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Purpose Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. Methods From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. Results 144 Patients were identified. The median age was 62 (23–90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p

Background We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (>4 cc) brain metastases (BrM). Methods We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method. Results We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P < .001), BrM quantity [HR 1.13 (1.06–1.22) (P < .001)]; performance status (PS) [HR 2.78 (1.73–4.46) (P < .001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P < .001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46–073) (P < .001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P < .0054)], SRS target volume [HR 1.03 (1.01,1.06) (P < .0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P < .015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20–2.19) (P = 0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89–4.69) (P = .091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS. Conclusion SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM.

BACKGROUND We aimed to identify factors predicting survival following treatment to large (>4cc) BrM. METHODS From a prospective registry database, we identified 364 adult patients treated for brain metastases (BrM) or surgical cavities larger than >4 cc: 127 and 237 treated with surgery plus stereotactic radiosurgery (S+SRS) and SRS alone, respectively. We compared the 2 treatment arms using propensity score-matched (PSMA) and multivariate analyses (MVA). P values RESULTS Median target volume was 6.6cc (4-36.9cc) for intact BrM and 15cc (4-54) for cavities. Median OS was 19 and 12 months for the S+SRS and SRS groups, respectively [HR 1.73 (1.35-2.22) (P CONCLUSION Reduced SRS target volume, treatment with systemic therapy following BrM treatment, and surgical resection prior to SRS correlate with survival in patients with large BrM. PMSA supports the hypothesis that surgery prior to SRS improves survival in patients with large BrM.

Background Brain metastasis quantity may be a negative prognostic factor for patients requiring resection of at least one lesion. Methods We retrospectively reviewed patients who underwent surgical resection of brain metastases from July 2018 to June 2019 at our institution, and examined outcomes including overall survival (OS), progression free survival (PFS), and rates of local failure (LF). Patients were grouped according to the number of metastases at the time of surgery (single vs multiple). Results We identified 130 patients who underwent surgical resection as the initial treatment modality. At the time of surgery, 87 patients had only one lesion (control) and 43 had multiple (>1). Two-year OS for the entire cohort was 46%, with equal rates in both the multiple metastases group and the control group (P = .335). 2-year PFS was 27%; 21% in the multiple metastases group and 31% in the control group (P = .766). The rate of LF at 2 years was 32%, with equal rates in both the multiple lesion group and control group (P = .889). On univariate analysis, multiplicity was not significantly correlated to OS (HR = 0.80, 95% CI: 0.51–1.26, P = .336), PFS (HR = 1.06, 95% CI: 0.71–1.59, P = .766) or LF (HR = 1.06, 95% CI: 0.57–1.97, P = .840). Multivariate analysis revealed preoperative tumor volume of the resected lesion to be the single correlate for OS (P = .0032) and PFS (P = .0081). Conclusions Having more than one metastasis does not negatively impact outcomes in patients treated with surgery. In carefully selected patients, especially those with large tumors, surgery should be considered regardless of the total number of lesions.

