Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment. (c) 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

PURPOSE:The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. METHODS AND MATERIALS:Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up. RESULTS:Three hundred and eighty-three patients (102 DHL, 281 non-DHL, and 44% curative) were treated at 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% of patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post-stem cell transplant. Median biological equivalent dose (alpha/beta: 10) was 28 Gy (range: 3.2-60.0) for palliative and 46.9 Gy (range: 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, the response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI: 1.05-3.67, P = .03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative). CONCLUSIONS:Relapsed/refractory LBCL remains radioresponsive with a 60%-80% response rate to RT. Although DHL pathology does not appear to influence RT response, its presence is associated with higher rates of LR, suggesting that it may be more radioresistant.

Abstract Objective: The recently introduced Gamma Knife (GK) Lightning (Elekta) fast inverse planning dose optimizer allows concurrent optimization of multiple targets, but the optimizer’s use for generating a simultaneous integrated boost (SIB) plan has not been described and validated for accuracy of dose delivery. Here, we describe a method for creating an SIB using the GK Lightning optimizer and conduct validation of dose delivery. Materials and Methods: Radiochromic film was positioned in an anthropomorphic phantom. A 15.7-cm3 irregular contour was drawn to represent a brain metastasis resection cavity, a uniform 2-mm radial-expansion contour created, and a 1.6-cm3 contour drawn representing a nodule of residual disease within the cavity. Targets were prescribed 3 Gy (2-mm expansion), 4 Gy (cavity), and 5 Gy (residual disease) in 1 fraction. Within the GammaPlan Lightning optimizer, “beam-on time” and “low-dose” settings were iteratively adjusted to create a clinically acceptable plan. Treatment was delivered using the GK Icon system. The film was scanned and calibrated for absolute dosimetry. Global gamma index analyses were performed at various dose and distance tolerances. Results: An 18-minute treatment plan with 40 shots was delivered. Prescription isodose lines were 3 Gy at 55% (2-mm expansion), 4 Gy at 69% (resection cavity), and 5 Gy at 75% (residual disease). All target volumes had greater than or equal to 99% prescription dose coverage and the maximum dose was 6.9 Gy. Paddick conformality indices were 0.79 (2-mm expansion), 0.74 (resection cavity), and 0.15 (residual disease). Gamma index pass rate, mean, and median values were 77%, 0.68, and 0.54 at 1%/1-mm tolerance, 85%, 0.58, and 0.49 at 2%/1-mm tolerance, and 97%, 0.34, and 0.28 at 2%/2-mm tolerance. Conclusion: We successfully created an SIB plan with the GK Lightning optimizer, verifying dose delivery within clinically acceptable tolerances. Future work is needed to determine optimal dose levels for use in clinical practice and determine what disease entities may benefit from an SIB.

