CA : A Cancer Journal for Clinicians

Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority.

The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9–12, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.

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Comprehensive molecular characterization of gastric adenocarcinoma

Infectious Diseases Society of America.

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Patterns of Somatic Mutation in Human Cancer Genomes

Purpose
To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases.

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Prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases.

Background Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. Patients and methods We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score positivity. Results Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p = 0.002) and PFS (7.8 vs. 5.4 months, p = 0.005) than those who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer. Conclusion This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.

Programmed Death Ligand 1 Expression as a Prognostic Marker in Patients with Advanced Biliary Tract Cancer.

Background: The aim of this study was to identify subgroups that benefit from preoperative or postoperative chemoradiotherapy (CRT) for rectal cancer of intermediate stage. Patients and Methods: Between 1999 and 2004, 118 and 177 patients matched with respect to clinical T stage, circumferential tumor extent (= 60% / > 60%), lymph node metastasis, and lymph node size (Results: Local recurrence, distant metastasis, disease-free survival, and disease-specific survival were not different between the two schemes. For a circumferential tumor extent of = 60%, local recurrence in preoperative CRT (3.6%) was lower than in postoperative CRT (11.9%) (p = 0.084, hazard ratio (HR) = 0.274, 95% confidence interval (CI) = 0.058–1.032). For a tumor located Conclusions: Our findings suggest that preoperative CRT might be appropriate in rectal cancer involving the limited circumferential lumen and located in the low rectum. However, further prospective studies are required.

Which Patients Benefit from Preoperative Chemoradiotherapy for Intermediate Staged Rectal Cancer

// Hee Kyung Kim 1 , Sang Yun Ha 2 , Jeeyun Lee 1 , Se Hoon Park 1 , Joon Oh Park 1 , Ho Yeong Lim 1 , Won Ki Kang 1 , Young Suk Park 1 and Seung Tae Kim 1 1 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Correspondence to: Seung Tae Kim, email: seungtae1.kim@samsung.com Keywords: pathologic differentiation, Ki67 index, gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)s Received: October 17, 2016      Accepted: May 12, 2017      Published: May 25, 2017 ABSTRACT We investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum (EP)-based therapy, and evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from EP-based therapy. A total of 31 patients with metastatic grade 3 GEP-NECs receiving EP-based therapy were included in this study. Primary sites included 13 foregut-derived GEP-NECs [stomach ( n = 4), duodenum ( n = 4), and pancreas ( n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. 14 patients had well differentiated (WD) and 17 had poorly differentiated (PD). Between WD and PD grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between WD and PD grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67 ≤ 60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). Among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between WD and PD NECs. Higher levels (> 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs.

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The impact of pathologic differentiation (well/poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs

11534Background: Analysis of cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is a promising method to identify druggable genomic alterations, especially when tumor speci

Won Ki Kang

Papers

Prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases.

Programmed Death Ligand 1 Expression as a Prognostic Marker in Patients with Advanced Biliary Tract Cancer.

Which Patients Benefit from Preoperative Chemoradiotherapy for Intermediate Staged Rectal Cancer

The impact of pathologic differentiation (well/poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs

Cell-free DNA sequencing-guided therapy in a prospective clinical trial: NEXT-2 trial—A feasibility analysis.