pathophysiology and optimal disease management.
AIM To study feasibility of optical coherence tomography angiography (OCTA) for investigating subsurface vascular alterations in CRP and response to RFA treatment.
METHODS Two patients with normal rectum and 8 patients referred for, or undergoing endoscopic RFA treatment for CRP were imaged with a prototype ultrahigh-speed optical coherence tomography (OCT) system over 15 OCT/colonoscopy visits (2 normal patients, 5 RFA-naïve patients, 8 RFA-follow-up visits). OCT and OCTA was performed by placing the OCT catheter onto the dentate line and rectum without endoscopic guidance. OCTA enabled depth-resolved microvasculature imaging using motion contrast from flowing blood, without requiring injected dyes. OCTA features of normal and abnormal microvasculature were assessed in the mucosa and submucosa. Blinded reading of OCTA images was performed to assess the association of abnormal rectal microvasculature with CRP and RFA treatment, and rectal telangiectasia density endoscopic scoring.
RESULTS OCTA/OCT images are intrinsically co-registered and enabled depth-resolved visualization of microvasculature in the mucosa and submucosa. OCTA visualized normal vascular patterns with regular honeycomb patterns vs abnormal vasculature with distorted honeycomb patterns and ectatic/tortuous microvasculature in the rectal mucosa. Normal arterioles and venules < 200 μm in diameter versus abnormal heterogenous enlarged arterioles and venules > 200 μm in diameter were visualized in the rectal submucosa. Abnormal mucosal vasculature occurred in 0 of 2 normal patients and 3 of 5 RFA-naïve patients, while abnormal submucosal vasculature occurred more often, in 1 of 2 normal patients and 5 of 5 RFA-naïve patients. After RFA treatment, vascular abnormalities decreased, with abnormal mucosal vasculature observed in 0 of 8 RFA-follow-up visits and abnormal submucosal vasculature observed in only and 2 of 8 RFA-follow-up visits.
CONCLUSION OCTA visualizes depth-resolved microvascular abnormalities in CRP, allowing assessment of superficial features which are endoscopically visible as well as deeper vasculature which cannot be seen endoscopically. OCTA/OCT of the rectum can be performed in conjunction with, or independently from endoscopy. Further studies are warranted to investigate if OCTA/OCT can elucidate pathophysiology of CRP or improve management.
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Affiliation(s)
- Osman Oguz Ahsen
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
| | - Kaicheng Liang
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
| | - Hsiang-Chieh Lee
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
| | - Zhao Wang
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
| | - James G Fujimoto
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
| | - Hiroshi Mashimo
- Gastroenterology Section, VA Boston Healthcare System, Harvard School of Medicine, Boston, MA 02130, United States
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Valvo F, Ciurlia E, Avuzzi B, Doci R, Ducreux M, Roelofsen F, Roth A, Trama A, Wittekind C, Bosset JF. Cancer of the anal region. Crit Rev Oncol Hematol 2019; 135:115-127. [DOI: 10.1016/j.critrevonc.2018.12.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 12/06/2018] [Accepted: 12/19/2018] [Indexed: 11/25/2022] Open
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27
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Koerber SA, Seither B, Slynko A, Haefner MF, Krug D, Liermann J, Adeberg S, Herfarth K, Debus J, Sterzing F. Chemoradiation in female patients with anal cancer: Patient-reported outcome of acute and chronic side effects. TUMORI JOURNAL 2018; 105:174-180. [PMID: 30484384 DOI: 10.1177/0300891618811273] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION We evaluated acute and chronic side effects of 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in female patients with anal carcinoma and accessed correlations between dosimetric parameters and the considered toxicities. METHODS For 70 women with anal cancer treated at our department, acute and chronic side effects and quality of life (QoL) were evaluated with questionnaires using the Common Terminology Criteria for Adverse Events (CTCAE v. 4.0.) and Late Effects in Normal Tissue, Subjective, Objective Management and Analytic Scales (LentSoma) before, during, and after the treatment. RESULTS Forty-seven out of 70 (67%) patients completed the questionnaire and were enrolled in the study. Only poor urinary stream, loss of pubic hair during chemoradiation, and chronic vaginal dryness were observed more frequently in the 3D-CRT group compared to the IMRT group (univariable logistic regression p = .032, p = .04, p = .049, respectively). After the treatment, 43% in the 3D-CRT group and 29% in the IMRT group reported a severe loss of QoL. A higher proportion among the patients receiving a genital V20 ⩾35% showed grade 1-3 side effects such as chronic dyspareunia ( p = .035; Fisher exact test). CONCLUSION Our results suggest that the use of IMRT decreases acute and chronic adverse effects although reduced QoL also occurred in the IMRT group. These effects are likely to be underreported in retrospective studies using physician-reported outcome measures.
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Affiliation(s)
- Stefan A Koerber
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Ben Seither
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany
| | - Alla Slynko
- 4 Institute of Biostatistics, German Cancer Research Center, Heidelberg, Germany
| | - Matthias F Haefner
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - David Krug
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Jakob Liermann
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Sebastian Adeberg
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Klaus Herfarth
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Juergen Debus
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
| | - Florian Sterzing
- 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.,3 National Center of Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
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Ghareeb A, Paramasevon K, Mokool P, van der Voet H, Jha M. Toxicity and survival of anal cancer patients treated with intensity-modulated radiation therapy. Ann R Coll Surg Engl 2018; 101:168-175. [PMID: 30482037 DOI: 10.1308/rcsann.2018.0202] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
INTRODUCTION The definitive treatment of anal cancer with chemoradiotherapy spares abdominoperineal resection for salvage treatment but carries a high burden of toxicity. Intensity-modulated radiation therapy has been implemented to reduce toxicity, reduce treatment breaks and improve survival. However, large and long-term studies are lacking. We aimed to investigate the toxicities and long-term survival of anal cancer patients treated with intensity-modulated radiation therapy at James Cook University Hospital, Middlesbrough. MATERIALS AND METHODS We conducted a retrospective analysis of all patients with squamous cell anal cancer treated at James Cook University Hospital between July 2010 and April 2017. All patients were uniformly treated with intensity-modulated radiation therapy-based chemoradiation with curative intent. A subset of these patients was followed-up prospectively by an oncologist for acute and late toxicity. We calculated Kaplan-Meier estimates of survival statistics and compared our results with those of previous trials which used conventional radiotherapy. RESULTS We studied 132 patients, including a toxicity subset of 64, for a median follow-up time of 43 months (range 3-84 months). Eleven patients (8.3%) underwent salvage abdominoperineal resection. Grade 3+ acute non-haematological, gastrointestinal, genitourinary and dermatological toxicity were found in 56.2%, 12.3%, 0% and 50.7% of the toxicity subset (n = 64). Median treatment duration was 37 days. Overall and colostomy-free survival at five years were 68.3% and 85.3%, respectively. Tumour size (P = 0.006) and age (P = 0.002) predicted shorter overall survival. CONCLUSIONS Intensity-modulated radiation therapy probably reduces acute gastrointestinal and genitourinary toxicity compared with conventional radiotherapy, while resulting in similar overall and colostomy-free survival. We suggest that further dose escalation may improve survival in patients with T3/T4 tumours.
