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11547 Background: Surgery and (neo)adjuvant radiotherapy are the mainstay curative treatments for localized STS. Despite treatment, approximately 50% of STS patients (pts) experience metastatic relapse and routine use of adjuvant systemic therapy (AST) remains controversial. The presence of ctDNA following curative treatment of STS is a potential biomarker for MRD and may identify patients who benefit from AST. Given the genomic heterogeneity of STS, a histology-agnostic approach to ctDNA detection in this population is desirable. Methods: Pts with localized, high risk (size ≥ 5cm, grade ≥ 2) disease were enrolled prior to (neo) adjuvant radiotherapy and surgery. Blood for ctDNA was collected at diagnosis; post-radiotherapy, post-surgery and every 3 months for up to 2 years. Whole exome sequencing (WES) of archival tumor- and matched buffy coat-DNA were carried out to identify somatic variants. Personalized and tumor-informed, multiplex PCR next generation sequencing-based ctDNA assay (Signatera™ assay) was performed on plasma obtained at the serial timepoints. A sample level positive call required ≥ 2 variants above a confidence calling threshold. Absolute ctDNA levels were expressed as mean tumor molecules per milliliter (MTM/ml) of plasma, based on variant allele frequencies and quantity of cell free DNA. Standard radiologic surveillance (every 3 months) was performed following surgery. The primary endpoint was a ctDNA detection rate of 70% at diagnosis. Secondary endpoints included MRD detection and correlation of ctDNA levels with disease relapse. Results: Seventy-six plasma samples from 10 pts [8 males and 2 females; median age 64 years (range 46–84)] were obtained prospectively. STS subtypes were undifferentiated pleomorphic sarcoma (n = 4), myxofibrosarcoma (n = 2), dedifferentiated liposarcoma (n = 2), myxoid liposarcoma (n = 1), and pleomorphic liposarcoma (n = 1). All tumors successfully underwent WES with adequate data quality for Signatera™ assay design. The personalized ctDNA assay was performed on a median of 7 plasma samples per patient (range: 5 – 10). ctDNA was detected in 7 pts (70%) at diagnosis, with median ctDNA level of 1.6 MTM/ml (range: 0.2 – 137.8), achieving the study primary endpoint. Immediate post-surgery samples were negative in all pts. However, ctDNA was detected in 2 out of 2 pts who developed metastatic disease during follow-up. Conclusions: Personalized tumor-informed ctDNA assays in localized high-risk STS at diagnosis are feasible. In this series, all patients had undetectable levels of ctDNA post-surgery and patients who experienced disease relapse demonstrated a detectable rise in ctDNA levels. Further interrogation of this approach for detection of post-treatment MRD as a possible biomarker of benefit from AST is ongoing.

