Dataset Information

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study.

ABSTRACT:

Importance

The treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking.

Objective

To assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing perioperative morbidity.

Design, setting, and participants

This cohort study included patients with LARC from 6 referral centers who completed NAT and underwent TME between January 2005 and December 2020. The cohort was divided into 3 groups depending on the time interval between NAT completion and surgery: short (≤8 weeks), intermediate (>8 and ≤12 weeks), and long (>12 weeks). The median follow-up duration was 33 months. Data analyses were conducted from May 1, 2021, to May 31, 2022. The inverse probability of treatment weighting method was used to homogenize the analysis groups.

Exposure

Long-course chemoradiotherapy or short-course radiotherapy with delayed surgery.

Main outcome and measures

The primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes.

Results

Among the 1506 patients, 908 were male (60.3%), and the median (IQR) age was 68.8 (59.4-76.5) years. The short-, intermediate-, and long-interval groups included 511 patients (33.9%), 797 patients (52.9%), and 198 patients (13.1%), respectively. The overall pCR was 17.2% (259 of 1506 patients; 95% CI, 15.4%-19.2%). When compared with the intermediate-interval group, no association was observed between time intervals and pCR in short-interval (odds ratio [OR], 0.74; 95% CI, 0.55-1.01) and long-interval (OR, 1.07; 95% CI, 0.73-1.61) groups. The long-interval group was significantly associated with lower risk of bad response (tumor regression grade [TRG] 2-3; OR, 0.47; 95% CI, 0.24-0.91), systemic recurrence (hazard ratio, 0.59; 95% CI, 0.36-0.96), higher conversion risk (OR, 3.14; 95% CI, 1.62-6.07), minor postoperative complications (OR, 1.43; 95% CI, 1.04-1.97), and incomplete mesorectum (OR, 1.89; 95% CI, 1.02-3.50) when compared with the intermediate-interval group.

Conclusions and relevance

Time intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

SUBMITTER: Guzman Y

PROVIDER: S-EPMC10339219 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study.

Guzmán Yoelimar Y Ríos José J Paredes Jesús J Domínguez Paula P Maurel Joan J González-Abós Carolina C Otero-Piñeiro Ana A Almenara Raúl R Ladra María M Prada Borja B Pascual Marta M Guerrero María Alejandra MA García-Granero Álvaro Á Fernández Laura L Ochogavia-Seguí Aina A Gamundi-Cuesta Margarita M González-Argente Francesc Xavier FX Pons Lorenzo Viso LV Centeno Ana A Arrayás Ángela Á de Miguel Andrea A Gil-Gómez Elena E Gómez Beatriz B Martínez José Gil JG Lacy Antonio M AM de Lacy F Borja FB

JAMA surgery 20230901 9

<h4>Importance</h4>The treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking.<h4>Objective</h4>To assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing pe ...[more]

PMID: 37436726

Similar Datasets

Project description:BackgroundThe focus of this study was to determine the optimal time interval between neoadjuvant chemoradiotherapy (nCRT) and surgery in patients with locally advanced rectal cancer (LARC) who had an unfavorable pathological response, as well as to investigate the correlation between long-term outcomes and the duration of this interval.MethodsThe present study retrospectively analyzed patients with locally advanced rectal cancer who underwent nCRT followed by total mesorectal excision between (TME) January 2018 and September 2021. Patients included in this study had an unfavorable pathological response, confirmed as tumor regression grade (TRG) 2-3. X-tile analysis was subsequently conducted to determine the optimal cut-off value for the time interval between nCRT and surgery. Furthermore, Cox proportional hazards regression analyses were performed to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate long-term survival.ResultsThe study cohort comprised of 114 patients (51.35%) in the longer interval group (>8 weeks), while the remaining 108 patients (48.65%) belonged to the shorter interval group (≤8 weeks). Univariable and multivariate Cox proportional hazards regression analyses revealed that a longer interval time was identified as an independent risk factor for overall survival (HR: 2.14, 95% CI: 1.01-4.55, P=0.048) and disease-free survival (HR: 2.03, 95% CI: 1.09-3.77, P=0.025) among these patients. Moreover, patients in the longer interval group exhibited significantly worse OS and DFS compared to those in the shorter interval group (3-year OS: 87.2% vs 68.2%, P=0.001; 3-year DFS: 80.4% vs 62.7%, P=0.003). Furthermore, similar results were observed in subgroup analyses based on different TRG scores.ConclusionsThe surveillance and monitoring should be promptly conducted following nCRT in order to promptly identify patients with an unfavorable pathological response, who would benefit from timely radical surgery within 8 weeks.

Project description:ImportanceTreatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases.ObjectiveTo compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC.Design, setting, and participantsA retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified.ExposuresOf the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT).Main outcomes and measuresTreatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK.ResultsOf the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort.Conclusions and relevanceOur findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

Dataset Information

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study.

Importance

Objective

Design, setting, and participants

Exposure

Main outcome and measures

Results

Conclusions and relevance

Publications

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets