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Strategies to Optimize Treatment for Locally Advanced Rectal Cancer.

ABSTRACT: Neoadjuvant long-course concurrent chemoradiation plus surgery, followed by optional adjuvant chemotherapy, is a standard of care for locally advanced rectal cancer (LARC). However, this traditional approach has several limitations, including low pathological complete response (pCR) (10-25%), high metastasis rate (30-35%), and highly inconsistent compliance with adjuvant chemotherapy (25-75%). Treatment modalities for LARC have dramatically evolved in recent years. Multiple clinical trials have focused on optimizing strategies to achieve a win-win situation for oncologic outcomes and functions. Here, we review the latest studies into optimizing neoadjuvant treatment for LARC.

SUBMITTER: Hu X

PROVIDER: S-EPMC9818694 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Strategies to Optimize Treatment for Locally Advanced Rectal Cancer.

Hu Xiaoyu X Xue Zhuang Z He Kewen K Tian Yaru Y Chen Yu Y Zhao Mengyu M Yu Jinming J Yue Jinbo J

Cancers 20221229 1

Neoadjuvant long-course concurrent chemoradiation plus surgery, followed by optional adjuvant chemotherapy, is a standard of care for locally advanced rectal cancer (LARC). However, this traditional approach has several limitations, including low pathological complete response (pCR) (10-25%), high metastasis rate (30-35%), and highly inconsistent compliance with adjuvant chemotherapy (25-75%). Treatment modalities for LARC have dramatically evolved in recent years. Multiple clinical trials have ...[more]

PMID: 36612213

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Project description:BackgroundPelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain.MethodsWe conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects.ResultsFrom June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy.ConclusionsIn patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Project description:BackgroundNeoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits.MethodsWe performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group.ResultsTwenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67-0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60-0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87-1.24) or DFS (HR = 0.98, 95%CI = 0.76-1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups.ConclusionsFor patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.

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Strategies to Optimize Treatment for Locally Advanced Rectal Cancer.

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Strategies to Optimize Treatment for Locally Advanced Rectal Cancer.

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