Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer.

The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy (RT). The panel developed three key questions to guide systematic review: can radiotherapy be deferred in patients receiving EGFR or ALK TKIs at (1) diagnosis or (2) recurrence? Should TKI be administered concurrently with RT (3)? Two literature searches were performed (May 2019 and December 2023). The panel developed 8 model cases and voted on treatment options using a 9-point scale, with 1-3, 4-6 and 7-9 corresponding to usually not appropriate, may be appropriate, and usually appropriate (respectively), per the UCLA/RAND Appropriateness Method. Consensus was achieved in only 4 treatment scenarios, all consistent with existing ARS-AUC guidelines for multiple BrM. The panel did not reach consensus that RT can be appropriately deferred in patients with BrM receiving CNS penetrant ALK or EGFR TKIs, though median scores indicated deferral may be appropriate under most circumstances. Whole brain RT with concurrent TKI generated broad disagreement except in cases with 2-4 BrM, where it was considered usually not appropriate. We identified no definitive studies dictating optimal sequencing of TKIs and RT for EGFRm and ALK+ BrM. Until such studies are completed, the committee hopes these cases guide decision- making in this complex clinical space.

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors.

PURPOSE: 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. METHODS: 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. RESULTS: 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%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89-481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively. CONCLUSIONS: CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

Craniospinal irradiation for CNS leukemia: rates of response and durability of CNS control.

PURPOSE: Management of CNS involvement in leukemia may include craniospinal irradiation (CSI), though data on CSI efficacy are limited. METHODS: We retrospectively reviewed leukemia patients who underwent CSI at our institution between 2009 and 2021 for CNS involvement. CNS local recurrence (CNS-LR), any recurrence, progression-free survival (PFS), CNS PFS, and overall survival (OS) were estimated. RESULTS: Of thirty-nine eligible patients treated with CSI, most were male (59%) and treated as young adults (median 31 years). The median dose was 18 Gy to the brain and 12 Gy to the spine. Twenty-five (64%) patients received CSI immediately prior to allogeneic hematopoietic cell transplant, of which 21 (84%) underwent total body irradiation conditioning (median 12 Gy). Among 15 patients with CSF-positive disease immediately prior to CSI, all 14 assessed patients had pathologic clearance of blasts (CNS-response rate 100%) at a median of 23 days from CSI start. With a median follow-up of 48 months among survivors, 2-year PFS and OS were 32% (95% CI 18-48%) and 43% (95% CI 27-58%), respectively. Only 5 CNS relapses were noted (2-year CNS-LR 14% (95% CI 5-28%)), which occurred either concurrently or after a systemic relapse. Only systemic relapse after CSI was associated with higher risk of CNS-LR on univariate analysis. No grade 3 or higher acute toxicity was seen during CSI. CONCLUSION: CSI is a well-tolerated and effective treatment option for patients with CNS leukemia. Control of systemic disease after CSI may be important for CNS local control. CNS recurrence may reflect reseeding from the systemic space.

Emergent radiotherapy for brain and leptomeningeal metastases: a narrative review.

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.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Improved lateral penumbra for proton ocular treatments on a general-purpose spot scanning beamline.

PURPOSE: An ocular applicator that fits a commercial proton snout with an upstream range shifter to allow for treatments with sharp lateral penumbra is described. MATERIALS AND METHODS: The validation of the ocular applicator consisted of a comparison of range, depth doses (Bragg peaks and spread out Bragg peaks), point doses, and 2-D lateral profiles. Measurements were made for three field sizes, 1.5, 2, and 3 cm, resulting in 15 beams. Distal and lateral penumbras were simulated in the treatment planning system for seven range-modulation combinations for beams typical of ocular treatments and a field size of 1.5 cm, and penumbra values were compared to published literature. RESULTS: All the range errors were within 0.5 mm. The maximum averaged local dose differences for Bragg peaks and SOBPs were 2.6% and 1.1%, respectively. All the 30 measured point doses were within +/-3% of the calculated. The measured lateral profiles, analyzed through gamma index analysis and compared to the simulated, had pass rates greater than 96% for all the planes. The lateral penumbra increased linearly with depth, from 1.4 mm at 1 cm depth to 2.5 mm at 4 cm depth. The distal penumbra ranged from 3.6 to 4.4 mm and increased linearly with the range. The treatment time for a single 10 Gy (RBE) fractional dose ranged from 30 to 120 s, depending on the shape and size of the target. CONCLUSIONS: The ocular applicator's modified design allows lateral penumbra similar to dedicated ocular beamlines while enabling planners to use modern treatment tools such as Monte Carlo and full CT-based planning with increased flexibility in beam placement.

