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Novelties in treatment of locally advanced rectal cancer.

ABSTRACT: Treatment of locally advanced rectal cancer is evolving through surgical innovation and paradigm shifts in neoadjuvant treatment. Whereas local recurrence was a significant concern before the systematic implementation of neoadjuvant chemoradiation therapy and surgery according to total mesorectal excision principles, distant relapse remains a major drawback. Hence, efforts in recent years have focused on delivering preoperative chemotherapy regimens to overcome compliance issues with adjuvant administration. In parallel, new surgical techniques, including transanal video-assisted total mesorectal excision and robot-assisted surgery, emerged to face the challenge to navigate in the deep and narrow spaces of the pelvis. Furthermore, patients experiencing a complete response after neoadjuvant treatment might even escape surgery within a close surveillance strategy. This novel "watch and wait" concept has gained interest to improve quality of life in highly selected patients. This review summarizes recent evidence and controversies and provides an overview on timely and innovative aspects in the treatment of locally advanced rectal cancer.

SUBMITTER: Grass F

PROVIDER: S-EPMC6281002 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Novelties in treatment of locally advanced rectal cancer.

Grass Fabian F Mathis Kellie K

F1000Research 20181129

Treatment of locally advanced rectal cancer is evolving through surgical innovation and paradigm shifts in neoadjuvant treatment. Whereas local recurrence was a significant concern before the systematic implementation of neoadjuvant chemoradiation therapy and surgery according to total mesorectal excision principles, distant relapse remains a major drawback. Hence, efforts in recent years have focused on delivering preoperative chemotherapy regimens to overcome compliance issues with adjuvant ad ...[more]

PMID: 30631423

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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.

Project description:BackgroundAccumulating evidence has identified Fusobacterium as an important pathogenic gut bacterium associated with colorectal cancer. Nevertheless, only limited data exist about the role of this bacterium in locally advanced rectal cancer (LARC). In this study, we quantified Fusobacterium nucleatum in untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients and investigated its association with therapy response and survival.Patients and methodsA total of 254 samples from 143 patients with rectal adenocarcinomas were analyzed for the presence and abundance of F. nucleatum using RNA in situ hybridization and digital image analysis. Assay accuracy was determined using infected cell lines and tumor samples with available quantitative PCR data. We studied the impact of F. nucleatum load on pathologic complete response and relapse-free survival. Treatment-induced changes were evaluated in paired pre- and post-nCRT samples (n = 71). Finally, tumor microenvironment changes during nCRT were assessed in paired samples (n = 45) by immune contexture analysis.ResultsF. nucleatum tissue levels by RNA in situ hybridization strongly correlated with quantitative PCR (r = 0.804, P < 0.001). F. nucleatum abundance was higher in untreated [median, 7.4; 95% confidence interval (3.7-16.2)] compared with treated [median, 1.6; 95% confidence interval (1.3-2.4)] tumors (P <0.001) with 58% (73/126) and 26% (22/85) positive tumors, respectively (P < 0.001). Baseline F. nucleatum levels were not associated with pathologic complete response. F. nucleatum positivity after nCRT, but not baseline status, significantly increased risk of relapse [hazard ratio = 7.5, 95% confidence interval (3.0-19.0); P < 0.001]. Tumors that turned F. nucleatum-negative after nCRT had a strong increase in CD8+ T cells post-nCRT (P < 0.001), while those that persisted F. nucleatum-positive after nCRT lacked CD8+ T cells induction in post-nCRT samples compared with baseline (P = 0.69).ConclusionF. nucleatum persistence post-nCRT is associated with high relapse rates in LARC, potentially linked to suppression of immune cytotoxicity.

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Novelties in treatment of locally advanced rectal cancer.

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Novelties in treatment of locally advanced rectal cancer.

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