Neoadjuvant Nivolumab Plus Chemotherapy Followed by Response-Stratified Chemoradiation Therapy in HPV-Negative Head and Neck Cancer: The DEPEND Phase 2 Nonrandomized Clinical Trial.

Importance: Neoadjuvant immunotherapy in human papillomavirus (HPV)-negative locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) appears promising, yet its role in nonsurgical treatment for head and neck cancer remains undefined. Neoadjuvant nivolumab plus chemotherapy followed by response-stratified de-escalated chemoradiation therapy (CRT) in HPV-negative LA stage IVa/b HNSCC may improve treatment efficacy while reducing treatment-related toxic effects.

Objective: To determine the deep response rate and tolerability of neoadjuvant nivolumab plus chemotherapy followed by response-stratified CRT in nonvirally mediated stage IVa/b HNSCC.

Analysis of AI foundation model features decodes the histopathologic landscape of HPV-positive head and neck squamous cell carcinomas.

Objectives: Human papillomavirus (HPV) influences the pathobiology of Head and Neck Squamous Cell Carcinomas (HSNCCs). While deep learning shows promise in detecting HPV from hematoxylin and eosin (H&E) stained slides, the histologic features utilized remain unclear. This study leverages artificial intelligence (AI) foundation models to characterize histopathologic features associated with HPV presence and objectively describe patterns of variability in the HPV-positive space.

Safety of combined ablative radiotherapy and immune checkpoint inhibitors in three phase I trials.

Background: Stereotactic body radiotherapy (SBRT) is safe and effective for treatment of extracranial metastatic disease, but its safety when combined with immune checkpoint inhibitors (ICI) has not yet been comprehensively reported. Here we report adverse events (AEs) associated with combined SBRT and ICI using prospectively-collected data on patients in three trials investigating multi-site SBRT combined with ICI.

Methods: Patients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1-4 sites.

Point/Counterpoint #2: Current Clinical Considerations With Nonoperative Management of Rectal Cancer.

Locally advanced rectal cancer has historically been treated with multimodal therapy consisting of radiation therapy, chemotherapy, and total mesorectal excision. However, recent prospective trials and registry studies have demonstrated similar disease outcomes with nonoperative management for patients who experience an excellent clinical response to radiation and chemotherapy. This article reviews data regarding nonoperative management for rectal cancer, and highlights current challenges and limitations in a point-counterpoint format, in the context of two clinical cases.

Sharing the Burden: The Case for Definitive Local Therapy in Place of Immune Checkpoint Blockade for Patients With a Low-Volume Burden of Metastatic Disease.

Sharing the burden of low-volume metastatic cancer between ICB and local treatments.

SBRT for Liver Tumors: What the Interventional Radiologist Needs to Know.

This review summarizes the clinical evidence supporting the utilization of stereotactic body radiotherapy (SBRT) for liver tumors, including hepatocellular carcinoma, liver metastases, and cholangiocarcinoma. Emerging prospective evidence has demonstrated the benefit and low rates of toxicity across a broad range of clinical contexts. We provide an introduction for the interventional radiologist, with a discussion of underlying themes such as tumor dose-response, mitigation of liver toxicity, and the technical considerations relevant to performing liver SBRT.

Combined Stereotactic Body Radiation Therapy and Immune Checkpoint Inhibition for Liver Metastases: Safety and Outcomes in a Pooled Analysis of 3 Phase 1 Trials.

Purpose: Stereotactic body radiation therapy (SBRT) safely and effectively controls liver metastases (LMs), but its safety and efficacy when combined with immune checkpoint inhibitors (ICIs) are not well characterized. This analysis of 3 phase 1 trials of combination SBRT and ICI evaluates whether LM-SBRT increases the risk for hepatotoxicity when combined with ICI and explores efficacy endpoints.

Methods And Materials: Data were analyzed from 3 phase 1 trials of combination SBRT and ICI for patients with metastatic solid tumors conducted between 2016 and 2020.

Integrated Clinical-Molecular Classification of Colorectal Liver Metastases: A Biomarker Analysis of the Phase 3 New EPOC Randomized Clinical Trial.

Importance: Personalized treatment approaches for patients with oligometastatic colorectal liver metastases are critically needed. We previously defined 3 biologically distinct molecular subtypes of colorectal liver metastases: (1) canonical, (2) immune, and (3) stromal.

Objective: To independently validate these molecular subtypes in the phase 3 New EPOC randomized clinical trial.

Oligometastases: Characterizing the Role of Epigenetic Regulation of Epithelial-Mesenchymal Transition.

