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International audience; Purpose: To evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa).Methods: A prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer's perspective, with a time horizon of 48 months. Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY). We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap.Results: Total costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: - 0.016 to 0.099).Conclusions: Treating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.

The rapidly increasing number of prostate cancer survivors in tandem with a forthcoming shortage of oncology specialists in our health system poses a barrier to ensuring that high-quality survivorship care is available to support this population. As such, there is a need to consider ways to optimize survivorship care, while taking health system constraints into account. The purpose of this study is to explore the perceptions of survivorship self-management between oncology specialists, primary care providers (PCPs), and survivors themselves.A single cross-sectional survey, relating to how prostate cancer survivorship care could be improved, was administered to each group.Two hundred forty-three participants (N = 206 survivors, N = 10 oncology specialists, N = 27 PCPs) completed the study survey. Most PCPs (90%) and oncology specialists (84%) perceived that an opportunity for prostate cancer survivors to have an expanded role in their care would be beneficial. Nearly half (49%) of survivors reported that it would be beneficial to have an expanded role in their survivorship care with only 11% indicating that it would not be beneficial at all.Barriers to developing this model involve limited oncology specialist time to execute survivorship plans, limited communication between oncology specialists and PCPs, and a lack of primary care and survivor education targeted specifically to prostate cancer survivorship.

Introduction: Prostate cancer survivors experience a multitude of late treatment effects, resulting in greater unmet needs, elevated symptom burden, and reduced quality of life. Survivors can engage in appropriate self-management strategies post-treatment to help reduce the symptom burden. The objectives of this study were to: 1) explore the unmet needs of prostate cancer survivors using the validated Cancer Survivor Unmet Needs instrument; 2) explore predictors of high unmet needs; and 3) explore prostate cancer survivors’ willingness to engage in self-management behaviors. Methods: Survivors were recruited from a prostate clinic and a cross-sectional survey design was employed. Inclusion criteria was having completed treatment two years prior. Descriptive statistics were used to summarize participant characteristics. Univariate and multivariate analyses were done to determine predictors of unmet needs and readiness to engage. Results: A total of 206 survivors participated in the study, with a mean age of 71 years. Most participants were university/college-educated (n=123, 61%) and had an annual household income of >$99 999 (n=74, 38%). Participants reported erectile dysfunction (81%) and nocturia (81%) as the most frequently experienced symptoms with the greatest symptom severity (x ̅=5.8 and x ̅=4.5, respectively). More accessible parking was the greatest unmet need in the quality-of-life domain (n=34/57, 60%). Overall, supportive care unmet needs were predicted by symptom severity on both univariate (p

To compare the long-term oncologic outcomes of intermediate risk (IR) prostate cancer (PCa) patients treated with low dose-rate brachytherapy (LDR-BT) or moderate hypofractionated external beam radiotherapy (HF-EBRT).Patients diagnosed with IR PCa and treated with LDR-BT or HF-EBRT between January 2005 and December 2013 were included. Brachytherapy treatment involved a transperineal implant of iodine-125 to a dose of 145 Gy to the PTV, while HF-EBRT was delivered using intensity modulated radiotherapy with 60 Gy in 20 fractions. The Phoenix ''nadir +2'' threshold was used to define biochemical relapse (BR). The cumulative incidence function (CIF) of BR and metastases was reported for each group and compared using the Gray's test to account for the competing risk of death. The Kaplan-Meier (KM) method was used to estimate overall survival (OS) and prostate cancer specific survival (PCSS). Univariate (UVA) and multivariable (MVA) analysis of the CIF of BR and metastases were performed. A 2-tailed p-value ≤ 0.05 was considered statistically significant.Overall, 122 and 124 patients were treated with LDR-BT and HF-EBRT respectively. Median follow-up was 95 months [interquartile range (IQR): 79-118] in the LDR-BT group and 96 months (IQR: 63-123) in the HF-EBRT group. BR was observed in 5 patients treated with LDR-BT and 34 treated with HF-EBRT. At 60 and 90 months, the CIF of BR was 0.9% and 3.5% in the LDR-BT group vs. 16.6% and 23.7% in the HF-EBRT (p0.001). The CIF of metastases at 90 and 108 months, was 0% and 1.6% vs. 3.4% and 9.1% in the LDR-BT and HF-EBRT groups (p = 0.003), respectively. At the last follow-up, 3 patients treated with HF-EBRT died from their cancer [PCSS of 97.5% at 8 years and none died in the LDR-BT group (p = 0.09). On UVA and MVA risk group and treatment modality were independently associated with CIF of BR. On UVA HF-EBRT and ISUP grade group 3 were associated with metastases.LDR-BT was associated with higher biochemical and metastases control in our cohort when compared to moderately HF-EBRT. In the absence of a randomized trial, LDR-BT when feasible should be offered to patients with a life expectancy of8 years.