2063 Background: Treatment options are limited for recurrent WHO Grade 3-4 glioma (HGG). Reirradiation (ReRT) is an option, but the ideal treatment regimen and the benefit of concurrent and adjuvant systemic therapy in the recurrent setting remains unclear. Methods: A retrospective review of patients with recurrent HGG treated with reRT was conducted at 12 institutions. Eligible patients were treated with two courses of fractionated RT (>3 fractions) for glioma with the second course being for HGG. To estimate overall and progression free survival times, the Kaplan-Meier method was used. To assess the relationship between survival times and study variables, Cox proportional hazard regression models were used to calculate hazard ratios and the corresponding 95% confidence interval along with the p-value. SAS (version 9.4, Cary, NC, USA) was used for all analyses. P values < 0.05 were assumed to be statistically significant. Results: 482 eligible patients were identified from 1997 to 2023. 235 (54%) had histologic confirmation of glioblastoma at reRT. The median age at reRT was 53.1 years and median KPS was 80. 196 patients (51%) were treated with reRT at their initial recurrence and 122 (30%) had an IDH mutation. The most common reRT dose and number of fractions were 35 Gy and 10 fractions. 192 patients (44%) and 95 (24%) received concurrent (conc) and adjuvant (adj) temozolomide (TMZ) respectively and 116 (27%) and 110 (28%) received conc and adj bevacizumab (BEV) respectively with reRT. Median OS and PFS were 9.8 and 5.3 months. OS (16.6 vs 7.8 months, HR 2.44 p < 0.01) and PFS (8.6 vs 4.6 months, HR 1.85 p < 0.01) were longer in patients with IDH mutations. Receipt of conc and adj TMZ with reRT was associated with improved OS (HR 0.67 p < 0.01 and HR 0.49 p < 0.01 respectively) and PFS (HR 0.66 p <0.01 and HR 0.47 p < 0.01 respectively). Receipt of concBEV with reRT was associated with worse OS (HR 1.66 p < 0.01) but not PFS (HR 1.15 p = 0.28). AdjBEV was not associated with OS or PFS. Concurrent and adjTMZ were associated with improved OS ( p = 0.04 and <0.01) and PFS ( p = 0.01 and <0.01) for IDHwt tumors. In IDHmt tumors, concTMZ was associated with improved OS but not PFS ( p = 0.03 and 0.11), while adjTMZ was associated with improved OS and PFS ( p = 0.05 and <0.01). Symptomatic adverse radiation effects and Grade 3 or greater neurologic toxicity were seen in 107 (25%) and 86 (20%) of patients respectively. Neither conc nor adjBEV nor TMZ were associated with symptomatic ARE. ConcBEV was associated with lower (13% vs 23%, p = 0.03) and concTMZ was associated with higher rates (25% vs 15%, p = 0.01) of Grade 3 or greater neurologic toxicity. Conclusions: The use of concurrent and adjuvant TMZ with reRT are associated with improved OS and PFS in recurrent HGG. OS and PFS are improved with conc and adjTMZ for IDHwt tumors, while there was no PFS benefit to concTMZ in IDHmt tumors. The rate of high grade neurologic toxicity was decreased with the use of concurrent BEV and increased with the use of concTMZ.

Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors. We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival. Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7–639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5

Purpose/Objective(s) Reirradiation (reRT) is a treatment option for recurrent high grade glioma (HGG). However, the ideal treatment regimen and patient selection criteria remain unclear. Materials/Methods A retrospective review of patients with recurrent HGG who received fractionated reRT (>3 fractions) was performed at 12 institutions. The Kaplan-Meier Method was used to estimate overall survival (OS). Cox proportional hazards regression models were used to identify factors associated with OS. Toxicity outcomes were assessed using logistic regression. Significance was assumed if p<0.05. SAS (version 9.4, Cary, NC, USA) was used for all analyses. Results 482 eligible patients were identified. 336 (69.7%) had glioblastoma (GBM), with the remainder having Grade 3 gliomas. At reRT, the median age was 53.1 years (IQR 41.7-62.7 years) and the median KPS was 80 (IQR 70-90). 196 patients (51.0%) received reRT for their initial recurrence, 122 (30.0%) had IDH-mutant tumors, and 161 (46.4%) had MGMT methylation. The median dose at reRT was 47 Gy BED10 (IQR 47-53). 192 (44.4%) and 116 (26.9%) received concurrent temozolomide (TMZ) and bevacizumab (BEV), respectively. Median OS was 9.8 months, with a 1 year survival rate of 40.5%. In a multivariate Cox proportional hazards model, dose > 47.25 Gy BED10 (equivalent to 35 Gy in 10 fractions) was associated with improved OS (HR 0.59, p <0.01). Benefits to dose escalation were seen in both IDH-mutant (median OS 21.3 vs 11.3 months, p = 0.01) and IDH-wild type tumors (median OS 10.2 vs 6.5 months, p < 0.01), and in tumors with (median OS 13.3 vs 6.5 months, p < 0.01) and without MGMT methylation (median OS 9.6 vs 6.5 months, p < 0.01). In addition to dose, statistically significant predictors of OS in the multivariate model were glioblastoma histology (HR 1.98, 95% p < 0.01), tumor diameter > 5 cm (HR 1.47, p < 0.01), a window of < 12 months between RT courses (HR 1.88, p < 0.01), and an increasing number of recurrences prior to reRT (HR 1.25, p < 0.01 per recurrence). 107 patients (25.1%) developed Grade 2 or greater adverse radiation effects (ARE), including both pseudoprogression and radionecrosis. On univariate analysis, only one variable showed prognostic significance-patients with T2 FLAIR abnormality intentionally targeted at reRT were less likely to develop Grade 2 or greater ARE (HR 0.41, 95% p < 0.01). Receipt of BEV was not associated with development of Grade 2 or greater ARE (HR 0.67, p = 0.15). Conclusion Doses greater than the BED-equivalent of 35 Gy in 10 fractions are associated with improved survival at reRT for recurrent HGG. This benefit to dose escalation is particularly profound in IDH-mutant tumors and in MGMT-methylated tumors. Increased dose was not associated with an increase in Grade 2 or greater ARE. Factors that can potentially guide optimal patient selection for reRT include histology (non-GBM), a tumor diameter of < 5cm, an interval of at least 12 months between RT courses, and a small number of recurrences.