Purpose: Partial Breast Irradiation (PBI) treats the tumor bed plus a margin in low risk early stage breast cancers, reducing exposure to organs at risk. Randomized trials have shown that PBI with external beam radiotherapy is non-inferior to whole breast irradiation in terms of local control with fewer late normal tissue adverse events. We aimed to determine the proportion of women with early stage breast cancer suitable for external beam PBI at our institution using adapted ASTRO guidelines for accelerated PBI whereby both clinical-pathological factors and visualization of the tumor bed/cavity on planning scans were determined to quantify PBI eligibility. Methods: Patients were identified retrospectively from January 1, 2013 to November 1, 2018 based on age (≥55), tumor size (≤2cm invasive, ≤2.5cm DCIS), nodal negativity and grade (1 or 2). Cases identified were unifocal, lymphovascular invasion negative, ER positive, HER2 negative, with margins ≥2mm (invasive) and ≥3mm (DCIS), no chemotherapy, non-lobular, no extensive intraductal component, no previous/ bilateral cancers and endocrine therapy optional. Planning scans were reviewed to assess for presence of surgical clips and assigned cavity visualization scores (CVS); CVS 1=cavity not visualized, CVS 2=cavity visualized with indistinct margins, CVS 3=cavity visualised with some distinct margins and heterogeneous appearance, CVS 4= cavity visualised with mostly distinct margins and mildly heterogeneous appearance, CVS 5= all cavity margins clearly defined and homogeneous appearance. These features were used to determine if cases were considered radiologically suitable for PBI. Results: Thirty-seven percent (1051/2824) of cases identified were deemed eligible based on age, grade and T1N0/Tis. Of the 1051, 306 (29%) met all the pathologic criteria; the main reasons for exclusion were previous breast cancer, lobular histology, or multifocality. Median age of eligible cases was 65 years (range 55-88 years). The majority (254) had invasive disease (T1mi: 6, T1a: 17, T1b: 98, T1c: 133); 52 had DCIS. There were 169 right-sided and 137 left-sided cases. Endocrine therapy was documented in 55% of cases. CVS (1-5) were: 11%, 22%, 30%, 29%, 8%. Overall, 66% (201/306) of cases were considered radiologically suitable for PBI (of the 201 cases, 97% had CVS ≥3). Seventy-two cases (72/306; 24%) had tumor bed clips, of which, 34 were considered suitable for PBI (91% CVS ≥3; 9% CVS 2). Conclusions: Overall, a low proportion of all patients were eligible for PBI based on clinical features, but two-thirds of eligible cases were suitable for PBI based on CVS score alone. In contrast, the suitability for PBI within the cohort with surgical clip placement was low. Visualization of the tumor bed is essential to safely deliver PBI and is guided by identification of the cavity seroma and/or surgical clips. Development of standard practice guidelines for surgical clip positioning to identify the tumor bed will potentially assist in increasing the proportion of early stage breast cancer patients suitable to receive PBI, even if the CVS is less favorable. Citation Format: Christine Anne Koch, Gemma Corey, Kathy Han, Grace Lee, Tom Purdie, Chris McIntosh, Patricia Lindsay, Fei-Fei Liu, Anthony Fyles, Wilf Levin, Jennifer Croke, Aisling Barry, Danielle Rodin, Nhu Tram Nguyen, Tatiana Conrad. Evaluation of partial breast irradiation suitability in early stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-24.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

Background Brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative cavity boost stereotactic radiosurgery (POCBS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (NaSRS) followed by resection was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation toxicity compared to a comparative cohort of patients treated with postoperative SRS. Objective To determine if the rate of symptomatic radiation toxicity at 1 yr in patients who receive NaSRS differs significantly from historical rates for patients treated with POCBS. Methods This is a multi-center, non-randomized, open phase II clinical trial. A total of 30 patients with up to 10 brain metastases, at least 1 of which is appropriate for surgical resection, will be enrolled for over 4 yr. All enrolled patients will be assigned to receive NaSRS followed by surgery. Expected outcome This study will clarify whether symptomatic radiation toxicity caused by NaSRS is significantly decreased compared to historical rates associated with POCBS. Secondary endpoints will include 1-yr local control (LC) of the treated lesion, 1-yr rates of LMD, median survival and 2-yr rates of progression-free and overall survival. Tertiary analyses will include correlation between LC and radiation toxicity with pretreatment clinical factors, serum markers, radiomic features, and molecular assessments of the resected tumors. Discussion This prospective study will determine the toxicity associated with NaSRS and provide additional quantitative metrics of efficacy for future comparative trials.