The risk of tumor recurrence after resection of soft tissue sarcoma (STS) necessitates surveillance in follow-up. The objective of this study was to determine the frequency/timing of metastasis and local recurrence following treatment for soft tissue sarcoma, and to use these data to justify an evidence-based follow-up schedule. Utilizing a prospective database, a retrospective single center review was performed of all patients with minimum 2-year follow-up after resection of a localized extremity STS. Kaplan–Meier estimates were used to calculate the incidence of local recurrence and metastases on an annual basis for 10 years. We identified a total of 230 low-grade, 626 intermediate-grade and 940 high-grade extremity STS and a total of 721 events, 150 local recurrences and 571 metastases. Based on tumor size and grade, follow-up cohorts were developed that had similar metastatic risk. Using pre-determined thresholds for metastatic event, a follow-up schedule was established for each cohort. Based on our results we recommend that patients with small low-grade tumors undergo annual follow-up for 5 years following definitive local treatment. Patients with large low-grade tumors, small intermediate-grade and small high-grade tumors should have follow-up every 6 months for the first 2 years, then yearly to 10 years. Only patients with large intermediate- or high-grade tumors require follow-up every 3 months for the first 2 years, then every 6 months for years 3–5, followed by annually until 10 years.

Purpose The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

Introduction: Radical cystectomy (RC) is the historic gold standard treatment for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has emerged as a valid therapeutic option for selected patients. Given that prospective clinical trials have been difficult to perform in this area, our aim was to compare these two primary treatment strategies using decision analytic methods. Method: A two-dimensional Markov microsimulation model was constructed using TreeAge Pro to compare RC and TMT for patients with newly diagnosed MIBC. A comprehensive literature search was used to populate model probabilities and utilities. Our primary outcome was quality-adjusted life expectancy (QALE). Secondary outcomes included crude life expectancy (LE) and bladder cancer recurrences. The simulated patient for our model was an adult with MIBC (pT2-4 N0 M0) who was a candidate for either RC or TMT. Results: A total of 500 000 patients were simulated. TMT resulted in an estimated mean QALE of 7.48 vs. 7.41 for RC. However, the average LE for patients treated with TMT was lower compared with RC (10.20 vs. 10.74 years). A sensitivity analysis evaluating the impact of age showed that younger patients treated with RC had greater QALE and longer LE than those treated with TMT; inverse findings were observed for elderly patients. Overall, 39.4% of patients treated with TMT experienced a bladder recurrence. Conclusions: RC results in a longer LE compared to TMT (0.54 years), but with a lower QALE (-0.07 years). The preferred treatment strategy varied with patient age.

Retroperitoneal sarcoma (RPS)-specific nomograms provide estimates of survival and recurrence risk following resection in the individual patient. The effect of preoperative treatment on nomogram performance has not been previously examined. Our aim was to evaluate the predictive accuracy of existing RPS-specific nomograms in patients managed at our center, where the majority of patients received preoperative radiation.All patients who underwent curative treatment for primary RPS at Mount Sinai Hospital/Princess Margaret Hospital between 1996 and 2016 were identified. The performance of four previously published nomograms was assessed by measuring the agreement between nomogram-predicted and observed outcomes using Harrell's C-Index and level of calibration. Outcomes included in each of the nomograms [overall survival (OS), disease-free survival (DFS), disease-specific death (DSD), local recurrence (LR), distant recurrence (DR)] at each of the specified post-resection timepoints were examined.In total, 253 patients were included. When observed outcomes were compared with those predicted by each of the four nomograms, the C-Index ranged from 0.60 to 0.81, representing a wide range of predictive accuracy. The lowest C-Index was for prediction of LR. Calibration plots revealed that the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram predicted a 5-year LR of 45%, whereas the observed LR was 24%. Overprediction of LR was detected in patients who had undergone preoperative radiotherapy, but not in patients treated with surgery alone.Preoperative radiotherapy appeared to preclude the use of the LR component of existing nomograms for primary RPS. Updated nomograms should be created to reflect this variable, particularly in light of the recently published STRASS trial results.

ObjectivesStandardised reporting of patient and public involvement (PPI) in research studies is needed to facilitate learning about how to achieve effective PPI. The aim of this evaluation was to explore the impact of PPI in a large UK study, the Life After Prostate Cancer Diagnosis (LAPCD) study, and to explore the facilitators and challenges experienced.DesignMixed-methods study using an online survey and semistructured interviews. Survey and topic guide were informed by systematic review evidence of the impact of PPI and by realist evaluation. Descriptive analysis of survey data and thematic analysis of interview data were conducted. Results are reported using the GRIPP2 (Guidance for Reporting Involvement of Patients and the Public, Version 2) reporting guidelines.SettingLAPCD study, a UK-wide patient-reported outcome study.ParticipantsUser Advisory Group (UAG) members (n=9) and researchers (n=29) from the LAPCD study.ResultsImpact was greatest on improving survey design and topic guides for interviews, enhancing clarity of patient-facing materials, informing best practices around data collection and ensuring steering group meetings were grounded in what is important to the patient. Further impacts included ensuring patient-focused dissemination of study findings at conference presentations and in lay summaries.Facilitating context factors included clear aims, time to contribute, confidence to contribute, and feeling valued and supported by researchers and other UAG members. Facilitating mechanisms included embedding the UAG within the study as a separate workstream, allocating time and resources to the UAG reflecting the value of input, and putting in place clear communication channels. Hindering factors included time commitment, geographical distance, and lack of standardised feedback mechanisms.ConclusionIncluding PPI as an integral component of the LAPCD study and providing the right context and mechanisms for involving the UAG helped maximise the programme’s effectiveness and impact.

