The current landscape of neoadjuvant therapy for resectable colon cancer.

Introduction: Neoadjuvant therapy has been proposed as a safe and effective treatment option for resectable colon cancer, providing several advantages over the current standard adjuvant protocol.

Areas Covered: This review summarizes the recent developments in neoadjuvant strategies for resectable colon cancer, highlighting key clinical trial data, current and emerging challenges, and the role of precision medicine in guiding treatment. Sources for this review were obtained through searches of PubMed, ClinicalTrials.

Aligning kidney function assessment in patients with cancer to global practices in internal medicine.

Unlabelled: The kidney disease: Improving Global Outcomes (KDIGO) guideline recommends assessing kidney function using glomerular filtration rate (GFR) either through direct measurement or through estimation (eGFR) and describes a standardised classification of reduced kidney function. KDIGO guidelines have been adopted by most internal medicine specialities for the assessment and classification of kidney function, but not by cancer medicine. The development of the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) aims to overcome the perceived challenges with KDIGO recommendations by describing their utility in patients with cancer.

Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practice.

Unlabelled: Part 2 of the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) offers drug-specific consensus recommendations based on both evidence and practical experience. These recommendations build upon the kidney function assessment and classification guidelines established in Part 1 of ADDIKD. Here we illustrate how dosing recommendations differ between ADDIKD and existing guidance for four commonly used drugs: methotrexate, cisplatin, carboplatin and nivolumab.

Machine Learning Models of Early Longitudinal Toxicity Trajectories Predict Cetuximab Concentration and Metastatic Colorectal Cancer Survival in the Canadian Cancer Trials Group/AGITG CO.17/20 Trials.

Purpose: Cetuximab (CET), targeting the epidermal growth factor receptor, is a systemic treatment option for patients with colorectal cancer. One known predictive factor for CET efficacy is the presence of CET-related rash; other putative toxicity factors include fatigue and nausea. Analysis of early CET-associated toxicities may reveal patient subpopulations that clinically benefit from long-term CET treatment.

Myocardial Injury Following Immune Checkpoint Inhibitors: An Australian Experience.

Background: Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment, becoming a cornerstone therapy for various malignancies. Despite their efficacy, there are concerns about their potential cardiotoxicity, particularly, subclinical myocardial injury. However, there remains a scarcity of local data on the precise incidence of such cardiac complications.

Evaluation of hyperprogressive disease with atezolizumab plus bevacizumab for hepatocellular carcinoma: A secondary analysis of the IMbrave150 trial.

The use of Immune checkpoint inhibitors (ICIs) as monotherapy for patients with hepatocellular carcinoma (HCC) has been associated with an increased risk of hyperprogressive disease (HPD), the occurrence of which carries a poor prognosis. However, it is unknown whether contemporary frontline treatment with the combination of atezolizumab and bevacizumab causes significant HPD. This study conducted a secondary analysis of patient-level data from the IMbrave150 randomized controlled trial of atezolizumab plus bevacizumab versus sorafenib for frontline treatment of HCC.

Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial.

Early data from the DYNAMIC study of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy (ACT) versus standard approach met its primary outcome demonstrating reduced ACT use without compromising 2-year recurrence-free survival (RFS) for stage II colon cancer. We report here other prespecified analyses of overall survival, ctDNA clearance and ctDNA level. At a median follow-up of 59.

AGITG MONARCC: A Randomized Phase 2 Study of Panitumumab Monotherapy and Panitumumab Plus 5-Fluorouracil as First-Line Therapy for Older Patients With RAS and BRAF Wild Type Metastatic Colorectal Cancer. A Study by the Australasian Gastro-Intestinal Trials Group (AGITG).

Background: Panitumumab (pan) plus chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type metastatic colorectal cancer (mCRC). Older patients may not be suitable for combination regimens. We investigated 2 lower intensity pan-containing regimens.

Tumour Mutational Burden and Immune Checkpoint Inhibitor Response in Non-small Cell Lung Cancer: A Continuous Modelling Approach.

Background: Tumour mutational burden (TMB) is an established biomarker for patients treated with immune checkpoint inhibitors (ICIs). The optimal TMB cut-off is uncertain. It is also uncertain whether there is a sharp TMB threshold or a more graduated change in clinical outcomes as TMB increases.

Role of locoregional therapy including liver transplantation in liver-only metastatic colorectal cancer: a review paper.