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Affiliation(s)
- A Ghareeb
- Department of General Surgery, James Cook University Hospital , Middlesbrough , UK.,Institute of Genetic Medicine, Newcastle University, International Centre for Life , Newcastle upon Tyne , UK
| | - K Paramasevon
- Department of General Surgery, James Cook University Hospital , Middlesbrough , UK
| | - P Mokool
- Department of General Surgery, James Cook University Hospital , Middlesbrough , UK
| | - H van der Voet
- Cancer Services, James Cook University Hospital , Middlesbrough , UK
| | - M Jha
- Department of General Surgery, James Cook University Hospital , Middlesbrough , UK
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29
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Peiffert D, Baumann AS, Serre AA, Vendrely V, Rouard N, Faivre JC, Vogin G. [Anal canal cancer: In the era of intensity-modulated radiotherapy, outstanding issues]. Cancer Radiother 2018; 22:509-514. [PMID: 30181029 DOI: 10.1016/j.canrad.2018.07.131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 07/15/2018] [Indexed: 02/07/2023]
Abstract
Intensity-modulated radiotherapy makes possible to optimize the irradiation and spare normal tissues. The toxicity remains important with concomitant chemotherapy often associated. The improvement of MRI and PET-CT define more precisely the target volumes, which need a higher dose, but necessitates to respect the rules of contouring. The treatment is uniform whatever the stage but should be individualized based on clinical stage and tumor response. New paradigms concern biology, staging, volumes and doses, fractionation and combined treatments.
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Affiliation(s)
- D Peiffert
- Service de radiothérapie, institut de cancérologie de Lorraine centre Alexis-Vautrin, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France; EA 4360 Apemac, université de Lorraine, 9, avenue de la Forêt-de-Haye, 54500 Nancy, France.
| | - A S Baumann
- Service de radiothérapie, institut de cancérologie de Lorraine centre Alexis-Vautrin, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France
| | - A A Serre
- Service de radiothérapie, institut de cancérologie de Lorraine centre Alexis-Vautrin, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France
| | - V Vendrely
- Service de radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, avenue de Magellan, 33604 Pessac, France
| | - N Rouard
- Hôpital Édouard-Hériot, 69000 Lyon, France
| | - J C Faivre
- Service de radiothérapie, institut de cancérologie de Lorraine centre Alexis-Vautrin, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France
| | - G Vogin
- Service de radiothérapie, institut de cancérologie de Lorraine centre Alexis-Vautrin, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France
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30
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Masson I, Delpon G, Vendrely V. [Image-guided radiotherapy contribution and patient setup for anorectal cancer treatment]. Cancer Radiother 2018; 22:622-630. [PMID: 30143462 DOI: 10.1016/j.canrad.2018.06.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 06/27/2018] [Indexed: 01/24/2023]
Abstract
Intensity-modulated radiation therapy is recommended in anal squamous cell carcinoma treatment and is increasingly used in rectal cancer. It adapts the dose to target volumes, with a high doses gradient. Intensity-modulated radiation therapy allows to reduce toxicity to critical normal structures and to consider dose-escalation studies or systemic treatment intensification. Image-guided radiation therapy is a warrant of quality for intensity-modulated radiation therapy, especially for successful delivery of the dose as planned. There is no recommended international or national anorectal cancer image-guided radiation therapy protocol currently available. Dose-escalation trials or expert opinions about intensity-modulated/image-guided radiation therapy good practice guidelines recommend daily volumetric imaging throughout the treatment or during the five first fractions and weekly thereafter as a minimum. Image-guided radiation therapy allows to reduce margins related to patient setup errors. Internal margin, related to the internal organ motion, needs to be adapted according to short- or long-course radiotherapy, gender, rectal location; it can be higher than current recommended planning target volume margins, particularly in the upper and anterior part of mesorectum, which has the most significant movement. Image-guided radiation therapy based on volumetric imaging allows to take target volume shrinkage into account and to develop adaptive strategies, in particular for mesorectum shrinkage during rectal cancer treatment. Lastly, the emergence of new image-guided radiation therapy technologies including MRI (which plays a major role in pelvic tumours assessment and diagnosis) opens up interesting perspectives for adaptive radiotherapy, taking into account both organs' movements and tumour shrinkage.
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Affiliation(s)
- I Masson
- Département de radiothérapie, institut de cancérologie de l'Ouest René-Gauducheau, boulevard Jacques-Monod, 44805 Saint-Herblain, France.
| | - G Delpon
- Département de physique médicale, institut de cancérologie de l'Ouest René-Gauducheau, boulevard Jacques-Monod, 44805 Saint-Herblain, France
| | - V Vendrely
- Service de radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, avenue de Magellan, 33604 Pessac, France
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Klausner G, Blais E, Jumeau R, Biau J, de Meric de Bellefon M, Ozsahin M, Zilli T, Miralbell R, Thariat J, Troussier I. Management of locally advanced anal canal carcinoma with intensity-modulated radiotherapy and concurrent chemotherapy. Med Oncol 2018; 35:134. [PMID: 30128811 DOI: 10.1007/s12032-018-1197-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 08/15/2018] [Indexed: 01/14/2023]
Abstract
The best curative option for locally advanced (stages II-III) squamous-cell carcinomas of the anal canal (SCCAC) is concurrent chemo-radiotherapy delivering 36-45 Gy to the prophylactic planning target volume with an additional boost of 14-20 Gy to the gross tumor volume with or without a gap-period between these two sequences. Although 3-dimensional conformal radiotherapy led to suboptimal tumor coverage because of field junctions, this modality remains a standard of care. Recently, intensity-modulated radiotherapy (IMRT) techniques improved tumor coverage while decreasing doses delivered to organs at risk. Sparing healthy tissues results in fewer severe acute toxicities. Consequently, IMRT could potentially avoid a gap-period that may increase the risk of local failure. Furthermore, these modalities reduce severe late toxicities of the gastrointestinal tract as well as better functional conservation of anorectal sphincter. This report aims to critically review contemporary trends in the management of locally advanced SCCAC using IMRT and concurrent chemotherapy.
