Preoperative treatment of locally advanced rectal cancer: less is more.
Ontology highlight
ABSTRACT:
SUBMITTER: Weng S
PROVIDER: S-EPMC10701462 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
Publications
Preoperative treatment of locally advanced rectal cancer: less is more.
Weng Shanshan S Zhong Chenhan C Sun Weijing W Yuan Ying Y
MedComm 20231207 6
Similar Datasets
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.).
| S-EPMC10775881 | biostudies-literature
Project description:BackgroundLocally advanced rectal cancer (LARC) poses unique challenges in treatment, with current neoadjuvant chemoradiotherapy (NA-CRT) showing limitations. The CapeOX regimen emerges as a potential less aggressive neoadjuvant chemotherapy (NAC) for LARC.MethodsWe conducted a retrospective study involving treatment-naïve patients with LARC from March 2014 to March 2021 who received 2-4 cycles of CapeOX NAC followed by radical surgery. Treatment response was evaluated using tumor regression grade (TRG), MRI-based TRG (MRI-TRG), and Neoadjuvant Rectal (NAR) score.Results94.7% of patients experienced symptom improvement and 96.4% achieved sphincter-preserving surgery. Post-NAC showed significant tumor regression and MRI confirmed a tumor length reduction (P < 0.001). Clinical and pathological staging discrepancies post-NAC suggest broader therapeutic advantages. 5-year overall and disease-free survival rates were 78.4% and 73.4%. NAR scores provided better prognostic accuracy than MRI-TRG.ConclusionCapeOX NAC presents notable benefits for LARC patients and its clinical significance may be underestimated. The NAR score demonstrates superior prognostic value over MRI-TRG.
| S-EPMC11463052 | biostudies-literature
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.
| S-EPMC7542577 | biostudies-literature
Project description: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.
| S-EPMC6281002 | biostudies-literature
Project description:BackgroundNeoadjuvant chemoradiotherapy is recommended for locally advanced rectal cancer, allowing preoperative down-staging of the primary tumor to facilitate complete surgical removal. However, further investigation is warranted for identifying whether radiotherapy is necessary for rectal mucinous adenocarcinoma (RMAC). Thus, this study was designed to explore the relationship between mFOLFOX6 with or without preoperative radiotherapy and therapeutic efficacy in locally advanced RMAC.MethodsA total of 81 patients were retrospectively enrolled, with MRI-defined clinical stage II/III RMAC received neoadjuvant treatment with mFOLFOX6 alone (group A) or mFOLFOX6 plus radiation (group B), followed by total mesorectal excision. Tumor down-staging and tumor response were assessed based on post-treatment MRI-defined radiographical and pathological findings. Follow-up data were retrieved, and the Kaplan-Meier curve was used to determine the relationship between the 3-year disease-free survival (DFS) and overall survival (OS) in the two groups.ResultsThere were no significant differences in the clinical baseline characteristics of patients between group A and group B. The sphincter preservation rate in group B was 60.9%, higher than in group A (20.0%) (P=0.031). The rate of pathological complete response (pCR) was 14.0% in group B, while no patients had pCR in group A (P=0.029), and the tumor response rate in group B was higher than in group A (52.0% vs. 16.1%, P=0.001). The 3-year probability of OS in group A and B was 77.4% and 72.0% (P=0.509), and 3-year DFS was 58.1% and 56.0% (P=0.592), respectively.ConclusionsNeoadjuvant mFOLFOX6-based chemoradiotherapy could be a promising therapeutic option for patients with RMAC, which was associated with a high rate of pCR and sphincter preservation in comparison to treated with mFOLFOX6 alone.
| S-EPMC9660069 | biostudies-literature
Project description: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.
| S-EPMC9818694 | biostudies-literature
Project description:Patients with locally advanced rectal cancer (LARC) are recommended to receive preoperative chemoradiotherapy (PCRT) followed by surgery. Response to PCRT varies widely: 60%-70% of patients with LARC do not derive therapeutic benefit from PCRT, whereas 15%-20% of patients achieve pathologic complete response (pCR). We sought to develop a liquid biopsy assay for identifying response to PCRT in patients with LARC. We analyzed two genome-wide microRNA (miRNA) expression profiling data sets from tumor tissue samples for in silico discovery (GSE68204) and validation (GSE29298). We prioritized biomarkers in pretreatment plasma specimens from clinical training (n = 41; 15 responders and 26 nonresponders) and validation (n = 65; 29 responders and 36 nonresponders) cohorts of patients with LARC. We developed an integrated miRNA panel and established a risk assessment model, which was combined with the miRNA panel and carcinoembryonic antigen levels. Our comprehensive discovery effort identified an 8-miRNA panel that robustly predicted response to PCRT, with an excellent accuracy in the discovery (area under the curve [AUC] = 0.95) and validation (AUC = 0.92) cohorts. We successfully established a circulating miRNA panel with remarkable diagnostic accuracy in the clinical training (AUC = 0.82) and validation (AUC = 0.81) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to conventional clinical factors in both cohorts (P < .01) and the risk assessment model was superior (AUC = 0.83). Finally, we applied our model to detect patients with pathologic complete response and showed that it was dramatically superior to currently used pathologic features (AUC = 0.92). Our novel risk assessment signature for predicting response to PCRT has a potential for clinical translation as a liquid biopsy assay in patients with LARC.
| S-EPMC8668014 | biostudies-literature
Project description:Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT.A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D50,i, and the normalized dose-response gradient, ?50,i.A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D50,TRG1=92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), ?50,TRG1=0.982 (CI 0.533-1.429), and for major response (TRG1-2) D50,TRG1&2=72.1 Gy (CI 65.3-94.0 Gy), ?50,TRG1&2=0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships.This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.
| S-EPMC3539741 | biostudies-literature
Project description:BackgroundThe addition of consolidation chemotherapy to preoperative short-course radiotherapy during the prolonged interval between the completion of radiation and surgery in locally advanced rectal cancer (LARC) could enhance pathologic response and might act on potential micrometastasis. We performed this meta-analysis to evaluate whether short-course radiotherapy followed by consolidation chemotherapy (SCRT/CCT) could be a neoadjuvant treatment option compared with conventional long-course chemoradiotherapy (LCCRT).MethodsWe searched the PubMed, EMBASE, MEDLINE, and Cochrane Library databases. The primary endpoints were pathological outcomes, and the secondary endpoints included survival rate, sphincter preservation rate, R0 resection rate and toxicity. RevMan 5.3 was used to calculate pooled risk ratio (RRs) and 95% confidence intervals (CIs).ResultsA total of seven eligible studies and 1865 participants were included in this meta-analysis. Compared with the LCCRT, SCRT/CCT increased pathologic complete response (pCR) rate [RR = 1.74, 95% CI (1.41, 2.15), P < 0.01] and led to a lower proportion of patients with adjuvant pathologic tumor stage 3-4 (ypT3-4) disease [RR = 0.88, 95% CI (0.80, 0.97), P = 0.01] or lymph node positive (ypN +) disease [RR = 0.83, 95% CI (0.71, 0.98), P = 0.02]. In addition, the disease-free survival (DFS) was better in SCRT/CCT group [RR = 1.10, 95% CI (1.02, 1.18), P = 0.01], while overall survival rate and toxicity and surgical procedures were similar between two groups.ConclusionBased on better pathological outcomes and DFS in SCRT/CCT group, we recommended preoperative short-course radiotherapy followed by consolidation chemotherapy as the optional neoadjuvant treatment for LARC.
| S-EPMC8785003 | biostudies-literature
Project description:Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era.
| S-EPMC4559608 | biostudies-literature