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune responses in a patient with lymphoma and recent programmed death 1 (PD-1) inhibitor therapy with late onset of severe coronavirus disease 2019 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR+/CD38+ activation, interleukin 6, and interleukin 18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2–specific antibody responses were absent and SARS-CoV-2–specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses., We describe defects in severe acute respiratory syndrome coronavirus 2–specific immune responses and persistent viral replication in a patient with lymphoma. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.

The etiology of multiple myeloma (MM) remains incompletely understood; however, epidemiologic studies have suggested a possible link between exposure to environmental aromatic hydrocarbons-which serve as exogenous ligands for the aryl hydrocarbon receptor (AHR), which has been implicated in cancer biology-and development of monoclonal gammopathy of undetermined significance (MGUS) and MM. Herein, we demonstrate the functional expression of AHR in MM cell lines and primary human MM samples. AHR is expressed in putative MM 'stem cells' and advanced clinical stages of MM, and functionally contributes to MM tumor cell phenotype and proliferation. Antagonism of AHR directly impairs MM cell viability and increases MM cell susceptibility to immune-mediated clearance. Furthermore, our findings indicate that AHR antagonism may represent an effective means to enhance the function of other drugs, such as anti-CD38 antibodies, in future clinical studies. Taken together, these data identify AHR as a novel target for MM therapy.

PurposeOnly retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy.Methods and materialsEligible patients had low- or intermediate-risk prostate cancerbefore EBRT and biopsy-proven recurrence >30months after EBRT, with prostate-specific antigen levels

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.

Purpose/objective(s) Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. Materials/methods A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. Results Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for Conclusion HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

Introduction and objective Bladder preservation with trimodal therapy (TMT) has emerged as a feasible alternative strategy to treat localized muscle invasive bladder cancer (MIBC). There is lack of consensus regarding the treatment of local recurrence following TMT. The aim of this paper is to determine whether traditional NMIBC therapies can be applied to the management of NMIBC recurrences following TMT. Methods Using our institutional bladder cancer radiotherapy database, all patients with recurrent NMIBC following TMT were identified between 2008-2019. TMT patients were initially treated with maximal TURBT followed by combination chemotherapy/radiotherapy (weekly cisplatin 40 mg/m2 and 64-66 Gy to the bladder) with localizing Lipiodol injections. We compared NMIBC recurrent patients to a cohort of matched controls with primary NMIBC, hypothesizing that post-TMT patients treated with traditional NMIBC therapies would have outcomes similar to patients with primary NMIBC. Primary NMIBC patients were derived from our local NMIBC database and matching was based on clinical stage and grade in a 5:1 manner (controls:cases). Recurrences in the TMT group were managed according to the standard therapy for NMIBC. A descriptive analysis was performed between patients undergoing TMT with NMIBC recurrence and patients initially diagnosed with de novo NMIBC. Overall survival was calculated for each group and analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. Recurrence-free and cystectomy-free survival were analyzed using competing risk methods. Results Twelve patients out of 124 patients in the TMT cohort had NMIBC recurrence and were compared to 60 patients in a control group who were diagnosed with de-novo NMIBC. Median age of the TMT group was 78 [54 – 84] years versus 66 [23 – 88] years for the non-TMT group. Median follow-up for was 3.6 years versus 5.4 years in the non-TMT group. The clinical stage of the TMT NMIBC recurrences was Ta (n = 4), T1 (n = 3), CIS (n = 5). During the follow-up period, 38 (63%) further recurrences occurred in the non-TMT group compared to 2 (17%) in TMT group (P = 0.004). One patient (8%) from the TMT group required a cystectomy compared to 11 (18%) in the non-TMT group (P = 0.68). There were 2 non-cancer deaths (17%) in TMT group compared to one (2%) in the non-TMT group. Conclusion Our study demonstrates NMIBC recurrences post TMT can be successfully managed with endoscopic and adjuvant intravesical therapies.

Background Serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complements nucleic acid tests for patient diagnosis and enables monitoring of population susceptibility to inform the coronavirus disease 2019 (COVID-19) pandemic response. It is important to understand the reliability of assays with different antigen or antibody targets to detect humoral immunity after SARS-CoV-2 infection and to understand how antibody (Ab) binding assays compare to those detecting neutralizing antibody (nAb), particularly as we move into the era of vaccines. Methods We evaluated the performance of 6 commercially available enzyme-linked immunosorbent assays (ELISAs), including a surrogate virus neutralization test (sVNT), for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total or nAb. A result subset was compared with a cell culture–based microneutralization (MN) assay. We tested sera from patients with prior reverse transcription polymerase chain reaction–confirmed SARS-CoV-2 infection, prepandemic sera, and potential cross-reactive sera from patients with other non-COVID-19 acute infections. Results For sera collected >14 days post–symptom onset, the assay achieving the highest sensitivity was the Wantai total Ab at 100% (95% CI, 94.6%–100%), followed by 93.1% for Euroimmun NCP-IgG, 93.1% for GenScript sVNT, 90.3% for Euroimmun S1-IgG, 88.9% for Euroimmun S1-IgA, and 83.3% for Wantai IgM. Specificity for the best-performing assay was 99.5% for the Wantai total Ab, and for the lowest-performing assay it was 97.1% for sVNT (as per the Instructions for Use [IFU]). The Wantai Total Ab had the best agreement with MN at 98% followed by Euroimmun S1-IgA, Euro NCP-IgG, and sVNT (as per IFU) with 97%, 97% and 95%, respectively; Wantai IgM had the poorest agreement at 93%. Conclusions Performance characteristics of the SARS-CoV-2 serology assays detecting different antibody types are consistent with those found in previously published reports. Evaluation of the surrogate virus neutralization test in comparison to the Ab binding assays and a cell culture–based neutralization assay showed good result correlation between all assays. However, correlation between the cell-based neutralization test and some assays detecting Ab’s not specifically involved in neutralization was higher than with the sVNT. This study demonstrates the reliability of different assays to detect the humoral immune response following SARS-CoV-2 infection, which can be used to optimize serological test algorithms for assessing antibody responses post–SARS-CoV-2 infection or vaccination.