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Affiliation(s)
- Guillaume Klausner
- Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Eivind Blais
- Radiation Oncology Department, Centre Hospitalier Universitaire (CHU) La Pitié-Salpêtrière Charles-Foix, Sorbonne University, 47-83 Boulevard de l'Hôpital, 75013, Paris, France
| | - Raphaël Jumeau
- Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Julian Biau
- Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Mailys de Meric de Bellefon
- Radiation Oncology Department, Institut du Cancer de Montpellier Val d'Aurelle, Montpellier University, 208 Avenue des Apothicaires, 34298, Montpellier, France
| | - Mahmut Ozsahin
- Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Thomas Zilli
- Radiation Oncology Department, Hôpitaux Universitaires de Genève (HUG), Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland
| | - Raymond Miralbell
- Radiation Oncology Department, Hôpitaux Universitaires de Genève (HUG), Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland
| | - Juliette Thariat
- Radiation Oncology Department, François Baclesse Center/ARCHADE, Normandy University, 3 Avenue du Général Harris, 14000, Caen, France
| | - Idriss Troussier
- Radiation Oncology Department, Hôpitaux Universitaires de Genève (HUG), Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland.
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Haque W, Verma V, Butler EB, Teh BS. Utilization of intensity modulated radiation therapy for anal cancer in the United States. J Gastrointest Oncol 2018; 9:466-477. [PMID: 29998012 DOI: 10.21037/jgo.2018.03.03] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Background Chemoradiotherapy for anal cancer (AC) can incur substantial treatment-related toxicities. Whereas radiotherapy (RT) for AC has historically been delivered with two- or three-dimensional conformal RT (2D/3DCRT) techniques, intensity-modulated RT (IMRT) is associated with improved target conformality and lower doses to organs-at-risk (OARs). This is the first investigation to date evaluating trends of IMRT utilization in the United States. Methods The National Cancer Data Base (NCDB) was queried [2004-2015] for AC patients receiving definitive chemoradiotherapy with a defined RT technique (3DCRT versus IMRT). Following analysis based on temporal trends, multivariate logistic regression determined factors associated with receipt of IMRT. Secondarily, Kaplan-Meier analysis compared OS between the 3DCRT and IMRT groups, and Cox proportional hazards modeling determined variables associated with OS. Results Altogether, 11,396 patients met study criteria; 1,288 (11%) were treated with 3DCRT and 10,108 (89%) with IMRT. Temporally, utilization of IMRT rose significantly, from 28% in 2004 to 96% in 2015, corresponding with a progressive decrease in 3DCRT usage. IMRT was more likely delivered in node-positive disease, at academic centers, and in southern/western regions (P<0.05 for all). T3-4 disease was less likely to receive IMRT (P<0.05). As expected, there were no OS differences based on RT technique (P=0.402). Predictors of worse OS included advancing age, male gender, increasing comorbidities, advanced T-stage, and nodal positivity (P<0.05 for all). In addition to racial- and insurance-related factors, receipt of therapy at academic centers independently predicted for improved OS (P<0.05 for all). Conclusions Based on findings from this large, contemporary dataset, IMRT is now the most widely utilized RT technique for AC, and 3DCRT is used in a very small minority of patients. IMRT utilization is impacted by multiple characteristics, such as disease- and regional-related factors. These observations have implications for payers and insurance coverage; improved survival at academic centers has ramifications for patient counseling.
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Affiliation(s)
- Waqar Haque
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
| | - Vivek Verma
- Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA
| | - E Brian Butler
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
| | - Bin S Teh
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
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Intensity Modulated Radiation Therapy Versus Conventional Radiation for Anal Cancer in the Veterans Affairs System. Int J Radiat Oncol Biol Phys 2018; 102:109-115. [PMID: 30102186 DOI: 10.1016/j.ijrobp.2018.05.044] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 04/28/2018] [Accepted: 05/16/2018] [Indexed: 01/26/2023]
Abstract
PURPOSE Compared with conventional radiation therapy, intensity modulated radiation therapy (IMRT) may reduce acute toxicity from anal cancer treatment, potentially leading to improved long-term outcomes. We analyze the effect of IMRT on short- and long-term outcomes among a large sample of US veterans. METHODS AND MATERIALS From a national Veterans Affairs database, we identified 779 patients (n = 403 conventional radiation therapy, n = 376 IMRT) with locally advanced anal squamous cell carcinoma diagnosed between 2000 and 2015 and treated with concurrent chemoradiation therapy. Radiation treatment planning and dosimetric constraints were not standardized across patients. We analyzed the effect of IMRT on short-term outcomes (acute toxicity, treatment breaks, and incomplete chemotherapy) and long-term outcomes (survival and ostomy placement) in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders. RESULTS IMRT was associated with decreased radiation treatment breaks ≥5 days (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.37-0.91; P = .02), increased rates of receiving 2 cycles of mitomycin C chemotherapy (OR 2.04; 95% CI 1.22-3.45; P = .007), increased rates of receiving 2 cycles of any chemotherapy (OR 3.45; 95% CI 1.82-6.25; P < .001), and decreased risk of ostomy related to tumor recurrence or progression (subdistribution hazard ratio 0.60; 95% CI 0.37-0.99; P = .045). IMRT was not associated with a decrease in grade 3 to 4 hematologic toxicity (P = .79), hospitalization for gastrointestinal toxicity (P = .59), or cancer-specific survival (P = 0.18). CONCLUSIONS Among a large sample of US veterans with anal cancer, IMRT was associated with higher rates of receiving 2 chemotherapy cycles, decreased radiation treatment breaks, and decreased rates of ostomy placement. IMRT appears to offer substantial benefits over conventional radiation therapy for patients undergoing concurrent chemoradiation therapy for anal cancer.
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Ludmir EB, Kachnic LA, Czito BG. Evolution and Management of Treatment-Related Toxicity in Anal Cancer. Surg Oncol Clin N Am 2018; 26:91-113. [PMID: 27889040 DOI: 10.1016/j.soc.2016.07.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Over the past several decades, clinical trials have demonstrated improved disease-related outcomes in the definitive treatment of anal cancer. Although treatment with radiation and concurrent chemotherapy results in high rates of cure, significant acute and late toxicities are seen. This review focuses on the evolution of treatment-related toxicity for anal cancer. Management of these adverse effects is reviewed, as are future directions in anal cancer treatment and their impact on toxicity.
