Framework Development: Standardizing Definition of Advanced Practice Radiation Therapy Activities for Clinical Workload Quantification.

Purpose: Advanced practice (AP) in radiation therapy (RT) is being implemented around the globe. In an effort to advance the understanding of the similarities and differences in APRT roles in Ontario, Canada, a community of practice (CoP) sought ways to provide quantitative data on the nature of APRT clinical activities and the frequency with which these activities were being executed. Methods: In 2017, a consensus building project involving 20 APRTs and 14 radiation therapy (RT) department managers in Ontario was completed to establish a mechanism to quantify APRTs' clinical impact. In Round 1 & 2, expert feedback was gathered to generate an Advanced Practice (AP) Activity List. In Round 3: 20 APRTs completed an online survey to assess the importance and applicability of each AP Activity to their role using Likert scale (0-5). A final AP Activity List & Definitions was generated. Results & discussion: Round 1: Forty-seven AP activities were identified. Round 2: 3/14 RT managers provided 145 feedback statements on Round 1 AP Activity List. The working group used RT managers' feedback to clarify AP activities and definitions, specifically merging 33 unique AP activities to create 11 inclusive AP activities and eliminating 8 activities identified from Round 1. The most inclusive AP activity created was #1 New Patient Consultation, this AP Activity is merged from 7 unique AP activities. Incorporating RT managers' feedback with the internal AP clinical workload lists from 2 Ontario cancer centres resulted in a revised AP Activity List with 20 AP inclusive activities. Round 3: 14/20 APRTs provided Likert scores on this revised list. The most applicable AP activities (mean score) were #16 Technical Consultation (4.0), #15 Contouring Target Volume (3.8) and #2 Planning Consultation (3.8); the least applicable was #18 MR Applicator Assessment (0.9). Conclusions: This is the first systematic attempt to build consensus on AP clinical activities. Non-clinical APRT activities related to research, education, innovation, and program development were not in the scope of this project. The Final AP Activity List & Definitions serves as a framework that allows standardized and continuous monitoring of AP clinical activities and impact.

Stereotactic body radiotherapy for distant metastases to the head and neck.

PURPOSE: To report clinical outcomes for patients with metastatic disease to the head and neck (HN) treated with stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of patients treated with SBRT to HN sites from 2012 to 2020 was conducted. Treatment indications included the following: oligometastases, oligoprogression, and control a dominant area of progression (DAP). Kaplan-Meier method was used to estimate local control (LC), regional control (RC), overall survival (OS), and progression-free survival (PFS). Univariable (UVA) and multivariable analyses (MVA) were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: Fifty-six patients (58 lesions) were analysed with a median follow-up of 16 months. Primary sites included lung (25.0%), kidney (19.6%), breast (19.6%) and other (35.8%). SBRT indications were as follows: oligometastases (42.9%), oligoprogression (19.6%) and local control of a dominant area of progression (37.5%). Most patients received SBRT to a single neck node (n = 47, 81.0%). Median SBRT dose was 40 Gy (range 25-50 Gy) in five fractions, with a median biologically effective dose (BED10) of 72 Gy (range 37.5-100 Gy). One- and 2-year LC and RC rates were 97.6% and 72.7% as well as 100% and 86.7%, respectively. Median OS was 19.2 months (95% [CI] 14.8-69.4), and median PFS was 7.4 months (95% [CI] 5.2-11.9). The 1-year OS and PFS rates for oligometastases, oligoprogression and DAP were 95.8%, 63.6% and 38.1% (p = 0.0039) as well as 56.5%, 27.3% and 19.1% (p = 0.0004), respectively. On MVA, treatment indication and histology were predictive for OS, while indication and prior systemic therapy were predictive for PFS. Cumulative late grade 3 + toxicity rate was 11.3%, without grade 5 events. CONCLUSION: The use of SBRT for metastatic disease to the HN provided excellent LC rates with low rates of regional failure and an acceptable toxicity profile, highlighting its utility in these patients. Patients with oligometastatic disease had better OS and PFS than others.

Outcomes for oligometastatic head and neck cancer treated with stereotactic body radiotherapy: Results from an international multi-institutional consortium.

