Adjuvant chemotherapy for rectal cancer: Is it needed?
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ABSTRACT:
SUBMITTER: Milinis K
PROVIDER: S-EPMC4675908 | biostudies-literature | 2015 Dec
REPOSITORIES: biostudies-literature
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Project description:PURPOSES:Although adjuvant chemotherapy (AC) has been established as a standard of treatment for advanced rectal cancer, there is no guideline regarding the timing of AC initiation. In this study, we aimed to evaluate the oncologic outcome of early AC initiation and clarify the ideal time to AC among rectal cancer patients receiving preoperative chemo-radiotherapy (preCRT). METHODS:The medical records of 719 patients who underwent curative resection followed by AC for rectal cancer were analyzed retrospectively. Data distributions were compared according to the calculated cut-off for AC initiation, survival results, and chemotherapy-induced toxicity. Additionally, patients were divided into two groups according to preCRT status and compared with respect to differences in the optimal time to AC. RESULTS:Overall, a cut-off time point of 20 days after surgery for AC initiation was identified as the optimal interval; this yielded a significant difference in disease-free survival but no significant difference in AC toxicity. In the cut-off analysis of patients treated without preCRT, 19 days was identified as the optimal time to AC. However, for patients treated with preCRT, no significant value affected the survival outcome. CONCLUSIONS:Earlier initiation of AC (within approximately 3 weeks) was associated with better oncological outcomes among patients with rectal cancer. Additionally, the optimal timing of AC was unclear among patients who received preCRT; this might be attributable to an undetermined role of AC after preCRT or the effects of complications such as anastomotic leakage.
| S-EPMC6993968 | biostudies-literature
Project description:BackgroundProtective ileostomy can effectively prevent severe anastomotic leakage after rectal cancer surgery; however, the optimal timing for ileostomy closure during adjuvant chemotherapy remains unclear. This study aimed to explore the safety and long-term outcomes of early ileostomy closure during adjuvant chemotherapy.MethodPatients who underwent laparoscopic rectal cancer surgery combined with protective ileostomy and adjuvant chemotherapy between April 2017 and April 2021 were retrospectively evaluated. Patients were divided into an early closure group during chemotherapy (group A) and a late closure group after chemotherapy (group B).ResultsA total of 215 patients were included in this study, with 115 in group A and 100 in group B. There were no significant differences in demographic and clinical characteristics between the two groups. In group A, durations of stoma status (p < 0.001) and low anterior resection syndrome (LARS) (p < 0.001) were shorter, and rectal stenosis (p=0.036) and stoma-related complications (p=0.007), especially stoma stenosis (p=0.041), were less common. However, compliance with chemotherapy was worse (p=0.009). There were no significant differences in operative time, postoperative hospital stay, postoperative complications, incidence and severity of LARS, disease-free survival, or overall survival between groups.ConclusionEarly ileostomy closure can effectively reduce the duration of stoma status, duration of LARS, rectal stenosis, and stoma-related complications while not affecting surgical complications and oncological outcomes. Ileostomy closure should not be delayed because of adjuvant chemotherapy. However, follow-up should be strengthened to increase compliance and integrity with chemotherapy.
| S-EPMC10977340 | biostudies-literature
Project description:Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer.Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life.Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.ClinicalTrials.gov NCT01558921.