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Affiliation(s)
- Ethan B Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1422, Houston, TX 77030, USA
| | - Lisa A Kachnic
- Department of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, Suite B1034, Nashville, TN 37232, USA
| | - Brian G Czito
- Department of Radiation Oncology, Duke University Medical Center, Box 3085, Durham, NC 27710, USA.
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35
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Thompson SR, Lee ISY, Carroll S, Bishop S, Douglas P, Lam F, Brown C, Williams J, Goldstein D. Radiotherapy for anal squamous cell carcinoma: must the upper pelvic nodes and the inguinal nodes be treated? ANZ J Surg 2018. [PMID: 29514401 DOI: 10.1111/ans.14398] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Loco-regional failure is the predominant cause of death in anal squamous cell carcinoma. We assessed patterns of loco-regional recurrence to determine the impact of radiotherapy (RT) volumes on patient outcome. METHODS Retrospective clinical study, including patients treated curatively with RT or chemo-radiotherapy between 1994 and 2007. RT fields/volumes were reviewed and compared with patterns of failure. Patients were classified as having whole pelvic radiotherapy (WPRT) if RT extended to L5/S1 or lower pelvic radiotherapy (LPRT) if it extended to the lower sacroiliac joints or below. Patients with negative inguinal nodes either underwent prophylactic inguinal radiotherapy (PIRT) or had inguinal observation (IO). Patterns of failure were compared. RESULTS Twenty-seven patients (53%) had WPRT and 24 (47%) had LPRT. Forty-two patients had negative inguinal nodes: 29 (69%) had PIRT and 13 (31%) had IO. Median follow-up was 5.8 years. Twelve regional failures occurred in eight patients: three pelvic, one inguinal and four pelvic and inguinal. All patients with regional failure died of disease. Pelvic nodal failure was 7.7% in N0 and 33% in N1-3 patients (P = 0.012). There was no difference in pelvic regional failure between WPRT and LPRT (11% versus 16%, P = 0.64). There was only one possible regional failure above LPRT in this group (4%). Inguinal failure was 0% in the PIRT group compared with 23% in IO group (P = 0.009). CONCLUSION There was no difference in pelvic regional failure between WPRT and LPRT. LPRT is likely to be safe in N0 patients. Inguinal nodes should be treated in all patients.
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Affiliation(s)
- Stephen R Thompson
- Department of Radiation Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia.,Prince of Wales Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Isabel S Y Lee
- Department of Radiation Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Susan Carroll
- Department of Radiation Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Sarah Bishop
- Department of Radiation Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | | | - Francis Lam
- Department of Colorectal Surgery, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Chris Brown
- National Health and Medical Research Council, Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Janet Williams
- Department of Radiation Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - David Goldstein
- Prince of Wales Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia.,Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia
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Martin D, Balermpas P, Winkelmann R, Rödel F, Rödel C, Fokas E. Anal squamous cell carcinoma - State of the art management and future perspectives. Cancer Treat Rev 2018; 65:11-21. [PMID: 29494827 DOI: 10.1016/j.ctrv.2018.02.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 01/30/2018] [Accepted: 02/01/2018] [Indexed: 02/07/2023]
Abstract
Anal squamous cell carcinoma (ASCC) is associated with infection with high-risk strains of human papilloma virus (HPV) in 70-90% of cases and a rise in incidence has been observed in the last decades. Definitive chemoradiotherapy (CRT) using 5-fluorouracil and mitomycin C constitutes the standard treatment for localized disease, but about 30% of patients do not respond or relapse locally. Phase I/II trials testing targeted agents, such as epidermal-growth-factor receptor (EGFR) inhibitors, have failed to improve clinical outcome and resulted in increased toxicities. Modern imaging methods and biomarkers, also in the context of HPV status, should be further explored to improve patient stratification. In the present review, we will discuss the current clinical evidence and future perspectives in the management of ASCC. HPV-positive ASCC is more immunogenic with a higher density of tumor infiltrating lymphocytes that correlate with better response to CRT and more favorable prognosis compared to HPV-negative tumors. Immunotherapies including immune checkpoint inhibitors have brought new hope and promising results were recently demonstrated in metastatic ASCC. The addition of immunotherapies to CRT for localized disease is tested in early phase trials, and these results could have a profound impact on the way we treat ASCC in near future. Further research and novel approaches are expected to enhance our understanding of tumor biology and immunology, and improve patient stratification and treatment adaptation in the context of personalized medicine.
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Affiliation(s)
- Daniel Martin
- Department of Radiotherapy and Oncology, University of Frankfurt, Germany
| | - Panagiotis Balermpas
- Department of Radiotherapy and Oncology, University of Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site: Frankfurt a. M., Germany
| | - Ria Winkelmann
- Senckenberg Institute for Pathology, University of Frankfurt, Germany
| | - Franz Rödel
- Department of Radiotherapy and Oncology, University of Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site: Frankfurt a. M., Germany
| | - Claus Rödel
- Department of Radiotherapy and Oncology, University of Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site: Frankfurt a. M., Germany
| | - Emmanouil Fokas
- Department of Radiotherapy and Oncology, University of Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site: Frankfurt a. M., Germany.
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Chin AL, Pollom EL, Qian Y, Koong AC, Chang DT. Impact of Intensity-Modulated Radiotherapy on Health Care Costs of Patients With Anal Squamous Cell Carcinoma. J Oncol Pract 2017; 13:e992-e1001. [PMID: 29035618 PMCID: PMC6202035 DOI: 10.1200/jop.2017.024810] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Drivers of variation in the cost of care after chemoradiotherapy for the management of anal squamous cell carcinoma (SCC) have not been fully elucidated. We sought to characterize the direct and indirect impact of radiotherapy modality on health care costs among patients with anal SCC. PATIENTS AND METHODS A retrospective cohort study was performed using the 2014 linkage of the SEER-Medicare database. We identified 1,025 patients with anal SCC diagnosed between 2001 and 2011 and treated with chemoradiotherapy. Propensity score matching was used to balance baseline differences between patients treated with intensity-modulated radiotherapy (IMRT) and those treated with three-dimensional conformal radiotherapy (3D-CRT). Differences in total, cancer-attributable, and procedure-specific costs between groups were measured. RESULTS Radiation-related, patient out-of-pocket, and total costs in the 1-year period after radiotherapy start were all higher for the IMRT group than the 3D-CRT group (median total cost, $35,890 v $27,262, respectively; P < .001). Patients who received IMRT had lower cumulative costs associated with urgent hospitalizations and emergency department visits at both 9 months and 1 year after treatment start compared with a matched cohort of patients who received 3D-CRT (median, $711 v $4,957 at 1 year, respectively; P = .021). CONCLUSION Although total costs of care were higher for IMRT compared with 3D-CRT, primarily as a result of higher radiotherapy-specific costs, IMRT was associated with decreased unplanned health care utilization costs starting at 9 months after treatment start. Radiotherapy-centered episodes of care may need to encompass a longer time horizon to capture the full cost savings associated with more advanced radiation modalities.