11548 Background: The mainstay therapy of operable STS remains surgery, which may include (neo)adjuvant therapies. Within the TSP, marginally inoperable STS are often treated with sequential chemo (CTX) and radiation (RT) therapy, followed by surgery (SX). Herein we present our experience of multi-modality therapies for marginally inoperable STS patients (pts). Methods: This was a dual-center, single program, retrospective review. Pts were included if deemed to have marginally inoperable primary or recurrent STS, as determined at the TSP tumor board. Pts included must have had CTX with the intent of having RT and SX after. Pts demographics, treatment details and clinical outcomes data were collected. Relapse free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multivariate analysis of the influence of disease characteristics and treatment on outcomes was assessed using Cox regression. Results: From June 2005 to May 2019, 75 pts were identified. Median age was 52 years (range 16-72). Pts were predominantly male (55%). Histological subtypes included dedifferentiated liposarcoma (29%), leiomyosarcoma (27%), synovial sarcoma (19%) and others (25%). Primary tumor was located in the retroperitoneum (48%), extremity (23%), pelvis (12%), thorax (9%), and other sites (8%). All pts had doxorubicin and ifosfamide CTX (median 4 cycles; range 1-6), while RT dose delivered was 50.4Gy/28 fractions in 58 (77%) of cases. Twenty three pts (31%) achieved partial response, 40 pts (53%) had stable disease and 12 pts (16%) had progression of disease (PD) on CTX, of which half (8%) did not undergo further treatment. Nine pts (12%) underwent CTX followed by SX due to significant response, 9 pts (12%) underwent CTX and RT without SX due to persistent tumor unresectability or PD. The final 50 pts (67%) completed multi-modality treatment (CTX, RT & SX). Overall, 59 pts (79%) had SX; negative margins were achieved in 53 (71%). 19 pts (25%) had postoperative complications, causing death in 2 pts (2.7%). With a median follow-up of 72 months, median RFS and OS were 26.9 months (95% CI: 0-86.0), and 65 months (95% CI: 13.5-116.4). Extremity location was associated with superior RFS (median not reached [NR], HR 0.28 95% CI 0.09-0.83, p = 0.022), and OS (median NR, HR 0.29 95% CI 0.09-0.90, p = 0.032). Receipt of RT was associated with superior RFS (median NR, HR 0.23 95% CI 0.10-0.52, p < 0.001); and OS (median NR, HR 0.21 95% CI 0.09-0.50, p < 0.001). Pts who had PD after CTX were associated with poor outcomes - RFS (median 4.7 months, HR 2.03 95% CI 0.61-6.76, p = 0.24); and OS (median 21.9 months, HR 2.48 95% CI 0.73-8.47, P = 0.144). Conclusions: Multi-modality approach resulted in successful resection for most pts with marginally inoperable STS. Extremity location and RT administration were associated with better RFS and OS, while progression on CTX confers worse survival outcomes.

e14505 Background: Anti-tumor lymphocytes activated in response to ICIs may cross the blood brain barrier with effect on brain metastases (BM). Preliminary evidence suggests that ICIs alone are effective for melanoma BMs. However, the ability of ICI to effectively control NSCLC BMs without radiotherapy is controversial. By comparing serial MRIs and patterns of progression in ICI and chemotherapy treated patients, we sought to investigate the role of ICI in BM control in NSCLC patients. Methods: Serial MRIs were reviewed in ICI treated NSCLC patients with known BMs. Eligible patients must have a minimum of one baseline MRI and a follow-up within 3 months of CNS directed treatment. Patients with EGFR/ ALK mutations were excluded. A control cohort of patients who had never received ICIs was selected using the same criteria. The primary outcome was cumulative CNS progression and intracranial progression free survival (iPFS) analyzed using an accelerated failure time model and competing risk analysis. Results: We identified 137 ICI treated NSCLC patients with known BMs. After excluding for patients without serial MRIs, we analyzed 40 ICI treated patients and 39 controls. All patients received upfront radiotherapy or surgery and the modality used was similar (p = 0.13). CNS failure was less common in the ICI group (p = 0.02). ICI treated patients had a trend to longer iPFS in the PD-L1 ≥50% subgroup (p = 0.058). Cumulative incidence of progressive BM at 12 and 24 months were significantly lower in the ICI treated PD-L1 ≥50% subgroup: 19%/19% vs 50%/56% (p = 0.02). Patients in the PD-L1 ≥50% subgroup who achieved a systemic partial response (n = 10) did not experience any CNS events despite extracranial progression in some. Conclusions: Durable CNS disease control is observed with ICIs in NSCLC with PD-L1 ≥50% and demonstrates a high level of concordance with systemic response. The need for radiotherapy in PD-L1 ≥50% disease should be investigated and may be reasonably delayed in asymptomatic patients with small BMs. Importantly, the same trend was not observed in PDL1 < 50% patients and caution is needed in employing this strategy in this subset of patients.

