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BACKGROUND Disparity in mental health care among cancer patients remains understudied. METHODS A large, retrospective, single tertiary-care institution cohort study was conducted based on deidentified electronic health record data of 54,852 adult cancer patients without prior mental health diagnosis (MHD) diagnosed at the University of California, San Francisco between January 2012 and September 2019. The exposure of interest was early-onset MHD with or without psychotropic medication (PM) within 12 months of cancer diagnosis and primary outcome was all-cause mortality. RESULTS There were 8.2% of patients who received a new MHD at a median of 197 days (interquartile range, 61-553) after incident cancer diagnosis; 31.0% received a PM prescription; and 3.7% a mental health-related visit (MHRV). There were 62.6% of patients who were non-Hispanic White (NHW), 10.8% were Asian, 9.8% were Hispanic, and 3.8% were Black. Compared with NHWs, minority cancer patients had reduced adjusted odds of MHDs, PM prescriptions, and MHRVs, particularly for generalized anxiety (Asian odds ratio [OR], 0.66, 95% CI, 0.55-0.78; Black OR, 0.60, 95% CI, 0.45-0.79; Hispanic OR, 0.72, 95% CI, 0.61-0.85) and selective serotonin-reuptake inhibitors (Asian OR, 0.43, 95% CI, 0.37-0.50; Black OR, 0.51, 95% CI, 0.40-0.61; Hispanic OR, 0.79, 95% CI, 0.70-0.89). New early MHD with PM was associated with elevated all-cause mortality (12-24 months: hazard ratio [HR], 1.43, 95% CI, 1.25-1.64) that waned by 24 to 36 months (HR, 1.18, 95% CI, 0.95-1.45). CONCLUSIONS New mental health diagnosis with PM was a marker of early mortality among cancer patients. Minority cancer patients were less likely to receive documentation of MHDs or treatment, which may represent missed opportunities to identify and treat cancer-related mental health conditions.

Background The Decipher genomic classifier (GC) is increasingly being used to determine metastasis risk in men with localized prostate cancer (PCa). Whether GCs predict for the presence of occult metastatic disease at presentation or subsequent metastatic progression is unknown. Objective To determine if GC scores predict extraprostatic 68Ga prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography (PET) positivity at presentation. Design, setting, and participants Between December 2015 and September 2018, 91 PCa patients with both GC scores and pretreatment 68Ga-PSMA-11 PET scans were identified. Risk stratification was performed using the National Comprehensive Cancer Network (NCCN), Cancer of the Prostate Risk Assessment (CAPRA), and GC scores. Outcome measurements and statistical analysis Logistic regression was used to identify factors correlated with PSMA-positive disease. Results and limitations The NCCN criteria identified 23 (25.3%) and 68 patients (74.7%) as intermediate and high risk, while CAPRA scores revealed 28 (30.8%) and 63 (69.2%) as low/intermediate and high risk, respectively. By contrast, only 45 patients (49.4%) had high-risk GC scores. PSMA-avid pelvic nodal involvement was identified in 27 patients (29.7%). Higher GC score was significantly associated with pelvic nodal involvement (odds ratio [OR] 1.38 per 0.1 units; p = 0.009) and any PSMA-avid nodal involvement (pelvic or distant; OR 1.40 per 0.1 units; p = 0.007). However, higher GC score was not significantly associated with PSMA-avid osseous metastases (OR 1.11 per 0.1 units; p = 0.50). Limitations include selection bias for patients able to receive both tests and the sample size. Conclusions Each 0.1-unit increase in GC score was associated with an approximate 40% increase in the odds of PSMA-avid lymph node involvement. These data suggest that patients with GC high risk might benefit from more nodal imaging and treatment intensification, potentially via pelvic nodal dissection, pelvic nodal irradiation, and/or the addition of chemohormonal agents. Patient summary Patients with higher genomic classifier scores were found to have more metastatic lymph node involvement on prostate-specific membrane antigen imaging.

