Treatment of locally advanced rectal cancer and synchronous liver metastases: multicentre comparison of two treatment strategies.
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ABSTRACT:
SUBMITTER: van Rees JM
PROVIDER: S-EPMC10416702 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Treatment of locally advanced rectal cancer and synchronous liver metastases: multicentre comparison of two treatment strategies.
van Rees Jan M JM Krul Myrtle F MF Kok Niels F M NFM Grünhagen Dirk J DJ Kok E N D END Nierop Pieter M H PMH Havenga Klaas K Rutten Harm H Burger Jacobus W A JWA de Wilt Johannes H W JHW Hagendoorn Jeroen J Peters Femke P FP Buijsen Johannes J Tanis Pieter J PJ Verhoef Cornelis C Kuhlmann Koert F D KFD
The British journal of surgery 20230801 9
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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:Rectal cancer remains a significant problem worldwide. Outcomes vary significantly according to the stage of disease and prognostic factors, including the distance of the tumor from the circumferential resection margin. Accurate staging, including high-resolution magnetic resonance imaging, allows stratification of patients into low-, moderate-, and high-risk disease; this information can be used to inform multidisciplinary team decisions regarding the role of neoadjuvant therapy. Both neoadjuvant short-course radiotherapy and long-course chemoradiation reduce the risk of local recurrence compared with surgery alone, but they have little impact on survival. Although there remains a need to reduce overtreatment of those patients at moderate risk, evaluation of intensified regimens for those with high-risk disease is still required to reduce distant failure rates and improve survival in these patients with an otherwise poor prognosis.
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Project description:BACKGROUND:The present study aimed to compare the perioperative safety and long-term survival of patients with synchronous colorectal liver metastases undergoing sequential resection (SeR), delayed resection (DeR) and simultaneous resection (SiR). METHODS:From January 2007 to December 2016, data from patients undergoing surgery at Peking University Cancer Hospital for synchronous colorectal liver metastases were retrospectively collected. The above three different surgical strategies were compared. RESULTS:A total of 233 cases were included, with 49 in the SeR group, 98 in the DeR group and 86 in the SiR group. The incidence of severe complications was 26.7% in the SiR group, higher than that in the DeR group (11.2%, P = 0.007) and the SeR group (16.3%, P = 0.166). The overall survival at 1 and 3 years in the SeR group (93.9 and 50.1%) was lower than that in the DeR group (94.9 and 64.8%, P = 0.019), but not significantly different from that in the SiR group (93.0 and 55.2%, P = 0.378). Recurrence-free survival at 1 and 3 years in the SeR group (22.4 and 18.4%) was lower than that in the DeR group (43.9 and 24.2%, P = 0.033) but not significantly different from that in the SiR group (31.4 and 19.6%, P = 0.275). Cox multivariate analysis indicated that T4, lymph node-positive primary tumour, liver metastases > 30 mm and SiR (compared with DeR) were correlated with poor prognosis. CONCLUSION:Simultaneous resection has a relatively higher incidence of severe complications, and with a staged resection strategy, the prognosis of delayed resection was better than that of sequential resection.
| S-EPMC6969459 | biostudies-literature
Project description:The current standard treatment for locally advanced rectal cancer (LARC) in Korea and Western countries is a multimodal approach incorporating preoperative long-course chemoradiotherapy (LCRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy. This approach has significantly improved local control and reduced recurrence rates; however, the overall survival benefit has not been established. Although LCRT is a good option, there remain challenging unresolved problems for colorectal surgeons. We focused on four challenging issues in this review article. The first is LARC with resectable liver metastases, for which there has been no consensus regarding optimal management and practice thus far. The second is cancer progression at the time of restaging after completion of preoperative LCRT. To date, there have been few reports on this issue. The third is early recurrence after TME following preoperative LCRT, the reason for which is thought to be the delayed systemic chemotherapy in the preoperative LCRT protocol. The fourth is cost-effectiveness. The preoperative LCRT protocol takes 5 weeks. After a 6-8-week waiting period, surgery is performed. Therefore, it is more time-consuming than short-course chemoradiotherapy. To overcome these issues, total neoadjuvant treatment (TNT) modalities, performed using various protocols, have been conducted globally based on cumulative experience. We also attempted to discuss previous TNT protocols in this article. One treatment strategy is not sufficient for patients with varying clinical characteristics. Therefore, we should revisit current treatment strategies based on recent clinical experience.