The "oligometastasis" hypothesis proposes that metastases exist as a spectrum and are not always disseminated. According to this theory, a subset of patients with metastatic disease could benefit from aggressive local therapies. However, the identification of patients most likely to exhibit an oligometastatic phenotype remains challenging.

Inactivation Predicts Rapid Recurrence in Inoperable Early-Stage Non-Small-Cell Lung Cancer.

Purpose: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC.

Materials And Methods: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling.

A proliferative subtype of colorectal liver metastases exhibits hypersensitivity to cytotoxic chemotherapy.

Personalized treatment approaches for patients with limited liver metastases from colorectal cancer are critically needed. By leveraging three large, independent cohorts of patients with colorectal liver metastases (n = 336), we found that a proliferative subtype associated with elevated CIN70 scores is linked to immune exclusion, increased metastatic proclivity, and inferior overall survival in colorectal liver metastases; however, high CIN70 scores generate a therapeutic vulnerability to DNA-damaging therapies leading to improved treatment responses. We propose CIN70 as a candidate biomarker to personalize systemic treatment options for patients with metastatic colorectal cancer.

Phase 1 Randomized Trial of Stereotactic Body Radiation Therapy Followed by Nivolumab plus Ipilimumab or Nivolumab Alone in Advanced/Unresectable Hepatocellular Carcinoma.

Purpose: Immunotherapy has emerged as a promising therapeutic option for advanced or unresectable hepatocellular carcinoma (HCC). However, survival remains poor with only a subset of patients deriving benefit. This trial investigated the safety and efficacy of stereotactic body radiation therapy (SBRT) with immunotherapy in HCC.

Metastasis.

Metastasis, the major cause of cancer death, represents one of the major challenges in oncology. Scientists are still trying to understand the biological basis underlying the dissemination and outgrowth of tumor cells, why these cells can remain dormant for years, how they become resistant to the immune system or cytotoxic effects of systemic therapy, and how they interact with their new microenvironment. We asked experts to discuss some of the unknowns, advances, and areas of opportunity related to cancer metastasis.

The oligometastatic spectrum in the era of improved detection and modern systemic therapy.

Metastases remain the leading cause of cancer-related mortality. The oligometastasis hypothesis postulates that a spectrum of metastatic spread exists and that some patients with a limited burden of metastases can be cured with ablative therapy. Over the past decade, substantial advances in systemic therapies have resulted in considerable improvements in the outcomes of patients with metastatic cancers, warranting re-examination of the oligometastatic paradigm and the role of local ablative therapies within the context of the improved therapeutic responses, shifting patterns of disease recurrence and possible synergy with systemic treatments.

Predictors of Pneumonitis in Combined Thoracic Stereotactic Body Radiation Therapy and Immunotherapy.

Purpose: Thoracic stereotactic body radiation therapy (SBRT) is associated with high rates of local control but carries a risk of pneumonitis. Immunotherapy is a standard treatment for patients with metastatic disease but can also cause pneumonitis. To evaluate the feasibility and safety of thoracic SBRT with systemic immunotherapy, clinical outcomes of patients treated with immune checkpoint blockade (ICB) and SBRT on prospective trials were reviewed.

Increased Disparities in Patients Diagnosed with Metastatic Lung Cancer Following Lung CT Screening in the United States.

Objectives: We sought to determine if implementation of low dose computed tomography (LDCT) screening for lung cancer in the United States had led to changes in patients being diagnosed with metastatic lung cancer over time.

Materials And Methods: The Surveillance, Epidemiology, and End Result (SEER) database was utilized to determine the proportion of lung cancers diagnosed as stage I to III and stage IV from 2009-2018. Changes in lung cancer stage distribution were compared in the overall population and by race.

Radiation Therapy for Cutaneous Malignancies of the Head and Neck.

Radiation therapy plays an integral role in the management of cutaneous malignancies of the head and neck. This article highlights the use of radiation therapy in the definitive and adjuvant setting for basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma, and Merkel cell carcinoma. Themes that emerge include the overall efficacy of radiation therapy as a local therapy, the relevance of cosmesis, functional outcomes, late toxicities as secondary end points, and the multitude of treatment modalities that are used.

Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.

Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls.

Structural connectivity analysis reveals abnormal brain connections in agenesis of the corpus callosum in children.

Objectives: Structural connectivity analysis is an ideal tool to study connections in brain malformations. We aimed to characterize the topological network measures and study sub-networks in children with agenesis of the corpus callosum (AgCC). We hypothesized a more segregated structural network in children with AgCC.