Objective To identify locations of recurrence after radical prostatectomy (RP) with prostate-specific antigen (PSA) Materials and Methods We performed a retrospective review of patients with PSMA-PET imaging for biochemical recurrence following RP with PSA ≤2.0 ng/mL and assessed if the recurrent disease was within standard radiation target volumes. We compared patient and clinical variables between men with recurrences covered by standard salvage radiation fields and those with recurrences outside of standard fields. Results We identified 125 patients for study inclusion. The median PSA at imaging was 0.40 ng/mL (interquartile range 0.28-0.63). PSMA-avid disease was found in 66 patients (53%). Of these, 25 patients (38%) had PSMA-avid lesions found outside of the pelvis, 33 (50%) had lesions confined to the pelvic lymph nodes and prostate bed, and 8 (12%) men had PSMA-avid recurrence only in the prostate bed. Salvage radiation including standard Intensity Modulated Radiation Therapy (IMRT) pelvic nodal volumes would not cover PSMA-avid nodal disease in 38 men (30%). PSA at the time of imaging was statistically associated with having PSMA-avid disease outside of standard nodal fields (P Conclusion The 68Ga-PSMA-11 PET detects disease in a majority of patients with PSA ≤2.0 following RP. Nearly one-third of men had PSMA-avid disease that would be missed by standard radiation fields. This imaging modality may dramatically impact the design and use of post-RP salvage radiotherapy.

Objective To evaluate the impact of staging 68Ga-PSMA-11 PET imaging on radiotherapy (RT) dose and volumes in patients with prostate cancer. Methods Forty-five patients (89% high or very high risk by NCCN criteria) who underwent 68Ga-PSMA-11 PET imaging prior to definitive treatment for prostate cancer between December 2015 and December 2016 were included. Locations of 68Ga-PSMA-11-avid lesions were compared to Radiation Therapy Oncology Group consensus pelvic nodal volumes (clinical target volume [CTV]); coverage of lesions outside the consensus CTV was considered a major change, while dose-escalation to lesions within the consensus CTV was considered a minor change. Results All patients had 68Ga-PSMA-11 PET uptake in the prostate. Twenty-five patients (56%) had N1/M1a disease on 68Ga-PSMA-11 PET scan, of whom 21 (47%) were previously N0. Six patients (13%) had bone metastases on 68Ga-PSMA-11 PET scan, of whom 4 had prior negative bone scans. Eight patients (18%) had lymph node metastases outside the consensus CTV. Twelve patients (27%) received a RT boost to nodes within the consensus CTV. Six patients (13%) had limited bone metastases treated with focal RT. Overall PSMA PET imaging resulted in major and/or minor changes to RT plans in 24 patients (53%). Conclusion 68Ga-PSMA-11 PET imaging resulted in RT changes in 53% of patients. Prospective investigation is needed to evaluate the clinical benefit of RT changes based on staging 68Ga-PSMA-11 PET imaging.

Purpose/objective(s) Management of progressive brain tumors following high dose radiotherapy is controversial. In select cases, surgical resection can provide rapid relief of regional mass effect and edema, and highly focal adjuvant re-irradiation can be administered in the form of brachytherapy. Permanent low-dose rate cesium-131 brachytherapy may offer dosimetric and radiobiologic advantages over other isotopes. The purpose of this study was to examine the safety and efficacy of intracranial cesium-131 brachytherapy after surgical resection in a heavily pre-treated patient cohort. Materials/methods A retrospective chart review was conducted of all patients treated with intraoperative intracranial cesium-131 brachytherapy from an institutional database. Treatment consisted of maximal safe resection followed by implantation of suture-stranded cesium-131 seeds, maintaining approximately 10mm spacing between seeds, with a planned target dose of 80 Gy to 5mm depth. Local failure was defined as recurrence in or contacting the resection cavity after salvage resection and brachytherapy. Regional failure was defined as recurrence within 10mm of the resection cavity. Recurrence was defined as a new lesion or growth of ≥25% in any axial dimension on interval MRI. Toxicity was collected based on CTCAE 4.0. Results A total of 35 patients with a median imaging follow up of 17.0 months (interquartile range [IQR] 9.7-25.9) underwent 41 consecutive cesium-131 implants between 2016 and 2020. 20 patients (59%; N = 22 implants) were treated for recurrent brain metastasis, 12 patients (34%; N = 16 implants) were treated for recurrent atypical (N = 8) or anaplastic meningioma (N = 4), and 3 patients (9%) were treated for recurrent glioma (N = 2) or hemangiopericytoma (N = 1). A majority of lesions had received prior surgery (N = 28, 66.7%, range 0-3 prior surgeries) and 34 patients had received prior high dose radiation. 34 of 41 (82.9%) tumors had received prior radiosurgery, and 12 (29.2%) had undergone prior external beam radiation (range 50-60 Gy). 17 of 41 lesions (41.5%) had radiologic evidence of adverse radiation/treatment effect (ARE) prior to salvage therapy. Median tumor size was 3.0cm (IQR 2.3-3.7). Overall actuarial local/loco-regional control at 1-year was 91.6%/84.7% (89.8%/88.9% for metastases and 100%/82.5% for meningiomas). Crude loco-regional control was 86.3% for metastases, 75% for meningiomas, and 66.7% for other lesions. Symptomatic ARE following treatment was observed in 9.8% (N = 4) resection cavities. The surgical complication rate was 14.6% (N = 6 total, N = 3 [7.3%] grade 3-5) including 1 peri-operative death. Conclusion Cesium-131 brachytherapy in this heavily pre-treated cohort resulted in good local control and an acceptable rate of symptomatic adverse radiation effect and toxicity and may be a reasonable treatment option for this select population. Author disclosure W.C. Chen: None. M. Lafreniere: None. C. Phuong: None. M. Lometti: None. O. Morin: None. B.P. Ziemer: None. H. Vasudevan: Research Grant; Children's Tumor Foundation. Patent/License Fees/Copyright; Genentech, Eli Lilly. S. Hervey-Jumper: None. P.V. Theodosopoulos: None. S. Magill: None. S.E. Fogh: Independent Contractor; Accuray. J.L. Nakamura: None. L. Boreta: None. P.K. Sneed: None. M.W. McDermott: Chair; Miami Baptist. D. Raleigh: None. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC.