Purpose/Objective(s) Fast Neutron Radiotherapy (NRT) is a high linear energy transfer modality that can overcome tumor radioresistance to conventional radiotherapy (RT). This may be particularly beneficial in the palliative recurrent/metastatic setting. An ideal dose-fractionation in this setting is unknown. This study evaluates clinical and early toxicity outcomes of short course (2-4 fraction) palliative hypofractionated NRT (hNRT). Materials/Methods Clinical characteristics, oncologic treatment history, clinical (tumor shrinkage and/or symptom response) and radiographic responses were reviewed in a single-institution, IRB-approved retrospective review of patients who received at least one palliative treatment course with 3D conformal hNRT from 11/2016 to 12/2022. Results Twenty-seven patients with Stage IV cancer received hNRT at median age of 79yr (range = 47–100) with median follow-up of 5.4mo (range = 0.1-75.6). Histology included squamous (n = 7), urothelial (n = 6), Merkel (n = 5), adenocarcinoma (n = 3), renal cell (n = 2), and other (n = 4). Median hNRT dose was 6 Gy in 3 fractions (range = 3.45-10 Gy, 2-4 fractions), equivalent to around 18-30 Gy of x-rays. There were 48 hNRT treatment courses across 32 unique anatomic sites, which included head-and-neck (HN) (n = 14), bone (n = 5), genitourinary (n = 4), non-HN lymph nodes (n = 7), and non-HN skin (n = 2). Twenty-three unique treatment sites (across 19 patients) received a single hNRT course, whereas nine sites (across 9 patients) received 2-4 successive courses (median 37d between courses). 16 patients (60%) were on concurrent systemic therapy and 8 sites (25%) were previously irradiated with photon RT. Median overall survival time from the end of the first hNRT course was 400d (95% CI = 221-not reached). Of treatment sites receiving one hNRT course, 18 (78%) of 23 had clinical response, and 11 of 13 (85%) sites with radiographic follow-up had radiographic response. Of sites receiving 2 or more successive courses, 9 (100%) of 9 had clinical response and 6 of 8 (75%) sites with radiographic follow-up had radiographic response. Of 8 sites previously irradiated with photon RT, 6 (75%) had a clinical response of which 4 (50%) had a concurrent radiographic response. Of 20 sites receiving hNRT for pain relief/bleeding, 3 (15%) had symptom stability and 17 (85%) had partial-to-full clinical response, 11 of which had symptom progression at a median of 145d post-response. Of 12 sites receiving hNRT to slow disease progression and/or stimulate an immune response (n = 11 on concurrent immunotherapy or ADT), 10 (83%) had partial-to-full clinical response with radiographically stable-to-improved disease and 1 had radiographic progression. Overall, RTOG Grade 2 (n = 1) or 3 (n = 2) side effects were uncommon. No patients experienced pain flares. Conclusion Most patients treated with hNRT had symptom relief and radiographic response. None had pain flares and high-grade side effects were rare. Single or repeat-course hNRT may be a safe and effective method of palliation.