Purpose Brain metastases (BrM) are common in patients with epidermal growth factor receptor (EGFRm) mutant non-small cell lung cancer (NSCLC). We sought to determine the rate of neurologic death (ND) in this population. Methods and Materials We analyzed data from 198 patients who received a diagnosis of BrM from EGFRm NSCLC between 2004 and 2016, comparing patients whose initial treatment for BrM was stereotactic radiosurgery with or without tyrosine kinase inhibitors (TKI), whole brain radiation therapy (WBRT) with or without TKI, or TKI alone. The incidence of ND was determined using a competing risks analysis. Univariate and multivariate analyses were used to identify clinical variables associated with this outcome. Results The percentage of patients who initially received stereotactic radiosurgery, whole brain radiation therapy, or TKI alone was 22%, 61%, and 17%, respectively. Median overall survival in these subgroups was 31.1, 14.6, and 24.6 months, respectively (P = .0016). The 5-year incidence of ND among all patients was 40% and did not significantly vary according to treatment group. In a multivariable model, only leptomeningeal disease at any point in a patient’s disease course significantly correlated with ND (hazard ratio 4.75, P Conclusions Among our cohort of patients with BrM from EGFRm NSCLC, the incidence of ND was significantly higher than suggested by previous reports. BrM should be considered a driver of mortality in many patients with EGFRm NSCLC, and treatments providing better control of BrM, lower neurocognitive side effects, and maintenance of quality of life are needed.

OBJECTIVE Neurosurgery (NS) is an essential modality for large brain metastases (BM). As an adjuvant treatment, stereotactic radiosurgery (SRS) reduces neurocognitive toxicity without affecting post-treatment overall survival (OS) compared to whole brain radiation therapy. Pachymeningeal failure (PMF) beyond the SRS field is a relatively newly described entity, distinct from classical leptomeningeal failure (LMF), and unique to postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS+SRS. METHODS We reviewed a prospective registry (2009 to 2020) and identified all patients treated with NS+SRS. Clinical, radiological, pathological and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model and differences between cohorts were measured using the Fine-Gray method. RESULTS 144 Patients were identified. Median age was 62 (23-90). PMF occurred in 22.2% (32/144) patients). Univariate analysis indicated female gender (HR 2.65, p=0.013), higher GPA status (HR 2.4, p CONCLUSIONS PMF is an underrecognized phenomenon that correlates with pre-operative pia/dura contact and piecemeal resection in patients treated with NS+SRS for BM. While less morbid than LMF, it is a critical event that deserves increased vigilance and analysis.

INTRODUCTION Approximately 20% of brain metastases (BM) occur in the posterior fossa (PF). However, the criteria to treat large PF BM with surgery (S) followed by stereotactic radiosurgery (SRS) or SRS alone are still unclear. We aim to identify parameters that can help in the decision of treating PF BM with S+SRS or SRS and to compare outcomes between the two groups. METHODOLOGY We reviewed a prospective registry database (2009 to 2020) and identified all patients with PF BM (≥4cc in volume) treated with SRS or S+SRS. Clinical and radiological, parameters were analyzed. We examined two endpoints: Overall Survival (OS) and Local Failure (LF). RESULTS 64 patients were identified; 30 were treated with S+ SRS and 34 with SRS. Gait imbalance and Intracranial pressure symptoms were significantly different between the groups; 97% and 80% for S+SRS vs 47% and 35% for SRS, respectively. Radiologically, there were significant differences in the mean volume of the lesions [6.7 cm3 in SRS vs 29.8cm3 in S+SRS cohort] (p CONCLUSIONS Patients treated with S+SRS were more likely to be symptomatic, have larger tumors, and have compression of the IV ventricle with hydrocephalus. Non-symptomatic patients with moderately sized lesions were safely managed with SRS. S+SRS treatment and higher GPA were associated with improved OS.

