Dataset Information

Potentially Curable Cancers of the Esophagus and Stomach.

ABSTRACT: Gastric and gastroesophageal adenocarcinomas continue to be a major health burden globally and collectively represent the third leading cause of cancer death. Among patients with metastatic disease, most die of their cancer because of the limited number of modestly effective treatment regimens available today. The progress against these cancers has been slow compared with many other solid tumors despite many attempts. In-depth molecular profiling has also not been completed. Even when these cancers are localized, they impose considerable challenges for the patient, relatives, and treatment team alike. Localized gastric or gastroesophageal cancer is best managed with a multidisciplinary approach. This review focuses on the management of localized cancers by reviewing the current literature and explaining certain principles that help guide therapy for these patients. The future, however, will afford numerous opportunities, including exploitation of initial data from The Cancer Genome Atlas, to identify novel targets and drugs, harness the prowess of the immune system, and customize therapy for each patient.

SUBMITTER: Elimova E

PROVIDER: S-EPMC5712474 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Potentially Curable Cancers of the Esophagus and Stomach.

Elimova Elena E Mizrak Kaya Dilsa D Harada Kazuto K Ajani Jaffer A JA

Mayo Clinic proceedings 20160901 9

Gastric and gastroesophageal adenocarcinomas continue to be a major health burden globally and collectively represent the third leading cause of cancer death. Among patients with metastatic disease, most die of their cancer because of the limited number of modestly effective treatment regimens available today. The progress against these cancers has been slow compared with many other solid tumors despite many attempts. In-depth molecular profiling has also not been completed. Even when these canc ...[more]

PMID: 27594190

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Project description:One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P?=?0.005) and stomach cancer (posterior homogeneity P?=?0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P?=?0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the associations between MTR/MTRR polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway.

Project description:BackgroundPerioperative chemotherapy/chemoradiation is standard in esophageal/gastric/gastroesophageal junction (GEJ) adenocarcinoma, immune checkpoint inhibitors (ICI) effect in setting of metastatic and postoperatively. This study is to assess ICI + chemotherapy perioperatively.MethodsPatients with locally advanced (T1N1-3M0 or T2-3NanyM0) potentially resectable esophageal/gastric/GEJ adenocarcinoma by PET/EUS/CT and staging-laparoscopy, were treated preoperative 4 cycles mFOLFOX6 (Oxaliplatin 85 mg/m2 /Leucovorin 400 mg/m2 /5-FU bolus 400 mg/m2 then infusion 2400 mg/m2 for 46 h q2weeks) and 3 cycles pembrolizumab (200 mg q3week). Those without distal disease post-neoadjuvant and eligible for resection underwent surgery. Postoperative treatment was initiated at 4-8 weeks with 4 cycles mFOLFOX and 12 cycles pembrolizumab. The primary objective is pathological response (ypRR with tumor regression score, TRS ≤2). The expression of ICI-related markers PD-L1 (CPS), CD8, and CD20 were analyzed before and after preoperative therapy.ResultsThirty-seven patients completed the preoperative treatment. Twenty-nine patients had curative R0 resection. 6/29 (21%; 95% CI: 0.08-0.40) achieved ypCR with TRS 0 in resected patients. 26/29 (90%; 95% CI: 0.73-0.98) had ypRR with TRS ≤2. Twenty-six patients finished adjuvant therapy with a median 36.3-month follow-up. Three patients had recurrence/metastatic disease (at 9-, 10-, 22 months enrollment) with one dead at 23 months, and two are still alive at 28 and 36.5 months. The remaining (23/26) are free of disease with 3 years DFS of 88.5% and 3 years OS of 92.3%. There were no unexpected toxicities. Preoperative ICI + chemotherapy enhanced immune responses significantly with increasing expression of PD-L1 (CPS ≥10, p = 0.0078) and CD8 (>5%, p = 0.0059).ConclusionsThe perioperative pembrolizumab and mFOLFOX combination in resectable esophageal/gastric/GEJ adenocarcinoma is very effective with 90% ypRR, 21% ypCR, and impressive long-time survival benefits.

Project description:ImportanceThere is limited information on the association among complementary medicine (CM), adherence to conventional cancer treatment (CCT), and overall survival of patients with cancer who receive CM compared with those who do not receive CM.ObjectivesTo compare overall survival between patients with cancer receiving CCT with or without CM and to compare adherence to treatment and characteristics of patients receiving CCT with or without CM.Design, setting, and participantsThis retrospective observational study used data from the National Cancer Database on 1?901?815 patients from 1500 Commission on Cancer-accredited centers across the United States who were diagnosed with nonmetastatic breast, prostate, lung, or colorectal cancer between January 1, 2004, and December 31, 2013. Patients were matched on age, clinical group stage, Charlson-Deyo comorbidity score, insurance type, race/ethnicity, year of diagnosis, and cancer type. Statistical analysis was conducted from November 8, 2017, to April 9, 2018.ExposuresUse of CM was defined as "Other-Unproven: Cancer treatments administered by nonmedical personnel" in addition to at least 1 CCT modality, defined as surgery, radiotherapy, chemotherapy, and/or hormone therapy.Main outcomes and measuresOverall survival, adherence to treatment, and patient characteristics.ResultsThe entire cohort comprised 1?901?815 patients with cancer (258 patients in the CM group and 1?901?557 patients in the control group). In the main analyses following matching, 258 patients (199 women and 59 men; mean age, 56 years [interquartile range, 48-64 years]) were in the CM group, and 1032 patients (798 women and 234 men; mean age, 56 years [interquartile range, 48-64 years]) were in the control group. Patients who chose CM did not have a longer delay to initiation of CCT but had higher refusal rates of surgery (7.0% [18 of 258] vs 0.1% [1 of 1031]; P?<?.001), chemotherapy (34.1% [88 of 258] vs 3.2% [33 of 1032]; P?<?.001), radiotherapy (53.0% [106 of 200] vs 2.3% [16 of 711]; P?<?.001), and hormone therapy (33.7% [87 of 258] vs 2.8% [29 of 1032]; P?<?.001). Use of CM was associated with poorer 5-year overall survival compared with no CM (82.2% [95% CI, 76.0%-87.0%] vs 86.6% [95% CI, 84.0%-88.9%]; P?=?.001) and was independently associated with greater risk of death (hazard ratio, 2.08; 95% CI, 1.50-2.90) in a multivariate model that did not include treatment delay or refusal. However, there was no significant association between CM and survival once treatment delay or refusal was included in the model (hazard ratio, 1.39; 95% CI, 0.83-2.33).Conclusions and relevanceIn this study, patients who received CM were more likely to refuse additional CCT, and had a higher risk of death. The results suggest that mortality risk associated with CM was mediated by the refusal of CCT.

Dataset Information

Potentially Curable Cancers of the Esophagus and Stomach.

Publications

Potentially Curable Cancers of the Esophagus and Stomach.

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