Purpose: Stereotactic body radiotherapy (SBRT) delivers ablative doses with excellent local control. However, implementing SBRT for abdominal and pelvic tumors has been limited by the risk for treatment‐related gastrointestinal toxicity. MRI‐guided radiotherapy may ameliorate these risks and increase the therapeutic ratio. We report the clinical outcomes of stereotactic MRI‐guided adaptive radiotherapy (SMART) for primary and metastatic tumors in the abdomen and pelvis.Methods: From November 2014 to August 2017, the first 106 consecutive patients with 121 tumors in the abdomen and pelvis were treated with SMART at a single institution. Of the cohort, 41.5%, 15.1%, and 43.4% had primary, locally recurrent, and oligometastatic tumors, respectively. SMART was delivered using a tri‐cobalt‐60 gantry with on‐board 0.35 Tesla MRI with respiratory breath‐hold and daily adaptive re‐planning when anatomically necessary. A median of 40Gy in five fractions was prescribed. The Common Terminology Criteria for Adverse Events v.4.03 was used to score treatment‐related toxicities. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method.Results: Of the 510 treatments, seventy‐one (13.9%) were adapted. Fatigue, nausea, and pain were the most common acute toxicities. 0.9 and 0% of patients experienced acute grade three and four toxicities, respectively. 5.2 and 2.1% of patients experienced late grade three and four toxicities, respectively. After a median follow‐up of 20.4 months, the 2‐year LC rate was 74% on a per‐lesion basis. Two‐year LC was 96% for lesions that were treated with BED₁₀≥100 versus 69% for BED₁₀<100 (p = 0.02). PFS was significantly different between patients with and without locally controlled tumors (2‐year PFS 21 vs. 8%, p = 0.03). Two‐year OS was 57% for the entire cohort.Conclusions: Favorable LC and PFS outcomes were observed with minimal morbidity for tumors in the abdomen and pelvis treated with SMART. Future prospective clinical trials to validate these findings are warranted.

Non-small cell lung cancer (NSCLC) has a high rate of brain metastasis. The purpose of this study was to assess the differential distribution of brain metastases from primary NSCLC based on mutation status. Brain MRI scans of patients with brain metastases from primary NSCLC were retrospectively analyzed. Brain metastatic tumors were grouped according to mutation status of their primary NSCLC and the neuroimaging features of these brain metastases were analyzed. A total of 110 patients with 1386 brain metastases from primary NSCLC were included in this study. Gray matter density at the tumor center peaked at ~0.6 for all mutations. The median depths of tumors were 7.9 mm, 8.7 mm and 9.1 mm for EGFR, ALK and KRAS mutation groups, respectively (p = 0.044). Brain metastases for the EGFR mutation-positive group were more frequently located in the left cerebellum, left cuneus, left precuneus and right precentral gyrus. In the ALK mutation-positive group, brain metastases were more frequently located in the right middle occipital gyrus, right posterior cingulate, right precuneus, right precentral gyrus and right parietal lobe. In the KRAS mutation-positive patient group, brain metastases were more frequently located in the posterior left cerebellum. Our study showed differential spatial distribution of brain metastases in patients with NSCLC according to their mutation status. Information regarding distribution of brain metastases is clinically relevant as it could be helpful to guide treatment planning for targeted therapy, and for predicting prognosis.

Purpose: Though utilization of medical procedures has been shown to vary considerably across the United States, similar efforts to characterize variation in the delivery of radiation therapy (RT) procedures have not been forthcoming. Our aim was to characterize variation in the delivery of common RT procedures in the Medicare population. We hypothesized that delivery would vary significantly based on provider characteristics.Methods: The Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File was linked to the CMS Physician Compare (PC) database by physician NPI to identify and sum all treatment delivery charges submitted by individual radiation oncologists in the non‐facility‐based (NFB) setting in 2016. Multivariable logistic regression analysis was carried out to determine provider characteristics (gender, practice rurality, practice region, and years since graduation) that predicted for the delivery of 3D conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic body RT (SBRT), stereotactic radiosurgery (SRS), low dose rate (LDR) brachytherapy, and high dose rate (HDR) brachytherapy delivery in the Medicare patient population. The overall significance of categorical variables in the multivariable logistic regression model was assessed by the likelihood ratio test (LRT).Results: In total, 1,802 physicians from the NFB practice setting were analyzed. Male gender predicted for greater LDR brachytherapy delivery (OR 8.19, 95% CI 2.58–26.05, p < 0.001), but not greater delivery of other technologies. Metropolitan practice was the only predictor for greater HDR brachytherapy utilization (OR 12.95, 95% CI 1.81–92.60, p = 0.01). Practice region was predictive of the delivery of 3DCRT, SRS and SBRT (p < 0.01, p < 0.001, and p < 0.001, respectively). With the Northeast as the reference region, 3DCRT was more likely to be delivered by providers in the South (OR 1.33, 95% CI 1.09–1.62, p < 0.01) and the West (OR 1.38, 95% CI 1.11–1.71, p < 0.01). At the same time, SRS use was less likely in the Midwest (OR 0.71, 95% CI 0.55–0.91, p < 0.01), South (OR 0.49, 95% CI 0.40–0.61, p < 0.001), and West (OR 0.43, 95% CI 0.34–0.55, p < 0.001). SBRT, on the other hand, was more commonly utilized in the Midwest (OR 2.63, 95% CI 1.13–6.13, p = 0.03), South (OR 3.44, 95% CI 1.58–7.49, p < 0.01), and West (OR 4.87, 95% CI 2.21–10.72, p < 0.001). HDR brachytherapy use was also more likely in the Midwest (OR 1.97, 95% CI 1.11–3.49, p = 0.02) and West (OR 1.87, 95% CI 1.08–3.24, p = 0.03). While the degree held by the billing physician did not predict for delivery of a given procedure, greater years since graduation was related to decreased likelihood of SBRT use (OR 0.98, 95% CI 0.96–0.99, p < 0.001) and increased likelihood of LDR brachytherapy use (OR 1.02, 95% CI 1.00–1.04, p = 0.02).Conclusions: Substantial geographic variation in the use of specific RT technologies was identified. The degree to which this variation reflects effective care, preference‐sensitive care, or supply‐sensitive care warrants further investigation.

Background: Clinical trials have shown mixed results regarding the benefit of metastasis-directed radiation therapy (MDRT) in oligoprogressive (OP) metastatic breast cancer (MBC), leading to ongoing debate about its role. This study aimed to investigate whether MDRT can prolong the duration of systemic therapy for ≥6 months in patients with OP MBC. Methods: This retrospective cohort study included patients with MBC who received MDRT for OP disease between December 2017 and March 2023. Patients who received MDRT to the brain were excluded. Medical records were reviewed through July 2024. The primary endpoint was the proportion of patients remaining on the same systemic therapy for ≥6 months post-MDRT. Results: In total, 52 patients with OP MBC treated with MDRT were included, with 36 (69%) with HR+/HER2- disease, 10 (19%) with HER2+ disease, and 6 (12%) with TNBC. Among the 47 patients with follow-up data available, 28 (60%) remained on their systemic therapy at 6 months, including 65% (22/34) of patients with HR+/HER2- disease, 56% (5/9) with HER2+ disease, and 25% (1/4) with TNBC (p = 0.30). Among the 38 patients with a follow-up time of at least 1 year post-MDRT, 47% (18/38) remained on the same systemic therapy. The median time to next systemic therapy and median PFS were 6.9 months (95% CI, 5.7–14.7) and 6.2 months (95% CI, 4.1–9.7), respectively. Conclusions: Over half of patients with OP MBC remained on the same systemic therapy for at least 6 months following MDRT, which suggests that MDRT may help prolong systemic therapy duration for select patients.

Background/Objectives: Cancer survivors frequently experience long-term neurocognitive impairments following chemotherapy and cranial irradiation, yet experimental models that enable mechanistic investigation of therapy-induced neurotoxicity at the transcriptional level remain limited. This study aimed to develop a human three-dimensional (3D) neural tissue model derived from L-MYC-immortalized neural stem cells (LMNSCs) and use transcriptomic profiling to identify molecular pathways underlying chemotherapy- and radiation-induced neural injury and extracellular vesicle (EV)-mediated recovery. Methods: LMNSCs were differentiated in a 3D, methylcellulose-based culture to generate neural tissue containing neurons, astrocytes, and oligodendrocytes in the absence of microglia. Cultures were exposed to methotrexate (MTX) or ionizing radiation to induce neural injury and subsequently treated with LMNSC-derived EVs. Neural injury and repair mechanisms were evaluated by immunocytochemistry and bulk transcriptomics. Results: MTX and irradiation induced dose-dependent injury, exhibited by loss of neuronal complexity and reduced glial populations. LMNSC-EV treatment promoted recovery of neuronal and glial populations following MTX- and irradiation-induced injury. Transcriptomic analysis of irradiated cultures revealed activation of inflammation, DNA damage, and stress-response pathways, which were attenuated after treatment with LMNSC-EVs. Conclusions: LMNSC-based 3D neural tissue provides a platform for modeling cancer therapy-induced neurotoxicity. Furthermore, LMNSC-EVs represent a promising cell-free regenerative therapeutic that modulates injury-associated inflammatory, stress, and metabolic transcriptional programs after radiation-induced neural injury. Simple Summary: Many cancer survivors experience persistent problems with memory, attention, and learning after chemotherapy or radiotherapy, yet the biological mechanisms underlying these cognitive side effects remain poorly understood. Progress has been limited by the lack of human laboratory models that accurately reproduce treatment-induced brain injury. To address this need, we developed a three-dimensional human neural tissue model containing immature neurons, astrocytes, and oligodendrocytes derived from L-MYC-immortalized human neural stem cells, lacking microglia. This platform was used to model cancer therapy-induced neural injury and evaluate the regenerative potential of neural stem cell-derived extracellular vesicles (EVs)—small bioactive particles released by stem cells. We found that cancer therapies caused significant injury to neuronal, oligodendroglial, and astrocytic cell populations, whereas EV treatment promoted recovery of these cells and activated biological pathways associated with tissue repair. These findings establish a reproducible human neural tissue platform for studying cancer therapy-related neurotoxicity and support neural stem cell-derived EVs as a promising regenerative therapeutic strategy to prevent or reduce treatment-induced cognitive impairment.