Combining Immunotherapy With Neoadjuvant Chemoradiation in the Treatment of Locally Advanced, Resectable Esophago-Gastric Cancers

2022 ◽  
Keyword(s):  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Gastric Cancers

scholarly journals Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

2021 ◽  
Vol 9 (3) ◽  
pp. e001610
Author(s):  
Incheol Seo ◽  
Hye Won Lee ◽  
Sang Jun Byun ◽  
Jee Young Park ◽  
Hyeonji Min ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Enrichment Analysis ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Cytolytic Activity ◽  
Gene Set Enrichment Analysis ◽  
Preoperative Treatment ◽  
Rna Seq

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.

scholarly journals Demographic Trends in Carcinoma Esophagus from India along with a Brief Comparative Review of the Global Trends

2020 ◽  
Vol 09 (03) ◽  
pp. 163-167
Author(s):  
Arvind Krishnamurthy ◽  
Siva Shankar Behuria
Keyword(s):  
East Asian ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Histological Subtype ◽  
The West ◽  
Demographic Trends ◽  
Global Trends ◽  
Comparative Review ◽  
Periodic Monitoring ◽  
Total Cancer

Abstract Background Esophageal cancers (ECs) are more prevalent in the East Asian countries of the world, wherein squamous cell carcinomas (SCCs) are the predominant histological subtype. In contrast, the patterns in the West are a bit heterogeneous, with esophageal adenocarcinoma (AC) being the more frequent histological subtype. There is very sparse published Indian data pertaining to the demographic trends of ECs. Materials and Methods Our study was a retrospective analysis of the demographic trends of 917 patients afflicted with ECs who were managed at our center over a 10-year period. Results and Discussion EC accounted for nearly 4.1% of the total cancer burden managed at our center from January 2002 to December 2011. The mean age of our patient cohort was 54.2 years. The male:female ratio was nearly 1.7:1. Tobacco chewing was noted in 25.4%, smoking in 37%, while alcohol consumption was noted in approximately 20% of the patients. SCC was the most common histological subtype (78.3%), while ACs constituted only 9.9%. Eighty-nine percent of our patients presented with locally advanced staged tumors. Definitive chemoradiation was the most common modality of definitive management then; however, over the years, our preferred choice of the management of ECs has shifted to neoadjuvant chemoradiation, followed by surgery in the carefully selected patients of locally advanced resectable ECs. Conclusion Our study clearly shows SCC to be the most common histological subtype among ECs, a trend that has been observed in the vast majority of the East Asian nations. The epidemic rise in the incidence of esophageal ACs as seen in the West is not seen in our study. Periodic monitoring of the demographic trends of ECs is of great importance both for clinicians and policymakers. We hope that our study will enlighten both policy holders and clinicians to better channelize the efforts toward prevention and more effective management of this deadly cancer.

scholarly journals Cost Effectiveness of Watch and Wait Versus Resection in Rectal Cancer Patients with Complete Clinical Response to Neoadjuvant Chemoradiation

2021 ◽  
Author(s):  
Christina Liu Cui ◽  
William Yu Luo ◽  
Bard Clifford Cosman ◽  
Samuel Eisenstein ◽  
Daniel Simpson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cost Effectiveness ◽  
Clinical Response ◽  
Disease Progression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Complete Clinical Response ◽  
Watch And Wait ◽  
Recurrence Rates ◽  
Life Years

Abstract Background Watch and wait (WW) protocols have gained increasing popularity for patients diagnosed with locally advanced rectal cancer and presumed complete clinical response after neoadjuvant chemoradiation. While studies have demonstrated comparable survival and recurrence rates between WW and radical surgery, the decision to undergo surgery has significant effects on patient quality of life. We sought to conduct a cost-effectiveness analysis comparing WW with abdominoperineal resection (APR) and low anterior resection (LAR) among patients with stage II/III rectal cancer. Methods In this comparative-effectiveness study, we built Markov microsimulation models to simulate disease progression, death, costs, and quality-adjusted life-years (QALYs) for WW or APR/LAR. We assessed cost effectiveness using the incremental cost-effectiveness ratio (ICER), with ICERs under $100,000/QALY considered cost effective. Probabilities of disease progression, death, and health utilities were extracted from published, peer-reviewed literature. We assessed costs from the payer perspective. Results WW dominated both LAR and APR at a willingness to pay (WTP) threshold of $100,000. Our model was most sensitive to rates of distant recurrence and regrowth after WW. Probabilistic sensitivity analysis demonstrated that WW was the dominant strategy over both APR and LAR over 100% of iterations across a range of WTP thresholds from $0–250,000. Conclusions Our study suggests WW could reduce overall costs and increase effectiveness compared with either LAR or APR. Additional clinical research is needed to confirm the clinical efficacy and cost effectiveness of WW compared with surgery in rectal cancer.

scholarly journals Mucinous Adenocarcinoma Associated with Fistula in an 87-Year-Old Managed with Neoadjuvant Chemoradiation and ELAPE at Tata Memorial Hospital, in Mumbai

2020 ◽  
pp. 1-4
Author(s):  
Avanish Saklani ◽  
Seke Manase Ephraim KAZUMA ◽  
Vivek Sukumar ◽  
Avanish Saklani
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Mucinous Adenocarcinoma ◽  
Poor Prognosis ◽  
Locally Advanced ◽  
Delayed Diagnosis ◽  
Neoadjuvant Chemoradiation ◽  
Tata Memorial Hospital ◽  
The Third ◽  
Cutaneous Flap

Colorectal cancer is the third most diagnosed cancer and the fourth leading cancer-related death worldwide. Mucinous adenocarcinoma associated with anal fistula is a rare variant of adenocarcinoma, presents with delayed diagnosis, locally advanced, low nodal, and no distant metastasis. Adenocarcinoma associated with fistula (ACAF) is rare, has delayed diagnosis and poor prognosis but can be managed with neoadjuvant chemoradiation (NACRT) and complete curative resections with reconstruction by V-Y advancement cutaneous flap.

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