BackgroundPrognostic markers for meningioma are needed to risk-stratify patients and guide postoperative surveillance and adjuvant therapy.ObjectiveTo identify a prognostic gene signature for meningioma recurrence and mortality after resection using targeted gene-expression analysis.MethodsTargeted gene-expression analysis was used to interrogate a discovery cohort of 96 meningiomas and an independent validation cohort of 56 meningiomas with comprehensive clinical follow-up data from separate institutions. Bioinformatic analysis was used to identify prognostic genes and generate a gene-signature risk score between 0 and 1 for local recurrence.ResultsWe identified a 36-gene signature of meningioma recurrence after resection that achieved an area under the curve of 0.86 in identifying tumors at risk for adverse clinical outcomes. The gene-signature risk score compared favorably to World Health Organization (WHO) grade in stratifying cases by local freedom from recurrence (LFFR, P

Author(s): Wu, Susan Y; Yee, Emily; Chan, Jason W; Chapman, Christopher H; Boreta, Lauren; Braunstein, Steve E | Abstract: PurposeUrgent indications for palliative radiation therapy (RT) include malignant spinal cord compression, symptomatic brain metastases, pain, airway obstruction, and bleeding. Data on the timing of palliative RT in the inpatient setting are limited. We report our experience with inpatient palliative RT at a tertiary academic center and evaluate the effect of a dedicated inpatient palliative RT nurse practitioner (NP) on treatment timelines.Methods and materialsWe performed a retrospective, single-institution review of 219 inpatients consulted for RT to sites of metastatic disease between May 2012 and May 2018. We compared time-to-treatment intervals before and after integrating an NP for palliative RT in Augustn2017.ResultsThe median age of the 219 patients receiving RT was 61 years (interquartile range [IQR], 51-69 years). The most frequent indications were symptomatic brain metastases (73 patients [33%]), pain (61 patients [28%]), and cord/cauda compression (48 patients [22%]). The median time from consultation request to consult was 1 day (IQR, 0-2 days), and the median time from consultation request to first RT fraction was 3 days (IQR, 2-6 days). The median time from consultation request to RT was shorter for cord compression (2 [IQR, 1-4] days) than for pain (5 [IQR, 2-7] days) (P = .001) or symptomatic brain metastases (3 [IQR, 1-6] days; P = .037). With an NP, patients were more likely to undergo same-day consultation and simulation (75% vs 60%; P = .045), which was associated with shorter median duration from consultation to initiation of RT (1 [IQR, 0-3] days vs 4 [IQR, 2-7] days; P l.001). After the integration of an NP for palliative RT, patients had a higher median Karnofsky Performance Score (70 [IQR, 60-80] vs 50 [IQR, 40-60]; P l .001) and were more likely to complete their prescribed RT course (93% vs 82%; P = .05).ConclusionsTime from consultation request to RT is necessarily short for urgent inpatient palliative RT. Advanced practice providers may facilitate and potentially expedite treatment, with significantly shorter times to treatment among patients who undergo same-day consultation and simulation.

