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Inverse planning simulated annealing (IPSA) produces highly conformal dose distributions and quick optimizations for high-dose-rate interstitial brachytherapy (HDRBT). We report our dosimetry and overall outcomes using this approach for the accelerated post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue (OTSCC) with high risk of local recurrence.Patients with newly diagnosed pN0 OTSCC treated with partial glossectomy, neck dissection, and post-operative HDRBT alone from 2007 to 2021 were retrospectively reviewed. Patients received 30 Gy in 5 fractions over 2.5 days. Target volume and mandible dosimetry are reported. Actuarial rates of local control, regional control, disease-specific survival, and overall survival were estimated using the Kaplan-Meier method. Toxicity was categorized using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.19 consecutive patients were reviewed. Median follow-up was 3.2 years (IQR 1.4-8.2 years) with a 3-year estimated local control rate of 81%. Target volumes were generally small, as the median volume was 12.66 cc. Median V150% and V200% were 52% and 24%, respectively. D1cc and D2cc to the mandible were 17.31 Gy and 14.42 Gy, respectively.IPSA-HDRBT is feasible and highly efficient for post-operative treatment of the primary tumor bed in patients with pathologically node-negative squamous cell carcinomas of the oral tongue. Further technical optimization and prospective clinical evaluation in a larger patient cohort are planned.

Background Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Recent studies have proposed prognostic meningioma classification systems using DNA methylation profiling, copy number variants, DNA sequencing, RNA sequencing, histology, or integrated models based on multiple combined features. Targeted gene expression profiling has generated robust biomarkers integrating multiple molecular features for other cancers, but is understudied for meningiomas. Methods Targeted gene expression profiling was performed on 173 meningiomas and an optimized gene expression biomarker (34 genes) and risk score (0 to 1) was developed to predict clinical outcomes. Clinical and analytical validation was performed on independent meningiomas from 12 institutions across 3 continents (N = 1856), including 103 meningiomas from a prospective clinical trial. Gene expression biomarker performance was compared to 9 other classification systems. Results The gene expression biomarker improved discrimination of postoperative meningioma outcomes compared to all other classification systems tested in the independent clinical validation cohort for local recurrence (5-year area under the curve [AUC] 0.81) and overall survival (5-year AUC 0.80). The increase in area under the curve compared to the current standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval [CI] 0.07–0.17, P

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Purpose/objective(s) Sarcoma is a rare, diverse oncologic diagnosis with a complex spectrum of presentation. Advances in multimodality therapy including treatment with radiotherapy have shifted the paradigm from amputation to limb-sparing surgery (LSS) or limited resections. Management of recurrent sarcoma after LSS is challenging and may require subsequent amputation. Here, we sought to identify factors associated with amputation or radical excision as salvage therapy for recurrent sarcoma. Materials/methods Sarcomas treated at a single institution were identified. Patients who required any salvage surgery for recurrent sarcoma were selected. Comparison was made between patients receiving LSS or limited re-excision versus amputation or radical, whole organ excision at the time of first salvage surgery. Demographic, tumor, and treatment characteristics were retrospectively reviewed. Univariate comparison was made using Chi squared test and analysis of variance. Multivariate logistic regression was completed to assess factors associated with salvage surgery type. Results A total 5,774 sarcoma patients were evaluated between 2000 and 2018. Salvage surgery for recurrent sarcoma was required for 519 patients (9%). Patients requiring upfront radical surgery (n = 17) were excluded. The study included 502 patients with 375 (75%) receiving salvage limb sparing surgery and 127 (25%) receiving salvage amputation or radical surgery at the time of their second surgery. Soft tissue sarcoma (STS, n = 455, 91%) was more common than osseous sarcoma (n = 47, 9%), including 173 (34%) STS of extremities. Univariate analysis revealed that age, gender, and race were not associated with amputation or radical surgery; however, higher stage, higher grade, and no radiation in primary treatment were associated with subsequent amputation (P Conclusion In a single institution cohort, need for amputation or radical excision at the time of salvage surgery after LSS for recurrent disease was rare, in keeping with modern sarcoma experiences. Retrospective review suggests that higher stage is associated with radical salvage options while receipt of radiation during primary treatment is inversely related. Further inquiry into the clinical characteristics and the patterns of failure may clarify the relationship between stage, radiation and radical salvage therapy. Future work may aid in avoiding morbid salvage therapy.

PURPOSE To understand trends, pathways, and experiences and to establish a framework for radiation oncology (RO) programs interested in developing global health (GH) initiatives. METHODS An in-depth interview was conducted of all US RO programs with established GH initiatives. Programs were identified by reviewing results of the 2018 Association of Residents in Radiation Oncology Global Health Resident Survey and individualized outreach to screen for additional programs meeting the following criteria: (1) active resident involvement in RO-specific GH opportunities, (2) active faculty involvement in these initiatives, and (3) department chair or program director awareness and support for ongoing opportunities. Among 88 residency programs, 11 were identified. Standardized questions explored the type of initiative, planning, staff and resident involvement, challenges, components to success, and history of programs through December 2018. RESULTS Between 2010 and 2018, 11 programs started initiatives. Total resident participants ranged from one to 13 (median = 3) in each program's history. Initiatives spanned education (n = 9 [82%]), clinical mentorship (73%), innovative technology (55%), bilateral hosting programs (45%), clinical development and equipment (45%), promotion of local research (36%), clinical care (36%), industry partnerships (27%), and remote tumor board (18%). Faculty involvement included radiation oncologists (91%), medical physicists (55%), and non-RO department faculty (27%). Six programs (55%) had faculty with prior GH experience. Four (36%) programs reported medical student involvement in projects. Barriers included international communication (36%), time for faculty (18%), funding (9%), and legal (9%) concerns. Commonest components of success included fostering relationships with international sites and identifying needs before solutions. CONCLUSION RO GH initiatives were reported as positive, educational, and feasible across 11 US residency programs. Growth is expected, representing opportunities for innovation and service among US programs.

Hypofractionated whole-breast radiation therapy (RT) has proved to be equivalent to conventionally fractionated RT in multiple randomized trials. There is controversy regarding its use in younger women because of their underrepresentation in trials and the concern for late toxicity. We evaluated disease control and cosmetic outcomes in patients aged50 years treated with hypofractionated RT in 4 prospective single-institutional trials.From 2003 to 2015, 1313 patients were enrolled in 4 prospective protocols investigating the use of adjuvant hypofractionated RT after breast-conserving surgery with a daily or weekly concomitant boost. We identified the records of 348 patients aged50 years at consultation for this analysis. Overall survival, disease-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier method by study and across studies using meta-analytic methods. The late effects of RT, clinician-rated cosmesis, and patient-rated cosmesis were also evaluated.With a median follow-up period of 66.9 months, the overall survival rate was 99.6%, the disease-free survival rate was 96.3%, and the local recurrence-free survival rate was 97.7% at 3 years. Clinician-rated cosmesis (n = 242) was excellent or good in 93.4% of cases and fair or poor in 6.6%. Patient-rated cosmesis (n = 259) was excellent or good in 86.1% and fair or poor in 13.9%. When patients rated themselves differently than their physicians, patients more often rated themselves poorly compared with their physicians (P = .0044, Cochran-Mantel-Haenszel test).At a median follow-up of 5 years, an analysis of patients aged 50 years demonstrated that hypofractionated RT was safe and effective, with good to excellent cosmesis as assessed by both clinicians and patients.

PURPOSE/OBJECTIVE(S) Patients with large brain metastases may receive fractionated stereotactic radiosurgery (FSRS) if they are not surgical candidates yet still pursuing cancer-directed therapy. FSRS with limited margins can allow for optimal sparing of uninvolved regional brain tissue. However, due to required treatment planning process, there is often elapsed time between MRI brain and treatment start which may contribute to marginal misses. Growth rates of large brain metastases and implications for optimal margin to account for growth rate and time interval between planning MRI and FSRS are incompletely characterized. MATERIALS/METHODS Patients treated at a single institution from 2018-2020 who received frameless FSRS on a Cobalt-60 treatment unit for large (> 2cm diameter) brain metastases were identified. Patients with a prior diagnostic brain MRI scan with technically similar parameters to a second MRI obtained for treatment planning were included. Resection cavities and lesions undergoing re-treatment after prior SRS were excluded. Brain metastasis volumes were obtained by contouring on both diagnostic and planning MRIs. Patient characteristics and treatment details were also collected. Analysis was conducted using paired Student's t test and Pearson's R and growth rate was determined using a linear model. RESULTS Thirty-six patients with 54 brain metastases met inclusion criteria. The most common primary cancer sites were lung (36%), colorectal (14%), and skin (14%), and most common histologies were adenocarcinoma (53%) and melanoma (17%). Nearly half (47%) of patients were on systemic therapy at the time of FSRS and the majority (85%) received steroids prior to starting FSRS. Treatment dose ranged from 24-32.5 Gy in 3-5 fractions, with median of 30 Gy in 5 fractions with zero margin. Median time from diagnostic to planning MRI was 15 days (IQR: 11-21) and planning MRI to FSRS was 1 day (IQR 1-3). The median size of included brain metastases on planning MRI was 7.38cc (IQR: 5.09-11.55) compared to 6.03cc (IQR: 3.87-8.95) on prior diagnostic MRI (P 90% of lesions over 3, 7, 10, and 14 days between planning and treatment, respectively. CONCLUSION In the absence of expedited planning, FSRT for intact large brain metastases with limited margins may result in geometric under treatment. An adaptive margin strategy based upon initial tumor size, and time between planning imaging and treatment delivery may be afforded to maintain ideal conformity, properly targeting a growing target lesion while maximally sparing uninvolved regional brain. AUTHOR DISCLOSURE J. Chew: None. S. Sinha: None. S.J. Liu: None. S.E. Fogh: Independent Contractor; Accuray. L. Boreta: None. D. Raleigh: None. L. Ma: Patent/License Fees/Copyright; University of California Regents. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC.

BACKGROUND WHO grade III meningiomas are rare, and clinical outcomes data are limited. To address this problem, we analyzed a single institution retrospective cohort of patients with WHO grade III meningiomas. METHODS Patients who underwent resection of WHO grade III meningiomas between 1983 and 2019 with available follow-up data were included. Treatment, local recurrence, and overall survival rates were obtained. Kaplan-Meier analysis, log rank tests, and Student’s t tests were used for statistical analyses. RESULTS Ninety consecutive patients met inclusion criteria. Median follow-up was 3.2 years (IQR: 1.2-7.9), median age was 58 years (IQR: 46-67). Twenty-three patients (26%) underwent resection alone, and 58 (64%) underwent resection with adjuvant radiotherapy. Fifty-one patients developed local recurrences, with median time to recurrence of 1.0 year (IQR: 0.6-2.9) and higher MIB-1 labeling index for tumors that recurred within 1 year (25% versus 17%, p=0.04). There was a median of 2 recurrences per patient (IQR: 1-3), with a median of 2 resections and 2 radiotherapy courses for initial and salvage treatments. Thirty-nine patients with recurrences died, with median overall survival of 3.7 years (IQR: 1.8-8.8). Thirty-seven patients (41%) had prior low grade meningioma diagnoses with subsequent transformation to grade III, including 6 (7%) with grade I, 16 (18%) with grade II, and 15 (17%) with unknown grade. There was a median of 1 low grade recurrence per patient (IQR: 0-3) before transformation to grade III, which occurred a median of 4.3 years (IQR: 2.4-9.9) after initial diagnosis. Prior low grade diagnosis was associated with shorter time to recurrence of WHO grade III meningioma (p=0.01), and worse overall survival (p=0.03). CONCLUSION Patients with WHO grade III meningioma have poor outcomes despite aggressive multimodal therapy, and there is an urgent, unmet need for new high grade meningioma treatments.