Clinical outcomes and toxicities of 100 patients treated with proton therapy for chordoma on the proton collaborative group prospective registry.

BACKGROUND: We present efficacy and toxicity outcomes among patients with chordoma treated on the Proton Collaborative Group prospective registry. METHODS: Consecutive chordoma patients treated between 2010-2018 were evaluated. One hundred fifty patients were identified, 100 had adequate follow-up information. Locations included base of skull (61%), spine (23%), and sacrum (16%). Patients had a performance status of ECOG 0-1 (82%) and median age of 58 years. Eighty-five percent of patients underwent surgical resection. The median proton RT dose was 74 Gy (RBE) (range 21-86 Gy (RBE)) using passive scatter proton RT (PS-PBT) (13%), uniform scanning proton RT (US-PBT) (54%) and pencil beam scanning proton RT (PBS-PBT) (33%). Rates of local control (LC), progression-free survival (PFS), overall survival (OS) and acute and late toxicities were assessed. RESULTS: 2/3-year LC, PFS, and OS rates are 97%/94%, 89%/74%, and 89%/83%, respectively. LC did not differ based on surgical resection (p = 0.61), though this is likely limited by most patients having undergone a prior resection. Eight patients experienced acute grade 3 toxicities, most commonly pain (n = 3), radiation dermatitis (n = 2), fatigue (n = 1), insomnia (n = 1) and dizziness (n = 1). No grade ≥ 4 acute toxicities were reported. No grade ≥ 3 late toxicities were reported, and most common grade 2 toxicities were fatigue (n = 5), headache (n = 2), CNS necrosis (n = 1), and pain (n = 1). CONCLUSIONS: In our series, PBT achieved excellent safety and efficacy outcomes with very low rates of treatment failure. CNS necrosis is exceedingly low (<1%) despite the high doses of PBT delivered. Further maturation of data and larger patient numbers are necessary to optimize therapy in chordoma.

Radiation Oncology Residency Training Program Integration of Diversity, Equity, and Inclusion: An Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Inaugural Program Director Survey.

PURPOSE: The aim of this study was to investigate United States (US) radiation oncology (RO) program directors' (PDs) attitudes and practices regarding racial/ethnic diversity, equity, and inclusion (DEI) to better understand potential effects on underrepresented in medicine (UIM) residents in RO. METHODS AND MATERIALS: A 28-item survey was developed using the validated Ethnic Harassment Experiences Scale and the Daily Life Experiences subscale, as well as input from DEI leaders in RO. The survey was institutional review board-approved and administered to RO PDs. PDs were provided with the American Association of Medical Colleges definition of UIM, that is, "Underrepresented in medicine means those racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population." Descriptive statistics were used in analysis. RESULTS: The response rate was 71% (64/90). Institutional Culture and Beliefs: 42% responded that they had a department DEI director. A minority (17%, n = 11) agreed "I believe that people from UIM backgrounds have equal access to quality tertiary education in the US." The majority (97%, n = 62) agreed "My program values residents from UIM backgrounds." Support and Resources: The majority (78%, n = 50) agreed "My program has resources in place to assist/provide support for resident physicians from UIM backgrounds." Interview and Recruitment: Most PDs (53%) had not taken part in activities aimed at recruiting UIM residents and 17% had interviewed no UIM applicants in the past 5 years for residency. Resident Experiences of Racism: 17% (n = 11) agreed "UIM residents in my program have reported incidents of racism to me," and 28% (n = 18) agreed "I believe that UIM residents in my program have been treated differently because of their race/ethnicity by faculty, staff, coresidents or patients." CONCLUSIONS: Most PDs reported that they did not believe that UIM residents were treated differently in their department because of their race/ethnicity, and only a minority had received reports of racial discrimination experienced by residents. These data contrast resident experiences and suggest a disconnect between DEI perceptions and resident experiences among US RO PDs that should be addressed through increased programmatic action and evaluation.

