A deep learning-informed interpretation of why and when dose metrics outside the PTV can affect the risk of distant metastasis in SBRT NSCLC patients.

Purpose: Recent papers suggested a correlation between the risk of distant metastasis (DM) and dose outside the PTV, though conclusions in different publications conflicted. This study resolves these conflicts and provides a compelling explanation of prognostic factors.

Materials And Methods: A dataset of 478 NSCLC patients treated with SBRT (IMRT or VMAT) was analyzed.

Consolidation ALK Tyrosine Kinase Inhibitors Versus Durvalumab or Observation After Chemoradiation in Unresectable Stage III ALK-Positive NSCLC.

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally.

Surgery and Stereotactic Radiotherapy for Stage I Small-Cell Lung Carcinoma: A 25-Year Experience.

Objectives: Small-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients.

Materials And Methods: Electronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed.

Structure-specific rigid dose accumulation dosimetric analysis of ablative stereotactic MRI-guided adaptive radiation therapy in ultracentral lung lesions.

Background: Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions.

Methods: We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021.

Intricacies of Human-AI Interaction in Dynamic Decision-Making for Precision Oncology: A Case Study in Response-Adaptive Radiotherapy.

Background: Adaptive treatment strategies that can dynamically react to individual cancer progression can provide effective personalized care. Longitudinal multi-omics information, paired with an artificially intelligent clinical decision support system (AI-CDSS) can assist clinicians in determining optimal therapeutic options and treatment adaptations. However, AI-CDSS is not perfectly accurate, as such, clinicians' over/under reliance on AI may lead to unintended consequences, ultimately failing to develop optimal strategies.

Improved outcome models with denoising diffusion.

Purpose: Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new synthetically generated datapoints, using generative models, such as Denoising Diffusion Probabilistic Models (DDPM). In this study, we implemented DDPM to improve performance of a tumor local control model, trained on imbalanced dataset, and compare this approach with other common techniques.

Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study.

Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown.

Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022.

Deep Learning-Guided Dosimetry for Mitigating Local Failure of Patients With Non-Small Cell Lung Cancer Receiving Stereotactic Body Radiation Therapy.

Purpose: Non-small cell lung cancer (NSCLC) stereotactic body radiation therapy with 50 Gy/5 fractions is sometimes considered controversial, as the nominal biologically effective dose (BED) of 100 Gy is felt by some to be insufficient for long-term local control of some lesions. In this study, we analyzed such patients using explainable deep learning techniques and consequently proposed appropriate treatment planning criteria. These novel criteria could help planners achieve optimized treatment plans for maximal local control.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM.

Magnetic Resonance-Guided Stereotactic Body Radiation Therapy/Hypofractionated Radiation therapy for Metastatic and Primary Central and Ultracentral Lung Lesions.

Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions.

Methods: Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation.

Early-Stage Primary Lung Neuroendocrine Tumors Treated With Stereotactic Body Radiation Therapy: A Multi-Institution Experience.

Purpose: Current guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes.

Dose-Limiting Pulmonary Toxicity in a Phase 1/2 Study of Radiation and Chemotherapy with Ipilimumab Followed by Nivolumab for Patients With Stage 3 Unresectable Non-Small Cell Lung Cancer.

Purpose: We hypothesized that concurrent ipilimumab with chemoradiationtherapy (chemoRT) followed by maintenance nivolumab would be safe for patients with unresectable stage III non-small cell lung cancer (NSCLC). We aimed to assess the safety (phase 1) and the 12-month progression-free survival (PFS) (phase 2) in a multi-institution prospective trial.

Methods And Materials: Eligible patients had unresectable stage III NSCLC.

Artificial Intelligence for Outcome Modeling in Radiotherapy.

Outcome modeling plays an important role in personalizing radiotherapy and finds applications in specialized areas such as adaptive radiotherapy. Conventional outcome models that are based on a simplified understanding of radiobiological effects or empirical fitting often only consider dosimetric information. However, it is recognized that response to radiotherapy is multi-factorial and involves a complex interaction of radiation therapy, patient and treatment factors, and the tumor microenvironment.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Longitudinal patient-reported outcomes and survival among early-stage non-small cell lung cancer patients receiving stereotactic body radiotherapy.

Background And Purpose: The study objective was to determine whether longitudinal changes in patient-reported outcomes (PROs) were associated with survival among early-stage, non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiation therapy (SBRT).

Materials And Methods: Data were obtained from January 2015 through March 2020. We ran a joint probability model to assess the relationship between time-to-death, and longitudinal PRO measurements.

ERK Inhibition Improves Anti-PD-L1 Immune Checkpoint Blockade in Preclinical Pancreatic Ductal Adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) do not benefit from immune checkpoint blockade (ICB) along the PD-1/PD-L1 axis. Variable PD-L1 expression in PDAC indicates a potential access issue of PD-L1-targeted therapy. To monitor target engagement of PD-L1-targeted therapy, we generated a PD-L1-targeted PET tracer labeled with zirconium-89 (Zr).

Artificial Intelligence Applications to Improve the Treatment of Locally Advanced Non-Small Cell Lung Cancers.

Locally advanced non-small cell lung cancer patients represent around one third of newly diagnosed lung cancer patients. There remains a large unmet need to find treatment strategies that can improve the survival of these patients while minimizing therapeutical side effects. Increasing the availability of patients' data (imaging, electronic health records, patients' reported outcomes, and genomics) will enable the application of AI algorithms to improve therapy selections.

A participant-derived xenograft model of HIV enables long-term evaluation of autologous immunotherapies.

HIV-specific CD8+ T cells partially control viral replication and delay disease progression, but they rarely provide lasting protection, largely due to immune escape. Here, we show that engrafting mice with memory CD4+ T cells from HIV+ donors uniquely allows for the in vivo evaluation of autologous T cell responses while avoiding graft-versus-host disease and the need for human fetal tissues that limit other models. Treating HIV-infected mice with clinically relevant HIV-specific T cell products resulted in substantial reductions in viremia.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Developing a Dedicated Leadership Curriculum for Radiation Oncology Residents.

The increasing complexity of healthcare emphasizes the need for continued physician leadership and leadership training. This study aims to determine baseline attitudes toward the perceptions and utility of a leadership development curriculum (LDC) for radiation oncology (RO) residents. A novel longitudinal LDC was implemented for RO residents at our institution from 2018 to 2019.