OBJECTIVES This single institution retrospective study aims to evaluate the association between body mass index (BMI) and survival in glioblastoma (GBM). METHODS Patients were identified using a single institution cancer registry. Baseline height and weight were obtained at first clinical visit after diagnosis. Inclusion criteria were GBM diagnosis after 1999 with available height and weight data. Follow up was through July 2018. RESULTS 779 patients were included who had available BMI data. Median age was 58 (IQR 48–66). 38% of patients were female and 62% were male. Median overall survival (OS) was 1.34 years (IQR 0.78–2.12) and median BMI was 26.01 (IQR 23.3–29.1). There was no strong linear correlation between OS and BMI using Pearson correlation (r=0.045). Patients with higher BMI had significantly improved OS when comparing the top 50% to bottom 50% (2.20 vs 1.89 years, p=0.03) and top 25% to bottom 25% (2.25 vs 1.84 years, p=0.03). When comparing patients classified as overweight or obese (BMI >/= 25) to those within normal range or below (BMI < 25), there was a trend towards increased OS (2.14 vs 1.90 years, p=0.075). There was no significant trend for BMI when comparing patients with higher OS with lower OS. There was also no significance for BMI on Cox proportional hazard multivariate analysis. CONCLUSIONS There was no significant linear correlation between BMI and survival for GBM patients, although there appears to be statistically significant improved survival benefit for patients with higher BMI compared to patients with lower BMI. Further investigation is warranted to explore this finding and if BMI could be used as a potential prognostic marker for GBM.

FDG-PET is a valuable tool that will continue to aid in identifying AD in its prodromal and early dementia stages, distinguishing it from other causes of dementia, and tracking progression of the disease. As brain FDG-PET scans and well-trained readers of these scans are becoming more widely available to clinicians who are becoming more informed about the role FDG-PET can play in early AD diagnosis, its use is expected to increase.

The majority of patients with pancreatic cancer are diagnosed with metastatic disease at presentation. Nevertheless, local progression is responsible for up to 30% of deaths and can lead to significant morbidity. As a consequence, further exploration of effective methods of local control and palliation is essential. Stereotactic body radiation therapy (SBRT) is a widely utilized technique for the treatment of localized pancreatic cancer. Here, we report our experience with SBRT and chemotherapy for the local treatment of the metastatic patient population. This single institution retrospective review analyzed 20 patients with pathologically diagnosed metastatic adenocarcinoma of the pancreas. All patients underwent fiducial placement under endoscopic ultrasound (EUS) guidance. SBRT was delivered in five fractions to a total dose of 25 to 30 Gy. Patients received concurrent (given within 1 week of the start of SBRT) or sequential chemotherapy. Local tumor control was evaluated using Response Evaluation Criteria in Solid Tumors. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.03. Local control and overall survival were reported using the Kaplan-Meier method. Patient median age was 64 years, and the median pre-treatment Eastern Cooperative Oncology Group performance status was 1. All patients received chemotherapy and half of the patients (10 of 20) received concurrent chemotherapy with folinic acid, fluorouracil, and oxaliplatin or fluorouracil, leucovorin, irinotecan, and oxaliplatin. Nearly all patients (19 of 20) received post-SBRT chemotherapy. Median time from pathological diagnosis to SBRT was 3.9 months. The twelve-month local control and overall survival were 43 and 53%, respectively. However, in patients with planning target volume (PTV) targets smaller than the population median, the 12-month local control was 78%. Median time to local progression (17.8 vs. 3.0 months, p = 0.02) and overall survival (24.9 vs. 8.8, p = 0.001) were also significantly improved in this smaller PTV cohort. Though not statistically significant, there was a trend towards improvement in local control (17.8 vs. 4.3 months, p = 0.17) and overall survival (16.7 vs. 9.7 months, p = 0.087) for those who received concurrent versus sequential chemotherapy, respectively. Lastly, there were no reported grade 3–5 late toxicities. As systemic therapies improve, the local management of pancreatic cancer will become increasingly important. Here, we report significantly improved local control with SBRT of smaller PTV tumors with concurrent chemotherapy. Five-fraction SBRT offers a quick and effective modality of local tumor control with minimal toxicity in the metastatic pancreatic cancer population.