Purpose: Leptomeningeal disease (LMD) is clinically detected in 5% to 10% of patients with solid tumors and is a source of substantial morbidity and mortality. Prognosis for this entity remains poor and treatments are palliative. Radiation therapy (RT) is an essential tool in the management of LMD, and a recent randomized trial demonstrated a survival benefit for proton craniospinal irradiation (CSI) in select patients. In the setting of this recent advance, we conducted a review of the role of RT in LMD from solid tumors to evaluate the evidence basis for RT recommendations. Methods and Materials: In November 2022, we conducted a comprehensive literature search in PubMed, as well as a review of ongoing clinical trials listed on ClinicalTrials.gov, to inform a discussion on the role of RT in solid tumor LMD. Because of the paucity of high -quality published evidence, discussion was informed more by expert consensus and opinion, including a review of societal guidelines, than evidence from clinical trials. Results: Only 1 prospective randomized trial has evaluated RT for LMD, demonstrating improved central nervous system progressionfree survival for patients with breast and lung cancer treated with proton CSI compared with involved -field RT. Modern photon CSI techniques have improved upon historical rates of acute hematologic toxicity, but the overall benefit of this modality has not been prospectively evaluated. Multiple retrospective studies have explored the use of involved -field RT or the combination of RT with chemotherapy, but clear evidence of survival benefit is lacking. Conclusions: Optimal management of LMD with RT remains reliant upon expert opinion, with proton CSI indicated in patients with good performance status and extra -central nervous system disease that is either well -controlled or for which effective treatment options are available. Photon -based CSI traditionally has been associated with increased marrow and gastrointestinal toxicities, though intensity modulated RT/volumetric-modulated arc therapy based photon CSI may have reduced the toxicity profile. Further work is needed to understand the role of radioisotopes as well as combined modality treatment with intrathecal or central nervous system penetrating systemic therapies. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Higher dose of re-RT and use of concurrent TMZ led to improved OS in recurrent HGG patients without an associated increased rate of ARE. Use of BEV decreased the likelihood of Grade 2 or greater ARE in the re-RT setting for these recurrent HGG patients.

Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited to cT1a tumors without proximity to the renal pelvis or ureter. Active surveillance is another management option for small renal masses, but many patients desire treatment or are poor candidates for active surveillance. For poor surgical candidates, a growing body of evidence supports stereotactic ablative radiotherapy (SABR) as a safe and effective non-invasive treatment modality. For example, a recent multi-institution individual patient data meta-analysis of 190 patients managed with SABR estimated a 5.5% five-year cumulative incidence of local failure with one patient experiencing grade 4 toxicity, and no other grade ≥3 toxic events. Here, we discuss the recent developments in SABR for the management of localized renal cell carcinoma, highlighting key concepts of appropriate patient selection, treatment design, treatment delivery, and response assessment.

Artificial intelligence (AI) includes a broad range of computational models, such as natural language processing (NLP) [1], and has a variety of current and future applications in the healthcare setting [2,3]. In November 2022, the AI language model ChatGPT was publicly released (chat.openai.com) and quickly demonstrated proficiency on a diverse set of tasks, including United States Medical Licensing Examination questions [4]. ChatGPT was pre-trained on a large volume of text data and designed to process and analyze human language, thus ChatGPT is classified as an NLP and large language model.

This is a case of a young woman with an extensive grade 2 left skull base meningioma with unusual involvement of cervical lymph nodes, now suffering from short interval tumor progression after subtotal resection. 1 Francis DM Brower JV Atypical nodal involvement from an atypical meningioma. Int J Radiat Oncol Biol Phys. 2023; 115: 545-546 Google Scholar Gross total resection is still not feasible; however, if resection of the prepontine tumor extension was possible, this would enable safer delivery of radiation with reduced risk to the brain stem. Atypical Nodal Involvement From an Atypical MeningiomaInternational Journal of Radiation Oncology, Biology, PhysicsVol. 115Issue 3PreviewA 40-year-old female patient with a 20-year history of periodic left-sided Bell's palsy eventually developed diplopia over a 2-year period. She presented to neurology with a left medial rectus palsy. Magnetic resonance imaging (MRI) of the orbits and neck was performed, revealing a lobulated, mildly heterogeneously, enhancing lesion involving the left temporooccipital bones, which was deemed to represent fibrous dysplasia. The patient sought a second opinion, and a computed tomography (CT) scan of the head skull base/temporal bone was performed 3 months later, revealing a destructive soft-tissue mass centered in the left jugular fossa and left occipital bone, with partial destruction of the left carotid canal, and extension to the left middle ear, left cerebellopontine angle, and left poststyloid space (Fig. Full-Text PDF

In this analysis of prostate cancer patients with mesorectal involvement, we found a high incidence of high grade, T3-4 disease, and cribriform pattern, especially in ND patients. For BF patients, there was a high incidence of pT3-4 and pN1 disease at time of initial treatment. Overall, most patients had concurrent regional nodal disease on PET. Longer follow up of clinical outcomes and comparison to high-risk patients without mesorectal LN involvement is needed to understand the prognostic significance and predictors of mesorectal LN spread. Additional studies are needed to identify patients at highest risk in whom elective coverage of mesorectal lymphatics with elective pelvic nodal RT may be warranted.