Radiation Oncology Resident Perspectives on Diversity, Equity, and Inclusion: An Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Inaugural Resident Survey.

PURPOSE: In this study, radiation oncology residents were surveyed on perceptions of diversity, equity, inclusion, and belonging in their residency training programs. METHODS AND MATERIALS: A 23-item survey was developed by the Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee resident members and faculty advisors. The survey was divided into 4 sections: institutional culture, support and resources, interview and recruitment, and experiences of bias. The survey was sent individually to residents from all Accreditation Council for Graduate Medical Education-accredited radiation oncology programs. RESULTS: The survey was issued to 757 residents. A total of 319 residents completed the survey, for a response rate of 42%. All postgraduate years and geographic regions were represented. Significant racial, ethnic, and gender differences were present in survey response patterns. White residents (94%, 164 of 174) and male residents (96%, 186 of 194) were more likely to strongly agree/agree that they were treated with respect by their colleagues and their coworkers than other racial groups (P < .005) or gender groups (P < .008). Only 3% (5 of 174) of White residents strongly agreed/agreed that they were treated unfairly because of their race/ethnicity, while 31% (5 of 16) of Black residents and 10% (9 of 94) of Asian residents strongly agreed/agreed (P < .0001). Similarly, Hispanic residents were more likely to strongly agree/agree (24%, 5 of 21) than non-Hispanic residents (7%, 20 of 298) (P = .003). Regarding mentorship, there were no differences by gender or ethnicity. There were differences by race in residents reporting that they had a supportive mentor (P = .022), with 89% (154 of 174) of White residents who strongly agreed/agreed, 88% (14 of 16) of Black residents, and 91% of Asian residents (86 of 94). CONCLUSIONS: This survey reveals that experiences of support, mentorship, inclusion, and bias vary significantly among radiation oncology residents based on race, ethnicity, and gender. Radiation oncology has opportunity for growth to ensure an equitable experience for all residents.

Surveillance of long-term complications after treatment of adult brain tumor survivors-review and evidence-based recommendations.

As a result of treatment and diagnosis, adults with primary or metastatic brain tumors experience comorbidities that impacts their health and well-being. The Children's Oncology Group has guideline recommendations for childhood survivors of brain tumors; however, guidelines for monitoring long-term sequela among adult brain tumor survivors are lacking. The purpose of this review is to present the screening recommendations for the long-term complications after brain tumor treatment from a multidisciplinary panel of healthcare professionals. Chronic complications identified include cognitive dysfunction, vasculopathy, endocrinopathy, ophthalmic, ototoxicity, physical disability, sleep disturbance, mood disorder, unemployment, financial toxicity, and secondary malignancy. We invited specialists across disciplines to perform a literature search and provide expert recommendations for surveillance for long-term complications for adult brain tumor survivors. The Brain Tumor Center Survivorship Committee recommends routine screening using laboratory testing, subjective assessment of symptoms, and objective evaluations to appropriately monitor the complications of brain tumor treatments. Effective monitoring and treatment should involve collaboration with primary care providers and may require referral to other specialties and support services to provide patient-centered care during neuro-oncology survivorship. Further research is necessary to document the incidence and prevalence of medical complications as well as evaluate the efficacy of screening and neuro-oncology survivorship programs.