The University of Toronto – Department of Radiation Oncology (UTDRO) has had a well-established Fellowship Program for over 20 years. An assessment of its graduates was conducted to evaluate training experience and perceived impact on professional development. Graduates of the UTDRO Fellowship Program between 1991 and 2015 were the focus of our review. Current employment status was collected using online tools. A study-specific web-based questionnaire was distributed to 263/293 graduates for whom active e-mails were identified; questions focused on training experience, and impact on career progression and academic productivity. As a surrogate measure for the impact of UTDRO Fellowship training, a comparison of current employment and scholarly activities of individuals who obtained their Fellow of the Royal College of Physicians of Canada (FRCPC) designation in Radiation Oncology between 2000 and 2012, with (n = 57) or without (n = 230) UTDRO Fellowship training, was conducted. Almost all UTDRO Fellowship graduates were employed as staff radiation oncologists (291/293), and most of those employed were associated with additional academic (130/293), research (53/293), or leadership (68/293) appointments. Thirty-eight percent (101/263) of alumni responded to the online survey. The top two reasons for completing the Fellowship were to gain specific clinical expertise and exposure to research opportunities. Respondents were very satisfied with their training experience, and the vast majority (99%) would recommend the program to others. Most (96%) felt that completing the Fellowship was beneficial to their career development. University of Toronto, Department of Radiation Oncology Fellowship alumni were more likely to hold university, research, and leadership appointments, and author significantly more publications than those with FRCPC designation without fellowship training from UTDRO. The UTDRO Fellowship Program has been successful since its inception, with the majority of graduates reporting positive training experiences, benefits to scholarly output, and professional development for their post-fellowship careers. Key features that would optimize the fellowship experience and its long-term impact on trainees were also identified. Electronic supplementary material The online version of this article (10.1007/s13187-020-01767-5) contains supplementary material, which is available to authorized users.

BACKGROUND Lymph node metastases (LNM) rarely occur in adult extremity soft-tissue sarcoma (STS), affecting approximately 5% of patients. To the authors' knowledge, few studies to date have evaluated the prognosis and survival of patients with LNM. METHODS A retrospective review was performed of a single-center, prospectively collected STS database. Demographic, treatment, and oncologic data for patients with STS of the extremity with LNM were obtained from clinical and radiographic records. RESULTS Of 2689 patients with extremity STS, a total of 120 patients (4.5%) were diagnosed with LNM. LNM occurred most frequently among patients diagnosed with clear cell sarcoma (27.6%), epithelioid sarcoma (21.9%), rhabdomyosarcoma (17.3%), angiosarcoma (14.0%), and extraskeletal myxoid chondrosarcoma (9.3%). A total of 98 patients (81.7%) underwent LNM surgical resection. Patients with isolated LNM had a greater 5-year overall survival (57.3%) compared with patients with American Joint Committee on Cancer (AJCC) eighth edition stage IV STS with only systemic metastases (14.6%) or both LNM and systemic disease (0%; P

IntroductionThe oligometastatic (OM) disease hypothesis of an intermediate metastatic state with limited distant disease deposits amenable for curative therapies remains debatable. Over a third of prostate cancer (PCa) patients treated with radical prostatectomy and postoperative radiotherapy experience disease recurrence; these patients are considered incurable by current standards. Often the recurrence cannot be localised by conventional imaging (CT and bone scan). Combined anatomical imaging with CT and/or MR with positron emission tomography (PET) using a novel second-generation prostate-specific membrane antigen (PSMA) probe, [18F]DCFPyL, is a promising imaging modality to unveil disease deposits in these patients. A new and earlier molecularly defined oligorecurrent (OR) state may be amenable to focal-targeted ablative curative-intent therapies, such as stereotactic ablative radiotherapy (SABR) or surgery, thereby significantly delaying or completely avoiding the need for palliative therapies in men with recurrent PCa after maximal local treatments.Methods and analysisThis ongoing single-institution phase II study will enrol up to 75 patients total, to include up to 37 patients with response-evaluable disease, who have rising prostate-specific antigen (range 0.4–3.0 ng/mL) following maximal local therapies with no evidence of disease on conventional imaging. These patients will undergo [18F]DCFPyL PET-MR/CT imaging to detect disease deposits, which will then be treated with SABR or surgery. The primary endpoints are performance of [18F]DCFPyL PET-MR/CT, and treatment response rates following SABR or surgery. Demographics and disease characteristics will be summarised and analysed descriptively. Response rates will be described with waterfall plots and proportions.Ethics and disseminationEthics approval was obtained from the institutional Research Ethics Board. All patients will provide written informed consent. [18F]DCFPyL has approval from Health Canada. The results of the study will be disseminated by the principal investigator. Patients will not be identifiable as individuals in any publication or presentation of this study.Trial registration numbersNCT03160794