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Affiliation(s)
- Alexander L. Chin
- Stanford Cancer Institute, Stanford, CA; and MD Anderson Cancer Center, Houston TX
| | - Erqi L. Pollom
- Stanford Cancer Institute, Stanford, CA; and MD Anderson Cancer Center, Houston TX
| | - Yushen Qian
- Stanford Cancer Institute, Stanford, CA; and MD Anderson Cancer Center, Houston TX
| | - Albert C. Koong
- Stanford Cancer Institute, Stanford, CA; and MD Anderson Cancer Center, Houston TX
| | - Daniel T. Chang
- Stanford Cancer Institute, Stanford, CA; and MD Anderson Cancer Center, Houston TX
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Prevalence of patient-reported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer. Qual Life Res 2017; 27:97-103. [DOI: 10.1007/s11136-017-1700-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/02/2017] [Indexed: 12/31/2022]
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Arcadipane F, Franco P, Ceccarelli M, Furfaro G, Rondi N, Trino E, Martini S, Iorio GC, Mistrangelo M, Cassoni P, Racca P, Morino M, Ricardi U. Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer. Asia Pac J Clin Oncol 2017; 14:217-223. [PMID: 28856848 DOI: 10.1111/ajco.12768] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 08/02/2017] [Indexed: 11/29/2022]
Abstract
AIM To report on clinical outcomes of simultaneous integrated boost intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy as per Radiation Therapy Oncology Group (RTOG) 0529 protocol in anal cancer patients. METHODS Clinical stage T1-T4 N0-N3 anal cancer patients were submitted to concomitant chemoradiation. Patients with cT2N0 disease were prescribed 50.4 Gy/28 fractions to the gross tumor planning target volume (PTV) and 42 Gy/28 fractions to the elective nodal PTV. Patients staged as cT3-T4/N0-N3 were given 54 Gy/30 fractions to the macroscopic anal PTV, while clinical nodes were prescribed 50.4 Gy/30 fractions if <3 cm or 54 Gy/30 fractions if ≥3 cm; elective nodal PTV was prescribed 45 Gy/30 fractions. Two cycles of concomitant 5-fluorouracil and mitomycin C were planned for all patients. Oncological outcomes, acute and late toxicity profiles and pattern of failure were reported. RESULTS The 3-year colostomy-free survival rate was 64% (95% CI 0.52-0.75). The 3-year local control, disease-free and overall survival rates were 69% (95% CI 0.57-0.79), 71% (95% CI 0.59-0.80) and 79% (95% CI 0.66-0.87), respectively. The cumulative incidence of colostomies was 15.1% (95% CI 8.15-23.88) at 24 months. The cumulative incidence of cancer-specific deaths was 16.4% (95% CI 8.60-26.47) at 36 months. Major acute toxicity consisted of hematological (G3-G4: 26%) and cutaneous (G3-G4: 16%) events. Only one case of ≥G3 late toxicity was documented. CONCLUSIONS Simultaneous integrated boost IMRT and concurrent chemotherapy as per RTOG 0529 protocol seems to be safe and feasible with consistent oncological outcomes and a mild acute and late toxicity profile in anal cancer patients.
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Affiliation(s)
| | | | - Manuela Ceccarelli
- Unit of Cancer Epidemiology and CPO Piedmont, AOU Citta' della Salute e della Scienza, Turin, Italy
| | - Gabriella Furfaro
- Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy
| | - Nadia Rondi
- Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy
| | - Elisabetta Trino
- Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy
| | - Stefania Martini
- Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy
| | | | | | - Paola Cassoni
- Department of Medical Sciences Pathology, University of Turin, Turin, Italy
| | - Patrizia Racca
- Department of Oncology, Oncological Centre for Gastrointestinal Neoplasm, AOU Città della Salute e della Scienza, Turin, Italy
| | - Mario Morino
- Unit of Cancer Epidemiology and CPO Piedmont, AOU Citta' della Salute e della Scienza, Turin, Italy
| | - Umberto Ricardi
- Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy
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Fredman ET, Abdel-Wahab M, Kumar AMS. Influence of radiation treatment technique on outcome and toxicity in anal cancer. ACTA ACUST UNITED AC 2017; 6:413-421. [PMID: 29213359 PMCID: PMC5700990 DOI: 10.1007/s13566-017-0326-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 08/09/2017] [Indexed: 01/26/2023]
Abstract
Objective Intensity-modulated radiation therapy (IMRT) has largely supplanted three-dimensional conformal radiation (3D-CRT) for definitive anal cancer treatment due to decreased toxicity and potentially improved outcomes. Convincing data demonstrating its advantages, however, remain limited. We compared outcomes and toxicity with concurrent chemotherapy and IMRT vs 3D-CRT for anal cancer. Methods We performed a single-institution retrospective review of patients treated with IMRT or 3D-CRT as part of definitive mitomycin-C/5-fluorouricil-based chemoradiation for anal cancer from January 2003 to December 2012. Results One hundred sixty-five patients were included, with 61 and 104 receiving IMRT and 3D-CRT, respectively. Overall, 92.7% had squamous cell carcinoma. The mean initial pelvic dose was 48.3 and 44 Gy for IMRT and 3D-CRT, respectively. Complete response, partial response, and disease progression rates were similar (IMRT 83.6, 8.2, 8.2%; 3D-CRT 85.6, 6.7, 7.7%; p = 0.608, p = 0.728, p = 0.729). There was no significant difference in overall survival (p = 0.971), event-free survival (p = 0.900), or local or distant recurrence rates (p = 0.118, p = 0.373). IMRT caused significantly less acute grade 1–2 incontinence (p = 0.035), grade 3–4 pain (p = 0.033), and fatigue (p = 0.030). IMRT patients had significantly fewer chronic post-treatment toxicities (p = 0.008), outperforming 3D-CRT in six of eight toxicities reviewed. Though total treatment length was comparable (43.6 and 44.5 days), IMRT recipients had fewer (27.9 vs 41.3% of patients, p = 0.89), shorter treatment breaks (mean 2.9 vs 4.1 days, p = 0.229). Conclusion This report represents the largest series directly comparing concurrent chemotherapy with IMRT vs 3D-CRT for definitive treatment of anal cancer. IMRT significantly reduced acute and post-treatment toxicities and allowed for safe and effective pelvic dose escalation.
