Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression

Viani, Gustavo Arruda; Stefano, Eduardo Jose; Soares, Francisco V; Afonso, S.

doi:10.1016/j.ijrobp.2010.03.008

Cited by 30 publications

(21 citation statements)

References 35 publications

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“…A meta-analysis of randomized trials of preoperative RT (without chemotherapy) suggested a minimum dose of ~30Gy / 15 fractions to effectively prevent local recurrences (35), but the analysis was limited by the potential bias resulting from higher radiation doses being prescribed in later time periods, where RT and surgery techniques were more developed, and no trials considered doses above ~45Gy. The only prior randomized trial to isolate the effect of dose-escalation is the Lyon R 96-02 randomized trial (14, 36), which compared external beam RT (39Gy in 13 fractions) with external beam plus contact x-ray therapy (85Gy in 3 fractions) and found improved sphincter preservation with higher doses.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Results of a Randomized Trial in Locally Advanced Rectal Cancer: No Benefit From Adding a Brachytherapy Boost

Appelt

Vogelius

Pløen

et al. 2014

International Journal of Radiation Oncology*Biology*Physics

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Purpose/Objective(s) Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer. Methods and Materials Between March 2005 and November 2008, 248 patients withT3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4Gy in 28 fractions, peroral UFT and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10Gy in 2 fractions). Primary trial endpoint was pathological complete response (pCR) at time of surgery; secondary endpoints included overall survival (OS), progression-free survival (PFS) and freedom from locoregional failure. Results Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, HR=1.24, p=0.34) and PFS (63.9% vs 52.0%, HR=1.22, p=0.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, 1.00–6.73, p=0.06) in the standard and in the brachytherapy arm, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration. Conclusions Despite increased pathological tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery.

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Section: Discussionmentioning

confidence: 99%

Long-Term Results of a Randomized Trial in Locally Advanced Rectal Cancer: No Benefit From Adding a Brachytherapy Boost

Appelt

Vogelius

Pløen

et al. 2014

International Journal of Radiation Oncology*Biology*Physics

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“…Previous study had shown that RT with a BED 10 of >30 Gy is more efficient in reducing local recurrence rates than a BED 10 of r30 Gy. 14 68, and 62 Gy, respectively. The BED 3 of the study's schedule was 16% less than SC RT and 8% less than LC RT.…”

Section: Discussionmentioning

confidence: 96%

Two-week Course of Preoperative Radiotherapy for Locally Advanced Rectal Adenocarcinoma

Zhu

et al. 2017

American Journal of Clinical Oncology

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“…The primary tumor and distant metastases are communicating ecosystems, which are characterized by a diversity of host cells that are both recruited from the bone marrow and locally 20. The ecosystems are also elucidated by the diversity of biological pathways responsible for the communication of the tumor cells with each of the host cells 21, 22…”

Section: Discussionmentioning

confidence: 99%

Phase II study on early start of chemotherapy after excising primary colorectal cancer with distant metastases (Pearl Star 02)

Yoshida

Aisu

Kojima

et al. 2017

Annals of Gastroent Surgery

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Initiating chemotherapy usually requires a delay of more than 4 weeks after surgically resecting colorectal cancer. However, there is little evidence regarding the required delay interval. We have previously reported a pilot study to determine the safety and feasibility of early initiation of chemotherapy after resecting primary colorectal cancer with distant metastases. We aimed to determine the safety and efficacy of early initiation of chemotherapy after resecting colorectal cancer with distant metastases.This phase II study (trial number UMIN000006310) was a prospective, single‐arm trial. A total of 20 patients (men, 15 and women, 5) were enrolled. They underwent XELOX therapy (130 mg/m2 oxaliplatin on day 1+1000 mg/m2 capecitabine twice daily on days 1‐4) on postoperative day 7 and XELOX+bevacizumab (7.5 mg/kg bevacizumab on day 1) after the second chemotherapy cycle.Baseline characteristics included a median age of 64 (range, 43‐72) years. Surgical procedures included right hemicolectomy in six patients, sigmoidectomy in three, anterior resection in five, and Hartmann procedure in six. All patients started chemotherapy on postoperative day 7. Median progression‐free survival was 14.9 months; overall response rate was 80%. Disease control rate was 100%. Grade 3 or higher hemotoxicity and grade 3 or higher non‐hematological toxicity was noted in 5.0% and 25.0% of patients, respectively. Postoperative complications were observed in two patients (superficial incisional surgical site infection and ileus).Early initiation of chemotherapy after surgery is feasible. These findings suggest future changes of the start time of chemotherapy after surgery.

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Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression

Cited by 30 publications

References 35 publications

Long-Term Results of a Randomized Trial in Locally Advanced Rectal Cancer: No Benefit From Adding a Brachytherapy Boost

Long-Term Results of a Randomized Trial in Locally Advanced Rectal Cancer: No Benefit From Adding a Brachytherapy Boost

Two-week Course of Preoperative Radiotherapy for Locally Advanced Rectal Adenocarcinoma

Phase II study on early start of chemotherapy after excising primary colorectal cancer with distant metastases (Pearl Star 02)

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