Background and purpose To identify a PSA threshold value at an intermediate follow-up time after low dose rate (LDR) prostate brachytherapy associated with cure, defined as long-term (10–15 year) freedom from prostate cancer. Materials and methods Data from 7 institutions for 14,220 patients with localized prostate cancer treated with LDR brachytherapy, either alone (8552) or with external beam radiotherapy (n = 1175), androgen deprivation (n = 3165), or both (n = 1328), were analyzed. Risk distribution was 42.4% favorable, 49.2% intermediate, and 8.4% high-risk. Patients with clinical failure before 3.5 years were excluded. Kaplan-Meier analysis was used with clinical failure (local, distant, regional or biochemical triggering salvage) as an endpoint for each of four PSA categories: PSA ≤ 0.2, >0.2 to ≤0.5, >0.5 to ≤1.0, and >1.0 ng/mL. PSA levels at 4 years (±6 months) in 8746 patients without clinical failure were correlated with disease status at 10–15 years. Results For the 77.1% of patients with 4-year PSA ≤ 0.2, the freedom-from-recurrence (FFR) rates were 98.7% (95% CI 98.3–99.0) at 10 years and 96.1% (95% CI 94.8–97.2) at 15 years. Three independent validation cohorts confirmed 97–99% 10-year FFR rates with 4-year PSA ≤ 0.2. Successive PSA categories were associated with diminished disease-free rates at 10 and 15 years. PSA category was strongly associated with treatment success (p Conclusions Since 98.7% of patients with PSA ≤ 0.2 ng/mL at 4 years after LDR prostate brachytherapy were disease-free beyond 10 years, we suggest adopting this biochemical definition of cure for patients with ≥4 years’ follow-up after LDR brachytherapy.

To report dosimetry, preliminary toxicity and health-related quality of life (HRQoL) outcomes of tumor-targeted dose-escalation delivered by integrated boost volumetric arc therapy (IB-VMAT) or MR-guided HDR brachytherapy (HDR) boost for prostate cancer.Patients diagnosed with localized prostate cancer, with at least 1 identifiable intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled in a prospective non-randomized phase II study. All patients received VMAT to the prostate alone (76 Gy in 38 fractions) plus a GTV boost: IB-VMAT (95 Gy in 38 fractions) or MR-guided HDR (10 Gy single fraction). GTV was delineated on mpMRI and deformably registered to planning CT scans. Comparative dosimetry using EQD2 assuming α/β 3 Gy was performed. Toxicity and health-related quality of life data (HRQoL) data were collected using CTCAE v.4.0, International Prostate Symptom Score (IPSS) and the Expanded Prostate Index Composite (EPIC).Forty patients received IB-VMAT and 40 HDR boost. Organs at risk and target minimal doses were comparable between the two arms. HDR achieved higher mean and maximal tumor doses (p 0.05). Median follow-up was 31 months (range 25-48); Acute grade G2 genitourinary (GU) toxicity was 30% and 37.5% in IB-VMAT and HDR boost, while gastrointestinal (GI) toxicity was 7.5% and 10%, respectively. Three patients developed acute G3 events, two GU toxicity (one IB-VMAT and one HDR boost) and one GI (IB-VMAT). Late G2 GU toxicity was 25% and 17.5% in the IB-VMAT and HDR boost arm and G2 GI was 5% and 7.5%, respectively. Two patients, both on the IB-VMAT arm, developed late G3 toxicity: one GI and one GU. No statistically significant difference was found in HRQoL between radiotherapy techniques (p 0.2). Urinary and bowel HRQoL domains in both groups declined significantly by week 6 of treatment in both arms (p 0.05) and recovered baseline scores at 6 months.Intraprostatic tumor dose escalation using IB-VMAT or MR-guided HDR boost achieved comparable OAR dosimetry, toxicity and HRQOL outcomes, but higher mean and maximal tumor dose were achieved with the HDR technique. Further follow-up will determine long-term outcomes including disease control.

