|
1
|
Yacoub H, Zenzri Y, Cherif D, Ben Mansour H, Attia N, Mokrani C, Ben Zid K, Letaief F, Maamouri N, Mezlini A. Predictors of pathological complete response after total neoadjuvant treatment using short course radiotherapy for locally advanced rectal cancer. BMC Gastroenterol 2025; 25:208. [PMID: 40165151 PMCID: PMC11956259 DOI: 10.1186/s12876-025-03709-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 02/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Total neoadjuvant treatment (TNT) has become a standard treatment approach for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following TNT have better outcomes (overall survival, relapse free survival). However, not all patients treated for LARC with neoadjuvant treatment achieve pCR. AIM The aim of our study was to assess the rate and predictors of pCR. MATERIALS AND METHODS We performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive LARC patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and January 2023 were included in the research. Pathological response to neoadjuvant treatment was assessed using Mandard grading system and response was categorized as pCR or not‑pCR. Two different standardized protocols for the neoadjuvant treatment were used: the first group was treated with induction chemotherapy followed by short course radiotherapy and the second group was treated with the RAPIDO protocol. Correlation between different studied parameters and pCR was determined using univariate and multivariate logistic regression analysis. RESULTS The mean age of the 91 included patients (46 men and 45 women) was 58.53 ± 10.3 years. Twenty (22%) were found to have a pCR (Mandard TRG1) in the operative specimen. In univariate analysis, patients less than 60 years, continuation of chemotherapy and patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p = 0.043, p = 0.0001 and p = 0.021 respectively). Patients with mucinous component had low pCR rates (p = 0.021). On logistic regression analysis, chemotherapy continuation (OR = 10.27, 95% CI = 2,14-49.32), and absence of mucinous component (OR = 12.6, 95% CI = 3.1-40.32) were significant predictors of pCR. The median survival was 37.7 months. CONCLUSION Mucinous component and chemotherapy interruption are associated with lower pCR rates. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve outcomes for patients with LARC.
Collapse
Affiliation(s)
- Haythem Yacoub
- Gastroenterolgy department, La Rabta Hospital, Tunis, Tunisia.
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia.
| | - Yosr Zenzri
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Dhouha Cherif
- Gastroenterolgy department, La Rabta Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Hajer Ben Mansour
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Najla Attia
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Cyrine Mokrani
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Khadija Ben Zid
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Feryel Letaief
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Nadia Maamouri
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Amel Mezlini
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| |
Collapse
|
|
2
|
Hou W, Song X, Pan Q, Liu S, Zhao Q, Hong D. Clinical efficacy of Neoadjuvant Chemotherapy combined with Laparoscopic Surgery in patients with Middle and Low Rectal Cancer and its Effect on serum VEGF Levels and quality of life. Pak J Med Sci 2023; 39:1568-1572. [PMID: 37936766 PMCID: PMC10626124 DOI: 10.12669/pjms.39.6.6763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 12/12/2022] [Accepted: 07/17/2023] [Indexed: 11/09/2023] Open
Abstract
Objective To observe the clinical efficacy of neoadjuvant chemotherapy combined with laparoscopic surgery in patients with middle and low rectal cancer and its effect on serum VEGF level and quality of life. Methods Retrospective analysis was performed on 80 patients with middle and low rectal cancer admitted to Baoding No.1 Central Hospital from June 2018 to June 2020.They were randomly divided into two groups. Patients in the control group underwent laparoscopic radical rectal cancer surgery, while those in the experimental group underwent neoadjuvant chemotherapy before surgery. The differences of various surgical indicators between the two groups were compared. The incidence of surgical complications, the serum VEGF levels and the improvement of quality of life were compared. The differences in local recurrence, metastasis and overall survival with in two years after surgery were compared. Results The various surgical indicators of the experimental group were significantly better than the control group (p<0.05). After treatment, the VEGF levels in the experimental group were significantly lower than those in the control group (p=0.00), while the SF-36 score was significantly higher than that of the control group (p=0.00). The total incidence of surgical complications in experimental group was significantly lower (p=0.03), the local recurrence rate was significantly lower (p=0.02), and the overall survival rate was significantly higher than that in control group (p=0.04). Conclusion Neoadjuvant chemotherapy combined with laparoscopic surgery is superior to direct surgery alone in the treatment of middle and low rectal cancer and it needs to be promoted.