| S-EPMC7382439 | biostudies-literature
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:Approximately 10-12% of patients with oesophageal or gastric cancer (OGC) present with oligometastatic disease at diagnosis. It remains unclear if there is a role for radical surgery in these patients. We aimed to assess the outcomes of OGC patients who underwent simultaneous treatment for the primary tumour and synchronous liver metastases. Patients with OGC who underwent surgical treatment between 2008 and 2020 for the primary tumour and up to five synchronous liver metastases aiming for complete tumour removal or ablation (i.e., no residual tumour) were identified from four institutional databases. The primary outcome was overall survival (OS), calculated with the Kaplan-Meier method. Secondary outcomes were disease-free survival and postoperative outcomes. Thirty-one patients were included, with complete follow-up data for 30 patients. Twenty-six patients (84%) received neoadjuvant therapy followed by response evaluation. Median OS was 21 months [IQR 9-36] with 2- and 5-year survival rates of 43% and 30%, respectively. While disease recurred in 80% of patients (20 of 25 patients) after radical resection, patients with a solitary liver metastasis had a median OS of 34 months. The number of liver metastases was a prognostic factor for OS (solitary metastasis aHR 0.330; p-value = 0.025). Thirty-day mortality was zero and complications occurred in 55% of patients. Long-term survival can be achieved in well-selected patients who undergo surgical resection of the primary tumour and local treatment of synchronous liver metastases. In particular, patients with a solitary liver metastasis seem to have a favourable prognosis.
| S-EPMC10887104 | biostudies-literature
Project description:ObjectivesControversy surrounds the management of patients with locally advanced rectal cancer with synchronous resectable liver metastases (LMs). This study was designed to improve both systemic and local control in these patients.MethodsPatients with locally advanced rectal cancer (cT3-4N0 or cTanyN1-2) and synchronous resectable liver-limited metastases (cM1a) were randomly assigned to receive either preoperative treatments of induction CapeOx, followed by chemoradiotherapy with CapeOx (CapeOx-RT) (arm A) or CapeOx-RT alone (arm B). Induction CapeOx consisted of oxaliplatin 130 mg/m on day 1 and capecitabine 1000 mg/m twice daily on days 1 to 14, every 3 weeks for 2 cycles; CapeOx-RT consisted of radiotherapy with 45 Gy/25 daily fractions±5.4 Gy/3 fractions, oxaliplatin 50 mg/m weekly for 5 weeks, and capecitabine 825 mg/m twice daily on days 1 to 38. Total mesorectal excision and simultaneous liver metastasectomy were planned within 6 weeks after completion of preoperative treatments. The primary endpoint was R0 resection rate of both the primary tumor and LMs.ResultsThirty-eight patients were randomly assigned to the present study, 18 to arm A and 20 to arm B. The overall R0 resection rate for both the primary tumor and LMs was 77.8% in arm A and 70.0% in arm B (P=0.72). The median progression-free survival was 14.2 versus 15.1 months (P=0.422) and the 3-year overall survival rate was 75.0% versus 88.8% (P=0.29), respectively.ConclusionsBoth treatment strategies showed considerable R0 resection rates; however, further study will be warranted to apply these intensified strategies in clinical practice.
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Project description:Synchronous liver metastasis (SLM) remains a major challenge for rectal cancer. Early detection of SLM is a key factor to improve the survival rate of rectal cancer. In this radiomics study, we predicted the SLM based on the radiomics of primary rectal cancer. A total of 328 radiomics features were extracted from the T2WI images of 194 patients. The least absolute shrinkage and selection operator (LASSO) regression was used to reduce the feature dimension and to construct the radiomics signature. after LASSO, principal component analysis (PCA) was used to sort the features of the surplus characteristics, and selected the features of the total contribution of 85%. Then the prediction model was built by linear regression, and the decision curve analysis was used to judge the net benefit of LASSO and PCA. In addition, we used two independent cohorts for training (n = 135) and validation (n = 159). We found that the model based on LASSO dimensionality construction had the maximum net benefit (in the training set (AUC [95% confidence interval], 0.857 [0.787-0.912]) and in the validation set (0.834 [0.714-0.918]). The radiomics nomogram combined with clinical risk factors and LASSO features showed a good predictive performance in the training set (0.921 [0.862-0.961]) and validation set (0.912 [0.809-0.97]). Our study indicated that radiomics based on primary rectal cancer could provide a non-invasive way to predict the risk of SLM in clinical practice.
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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.
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Project description:Standard use of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy in locally advanced rectal cancer has tremendously improved oncologic outcomes over the past several decades. However, these improvements come with costs of significant morbidity and poor quality of life. Along with developments in imaging techniques, clinical experience and evidence have identified a certain subgroup of patients that have exceptionally good clinical outcomes while preserving quality of life. Driven by patient demand and interest in preserving quality of life, numerous organ preservation treatment strategies for managing rectal cancer are rapidly evolving. Herein, the flow of research in organ preservation strategies and counter arguments are discussed.
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