Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

Importance: This was a clinical study of total neoadjuvant therapy (TNT) for rectal cancer.

Objective: To assess the use and outcomes of TNT in routine practice.

Design, Setting, And Participants: This international, multicenter study was conducted at 61 centers across 21 countries and included consecutive patients treated off trial with TNT for stage II/III rectal adenocarcinoma from September 2012 to December 2023.

Characteristics of Patients and Prognostic Factors Across Treatment Lines in Metastatic Colorectal Cancer: An Analysis From the Aide et Recherche en Cancérologie Digestive Database.

Purpose: Several lines of treatment can be used sequentially in patients with metastatic colorectal cancer. We investigated the evolution of patient/tumor characteristics and their prognostic impact across treatment lines to develop an overall prognostic score (OPS).

Patients And Methods: Individual patient data from 48 randomized trials were analyzed.

Neoadjuvant Treatment of Rectal Cancer: A Repeat UK-wide Survey After Implementation of National Intensity Modulated Radiotherapy Guidance.

Aims: Rectal cancer management has changed significantly in the last decade with the introduction of total neoadjuvant therapy (TNT), minimally invasive surgery, brachytherapy, and organ preservation. A national survey of intensity modulated radiotherapy (IMRT) was carried out in 2020 to support the development of national Royal College of Radiologists (RCR) guidance, published in 2021. We performed a repeat survey in collaboration with the RCR, to inform iterations of the RCR Guidance and establish treatment patterns across the UK to facilitate future research and development.

Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment.

Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase.

Efficacy of immune checkpoint inhibitors for metastatic colorectal cancer with microsatellite instability in second or latter line using synthetic control arms: A non-randomised evaluation.

Purpose: Immune checkpoint inhibitors (ICIs) appeared active in single-arm trials for patients with chemoresistant metastatic colorectal cancer (mCRC) harboring microsatellite instability (MSI). Given the paucity of randomised controlled trials (RCTs) in this setting, we evaluated the effect size of ICIs using intra-patients comparison and ARCAD database as historical controls.

Patients And Methods: Individual-patient data from NIPICOL and CheckMate 142 phase II trials that evaluated a combination of ICIs for MSI mCRC patients (N = 176) and from five non-ICI mCRC historical RCTs in second-line or latter (N = 4026) were analyzed.

Randomized Phase 3 Trial of the Hypoxia Modifier Nimorazole Added to Radiation Therapy With Benefit Assessed in Hypoxic Head and Neck Cancers Determined Using a Gene Signature (NIMRAD).

Purpose: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT).

Methods And Materials: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689).

Safety and tolerability of long-term treatment with darolutamide in patients with metastatic castration-resistant prostate cancer.

Background: In patients with metastatic castration-resistant prostate cancer, darolutamide was well tolerated for 25 months, but minimal long-term safety data are available.

Methods: Treatment-emergent adverse events (TEAEs) for patients receiving darolutamide for a median of 38 months (n = 13) are described in this pooled analysis of individual patient data from phase 1/2 studies.

Results: All patients reported TEAEs (mostly grade 1/2).

Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for gastric cancer with peritoneal metastases: A systematic review by the PIPAC UK collaborative.

Introduction: Gastric cancer with peritoneal metastases (GCPM) carries a poor prognosis. Pressurised Intraperitoneal Aerosolised Chemotherapy (PIPAC) offers pharmacokinetic advantages over intravenous therapy, resulting in higher chemotherapy concentrations in peritoneal deposits, and potentially reduced systemic absorption/toxicity. This review evaluates efficacy, tolerability and impact on quality of life (QOL) of PIPAC for GCPM.

Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database.

Background: Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown.

Methods: We analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006.

Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical Trials.

Background: We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials.

Methods: Associations between clinical and disease characteristics, time to initial progression, and rate of receipt of second-line therapy were evaluated. TTP and overall survival (OS) were compared between older and younger adults in first- and second-line trials by Cox regression, adjusting for age, sex, Eastern Cooperative Oncology Group Performance Status, number of metastatic sites and presence of metastasis in the lung, liver, or peritoneum.

A Road Map for Designing Phase I Clinical Trials of Radiotherapy-Novel Agent Combinations.

Radiotherapy has proven efficacy in a wide range of cancers. There is growing interest in evaluating radiotherapy-novel agent combinations and a drive to initiate this earlier in the clinical development of the novel agent, where the scientific rationale and preclinical evidence for a radiotherapy combination approach are high. Optimal design, delivery, and interpretation of studies are essential.

Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer ≥ 70 years.

Purpose: Colorectal cancer (CRC) affects many older adults. We investigated the efficacy and safety of adding anti-epidermal growth factor receptor (EGFR) agents to doublet chemotherapy (DC) in older patients.

Methods: Patients with RAS wild-type (WT) metastatic CRC (mCRC) receiving first-line DC + anti-EGFR (n = 1191) or DC alone (n = 729) from seven trials in the Aide de Recherche en Cancerologie Digestive database were included.

Treatment breaks in first line treatment of advanced colorectal cancer: An individual patient data meta-analysis.

Background: Intermittent systemic anti-cancer therapy in patients with advanced colorectal cancer (aCRC) may improve quality of life without compromising overall survival (OS). We aimed to use individual patient data meta-analysis (IPDMA) from multiple randomised controlled trials evaluating intermittent strategies to inform clinical practice. We also aimed to validate whether thrombocytosis as a predictive biomarker identified patients with significantly reduced OS receiving a complete treatment break.

Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer.

Background: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients.

Methods: PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled.

Immune Checkpoint Inhibition as a Strategy in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer.

The treatment of locally advanced rectal cancer (LARC) has seen major advances over the past 3 decades, with multimodality treatment now standard of care. Combining surgical resection with radiotherapy and/or chemotherapy can reduce local recurrence from around 20% to approximately 5%. Despite improvements in local control, distant recurrence and subsequent survival rates have not changed.

BRAF V600E Mutation in First-Line Metastatic Colorectal Cancer: An Analysis of Individual Patient Data From the ARCAD Database.

Background: First-line therapeutic strategies for patients with BRAFV600E-mutated (BRAFmt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed to assess the prognostic and predictive impact of BRAFmt on the efficacy of targeted therapies with first-line chemotherapy.

Methods: Individual patient data from first-line RCTs with BRAF and KRAS status data in the ARCAD database were pooled.

Impact of deviations in target volume delineation - Time for a new RTQA approach?

The international radiotherapy community has recognised that non-adherence to RT protocols can influence trial endpoints. However this conclusion is based on studies predominantly assessing the impact of deviations in dosimetric or treatment delivery protocol parameters rather than target volume delineation (TVD). This review evaluates the assessment of TVD within Radiation Therapy Quality Assurance (RTQA) programmes in clinical trials and the clinical impact of TVD protocol deviations.

Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL).

Purpose: To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers.

Methods And Materials: In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group.