BACKGROUND: We report the results of an international multi-institutional cohort of oligometastatic (OMD) head and neck cancer (HNC) patients treated with SBRT. METHODS: Patients with OMD HNC (≤5 metastases) treated with SBRT between 2008 and 2016 at six institutions were included. Treated metastasis control (TMC), progression-free survival (PFS), and overall survival (OS) were analyzed by multivariable analysis (MVA). RESULTS: Forty-two patients with 84 HNC oligometastases were analyzed. The TMC rate at 1 and 2 years were 80% and 66%, with a median time to recurrence of 10.1 months. The median PFS and OS were 4.7 and 23.3 months. MVA identified a PTV point maximum (BED)10 > 100 Gy as a predictor of improved TMC (HR = 0.31, p = 0.034), and a cumulative PTV > 48 cc as having worse PFS (HR = 2.99, p < 0.001). CONCLUSION: Favorable TMC and OS was observed in OMD HNCs treated with SBRT.

Predictors of pathologic fracture and local recurrence following stereotactic body radiation therapy to 505 non-spine bone metastases.

PURPOSE: Stereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this retrospective study, we report outcomes and predictors of local failure (LF) and pathological fracture (PF) post-SBRT for NSBM using a mature single-institution database. METHODS: Patients with NSBM treated with SBRT between 2011 and 2021 were identified. The primary objective was to assess the rates of radiographic LF. Secondary objectives were to assess the rates of in-field PF, overall survival (OS), and late grade ≥ 3 toxicity. Competing risks analysis was used to assess rates of LF and PF. Univariable regression and multivariable regression (MVR) were performed to investigate predictors of LF and PF. RESULTS: A total of 373 patients with 505 NSBM were included in this study. Median follow-up was 26.5 months. The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. Lytic NSBM (HR = 2.18; p < 0.01), a lower biologically effective dose (HR = 1.11 per 5 Gy10 decrease; p = 0.04), and a PTV ≥ 54 cc (HR = 4.32; p < 0.01) predicted for a higher risk of LF on MVR. Lytic NSBM (HR = 3.43; p < 0.01), mixed (lytic/sclerotic) lesions (HR = 2.70; p = 0.04), and rib metastases (HR = 2.68; p < 0.01) predicted for a higher risk of PF on MVR. CONCLUSION: SBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of PF. We identify predictors of both LF and PF that can serve to inform practice and trial design.

The impact of local control on widespread progression and survival in oligometastasis-directed SBRT: Results from a large international database.

PURPOSE: We investigated the impact of local control (LC) on widespread progression (WSP) and overall survival (OS) in patients treated to all extracranial oligometastases (OMs) at presentation to SBRT in this retrospective review across 6 international centers. MATERIALS/METHODS: Relationships between LC status of SBRT-directed OMs and OS and WSP (>5 new active/untreated lesions) were explored using Cox and Fine-Gray regression models, adjusting for radioresistant histology and pre-SBRT systemic therapy receipt. The association between LC and dosimetric predictors was analyzed with competing risk regression using death as a competing risk and across a wide range of simulated α/ßratios. RESULTS: In total, 1700 OMs in 1033 patients were analyzed, with 25.2% NSCLC, 22.7% colorectal, 12.8% prostate, and 8.1% breast histology. Patients who failed locally in any SBRT-directed OM within 6 mo were at 3.6-fold higher risk of death and 2.7-fold higher risk of WSP compared to those who remained locally-controlled (p < 0.001). Similar associations existed for each duration of LC investigated through 3 yrs post-SBRT. There was no significant difference in risk of WSP or death between patients who failed in a subset of SBRT-treated lesions vs. patients who failed in all lesions. Minimum dose (Dmin) to the GTV/ITV was most predictive of LC when compared to prescription dose, PTV Dmin, and PTV Dmax. Sensitivity analysis for achieving 1-yr LC > 95% found thresholds of 41.2 Gy and 55.2 Gy in 5 fractions for smaller (< 27.7 cc) and larger radioresistant lesions, respectively. CONCLUSION: This large multinational cohort suggests that the duration of LC following OM-directed SBRT strongly correlates with WSP and OS.

Toxicity and Efficacy of Multitarget Thoracic Stereotactic Body Radiation Therapy.

