Impact of Higher Cell-Free DNA Yields on Liquid Biopsy Testing in Glioblastoma Patients.

Background: Minimally invasive molecular profiling using cell-free DNA (cfDNA) is increasingly important to the management of cancer patients; however, low sensitivity remains a major limitation, particularly for brain tumor patients. Transiently attenuating cfDNA clearance from the body-thereby, allowing more cfDNA to be sampled-has been proposed to improve the performance of liquid biopsy diagnostics. However, there is a paucity of clinical data on the effect of higher cfDNA recovery.

Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.

Prospective Evaluation of Supplemental External Beam Radiation Therapy With Palladium-103 Prostate Brachytherapy: Long-Term Results of the 44/20/0 Trials.

Purpose: The 44/20 and 20/0 randomized trials evaluated whether different external beam radiation therapy (EBRT) dosing regimens prior to brachytherapy affected biochemical failure (BF). We report long-term outcomes of both trials and evaluate whether biological equivalent dose (BED) was associated with reduced BF in the combined trial cohort.

Methods And Materials: Both trials enrolled patients with clinical T1c to T2b, Gleason scores 7 to 9, and/or a pretreatment prostate-specific antigen (PSA) 10 to 20 ng/mL disease.

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer.

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC.

Second primary non-breast cancers in young breast cancer survivors.

Purpose: We evaluated the incidence, timing, and risk factors for second primary non-breast cancers (SPNBC) among young breast cancer (BC) survivors.

Methods: This study included participants of the Young Women's BC Study (YWS) who were diagnosed with stage 0-III BC between 2006 and 2016 and age 40 or younger at diagnosis (N = 1,230). Patient characteristics, treatment information, and clinical events were collected via serial surveys.

Long-Term Analysis of NRG Oncology RTOG 0415: A Randomized Phase III Noninferiority Study Comparing Two Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

JCO NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.

MAESTRO-Pool Enables Highly Parallel and Specific Mutation-Enrichment Sequencing for Minimal Residual Disease Detection in Cohort Studies.

Background: Tracing patient-specific tumor mutations in cell-free DNA (cfDNA) for minimal residual disease (MRD) detection is promising but challenging. Assaying more mutations and cfDNA stands to improve MRD detection but requires highly accurate, efficient sequencing methods and proper calibration to prevent false detection with bespoke tests.

Methods: MAESTRO (Minor Allele Enriched Sequencing Through Recognition Oligonucleotides) uses mutation-specific oligonucleotide probes to enrich cfDNA libraries for tumor mutations and enable their accurate detection with minimal sequencing.

Dose-Volume Predictors of Radiation Pneumonitis After Thoracic Hypofractionated Radiation Therapy.

Purpose: Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis.

Methods And Materials: All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020.

Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.

Purpose: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ.

Methods: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques.

Enhancing Symptom Screening and Patient Education Among Patients with Metastatic Lung Cancer: a Qualitative Analysis.

We explored perspectives of patients with metastatic non-small cell lung cancer (mNSCLC) on symptom screening and population-level patient-reported outcome (PRO) data regarding common symptom trajectories in the year after diagnosis. A qualitative study of patients with mNSCLC was conducted at a Canadian tertiary cancer centre. English-speaking patients diagnosed ≥ 6 months prior to study invitation were recruited, and semi-structured one-on-one interviews were conducted.

Cardiorespiratory Fitness in Patients With Early-Stage Breast Cancer and Radiation Therapy-Related Fatigue: A Prospective Pilot Study.

Purpose: Fatigue is among the most common but most poorly understood radiation therapy-associated toxicities. This prospective study sought to investigate whether cardiorespiratory fitness, an integrative measure of whole-body cardiopulmonary function, is associated with patient-reported fatigue in women with early-stage breast cancer undergoing radiation therapy.

Methods And Materials: Patients with stage Tis-T2N0M0 breast cancer and an Eastern Cooperative Oncology Group performance status of 0 to 1 undergoing breast radiation therapy performed a symptom-limited cardiopulmonary exercise test (CPET) on a motorized treadmill to assess cardiorespiratory fitness as measured by peak oxygen uptake (VOpeak).

Association of Somatic TET2 Mutations With Giant Cell Arteritis.

Objective: Giant cell arteritis (GCA) is an age-related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HMs). How the presence of somatic mutations that drive the development of HMs, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood.

Development and Validation of an Automated Image-Based Deep Learning Platform for Sarcopenia Assessment in Head and Neck Cancer.

Importance: Sarcopenia is an established prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC); the quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical skeletal muscle segmentation and cross-sectional area. However, manual muscle segmentation is labor intensive, prone to interobserver variability, and impractical for large-scale clinical use.

