Rationale and Design of the COPERNIC Trial: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients.

Background: Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.

Methods: COPERNIC is an international, multicenter clinical trial.

PD-L1 Expression in Paired Samples of Rectal Cancer.

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS).

Streamlining the diagnostic pathway for Lynch syndrome in colorectal cancer patients: a 10-year experience in a single Italian Cancer Center.

Background: Universal screening of colorectal cancer (CRC) patients for Lynch syndrome (LS) through MisMatch Repair (MMR) testing is recommended. BRAF V600E mutation and/or MLH1 promoter methylation (Reflex Testing, RefT)generally rule out LS in MLH1-deficient (dMLH1) patients. We estimated the impact of RefTon genetic counseling (GC) and on the diagnostic yield of genetic testing (GT).

Prognostic Value of Circulating Cytokines in Chemorefractory Colorectal Cancer.

Circulating cytokines could be optimal biomarkers for prognostication and management decisions in colorectal cancer (CRC). Chemorefractory CRC patients with available plasma samples were included in this study. In the discovery cohort ( = 85), 182 circulating cytokines were tested with a semi-quantitative multiplex assay, and prognostic cytokines were analyzed in the validation cohort ( = 111) by ELISA.

Preexisting evidence and outcome of phase III trials in gastrointestinal oncology: a systematic review.

Background: A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome and the level and characteristics of preexisting evidence.

Methods: EMBASE, PubMed, and proceedings from international meetings were searched for phase III gastrointestinal cancer trials (gastroesophageal, hepatocellular, biliary tract, pancreatic, small bowel, colorectal, anal, stromal, and neuroendocrine) between January 2000 and June 2020.

Regorafenib Induces Senescence and Epithelial-Mesenchymal Transition in Colorectal Cancer to Promote Drug Resistance.

Potential intrinsic resistance mechanisms to regorafenib were explored after short exposure (3 days) on five CRC cell lines (HCT-116, SW1116, LS-1034, SW480, Caco-2). The observation of senescence-like features led to the investigation of a drug-initiated phenotype switch. Following long-term exposure (12 months) of HCT-116 and SW480 cell lines to regorafenib, we developed resistant models to explore acquired resistance.

Pre-trial quality assurance of diffusion-weighted MRI for radiomic analysis and the role of harmonisation.

Purpose: The aim of this study was to perform a quantitative quality assurance of diffusion-weighted MRI to assess the variability of the mean apparent diffusion coefficient (ADC) and other radiomic features across the scanners involved in the REGINA trial.

Materials And Methods: The NIST/QIBA diffusion phantom was acquired on six 3 T scanners from five centres with a rectum-specific diffusion protocol. All sequences were repeated in each scan session without moving the phantom from the table.

Regorafenib in combination with immune checkpoint inhibitors for mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer.

Immune checkpoint inhibitors (ICIs) have marked a new era of cancer treatment, showing remarkable efficacy in a wide range of solid malignancies. In colorectal cancer (CRC), however, the therapeutic potential of ICIs is limited to the small group (≈5%) of patients with mismatch repair deficient (dMMR)/high microsatellite instable (MSI-H) tumours, which are characterised by high mutational/neo-antigen burden, and an inflammatory tumour microenvironment with abundant tumour-infiltrating lymphocytes. Over the last few years, research has focused on immuno-modulatory strategies that could overcome the inherent resistance to ICIs that is observed in the vast group (≈95%) of patients with mismatch repair proficient (pMMR)/microsatellite stable (MSS) tumours.

Circulating DNA in the neoadjuvant setting of early stage colon cancer.

Background: While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy. We sought to fill this gap by using prospectively collected plasma samples from 80 stage III colon cancer patients, receiving one cycle of neoadjuvant FOLFOX followed by surgery +/- adjuvant FOLFOX in the PePiTA trial.

Material And Methods: Samples were collected at baseline, 2 weeks and surgery.

Mind the target: human epidermal growth factor receptor 2 in colorectal cancer.

Purpose Of Review: In this article, we briefly summarise the current knowledge about human epidermal growth factor receptor 2 (HER2) alterations in colorectal cancer (CRC) and provide an overview of the latest published evidence especially regarding standardisation of detection methods/diagnostic criteria, prognostication, prediction and targeted treatments.

Recent Findings: Over the last 18 months, the results of many studies have been presented confirming the therapeutic potential of established anti-HER2 agents either as a monotherapy or in combination, as well as new anti-HER2 agents like antibody-drug-conjugates and tyrosine kinase inhibitors. Also, we have seen confirmation of the utility of liquid biopsy and ctDNA analyses as tool for HER2 detection and patient selection.

Toward Targeted Therapies in Oesophageal Cancers: An Overview.

Oesophageal cancer is one of the leading causes of cancer-related death worldwide. Oesophageal cancer occurs as squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). Prognosis for patients with either ESCC or EAC is poor, with less than 20% of patients surviving more than 5 years after diagnosis.

Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives.

