Evaluation of blood MSI burden dynamics to trace immune checkpoint inhibitor therapy efficacy through the course of treatment.

Analysis of serial liquid biopsy (LB) samples has been found to be a promising approach for the monitoring of tumor dynamics in the course of therapy for patients with colorectal cancer (CRC). Currently, somatic mutations are used for tracing the dynamics of the tumor via LB. However, the analysis of the dynamic changes in the molecular signatures such as microsatellite instability (MSI) is not currently used.

Failure of immune checkpoint inhibitors for microsatellite instability-positive pancreatic adenocarcinoma with atypical pattern of short tandem repeat mutation.

Microsatellite instability (MSI) is an important biomarker in cancer. While routine methods can detect MSI in certain tumor types, in other tumor types the results may be incorrect due to differences in the MSI loci pattern. Here, we report the case of a patient with pancreatic adenocarcinoma, with confirmed MSI by two independent next-generation sequencing tests, but not by routine methods, who had progression on pembrolizumab.

Evidence blocks for effective presentation of genomic findings at molecular tumor boards: Single institution experience.

Genomic profiling, or molecular profiling of the tumor, is becoming a key component of therapeutic decision making in clinical oncology, and is typically carried out via next generation sequencing. However, the interpretation of the results and evaluation of rationale for targeting the uncovered alterations is challenging and requires a deep understanding of cancer biology, genetics, genomics and oncology. Multidisciplinary molecular tumor boards represent a promising strategy in the facilitation of molecularly-informed therapeutic decisions, and usually consist of specialists with various fields of expertise.

Prognostic and predictive role of immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide. The traditional classification of CRC is based on pathomorphological and molecular characteristics of tumor cells (mucinous, ring-cell carcinomas, ), analysis of mechanisms of carcinogenesis involved (chromosomal instability, microsatellite instability, CpG island methylator phenotype) and mutational statuses of commonly altered genes (KRAS, NRAS, BRAF, APC, ), as well as expression signatures (CMS 1-4). It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.

Case Report: Progressive disease of BRCA2-mutant colon adenocarcinoma following talazoparib therapy.

Colorectal cancer (CRC) is currently one of the most common tumor types diagnosed worldwide. In the early stages, the disease responds well to surgical and chemotherapeutic treatment, but in the later stages when therapeutic options are exhausted, comprehensive genomic profiling can guide further treatment decisions. We present the case of a 46-year-old man of Ashkenazi Jewish ancestry who was diagnosed with KRAS-mutated metastatic colorectal cancer.

Detecting Microsatellite Instability in Endometrial, Colon, and Stomach Cancers Using Targeted NGS.

Purpose: To develop a method for testing the MSI based on targeted NGS.

Methods: Based on the results of previous studies, 81 microsatellite loci with high variability in MSI-H tumors were selected, and a method for calculating the MSI score was developed. Using the MSI score, we defined the MSI status in endometral (162), colon (153), and stomach (190) cancers.

Precision oncology strategy in cetuximab-resistant ERRFI1-mutant colon cancer: case report of disease progression on afatinib.

Despite the existence of effective first and second line therapy options for patients with colorectal cancer, heavily treated patients have limited additional therapies. Genomic profiling is a promising tool for guiding subsequent treatment selection. Here, we describe the results of treating a colorectal cancer patient with molecularly-matched therapy based on the results of genomic profiling.

Risk Factors for Relapse in Nonseminomatous Testicular Cancer After Postchemotherapy Retroperitoneal Lymph Node Dissection With Viable Residual Cancer.

Purpose: No consensus exists on the management of men with nonseminoma and viable nonteratomatous germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection (pcRPLND) specimen after first-line chemotherapy. We analyzed surveillance versus different adjuvant chemotherapy regimens and the influence of time to pcRPLND on oncologic outcomes.

Methods: Data on 117 men treated with cisplatin-based first-line chemotherapy between 1990 and 2018 were collected from 13 institutions.

Microsatellite Instability: A Review of Molecular Epidemiology and Implications for Immune Checkpoint Inhibitor Therapy.

Microsatellite instability (MSI) is one of the most important molecular characteristics of a tumor, which occurs among various tumor types. In this review article, we examine the molecular characteristics of MSI tumors, both sporadic and Lynch-associated. We also overview the risks of developing hereditary forms of cancer and potential mechanisms of tumor development in patients with Lynch syndrome.

Utility of public knowledge bases for the interpretation of comprehensive tumor molecular profiling results.

With the growing use of comprehensive tumor molecular profiling (CTMP), the therapeutic landscape of cancer is rapidly evolving. NGS produces large amounts of genomic data requiring complex analysis and subsequent interpretation. We sought to determine the utility of publicly available knowledge bases (KB) for the interpretation of the cancer mutational profile in clinical practice.

Clinical significance of molecular subtypes of gastrointestinal tract adenocarcinoma.

Adenocarcinomas of the gastrointestinal tract (esophagus, stomach, and colon) represent a heterogeneous group of diseases with distinct etiology, clinical features, treatment approaches, and prognosis. Studies are ongoing to isolate molecular genetic subtypes, perform complete biological characterization of the tumor, determine prognostic groups, and find predictive markers to the effectiveness of therapy. Separate molecular genetic classifications were created for esophageal adenocarcinoma [The Cancer Genome Atlas (TCGA)], stomach cancer (TCGA, Asian Cancer Research Group), and colon cancer (Colorectal Cancer Subtyping Consortium).