Advances in treatment of oligodendroglioma represent arguably the most significant recent development in the treatment of brain tumors, with multiple clinical trials demonstrating that median survival is approximately doubled in patients with World Health Organization grade II and III 1p/19q codeleted gliomas (ie, oligodendrogliomas) treated with procarbazine, lomustine, vincristine chemotherapy and radiation vs radiation alone. However, chemoradiotherapy itself is not without morbidity, including both short-term toxicities primarily related to chemotherapy and longer-term cognitive issues likely due to radiation. Patients and physicians both desire maximally effective therapy with minimal toxicity, and it remains unclear whether some patients with macroscopic residual disease after surgery can safely delay therapy, to avoid or delay toxicity, while simultaneously preserving the full benefits of treatment. In this article, experts in the field discuss the rationale for the approaches of up-front treatment with chemoradiotherapy and initial observation, respectively.

Purpose Hydrogel spacers have been suggested to limit rectal radiation dose with improvements in clinical outcomes in patients undergoing external beam radiation treatment for prostate cancer. No studies to date have assessed the utility and dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and Drug Administration–approved hydrogel rectal spacer, for high-dose-rate (HDR) brachytherapy. Methods Eighteen consecutive patients scheduled for HDR brachytherapy in the treatment of prostate cancer underwent transperineal ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter implantation. Treatment plans were generated using an inverse planning simulated annealing algorithm. Rectal dosimetry for these 18 patients was compared with the 36 preceding patients treated with HDR brachytherapy without SpaceOAR. Results Fifty-four plans were analyzed. There was no difference in age, pretreatment prostate-specific antigen, Gleason score, clinical stage, prostate volume, or contoured rectal volume between those who received SpaceOAR and those who did not. Patients who received SpaceOAR hydrogel had significantly lower dose to the rectum as measured by percent of contoured organ at risk (median, V80 Conclusions Transperineal insertion of SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases rectal radiation dose. Further investigation is needed to assess the clinical impact of this dosimetric improvement and potential toxicity reduction.

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.

Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non–small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

BACKGROUND Clinical biomarkers for identifying patients at risk for recurrence after resection of meningioma are lacking and are needed for guiding adjuvant therapy. The aim of this study was to identify a prognostic gene expression signature for meningioma. METHODS Targeted gene expression analysis was performed on a discovery dataset of 96 meningiomas with suitable tissue identified from a retrospective institutional biorepository. Recurrence was dichotomized based on the median time to local recurrence (TTR). With median follow-up of 6.4 years, the discovery dataset was enriched for clinical endpoints of local recurrence (58%), mortality (42%), and disease-specific mortality (49% of deaths). A 266 gene expression panel was used to interrogate the discovery dataset, and a prognostic gene signature and risk score was generated using prediction analysis for microarrays (PAM) and elastic net regression. The risk score was validated using gene expression data (GSE58037) from 56 meningiomas resected at an independent institution (20% local recurrence, 18% mortality, median follow-up 5.4 years). RESULTS A 36-gene signature was identified achieving an AUC of 0.86 for TTR faster than the median in the discovery cohort. A risk score between 0 and 1 based on this signature was strongly associated with shorter TTR (F-test, P< 0.0001), and on multivariate Cox regression (MVA), was independently associated with recurrence (RR 1.56 per 0.1 increase, 95% CI 1.30–1.90, P< 0.0001) and mortality (RR 1.32 per 0.1 increase, 1.07–1.64, P=0.01) after adjusting for WHO grade, age, extent of resection, and sex. Similarly, in the validation dataset, the gene risk score was correlated with shorter TTR (P=0.002) and associated with mortality on MVA (RR 1.86 per 0.1 increase, 1.19–2.88, P=0.005) after adjustment for WHO grade. CONCLUSIONS The prognostic meningioma gene expression risk score presented here could be useful in identifying patients at higher risk of progression after resection.