Purpose To evaluate standardized uptake value (SUV) stability on pretreatment and intratreatment 18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in patients undergoing definitive CRT for head and neck cancer (HNC). Methods Primary tumor and nodal volumes of interest (VOIs) from HNC patients were contoured on the pretreatment and intratreatment PET-CT by two independent observers. SUV stability was measured with intersection calculations (DICE, overlap fraction, center to center) between the VOIs at threshold levels of 50%, 60%, 70%, 80%, and 90% of the SUV maximum. Results The mean calculated DICE of the 50%, 60%, 70%, 80%, 90% SUV threshold was 0.53, 0.48, 0.41, 0.28, and 0.12, respectively. The mean calculated overlap fraction was 0.71, 0.65, 0.58, 0.43, and 0.2, respectively. Center-center difference demonstrates spatial variability of 7.8, 8.2, 8.6, 9.5, and 11.2 mm for these SUV subvolumes of interest. Conclusions HNC subvolumes defined by SUV thresholding technique in FDG PET-CT imaging do not remain physically stable during (chemo)RT. Highlights All pretreatment and intratreatment SUV thresholds (50%-90%) overlap indexes are low during the course of (chemo)radiation. Pretreatment and intratreatment center to center variation further corroborates that all FDG threshold volumes do not remain stable during treatment. No difference in SUV threshold stability was seen between p16 positive and negative tumors.

Background: The purpose of our study was to characterize clinical features among brain metastasis (BM) patients who were long term survivors (LTS). Methods: We reviewed a registry of BM patients referred to our multidisciplinary BM clinic between 2006 and 2014 and identified 97 who lived &ge, 3 years following BM diagnosis. The clinical and treatment characteristics were obtained from a prospectively maintained database, and additional information was obtained through review of electronic medical records and radiologic images. Survival analyses were performed using the Kaplan-Meier method. Results: Median follow up for LTS was 67 months (range 36&ndash, 181). Median age was 54 years, 65% had single BM, 39% had stable extracranial disease at the time of BM treatment, and brain was the first site of metastasis in 76%. Targetable mutations were present in 39% of patients and 66% received treatment with targeted-, hormonal-, or immuno-therapy. Brain surgery at the time of diagnosis was performed in 40% and stereotactic radiosurgery (SRS) or whole brain radiotherapy (alone or combination) in 52% and 56%, respectively. Following initial BM treatment, 5-year intracranial disease-free survival was 39%, and the cumulative incidence of symptomatic radio-necrosis was 16%. Five and ten-year overall survival was 72% and 26%, respectively. Conclusion: Most LTS were younger than 60 years old and had a single BM. Many received treatment with surgery or targeted, immune, or hormonal therapy.

Brain metastases (BM) are the most common intracranial neoplasm and represent a major clinical challenge across many medical disciplines. The incidence of BM is increasing, largely due to improvements in primary disease therapeutics conferring greater systemic control, and advancements in neuroimaging techniques and availability leading to earlier diagnosis. In recent years, the landscape of BM treatment has changed significantly with the advent of personalized targeted chemotherapies and immunotherapy, the adoption of focal radiotherapy (RT) for higher intracranial disease burden, and the implementation of new surgical strategies. The increasing permutations of options available for the treatment of patients diagnosed with BM necessitate coordinated care by a multidisciplinary team. This review discusses the current treatment regimens for BM as well as examines the salient features of a modern multidisciplinary approach.

Introduction An important but often overlooked component of caring for cancer patients is survivorship care, provided after the completion of active treatment in order to facilitate transition into the next surveillance phase. A survivorship program was developed to deliver a one-on-one education session on healthy lifestyle behaviours and available resources to help patients transition to their post-treatment life. This study reports the outcome of this pilot survivorship care program provided to breast cancer patients completing radiation therapy. Program delivery format and content were evaluated for effectiveness, applicability, and feasibility. Methods and materials Between March 2017 and August 2018, 124 breast cancer patients, nearing completion of their curative intent radiation treatments, participated in this centre-specific survivorship program. The survivorship program entailed a one on one education session delivered to breast cancer patients within the last two weeks of their radiation treatment. Participants were provided a Microsoft PowerPoint presentation, information pamphlet, and evaluation form to provide feedback on materials and presentation. Survivorship education sessions were delivered by study staff or staff scheduled in the Pre-Radiotherapy Patient Assessment role. Follow-up phone calls were conducted post-session delivery to determine the ongoing applicability of survivorship material. Staff was also given an evaluation form upon completion of the trial to measure the session feasibility. Results Of the 124 participants in the study, 69 (56%) provided feedback. Results showed that 98% of participants felt the information provided either confirmed what they were already doing (44%) or encouraged them to consider a lifestyle change (54%). Additionally, 70% reported feeling more confident after completing the session. Staff survey results reported that 87.5% agreed or strongly agreed that these sessions were beneficial and valuable to patients Conclusions Delivering one-on-one education sessions to individual participants focusing on healthy lifestyle measures garnered a positive response from participants, increasing their confidence and knowledge for making lifestyle changes. While staff survey results pointed strongly in favour of continuing with the survivorship sessions, it was shown that the methods of delivery trialed in this study were not feasible to be implemented on a larger scale. With some workflow modification, implementing a survivorship care program in our cancer centre is a possible and important aspect of a patient’s treatment journey.