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

Purpose: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients.

Methods: Files from two registry studies and one single-institution database were analyzed retrospectively.

Efficacy of platinum-based chemotherapy and prognosis of patients with pancreatic cancer with homologous recombination deficiency: comparative analysis of published clinical studies.

The aim of our study was to determine the effect of homologous recombination deficiency (HRD) on prognosis and efficacy of platinum-based chemotherapy in patients with pancreatic cancer (PC). We performed PubMed and Embase database queries. We included 4 studies into the meta-analysis and 16 studies in the systematic review.

Epstein-Barr virus-associated gastric cancer: disease that requires special approach.

Epstein-Barr virus-associated gastric cancer [EBV-associated GC, EBV( +) GC] is a distinct molecular subtype of gastrointestinal (GI) cancers. It accounts for up to 10% of all molecular subtypes of gastric cancer (GC). It has unique genetic and epigenetic features, which determine its definitive phenotype with male and younger age predominance, proximal stomach localization, and diffuse adenocarcinoma histology.

Human chorionic gonadotropin-positive seminoma patients: A registry compiled by the global germ cell tumor collaborative group (G3).

Background: The prognostic role of human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH) serum levels in seminoma patients remains uncertain. This observational study evaluates the prognostic impact of tumour marker levels, and other clinicopathological findings, in hCG-positive seminoma patients.

Methods: Seminoma patients with serum hCG levels above normal at first diagnosis were eligible for recruitment.

Aflibercept Plus FOLFIRI for Second-line Treatment of Metastatic Colorectal Cancer: Observations from the Global Aflibercept Safety and Health-Related Quality-of-Life Program (ASQoP).

Background: The objectives of this study were to evaluate the safety profile of aflibercept and health-related quality of life (HRQL) in patients with metastatic colorectal cancer (mCRC) provided with aflibercept access before marketing authorization.

Patients And Methods: Patients received aflibercept followed by FOLFIRI (fluorouracil, leucovorin, irinotecan) on day 1 of a 2-week cycle until disease progression, unacceptable toxicity, death, or patient/investigator decision to discontinue. Treatment-emergent adverse events (TEAEs) were evaluated, and HRQL was assessed at baseline, cycle 3, and every other cycle using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29, and EuroQol 5-Dimensions 3-Levels questionnaires (NCT01571284).

Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry.

Purpose: Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions < 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography (PET)-negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking.

Dose-reduced first cycle of chemotherapy for prevention of life-threatening acute complications in nonseminomatous germ cell tumor patients with ultra high tumor markers and/or poor performance status.

Purpose: Patients with metastatic nonseminomatous germ cell tumors (mNSGCT) and a high tumor burden or a poor performance status at initial diagnosis are at risk from potentially life-threatening early complications during or after the first chemotherapy cycle. The outcomes with dose-reduced first cycle of chemotherapy in this population of patients are not well established.

Methods: We performed a retrospective analysis of patients with mNSGCT and International Germ Cell Cancer Collaborative Group (IGCCCG) poor risk features.

Intratumoral Heterogeneity of SMAD4 Immunohistochemical Expression and Its Role in Prediction of Recurrence Pattern in Patients with Resectable Pancreatic Cancer.

Background: The aim of our study was to evaluate consistency of SMAD4 expression in different tumor areas and its correlation with recurrence pattern in patients after resection for pancreatic cancer (PC).

Methods: Records of patients who underwent resection for nonmetastatic PC between 2001 and 2015 were analyzed. Formalin-fixed, paraffin-embedded tissue sections from different areas of primary tumor and lymph node metastases were analyzed immunohistochemically (IHC) for SMAD4 expression using TMA technology.

Concurrent paclitaxel, capecitabine, mitomycin C and pelvic radiation therapy for patients with squamous cell anal carcinoma.

Purpose: The goals of this study were to assess safety and efficacy of triplet chemoradiotherapy (CRT) with paclitaxel for squamous cell anal carcinoma (SCAC).

Methods: Patients with stage I-IIIB SCAC were enrolled and received 52-58 Gy intensity-modulated radiotherapy (IMRT) (with dose based on the T stage) in consecutive daily 1.8-2.

Role of Stem Cells in Colorectal Cancer Progression and Prognostic and Predictive Characteristics of Stem Cell Markers in Colorectal Cancer.

In the last decade, an increasing number of studies on tumor stem cell theory stating that there is only a small fraction of tumor cells capable of inducing tumor growth have been published. These cells can not only differentiate into more mature tumor cells, but also can maintain their own pool, that is the capacity for self-renewal. There are distinct subpopulations of cells within a tumor that express different combinations of stem cell markers and have different functions.

Preoperative chemotherapy in patients with resectable esophageal carcinoma: a single center Phase II study.

Objective: The role of preoperative chemotherapy in squamous cell esophageal carcinoma remains controversial. A prospective trial was initiated to investigate whether preoperative chemotherapy followed by surgery results in increased progression-free survival in patients with resectable thoracic esophageal carcinoma.

Methods: Patients with Stage IIb-IIIa/b resectable esophageal carcinoma were eligible for the study.

Second-line treatment of metastatic gastric cancer: Current options and future directions.

Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time.