BackgroundA significant proportion of patients with advanced cancer undergo palliative radiotherapy (RT) within their last 30 days of life. This study characterizes palliative RT at our institution and aims to identify patients who may experience limited benefit from RT due to imminent mortality.MethodsFive hundred and-eighteen patients treated with external beam RT to a site of metastatic disease between 2012 and 2016 were included. Mann-Whitney U and chi-squared tests were used to identify factors associated with RT within 30 days of death (D30RT).ResultsMedian age at RT was 63 years (IQR 54-71). Median time from RT to death was 74 days (IQR 33-174). One hundred and twenty-five patients (24%) died within 30 days of RT. D30RT was associated with older age at RT (64 vs. 62 years, p= 0.04), shorter interval since diagnosis (14 vs. 31 months, p&nbsp

Palliative radiotherapy (RT) is frequently an effective treatment option for patients with advanced cancer; however, a substantial proportion will receive RT at the end of life.1 Prognostic tools, including the TEACHH (Type of cancer, ECOG [Eastern Cooperative Oncology Group] performance status, Age, prior palliative Chemotherapy, prior Hospitalizations, and Hepatic metastases),2 the model developed by Chow et al,3 and NEAT (Number of active tumors, ECOG performance status, Albumin, primary Tumor)4 models, can help guide decision-making to better align treatment intensity and prognosis. However, these may not generalize to all clinical scenarios, particularly for patients at imminent risk of death.5 Given this important unmet clinical need, we sought to identify prognostic criteria for 30-day mortality among patients with metastatic cancer undergoing palliative RT at our institution.

Brain metastases are the most common intracranial neoplasm yet clinical outcomes remain poor. The purpose of this study was to evaluate the efficacy of multimodal therapy comprising surgery followed by focal radiation, and/or systemic therapy and elucidate clinically significant biomarkers for resected melanoma brain metastases. Forty consecutive patients with newly diagnosed melanoma brain metastases who underwent surgical resection and targeted mutational analysis at UCSF between 2011 and 2020 were identified. Demographic, clinical, and outcome data were extracted from the medical record and institutional cancer registry. Surgical cavity local recurrence free survival (LRFS), intracranial progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median age of patients in this cohort was 58 years (range: 27-75 years) with median MRI follow up of 13.15 months. Twenty patients (50%) were treated with concurrent stereotactic radiation (1-5 fractions) and systemic therapy while 16 patients (40%) were treated with systemic therapy only. Mutational testing demonstrated the most common pathogenic variant was BRAF V600E, found in 16 patients (40%), while the remaining 24 patients (60%) did not harbor this mutation. Microsatellite instability (MSI) estimation was available for 8 patients (20%), all of which were found to be MSI low ( Citation Format: Harish N. Vasudevan, Matthew S. Susko, Lijun Ma, Jean L. Nakamura, David R. Raleigh, Lauren Boreta, Shannon Fogh, Philip V. Theodosopoulos, Michael W. McDermott, Katy K. Tsai, Penny K. Sneed, Steve E. Braunstein. Mutational status and clinical outcomes following systemic therapy and focal radiation for melanoma brain metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-073.

OBJECTIVES Brain metastases are a common sequelae of advanced melanoma, and can lead to significant morbidity and mortality. Systemic therapy, inclusive of BRAF/MEK inhibitors and immunotherapy, are increasingly being utilized for metastatic melanoma brain metastases. This study sought to evaluate the clinical outcomes of resected melanoma brain metastases treated with systemic therapy, with or without focal radiotherapy. METHODS Patients at a single institution who underwent resection of a melanoma brain metastasis were retrospectively identified and reviewed. Patients were required to have received immunotherapy or BRAF/MEK inhibitors in the 3-month perioperative time period. This cohort was then analyzed by receipt of focal radiotherapy, including SRS and brachytherapy, for resection cavity failure, distant CNS progression, and adverse radiation effect, using the Kaplan Meier method. RESULTS From 2011-2020, 43 resections for melanoma brain metastases were performed, of which 29 patients and 37 resection cavities met criteria for analysis. Median MRI follow up was 15 months (IQR: 6-38). Twenty-two (59%) lesions were treated with focal radiotherapy and systemic therapy, and 15 (41%) were treated with systemic therapy alone. 12-month freedom from local recurrence was 64.8% (95% CI: 42.1-99.8%) for systemic therapy alone, and 93.3% (95% CI: 81.5-100%) for focal radiotherapy with systemic therapy (p=0.01). 12-month CNS progression free survival was 35.7% (95% CI: 17.7-72.1%) for systemic therapy alone, and 31.8% (95% CI: 17.3-58.7%) for focal radiotherapy (p=0.51). UVA demonstrated focal radiotherapy (HR: 0.10; 95% CI: 0.01-0.85; p=0.04) was the only significant factor associated with reduction of risk for surgical cavity recurrence. CONCLUSIONS Use of focal radiotherapy with systemic therapy for resected melanoma brain metastases significantly reduced surgical cavity recurrence compared to systemic therapy alone. Focal radiotherapy did not delay initiation of systemic therapy and should be the preferred treatment option for optimal local control of the surgical cavity in melanoma brain metastases.

