A Prospective Observational Study Comparing Long-Course Conventional Neoadjuvant Chemoradiotherapy with Short-Course Radiotherapy Followed by Consolidation Chemotherapy with Delayed Surgery in Locally Advanced Rectal Cancer (original) (raw)
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BMC cancer, 2016
There still is no evidence which neoadjuvant therapy regimen for stage II-III rectal cancer is superior. The aim of this study was to compare results achieved after long-course chemoradiotherapy (CRT) with short-term radiotherapy (RT) followed by delayed surgery. A randomized trial was carried out between 2007-2013. One hundred fifty patients diagnosed with stage II-III rectal cancer were randomized into one of two neoadjuvant treatment arms: conventional chemoradiotherapy (CRT) and short-term radiotherapy (RT) followed by surgery after 6-8 weeks. Primary endpoints of this trial were downstaging and pathological complete response rate. Secondary endpoints were local recurrence rate and overall survival. The pathological complete response was found in 3 (4.4%) cases after RT and 8 (11.1%) after CRT (P = 0.112). Downstaging (stage 0 and I) was observed in 21 (30.9%) cases in RT group vs. 27 (37.5%) cases in CRT group (P = 0.409). Median follow-up time was 39.7 (range 4.9-79.7) months....
Background: Chemoradiotherapy followed by surgery followed by adjuvant chemotherapy is the mainstay of treatment in stage II and III rectal cancer.There are two approaches to pelvic RT for resectable rectal cancer: short-course radiation and long course chemoradiotherapy(CRT).Polish and Australian randomized studies compared short-course radiation and immediate surgery with long-course CRT and delayed surgery.In these studies similar long-term survival and local control have been reported for both these approaches but pathological complete response(pCR) is not better with short course RT. Moreover studies have shown better tumor downstaging with delayed surgery.So the idea is to combine the benefits of delayed surgery for improved tumor downstaging with short course RT by adding two cycles of chemotherapy between short course RT and surgery to improve pCR rates.In this context the use of short-course radiotherapy may have some advantages and needs to be tested in clinical trials. Aim: To compare the tumour response clinically, radiologically and histopathologically To compare the toxicities between the two arms Materials and Methods: This prospective randomized study was a two arm study in which short course radiotherapy followed by two cycles of chemotherapy was compared with conventional neoadjuvant chemoradiotherapy in rectal cancer.Patients assigned to study group(short course RT) were given 25 Gy (5 Gy/fraction) in 5 days.Following a gap of 1 week after RT, patients were given two cycles of Capecitabine and Oxaliplatin (CAPOX) based chemotherapy.Patients assigned to control group(conventional CRT) were given radiation of 50.4 Gy in 28 fractions along with tablet Capecitabine on RT days.Patients were assessed for surgery after 4-6 weeks of completion of chemoradiation.Overall treatment time to surgery was similar in both the arms i.e. 10-12 weeks. Results: Of the 28 entered patients, 27 were eligible for analysis; 14 in study arm and 13 in control arm.The pCR rate was 6.7% in study arm while it was 0 in control arm(p=0.343). 33.3% patients in study arm and 53.8% patients in control arm had partial response(p=0.274). 53.3% patients in study arm and 46.2% patients in control arm had stable disease(p=0.705).None of the patients in both the arms had progressive disease.Acute toxicities were lower in study arm.The absence of hematological toxicity in 60% patients in study arm was statistically significant (p=.001).20% patients in study arm and 92.3% patients in control arm had grade 2-3 toxicity (p=0.005).The absence of skin toxicity in 73.3% patients in study arm was statistically significant(p=.001).Grade 3 toxicity was seen in 15.4% patients in control arm and no patient in study arm(p=0.116). Conclusions: pCR rates in the two arms are comparable.But the major advantage for the 5*5 Gy regimen with chemotherapy in neo-adjuvant setting is the improved toxicity profile compared with conventional CRT with significant reduction in acute toxicities in short course RT arm.
Radiation Oncology Journal
Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m 2 from day 1-5 twice daily and oxaliplatin 50 mg/m 2 on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m 2 twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.
Optimal Timing to Surgery after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
Journal of The American College of Surgeons, 2016
BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) has demonstrated proven benefit in tumor regression and improved long-term local control for patients with locally advanced rectal cancer. However, precise analysis of the optimal waiting time that maximizes oncologic benefits of nCRT has not been established. STUDY DESIGN: The 2006e2012 National Cancer Data Base was queried for patients with stage II and III rectal adenocarcinoma who underwent nCRT followed by surgical resection. Time to surgery was defined as the difference between last date of radiotherapy and date of surgery. Primary study endpoints included resection margin positivity and pathologic downstaging. Multivariable regression modeling with restricted cubic splines was used to evaluate the adjusted association between time to surgery and our study endpoints, and to establish an optimal time threshold for surgery. RESULTS: A total of 11,760 patients were included. Median time to surgery was 53 days (interquartile range [IQR] 43 to 63 days). After adjusting for patient demographic, clinical, tumor, and treatment characteristics, our model determined an inflection point at 56 days after end of radiotherapy associated with the highest likelihood of complete resection and pathologic downstaging. With adjustment, the risk of margin positivity was increased in those who underwent surgery after 56 days from end of radiotherapy (odds ratio [OR] 1.40, 95% CI 1.21 to 1.61, p < 0.001). The likelihood of downstaging was increasing up to 56 days after radiotherapy (56 days vs <56 days, OR 1.2, 95% CI 1.02 to 1.23, p ¼ 0.01). CONCLUSIONS: This study objectively determined the optimal time for surgery after completion of nCRT for rectal cancer based on completeness of resection and tumor downstaging. Eight weeks appears to be the critical threshold for optimal tumor response.
Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology, 2014
Neoadjuvant chemoradiotherapy (NACTRT) improves local recurrence rate in locally advanced (LA) rectal cancer with no survival benefit. Pathological complete response (pCR) post-NACTRT is associated with improved outcome. Debate is ongoing as to when would be the opportune time to operate. To determine if greater down-staging can be achieved by a longer time interval from NACTRT to surgery (tumor regression score [TRS]) and whether this would impact sphincter saving surgery rates and early relapse rates. A retrospective analysis of a prospectively maintained database of patients with LA rectal adenocarcinoma treated from January 2012 to August 2013 was carried out. One hundred and ten patients who completed NACTRT (50 Gy/25 fractions with capecitabine 825 mg/m(2) twice daily) followed by surgical resection were included. For response evaluation patients were divided into two groups, Group 1 (TRS ≤60 days, n = 42) and 2 (TRS >60 days, n = 68). Tumor down-staging, pCR rate, tumor re...
Background: To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. Methods: A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7–12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. Results: Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adeno-carcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p < 0.001), respectively. The pCR relative risk comparison of 2nd to 1st group was 1.8, while 3rd to 2nd group was 1.3. Moreover, between the 3rd and 1st group, a pCR relative risk of 2.4 (p < 0.01) was noted. At univariate analysis, clinical stage III (p < 0.001), radiotherapy dose >5040 cGy (p = 0.002) and longer interval (p < 0.001) were significantly
Asian Pacific journal of cancer prevention : APJCP, 2016
PURPOSE To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. MATERIALS AND METHODS A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. RESULTS There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall s...
Journal of Oncology
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...