Intracranial Solitary Fibrous Tumor/Hemangiopericytoma Treated with Microsurgical Resection: Retrospective Cohort Analysis of a Single-Center Experience.

Objective: To provide benchmarks for further studies of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) of the central nervous system (CNS), we investigated the association of baseline demographic, clinico-pathologic, and treatment factors with outcomes in those treated at our center. Methods: We conducted a retrospective, cohort analysis of patients treated for SFT/HPC at the University of Washington 1990-2020. Kaplan-Meier and univariable Cox analyses assessed relationships between baseline variables and local or global CNS recurrence, extraneural recurrence, progression-free survival (PFS) and overall survival (OS). Results: Among 34 eligible patients, median duration of follow-up was 79 months (range 13-318 months). Local and global CNS recurrence occurred at a median of 81 m (95% CI 48-151) and 81 m (95% CI 47-112), respectively. Extraneural metastases occurred at a median 248 m (95% CI 180-Not Reached) and only in grade 3 tumors. Median PFS and OS were 76 months (95% CI: 47-109 months) and 210 months (95% CI 131-306 months), respectively. Univariable Cox analyses showed that age at diagnosis was associated with local (p = 0.01) and global CNS relapse (p = 0.01), and PFS (p = 0.03). Gross total resection was associated with decreased local or global CNS relapse (p = 0.02) and improved PFS (p = 0.03); peri-operative radiation was associated with decreased local CNS relapse (p = 0.02). Conclusion: Following microsurgical resection of SFT/HPC, CNS relapse is common and associated with age, extent of resection, and adjuvant radiation. Extraneural relapse occurs in some patients. Delayed time-to-initial relapse justifies prolonged surveillance, but optimal approaches have not been defined.

Radiation Therapy for IDH-Mutant Grade 2 and Grade 3 Diffuse Glioma: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for adults with isocitrate dehydrogenase (IDH)-mutant grade 2 and grade 3 diffuse glioma, as classified in the 2021 World Health Organization (WHO) Classification of Tumours. It includes indications for radiation therapy (RT), advanced RT techniques, and clinical management of adverse effects. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 4 key questions focused on the RT management of patients with IDH-mutant grade 2 and grade 3 diffuse glioma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: A strong recommendation for close surveillance alone was made for patients with oligodendroglioma, IDH-mutant, 1p/19q codeleted, WHO grade 2 after gross total resection without high-risk features. For oligodendroglioma, WHO grade 2 with any high-risk features, adjuvant RT was conditionally recommended. However, adjuvant RT was strongly recommended for oligodendroglioma, WHO grade 3. A conditional recommendation for close surveillance alone was made for astrocytoma, IDH-mutant, WHO grade 2 after gross total resection without high-risk features. Adjuvant RT was conditionally recommended for astrocytoma, WHO grade 2, with any high-risk features and strongly recommended for astrocytoma, WHO grade 3. Dose recommendations varied based on histology and grade. Given known adverse long-term effects of RT, consideration for advanced techniques such as intensity modulated radiation therapy/volumetric modulated arc therapy or proton therapy were given as strong and conditional recommendations, respectively. Finally, based on expert opinion, the guideline recommends assessment, surveillance, and management for toxicity management. CONCLUSIONS: Based on published data, the American Society for Radiation Oncology task force has proposed recommendations to inform the management of adults with IDH-mutant grade 2 and grade 3 diffuse glioma as defined by WHO 2021 classification, based on the highest quality published data, and best translated by our task force of subject matter experts.

An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.

Disparities in Access to Radiation Therapy by Race and Ethnicity in the United States With Focus on American Indian/Alaska Native People.

