The Use of Single-Agent Versus Multiple-Agent Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Rectal Cancer

2021 ◽  
Author(s):  
Thomas Peponis ◽  
Caitlin Stafford ◽  
James Cusack ◽  
Christy Cauley ◽  
Robert Goldstone ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Multiple Agent

The Use of Single-agent Versus Multiple-agent Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Rectal Cancer

2021 ◽  
Author(s):  
Thomas Peponis ◽  
Caitlin Stafford ◽  
James Cusack ◽  
Christy Cauley ◽  
Robert Goldstone ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Concurrent Chemoradiotherapy ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Resection Margins ◽  
Multiple Agent ◽  
Single Agent Chemotherapy

Abstract Purpose: The use of concurrent chemoradiotherapy is frequently recommended in the treatment of locally advanced rectal cancer however the ideal chemotherapy regimen remains unknown and there is variability in chemotherapy agents used among different institutions. We sought to examine differences in overall survival between patients receiving single versus multiple-agent concurrent chemoradiotherapy.Methods: The National Cancer Database was used to identify 31,025 patients with rectal cancer who received concurrent chemoradiotherapy between 01/2006 through 12/2016. We compared patients who received single-agent chemotherapy with those who received multiple-agent concurrent chemoradiotherapy. The primary outcome of interest was overall survival. The groups were compared using univariate analysis and Cox proportional hazard models to adjust for potential confounding factors. Results: 18,544 patients received single-agent and 12,481 patients received multiple-agent chemotherapy. The former were older with more comorbidities as evidenced by their higher Charlson-Deyo Scores. Those receiving multiple-agent chemotherapy were more likely to have clinical Stage III disease (52.9% vs 43.3%, p<0.001) and less likely to have well-differentiated cancer (6.9% vs 7.7%, p<0.001). The rates of negative resection margin were identical (p=0.225) between the two groups. On multivariable analysis after adjusting for comorbidities, radiation dose, and resection margins, single-agent chemotherapy was associated with worse overall survival (HR 1.09, 95% CI 1.057-1.124, p<0.001). Conclusion: Multiple-agent chemoradiotherapy is associated with improved overall survival in locally advanced rectal cancer, however chemotherapy regimen does not affect resection margins. The modest overall survival benefit with multiple agent chemotherapy must be balanced with the potential associated toxicity.

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

Phase I trial of neoadjuvant concurrent chemoradiotherapy with S-1 and weekly irinotecan in locally advanced rectal cancer

2008 ◽  
Vol 87 (3) ◽  
pp. 361-366 ◽  
Author(s):  
Hye Jin Choi ◽  
Nam-Kyu Kim ◽  
Ki Chang Keum ◽  
Seong Ha Cheon ◽  
Sang Jun Shin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

scholarly journals Neoadjuvant Concurrent Chemoradiotherapy in Treating Locally Advanced Rectal Cancer

2009 ◽  
Vol 72 (4) ◽  
pp. 179-182 ◽  
Author(s):  
Chia-Ming Twu ◽  
Hwei-Ming Wang ◽  
Joe-Bin Chen ◽  
Te-Hsin Chao ◽  
Hsiu-Feng Mar
Keyword(s):  
Rectal Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

scholarly journals High throughput proteomic analysis and machine learning algorithm identifies DUOX2 (dual oxidase 2) as a novel biomarker for response prediction of concurrent chemoradiotherapy for locally advanced rectal cancer.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 71-71
Author(s):  
Hyebin Lee
Keyword(s):  
Machine Learning ◽  
Rectal Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Response Prediction ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Machine Learning Algorithms ◽  
Dual Oxidase

71 Background: Although many efforts to predict treatment response of concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) have been made, no molecular has proved to be a robust biomarker. Methods: We performed mass spectrometry-based quantitative proteomic analysis of pretreatment Formalin-fixed, Paraffin-embedded (FFPE) biopsy samples of 13 patients with LARC, who were treated with CCRT followed by curative surgery. Based on pathologic report of surgical specimens, we divided thirteen patients as two response groups: complete response (CR) and non-complete response (nCR) groups. Results: A total of 3,637 proteins were identified and 498 proteins were confirmed as expressed at significantly different levels (DEPs; differently expressed proteins) between these two groups. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were also performed: the result showed that up-regulated DEPs enriched in biological processes (BP) were significantly different between two groups; immune response, cell migration & motility, protein transport in CR group; amide/peptide biosynthetic process, translation, posttranscriptional regulation of gene expression and detoxification in nCR group. To identify the best classifier to evaluate predictive power of signatures, we employed for different machine learning algorithms to classify samples between CR and nCR groups. As a result, we identified the predictive relevance of dual oxidase 2 (DUOX2) as the strongest predictive biomarker. Conclusions: This study identified a new biomarker, DUOX2, applicable to discrimination between CR and nCR after NACRT for LARC. To our knowledge, the present study provides the first identification of a clinical biomarker for response prediction based on in-depth proteomics and machine learning algorithms.

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