The Surgeon’s Perspective on Neoadjuvant Chemoradiation for Rectal Cancer

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

Download Full-text

Patient Risk Subgroups Predict Benefit of Adjuvant Chemotherapy in Stage II Rectal Cancer Patients Following Neoadjuvant Chemoradiation and Total Mesorectal Excision

Clinical Colorectal Cancer ◽

10.1016/j.clcc.2021.02.006 ◽

2021 ◽

Author(s):

Samer Naffouje ◽

Arvind Sabesan ◽

Benjamin D. Powers ◽

Sophie Dessureault ◽

Julian Sanchez ◽

...

Keyword(s):

Rectal Cancer ◽

Adjuvant Chemotherapy ◽

Total Mesorectal Excision ◽

Cancer Patients ◽

Neoadjuvant Chemoradiation ◽

Stage Ii ◽

Mesorectal Excision ◽

Patient Risk

Download Full-text

Multimodal Treatment of cT3 Rectal Cancer in a Prospective Multi-Center Observational Study: Can Neoadjuvant Chemoradiation Be Omitted in Patients with an MRI-Assessed, Negative Circumferential Resection Margin?

Visceral Medicine ◽

10.1159/000514800 ◽

2021 ◽

pp. 1-8

Author(s):

Henry Ptok ◽

Frank Meyer ◽

Ingo Gastinger ◽

Benjamin Garlipp

Keyword(s):

Rectal Cancer ◽

Observational Study ◽

Circumferential Resection Margin ◽

Resection Margin ◽

Anal Verge ◽

Final Analysis ◽

Radical Resection ◽

Distant Recurrence ◽

Neoadjuvant Chemoradiation ◽

Recurrence Rates

Background/Aim: Neoadjuvant chemoradiation (nCRT) in rectal cancer is associated with significant long-term morbidity. It is unclear whether nCRT in resectable mesorectal fascia circumferential resection margin (mrCRM)-negative rectal cancer treated by adequate total mesorectal excision (TME) is beneficial. The aim was to determine if nCRT can be omitted in patients with MRI-assessed cT3 rectal cancer and a negative mrCRM undergoing good-quality TME. Methods: By means of a prospective nationwide registry (n = 43.147; prospective multi-center observational study), patients with cT3 rectal cancer <12 cm from the anal verge with a negative (>1 mm) MRI-assessed CRM undergoing radical resection from 2006 to 2008 were selected. Overall, 87 patients were available for the final analysis (TME-alone, n = 25; nCRT+TME, n = 62). Groups were balanced for age, sex, and ASA score, with a nonsignificant predominance of males in the nCRT+TME group. As main outcome measures, local and distant recurrence rates were compared between patients undergoing primary surgery (TME-alone) vs. neoadjuvant chemoradiation + surgery (nCRT+TME). Results: In the TME-alone group, tumors were located closer to the anal verge (p = 0.018) and demonstrated a smaller minimal circumferential distance from the resection margin (p = 0.036). TME quality was comparable, as was median follow-up (48.9 vs. 44.9 months; p = 0.268). Local recurrences occurred at a similar rate in the TME-alone (n = 1; 5.3%) and nCRT+TME groups (n = 3; 5.5%) (p = 0.994) and were diagnosed at 10 months (TME-alone) and at 8, 13, and 18 months (nCRT+TME). Distant recurrences occurred in 28.9 and 17.4% of the cases, respectively (p = 0.626). The analysis was limited to cT3 cancers with a negative mrCRM. In addition, caution is required when appraising these results because of the limited number of evaluable subjects (especially in the TME-alone group), which adds some uncertainty to the statistical analysis. Conclusions: In this cohort of patients with rectal cancer located <12 cm from the anal verge and a negative mrCRM undergoing adequate TME, omission of nCRT had no impact onto the local recurrence rate.

Download Full-text