Johannes Peter Maarten Burbach1, Annemarie Maria den Harder2, Martijn Intven3, Marco van Vulpen3, Helena Marieke Verkooijen4, Onne Reerink3. 1. Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands. Electronic address: j.p.m.burbach-2@umcutrecht.nl. 2. Department of Radiology, University Medical Center, Utrecht, The Netherlands. 3. Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands. 4. Trial Bureau Imaging Division, University Medical Center, Utrecht, The Netherlands.
Abstract
PURPOSE: We conducted a systematic review and meta-analysis to quantify the pathological complete response (pCR) rate after preoperative (chemo)radiation with doses of ⩾60Gy in patients with locally advanced rectal cancer. Complete response is relevant since this could select a proportion of patients for which organ-preserving strategies might be possible. Furthermore, we investigated correlations between EQD2 dose and pCR-rate, toxicity or resectability, and additionally between pCR-rate and chemotherapy, boost-approach or surgical-interval. METHODS AND MATERIALS: PubMed, EMBASE and Cochrane libraries were searched with the terms 'radiotherapy', 'boost' and 'rectal cancer' and synonym terms. Studies delivering a preoperative dose of ⩾60 Gy were eligible for inclusion. Original English full texts that allowed intention-to-treat pCR-rate calculation were included. Study variables, including pCR, acute grade ⩾3 toxicity and resectability-rate, were extracted by two authors independently. Eligibility for meta-analysis was assessed by critical appraisal. Heterogeneity and pooled estimates were calculated for all three outcomes. Pearson correlation coefficients were calculated between the variables mentioned earlier. RESULTS: The search identified 3377 original articles, of which 18 met our inclusion criteria (1106 patients). Fourteen studies were included for meta-analysis (487 patients treated with ⩾60 Gy). pCR-rate ranged between 0.0% and 44.4%. Toxicity ranged between 1.3% and 43.8% and resectability-rate between 34.0% and 100%. Pooled pCR-rate was 20.4% (95% CI 16.8-24.5%), with low heterogeneity (I2 0.0%, 95% CI 0.00-84.0%). Pooled acute grade ⩾3 toxicity was 10.3% (95% CI 5.4-18.6%) and pooled resectability-rate was 89.5% (95% CI 78.2-95.3%). CONCLUSION: Dose escalation above 60 Gy for locally advanced rectal cancer results in high pCR-rates and acceptable early toxicity. This observation needs to be further investigated within larger randomized controlled phase 3 trials in the future.
PURPOSE: We conducted a systematic review and meta-analysis to quantify the pathological complete response (pCR) rate after preoperative (chemo)radiation with doses of ⩾60Gy in patients with locally advanced rectal cancer. Complete response is relevant since this could select a proportion of patients for which organ-preserving strategies might be possible. Furthermore, we investigated correlations between EQD2 dose and pCR-rate, toxicity or resectability, and additionally between pCR-rate and chemotherapy, boost-approach or surgical-interval. METHODS AND MATERIALS: PubMed, EMBASE and Cochrane libraries were searched with the terms 'radiotherapy', 'boost' and 'rectal cancer' and synonym terms. Studies delivering a preoperative dose of ⩾60 Gy were eligible for inclusion. Original English full texts that allowed intention-to-treat pCR-rate calculation were included. Study variables, including pCR, acute grade ⩾3 toxicity and resectability-rate, were extracted by two authors independently. Eligibility for meta-analysis was assessed by critical appraisal. Heterogeneity and pooled estimates were calculated for all three outcomes. Pearson correlation coefficients were calculated between the variables mentioned earlier. RESULTS: The search identified 3377 original articles, of which 18 met our inclusion criteria (1106 patients). Fourteen studies were included for meta-analysis (487 patients treated with ⩾60 Gy). pCR-rate ranged between 0.0% and 44.4%. Toxicity ranged between 1.3% and 43.8% and resectability-rate between 34.0% and 100%. Pooled pCR-rate was 20.4% (95% CI 16.8-24.5%), with low heterogeneity (I2 0.0%, 95% CI 0.00-84.0%). Pooled acute grade ⩾3 toxicity was 10.3% (95% CI 5.4-18.6%) and pooled resectability-rate was 89.5% (95% CI 78.2-95.3%). CONCLUSION: Dose escalation above 60 Gy for locally advanced rectal cancer results in high pCR-rates and acceptable early toxicity. This observation needs to be further investigated within larger randomized controlled phase 3 trials in the future.
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