2041 Background: Cancer patients are at increased risk of mental and emotional distress. The aim of this study is to investigate risk factors and timing of mental health disorder (MHD) onset following a cancer diagnosis, and evaluate its impact on emergency visits. Methods: All patients with a new onset diagnosis of malignancy ( ICD-10 codes C00-C97, with conversion of ICD-9 codes) were identified from an institutional de-identified electronic health data warehouse. Demographic data, Charlson comorbidity index excluding cancer, mortality, and time to onset of a new MHD diagnosis ( ICD-10 codes F00-F99) and emergency visits were extracted and used to calculate rates and Cox-model hazard ratios. A predictive logistic model of MHD was tested on an internal hold-out sample (25%). Results: A total of 110,306 patients with 338,208 person-years of follow up were identified with a new diagnosis of cancer from February 1980 to July 2019, of which 95,474 (86.5%) had no prior diagnosis of MHD. Actuarial rates of new MHD among previously MHD-free patients were 8.1% at 6 months, and 14.1% and 20.8% at 2 and 5 years. Median time to onset of MHD was fastest among head and neck cancer (57 days, HR 2.32 [2.1-2.6]), urinary organ cancer (94 days, HR 2.21 [2.0-2.4]), and lung and thoracic cancers (99 days, HR 2.47 [2.2-2.7]), compared to skin neoplasms (987 days, HR 1.0). Median time to onset was less than one year for all malignancies except for skin neoplasms and male genital cancers (840 days). Male sex, older age, Charlson score, divorce or legal separation, self-identification of a gender-neutral partner, African American or American Indian race, Hispanic ethnicity, current or former smoking status, and self-identification as Christian were associated with higher risk of MHD onset, while married status and native Hawaiian or Pacific Islander race were protective. A logistic model predicted new MHD with an AUROC of 0.72. Onset of new MHD was associated with greater rates of emergency visit (HR 1.92 [1.8-2.0], adjusted for cancer type and Charlson score), and patients with new MHD who experienced an emergency visit had a mean of 3.75+/-0.03 (SEM) total emergency visits versus 2.65+/-0.02 (p < 0.0001). Finally, onset of new MHD was associated with greater mortality even after adjusting for age, Charlson score and cancer type (HR 1.29, [1.23-1.35]). Conclusions: Onset of new mental health diagnosis after a cancer diagnosis was correlated with greater rates of emergency visits and mortality. Cancer patients with risk factors identified here may benefit from increased social and mental health support.

Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement. Survival was compared based on recurrence type, distance from the initial enhancing tumor (local ≤ 2 cm, distant > 2 cm), and the radiation dose at the recurrence site. Progression of enhancing subventricular tumor was common at both local (58%) and distant (42%) sites. Median survival was better after local SVZ recurrence than distant SVZ recurrence (8.7 vs. 4.3 months, p = 0.04). Radiation doses at local SVZ recurrence sites recurrence averaged 57.0 ± 4.0 Gy compared to 44.7 ± 6.7 Gy at distant SVZ recurrence sites (p = 0.008). Distant subventricular progression at a site receiving ≤ 45 Gy predicted worse subsequent survival (p = 0.05). Glioblastomas frequently recurred in the subventricular zone, and patient survival was worse when enhancing tumor occurred at sites that received lower radiation doses. This recurrent disease may represent disease undertreated at the time of diagnosis, and further study is needed to determine if improved treatment strategies, such as including the subventricular zone in radiation fields, could improve clinical outcomes.

This chapter will discuss radiation therapy for multiple myeloma and solitary plasmacytoma.

