Phase 2 Trial of Consolidative Stereotactic Body Radiation Therapy in Patients With Metastatic Oncogene-driven Non-small Cell Lung Carcinoma Treated With Tyrosine Kinase Inhibitors.

Purpose: The role of stereotactic body radiation therapy (SBRT) in the management of advanced EGFR/ALK/ROS1-driven non-small cell lung carcinoma (NSCLC) remains undefined. In EGFR-mutant NSCLC, 50-60% of recurrences on first-line tyrosine kinase inhibitors (TKIs) occur in originally involved sites and may lead to subsequent distant failures (DFs). We sought to determine whether consolidative SBRT to residual sites reduces DF.

Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes.

Purpose: Temozolomide plus PARP inhibition has shown promise in small cell lung cancer (SCLC). We previously reported outcomes from the first 50 patients (cohort 1) of a phase I/II trial of olaparib/temozolomide in recurrent SCLC. In this study, we report a final analysis of this trial, including a second cohort with an alternate dosing strategy and an exploratory analysis of central nervous system (CNS)-specific outcomes.

Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy Versus Intensity Modulated Radiation Therapy for Localized Prostate Cancer.

Purpose: Men with localized prostate cancer may receive either photon-based intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT). The PARTIQoL trial (NCT01617161) demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT with PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials.

Efficacy and Safety of Dose-Escalated Alectinib in Patients With Metastatic ALK-Positive NSCLC and Central Nervous System Relapse on Standard-Dose Alectinib.

Introduction: Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts.

Phantosmia during proton radiation and differences in frequency of phantosmia rates based on proton craniospinal irradiation technique for pediatric brain tumor patients.

Background: Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations.

Methods: We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021.

Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer.

Purpose: Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity.

Patients And Methods: Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223.

Health-related quality of life analyses in nonfunctioning pituitary macroadenoma patients identifies at-risk populations.

Purpose: The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to investigate associations between patient factors, clinical data, and patient-reported QoL in patients with NFPMA.

Methods: Patients with treated NFPMA and > 1 year of follow up after transsphenoidal surgery (TSS) and with no evidence of progressive disease were evaluated utilizing the following patient-reported outcome measures: RAND-36-Item Health Survey, Multidimensional Fatigue Inventory, Cognitive Failures Questionnaire.

Therapy-induced APOBEC3A drives evolution of persistent cancer cells.

Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined.

Recent trends of "manels": gender representation among invited panelists at an international oncology conference.

Background: Gender disparities in academic medicine are a long-acknowledged concern, particularly at medical conferences. We investigated gender representation and prevalence of "manels" (all-men panels) among invited speakers at the 2018-2021 American Society of Clinical Oncology Annual Meetings.

Methods: Using American Society of Clinical Oncology online programs, 2018-2021 faculty information was obtained, including perceived or self-reported gender, medical specialty, session type, and topic.

Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing.

Background: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB).

Fractionated Proton Radiation Therapy and Hearing Preservation for Vestibular Schwannoma: Preliminary Analysis of a Prospective Phase 2 Clinical Trial.

Background: Local management for vestibular schwannoma (VS) is associated with excellent local control with focus on preserving long-term serviceable hearing. Fractionated proton radiation therapy (FPRT) may be associated with greater hearing preservation because of unique dosimetric properties of proton radiotherapy.

Objective: To investigate hearing preservation rates of FPRT in adults with VS and secondarily assess local control and treatment-related toxicity.

Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial.

Overcoming intrinsic resistance to immune checkpoint blockade for microsatellite stable (MSS) colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) remains challenging. We conducted a single-arm, non-randomized, phase II trial (NCT03104439) combining radiation, ipilimumab and nivolumab to treat patients with metastatic MSS CRC (n = 40) and PDAC (n = 25) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The primary endpoint was disease control rate (DCR) by intention to treat.

Decade-long disease, secondary malignancy, and brainstem injury outcomes in pediatric and young adult medulloblastoma patients treated with proton radiotherapy.

Background: Survivors of pediatric medulloblastoma experience long-term morbidity associated with the toxic effects of postoperative radiotherapy (RT). Proton RT limits radiation dose to normal tissues thereby reducing side effects of treatment while maintaining high cure rates. However, long-term data on disease outcomes and long-term effects of proton RT remain limited.

Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations.

Purpose: We evaluated the efficacy and safety of poly-(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 inhibitor veliparib and temozolomide in metastatic breast cancer patients with and without germline BRCA1/2 mutations.

Methods: In this single-arm phase II trial, patients with metastatic breast cancer received veliparib 30 to 40 mg twice daily on days 1 to 7 with concurrent temozolomide 150 mg/m on days 1 to 5 of a 28-day cycle. The primary cohort was unselected for BRCA mutation status, and an expansion cohort enrolled only BRCA1/2 carriers.

Screening and Validation of Molecular Targeted Radiosensitizers.

The development of molecular targeted drugs with radiation and chemotherapy is critically important for improving the outcomes of patients with hard-to-treat, potentially curable cancers. However, too many preclinical studies have not translated into successful radiation oncology trials. Major contributing factors to this insufficiency include poor reproducibility of preclinical data, inadequate preclinical modeling of intertumoral genomic heterogeneity that influences treatment sensitivity in the clinic, and a reliance on tumor growth delay instead of local control (TCD50) endpoints.

Results and Molecular Correlates from a Pilot Study of Neoadjuvant Induction FOLFIRINOX Followed by Chemoradiation and Surgery for Gastroesophageal Adenocarcinomas.

Purpose: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer.

Patients And Methods: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate.

Mesothelioma Risk Score: A New Prognostic Pretreatment, Clinical-Molecular Algorithm for Malignant Pleural Mesothelioma.

Introduction: Prognostic models for malignant pleural mesothelioma have been limited to demographics, symptoms, and laboratory values. We hypothesize higher accuracy using both tumor and patient characteristics. The mesothelioma prognostic test (MPT) and molecular subtype based on claudin-15-to-vimentin expression ratio are molecular signatures associated with survival.

Assessment of a Contralateral Esophagus-Sparing Technique in Locally Advanced Lung Cancer Treated With High-Dose Chemoradiation: A Phase 1 Nonrandomized Clinical Trial.

Importance: Severe acute esophagitis occurs in up to 20% of patients with locally advanced lung cancer treated with chemoradiation therapy to at least 60 Gy once daily and represents a dose-limiting toxic event associated with poor outcomes.

Objective: To assess whether formalized sparing of the contralateral esophagus (CE) is associated with reduced risk of severe acute esophagitis.

Design, Setting, And Participants: This single-center phase 1 nonrandomized clinical trial assessing an empirical CE-sparing technique enrolled patients from July 2015 to January 2019.