332 Background: Patients (pts) with mRCC with SD have unfavorable outcomes and poor prognosis due to aggressive tumor behavior. Chemotherapy and targeted treatment are often of little benefit. However, recent studies have shown a survival benefit of immunotherapy (IO). Here, we report survival outcomes of pts with mRCC with SD treated with first line IO or chemotherapy or targeted treatment. In addition we performed a meta-analysis of recent practice changing phase III, IO trials in mRCC. Methods: This retrospective survival analysis was performed in pts with mRCC with SD treated with IO or non-IO treatment at Princess Margaret Cancer Centre (PM), Toronto. Demographics, disease characteristics and survival outcomes were collected. Progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method (log-rank). PFS and OS hazard ratios (HR) were calculated using cox proportional hazards model. We identified the major, practice changing clinical trials that reported survival outcomes of mRCC with SD treated with IO and performed a random-effects meta-analysis of HR for PFS and OS. We compared these pooled results to our single institution experience. Results: We identified 474 pts diagnosed with mRCC at PM between 2002 and 2019. In total, 44 (9.3%) pts had mRCC with SD who were treated with IO or non-IO. Of these, 29 (65.9%) pts had pure SD and 15 (34.1%) pts had mixed rhabdoid and SD features. Median age was 59.6 years (36-78) and 33 (75%) were male. Overall, as per the IMDC score, 3(6.8%), 21(47.7%) and 20(45.5%) pts were categorized as good, intermediate, and poor risk, respectively. Eight (18.2%) pts were treated with IO as first line of treatment, and 36 (81.8%) pts received non-IO. With a median follow up of 64.8 months (range, 45.7-83.8 months), the median OS for the whole mRCC with SD cohort was 15.6 months (95% CI: 8.6-22.5). The median OS in all pts treated with IO vs non-IO was not reached vs 10.3 months (95%CI: 1.49-19.1 months; p = 0.005), respectively. The HR for OS was 0.1 (95%CI: 0.01-0.78; p = 0.023) favoring IO receipt. The median PFS in all pts treated with IO vs non-IO was 24 months (95%CI: non-estimable) vs 5.4 months (95%CI: 2.9-7.8 months; p = 0.021), respectively. The HR for PFS was 0.3 (95%CI: 0.11-0.89; p = 0.03) favoring IO receipt. We identified through meta-analysis five phase III clinical trials reporting PFS and OS in pts with mRCC with SD who received IO. The overall HR for OS and PFS for the total cohort were 0.55 (95%CI: 0.41-0.74), and 0.53 (95%CI: 0.42-0.67), respectively. Conclusions: Our meta-analysis has confirmed the benefit of IO agents in mRCC with SD. While the numbers included in this retrospective review were small, they have provided real world corroboration of the trial findings. Pts with mRCC and SD benefit from IO treatment, which should be considered the standard of care for these patients.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A urologist referred a 69-year-old man for a radiotherapy opinion regarding a recently diagnosed adenocarcinoma of the prostate. Annual serum prostate-specific antigen (PSA) testing over 7 years demonstrated a rise in PSA from 1.36 ng/mL to 5.8 ng/mL, prompting a transrectal ultrasound that revealed a heterogeneous 37-mL gland containing no visualized hypoechoic nodules. Biopsy disclosed a Gleason score 3+4 (grade group 2) adenocarcinoma of the prostate. The synoptic report stated that six of 14 cores and 17% of the tissue were involved, with the greatest core involvement being 80% at the right apex. Perineural invasion was present without lymphovascular invasion. Disease was present bilaterally at the base, midgland, and apex.His medical history was significant only for treated peptic ulcer disease and he was taking no medication. His International Prostate Symptom Score was six of 35, and he reported being sexually active with good erectile function. There was no family history of prostate cancer. He is retired. Digital rectal examination revealed moderate benign prostatic hypertrophy with no suspicious nodules. A staging computerized tomography (CT) scan of the abdomen and pelvis and a whole-body bone scan ordered by his referring urologist reported no evidence of metastatic disease. The patient had discussed surgical options with his urologist and now wished to consider radiotherapy approaches.

To evaluate the ability of a multimodal patient education initiative to improve adherence to healthy bone behaviors (HBBs) in men with prostate cancer receiving androgen deprivation therapy (ADT). This was a pilot prospective, single-site, before-and-after clinical trial. The control arm (n = 51) received routine care. The intervention arm (n = 52) received multimodal HBB education which included a healthy bones prescription (BoneRx), focused face-to-face education with an oncology nurse or physician, and customized educational materials. The primary endpoints were feasibility of study methods and self-reported adherence to HBBs (vitamin D intake ≥ 1000 IU/day, calcium intake 1000–1500 mg/day, and exercise ≥ 150 min/week) at 3-month follow-up. Secondary endpoints included receipt of bone mineral density (BMD) testing. Patients were satisfied with the study intervention, found educational materials easy to understand, and felt that it increased their knowledge about osteoporosis. Although the intervention appeared to be associated with trends toward improved levels of vitamin D intake (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 0.74–4.5), calcium intake (OR 1.5, 95% CI 0.63–3.4), and exercise (OR 1.7, 0.75–3.9) as compared to the control arm, none of these were statistically significant. Patients who received the study intervention were more likely to receive BMD testing (OR 3.3, 95% CI 1.3–8.8). Although a brief, tailored educational intervention was feasible to implement and improve BMD test utilization, it did not increase HBB participation. Larger, well-designed trials are needed to clarify the effect of patient education interventions on HBB adherence. ClinicalTrials.gov ( NCT01973673 )