e22525 Background: Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma in adults. The PAX3-FOXO1 fusion gene is associated with alveolar rhabdomyosarcoma. PAX3-FOXO1 results from a stable reciprocal translocation of chromosomes 2 and 13, which fuses in-frame the DNA binding domain of PAX3 with the transactivation domain of FOXO1. Occasionally, PAX7-FOXO1 is expressed. In children, the PAX3-FOXO1 fusion gene is associated with worse outcome. We evaluated the prognostic role of FOXO1 fusion status in adults with RMS treated in a single, large volume sarcoma centre. Methods: A retrospective review of adult RMS patients (pts) diagnosed from 1984 to 2018 was done. Information on demographics, treatment, fusion status and survival was collected. Primary favourable site was defined as tumour arising in orbit, non-bladder/prostate genitourinary system and non-parameningeal head and neck. Factors were compared using Fisher’s Exact test. Event-free survival (EFS) was estimated by the Kaplan-Meier method and compared with log rank test. FOXO1 fusion status was coded as FP (fusion positive) or FN (fusion negative). Results: Of 134 pts identified in our database, fusion testing was performed in 55 (41%). Of these, PAX3 fusion was detected in 22 (40%). PAX7 was not detected. The median age of FP and FN pts was 25 yrs (range 18, 90) and 27 yrs (range 18, 65), respectively. Gender distribution was similar between FP and FN. Favourable site was seen in 13 (60%) FP and 21 (64%) FN. Nodal disease was present in 21 (95%) FP and 21 (64%) FN (p = 0.02). Distant metastases were present in 10 (45%) FP and 9 (27%) FN (n.s.). Treatment received was as follows for FP and FN, respectively: chemotherapy (21(95%), 33(100%)), radiation (14(64%), 22(67%)) and surgery (4(18%), 17(52%)). 5-yr EFS for pts without distant metastases was 27% (CI 22.6-76.6) and 46% (CI 21.5 – 70.5) for FP and FN respectively (n.s.). Conclusions: FP and FN RMS occurs in adults of all ages. Similar to children, adults with FP are more likely to present with nodal disease. Our study did not show that fusion status was associated with poorer EFS in adult RMS, however, larger series are needed to confirm this preliminary data.

200 Background: Brain metastasis is a common occurrence in many cancers. However, with new therapies (stereotactic radiotherapy) and longer survival due to improved systemic therapies, more contemporary estimates of health utility scores (HUS) are required for this specialized cancer population. Further, recent efforts have tried to incorporate routine collection of such data, especially in an era when new radiation and new systemic therapies, especially targeted therapies require such data when undergoing health technology assessments. Methods: In a cross-sectional study design, patients in the specialized brain metastases clinic at Princess Margaret Cancer Centre were approached to complete the Health-related quality of life (HRQoL) tool, FACT-Br, and the EQ-5D-5L (to derived HUS using Canadian reference values) on iPad or paper. In addition, consent was obtained to collect clinico-demographic data from the patient and chart. In addition to descriptive analysis and participation rates, HUS were correlated to FACT-Br and its subscales. Results: Of 204 eligible patients, 134 were recruited (66% participation rate) from May 2017- Feb 2018. Of 105 patients in this preliminary analysis, the median age was 60 (range: 25-94) years; 73% were female; 64% were Caucasian; 20% were Asian; 49% had lung, 15% had breast, 37% had other primary cancer; 81% received some form of radiotherapy. Median time from first treatment of brain metastasis to survey was 12 (range 0.03-100) months. There were correlations with the following FACT-Br subscales: physical well-being (WB) (rho = 0.70), emotional WB (rho = 0.42), social WB (rho = 0.25), functional WB (rho = 0.59), and brain-specific subscale (rho = 0.67); overall FACT-Br (rho = 0.73); all correlations were p < 0.001. Conclusions: Patients with brain metastasis were generally willing to complete EQ-5D-5L, and patients had good HUS. HUS as measured indirectly by EQ-5D-5L were correlated to HRQoL as measured by FACT-Br or its subscales, with high correlation to the overall FACT-Br. EQ-5D-5L is a practical and useful tool to assess HUS routinely in brain metastases patients.

e18089Background: Head and Neck Rhabdomyosarcoma (HN RMS) in adults is an aggressive and challenging approach to managing malignancy. Our goal was to describe the presentation, treatment, outcomes,...

2062Background: Patients with EGFR mutant non-small cell lung cancer (EGFRmNSCLC) have a high incidence of brain metastases (BM). We sought to determine the rate of neurologic death in EGFRmNSCLC p...