| S-EPMC3680047 | biostudies-literature
Project description: Not available
| S-EPMC10809453 | biostudies-literature
Project description:Importance:Adjuvant chemotherapy (AC) in patients with rectal cancer with pathologic complete response following neoadjuvant chemoradiotherapy (nCRT) and resection is recommended by treatment guidelines. However, its role in this setting is equivocal because data supporting benefits are lacking. Objective:To compare the overall survival (OS) between AC and postoperative observation (OB) in patients with rectal cancer with pathologic complete response following nCRT and resection. Design, Setting, and Participants:We identified a cohort of patients with rectal cancer and a complete pathological response (ypT0N0) after nCRT in the National Cancer Database between 2006 and 2012. Patients who received AC were compared with OB patients by propensity score matching. Overall survival was compared using the stratified log-rank test and stratified Cox regression model. The outcomes after AC vs OB were also evaluated in patient subgroups. The data analysis was completed in June 2017. Exposures:Adjuvant chemotherapy and OB. Main Outcomes and Measures:Overall survival. Results:We identified 2764 patients (mean [SD] age, 60.0 [12.3] years; 40% female) with clinical stage II or III resected adenocarcinoma of the rectum who had received nCRT and were complete responders (ypT0N0M0). Of this cohort, 741 patients in the AC group were matched by propensity score to 741 patients who underwent OB. The AC cohort had better OS compared with the OB cohort (hazard ratio, 0.50; 95% CI, 0.32-0.79). The 1-, 3-, and 5-year OS rates were 99.7%, 97.1%, and 94.7% for the AC group and 99.2%, 93.6%, and 88.4% for the OB group (P = .005). In subgroup analysis, patients with clinical stage T3/T4 and node-positive disease benefited most from AC (hazard ratio, 0.47; 95% CI, 0.25-0.91). Conclusions and Relevance:Adjuvant chemotherapy was associated with improved OS in patients with pathologic complete response after nCRT for resected locally advanced rectal cancer. This study supports the use of AC in this setting where there is currently paucity of data.
| S-EPMC6145733 | biostudies-literature
Project description:Importance:Although American guidelines recommend use of adjuvant chemotherapy in patients with locally advanced rectal cancer, individuals who achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy are less likely to receive adjuvant treatment than incomplete responders. The association and resection of adjuvant chemotherapy with survival in patients with pCR is unclear. Objective:To determine whether patients with locally advanced rectal cancer who achieve pCR after neoadjuvant chemoradiation therapy and resection benefit from the administration of adjuvant chemotherapy. Design, Setting, and Participants:This retrospective propensity score-matched cohort study identified patients with locally advanced rectal cancer from the National Cancer Database from 2006 through 2012. We selected patients with nonmetastatic invasive rectal cancer who achieved pCR after neoadjuvant chemoradiation therapy and resection. Exposures:We matched patients who received adjuvant chemotherapy to patients who did not receive adjuvant treatment in a 1:1 ratio. We separately matched subgroups of patients with node-positive disease before treatment and node-negative disease before treatment to investigate for effect modification by pretreatment nodal status. Main Outcome and Measures:We compared overall survival between groups using Kaplan-Meier survival methods and Cox proportional hazards models. Results:We identified 2455 patients (mean age, 59.5 years; 59.8% men) with rectal cancer with pCR after neoadjuvant chemoradiation therapy and resection. We matched 667 patients with pCR who received adjuvant chemotherapy and at least 8 weeks of follow-up after surgery to patients with pCR who did not receive adjuvant treatment. Over a median follow-up of 3.1 years (interquartile range, 1.94-4.40 years), patients treated with adjuvant chemotherapy demonstrated better overall survival than those who did not receive adjuvant treatment (hazard ratio, 0.44; 95% CI, 0.28-0.70). When stratified by pretreatment nodal status, only those patients with pretreatment node-positive disease exhibited improved overall survival with administration of adjuvant chemotherapy (hazard ratio, 0.24; 95% CI, 0.10-0.58). Conclusions and Relevance:The administration of adjuvant chemotherapy in patients with rectal cancer with pCR is associated with improved overall survival, particularly in patients with pretreatment node-positive disease. Although this study suggests a beneficial effect of adjuvant treatment on survival in patients with pCR, these results are limited by the presence of potential unmeasured confounding in this nonrandomized study.
| S-EPMC6145724 | biostudies-literature
Project description:BackgroundLARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection.MethodsSequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome.ResultsOur study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer.ConclusionsOur study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.
| S-EPMC11301854 | biostudies-literature
Project description:BackgroundIn this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence.MethodsIn the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included.ResultsBetween June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036).ConclusionsIn pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.
| S-EPMC5343389 | biostudies-literature
Project description: Not available
| S-EPMC6432933 | biostudies-literature
Project description:Neoadjuvant chemoradiotherapy (CRT) is used in locally advanced rectal cancer when tumours threaten the circumferential resection margin. A variable response to treatment remains, notwithstanding potentially significant morbidity, and no clinically routinely used predictive biomarkers guide decision making. This experimental study aimed to identify significantly differentially expressed proteins between patients responding or not to CRT, using novel temporal proteomic profiling, and to validate any proteins of interest.
2018-03-12 | PXD008436 | Pride