OBJECTIVES: Striking disparities in access to radiation therapy (RT) exist, especially among racial and ethnic-minority patients. We analyzed census block group data to evaluate differences in travel distance to RT as a function of race and ethnicity, socioeconomic status, and rurality. METHODS: The Directory of Radiotherapy Centers provided the addresses of facilities containing linear accelerators for RT. We classified block groups as majority (≥ 50%) American Indian/Alaska Native (AI/AN), black, white, Asian, no single racial majority, or Hispanic regardless of race. We used the Area Deprivation Index to classify deprivation and Rural-Urban Commuting Area codes to classify rurality. Generalized linear mixed models tested associations between these factors and distance to nearest RT facility. RESULTS: Median distance to nearest RT facility was 72 miles in AI/AN-majority block groups, but 4 to 7 miles in block groups with non-AI/AN majorities. Multivariable models estimated that travel distances in AI/AN-majority block groups were 39 to 41 miles longer than in areas with non-AI/AN majorities. Travel distance was 1.3 miles longer in the more deprived areas versus less deprived areas and 16 to 32 miles longer in micropolitan, small town, and rural areas versus metropolitan areas. CONCLUSIONS: Cancer patients in block groups with AI/AN-majority populations, nonmetropolitan location, and low socioeconomic status experience substantial travel disparities in access to RT. Future research with more granular community- and individual-level data should explore the many other known barriers to access to cancer care and their relationship to the barriers posed by distance to RT care.

Systemic Treatment Patterns and Outcomes in Patients With EGFR Mutated Non-small Cell Lung Cancer and Leptomeningeal Disease.

INTRODUCTION: Leptomeningeal (LM) disease occurs in 9% to 10% of EGFR mutated non-small cell lung cancer (NSCLC) cases. The natural history and optimal systemic treatment strategies for this disease are not well-characterized, particularly in the era of osimertinib. MATERIALS AND METHODS: We identified 54 patients with EGFR mutated NSCLC and LM disease diagnosed between January 3, 2000 to March 31, 2020 and treated at an academic oncology practice in Seattle, Washington. We abstracted demographic, tumor, treatment, and outcome data from the electronic medical record. Univariate Cox models were run to evaluate the association between post-LM disease systemic therapy and overall survival. Differences in LM disease natural history and healthcare utilization between groups were assessed using Student's t test or a chi-squared test. RESULTS: Patients that received osimertinib prior to LM disease had a longer median time to LM disease diagnosis and trended toward better performance status than those that did not. Patients that received any post-LM disease systemic therapy had a lower risk of death relative to those that did not (HR 0.17, P < .001), with a suggestion that osimertinib-containing regimens result in longer median overall survival. Emergency department, hospital and hospice utilization were not associated with receipt of post-LM disease systemic therapy. CONCLUSION: Prior exposure to osimertinib appears to favorably influence the natural history of LM disease. Any systemic therapy after LM disease diagnosis is associated with longer survival and does not increase healthcare utilization. Additional research is needed to assess whether an osimertinib-containing regimen confers a survival benefit after LM disease diagnosis among patients who received prior osimertinib.

Executive summary of American Radium Society's appropriate use criteria for the postoperative management of lower grade gliomas.

Postoperative management of lower grade gliomas (grade 2 and 3) is heterogeneous. The American Radium Society's brain malignancies panel systematically reviewed and evaluated the literature to develop consensus guidelines addressing timing of postoperative therapy, monotherapy versus combined modality therapy, type of chemotherapy used with radiotherapy, and radiotherapy dose. Thirty-six studies were included. Using consensus methodology (modified Delphi), the panel voted upon representative case variants using a 9-point appropriateness scale to address key questions. Voting results were collated to develop summarized recommendations. Following gross-total surgical resection, close surveillance is appropriate for well-selected grade 2, IDH-mutant oligodendrogliomas or astrocytomas with low-risk features. For grade 2 gliomas with high-risk features or any grade 3 glioma, immediate adjuvant therapy is recommended. When postoperative therapy is administered, radiation and planned chemotherapy is strongly recommended over monotherapy. For grade 2 and 3 IDH-mutant oligodendrogliomas and astrocytomas, either adjunctive PCV (procarbazine, lomustine, vincristine) or temozolomide is appropriate. For grade 3 IDH-mutant astrocytomas, radiotherapy followed by temozolomide is strongly recommended. The recommended radiotherapy dose for grade 2 gliomas is 45-54 Gy/1.8-2.0 Gy, and for grade 3 gliomas is 59.4-60 Gy/1.8-2.0 Gy. While multiple appropriate treatment options exist, these consensus recommendations provide an evidence-based framework to approach postoperative management of lower grade gliomas.

