Software-based versus visual assessment of the minimal ablative margin in patients with liver tumours undergoing percutaneous thermal ablation (COVER-ALL): a randomised phase 2 trial.

Background: Tumour coverage with an optimal minimal ablative margin is crucial for improving local control of liver tumours following thermal ablation. The minimal ablative margin has traditionally been assessed through visual inspection of co-registered CT images. However, rates of local tumour control after thermal ablation are highly variable with visual assessment.

IL-1R1 Blockade Enhances CD40 Agonist-Mediated Immune Responses but Fails to Increase Efficacy or Mitigate Hepatotoxicity in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of only 10% in the United States. While immune checkpoint blockade (ICB) has shown efficacy in many solid tumors, PDAC remains largely unresponsive. Agonistic CD40 antibodies can activate PDAC-associated myeloid cells, enhancing innate and adaptive anti-tumor immunity.

Incorporating Circulating Tumor DNA Testing Into Clinical Trials: A Position Paper by the National Cancer Institute GI Oncology Circulating Tumor DNA Working Group.

Purpose: Circulating tumor DNA (ctDNA) is an emerging tool in the evaluation of GI cancers. Challenges remain in defining its utility and role as a primary end point in therapeutic trials. The National Cancer Institute (NCI) ctDNA GI working group was created to evaluate current data and provide guidance on the inclusion of ctDNA in GI cancer trials.

Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal.

Background: Anti-PD-(L)1 antibodies are associated with responses in <25% of patients with metastatic human papillomavirus (HPV)-associated malignancies. VEGF signaling causes intratumoral immune evasion and immune suppression. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

BRAF mutant appendiceal adenocarcinoma differs from colorectal cancer but responds to BRAF-targeted therapy.

Appendiceal Adenocarcinoma (AA) is a rare gastrointestinal cancer with no FDA-approved targeted therapies. Here, we retrospectively compare BRAF-mutant AA and colorectal cancer (CRC). BRAF mutation is rare in AA (3%).

Time dependency for human papillomavirus circulating tumor DNA detection after chemoradiation as a prognostic biomarker for localized anal cancer.

Background: While detection of circulating tumor DNA (ctDNA) weeks after surgery is linked to recurrence for other solid tumors, the optimal time point for ctDNA assessment as a prognostic biomarker following chemoradiation for anal cancer is undefined.

Methods: Patients with stages I-III anal cancer treated with chemoradiation between 12/2020-5/2024 were evaluated for HPV ctDNA status at baseline, at the end of chemoradiation, and during surveillance using a droplet digital HPV ctDNA PCR assay targeting HPV E6 and E7 oncogenes for 13 oncogenic HPV types. Median recurrence-free survival (RFS) according to HPV ctDNA status was estimated via Kaplan-Meier and compared using a log-rank test.

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types.

Mutational and co-mutational landscape of early onset colorectal cancer.

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs.

Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma: ASCO Guideline.

Purpose: To provide evidence-based guidance for clinicians who treat patients with stage I-III anal cancer.

Methods: A systematic review of the literature conducted by the Minnesota Evidence-based Practice Center provided the evidence base for this guideline. An ASCO Expert Panel reviewed this evidence and came to consensus on a set of evidence-based recommendations.

The prognostic impact of tumor deposits in colorectal cancer: More than just N1c.

Background: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC.

Methods: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database.

Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer.

Purpose: BRAFV600E-mutated colorectal cancer exhibits a strong correlation with DNA hypermethylation, suggesting that this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E colorectal cancer in vivo.

Experimental Design: We randomized and treated mice implanted with patient-derived tumor xenografts harboring BRAFV600E mutation with control, 5-azacitidine, vemurafenib (BRAF inhibitor), or the combination.

Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival.

Importance: Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.

Objective: To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.

Design, Setting, And Participants: This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023.

Management of Locally Advanced Rectal Cancer: ASCO Guideline.

. .PURPOSETo provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.

First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors.

Rationale Of The Trial: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors.

Trial Design: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of 16 patients.

Advancements in combining targeted therapy and immunotherapy for colorectal cancer.

Colorectal cancer (CRC) is a prevalent gastrointestinal cancer posing significant clinical challenges. CRC management traditionally involves surgery, often coupled with chemotherapy. However, unresectable or metastatic CRC (mCRC) presents a complex challenge necessitating innovative treatment strategies.

Institution-Wide Retreats Foster Organizational Learning and Action at a Comprehensive Cancer Center.

Providing safe and informed healthcare for sexual and gender minority (SGM) individuals with cancer is stymied by the lack of sexual orientation and gender identity (SOGI) data reliably available in health records and by insufficient training for staff. Approaches that support institutional learning, especially around sensitive topics, are essential for hospitals seeking to improve practices impacting patient safety and research. We engineered annual institutional retreats to identify and unify stakeholders, promote awareness of gaps and needs, identify initiatives, minimize redundant projects, and coordinate efforts that promote improvements in SGM cancer care, education, and research.

Comprehensive Landscape of BRAF Variant Classes, Clonalities, and Co-Mutations in Metastatic Colorectal Cancer Using ctDNA Profiling.

Although V600E accounts for the majority of the mutations in metastatic colorectal cancer (mCRC), non-V600 variants have been shown in recent years to represent a distinct molecular subtype. This study provides a comprehensive profile of variants in mCRC using a large genomic database of circulating tumor DNA (ctDNA) and analyzing clinical outcomes in a cohort of patients with atypical (non-V600) variants (; class II, class III, unclassified). Overall, 1733 out of 14,742 mCRC patients in the ctDNA cohort had at least one variant.

Salvage Treatment of Recurrent or Persistent Anal Squamous Cell Carcinoma: The Role of Multi-modality Therapy.

Background: The standard treatment for recurrent or persistent anal squamous cell carcinoma is surgical salvage, but disease control and survival are suboptimal.

Patients/methods: Patients treated for recurrent or persistent anal squamous cell carcinoma at our institution from 2002 to 2022 were included. Patients were classified by type of salvage treatment received: surgery alone vs.

Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination.

Unlabelled: Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed.

Daily Vaginal Dilator Use During Radiation for Women With Squamous Cell Carcinoma of the Anus: Vaginal Wall Dosimetry and Patient-Reported Sexual Function.

Purpose: At our institution, we treat patients with a daily vaginal dilator (VD) during chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). We evaluated compliance with daily VD use, radiation dose to the vaginal wall (VW), and anterior vaginal wall (AVW), and patient-reported long-term sexual function.

Methods And Materials: We included women with SCCA who received definitive, intensity-modulated radiation therapy-based CRT.

Do resected colorectal cancer patients need early chest imaging? Impact of clinicopathologic characteristics on time to development of pulmonary metastases.

Background And Objectives: For patients with colorectal cancer (CRC), the lung is the most common extra-abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow-up imaging.

SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR V600E-mutant mCRC.

Patients with both V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated V600E-mutant mCRC.