Faculty Opinions recommendation of Promoter hypermethylation of SHOX2 and SEPT9 is a potential biomarker for minimally invasive diagnosis in adenocarcinomas of the biliary tract.

Background. Acute biliary diseases during pregnancy have been classically managed conservatively. Advances in minimally invasive surgery and the high recurrence rate of symptoms observed changed this management. Methods. This is a prospective observational study. Initial management was medical. Unresponsive patients were treated with minimally invasive techniques including gallbladder percutaneous aspiration or cholecystostomy, endoscopic retrograde cholangiography, and laparoscopic cholecystectomy, depending on the pregnancy trimester and underlying diagnosis. Results. 122 patients were admitted. 69 (56.5%) were unresponsive to medical treatment. Recurrent gallbladder colic was the most frequent indication for minimally invasive intervention, followed by acute cholecystitis, choledocholithiasis, and acute biliary pancreatitis. 8 patients were treated during the first trimester, 54 during the second, and 7 during the last trimester. There was no fetal morbidity or mortality. Maternal morbidity was minor with no mortality. Conclusion. Acute biliary tract diseases during pregnancy may be safely treated with minimally invasive procedures according to the underlying diagnosis and to the trimester of pregnancy.

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hSRBC promoter CpG island hypermethylation as resistant predictive biomarker of oxaliplatin based chemotherapy in metastasic colorectal cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14609 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14609-e14609

Author(s):

Catia Moutinho ◽

Anna Martinez-Cardus ◽

Cristina Santos ◽

Valentín Navarro-Perez ◽

Eva Martinez-Balibrea ◽

...

Keyword(s):

Cox Regression ◽

Cpg Island ◽

Methylation Status ◽

Stage Iv ◽

Predictive Biomarker ◽

Promoter Hypermethylation ◽

Chemotherapeutic Agents ◽

P Value ◽

Potential Biomarker

e14609 Background: Resistance acquisition to chemotherapeutic agents is one of the main problems that come up during cancer treatment. hSRBC is a tumor suppressor gene whose inactivation has been associated with malignant tumor progression. In a previous work, we investigated the influence of hSRBC promoter methylation alterations in oxaliplatin (OXA) resistance acquisition by using a CRC “in vitro” model, detecting an hSRBC promoter hypermethylation in OXA–resistant derived cells when compared with the sensitive counterpart. These results were validated by functional analyses in the same model. Taking this into account, our aim in the present work is to determine the role of hSRBC methylation status as a potential biomarker of OXA resistance, in metastatic CRC patients, treated at first line with fluouropirimidines plus OXA based chemotherapy. Methods: hSRBC promoter hypermethylation was analyzed in DNA extracted from paraffin embebbed tissue of 111 metastatic CRC tumors by using Methylation Specific PCR. Methylation data was correlated to overall response (OR) and progression free survival (PFS) by using F-Fisher test and Kaplan-Meyer Survival curves respectively. A multivariate analysis was carried out by Cox regression. p-values under 0.05 were considered statistic significant. Results: Two independent cohorts of stage IV CRC tumors were included. Twenty-two out of 111 patients received radical surgery for metastasis, that became to be a positive prognostic factor (p-value = 0.04). Gene hypermethylation was detected in a 33% of cases. Although OR was not associated with hSRBC methylation, we observed a significant correlation between hypermethylation of gene and a worse PFS in patients without metastasis surgery (Log Rank; p-value = 0.04). Conclusions: Remarkably, hSRBC promoter hypermethylation is associated with worse PFS in metastatic CRC patients. We suggest hSRBC methylation status as a predictive biomarker of OXA-based treatment outcome in metastatic CRC patients. However, further studies are warranted in order to elucidate the clinical application of these findings.

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Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response

Cancer Research and Treatment ◽

10.4143/crt.2019.493 ◽

2020 ◽

Vol 52 (2) ◽

pp. 594-603 ◽

Cited By ~ 2

Author(s):

Junho Kang ◽

Jae Ho Jeong ◽

Hee-Sang Hwang ◽

Sang Soo Lee ◽

Do Hyun Park ◽

...

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Objective Response ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Complete Response ◽

Current Standard ◽

Durable Response ◽

Tract Cancer ◽

Potential Biomarker

Purpose The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated. Materials and MethodsIn this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks. ResultsBetween May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049). Conclusion Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.

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