Collapse
Affiliation(s)
- Wei Hou
- Wei Hou, Department of Radiotherapy, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China
| | - Xin Song
- Xin Song Endoscopy Room, Baoding Dawu Hospital, Baoding 072550, Hebei, China
| | - Qingfang Pan
- Qingfang Pan Department of Medical Oncology, Chinese People’s Liberation Army No.82 Group Hospital, Baoding 071000, Hebei, China
| | - Sukun Liu
- Sukun Liu Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherap, Baoding 071000, Hebei, China, Department of Radiotherapy, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China
| | - Qinglian Zhao
- Qinglian Zhao, Department of Radiotherapy, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China
| | - Dan Hong
- Dan Hong, Department of Radiotherapy, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China
| |
Collapse
|
|
3
|
Integrated Intensified Chemoradiation in the Setting of Total Neoadjuvant Therapy (TNT) in Patients with Locally Advanced Rectal Cancer: A Retrospective Single-Arm Study on Feasibility and Efficacy. Cancers (Basel) 2023; 15:cancers15030921. [PMID: 36765878 PMCID: PMC9913523 DOI: 10.3390/cancers15030921] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/16/2023] [Accepted: 01/30/2023] [Indexed: 02/04/2023] Open
Abstract
While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).
Collapse
|
|
4
|
Bedrikovetski S, Fitzsimmons T, Perry J, Vather R, Carruthers S, Selva-Nayagam S, Thomas ML, Moore JW, Sammour T. Personalized total neoadjuvant therapy (pTNT) for advanced rectal cancer with tailored treatment sequencing based on clinical stage at presentation. ANZ J Surg 2023; 93:173-181. [PMID: 36059157 DOI: 10.1111/ans.18021] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 08/21/2022] [Accepted: 08/23/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND This study aimed to assess short-term outcomes of a personalized total neoadjuvant treatment (pTNT) protocol, with treatment sequencing based on clinical stage at presentation. METHODS A multidisciplinary pTNT protocol was implemented across two metropolitan hospitals. This consists of two-schema based on clinical stage: patients with distant failure risk were offered induction chemotherapy before chemoradiation (nCRT), and patients with locoregional failure risk received nCRT followed by consolidation chemotherapy. Patients underwent surgical resection unless a complete clinical response (cCR) was achieved, in which case non-operative management (NOM) was offered. A prospective cohort analysis of all patients with rectal cancer who underwent pTNT with curative intent between Jan 2019 and Aug 2022 was performed. RESULTS Of 270 patients referred with rectal cancer, 102 received pTNT with curative intent and 79 have completed their treatment thus far. Thirty-three patients (41.8%) received induction chemotherapy and 46 (58.2%) received consolidation chemotherapy per protocol. The percentage of patients with EMVI, resectable M1 disease, cT4 disease, and positive lateral lymph nodes were 54.4%, 36.7%, 27.8% and 15.2%, respectively. Overall, 32 (40.5%) patients had cCR and 4 (5.1%) pCR, and 40 (50.6%) patients had non-operative management. Grade 3 toxicity was reported in 10.1% of patients and only three patients (3.8%) experienced Grade 4 chemotherapy-related toxicity, with no treatment related mortality. CONCLUSION Early results with a defined two-schema pTNT protocol are encouraging and suggest that tailoring sequencing to disease risk at presentation may represent the optimal balance between local and distant disease control, as well as treatment toxicity.
Collapse
Affiliation(s)
- Sergei Bedrikovetski
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Tracy Fitzsimmons
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Joanne Perry
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Ryash Vather
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Scott Carruthers
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Sudarsha Selva-Nayagam
- Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Michelle L Thomas
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - James W Moore
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Tarik Sammour
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| |
Collapse
|
|
5
|
The Effect of Continuing Chemotherapy after Chemoradiotherapy during the Time to Surgery on Tumor Response and Survival for Local Advanced Rectal Cancer. JOURNAL OF ONCOLOGY 2022; 2022:4108677. [PMID: 36157223 PMCID: PMC9499766 DOI: 10.1155/2022/4108677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022]
Abstract
Aim The current standard treatment of locally advanced rectal carcinoma is total mesorectal excision and postoperative adjuvant chemotherapy after neoadjuvant concurrent chemoradiotherapy (NCRT). Many studies have shown that pathological complete response (pCR) is an important prognostic factor for patients receiving NCRT. Many studies have therefore been conducted to increase pCR rates by changing the perioperative treatment strategies. Prolonging the chemotherapy time may be a reasonable way to increase the effectiveness of NCRT, pCR, and survival rates. We investigated whether neoadjuvant consolidation chemotherapy had an effect on tumor response and survival. Methods The data of 163 patients diagnosed with locally advanced rectal carcinoma were evaluated. The data of 107 patients (Group 1) who were radiologically T3–T4 and/or N+ and received chemotherapy after NCRT until their operations were compared with the data of 56 patients (Group 2) who were operated after NCRT. Results Group 1 patients had tumor and node downstaging. Their pCR was found significantly higher than in Group 2 (p = 0.005). In Group 1 patients with T3, pCR was significantly higher than for those with T4. The elapsed time between NCRT and surgery was significantly longer in patients with pCR (respectively, p = 0.012 and p = 0.008). Conclusion Neoadjuvant consolidation chemotherapy after NCRT is a safe approach that can lead to higher pathological complete response rates. The time until surgery with neoadjuvant consolidation chemotherapy may provide the chance to follow the patient without surgery in addition to increasing pCR.