Background Breast angiosarcoma (AS) accounts for less than 1% of all breast cancers. The goal of this study was to determine patient outcomes in radiation-associated angiosarcoma of the breast (RAAS) and sporadic AS. We evaluated patterns of recurrence and predictors of breast AS survival. Methods Patients with pathologically confirmed AS from 1994 to 2014 referred to Mount Sinai Hospital/Princess Margaret Cancer Centre were included. Primary outcome was overall survival (OS). Secondary outcomes were disease-free survival (DFS), clinicopathologic characteristics, patterns of recurrence and factors predictive of survival. Kaplan-Meier and log-rank tests were used for OS and DFS. Results Twenty-six patients were included: 6 with sporadic AS and 20 with RAAS. Median follow-up was 24 months. Five-year OS for RAAS and sporadic subgroups were 44% and 40%, respectively (P = ns). Five-year DFS for RAAS and sporadic subgroups were 23% and 20%, respectively (P = ns). Overall recurrence rate was 67% with median time to recurrence of 11 months. Age, tumor depth, margin status, and tumor size were not statistically significant predictive factors for OS and DFS. Discussion Breast AS is associated with poor survival and high recurrence rates. Prognosis may be mainly determined by its aggressive biology. Referral to tertiary care centers for multimodality treatment is recommended.

Purpose/Objective(s) Tumor-targeted dose escalation may improve biochemical disease-free survival in patients with localized prostate cancer. We report outcomes of dose escalation using a strategy of simultaneous integrated boost or HDR brachytherapy boost. Materials/Methods Eighty patients with localized prostate cancer with gross tumor volume (GTV) identified on multiparametric magnetic resonance imaging (mpMRI) were enrolled in this phase 2 non-randomized trial (2012-2016). Patients with GTV > 5mm and less than 33% of total prostate volume were eligible. All patients received whole gland prostate volumetric arc therapy (VMAT), 76 Gy in 38 fractions. GTV dose escalation was delivered by integrated boost VMAT (IB-VMAT) of 95 Gy in 38 fractions (n = 40); or MR-guided HDR boost of 10 Gy in 1 fraction (n = 40). Choice of dose escalation strategy was by physician and/or patient choice. The primary end-point was 3-year local control rates determined by MR-guided biopsy and/or MRI alone. Toxicity data was collected using CTCAE v.4.0. Risk group categorization was similar between the arms; 5% low-, 75% intermediate-, and 20% high-risk. Three patients received 6-months ADT. Results Median (IQR) follow-up was 55.2 months (48.1-71.4). The overall 5-year biochemical failure-free survival was 92% (95% CI, 85-99), with 5 patients developing biochemical relapse (BCR); 1 IB-VMAT, 4 HDR boost. Local control data was available for 66 patients who agreed to the 3-year post-treatment biopsy (20) or MRI alone (46); 32 in IB-VMAT and 34 in HDR boost. Local control in the boost volume was achieved in 61 patients. One patient in the IB-VMAT arm had persistent disease on biopsy, and subsequently developed late BCR. Intraprostatic relapse outside the GTV was seen in 4 patients at last follow-up; 1 treated with IB-VMAT and 3 with HDR boost. All 4 patients developed BCR. Late G2 genitourinary (GU) toxicity was 22.5% and 27.5% in IB-VMAT and HDR boost, respectively. Late G2 gastrointestinal (GI) toxicity was 5% in each arm. Two G3 (1 GI, 1 GU) toxicities were seen in IB-VMAT. Conclusion Dose escalation to mpMRI-defined GTV provided high rates of local and biochemical control with limited severe late toxicity. Intraprostatic failures outside the boost volume appeared to correlate with BCR, which suggests that dose escalation to other subclinical intraprostatic regions may be required. Further characterization using molecular classification, beyond usual clinical parameters, may be warranted in order to improve local control.

Purpose The aim was to determine whether the enhanced soft tissue contrast provided by high-dose volumetric CT (HDVCT) can reduce inter-observer variability in delineating prostate compared to helical conventional CT (CCT) scans and 3T MRI scans for patients undergoing radical prostate cancer radiotherapy. Secondly, to quantify the potential PTV reduction with decreased inter-observer variability. Materials and methods A 320 slice volumetric CT scanner was used. The wide-detector coverage of 16 cm enabled volumetric image acquisition of prostate gland in one rotation. Three imaging studies were performed on ten patients. CCT and HDVCT were performed consecutively at the same coordinate system followed by MRI. Five radiation oncologists delineated the prostate. Results The inter-observer variability is 2.0 ± 0.6, 1.9 ± 0.4 and 1.8 ± 0.4 mm for CCT, HDVCT and MR respectively with the maximum at the apex region. Comparing inter-observer difference variability between CCT and HDVCT with MR indicates that observers have larger variations in contouring using CCT than HDVCT especially at apex. Jaccard index of HDVCT is significantly higher than CCT with a mean difference of 0.03 ( p = 0.011). Both MRI and HDVCT provide the opportunity for a 2 mm PTV margin reduction at the apex compared to CCT. Conclusion Inter-observer variability in delineation remains an important source of systematic error. HDCTV for treatment planning reduces this error without recourse to MRI and permits a PTV reduction of 2 mm at the apex. The margins required to account for residual error with any imaging modality are still greater than are used in typical current practice.

