Survival outcomes analysis according to mismatch repair status in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy

Abstract

BackgroundThe predictive role of mismatch repair (MMR) status for survival outcomes and sensitivity in neoadjuvant chemoradiotherapy settings for patients with locally advanced rectal cancer (LARC) has been inconclusive.MethodsA retrospective cohort of patients with LARC treated with neoadjuvant chemoradiotherapy (nCRT) was recruited. After adjusting for baseline characteristics, we used propensity score matching to reduce the effect of potential confounding factors on MMR status. The primary analysis was based on overall survival as the more important endpoint.ResultsThis study included 269 patients. Patients with defective MMR (dMMR) were younger (58.5% vs. 60.0%, p=0.0274) and had lower body mass indices (p=0.0091), higher differentiation grades (p=0.0889), and more advanced rectal cancers (clinical T4 or T4b, p=0.0851; M1, p=0.0055) than those with proficient MMR (pMMR). However, propensity score-matched patients with dMMR (p=0.0013) exhibited superior overall survival, even in the M1 subgroup. More importantly, patients with proficient MMR who undergo early pathological downstaging, especially lymph node pathological downstaging, can achieve a prognosis similar to that of patients with dMMR.ConclusionThe clinical significance of this retrospective study mainly includes two points: (1) Data from our study confirmed that LARC patients with dMMR status had better overall survival rates after nCRT, even in the M1 subgroup. (2) Similar survival outcomes were observed in older and female patients with early lymph node pathological downstaging, regardless of dMMR or pMMR.

Cytokeratin 7 Expression and Mismatch Repair Status for Survival Prediction in Patients With Low Rectal Cancer After Neoadjuvant Therapy

“… 24 Conversely, Chen et al found there were better overall survival rates for LARC patients with dMMR status after nCRT. 25 Kim JH et al also demonstrated the prognostic features of MSI-H CRCs include a favorable survival of patients. 26 There may be two main reasons for this: One possible explanation for the converse result involves different nCRT regimens, such as consolidation chemotherapy with Capeox or mFOLFOX6 regimens can significantly improve survival, 27 , 28 while a limited effects of fluoropyrimidines may happened during nCRT.…”

“…All patients underwent chemoradiotherapy before total mesorectal excision, which defined as neoadjuvant chemoradiotherapy, including chemotherapy regimens with fluorouracil/oxaliplatin, and radiotherapy was administered at 2.0 Gy in 25 fractions over 5 weeks, with a total dose of 50 Gy (24)(25)(26). Physical examinations and computed tomography scans were performed every 3-6 months for the first 1 year and every 6 months for the following 2 years after TME as a routine follow-up strategy for all patients.…”

New immunotherapy strategies and related therapeutic targets for gastrointestinal malignancies

“…The MYC oncogene is part of the gene superfamily, and its product is commonly activated in human cancers (94,95). The mechanisms by which MYC activation promotes tumor progression mainly involve cell proliferation, cell invasion, metabolic reprogramming, genomic instability, angiogenesis, and immune evasion (96,97). MYC can reshape the tumor microenvironment, evading host immune responses (98).…”

“…Following H. pylori infection, phagocytes that have gathered in the stomach mucosa produce O2•, HO•, and HOCl (95). Rat gastric mucosal cells have been shown to undergo apoptosis when exposed to NH 2 Cl (96).…”

“…Currently, neoadjuvant chemoradiotherapy followed by total mesorectal excision is considered the optimal treatment for LARC (74). However, recent results have shown that compared to neoadjuvant chemoradiotherapy alone (10.5%-38.0%), long-term radiation therapy (LCRT) or short-term radiation therapy (SCRT) combined with immunotherapy can significantly improve the pCR rate (37.5%-50.0%) of LARC patients without increasing the risk of AEs (96,97). Moreover, the determination of radiotherapy strategies may further improve the safety of combination therapy.…”