11 Background: As numbers of cancer survivors increase, health-related quality of life and healthcare service utilization warrant closer attention, which requires routine valuations such as health utility scores (e.g. EQ5D-5L). EQ5D-5L implementation into routine clinical practice requires systematic evaluation to assess project scalability with goals of eventual roll-out across all 15 Ontario cancer centres in all disease sites. Methods: We used the Canadian Institutes of Health Research’s Knowledge-to-Action (KTA) framework as a guide to assess implementation of EQ5D-5L in two outpatient cancer populations; St. Michael’s Hospital’s general breast cancer clinic (GBR) and Princess Margaret Cancer Centre’s multidisciplinary brain metastases clinic (MBM), chosen to represent two very different organizational structures and patient populations. KTA steps from landscape assessment and engagement of stakeholders through to pilot implementation using paper surveys are reported. Results: After assessing 270 patients (GBR = 137; MBM = 117) across 57 days, implementation issues at the two sites were noted. GBR clinic’s larger and more general patient base was associated with a lower average socioeconomic status than MBM clinic, which targets a specialized patient population. More barriers to implementation at GBR were systemic and organizational in nature, whereas barriers at MBM were associated with patient management, where patients’ functional disabilities or neglect to return completed questionnaires hindered data collection. For both sites, successful EQ5D-5L implementation was contingent on senior management support and engagement of multiple stakeholders throughout the implementation process, leading to site-specific suggestions. Conclusions: Differing implementation strategies at both sites is reflective of target sites’ distinctive systemic and organizational characteristics and findings can be used to inform the translation of EQ5D-5L to other sites. We present recommendations to aid scalability and implementation efforts, including future transition to electronic routine assessments.

145 Background: Central nervous system (CNS) metastases (mets) in gastroesophageal (GE) cancers are rare. There have only been limited studies examining the role of HER2 status in CNS mets in GE cancers. Methods: A retrospective analysis was performed for patients (pts) treated for GE cancers at the Princess Margaret Cancer Centre from 2011-2016. Quantitative and qualitative data were collected for all pts with CNS mets. Kaplan-Meier method was used to calculate overall survival (OS) and CNS progression free survival (PFS) for CNS mets pts. Results: Of 34 GE cancer pts diagnosed with CNS mets, 11 were HER2+, 11 HER2- and 12 had unknown HER2 status. Median time from initial cancer diagnosis to CNS mets was 10.3 months (13.4 in HER2+, 5.8 in HER2-, 11.7 in HER2 unknown). Characteristics at CNS mets diagnosis included: median age 63; 85% male; 74% had extracranial systemic mets; performance status ECOG 0-1 (64%), 2 (12%), 3-4 (24%). Treatment for CNS mets is shown in Table 1. Median OS from diagnosis of CNS mets was 6.1 months (95%CI 3.2-16.4) for all pts, 17.1 (95%CI 9.9-NA) in HER2+, 1.8 (95%CI 0.6-NA) in HER2-, 6.0 (95%CI 1.9-NA) in HER2 unknown, p=0.01. Median OS from initial cancer diagnosis was 18.5 months (95%CI 13.6-33.7) for all pts, 28.9 (95%CI 21.32-NA) in HER2+, 10.8 (95%CI 6.37-NA) in HER2-, 18.6 (95%CI 10-NA) in HER2 unknown, p=0.015. The 1 year CNS PFS rate was 35% (95%CI 22.1 – 55.5%) for all pts, 53% (95%CI 29.9 – 94%) in HER2+, 18.2% (95%CI 5.3 – 63.7%) in HER2-, 33% (95%CI 15 – 74.2%) in HER2 unknown, p=0.053. Conclusions: HER2+ pts tended to develop CNS mets later than HER2-. HER2+ pts were more likely to receive CNS-directed interventions, with more HER2+ pts having surgery for CNS mets while more HER2- had supportive care. This analysis is the first to suggest that in pts with CNS mets, HER2+ pts had longer survival than HER2-, both from initial diagnosis and after developing CNS metastases.[Table: see text]

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.