PURPOSE/OBJECTIVE(S) Surgical resection followed by adjuvant stereotactic radiosurgery (SRS) has become a widely accepted treatment modality for brain metastases (BM). Compared to Whole Brain Radiation (WBRT), this approach achieves equivalent overall survival (OS) while reducing cognitive toxicities and preserving quality of life. However, this method of treatment is associated with a unique pattern of treatment failure, ¨nodular leptomeningeal disease" (nLMD), that is distinct in terms of behavior, prognosis and management compared to classic leptomeningeal disease (cLMD). We aimed to identify factors associated with the incidence of nLMD in surgical cavities treated with SRS. MATERIALS/METHODS After identifying all patients treated with surgery and SRS of BM from a prospective registry, magnetic resonance imaging (MRI) before and after surgery were used to characterize tumors on the basis of dural contact, size and location. We also determined whether treatment volumes (TV) included the surgical tract or the pre-surgical areas of tumor contact with sinus or dura and, if so, whether that was expanded by a 1-5mm or 6-10mm margin. Failures were classified as nLMD, cLMD, or local failure (LF). Survival rates were calculated using the Kaplan Meier method. Outcomes for nLMD, cLMD, and LF were calculated using the cumulative incidence method. The difference in groups was tested using the Fine-Gray competing risk model. RESULTS 130 patients with 132 cavities were identified. Median patient age was 61.5 (23-90), median number of BM was 1 (1-10), median target volume was 15.1cc (4-54). Twenty-one percent of tumors were infra tentorial. Ninety-seven tumors contacted the dura pre-operatively. OS at 12 and 24 months was 68% and 39%, respectively. Cumulative incidence of nLMD at 12 and 24 months was 17% and 22%, respectively and for cLMD it was 3% and 6%, respectively. The incidence of LF at 12 and 24 months was 10% and 17%, respectively. OS following nLMD vs cLMD at 6 and 12 months were 49% and 29%, and 29% and 0%, respectively. Of the factors examined, only pre-surgical dural contact correlated with time to nLMD failure (HR 0.2 (0.05-0.81) (P = 0.024). No factors examined correlated with time to cLMD failure. Among 9 patients for whom a 6-10 mm dural margin was added to the region of pre-surgical dural contact, there were no nLMD. CONCLUSION Preoperative dural contact correlated with time to nLMD but not cLMD. Patients with nLMD lived longer than those with cLMD. Including the surgical tract, the radiation target did not influence time to nLMD or cLMD. AUTHOR DISCLOSURE E. Gutierrez: None. C.J. Villafuerte: None. B. Millar: None. N.J. Laperriere: None. T.D. Conrad: None. A. Kalyvas: None. G. Zadeh: None. M. Bernstein: None. J. Weiss: None. P. Kongkham: None. D.B. Shultz: None.