This chapter will cover brain metastases, bone metastases, spinal cord compression, liver metastases, airway obstruction, superior vena cava obstruction, and gynecologic bleeding.

Metastatic non-small cell lung cancer (NSCLC) is known to have a particularly poor prognosis, with a median overall survival of 8 months and a 10% survival rate at 2 years (1). Historically, treatment for metastatic NSCLC has been palliative chemotherapy (2) which has been shown to modestly prolong 1-year survival in comparison with best supportive care (3). Nowadays, with the advent of more sensitive imaging modalities, improvement in the specificity of radiation therapy delivery, and targeted systemic therapies, many patients with limited metastatic disease are being detected and treated more aggressively, in the absence of randomized, prospective data to support these practices. In patients with metastatic lung cancer, where obstructive or functionally limiting manifestations of disease can reduce performance status and diminish quality of life, there may be a uniquely important role for early enactment of locally directed therapy.

The majority of the approximately 1.7 million civilians in the United States who seek emergency care for traumatic brain injury (TBI) are classified as mild (MTBI). Premorbid and comorbid conditions that commonly accompany MTBI may influence neurocognitive and functional recovery. This study assessed the influence of chronic smoking and hazardous alcohol consumption on neurocognitive recovery after MTBI. A comprehensive neurocognitive battery was administered to 25 non-smoking MTBI participants (nsMTBI), 19 smoking MTBI (sMTBI) 38 ± 22 days (assessment point 1: AP1) and 230 ± 36 (assessment point 2: AP2) days after injury. Twenty non-smoking light drinkers served as controls (CON). At AP1, nsMTBI and sMTBI were inferior to CON on measures of auditory-verbal learning and memory; nsMTBI performed more poorly than CON on processing speed and global neurocognition, and sMTBI performed worse than CON on working memory measures; nsMTBI were inferior to sMTBI on visuospatial memory. Over the AP1-AP2 interval, nsMTBI showed significantly greater improvement than sMTBI on measures of processing speed, visuospatial learning and memory, visuospatial skills, and global neurocognition, whereas sMTBI only showed significant improvement on executive skills. At AP2, sMTBI remained inferior to CON on auditory-verbal learning and auditory-verbal memory; there were no significant differences between nsMTBI and CON or among nsMTBI and sMTBI on any domain at AP2. Hazardous alcohol consumption was not significantly associated with change in any neurocognitive domain. For sMTBI, over the AP1-AP2 interval, greater lifetime duration of smoking and pack-years were related to significantly less improvement on multiple domains. Results suggest consideration of the effects of chronic cigarette smoking is necessary to understand the potential factors influencing neurocognitive recovery after MTBI.

Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimer's disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimer's disease, mild cognitive impairment and normal ageing over short periods, e.g. 6-12 months, with MRI in the large multicentre setting of the Alzheimer's Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, such as the beta-amyloid (Abeta(1-42)) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimer's disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. The mild cognitive impairment and Alzheimer's disease groups showed hippocampal volume loss over 6 months and accelerated loss over 1 year. Moreover, increased rates of hippocampal loss were associated with presence of the ApoE allele epsilon4 gene in Alzheimer's disease and lower CSF Abeta(1-42) in mild cognitive impairment, irrespective of ApoE genotype, whereas relations with tau were only trends. The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimer's disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele epsilon4 and decreased CSF Abeta(1-42) supports the concept that increased hippocampal loss is an indicator of Alzheimer's disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimer's disease.