Treatment of ocular tumors through a novel applicator on a conventional proton pencil beam scanning beamline.

Treatment of ocular tumors on dedicated scattering-based proton therapy systems is standard afforded due to sharp lateral and distal penumbras. However, most newer proton therapy centers provide pencil beam scanning treatments. In this paper, we present a pencil beam scanning (PBS)-based ocular treatment solution. The design, commissioning, and validation of an applicator mount for a conventional PBS snout to allow for ocular treatments are given. In contrast to scattering techniques, PBS-based ocular therapy allows for inverse planning, providing planners with additional flexibility to shape the radiation field, potentially sparing healthy tissues. PBS enables the use of commercial Monte Carlo algorithms resulting in accurate dose calculations in the presence of heterogeneities and fiducials. The validation consisted of small field dosimetry measurements of point doses, depth doses, and lateral profiles relevant to ocular therapy. A comparison of beam properties achieved through the applicator against published literature is presented. We successfully showed the feasibility of PBS-based ocular treatments.

The Advantage of Proton Therapy in Hypothalamic-Pituitary Axis and Hippocampus Avoidance for Children with Medulloblastoma.

PURPOSE: Craniospinal irradiation (CSI) improves clinical outcomes at the cost of long-term neuroendocrine and cognitive sequelae. The purpose of this pilot study was to determine whether hypothalamic-pituitary axis (HPA) and hippocampus avoidance (HPA-HA) with intensity-modulated proton therapy (IMPT) can potentially reduce this morbidity compared with standard x-ray CSI. MATERIALS AND METHODS: We retrospectively evaluated 10 patients with medulloblastoma (mean, 7 years; range, 4-14 years). Target volumes and organs at risk were delineated as per our local protocol and the ACNS0331 atlas. An experienced neuroradiologist verified the HPA and hippocampus contours. The primary objective was CSI and boost clinical target volume (CTV) covering 95% of the volume (D95) > 99% coverage with robustness. Described proton therapy doses in grays are prescribed using a biological effectiveness relative to photon therapy of 1.1. The combined prescribed dose in the boost target was 54 Gy. Secondary objectives included the HPA and hippocampus composite average dose (Dmean ≤ 18 Gy). For each patient, volumetric modulated arc radiotherapy (VMAT) and tomotherapy (TOMO) plans existed previously, and a new plan was generated with 3 cranial and 1 or 2 spinal beams for pencil-beam scanning delivery. Statistical comparison was performed with 1-way analysis of variance. RESULTS: Compared with standard CSI, HPA-HA CSI had statistically significant decreases in the composite doses received by the HPA (32.2 versus 17.9 Gy; P < .001) and hippocampi (39.8 versus 22.8 Gy; P < .001). The composite HPA Dmean was lower in IMPT plans (17.9 Gy) compared with that of VMAT (21.8 Gy) and TOMO (21.2 Gy) plans (P = .05). Hippocampi composite Dmean was also lower in IMPT plans (21 Gy) compared with that of VMAT (27.5 Gy) and TOMO (27.2 Gy) plans (P = .02). The IMPT CTV D95 coverage was lower in IMPT plans (52.8 Gy) compared with that of VMAT (54.6 Gy) and TOMO (54.6 Gy) plans (P < .001) The spared mean volume was only 1.35% (19.8 cm3) of the whole-brain CTV volume (1476 cm3). CONCLUSION: We found that IMPT has the strong potential to reduce the dose to the HPA and hippocampus, compared with standard x-ray CSI while maintaining target coverage. A prospective clinical trial is required to establish the safety, efficacy, and toxicity of this novel CSI approach.