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Affiliation(s)
- Elisha T Fredman
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH 44106 USA
| | - May Abdel-Wahab
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency's (IAEA) Division of Human Health, Vienna, Austria
| | - Aryavarta M S Kumar
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH 44106 USA.,University Hospitals Parma Seidman Cancer Center, Parma, OH USA
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Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal. Am J Clin Oncol 2017; 40:386-392. [DOI: 10.1097/coc.0000000000000172] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Kent C, Bessell EM, Scholefield JH, Chappell S, Marsh L, Mills J, Sayers I. Chemoradiotherapy with Brachytherapy or Electron Therapy Boost for Locally Advanced Squamous Cell Carcinoma of the Anus-Reducing the Colostomy Rate. J Gastrointest Cancer 2017; 48:1-7. [PMID: 27412395 PMCID: PMC5310557 DOI: 10.1007/s12029-016-9850-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Purpose The aim of this study is to determine overall survival, disease-specific survival and stoma-free survival after treatment of squamous cell carcinoma of the anus with chemoradiotherapy followed by brachytherapy or electron boost in a recent cohort of patients. Methods Fifty-two patients (median age 62 years) were treated with radical chemoradiotherapy (mitomycin C, infusional 5-fluorouracil concurrently with conformal radical radiotherapy 45 Gy in 25 fractions over 5 weeks) followed by a radiotherapy boost between 1 December 2000 and 30 April 2011. Follow-up was to 30 November 2014. Thirty-six patients received a boost (15–20 Gy) over 2 days with 192Ir needle brachytherapy for anal canal tumours, and 16 patients received electron beam therapy (20 Gy in 10 fractions in 2 weeks) for anal margin tumours. A defunctioning stoma was only created prior to chemoradiotherapy for fistula or severe anal pain. Results The overall survival for the 36 patients treated with chemoradiotherapy followed by brachytherapy was 75 % (95 % CI, 61–89) at 5 years, the disease-specific survival was 91 % (95 % CI, 81–101 %), and the stoma-free survival was 97 % (95 % CI, 91–103 %) all at 5 years. For the 16 patients treated with an electron boost for anal margin tumours, the 5-year overall survival, disease-specific survival and stoma-free survival were 68 % (95 % CI, 44–92 %), 78 % (95 % CI, 56–100 %) and 80 % (95 % CI, 60–100 %), respectively. Conclusions A very low stoma formation rate can be obtained with radical chemoradiotherapy followed by a brachytherapy boost for squamous cell carcinoma of the anal canal but not with an electron boost for anal margin tumours.
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Affiliation(s)
- C Kent
- Department of Clinical Oncology, Nottingham, UK
| | - E M Bessell
- Department of Clinical Oncology, Nottingham, UK.
| | | | - S Chappell
- School of Life Sciences, University of Nottingham, Nottingham, UK
| | - L Marsh
- Department of Clinical Oncology, Nottingham, UK
| | - J Mills
- Department of Clinical Oncology, Nottingham, UK
| | - I Sayers
- Department of Clinical Oncology, Nottingham, UK
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Yordanov K, Cima S, Richetti A, Pesce G, Martucci F, Azinwi NC, Valli MC. Concurrent chemoradiation with volumetric modulated Arc therapy of patients treated for anal cancer-acute toxicity and treatment outcome. J Gastrointest Oncol 2017; 8:361-367. [PMID: 28480075 DOI: 10.21037/jgo.2017.03.09] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND to report the acute toxicity and clinical results in patients with anal cancer treated with volumetric modulated arc therapy (VMAT) concomitant with chemotherapy. METHODS A cohort of 21 patients with histologically confirmed squamous cell carcinoma of the anal canal was treated with VMAT and chemotherapy. Dose prescription was 39.6 Gy, 1.8 Gy/ fraction for the elective nodal PTV, the macroscopic (tumor and involved lymph nodes) PTV doses were 14.4 Gy up to a total dose of 54 Gy in 4 patients and 19.8 up to 59.4 Gy in 15 patients. One patient received a boost dose of 18 Gy up to a total dose of 57.6 Gy and another one was treated with 36 Gy and boost of 19.8 Gy up to a total dose of 55.8 Gy. Chemotherapy with MMC and 5-FU/Capecitabine was administered concomitantly. End points were local control (LC), disease-free survival (DFS) and overall survival (OS). RESULTS Median follow-up time was 35.5 months. Two year OS was 91%, DFS was 73% and LRC was 81%. Acute dermatological toxicity G3 was recorded in one patient, ten patients (47.6%) experienced a G2 skin toxicity, while G1 toxicity was registered in eight patients (38%). One patient developed Grade 3 acute gastrointestinal (GI) toxicity, two patients (9.5%) experienced grade 2 acute GI toxicity and ten patients (47.6%) G1 toxicity. Acute genitourinary toxicity G1 was recorded in ten patients (47.6%). CONCLUSIONS Our results support VMAT as standard radiotherapy technique in the treatment of patients with anal cancer.
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Affiliation(s)
- Kaloyan Yordanov
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona-Lugano, Ticino, Switzerland
| | - Simona Cima
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona-Lugano, Ticino, Switzerland
| | - Antonella Richetti
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona-Lugano, Ticino, Switzerland
| | - Gianfranco Pesce
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona-Lugano, Ticino, Switzerland
| | - Francesco Martucci
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona-Lugano, Ticino, Switzerland
| | - Ngwa Che Azinwi
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona-Lugano, Ticino, Switzerland
| | - Maria Carla Valli
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona-Lugano, Ticino, Switzerland
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Mitra D, Hong TS, Horick N, Rose B, Drapek LN, Blaszkowsky LS, Allen JN, Kwak EL, Murphy JE, Clark JW, Ryan DP, Cusack JC, Bordeianou LG, Berger DL, Wo JY. Long-term outcomes and toxicities of a large cohort of anal cancer patients treated with dose-painted IMRT per RTOG 0529. Adv Radiat Oncol 2017; 2:110-117. [PMID: 28740921 PMCID: PMC5514246 DOI: 10.1016/j.adro.2017.01.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 01/12/2017] [Accepted: 01/24/2017] [Indexed: 12/02/2022] Open
Abstract
PURPOSE To describe the outcomes and toxicities of the largest cohort to date of patients with anal squamous cell carcinoma uniformly treated with concurrent chemoradiation using dose-painted intensity modulated radiation therapy (DP-IMRT) according to RTOG 0529. METHODS AND MATERIALS We identified 99 eligible patients with anal cancer who were treated at our institution with definitive chemoradiation using DP-IMRT between 2005 and 2015 per RTOG 0529 dosing guidelines. Primary study endpoints included event-free survival (defined as recurrence, colostomy, or death) and overall survival. Secondary endpoints were treatment duration and acute and late toxicity. RESULTS At a median follow-up of 49 months (range, 2-114 months), 92% of patients had a clinical complete response. Fifteen percent underwent colostomy, including 4 pretreatment colostomies, 6 planned abdominoperineal resections (APRs), 4 salvage APRs, and 1 APR for treatment-related complications. Thirteen patients developed local recurrence, of whom 6 developed synchronous metastatic disease. The 4-year overall survival was 85.8%, and 4-year event-free survival was 75.5%. Median treatment duration was 43 days (range, 10-68 days). The overall rate of non-hematologic grade 3+ acute and grade 2+ late toxicities was 20% and 15%, respectively. CONCLUSIONS Long-term outcomes and tolerability were excellent In the largest cohort to date of patients with anal cancer who received DP-IMRT prescribed per RTOG 0529.
