A phase II trial of hepatic ablation of metastases to modulate and enhance immunotherapy response in non-small cell lung cancer (HAMMER-NSCLC).

Background: Anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-[L]1) immunotherapy promotes systemic anti-tumor immunity through expanding neoantigen-specific CD8 + T cells, but it is less effective in patients with liver metastases. Nearly 20% of non-small cell lung cancer (NSCLC) patients develop liver metastases, and these patients are characterized by fewer and less active effector T cells. Preclinical work has shown that liver metastases cause systemic immunosuppression through siphoning neoantigen-specific CD8 + T cells from systemic circulation with subsequent macrophage-mediated intrahepatic death.

Multi-Institutional Comparison of Ablative 5-Fraction Magnetic Resonance-Guided Online Adaptive Versus 15/25-Fraction Computed Tomography-Guided Moderately Hypofractionated Offline Adapted Radiation Therapy for Locally Advanced Pancreatic Cancer.

Background: Radiation dose escalation for locally advanced pancreatic cancer (LAPC) using stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) or computed tomography (CT)-guided moderately hypofractionated ablative radiation therapy (HART) can achieve favorable outcomes although have not previously been compared.

Methods: We performed a multi-center retrospective analysis of SMART (50 Gy/5 fractions) vs. HART (75 Gy/25 fractions or 67.

Development of Second Malignancies Following Chemotherapy With or Without Radiation Therapy for the Treatment of Locally Advanced Rectal Cancer.

Purpose: We sought to identify factors associated with second pelvic malignancies (SPM), as well as second nonpelvic malignancies (SNPM), after chemotherapy with or without radiation therapy (RT) for locally advanced rectal cancer (LARC).

Methods And Materials: Patients diagnosed with stage II-III LARC. Cumulative incidence of second malignancies was analyzed using a 2-year landmark analysis with death as a competing risk.

Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis.

The transition from benign to malignant growth is a pivotal yet poorly understood step in cancer progression that marks the shift from a pathologically inert condition to a clinically lethal disease. Here, we integrate lineage tracing, single-cell and spatial transcriptomics to visualize the molecular, cellular and tissue-level events that promote or restrain malignancy during the tumor initiation in mouse models of pancreatic ductal adenocarcinoma (PDAC). We identify a discrete progenitor-like population of -mutant cells that co-activates oncogenic and tumor-suppressive programs-including p53, CDKN2A, and SMAD4-engaging senescence-like responses and remodeling their microenvironment, ultimately assembling a niche that mirrors invasive PDAC.

Prospective Evaluation of a Novel Unidirectional Permanent Device for Intraoperative Brachytherapy.

Purpose: The CivaSheet is a novel radiation delivery device consisting of unidirectionally shielded Pd-103 sources embedded in a bioabsorbable polymer sheet. This facilitates intraoperative placement of permanent brachytherapy seeds in a surgical tumor bed, while minimizing dose to overlying structures. No clinical trial data have yet been published for this device.

Aging-dependent dysregulation of EXOSC2 is maintained in cancer as a dependency.

Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated with geriatric diseases including premature aging and cancer progression. We hypothesized that the age-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging traits (abnormal cell cycle and poor tissue differentiation).

Clocking Recurrence: Circulating Tumor HPV DNA Kinetics in Anal Cancer.

Detection of circulating tumor human papillomavirus (HPV) DNA 3 months after completing definitive chemoradiation for localized anal squamous cell carcinoma associates with disease recurrence and inferior recurrence-free survival. These findings provide valuable insights into the temporal significance of circulating tumor HPVDNA detection in anal cancer and its potential implications for early intervention. See related article by Morris et al.

Utilizing Patient Input in Rectal Cancer Trial Design.

Background: The treatment of locally advanced rectal cancer now includes "watch-and-wait" (WW) management for patients who exhibit a clinical complete response (cCR) to total neoadjuvant therapy (TNT). We assessed patients' knowledge and preferences regarding WW with the goal of incorporating patient input into clinical trial design.

Methods: Rectal cancer patients in advocacy groups (COLONTOWN/Rectalburgh and Fight CRC) were surveyed regarding perceptions about treatment strategies, tolerable risks of treatment failure, and preferences on clinical trial design.

Clinical and Genomic Characterization of Secondary Rectal Cancer After Radiotherapy for Prostate Cancer.

Importance: Patients treated with radiotherapy (RT) for prostate cancer (PC) have increased risk of secondary rectal cancer (SRC) and more limited treatment options.

Objective: To assess the tumor molecular profile, clinical characteristics, and oncologic outcomes of SRC after PC and compare them with those of primary rectal cancer (PRC).

Design, Setting, And Participants: This case-control study included patients with SRC diagnosed 5 or more years after RT for PC and patients with PRC who were treated at Memorial Sloan Kettering Cancer Center in New York between February 1, 1994, and September 31, 2022.

Integrating Tumor and Organoid DNA Methylation Profiles Reveals Robust Predictors of Chemotherapy Response in Rectal Cancer.

Rectal cancer patients display heterogeneous responses to neoadjuvant treatment-including the intensive total neoadjuvant therapy (TNT)-and reliable biomarkers are lacking to guide which tumors will benefit most from these regimens. Here, we profiled DNA methylation in tumor tissue and matched patient-derived organoids (PDOs) from 18 rectal cancer cases (50 total samples), leveraging the Illumina MethylationEPIC array and quality control filters that retained 771,964 CpG sites. Analyses used linear models (for tissue-only or PDO-only) and a joint linear mixed-effects approach (accounting for patient-level random effects) to identify significant CpGs associated with log-transformed FOLFOX IC50.

Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait.

Background: The watch-and-wait strategy provides an opportunity to pursue nonoperative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near-complete response remains controversial.

Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy.

Enhancing chemotherapy response prediction via matched colorectal tumor-organoid gene expression analysis and network-based biomarker selection.

Background: Colorectal cancer (CRC) presents significant challenges in chemotherapy response prediction due to its molecular heterogeneity. Current methods often fail to account for the complexity and variability inherent in individual tumors.

Methods: We developed a novel approach using matched CRC tumor and organoid gene expression data.

Increased occurrence of malignancy before and after chemoradiation for anal squamous cell carcinoma: a multi-institutional analysis.

Background: Anal squamous cell carcinoma is a rare cancer with increased occurrence of multiple cancers before and after the anal squamous cell carcinoma diagnosis. However, there are limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after anal squamous cell carcinoma, time trends, and impact on survival and to identify prognostic factors.

External Beam Radiation Therapy for Liver Metastases.

Stereotactic ablative radiotherapy (SABR) commonly is used for small liver metastases. Modern conformal radiotherapy techniques, including 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy, enable the safe delivery of SABR to small liver volumes. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs, such as the stomach, duodenum, and large intestine.

Penile-scrotal erythrodysesthesia among rectal cancer patients receiving fluoropyrimidine-based chemoradiation: a case report series.

Background: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine.

Salvage Ablative Radiotherapy for Isolated Local Recurrence of Pancreatic Adenocarcinoma following Definitive Surgery.

The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume.

Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation.

Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center.

Future direction of total neoadjuvant therapy for locally advanced rectal cancer.

Despite therapeutic advancements, disease-free survival and overall survival of patients with locally advanced rectal cancer have not improved in most trials as a result of distant metastases. For treatment decision-making, both long-term oncologic outcomes and impact on quality-of-life indices should be considered (for example, bowel function). Total neoadjuvant therapy (TNT), comprised of chemotherapy and radiotherapy or chemoradiotherapy, is now a standard treatment approach in patients with features of high-risk disease to prevent local recurrence and distant metastases.