PURPOSE: With the increasing use of stereotactic body radiation therapy (SBRT) for primary and metastatic cancer, use of multitarget thoracic (MTT) SBRT is rising. Given the limited safety and efficacy data, we report the experience of this strategy from a large academic center. METHODS AND MATERIALS: Between 2012 and 2021, patients who received SBRT for ≥2 thoracic targets separated by ≤1 year were retrospectively reviewed. The primary endpoint was clinically significant radiation pneumonitis (CSRP) requiring steroids, oxygen, or intubation. Secondary endpoints included local failure (LF), initiation or change of systemic therapy (ICST), progression-free survival, and overall survival. Competing risk analysis was used to evaluate the cumulative incidence of CSRP, LF, and ICST. Univariate and multivariable analyses were performed to look for clinical and dosimetric predictive factors of CSRP and LF. RESULTS: One hundred ninety patients (481 lesions) were treated with MTT SBRT with a median follow-up of 19.7 months. Indications for SBRT were oligometastases (n = 70; 36.8%), oligoprogression (n = 62; 32.6%), curative intent in patients with primary lung cancer (n = 37; 19.5%), and control of dominant areas of metastatic progression (n = 21; 11.0%). The number of irradiated tumors ranged from 2 to 7 and the majority of SBRT courses were delivered simultaneously (88.2%). Overall, 14 patients (7.4%) had CSRP, with 5 cases requiring oxygen. The cumulative incidence of CSRP at 6 and 12 months was 5.3% and 7.6%, respectively. The cumulative incidence of LF at 2 years was 10.5%. The cumulative incidence of ICST at 2 years was 41.1%. Median progression-free survival was 11.8 months and median overall survival was 51.3 months. On multivariable analysis, a higher lung V35Gy (hazard ratio, 2.59; P = .02) was a statistically significant predictor of CSRP and colorectal histology predicted for higher LF (hazard ratio, 2.12; P = .02). CONCLUSIONS: In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Optimizing plans to lower the lung V35Gy may decrease the risk of CSRP.

Stereotactic Body Radiation Therapy for Metastases in Long Bones.

PURPOSE: To evaluate the cumulative incidence of fracture and local failure and associated risk factors after stereotactic body radiation therapy (SBRT) for long bone metastases. METHODS AND MATERIALS: Data from 111 patients with 114 metastases in the femur, humerus, and tibia treated with SBRT in 7 international centers between October 2011 and February 2021 were retrospectively reviewed and analyzed using a competing risk regression model. RESULTS: The median follow-up was 21 months (range, 6-91 months). All but 1 patient had a Karnofsky performance status ≥70. There were 84 femur (73.7%), 26 humerus (22.8%), and 4 tibia (3.5%) metastases from prostate (45 [39.5%]), breast (22 [19.3%]), lung (15 [13.2%]), kidney (13 [11.4%]), and other (19 [16.6%]) malignancies. Oligometastases accounted for 74.8% of metastases and 28.1% were osteolytic. The most common total doses were 30 to 50 Gy in 5 daily fractions (50.9%). Eight fractures (5 in the femur, 2 in the tibia, and 1 in the humerus) were observed with a median time to fracture of 12 months (range, 0.8-33 months). In 6 out of 8 patients, fracture was not associated with local failure. The cumulative incidence of fracture was 3.5%, 6.1%, and 9.8% at 1, 2, and 3 years, respectively. The cumulative incidence of local failure (9/110 metastases with imaging follow-up) was 5.7%, 7.2%, and 13.5% at 1, 2, and 3 years, respectively. On multivariate analysis, extraosseous disease extension was significantly associated with fracture (P = .001; subhazard ratio, 10.8; 95% confidence interval, 2.8-41.9) and local failure (P = .02; subhazard ratio, 7.9; 95% confidence interval, 1.4-44.7). CONCLUSIONS: SBRT for metastases in long bones achieved high rates of durable local metastasis control without an increased risk of fracture. Similar to spine SBRT, patients with extraosseous disease extension are at higher risk of local failure and fracture.

Conditional Survival of Patients With Extracranial Oligometastatic Treated With Stereotactic Body Radiation Therapy: An International Consortium Study.