Purpose Large brain metastases (BRM) are challenging to manage. Therapeutic options include Stereotactic Radiosurgery (SRS) or surgery (S) with adjuvant SRS. We sought to compare overall survival (OS), radionecrosis (RN), local failure (LF), pachymeningeal (PMD) and leptomeningeal (LMD) disease in patients treated with SRS vs. S+SRS. Methods We reviewed a prospective registry database from 2009 to 2020 and identified all patients with BRM (≥4cc in volume) treated with SRS or S+SRS. WBRT or SRS re-targeting the index lesion were censoring events. Survival percentages were calculated using the Kaplan-Meier method. Differences between groups were tested using the Cox proportional hazards model. Results 383 patients were identified, 128 and 255 were treated with S+SRS and SRS, respectively. Median ages in the S+SRS and SRS groups were 62.2 (23.6–98.5) and 60.2 (20.2–97.4) (P 0.33). OS at 12 and 24 months was 69% and 41% vs 55% and 20% for the S+SRS and SRS groups, respectively hazard ratio (HR) 1.64 (1.23–2.18) (P Conclusion Surgical resection plus SRS correlated with improved OS and a trend towards a decreased incidence of LF compared to SRS alone. However, patients treated with S experienced an increased incidence of PMD.

BACKGROUND: At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. METHODS: We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs). RESULTS: We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4–100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub–hazard ratio, 2.3; 95% CI: 1.4–3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN. CONCLUSION: Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.

Objectives Surgery remains the primary therapy for locally advanced gastric cancer, but locoregional recurrence (LRR) has been documented in up to 68.6 % of patients with surgery alone. Peri- or post-operative adjuvant treatment improves survival. The objective of this study is to examine rates and patterns of recurrence following resection and adjuvant chemoradiation.

Purpose Active breathing control (ABC) is emerging as a tool to reduce heart and lung dose for lymphoma patients receiving mediastinal radiation therapy (RT). The objective of this study was to report our early institutional experience with this technique, with emphasis on quantifying the changes in normal tissue dose and exploring factors that could be used to select patients with the greatest benefit. Methods and materials Patients receiving mediastinal involved-field RT (IFRT) for lymphoma were eligible. The ABC was performed using a moderate deep-inspiration breath-hold (mDIBH) technique. All patients were replanned with free-breathing (FB) computed tomographic data sets and comparisons of lung, cardiac, and female breast tissue doses were made between mDIBH and FB plans. Logistic regression models were used to identify factors associated with improvement in mean lung and heart dose with mDIBH. Results Forty-seven patients were analyzed; the majority (87.2%) had Hodgkin lymphoma. Median prescribed dose was 30 Gy (range, 20-36 Gy), with 78.7% of cases being treated with parallel-opposed beams. The use of mDIBH significantly improved average mean lung dose (FB: 11.0 Gy; mDIBH: 9.5 Gy; P P P = .003), but increased the mean breast dose (FB: 3.0 Gy; mDIBH 3.6 Gy; P = .0005). The magnitude of diaphragmatic excursion on the inhale scan was significantly associated with dosimetric improvement in both heart and lung dose with mDIBH. Conclusions Mediastinal IFRT for lymphoma delivered with mDIBH can significantly reduce lung and heart dose compared with FB, although not for all patients, and may increase breast dose in females. Its implementation is achievable in both adult and pediatric populations. Further work is necessary to better predict which patients benefit from this technique.

Purpose: We identified key clinicopathologic features of brain metastasis (BM) patients who are long-term survivors (LTS). Methods: We screened a prospective database of 1892 patients (treated 2006-2017), identified 92 (5%) who lived > 3 years following BM diagnosis, and performed per patient analyses. Results: Median age at diagnosis of BM was 57 years (range 19-77), 77% were women. The most common tumors were lung (50%), breast (26%), thyroid (7%) and skin (5%). 42% had tumors with drug-targetable oncoproteins (e.g. EGFR mutant) and 15% expressed hormonal receptors. ECOG was