Objective: To develop and externally validate a fully automated image-based deep learning platform for cervical vertebral muscle segmentation and SMI calculation and evaluate associations with survival and treatment toxicity outcomes.

Expert-level pediatric brain tumor segmentation in a limited data scenario with stepwise transfer learning.

Purpose: Artificial intelligence (AI)-automated tumor delineation for pediatric gliomas would enable real-time volumetric evaluation to support diagnosis, treatment response assessment, and clinical decision-making. Auto-segmentation algorithms for pediatric tumors are rare, due to limited data availability, and algorithms have yet to demonstrate clinical translation.

Methods: We leveraged two datasets from a national brain tumor consortium (n=184) and a pediatric cancer center (n=100) to develop, externally validate, and clinically benchmark deep learning neural networks for pediatric low-grade glioma (pLGG) segmentation using a novel in-domain, stepwise transfer learning approach.

Gender-Affirming Surgery and Cancer: Considerations for Radiation Oncologists for Pelvic Radiation in Transfeminine Patients.

Access to gender-affirming surgery is increasing for many transgender and nonbinary people in the United States, and radiation oncologists must be equipped to care for patients who have undergone such surgery in the region of their planned radiation treatment field. There are no guidelines for radiation treatment planning after gender-affirming surgery, and most oncologists do not receive training in the unique needs of transgender people with cancer. We review common gender-affirming genitopelvic surgeries for transfeminine people, including vaginoplasty, labiaplasty, and orchiectomy, and summarize the existing literature on the treatment of cancers of the neovagina, anus, rectum, prostate, and bladder in these patients.

Protocol to establish a genetically engineered mouse model of IDH1-mutant astrocytoma.

Lower-grade gliomas exhibit a high prevalence of isocitrate dehydrogenase 1 (IDH1) mutations, but faithful models for studying these tumors are lacking. Here, we present a protocol to establish a genetically engineered mouse (GEM) model of grade 3 astrocytoma driven by the Idh1 oncogene. We describe steps for breeding compound transgenic mice and intracranially delivering adeno-associated virus particles, followed by post-surgical surveillance via magnetic resonance imaging.

A pulmonary vein atlas for radiotherapy planning.

Background And Purpose: Cardiac arrhythmia is a recognised potential complication of thoracic radiotherapy, but the responsible cardiac substructures for arrhythmogenesis have not been identified. Arrhythmogenic tissue is commonly located in the pulmonary veins (PVs) of cardiology patients with arrhythmia, however these structures are not currently considered organs-at-risk during radiotherapy planning. A standardised approach to their delineation was developed and evaluated.

Dual center validation of deep learning for automated multi-label segmentation of thoracic anatomy in bedside chest radiographs.

Background And Objectives: Bedside chest radiographs (CXRs) are challenging to interpret but important for monitoring cardiothoracic disease and invasive therapy devices in critical care and emergency medicine. Taking surrounding anatomy into account is likely to improve the diagnostic accuracy of artificial intelligence and bring its performance closer to that of a radiologist. Therefore, we aimed to develop a deep convolutional neural network for efficient automatic anatomy segmentation of bedside CXRs.

Pain and Interventions in Stage IV Non-Small Cell Lung Cancer: A Province-Wide Analysis.

Pain is a common symptom in stage IV non-small cell lung cancer (NSCLC). The objective of the study was to examine the use of interventions and factors associated with interventions for pain. A population-based cohort study in Ontario, Canada was conducted with patients diagnosed with stage IV NSCLC from January 2007 to September 2018.

Fully-automated sarcopenia assessment in head and neck cancer: development and external validation of a deep learning pipeline.

Purpose: Sarcopenia is an established prognostic factor in patients diagnosed with head and neck squamous cell carcinoma (HNSCC). The quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical neck skeletal muscle (SM) segmentation and cross-sectional area. However, manual SM segmentation is labor-intensive, prone to inter-observer variability, and impractical for large-scale clinical use.

Tumor Volume Nadir in Patients With -Rearranged Non-Small-Cell Lung Cancer Treated With Alectinib.

Purpose: Patients with oncogene-driven advanced non-small-cell lung cancer (NSCLC) treated with effective targeted therapy demonstrate characteristic tumor volume dynamics with initial response, nadir, and subsequent regrowth. This study investigated tumor volume nadir and time to nadir in patients with -rearranged advanced NSCLC treated with alectinib.

Materials And Methods: In patients with advanced -rearranged NSCLC treated with alectinib monotherapy, tumor volume dynamics were evaluated on serial computed tomography (CT) scans using a previously validated CT tumor measurement technique.