132 Background: Sinoatrial node (SAN) injury following stereotactic ablative radiation therapy (SABR) in the chest has not been reported in the literature. We report SAN dysfunction as a potential toxicity of SABR in the chest. Methods: We examined the clinical courses and SABR plans of 47 patients treated for T1 or T2 non-small cell lung cancer of the right upper lobe, middle lobe, lower lobe, or hilum. After developing a contouring atlas for the SAN, based upon the junction between the superior vena cava and the right atrium, dose to the SAN was retrospectively determined for each patient. We identified 13 patients whose treatment imparted significant dose to the SAN, as defined by the SAN encompassed within the 10% prescription isodose (IDL) line. Biologically effective doses (BED), acute and chronic, were correlated with SAN toxicity. Results: Patients underwent SABR to the right lung to a dose of 40-50 Gy in 4 or 5 fractions, with mean acute BED (alpha/beta ratio = 10) of 100.2 Gy and late BED (alpha/beta ratio = 3) of 222.7 Gy. Mean volume of the GTV and PTV were 26.1 and 75.1 mL, respectively. Mean follow-up was 25.5 months. The mean volume of the SAN was 0.37 mL. Average max dose and mean dose to the SAN were 24.7 and 70.7 Gy, respectively. Of the 13 patients whose treatment imparted significant dose to the SAN, one patient without prior arrhythmia developed symptomatic SAN dysfunction requiring pacemaker placement at 6 months after completion of treatment. The sinoatrial node of the patient received a maximum dose of 44.8 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 90 Gy and late BED (alpha/beta ratio = 3) of 194.1 Gy, and a mean dose of 35.5 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 71 Gy and late BED (alpha/beta ratio = 3) of 153.8 Gy. This was the third highest max dose and second highest mean dose to SAN in the cohort. Conclusions: We report sinoatrial node dysfunction as a potential toxicity of SABR in the chest for non-small cell lung cancer. Caution is advised when treatment imparts significant dose to the sinoatrial node.

4133 Background: NCIC Clinical Trials Group PA.3 (NCIC CTG PA.3) was a randomized control trial that demonstrated an overall survival (OS) benefit in patients receiving E in addition to G for local...

317 Background: To report updated outcomes and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma treated over the past 11 years from a single institution. Methods: One hundred and ninety-nine patients with primary, unresectable pancreatic adenocarcinoma were treated with SBRT at our institution from 2002 to 2013. One hundred and sixty-four had locally advanced disease, 12 had borderline resectable disease, 21 were medically inoperable, and 2 had resectable disease but refused surgery. Fifteen patients had metastases at the time of SBRT. Forty-six patients were treated with prior RT, 16 of whom were enrolled on a combined IMRT/SBRT trial. Most common treatment regimens were 25 Gy x 1 (51.3%), 6.6 Gy x 5 (25.6%), 6 Gy x 5 (15.0%). Fifty-seven patients had no prior/current chemo while 142 patients had prior/current chemo (134 had gemcitabine-based chemo). BED10 and BED3 were defined using the linear quadratic equation assuming an α/β of 10 and 3, respectively. Results: Median follow-up was 7.1 months (0.13-63.58). The 6- and 12-month cumulative incidence of local recurrence (CIR) were 7.93% (4.07-11.80%, 95% CI) and 12.48% (7.68-17.28%, 95% CI), respectively. Three patients converted to resection after SBRT. BED10 (median 87.5, range 19.5-97.5), prior RT, prior/current chemo, and tumor location did not predict for CIR. OS rates at 6 months and 12 months were 71.23% (65.02-78.0%, 95% CI) and 36.23% (29.54-44.4%, 95% CI), respectively. Median OS from date of diagnosis was 14.27 months (13.25-16.90 95% CI). Patients who received prior/current chemo had better OS (p=0.0035). There were 26 (13%) recorded GI ulcers/strictures/bleed (5 acute, 21 late) after treatment. BED3 (median 233.3, 30-233.3) predicted for these toxicities (OR 1.01, 1.00-1.01 95% CI, p=0.022), while age, prior RT, prior/current chemo, tumor location did not. Conclusions: SBRT for pancreatic adenocarcinoma is effective for local control with associated risk of toxicity. The risk of GI toxicity is correlated with BED3. Survival is associated with the use of chemotherapy. SBRT may be advantageous due to its good local control with shortened treatment duration that minimizes interruption in chemotherapy.