The Role of Radiotherapy in Lymphoma Patients Undergoing CAR T Therapy: Past, Present, and Future.

Chimeric antigen receptor (CAR) T-cell receptor therapy has transformed outcomes for patients with relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). It is currently approved in the third line for all patients and in the second line for early relapsed or primary refractory disease. Although CAR T cell therapy offers the potential for improved outcomes, its use may also include logistical delays related to referral, medical, social, and financial clearance as well as manufacturing time; more than half of patients experience disease recurrence or progression while awaiting CAR T infusion.

The contemporary spectrum of radiotherapy for hematologic malignancies involving the central nervous system: From focal therapy to craniospinal.

The contemporary landscape of systemic therapy options for hematologic malignancies involving the central nervous system (CNS-HM) is rapidly evolving; a key question is how radiotherapy (RT) can be optimally integrated to improve patient outcomes. Historically, use of RT to treat CNS-HM was defined by broad fields and high doses. While effective, this approach raised concerns of potential neurotoxicity which significantly decreased RT utilization.

Consolidation Regimen and Cerebral Atrophy in Patients with Primary Central Nervous System Lymphoma.

Background: In primary central nervous system lymphoma (PCNSL), the extent to which post-methotrexate consolidation contributes to neurotoxicity is unclear. Concerns for neurotoxicity from standard-dose whole-brain radiotherapy (WBRT) have led to declining use. Cerebral atrophy is an established surrogate for neurotoxicity; however, the relative extent to which modern consolidation (i.

Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

Background: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS).

Objective: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort.

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From and Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC).

Purpose: Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () mutations and anaplastic lymphoma kinase () rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.

Materials And Methods: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States.

CNS bridging radiotherapy achieves rapid cytoreduction before CAR T-cell therapy for aggressive B-cell lymphomas.

Chimeric antigen receptor (CAR) T-cell therapy (CART) for central nervous system lymphoma (CNSL) is a promising strategy, yet responses are frequently not durable. Bridging radiotherapy (BRT) is used for extracranial lymphoma in which it can improve CART outcomes through cytoreduction of high-risk lesions. We hypothesized that BRT would achieve similar, significant cytoreduction before CART for CNSL (CNS-BRT).

Prognostic Implications of Small Cell Lung Cancer Transcriptional Subtyping for CNS Metastases.

Purpose: Small cell lung cancer (SCLC) often metastasizes to the brain and has poor prognosis. SCLC subtypes distinguished by expressing transcriptional factors ASCL1 or NEUROD1 have been identified. This study investigates the impact of transcription factor-defined SCLC subtype on incidence and outcomes of brain metastases (BMs).

Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

Background: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data.

Methods: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated.

Conventional and novel [F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma.

Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T F-fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes.

Intracranial Outcomes of De Novo Brain Metastases Treated With Osimertinib Alone in Patients With Newly Diagnosed EGFR-Mutant NSCLC.

Introduction: Patients with EGFR-mutant NSCLC have a high incidence of brain metastases. The EGFR-directed tyrosine kinase inhibitor osimertinib has intracranial activity, making the role of local central nervous system (CNS)-directed therapies, such as radiation and surgery, less clear.

Methods: Patients with EGFR-mutant NSCLC and brain metastases who received osimertinib as initial therapy after brain metastasis diagnosis were included.

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases.

Importance: Adjuvant stereotactic radiosurgery (SRS) enhances the local control of resected brain metastases (BrM). However, the risks of local failure (LF) and potential for posttreatment adverse radiation effects (PTRE) after early postoperative adjuvant SRS have not yet been established.

Objective: To evaluate whether adjuvant SRS delivered within a median of 14 days after surgery is associated with improved LF without a concomitant increase in PTRE.

Lesion Dosimetry for [Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [Lu]Lu-PSMA-617 (7.

Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis.

Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we show CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples.

Retrospective characterization of nodal marginal zone lymphoma.

Nodal marginal zone lymphoma (NMZL) is a rare non-Hodgkin B-cell lymphoma that has historically been difficult to define, though is now formally recognized by the World Health Organization Classification. To better characterize the clinical outcomes of patients with NMZL, we reviewed a sequential cohort of 187 patients with NMZL to describe baseline characteristics, survival outcomes, and time-to-event data. Initial management strategies were classified into five categories: observation, radiation, anti-CD20 monoclonal antibody therapy, chemoimmunotherapy, or other.

Identification of incidental brain tumors in prostate cancer patients via PSMA PET/CT.

Purpose: Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in the setting of biochemical recurrence.

Characterization of Central Nervous System Clinico-Genomic Outcomes in ALK-Positive Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Alectinib.

Introduction: Highly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT.