Faculty Bibliography

BACKGROUND:Surgical stabilization followed by postoperative radiotherapy (RT) is the standard of care for impending pathologic fractures due to bone metastases. Compared with conventional RT, stereotactic body RT (SBRT) provides more durable tumor control and palliation, but treatment volume constraints often preclude postoperative use. Preoperative SBRT limited to the tumor volume offers a solution by delivering an ablative dose before intraoperative tumor dissemination, but its safety is not established. METHODS:We conducted a phase I, nonrandomized clinical trial at a quaternary care cancer center, with accrual between June 2021 and April 2024. Eligible patients (N=38) had pelvic or long bone metastases with impending pathologic fractures requiring surgical stabilization. Patients received preoperative SBRT (27-30 Gy in 3 fractions or 18-24 Gy in 1 fraction) followed by surgical stabilization within 1 week. The primary endpoint was rate of wound complications within 6 weeks after preoperative SBRT and surgical stabilization. Secondary endpoints were rates of tumor recurrence and grade ≥3 treatment-related toxicities within 1 year. RESULTS:A total of 7 patients were excluded due to inability to receive treatment or death prior to the primary endpoint. Thirty-one patients were evaluated at 6 weeks postoperatively, 26 at 3 months, and 16 at 1 year. The median age was 66 years (IQR, 59-71), and 15 (48%) patients were male. At 6 weeks, 2 of 31 patients (6.5%; 95% CI, 0.79-21.4) experienced wound complications. At 3 months, 1 of 26 patients (3.8%; 95% CI, 0.10-19.6) experienced grade ≥3 treatment-related toxicity. At 12 months, 1 of 16 patients (6.3%; 95% CI, 0.16-30.2) had tumor recurrence. CONCLUSIONS:Preoperative SBRT is associated with a low risk of wound complications and durable local tumor control. A randomized controlled trial examining its efficacy, potential to facilitate less invasive surgery, and impact on functional outcomes is warranted. CLINICALTRIALS/RESULTS:gov identifier: NCT05038124.

Leptomeningeal disease (LMD) or leptomeningeal metastases (LM) occurs when tumor cells invade the leptomeningeal and cerebrospinal fluid (CSF) space. Melanoma is the most common cancer causing LMD (M-LMD). Its biology and pathophysiology are very poorly understood. Research efforts are being made to explore the mechanisms underlying the immune landscape and antitumor response in LMD. The significant advances in immunocellular and targeted therapies in unresectable or metastatic melanoma in the last decade have not translated to patients with LMD and the prognosis for these patients remains dismal. While several reviews in LMD have provided an overview including challenges in diagnosis and treatment, herein we highlight evidence-based findings with a focus on immunocellular and radiation therapies, as well as the challenges that we need to overcome to help breach the existing gap in research and treatments in M-LMD. This could potentially guide additional research avenues and a better understanding of the needs and challenges of M-LMD to find novel therapies and improve patient survival.

PURPOSE/OBJECTIVE:Growing evidence supports stereotactic body radiation therapy (SBRT) over conventional radiation therapy for spine bone metastases, with an expanding role in non-spine bone metastases (NSBM). Our case-based review aims to inform radiation oncologists in the appropriate utilization of SBRT for representative cases of NSBM. METHODS AND MATERIALS/METHODS:Three cases were selected for discussion: (1) rib, (2) skull base, and (3) femur. Relevant literature was reviewed, and areas for future investigation were discussed. RESULTS:SBRT can be effectively delivered in NSBM with appropriate patient selection, target volume delineation, prescription dose, organs at risk dose constraints, and treatment planning. CONCLUSIONS:The Radiosurgery Society's case-based review offers guidance on the appropriate use of SBRT in NSBM with discussions and consensus recommendations from experts. SBRT can be considered for an oligometastatic patient with favorable prognosis in whom the goal is durable local control and/or symptom relief. It can be considered for radioresistant histologies and improved OAR sparing. Available MRI or PET/CT should be fused to improve target volume delineation. A CTV margin, generally of 5 mm, should be considered to cover microscopic disease. As bones are easily visualized on daily images acquired for accurate and precise set-up of patients, a PTV margin should be kept less than or equal to 3 mm. While SBRT can be delivered in 1 fraction, fractionated SBRT may be preferred to meet dose constraints when the CTV is adjacent to the OARs. NSBM of long bones that are weight bearing, lytic, or have a high MIRELS score should be evaluated by an orthopedic surgeon.

BACKGROUND:Early radiation therapy (RT) reduces the rate of skeletal-related events (SRE), which can affect patients' functionality and quality of life (QoL). We aimed to determine predictors of SRE and the effect of early RT on individual QoL dimensions. METHODS:We conducted a secondary analysis of a multicenter, randomized phase II trial (ClinicalTrials.gov identifier: NCT03523351) assessing early RT to asymptomatic, high-risk bone metastases. A competing risks analysis evaluated patient-level factors associated with SRE. Linear mixed models evaluated dimensions of the EuroQol 5-Dimension 5-Level (EQ-5D-5L) QoL assessment (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) over time by study arm. RESULTS:Overall, 78 patients with 122 bone metastases were enrolled; 71 (91%) patients were evaluable for the primary endpoint of SRE (35 patients in the early RT arm vs 36 in the control arm). A total of 15 SREs occurred among 11 unique patients during the 1-year follow-up period. Receipt of early RT was statistically significantly correlated with a lower risk of SRE (hazard ratio, 0.09; 95% CI, 0.01-0.66; P=.018). In the linear mixed model predicting self-care, the interaction between time and study arm was statistically significant (P=.022). At 6 months, the control arm had a decline in self-care, whereas patients in the RT arm experienced an improvement. Anxiety/depression was worse at 3 months in the RT arm, but this was not statistically significant (P=.120). CONCLUSIONS:Rates of SRE were high among patients with bone metastases, and these findings underscore the importance of early RT in their prevention. Patient-reported QoL suggests preservation of self-care with early RT, and that survival beyond 6 months may be needed to observe a benefit. Further research regarding patient selection and the impact of SRE on QoL and functionality are needed, and a phase III randomized trial (NRG CC014; NCT06745024) is in progress. CLINICALTRIALS/RESULTS:gov identifier: NCT03523351.

Leptomeningeal disease (LMD) from solid tumors carries a poor prognosis with limited treatment options. Radiotherapy to the involved sites of LMD can provide symptomatic relief in many patients. However, selected patients may derive substantially greater benefit from treating the entire neuroaxis with cerebrospinal irradiation (CSI). Ideal candidates for CSI include patients with good performance status (KPS≥60) and either systemic disease control or effective remaining systemic therapy options. Some patients with LMD, despite being otherwise ideal CSI candidates, may present with neurologic symptoms that require urgent intervention and cannot immediately be treated with CSI. In such cases, it is feasible to urgently deliver 3D radiotherapy to an involved site for urgent symptom palliation as a "bridge" to completion CSI after initial stabilization. Using this approach allows treatment of the entire neuroaxis with minimum elective dose to help minimize the risk of rapid out-of-field recurrence that is characteristic of leptomeningeal disease treated with focal-only radiation therapy. This approach allows for rapid initiation of treatment of neurologic symptoms while a more complex CSI plan is developed.

PURPOSE/UNASSIGNED:Radiation therapy has an increasing role in the management of metastatic cancers. Integrating radiation with surgical and systemic approaches is complex, and inappropriate management can lead to prolonged hospitalizations inconsistent with palliative goals. An inpatient radiation oncology consult (IROC) service was created in January 2020 to provide rapid access to specialized care for hospitalized patients. Here, we report outcomes of the IROC service, focusing on quality-of-care metrics including hospital length of stay (LOS), use of hypofractionated approaches, and treatments for patients discharged to hospice. METHODS AND MATERIALS/UNASSIGNED:= 1509) IROC, from 2019 to 2021. Continuous variables were analyzed using the Mann-Whitney test and categorical variables using Fisher's exact test. RESULTS/UNASSIGNED:= .036). CONCLUSIONS/UNASSIGNED:The IROC service was associated with reduced hospital LOS, increased use of hypofractionated approaches, and decreased treatments for patients discharged to hospice. Our findings demonstrate the value of a dedicated program addressing radiation delivery to hospitalized patients to improve goal-concordant treatments. The financial impact of reducing low-value care is an important subject for future investigations.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Bone metastases, affecting more than 4.8% of patients with cancer annually, and particularly spinal metastases require urgent intervention to prevent neurological complications. However, the current process of manually reviewing radiological reports leads to potential delays in specialist referrals. We hypothesized that natural language processing (NLP) review of routine radiology reports could automate the referral process for timely multidisciplinary care of spinal metastases. METHODS:We assessed 3 NLP models-a rule-based regular expression (RegEx) model, GPT-4, and a specialized Bidirectional Encoder Representations from Transformers (BERT) model (NYUTron)-for automated detection and referral of bone metastases. Study inclusion criteria targeted patients with active cancer diagnoses who underwent advanced imaging (computed tomography, MRI, or positron emission tomography) without previous specialist referral. We defined 2 separate tasks: task of identifying clinically significant bone metastatic terms (lexical detection), and identifying cases needing a specialist follow-up (clinical referral). Models were developed using 3754 hand-labeled advanced imaging studies in 2 phases: phase 1 focused on spine metastases, and phase 2 generalized to bone metastases. Standard McRae's line performance metrics were evaluated and compared across all stages and tasks. RESULTS:In the lexical detection, a simple RegEx achieved the highest performance (sensitivity 98.4%, specificity 97.6%, F1 = 0.965), followed by NYUTron (sensitivity 96.8%, specificity 89.9%, and F1 = 0.787). For the clinical referral task, RegEx also demonstrated superior performance (sensitivity 92.3%, specificity 87.5%, and F1 = 0.936), followed by a fine-tuned NYUTron model (sensitivity 90.0%, specificity 66.7%, and F1 = 0.750). CONCLUSION/CONCLUSIONS:An NLP-based automated referral system can accurately identify patients with bone metastases requiring specialist evaluation. A simple RegEx model excels in syntax-based identification and expert-informed rule generation for efficient referral patient recommendation in comparison with advanced NLP models. This system could significantly reduce missed follow-ups and enhance timely intervention for patients with bone metastases.

INTRODUCTION/UNASSIGNED:Gliomas are tumors that arise from glial cells in the central nervous system. Radiation provides local control for low-grade gliomas and improves survival for patients with high-grade gliomas; however, recurrence is common and treatment can be associated with long-term toxicities. Several strategies are under development to improve the anti-tumor efficacy of radiation and limit possible side effects. Novel molecular imaging agents can help diagnose new gliomas, delineate tumors for more accurate radiation planning, and differentiate tumor recurrence from treatment response changes on imaging. Radiotherapeutics provide an alternative method of delivering targeted radiation to tumors by leveraging molecular targets. New generation of radiosensitizers that target DNA damage response and cell cycle pathways aim to enhance radiation-induced cytotoxicity. AREAS COVERED/UNASSIGNED:This review summarizes emerging molecular imaging agents, radiotherapeutics, and radiosensitizers in glioma with a focus on agents currently in the early phase of clinical trials. EXPERT OPINION/UNASSIGNED:The development of new diagnostic and therapeutic agents has the potential of improving outcomes for glioma patients. As new agents are tested in clinical trials, it will be critical to consider questions regarding standardization of methodology in use/interpretation of molecular imaging techniques, appropriate dosimetry of radiotherapeutics, and cumulative toxicities with radiosensitizers.

IMPORTANCE/UNASSIGNED:Leptomeningeal metastasis (LM) is associated with limited survival and few treatment options. Photon involved-field radiotherapy (IFRT) is the most common radiotherapy treatment for patients with LM from solid tumors. OBJECTIVE/UNASSIGNED:To assess whether proton craniospinal irradiation (pCSI) would result in superior central nervous system progression-free survival (CNS-PFS) compared with IFRT. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A randomized, phase 2 trial of pCSI vs IFRT was conducted between April 16, 2020, and October 11, 2021, and included patients with non-small cell lung cancer and breast cancer with LM. Patients with other solid tumors were also enrolled in an exploratory pCSI cohort. INTERVENTION/UNASSIGNED:For the randomized groups, after stratifying by histology and systemic disease status, patients were assigned (2:1) to pCSI or IFRT. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end point was CNS-PFS. Secondary end points included overall survival (OS). RESULTS/UNASSIGNED:Of 98 total patients, 72 individuals (73.5%) were female, and the median (IQR) age was 59 (50-65) years. A total of 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively. At planned interim analysis, a significant benefit in CNS-PFS was observed with pCSI compared with IFRT, leading to the early discontinuation of the trial. In this final analysis, a significant benefit was continually observed in CNS-PFS with pCSI (median, 8.2 months; 95% CI, 6.6-15.3) vs IFRT (median, 2.3 months; 95% CI, 1.2-4.0; P < .001). A statistically significant and clinically meaningful OS benefit with pCSI (median, 11.3 months; 95% CI, 7.5-18.3) vs IFRT (median, 4.9 months; 95% CI, 3.9-15.0; P = .04) was also observed. For the exploratory pCSI cohort (n = 35), the median CNS-PFS was 5.8 months (95% CI, 4.4-9.1) and OS was 7.0 months (95% CI, 5.4-10.6). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This randomized clinical trial that assessed the optimal radiotherapy treatment for LM found improved CNS-PFS and OS with pCSI compared with IFRT. The results suggest that pCSI should be considered when available. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04343573.