Aims Breast radiotherapy treatment is commonly managed by a multidisciplinary team to ensure optimal delivery of care. We sought a new model of care whereby a clinical specialist radiation therapist (CSRT) delineates the cavity target for whole breast radiotherapy treatment planning and the radiation oncologist validates the contour during final plan review. This study evaluated the radiation oncologist's acceptance of these contours and identified characteristics of cavities suitable for CSRT-directed contouring. Materials and methods Following specialised breast oncology education and training by the radiation oncologist, the CSRT prospectively delineated cavities in 30 tangential breast radiotherapy cases and consulted the radiation oncologist in ‘complex' cases but directed ‘non-complex' cases for treatment planning. Changes to CSRT contours were evaluated using the conformity index. Breast density, time since surgery and cavity location, size and visualisation score [CVS: range 1 (no visible cavity) to 5 (homogenous cavity)] were captured. Results Of the 30 CSRT delineated cavities contours, the CSRT directed 20 (66.7%) cases for planning without radiation oncology review; 19 were accepted (without changes) by the radiation oncologist upon final plan review and one was changed by the radiation oncologist (conformity index = 0.93) for boost treatment and did not affect the tangential treatment plan. Ten (33.3%) cases, all CVS ≤ 3, were reviewed with the radiation oncologist before planning (conformity index = 0.88 ± 0.12). CVS was inversely correlated with breast density and cavity size ( P Conclusions The CSRT delineated cavities appropriate for clinical radiotherapy treatment planning in women with well-visualised cavities, whereas ‘complex' cases with dense breast parenchyma, CVS ≤ 3, and/or cases needing boost radiotherapy treatment required review with the radiation oncologist before planning.

Background: Brain tumors present unique challenges to patient and family quality of life (QOL). Cognitive dysfunction is common and functionally limiting, with no established treatments. These studies evaluate feasibility and preliminary efficacy of behavioral interventions developed for neuro-oncology patients. Study 1: A randomized controlled trial (N=25 primary brain tumor patients) compared an adapted version of Goal Management Training (GMT, a neuroscience-based integration of mindfulness and strategy training) and a newly-designed supportive psychoeducational intervention (Brain Health Program, BHP) to standard of care. Each intervention comprised 8 individual sessions and at-home practice between sessions. GMT patients’ executive functions improved immediately (p=.077, d=1.13), with maintenance at 4-month follow-up (p=.046, d=1.09). Both intervention groups reported improvements in everyday cognitive functioning immediately (p=.049; d’s GMT=0.43, BHP=0.79) and at follow-up (p=.001; d’s GMT=0.22, BHP=1.01). BHP patients also reported improved mood (p’s=.026 & .012, d’s=0.61 & 0.62). Study 2: Following a needs assessment about cognitive concerns and QOL in brain metastases patients (N=109) and caregivers (N=31), we developed a novel, brief (3 sessions + homework) Cognitive Support Program to provide education and strategy-training in key areas of concern: executive functions, memory, and communication. Options include caregiver co-training, and in-person or web-based delivery. Preliminary data from a pilot trial in progress demonstrate objective and subjective improvements. Conclusions: Cognitive rehabilitation may be a feasible and effective option for primary or metastatic brain tumor patients, addressing a need that is largely unmet in standard cancer care. Further development and larger trials appear warranted, with capacity for remote delivery recommended.

TPS2086 Background: Brain metastases occur in ~30% of cancer patients. While treatment options continue to evolve, prognosis remains poor in both morbidity and survival, and quality of life (QOL) is increasingly emphasized. Most patients will experience cognitive dysfunction. Deficits in executive and self-regulatory functions, memory, and communication interfere with patients’ functional independence, participation in valued activities, relationships and QOL; they also affect families and caregivers. There are currently no established interventions for oncology and supportive care teams to address cognitive dysfunction and its impact on patient and family QOL. This study targets this gap in knowledge and clinical practice through development and piloting of a novel cognitive support program (CSP) for brain metastasis patients and their primary caregivers. Methods: Building on relevant neuroscience and behavioral research in other cognitively-impaired populations, we designed the CSP as a brief, structured, client-centered program. Using a prospective longitudinal design, 24 cognitively-impaired patients are being recruited from an outpatient multidisciplinary brain metastasis clinic. Each patient, together with their primary caregiver, attends 3 weekly individual sessions to learn strategies for memory, communication and executive functions. At-home practice between sessions applies the strategies in daily activities. Feasibility will be assessed through retention and adherence. Preliminary efficacy will be assessed by reliable change on cognitive, functional and QOL measures completed by patients pre-, post-, and 3 months following the CSP intervention. Caregivers will complete ratings of patient functioning and their own QOL at the same intervals. Analyses of variance will examine CSP intervention effects, with regression analyses to explore moderating effects of participant demographics, baseline levels of cognitive impairment, disease and treatment factors (e.g., volume and location of brain lesions, CNS-directed treatments received). Results of this pilot trial will lay the groundwork for a future randomized trial and further development of cognitive supports for brain metastasis patients and their families.