As artificial intelligence (AI) models improve and become widely integrated into healthcare systems, healthcare providers must understand the strengths and limitations of AI tools to realize the full spectrum of potential patient-care benefits.However, most providers have a poor understanding of AI, leading to distrust and poor adoption of this emerging technology.To bridge this divide, this editorial presents a novel view of ChatGPT's current capabilities in the medical field of radiation oncology.By replicating the format of the oral qualification exam required for radiation oncology board certification, we demonstrate ChatGPT's ability to analyze a commonly encountered patient case, make diagnostic decisions, and integrate information to generate treatment recommendations.Through this simulation, we highlight ChatGPT's strengths and limitations in replicating human decision-making in clinical radiation oncology, while providing an accessible resource to educate radiation oncologists on the capabilities of AI chatbots.

This young patient requires definitive therapy for a progressive meningioma threatening multiple eloquent structures. 1 Francis DM Brower JV Atypical nodal involvement from an atypical meningioma. Int J Radiat Oncol Biol Phys. 2023; 115: 545-546 Google Scholar With tumor progression after initial excision, radiation therapy is an essential part of management. We favor maximal safe debulking prior to radiation therapy based on data from the RTOG 0539 trial showing worse 5-year progression-free survival for the high-risk cohort after subtotal resection (39.8% vs 52.4% with gross total resection) despite having more patients with grade 2 versus grade 3 meningioma. 2 Rogers CL Won M Vogelbaum MA et al. High-risk meningioma: Initial outcomes from NRG Oncology/RTOG 0539. Int J Radiat Oncol Biol Phys. 2020; 106: 790-799 Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar In addition, given that the tumor is in the prepontine cistern, further debulking allows for dose escalation to gross tumor while respecting brainstem tolerance. We would treat the gross residual tumor and postoperative bed with a 0.5- to 1-cm expansion along bony and dural planes to 59.4 Gy in 33 fractions. Atypical Nodal Involvement From an Atypical MeningiomaInternational Journal of Radiation Oncology, Biology, PhysicsVol. 115Issue 3PreviewA 40-year-old female patient with a 20-year history of periodic left-sided Bell's palsy eventually developed diplopia over a 2-year period. She presented to neurology with a left medial rectus palsy. Magnetic resonance imaging (MRI) of the orbits and neck was performed, revealing a lobulated, mildly heterogeneously, enhancing lesion involving the left temporooccipital bones, which was deemed to represent fibrous dysplasia. The patient sought a second opinion, and a computed tomography (CT) scan of the head skull base/temporal bone was performed 3 months later, revealing a destructive soft-tissue mass centered in the left jugular fossa and left occipital bone, with partial destruction of the left carotid canal, and extension to the left middle ear, left cerebellopontine angle, and left poststyloid space (Fig. Full-Text PDF