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Affiliation(s)
- Devarati Mitra
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Theodore S. Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Nora Horick
- Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Brent Rose
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Lorraine N. Drapek
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Jill N. Allen
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Eunice L. Kwak
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Janet E. Murphy
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jeffrey W. Clark
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - David P. Ryan
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - James C. Cusack
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | | | - David L. Berger
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Jennifer Y. Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
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Rose B, Mitra D, Hong TS, Jee KW, Niemierko A, Drapek LN, Blaszkowsky LS, Allen JN, Murphy JE, Clark JW, Ryan DP, Wo JY. Irradiation of anatomically defined pelvic subsites and acute hematologic toxicity in anal cancer patients undergoing chemoradiation. Pract Radiat Oncol 2017; 7:e291-e297. [PMID: 28462895 DOI: 10.1016/j.prro.2017.03.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 02/03/2017] [Accepted: 03/03/2017] [Indexed: 11/17/2022]
Abstract
PURPOSE Chemoradiation for the treatment of anal cancer is known to cause significant hematologic toxicity (HT). We sought to investigate if radiation dose to specific pelvic subsites is associated with increased HT risk. METHODS AND MATERIALS Forty-five patients with nonmetastatic anal cancer who received definitive chemoradiation with intensity modulated radiation therapy and concurrent mitomycin-C and 5-fluorouracil were studied. Total pelvic bone marrow (TBM) was divided into 3 subsites: lumbosacral bone marrow (LSBM), including the entire sacrum and L5 vertebral body; iliac bone marrow (IBM) extending from the iliac crests to the superior border of the femoral head; and lower pelvic bone marrow, including the pubic bones, ischia, acetabula, and proximal femurs. The primary endpoint was absolute neutrophil count (ANC) nadir during or within 2 weeks of treatment completion. Generalized linear modeling was used to analyze the correlation between the equivalent uniform dose (with an "a" value of 0.5) to the individual pelvic subsites and the various hematologic endpoints. Age, body mass index, sex, baseline blood counts, and immunosuppression were analyzed as potential covariates. RESULTS Mean ± standard deviation ANC nadir was 0.77 × 109/L (±0.66 × 109/L). Grades 3+ and 4+ neutropenia occurred in 71.1% and 44.4% of patients, respectively. In addition to radiation dose to pelvic bone marrow, baseline ANC was the only significant predictor of hematologic toxicity on multivariable analysis and was included in all models. The equivalent uniform doses of TBM, LSBM, and IBM were each significantly associated with neutropenia. The model performance of TBM (adjusted R2 = 0.226) was similar to both LSBM (adjusted R2 = 0.206) and IBM (adjusted R2 = 0.249). CONCLUSIONS Radiation doses to TBM, LSBM, and IBM were individually associated with HT, suggesting that sparing just a portion of pelvic bone marrow is insufficient to decrease rates of clinically significant bone marrow suppression.
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Affiliation(s)
- Brent Rose
- Department of Radiation Oncology, University of California San Diego, San Diego, California
| | - Devarati Mitra
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Kyung-Wook Jee
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Andrzej Niemierko
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Lorraine N Drapek
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Jill N Allen
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Janet E Murphy
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jeffrey W Clark
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - David P Ryan
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
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The Impact of Novel Radiation Treatment Techniques on Toxicity and Clinical Outcomes In Rectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2017; 13:61-72. [PMID: 29445322 DOI: 10.1007/s11888-017-0351-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Purpose of review Three-dimensional conformal radiation therapy (3DCRT) has been the standard technique in the treatment of rectal cancer. The use of new radiation treatment technologies such as intensity-modulated radiation therapy (IMRT), proton therapy (PT), stereotactic body radiation therapy (SBRT) and brachytherapy (BT) has been increasing over the past 10 years. This review will highlight the advantages and drawbacks of these techniques. Recent findings IMRT, PT, SBRT and BT achieve a higher target coverage conformity, a higher organ at risk sparing and enable dose escalation compared to 3DCRT. Some studies suggested a reduction in gastrointestinal and hematologic toxicities and an increase in the complete pathologic response rate; however, the clinical benefit of these techniques remains controversial. Summary The results of these new techniques seem encouraging despite conclusive data. Further trials are required to establish their role in rectal cancer.