PURPOSE: Prolonged survivorship is increasingly observed in patients with oligometastases (OM) treated with stereotactic body radiation therapy (SBRT). The purpose of this study was to study the conditional survival of patients with OM, which can provide more detailed prognostic information over time by considering time already survived. METHODS AND MATERIALS: A multi-institutional database consisting of 1033 patients with OM (≤5 metastases) treated with SBRT between 2006 and 2017 was analyzed. Conditional overall survival (OS) and progression-free survival (PFS) in 3 years were obtained at multiple time points for all patients and by primary cancer type. Cox regression was used to determine trends in conditional OS and PFS. Changes in the predictors of OS and PFS over time were also determined by multivariable Cox regression. RESULTS: The median follow-up was 24 months (0.3-105 months). Three-year OS and PFS at baseline were 56.7% and 23.2%, respectively. The OS in 3 years conditional on having survived for 3, 6, 12, and 24 months did not significantly change over time (56.7%, 55.4%, 55.8%, and 50.6%, respectively; P = .60). In contrast, the probability of PFS in 3 years conditional on having survived progression-free for 3, 6, 12, and 24 months significantly increased over time (23.6%, 27.3%, 35.1%, and 48.8%, respectively; P < .001). When stratified by primary site, conditional PFS significantly increased over time for patients with colorectal, breast, or kidney cancer. Conditional OS remained stable for patients with non-small cell lung cancer or kidney cancer but significantly decreased over time for patients with prostate, breast, or colorectal cancer. Changes in significant prognostic factors of OS and PFS over time were also observed. CONCLUSIONS: Analysis of conditional survival among patients with OM showed that as patients survived longer, their prognosis for further survival remained stable or decreased. However, patients who survived longer without disease progression had increased probability of PFS over time.

An analysis of a large multi-institutional database reveals important associations between treatment parameters and clinical outcomes for stereotactic body radiotherapy (SBRT) of oligometastatic colorectal cancer.

PURPOSE: In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database. METHODS: Patients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes. RESULTS: We identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression. CONCLUSION: This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED10 should be considered if feasible and safe.

Development of a Prognostic Model for Overall Survival in Patients With Extracranial Oligometastatic Disease Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Patients with oligometastatic disease (OMD) can experience durable disease control with ablative therapy to all sites of disease. Stereotactic body radiation therapy (SBRT) is an important modality in the management of OMD, although a validated prognostic model for OMD treated with SBRT is currently lacking. The purpose of this study was to develop a prognostic model for overall survival (OS) in patients with OMD treated with SBRT. METHODS AND MATERIALS: A multi-institutional database of patients with extracranial OMD treated with SBRT was used for model development. The final prognostic model was generated in a training set using recursive partitioning analysis representing 75% of the population. Model performance was evaluated in the reserved test set. RESULTS: The analysis included 1033 patients. The median OS for the entire cohort was 44.2 months (95% confidence interval [CI], 39.2-48.8 months). The variables used in the regression tree, in order of importance, were primary histology, lung-only OMD on presentation, the timing of OMD presentation, and age at the start of SBRT. A full 5-category risk stratification system based on the terminal nodes possessed fair to good discriminative power with a Harrell concordance statistic of 0.683 (95% CI, 0.634-0.731) and a time-dependent area under the receiver operating characteristic curve of 0.709 (95% CI, 0.706-0.711) in the test set, with good calibration. A simplified risk stratification system consisting of 3 risk categories was also proposed for greater ease of use with comparable performance. CONCLUSIONS: A clinical prognostic model for OS in patients with extracranial OMD treated with SBRT has been developed and validated.

A survey to explore the psychological impact of the COVID-19 pandemic on radiation therapists in Norway and Canada: A tale of two countries.

INTRODUCTION: Several studies have demonstrated the psychological impact of the COVID-19 pandemic on health care providers. However, there is little known about how the COVID-19 pandemic has impacted radiation therapists (RTs) in Norway or Canada. The aim of this investigation was to study the psychological impact of working during the COVID-19 pandemic among RTs in Canada and Norway. METHODS: Online surveys were administered to a convenience sample of RTs and RT department managers. Approximately 2000 and 300 RTs were invited to participate from Canada and Norway, respectively. The RT survey collected information on demographics, work-related stressors, psychological impact, quality of life, and workplace support programmes. The RT manager survey collected information on departmental changes, patient volumes, staff shortages and redeployment, personal protective equipment, and infection control measures. Descriptive analysis, group comparisons and logistic regression were used to examine the impact of COVID-19 on RTs in the two countries, while open-ended questions were examined through thematic analysis. RESULTS: Work-related stress and anxiety were prevalent among Canadian (n = 155) and Norwegian RTs (n = 124), with Canadian RTs reporting higher levels. Fear of transmission, changes in PPE usage, and changes in staffing were reported as the most frequent work-related stressors. Themes related to working during the pandemic included: generalised anxiety; physical, emotional and cognitive symptoms of stress; and loneliness, as well as negative impact on health and quality of relationships. Survey findings from RT department managers in Canada (n = 12) and Norway (n = 13) suggest that the pandemic had an organisational impact on RT departments due to implemented infection control measures and changes in staffing. CONCLUSION: The COVID-19 pandemic has led to similar stressors amongst Canadian and Norwegian RTs but relatively higher levels of psychological impact among Canadian RTs. Findings demonstrate the importance of mental health support programmes in the workplace to mitigate the psychological impact of the COVID-19 pandemic on RTs.