Introduction: Resection of primary tumor and liver metastases is the gold standard for colorectal cancer with liver-only metastases (CRLM). Although treatment options have expanded to enable conversion of unresectable to resectable CRLM, about 40% of patients will have definitively unresectable disease. Major advances in surgical techniques, immunosuppressive protocols and patient selection criteria for liver transplantation have resulted in improved outcomes.

DPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol.

Background: Fluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3-4 (≥ G3) toxicities that require hospital-based management ± intensive care admission.

The association of health-care contact days with physical function and survival in CCTG/AGITG CO.17.

Introduction: Although contact days-days with health-care contact outside home-are increasingly adopted as a measure of time toxicity and treatment burden, they could also serve as a surrogate of treatment-related harm. We sought to assess the association between contact days and patient-reported outcomes and the prognostic ability of contact days.

Methods: We conducted a secondary analysis of CO.

A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials.

Background: Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear.

Metastatic colorectal cancer- third line therapy and beyond.

Introduction: The outcome of patients with metastatic colorectal cancer (mCRC) has improved significantly in the last few decades. Metastatic colorectal cancer is a highly heterogenous cancer. Beyond second line chemotherapy, treatment decisions are often based on molecular testing.

Transverse Colon Primary Tumor Location as a Biomarker in Metastatic Colorectal Cancer: A Pooled Analysis of CCTG/AGITG CO.17 and CO.20 Randomized Clinical Trials.

Purpose: Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). Transverse colon has been historically excluded from several analyses of sidedness and the optimal division between left- and right-sided colorectal cancer is unclear. We investigated transverse colon primary tumor location as a biomarker in mCRC.

Plasma Cetuximab Concentrations Correlate With Survival in Patients With Advanced KRAS Wild Type Colorectal Cancer.

Background: Cetuximab is a standard of care therapy for patients with RAS wild-type (WT) advanced colorectal cancer. Limited data suggest a wide variation in cetuximab plasma concentrations after standard dosing regimens. We correlated cetuximab plasma concentrations with survival and toxicity.

Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures.

Survival outcomes for patients with colorectal cancer with synchronous liver only metastasis.

Background: Colorectal cancer with synchronous liver-only metastasis is managed with a multimodal approach, however, optimal sequencing of modalities remains unclear.

Methods: A retrospective review of all consecutive rectal or colon cancer cases with synchronous liver-only metastasis was conducted from the South Australian Colorectal Cancer Registry from 2006 to 2021. This study aimed to investigate how order and type of treatment modality affects overall survival.

A Bayesian approach for two-stage multivariate Mendelian randomization with mixed outcomes.

Many research studies have investigated the relationship between baseline factors or exposures, such as patient demographic and disease characteristics, and study outcomes such as toxicities or quality of life, but results from most of these studies may be problematic because of potential confounding effects (eg, the imbalance in baseline factors or exposures). It is important to study whether the baseline factors or exposures have causal effects on the clinical outcomes, so that clinicians can have better understanding of the diseases and develop personalized medicine. Mendelian randomization (MR) provides an efficient way to estimate the causal effects using genetic instrumental variables to handle confounders, but most of the existing studies focus on a single outcome at a time and ignores the correlation structure of multiple outcomes.

Evaluating the Time Toxicity of Cancer Treatment in the CCTG CO.17 Trial.

Purpose: The time spent in pursuing treatments for advanced cancer can be substantial. We have previously proposed a pragmatic and patient-centered metric of these time costs-which we term time toxicity-as any day with physical health care system contact. This includes outpatient visits (eg, bloodwork, scans, etc), emergency department visits, and overnight stays in a health care facility.

Understanding the Risk of Drug Interactions Between Ritonavir-Containing COVID-19 Therapies and Small-Molecule Kinase Inhibitors in Patients With Cancer.

Purpose: The introduction of COVID-19 therapies containing ritonavir has markedly expanded the scope of use for this medicine. As a strong cytochrome P450 3A4 inhibitor, the use of ritonavir is associated with a high drug interaction risk. There are currently no data to inform clinician regarding the likely magnitude and duration of interaction between ritonavir-containing COVID-19 therapies and small-molecule kinase inhibitors (KIs) in patients with cancer.

Immune and genomic biomarkers of immunotherapy response in cancer of unknown primary.

Background: Cancer of unknown primary (CUP) is a heterogeneous group of metastatic cancers where a primary tissue of origin (TOO) is uncertain. Most patients with CUP have limited treatment options and poor survival outcomes. Immune checkpoint inhibitors (ICIs) can be efficacious in some patients with CUP, but the optimal predictive biomarkers are unknown.