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Houard C, Pinaquy JB, Mesguich C, Henriques de Figueiredo B, Cazeau AL, Allard JB, Laharie H, Bordenave L, Fernandez P, Vendrely V. Role of 18F-FDG PET/CT in Posttreatment Evaluation of Anal Carcinoma. J Nucl Med 2017; 58:1414-1420. [DOI: 10.2967/jnumed.116.185280] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 02/10/2017] [Indexed: 12/27/2022] Open
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Muirhead R, Drinkwater K, O'Cathail SM, Adams R, Glynne-Jones R, Harrison M, Hawkins MA, Sebag-Montefiore D, Gilbert DC. Initial Results from the Royal College of Radiologists' UK National Audit of Anal Cancer Radiotherapy 2015. Clin Oncol (R Coll Radiol) 2017; 29:188-197. [PMID: 27810119 PMCID: PMC5304408 DOI: 10.1016/j.clon.2016.10.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 08/08/2016] [Accepted: 08/15/2016] [Indexed: 11/22/2022]
Abstract
AIMS UK guidance was recently developed for the treatment of anal cancer using intensity-modulated radiotherapy (IMRT). We audited the current use of radiotherapy in UK cancer centres for the treatment of anal cancer against such guidance. We describe the acute toxicity of IMRT in comparison with patient population in the audit treated with two-phase conformal radiotherapy and the previous published data from two-phase conformal radiotherapy, in the UK ACT2 trial. MATERIALS AND METHODS A Royal College of Radiologists' prospective national audit of patients treated with radiotherapy in UK cancer centres was carried out over a 6 month period between February and July 2015. RESULTS Two hundred and forty-two cases were received from 40/56 cancer centres (71%). In total, 231 (95%) underwent full dose radiotherapy with prophylactic nodal irradiation. Of these, 180 (78%) received IMRT or equivalent, 52 (22%) two-phase conformal (ACT2) technique. The number of interruptions in radiotherapy treatment in the ACT2 trial was 15%. Interruptions were noted in 7% (95% confidence interval 0-14%) of courses receiving two-phase conformal and 4% (95% confidence interval 1-7%) of those receiving IMRT. The percentage of patients completing the planned radiotherapy dose, irrelevant of gaps, was 90% (95% confidence interval 82-98%) and 96% (95% confidence interval 93-99%), in two-phase conformal and IMRT respectively. The toxicity reported in the ACT2 trial, in patients receiving two-phase conformal in the audit and in patients receiving IMRT in the audit was: any toxic effect 71%, 54%, 48%, non-haematological 62%, 49%, 40% and haematological 26%, 13%, 18%, respectively. CONCLUSIONS IMRT implementation for anal cancer is well underway in the UK with most patients receiving IMRT delivery, although its usage is not yet universal. This audit confirms that IMRT results in reduced acute toxicity and minimised treatment interruptions in comparison with previous two-phase conformal techniques.
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Affiliation(s)
- R Muirhead
- CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.
| | | | - S M O'Cathail
- Oxford University Hospitals NHS Trust, Department of Oncology, Churchill Hospital, Oxford, UK
| | - R Adams
- Cardiff University Department of Cancer and Genetics and Velindre Hospital, Cardiff, UK
| | - R Glynne-Jones
- Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK
| | - M Harrison
- Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK
| | - M A Hawkins
- CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK
| | - D Sebag-Montefiore
- University of Leeds, Cancer Research UK Leeds Centre, St. James's University Hospital, Leeds, UK
| | - D C Gilbert
- Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK
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Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Racca P, Morino M, Numico G, Ricardi U. Hematologic toxicity in anal cancer patients during combined chemo-radiation: a radiation oncologist perspective. Expert Rev Anticancer Ther 2017; 17:335-345. [PMID: 28277103 DOI: 10.1080/14737140.2017.1288104] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Hematologic toxicity is an important side effect occurring in patients affected with anal cancer, undergoing combined radio-chemotherapy, with consistent clinical meaningfulness. Areas covered: Since more than a half of bone marrow is comprised within the pelvic region, the radiation dose received by this functional compartment is crucial. Modern imaging modalities may provide a useful tool to identify bone marrow and new delivery technology may enhance the radiation oncologist's possibility to selectively spare these structures, potentially decreasing acute hematologic toxicity profile in this setting. Expert commentary: Correlation between dose to pelvic structures and acute hematologic toxicity has been studied in several oncological settings, mainly on a retrospective frame. Different dose metrics were found to be correlated including mean doses and different points within the dose-volume histogram ranging from low to medium-high doses. Several imaging modalities were used to identify bone marrow both morphological and functional. Several clinical endpoints were used. In general, accounting for bone marrow during the treatment planning process may be important to decrease the acute hematologic toxicity profile during concurrent chemo-radiation in anal cancer patients. The most appropriate strategy to address this issue need further investigation and deserve validation in a prospective clinical framework.
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Affiliation(s)
- Pierfrancesco Franco
- a Department of Oncology, Radiation Oncology , University of Turin , Turin , Italy
| | - Francesca Arcadipane
- a Department of Oncology, Radiation Oncology , University of Turin , Turin , Italy
| | - Riccardo Ragona
- a Department of Oncology, Radiation Oncology , University of Turin , Turin , Italy
| | | | - Paola Cassoni
- c Department of Medical Sciences , University of Turin , Turin , Italy
| | - Patrizia Racca
- d Department of Oncology , Oncological Centre for Gastrointestinal Neoplasm, AOU Città della Salute e della Scienza , Turin , Italy
| | - Mario Morino
- b Department of Surgical Sciences , University of Turin , Turin , Italy
| | - Gianmauro Numico
- e Department of Oncology , Medical Oncology, AO SS Antonio e Biagio e Cesare Arrigo , Alessandria , Italy
| | - Umberto Ricardi
- a Department of Oncology, Radiation Oncology , University of Turin , Turin , Italy
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The Impact of Intensity Modulated Radiation Therapy on Hospitalization Outcomes in the SEER-Medicare Population With Anal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys 2017; 98:177-185. [PMID: 28258896 DOI: 10.1016/j.ijrobp.2017.01.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 12/21/2016] [Accepted: 01/01/2017] [Indexed: 12/22/2022]
Abstract
PURPOSE We examined the impact of intensity modulated radiation therapy (IMRT) on hospitalization rates in the Surveillance, Epidemiology, and End Results (SEER)-Medicare population with anal squamous cell carcinoma (SCC). METHODS AND MATERIALS We performed a retrospective cohort study using the SEER-Medicare database. We identified patients with nonmetastatic anal SCC diagnosed between 2001 and 2011 and treated with chemoradiation therapy. We assessed the relation between IMRT and first hospitalization by use of a multivariate competing-risk model, as well as instrumental variable analysis, using provider IMRT affinity as our instrument. RESULTS Of the 1165 patients included in our study, 458 (39%) received IMRT. IMRT use increased over time and was associated more with regional and provider characteristics than with patient characteristics. The 3- and 6-month cumulative incidences of first hospitalization were 41.9% (95% confidence interval [CI], 37.3%-46.4%) and 47.6% (95% CI, 43.0%-52.2%), respectively, for the IMRT cohort and 46.7% (95% CI, 43.0%-50.4%) and 52.1% (95% CI, 48.4%-55.7%), respectively, for the non-IMRT cohort. IMRT was associated with a decreased hazard of first hospitalization compared with 3-dimensional radiation techniques (hazard ratio, 0.70; 95% CI, 0.58-0.84; P=.0002). Instrumental variable analysis suggested an even greater reduction in hospitalizations with IMRT after controlling for unmeasured confounders. There was a trend toward improved overall survival with IMRT, with an adjusted hazard ratio of 0.77 (95% CI, 0.59-1.00; P=.05). CONCLUSIONS The use of IMRT is associated with reduced hospitalizations in elderly patients with anal SCC. Further work is warranted to understand the long-term health and cost impact of IMRT, particularly for patient subgroups most at risk of toxicity and hospitalization.
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