Collapse
|
|
6
|
van den Berg K, Schaap DP, Voogt ELK, Buffart TE, Verheul HMW, de Groot JWB, Verhoef C, Melenhorst J, Roodhart JML, de Wilt JHW, van Westreenen HL, Aalbers AGJ, van 't Veer M, Marijnen CAM, Vincent J, Simkens LHJ, Peters NAJB, Berbée M, Werter IM, Snaebjornsson P, Peulen HMU, van Lijnschoten IG, Roef MJ, Nieuwenhuijzen GAP, Bloemen JG, Willems JMWE, Creemers GJM, Nederend J, Rutten HJT, Burger JWA. Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT). BMC Cancer 2022; 22:957. [PMID: 36068495 PMCID: PMC9446695 DOI: 10.1186/s12885-022-09947-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/29/2022] [Indexed: 11/14/2022] Open
Abstract
Background The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. Methods This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. Discussion This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. Trial registration Clinicaltrials.gov: NCT04838496, registered on 02–04-2021 Netherlands Trial Register: NL9790. Protocol version Version 3 dd 11–4-2022.
Collapse
Affiliation(s)
- K van den Berg
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands.,Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - D P Schaap
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - E L K Voogt
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - T E Buffart
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Medical Oncology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - H M W Verheul
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - J W B de Groot
- Department of Medical Oncology, Isala Oncology Centre, Zwolle, the Netherlands
| | - C Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - J Melenhorst
- Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - J M L Roodhart
- Department of Medical Oncology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - J H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | | | - A G J Aalbers
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - M van 't Veer
- Department of Research and Education, Catharina Hospital, Eindhoven, the Netherlands
| | - C A M Marijnen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - J Vincent
- Department of Medical Oncology, Elkerliek Hospital, Helmond, the Netherlands
| | - L H J Simkens
- Department of Medical Oncology, Maxima Medical Centre, Veldhoven, the Netherlands
| | - N A J B Peters
- Department of Medical Oncology, St. Jans Hospital, Weert, the Netherlands
| | - M Berbée
- Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - I M Werter
- Department of Medical Oncology, Rijnstate Hospital, Arnhem, the Netherlands
| | - P Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - H M U Peulen
- Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - I G van Lijnschoten
- Department of Pathology, PAMM Laboratory for Pathology and Medical Microbiology, Eindhoven, the Netherlands
| | - M J Roef
- Department of Nuclear Medicine, Catharina Hospital, Eindhoven, the Netherlands
| | | | - J G Bloemen
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - J M W E Willems
- Department of Medical Oncology, Anna Hospital, Geldrop, the Netherlands
| | - G J M Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J Nederend
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.,GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - J W A Burger
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
| |
Collapse
|
|
7
|
The clinic factors in evaluating long-term outcomes of patients with stage I colorectal cancer. Asian J Surg 2022; 45:2231-2238. [DOI: 10.1016/j.asjsur.2021.11.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/08/2021] [Accepted: 11/26/2021] [Indexed: 11/24/2022] Open
|
|
8
|
The concept and use of the neoadjuvant rectal score as a composite endpoint in rectal cancer. Lancet Oncol 2021; 22:e314-e326. [PMID: 34048686 DOI: 10.1016/s1470-2045(21)00053-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 01/16/2021] [Accepted: 01/20/2021] [Indexed: 12/20/2022]
Abstract
There is no universally accepted instrument to use as a validated surrogate endpoint for overall survival in phase 2 and phase 3 multimodal rectal cancer trials using chemoradiotherapy. Efforts are hampered by the inaccuracy of clinical TNM staging, the variability of indications for neoadjuvant treatment, and diverse definitions of tumour regression grade. Pathological complete response is commonly used, but fails to capture information from the majority of patients. The neoadjuvant rectal score categorises response and downstaging from the entire trial population to identify whether or not a novel treatment group in a chemoradiation trial is superior by predicting overall survival outcomes. Additionally, the neoadjuvant rectal score assesses the difference between initial clinical and pathological T stage and the presence or absence of nodal involvement after treatment. The neoadjuvant rectal score has been conceptually, but incompletely, statistically validated by two independent trial datasets. However, a fundamental weakness of the score is that no preoperative phase 3 trials in locally advanced rectal cancer in the past 20 years have provided a significant benefit in overall survival to statistically validate the neoadjuvant rectal score as a surrogate endpoint for overall survival. We review the robustness, practical value, applicability, generalisability, advantages, and disadvantages of the neoadjuvant rectal score as a surrogate endpoint for overall survival and recommend how this score could be improved and be acceptable as a standard endpoint in studies investigating neoadjuvant chemotherapy and chemoradiation in patients with rectal cancer.