246 Background: In patients with advanced prostate cancer (PCa), urinary obstruction (UO) can lead to urinary retention requiring indwelling or suprapubic catheterization, which negatively impacts quality of life. Palliative options for UO from advanced PCa include surgical and medical treatment. Surgical intervention, including prostatectomy, pelvic exenteration and TURP, may confer undue risk to patients with advanced disease. Medical palliation may require months to take effect. Stereotactic Body Radiotherapy (SBRT) is a non-invasive technique that delivers high-dose and highly conformal radiation in ≤5 fractions, often used to treat PCa and metastatic disease. Here, we reviewed the utility of SBRT to treat UO from advanced PCa. Methods: A retrospective review of patients undergoing SBRT for UO was completed at a single institution between 2011 and 2017. Stage, PSA at diagnosis and time of treatment were recorded. Assessment of urinary function by IPSS/SHIM and documentation of catheterization were reviewed at consultation andsubsequent follow-up. Results: A total of 3 patients were treated with SBRT to the prostate for the palliation of urinary obstruction. Patient ages were 67, 57 and 52 years, and all had high risk, stage IV disease, Gleason 4+4 or 4+5, T3 or T4, with regional nodal, bony or visceral metastases. All patients required indwelling catheterization for an average 4 months prior to SBRT. Two patients were treated with whole pelvis irradiation after SBRT. In those who received subsequent pelvic irradiation, the SBRT doses to the prostate were 19 Gy in 2 fractions. The patient treated with SBRT monotherapy received 38 Gy in 4 fractions. Catheters were successfully removed in all 3 patients, one at the completion of radiation, and the others within 4 weeks of completion. With follow-up ranging from 1.2 to 6 years, no patients required re-catheterization, and there were no reports of grade ≥3 acute or long-term toxicity. Conclusions: SBRT is an effective treatment to palliate UO from locally advanced PCa, leading to removal of urinary catheters and presumed improved in quality of life. Further investigation is required to establish the optimal dose and fractionation of palliative SBRT for UO from PCa.

Whether longitudinal diffusion tensor MRI imaging (DTI) can capture disease progression in patients with amyotrophic lateral sclerosis (ALS) is unclear. The primary goal of this study was to determine if DTI detects progression of the corticospinal tracts (CST) degeneration in ALS. Seventeen ALS patients and 19 age- and gender-matched healthy controls were scanned with DTI at baseline for cross-sectional analyses. For longitudinal analyses, the ALS patients had repeat DTI scans after eight months. Tractography of the CST was used to guide regions-of-interest (ROI) analysis and complemented by a voxelwise analysis. Cross-sectional study found that baseline FA of the right superior CST was markedly reduced in ALS patients compared to controls. The FA reductions in this region correlated with the disease severity in ALS patients. Longitudinal study found that FA change rate of the right superior CST significantly declined over time. In conclusion, longitudinal DTI study captures progression of upper motor fiber degeneration in ALS. DTI can be useful for monitoring ALS progression and efficacy of treatment interventions.

The alterations of the fornix in mild traumatic brain injury (mTBI) were investigated using diffusion tensor imaging (DTI) and T1-weighetd anatomical imaging. The primary goal of this study was to test that hypothesis that the fornix might play a major role in the memory and learning dysfunctions in the post-concussion syndrome, which may related to the white matter (WM) degradations following mild traumatic brain injury. N=24 mTBI patients were longitudinally studied in two time points with 6-month intervals using a 4-Tesla MRI scanner to measure the WM integrity of fornix and the fornix-to-brain ratio (FBR), and compared with matched healthy controls. Our data show that the WM degradation in fornix onset in the acute stage after mild TBI when the post-injury time was less than 6 weeks, and that this WM degradation continued during the following 6-month period of recovery. In summary, using DTI and structural MRI together can effectively detect the fornix changes in both cross-sectional and longitudinal investigations. Further studies are warranted to exam the association between the fornix alterations and neurocognitive performance of TBI patients.

Tensor-based morphometry (TBM) creates three-dimensional maps of disease-related differences in brain structure, based on nonlinearly registering brain MRI scans to a common image template. Using two different TBM designs (averaging individual differences versus aligning group average templates), we compared the anatomical distribution of brain atrophy in 40 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with amnestic mild cognitive impairment (aMCI), a condition conferring increased risk for AD. We created an unbiased geometrical average image template for each of the three groups, which were matched for sex and age (mean age: 76.1 years+/- 7.7 SD). We warped each individual brain image ( N = 120) to the control group average template to create Jacobian maps, which show the local expansion or compression factor at each point in the image, reflecting individual volumetric differences. Statistical maps of group differences revealed widespread medial temporal and limbic atrophy in AD, with a lesser, more restricted distribution in MCI. Atrophy and CSF space expansion both correlated strongly with Mini-Mental State Exam (MMSE) scores and Clinical Dementia Rating (CDR). Using cumulative p- value plots, we investigated how detection sensitivity was influenced by the sample size, the choice of search region (whole brain, temporal lobe, hippocampus), the initial linear registration method (9- versus 12-parameter), and the type of TBM design. In the future, TBM may help to (1) identify factors that resist or accelerate the disease process, and (2) measure disease burden in treatment trials.