Translating interprofessional collaboration competencies to an international research team.

INTRODUCTION: While there has been strong emphasis on enhancing interprofessional education and interprofessional care in the published literature, there is relatively little literature focused on advancing interprofessional research. In extrapolating from the current frameworks of interprofessional collaboration (IPC), it becomes clear that the core competencies of IPC are transferable to research teams. The aim of this paper is to present our experience of an international research team framed within core competencies for IPC. METHODS: A simplified narrative inquiry approach was used to share the experience of an international research team framed within six core competencies of IPC. RESULTS AND DISCUSSION: By way of our international research collaboration, we demonstrate the translation of key core competencies for IPC. We share key learnings and mitigation strategies for the successful outcomes of the research team. CONCLUSION: To embark on a successful international research collaboration requires integrating IPC core competencies across the entire research continuum. In addition to the core competencies of collaboration, enablers to success also include digital collaborative forums, existing professional relationships and research projects that offer global meaning and value.

Stereotactic body radiotherapy for head and neck skin cancer.

AIM: To report outcomes of Stereotactic Body Radiotherapy (SBRT) for head and neck skin cancer (HNSC) patients treated at a high-volume center. MATERIALS: A retrospective review of HNSC SBRT patients from 2012 to 2019 was conducted. Kaplan-Meier method was used to estimate local control (LC), locoregional control (LRC) outside of SBRT field, overall survival (OS), progression-free survival (PFS) and late toxicity (LT). Univariate and multivariate analyses were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: One hundred and six medically unfit HNSC patients (112 lesions) were included. Median follow-up was 8 months. Median patient age at diagnosis was 86 years (range: 56-102 years). The majority of patients had advanced disease (overall stage III-IV [n = 90, 85%]) with median gross tumor volumes (GTV) of 31 cm3 (range: 17-56 cm3). Treated sites were: primary (n = 51), nodal (n = 47) or primary plus nodal (n = 8). SBRT doses ranged from 32-50 Gy delivered twice weekly in 4-6 fractions to the gross tumor volume (GTV). One and 2-year LC rates were 78% (69-88) and 67% (53-82), respectively. One-year LRC outside of SBRT field, OS, PFS and LT rates were 72% (62-84), 53% (43-65), 52% (40-62), and 7% (2-17), respectively. Thirty-three patients (31%) developed acute grade ≥ 3 treatment-related toxicity, most commonly dermatitis (n = 31). Nine patients (8%) experienced late grade ≥ 3 toxicity, including 7 grade 3 fibrosis, 1 grade 3 bone radionecrosis and 1 grade 4 skin ulceration. No treatment-related deaths (grade 5) were observed. CONCLUSION: SBRT provides durable disease control with acceptable toxicity for medically unfit high-risk HNSC patients unable to undergo standard of care curative treatment approaches.

Volumetric burden of metastatic lesions drives outcomes in patients with extracranial oligometastatic disease.

BACKGROUND: We hypothesized that the total volume of metastases at initial oligometastatic (OM) presentation to stereotactic body radiation therapy (SBRT) is an important prognostic factor that can refine the definition of OM disease. METHODS: Patients with extracranial oligometastatic cancer (≤5 lesions) treated with SBRT were included in an international multi-institutional database. Multivariable Cox and competing risks regression models were used to determine the relationship between distant progression-free survival (DPFS), widespread progression (WSP), and overall survival (OS) with the total planning target volume (PTV) at initial OM presentation to SBRT. All models were adjusted for histology, pre-SBRT systemic therapy, osseous-only lesions, and number of metastases. RESULTS: In total, 961 patients were included. The median follow-up was 24.4 months (IQR: 13.8-37.5). Total PTV had a significant effect on DPFS in the first 18 months after SBRT and was most profound in the first 6 months, when each twofold increase in total PTV conferred a 40.6% increased risk of distant progression (p < 0.001). Each twofold increase in total PTV increased the risk of WSP by 45.4% in the first 6 months (p < 0.001). Total PTV had a significant effect on OS in the first 2 years after SBRT, with each twofold PTV change increasing the risk of death by 60.7% during the first 6 months (p < 0.001) and by 34% thereafter (p < 0.001). Exploratory gross tumor volume (GTV) analysis confirmed the PTV-based observations. CONCLUSION: The total volumetric burden of metastases at initial OM presentation to SBRT is strongly and independently prognostic for the risk of distant and widespread progression and survival. We propose that this metric should drive the definition of OM disease and guide treatment decision-making.