Abstract BACKGROUND Proton therapy may improve the side effect profile of re-irradiation for recurrent glioma by limiting the overlap with previous radiation dose received by the brain. Limited data exist regarding the outcomes or side effects after proton re-irradiation. METHODS We retrospectively reviewed the charts of 43 consecutive adult patients with glioma treated with uniform scanning or pencil beam scanning proton re-irradiation from June 2014-June 2022. Outcomes were estimated utilizing Kaplan-Meier analysis. RESULTS Median age of the cohort was 45 years (range 19-74). Initial histologic diagnosis was glioblastoma for 18 (42%), astrocytoma for 16 (37%), oligodendroglioma for 8 (19%) and diffuse glioma NOS for 1 (2%) patient. The median initial prescription dose was 60 Gy (range 54-61.2 Gy) with 86% receiving concurrent temozolomide. The median interval between initial radiation therapy (RT) and re-irradiation was 51 months (range 6-185 months). The median re-irradiation dose delivered was 37.5 cobalt gray equivalent (CGE) in 15 fractions (range 6-50.4 CGE in 2-28 fractions) with 34 patients receiving this dose fractionation. Concurrent systemic therapy included bevacizumab (8), chemotherapy (5), immunotherapy (2) or none (28). Overall, 40 (93%) finished the planned course and three stopped early given progression. Median survival was 11.5 months for the full cohort (95% confidence interval: 6.8-13.6 months). For patients with glioblastoma, median survival was 6.4 months (95%CI 5.0-13.5 months). For patients without glioblastoma, median survival was 11.6 months (95%CI 9.2-34.3 months). Twelve patients (28%) developed symptomatic pseudoprogression/radiation necrosis, with ten requiring increased steroids and four requiring bevacizumab. CONCLUSIONS Proton re-irradiation was well tolerated in patients with recurrent glioma, with 6.4 and 11.6 month median survival estimates for glioblastoma and non-glioblastoma histologies, respectively. Symptomatic pseudoprogression/radiation necrosis was common. Further study is needed to determine whether proton re-irradiation has improved tolerability compared to photons.

BACKGROUND AND OBJECTIVE:As novel systemic therapies allow patients to live longer with cancer, the risk of developing central nervous system (CNS) metastases increases and providers will more frequently encounter emergent presentation of brain metastases (BM) and leptomeningeal metastases (LM). Management of these metastases requires appropriate work-up and well-coordinated multidisciplinary care. We set out to perform a review of emergent radiotherapy (RT) for CNS metastases, specifically focusing on BM and LM.METHODS:We review the appropriate pathways for workup and initial management of BM and LM, while reviewing the literature supporting emergent treatment of these entities with surgery, systemic anti-cancer therapy, and RT. To inform this narrative review, literature searches in PubMed and Google Scholar were conducted, with preference given to articles employing modern RT techniques, when applicable. Due to the paucity of high-quality evidence for management of BM and LM in the emergent setting, discussion was supplemented by the authors' expert commentary.KEY CONTENT AND FINDINGS:This work highlights the importance of surgical evaluation, particularly for patients presenting with significant mass effect, hemorrhagic metastases, or increased intracranial pressure. We review the rare situations where emergent initiation of systemic anti-cancer therapy is indicated. When defining the role of RT, we review factors guiding selection of appropriate modality, treatment volume, and dose-fractionation. Generally, 2D- or 3D-conformal treatment techniques prescribed as 30 Gy in 10 fractions or 20 Gy in 5 fractions, should be employed in the emergent setting.CONCLUSIONS:Patients with BM and LM present from a diverse array of clinical situations, requiring well-coordinated multidisciplinary management, and there is a paucity of high-quality evidence guiding such management decisions. This narrative review aims to more thoroughly prepare providers for the challenging situation of emergent management of BM and LM.

Abstract BACKGROUND The novel Gamma Knife (GK) Lightning optimizer allows simultaneous automated optimization of multiple intracranial radiotherapy targets. We used this optimizer to create a dose-painting treatment plan where an escalated dose was prescribed to residual disease within a brain metastasis resection cavity. We validated this method by measuring dose-delivery accuracy using radiochromic film in an anthropomorphic phantom. METHODS A 15.7cc irregular contour was drawn to represent a brain metastasis resection cavity, a 2mm expansion contour created, and a 1.6cc contour drawn representing a nodule of residual disease. In GammaPlan v11.3.1, three targets were created with overlapping dose matrices. Targets were prescribed 3Gy (2mm expansion), 4Gy (resection cavity), and 5Gy (residual disease) in one fraction. On the GK Icon system, an occipital mold was made, an unexposed film placed in the phantom’s cranium, cone-beam coregistration conducted, and treatment delivered. The film was scanned and calibrated for absolute dosimetry. To evaluate dose-painting accuracy, global gamma index (GI) analyses were performed at various dose and distance tolerances, excluding points below 30% of the maximum dose. RESULTS An 18-minute treatment plan with 40 shots was created and delivered. Prescription isodose lines were 3Gy at 55% (2mm expansion, mean 4.8Gy), 4Gy at 69% (resection cavity, mean 5.2Gy), and 5Gy at 75% (residual disease, mean 6.1Gy). All target volumes had ≥ 99% prescription dose coverage and the maximum dose was 6.9Gy. Paddick conformality indices were 0.79 (2mm expansion), 0.74 (resection cavity), and 0.15 (residual disease). Gamma index pass rate/mean GI/median GI were 73%/0.68/0.55 at 1%/1mm tolerance, 85%/0.58/0.48 at 2%/1mm tolerance, and 97%/0.34/0.28 at 2%/2mm tolerance. An average of 17,883 points were evaluated per analysis. CONCLUSIONS We successfully performed GK dose painting with the Lightning optimizer, verifying dose delivery within clinically acceptable tolerances. Future work is needed to determine optimal dose levels for use in clinical practice.