Since the Intergroup 0116 study was published in 2000, adjuvant postoperative chemoradiotherapy using CT-planned and 3D conformal/intensity-modulated radiotherapy has been offered routinely to fit patients with resected gastric cancer at Princess Margaret Hospital .The objective of this study was to analyze patterns of disease recurrence with respect to the radiotherapy volumes. For the date and site (local, locoregional, or distant) of the first recurrence, medical records were reviewed for all patients treated at Princess Margaret Hospital with adjuvant chemoradiotherapy for resected gastric adenocarcinoma (January 1, 2000 to November 30, 2009). Patients whose recurrences were limited to local and/or regional sites were selected for further analysis. Available diagnostic imaging of the recurrence site was registered to the original planning radiotherapy dataset for contouring. If necessary to respect changes in anatomy, the contour was translocated on the basis of anatomic descriptors. The center of mass for each recurrence was identified as a point and its location was categorized according to the isodose encompassing it; in field (90 % or more), marginal (50–89 %), or out of field (less than 50 %). Of all 197 patients, 14 (7 %) had isolated locoregional failure, constituting 20 % of all 71 patients with a recurrence. Successful fusions were feasible in five cases. Of these recurrences, four were in field and one was marginal. In a further four cases, visual inspection was used, showing one in-field recurrence, one marginal recurrence, and two out-of-field recurrences. In five patients, either a useable original dataset or diagnostic imaging of the recurrence was not available. The rates of isolated local/locoregional tumor recurrence in this study were low. Of the small number of recurrences available for analysis, most (five of nine) were in field. Further studies involving a larger cohort of patients might allow a more meaningful analysis of trends in the recurrence site with evolving radiotherapy techniques.

patients. Histopathological analysis was used to confirm clinical treatment response. Results/Benefits/Challenges: Clinical responders showed a significant increase (p

68 Background: Since the Intergroup 0116 study in 2000, adjuvant post-operative chemoradiotherapy (CRT) has been offered routinely to similar patients with resected gastric cancer at Princess Margaret Hospital (PMH) using CT-planned and 3D conformal/intensity modulated radiotherapy (RT). The objective of this study was to analyze patterns of recurrence with respect to RT treatment volumes. Methods: Date and site (local, locoregional or distant) of first recurrence data was obtained from chart review for all patients treated at PMH with adjuvant CRT for resected gastric adenocarcinoma (Jan. 1, 2000-Nov. 30, 2009). Patients whose recurrences were limited to local (gastric remnant, duodenal margin, gastric bed recurrence) and/or regional sites (regional lymph node recurrence) were selected for analysis. When available, diagnostic imaging of recurrence site was registered to the original planning RT dataset. The center of mass for each recurrence was identified as a point and its location categorized according to the isodose encompassing it; in-field (≥ 90%), marginal (50%-89%), and out-of-field (< 50%). Results: Three-year OS, and RFS were 66% (95% CI: 58-73) and 58% (50-60), respectively. Of 203 patients treated, 75 recurrences were identified (Table). Of the 13 local/locoregional recurrences, 4 were in-field, 1 marginal, 1 could not be registered due to change in body habitus, and 7 did not have an available original dataset. Conclusions: Rates of isolated local and/or regional recurrence in this study were low. This represents a change in the pattern seen with surgery alone suggesting the addition of CRT results in decreased isolated local and/or regional recurrence. Of the small number of local and/or regional recurrences available for analysis, all were in-field or marginal. Further studies involving a larger cohort of patients might allow for more meaningful analysis of trends in recurrence site with evolving RT techniques. [Table: see text] No significant financial relationships to disclose.