Purpose To evaluate long-term radiation toxicity and biochemical control of two moderately hypofractionated radiotherapy regimens for prostate cancer. Material and methods Eligible men with localized prostate cancer received image-guided intensity modulated radiotherapy (IG-IMRT) to a dose of 60 or 66 Gy in 3 Gy fractions in a phase II trial. Endpoints included late gastrointestinal (GI) and genitourinary (GU) toxicity and biochemical failure (FFBF). Results Ninety-six men received 60 Gy and 27 received 66 Gy. Accrual to the 66 Gy cohort terminated early due to excessive Grade 3–4 late toxicity. Median follow-up was 128 months (60 Gy) and 108 months (66 Gy). In the 60 Gy cohort, cumulative late Grade ⩾2 GI and GU toxicity at 8 years was 4% and 12% respectively. In the 66 Gy cohort, late Grade ⩾2 GI and GU toxicity was 21% and 4% respectively at 8 years. The 5- and 8-year FFBF for 60 Gy was 81% and 66%, and for 66 Gy was 88% and 80%. Conclusions Moderate hypofractionation with IG-IMRT to 60 Gy was associated with favorable late toxicity although late urinary toxicity and biochemical failures were observed beyond 5 years. Dose escalation to 66 Gy was associated with significantly worse late toxicity.

Background Neoadjuvant or adjuvant radiotherapy (RT) for extremity soft tissue sarcoma (STS) confers significant local control benefit. To determine patterns of practice, a survey of RT planning practices was undertaken. Method Members of the Connective Tissue Oncology Society and Canadian Association of Radiation Oncology participated in this survey pertaining to general practice patterns of RT for extremity STS, patterns of contouring and planning, and use of quality control measures such as guidelines, tumor boards, and quality assurance rounds. Results A total of 58 radiation oncologists treating extremity STS from 12 countries responded. 89.7% work in academically affiliated centres, and 55.2% saw at least 20 cases of extremity STS per year. Most (96.7%) had access to multidisciplinary sarcoma boards (85.5% of those discussed every referred sarcoma case). 78.6% held quality assurance rounds. Most (92.9%) used planning guidelines. Pre-operative RT was used nearly twice as much as post-operative RT. CT simulation with MR fusion was used by 94.6%. Patterns of clinical target volume (CTV) contouring for both superficial and deep STS were variable. 69.8% contoured a normal soft tissue strip for extremity sarcoma, 13.5% without routine constraints and the remainder with various constraints. Most (91.1%) used 50 Gy in 25 fractions pre-operatively and 39.6% reported using post-operative RT boost for positive margins. Post-operative dose was more variable from 59.4 Gy to 70 Gy. Conclusion Major aspects of RT planning for extremity STS were similar among the responders, and most were academically affiliated. Over twice as many employed pre-operative as opposed to post-operative RT. There was considerable heterogeneity in use of: margins for contouring, normal soft tissue strip as an avoidance structure, and boost for positive margins. This survey shows variable patterns of practice and identifies areas that may require further research.

Background Patients with newly diagnosed non-metastatic prostate adenocarcinoma are typically classified as at low, intermediate, or high risk of disease progression using blood prostate-specific antigen concentration, tumour T category, and tumour pathological Gleason score. Classification is used to both predict clinical outcome and to inform initial management. However, significant heterogeneity is observed in outcome, particularly within the intermediate risk group, and there is an urgent need for additional markers to more accurately hone risk prediction. Recently developed web-based visualization and analysis tools have facilitated rapid interrogation of large transcriptome datasets, and querying broadly across multiple large datasets should identify predictors that are widely applicable. Methods We used camcAPP, cBioPortal, CRN, and NIH NCI GDC Data Portal to data mine publicly available large prostate cancer datasets. A test set of biomarkers was developed by identifying transcripts that had: 1) altered abundance in prostate cancer, 2) altered expression in patients with Gleason score 7 tumours and biochemical recurrence, 3) correlation of expression with time until biochemical recurrence across three datasets (Cambridge, Stockholm, MSKCC). Transcripts that met these criteria were then examined in a validation dataset (TCGA-PRAD) using univariate and multivariable models to predict biochemical recurrence in patients with Gleason score 7 tumours. Results Twenty transcripts met the test criteria, and 12 were validated in TCGA-PRAD Gleason score 7 patients. Ten of these transcripts remained prognostic in Gleason score 3 + 4 = 7, a sub-group of Gleason score 7 patients typically considered at a lower risk for poor outcome and often not targeted for aggressive management. All transcripts positively associated with recurrence encode or regulate mitosis and cell cycle-related proteins. The top performer was BUB1, one of four key MIR145-3P microRNA targets upregulated in hormone-sensitive as well as castration-resistant PCa. SRD5A2 converts testosterone to its more active form and was negatively associated with biochemical recurrence. Conclusions Unbiased mining of large patient datasets identified 12 transcripts that independently predicted disease recurrence risk in Gleason score 7 prostate cancer. The mitosis and cell cycle proteins identified are also implicated in progression to castration-resistant prostate cancer, revealing a pivotal role for loss of cell cycle control in the latter. Electronic supplementary material The online version of this article (10.1186/s12894-018-0433-5) contains supplementary material, which is available to authorized users.

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.