Substantial improvements have characterized the systemic treatment of metastatic colorectal cancer (mCRC) over the past 20 years. Besides strong evidence that supports the use of RAS and BRAF status as prognostic and predictive indicators of disease and response, novel technologies have made possible the incorporation of emerging biomarkers for the management of mCRC. On one hand, the discovery of point mutations, amplifications, fusions, and gene expression profiles highlights the genomic and dynamic complexity of CRC.

Sex and Regorafenib Toxicity in Refractory Colorectal Cancer: Safety Analysis of the RegARd-C Trial.

Background: Regorafenib is a standard treatment for refractory metastatic colorectal cancer (mCRC). In view of the toxicity burden, significant research efforts have been made to increase the therapeutic ratio of this multikinase inhibitor. Predictive factors for treatment-related adverse events (TRAEs), however, are still lacking.

Anal squamous cell carcinoma: standards of care, new data and ongoing clinical trials.

Purpose Of Review: To summarize current standards of care, discuss results of recent studies and present ongoing clinical trials for anal squamous cell carcinoma (ASCC).

Recent Findings: Over the last year, no practice changing studies have been reported in the setting of localised ASCC. A number of retrospective analyses, however, have provided practice-informing data, such as those confirming the negative impact of low compliance to chemoradiotherapy (CRT) on patient outcomes.

Total neoadjuvant therapy for rectal cancer: Making sense of the results from the RAPIDO and PRODIGE 23 trials.

A few months ago, results from two randomised phase III trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were presented (RAPIDO and PRODIGE 23), consistently showing better short- and long-term outcomes with TNT as compared with standard neoadjuvant long-course chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). These results represent corroborating evidence in support of a practice that many centres had already implemented based on promising preliminary data. Also, they provide new, high-level evidence to endorse TNT as a new management option in the treatment algorithm of stage II-III rectal cancer in those centres where CRT and SCRT have long remained the only accepted standard neoadjuvant treatments.

Prognostic Value of the Pace of Tumor Progression as Assessed by Serial F-FDG PET/CT Scan and Liquid Biopsy in Refractory Colorectal Cancer: The CORIOLAN Trial.

Introduction: Decision making in refractory colorectal cancer (rCRC) is challenging, with limited data available to predict patient outcome. We conducted a study to assess the pace of cancer progression as a potential prognostic and decision tool.

Methods: CORIOLAN was a prospective, single-center, single-arm trial recruiting refractory CRC patients with an ECOG performance status of ≤1 and an estimated life expectancy of ≥12 weeks.

Feasibility and clinical impact of routine molecular testing of gastrointestinal cancers at a tertiary centre with a multi-gene, tumor-agnostic, next generation sequencing panel.

Background: High-throughput sequencing technologies are increasingly used in research but limited data are available on the feasibility and value of these when routinely adopted in clinical practice.

Material And Methods: We analyzed all consecutive cancer patients for whom genomic testing by a 48-gene next-generation sequencing (NGS) panel (Truseq Amplicon Cancer Panel, Illumina) was requested as part of standard care in one of the largest Belgian cancer networks between 2014 and 2019. Feasibility of NGS was assessed in all study patients, while the impact of NGS on the decision making was analyzed in the group of gastrointestinal cancer patients.

MOMENTUM: A Phase I Trial Investigating 2 Schedules of Capecitabine With Aflibercept in Patients With Gastrointestinal and Breast Cancer.

Background: Although data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need.

Patients And Methods: Patients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m/day) capecitabine dosing arm.

Adjuvant chemotherapy for rectal cancer: Current evidence and recommendations for clinical practice.

While adjuvant chemotherapy is an established treatment for pathological stage II and especially stage III colon cancer, its role in the multimodal management of rectal cancer remains controversial. As a result, there is substantial variation in the use of this treatment in clinical practice. Even among centres and physicians who consider adjuvant chemotherapy as a standard treatment, notable heterogeneity exists with regard to patient selection criteria and chemotherapy regimens.

Predictive Impact of Mucinous Tumors on the Clinical Outcome in Patients with Poorly Differentiated, Stage II Colon Cancer: A TOSCA Subgroup Analysis.

Background: Although American Society of Clinical Oncology and European Society for Medical Oncology guidelines have identified the negative prognostic factors that clinicians have to consider when treating their patients with stage II colon cancer (CC), the role of histological subtype is controversial.

Subjects, Materials, And Methods: The randomized, multicenter, phase III TOSCA trial compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. The objective of this substudy was to evaluate the influence of histological subtypes on the impact of the treatment duration of adjuvant chemotherapy in terms of relapse-free survival (RFS) and overall survival (OS) in 85 mucinous adenocarcinoma (MUC) and 389 nonmucinous adenocarcinoma (NMUC) patients with high-risk stage II, grade 3 CC.

Grey areas and evidence gaps in the management of rectal cancer as revealed by comparing recommendations from clinical guidelines.

Background: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines.

Methods: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected.

PD-1 and PD-L1 inhibitors in oesophago-gastric cancers.

Oesophago-gastric cancers (OGCs) are aggressive tumours. While better peri-operative strategies, increased number of cytotoxic agents and availability of targeted therapies have improved survival, there remains an unmet need for novel treatment approaches. Immune checkpoint inhibitors (ICIs) have marked a new era in cancer management with unprecedented results in several malignancies.