Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study.

Purpose: The absence of postoperative circulating tumor DNA (ctDNA) identifies patients with resected colorectal cancer (CRC) with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. Our study presents the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection.

Experimental Design: TRACC (tracking mutations in cell-free tumor DNA to predict relapse in early colorectal cancer) included patients with stage I to III resectable CRC.

Comparison of different second line treatments for metastatic pancreatic cancer: a systematic review and network meta-analysis.

Background: In metastatic pancreatic ductal adenocarcinoma (mPDAC), first line treatment options usually include combination regimens of folinic acid, 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX or mFOLFIRINOX) or gemcitabine based regimens such as in combination with albumin-bound paclitaxel (GEM + nab-PTX). After progression, multiple regimens including NALIRI + 5-FU and folinic acid, FOLFIRINOX, 5-FU-based oxaliplatin doublets (OFF, FOLFOX, or XELOX), or 5-FU-based monotherapy (FL, capecitabine, or S-1) are considered appropriate by major guidelines. This network meta-analysis (NMA) aimed to compare the efficacy of different treatment strategies tested as second-line regimens for patients with mPDAC after first-line gemcitabine-based systemic treatment.

Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Pancreatic ductal adenocarcinoma (PDAC) has an aggressive tumor biology and is associated with poor survival outcomes. Most patients present with metastatic or locally advanced disease. In the 10-20% of patients with upfront resectable disease, surgery offers the only chance of cure, with the addition of adjuvant chemotherapy representing an established standard of care for improving outcomes.

Immune-Checkpoint Inhibitors in Platinum-Resistant Ovarian Cancer.

Platinum-resistant ovarian cancer (OC) has limited treatment options and is associated with a poor prognosis. There appears to be an overlap between molecular mechanisms responsible for platinum resistance and immunogenicity in OC. Immunotherapy with single agent checkpoint inhibitors has been evaluated in a few clinical trials with disappointing results.

How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches.

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy.

The Emergence of Immune-checkpoint Inhibitors in Colorectal Cancer Therapy.

Immunotherapy has revolutionized the treatment landscape in a number of solid tumors. In colorectal cancer, evidence suggests that microsatellite high (MSI-H) tumors are the most responsive to immune checkpoint blockade due to increased neo-antigen load and a favorable tumor microenvironment. Indeed, Pembrolizumab now represents a first-line option in such patients.

MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer.

Purpose: Response to preoperative chemo-radiotherapy (CRT) varies. We assessed whether circulating tumor DNA (ctDNA) might be an early indicator of tumor response or progression to guide therapy adaptation in rectal cancer.

Experimental Design: A total of 243 serial plasma samples were analyzed from 47 patients with localized rectal cancer undergoing CRT.

Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center.

The incidence of early onset colorectal cancer (EOCRC) is rapidly increasing, but there remains paucity of outcome data for young CRC patients. We reviewed the characteristics and outcomes of 241 adults, age <50, who were diagnosed with EOCRC between January 2009 and December 2014. Median age was 42, 56% were male, and 7% had hereditary etiology.

ACORN: Observational Study of Bevacizumab in Combination With First-Line Chemotherapy for Treatment of Metastatic Colorectal Cancer in the UK.

Introduction: Survival in metastatic colorectal cancer is worse than expected in the United Kingdom. Real-world data are needed to better understand UK-specific treatment practices that may explain this.

Patients And Methods: The Avastin ColORectal Non-interventional (ACORN) study is a multicenter, prospective, UK-based, observational, phase 4 study (ClinicalTrials.

Use of Antibiotics and Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

The association between antibiotic use and risk of cancer development is unclear, and clinical trials are lacking. We performed a systematic review and meta-analysis of observational studies to assess the association between antibiotic use and risk of cancer. PubMed, the Cochrane Library and EMBASE were searched from inception to 24 February 2019 for studies reporting antibiotic use and subsequent risk of cancer.

Surgery or Locoregional Approaches for Hepatic Oligometastatic Pancreatic Cancer: Myth, Hope, or Reality?

Despite extensive research, pancreatic ductal adenocarcinoma (PDAC) remains a difficult-to-treat cancer associated with poor survival. Due to the known aggressive disease biology, palliative chemotherapy is the only routinely recommended treatment in the metastatic setting in patients with adequate performance status. However, in a subset of patients with oligometastatic disease, multimodality treatment with surgery and/or locoregional approaches may provide long-term disease control and prolong survival.

Circulating tumour DNA, a promising biomarker for the management of colorectal cancer.

Circulating cell free tumour DNA (ctDNA) maintains the same genomic alterations that are present in the corresponding tumour, thereby allowing for quantitative and qualitative real-time evaluation in body fluids as an alternative to onerous repeat biopsies. Improvements in the sensitivity of techniques used to identify ctDNA has led to a surge of research investigating its role in the detection of: early disease, relapse, response to therapy and emerging drug resistance mechanisms. Following curative surgery, ctDNA detection is a promising marker of minimal residual disease and could better select patients for adjuvant chemotherapy.

A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial.

Background: Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided.

Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy.

Unlabelled: Peritoneal mesothelioma (MPeM) is a scarce abdominal-pelvic malignancy that presents with non-specific features and exhibits a wide clinical spectrum from indolent to aggressive disease. Due to it being a rare entity, there is a lack of understanding of its molecular drivers. Most treatment data are from limited small studies or extrapolated from pleural mesothelioma.