Collapse
|
|
9
|
Li C, Ngorsuraches S, Chou C, Chen L, Qian J. Risk Factors of Fluoropyrimidine Induced Cardiotoxicity among Cancer Patients: A Systematic Review and Meta-analysis. Crit Rev Oncol Hematol 2021; 162:103346. [PMID: 33930532 DOI: 10.1016/j.critrevonc.2021.103346] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 03/26/2021] [Accepted: 04/25/2021] [Indexed: 12/24/2022] Open
Abstract
Cancer patients experienced an increased risk of cardiotoxicity during fluoropyrimidine-based chemotherapy (5-fluorouracil or capecitabine). We searched PubMed, PsycINFO, IPA, CINAHL, Web of Science, and ClinicalTrials.gov for studies published between January 1, 1990 and December 31, 2019, in English, examining risk factors for cardiotoxicity induced by fluoropyrimidine. Included study-level data were converted to risk ratios (RRs) and pooled RRs were calculated for meta-analyses using a random-effects method. Among 690 publications identified for abstract and title screening, 22 unique studies were included in the review, and 20 had sufficient data for meta-analyses. Results indicated that patients undergoing capecitabine-based combination therapy had a higher risk than those with monotherapy (pooled RR = 1.61). Patients with pre-existing cardiac disease (pooled RR = 3.26), hypertension (pooled RR = 1.52) or smoking (pooled RR = 2.22) also had higher risks than their counterparts. Developing risk assessment tools to mitigate the risk could be a viable strategy to improve outcomes for cancer patients undergoing fluoropyrimidine-based treatments.
Collapse
Affiliation(s)
- Chao Li
- Department of Health Outcomes Research and Policy, Auburn University, Auburn, AL, USA
| | - Surachat Ngorsuraches
- Department of Health Outcomes Research and Policy, Auburn University, Auburn, AL, USA
| | - Chiahung Chou
- Department of Health Outcomes Research and Policy, Auburn University, Auburn, AL, USA; Department of Medical Research, China Medical University Hospital, Taichung City, Taiwan
| | - Li Chen
- Department of Biostatistics and Health Data Science, Center for Computational Biology and Bioinformatics, Indiana University, Indianapolis, IN, USA
| | - Jingjing Qian
- Department of Health Outcomes Research and Policy, Auburn University, Auburn, AL, USA.
| |
Collapse
|
|
10
|
Tuta M, Boc N, Brecelj E, Peternel M, Velenik V. Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure. World J Gastrointest Oncol 2021; 13:119-130. [PMID: 33643528 PMCID: PMC7896420 DOI: 10.4251/wjgo.v13.i2.119] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 12/22/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND For locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery. AIM To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure. METHODS In a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis. RESULTS Compared to standard therapy, TNT showed a higher proportion of pCR (23% vs 7%; P = 0.01), a lower neoadjuvant rectal score (median: 8.43 vs 14.98; P < 0.05), higher T-and N-downstaging (70% and 94% vs 51% and 86%), equivalent R0 resection (95% vs 93%), shorter time to stoma closure (mean: 20 vs 33 wk; P < 0.05), higher compliance during systemic ChT (completed all cycles 87% vs 76%; P < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% vs 14%, P < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% vs 9%; P < 0.05). CONCLUSION Compared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score.
Collapse
Affiliation(s)
- Mojca Tuta
- Division of Radiology, Institute of Oncology, Ljubljana 1000, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Nina Boc
- Division of Radiology, Institute of Oncology, Ljubljana 1000, Slovenia
| | - Erik Brecelj
- Division of Surgery, Institute of Oncology, Ljubljana 1000, Slovenia
| | - Monika Peternel
- Division of Radiotherapy, Institute of Oncology, Ljubljana 1000, Slovenia
| | - Vaneja Velenik
- Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
- Division of Radiotherapy, Institute of Oncology, Ljubljana 1000, Slovenia
| |
Collapse
|