Purpose/Objective(s) Presence of MYC, BCL2, and/or BCL6 translocations (i.e., double/triple-hit lymphoma [DHL/THL]) among patients with large cell lymphoma (LCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. Materials/Methods This retrospective, multi-institutional, international cohort included 211 patients with LCL and known DHL/THL status, who received RT in the relapsed/refractory (r/r) setting. Only the first RT course was included. Separate analyses were conducted for curative versus palliative intent. Response was defined as a radiographic or clinical complete or partial response (PR). Primary chemorefractory disease was defined as less than a PR to initial chemotherapy. Predictors for response and local recurrence (LR) were evaluated using Cox regression analysis. LR analyses and estimates were restricted to patients treated with curative intent to ensure adequate follow-up (median 39.6 months among surviving patients). Results Patients were heavily pretreated prior to RT (25% stem cell transplant, 8.5% CART, 41% >2 lines of therapy); 49% were irradiated with curative intent. Most patients (90% curative, 100% palliative) had macroscopic disease at RT. Response rates were similar among those with versus without DHL/THL pathology: 71.4% vs 81.2% (curative), 54.5% vs 64.7% (palliative). DHL/THL was not associated with response on univariate analysis in either the curative (HR 1.03, 95% CI 0.58-1.84, p=.91) or palliative setting (HR 1.42, 95% CI 0.73-2.76, p=.29). In contrast among patients irradiated with curative intent, presence of DHL/THL pathology was associated with increased LR risk (HR 2.38, 95% CI 1.15-4.92, p=.02), controlling for primary chemorefractory disease and radiation biologically effective dose (BED10). LR at 6 and 12 months was 21% and 30% among non-DHL/THL and 41% and 45% among DHL/THL, respectively. Conclusion R/R LCL is radioresponsive. Though presence of DHL/THL pathology does not appear to impact RT response, it is associated with increased LR risk, suggesting that it may influence radiation sensitivity. These findings require confirmation in other cohorts.

Context and objective Opioids have heterogeneous side effects including a well-known effect of sedation; however, the opposing effect of stimulation, or somatic activation, has been largely ignored or overlooked. The objective of this study is to determine the prevalence of opioid-induced somatic activation (OISA). Methods We conducted a retrospective chart review of 189 patients seen by a single clinical psychiatrist/pain specialist. During the initial encounter, the clinician took a standardized history of every opioid currently or previously taken by the patients, and enquired if the patients had experienced a somatically activating or sedating effect per opioid. Results Patients recalled an average exposure to 5.1 opioids (SD: 1.9). Ninety-one patients (48.1%; mean: 1.6) reported somatic activation, while 118 (62.4%; mean: 1.7) reported sedation from at least one opioid. Fifty-eight patients (30.7%) identified at least one opioid as activating, and another as sedating. The distribution of OISA did not significantly differ by gender, race, primary pain diagnosis, or depression. The distribution of OISA by oxycodone significantly differed compared to morphine sulfate (27.3% vs 8.9%; p: 0.005), while sedation did not (29.0% vs 24.3%; p: 0.46). Conclusions In this study, we quantified the previously unstudied phenomenon of OISA. This phenomenon appears dependent on opioid type with some opioids, such as oxycodone, appearing more likely to have this effect. Given current concerns about the risks of opioids in high-risk populations, future studies are needed to study this phenomenon to arrive at an accurate determination of the potential risks and benefits of OISA.