An international pooled analysis of SBRT outcomes to oligometastatic spine and non-spine bone metastases.

PURPOSE: There is a paucity of data on SBRT to non-spine bone (NSB) lesions compared to spine metastases. We report local recurrence (LR), widespread progression (WSP), and overall survival (OS) for oligometastatic patients treated to bone lesions with SBRT and investigate the hypothesis that outcomes are different between patients with spine and non-spine bone oligometastatic disease. METHODS: Patients with oligometastatic disease (≤5 cumulative extracranial metastases) treated with bone SBRT at 6 international institutions from 2007 to 2016 were reviewed. Fine and Gray competing risks and Cox regressions were used to analyze univariable and multivariable relationships between disease/treatment factors and outcomes. RESULTS: In total, 288 spine and 233 NSB lesions are reported in 356 patients. Cumulative incidence of LR across all bone lesions was 6.3%, 12.6% and 19.3% at 6 mo, 1 yr and 2 yrs. While univariable analysis suggested inferior LC and OS in spine patients, this did not hold true in multivariable analysis. The final regression model for LR in NSB lesions included PTV ≥ median of 31.8 cc (HR 5.02, p = 0.014) and primary histology, with RCC and NSCLC conferring a 10.8- and 6.5-fold increased risk of LR compared to prostate histology, respectively. The spine LR model included radioresistant histology (HR 2.11, p = 0.0051), PTV Dmin (BED10) ≥ median of 19.1 Gy (HR 0.46, p = 0.0085), and epidural disease (HR 1.99, p = 0.016). CONCLUSION: This large multi-institutional series reports comparably excellent response to SBRT for a balanced distribution of oligometastatic NSB and spine lesions. Dose escalation for large and/or radioresistant NSB lesions should be explored, given the typical lack of an immediately adjacent dose-limiting critical structure.

Late metastatic presentation is associated with improved survival and delayed wide-spread progression after ablative stereotactic body radiotherapy for oligometastasis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastatic disease (OMD), but the effect of metastasis timing on patient outcomes remains uncertain. METHODS: An international database of patients with OMD treated with SBRT was assembled with rigorous quality assurance. Early versus late metastases were defined as those diagnosed ≤24 versus >24 months from the primary tumor. Overall survival (OS), progression-free survival (PFS), and incidences of wide-spread progression (WSP) were estimated using multivariable Cox proportional hazard models stratified by primary tumor types. RESULTS: The database consists of 1033 patients with median follow-up of 24.1 months (0.3-104.7). Late metastatic presentation (N = 427) was associated with improved OS compared to early metastasis (median survival 53.6 vs. 33.0 months, hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.47-0.72, p < 0.0001). Patients with non-small cell lung cancer (NSCLC, N = 255, HR 0.49, 95% CI: 0.33-0.74, p = 0.0005) and colorectal cancer (N = 235, HR 0.50, 95% CI: 0.30-0.84, p = 0.008) had better OS if presenting with late metastasis. Late metastasis correlated with longer PFS (median 17.1 vs. 9.0 months, HR 0.71, 95% CI: 0.61-0.83, p < 0.0001) and lower 2-year incidence of WSP (26.1% vs. 43.6%, HR 0.60, 95% CI: 0.49-0.74, p < 0.0001). Fewer WSP were observed in patients with NSCLC (HR 0.52, 95% CI: 0.33-0.83, p = 0.006) and kidney cancer (N = 63, HR 0.37, 95% CI: 0.14-0.97, p = 0.044) with late metastases. Across cancer types, greater SBRT target size was a significant predictor for worse OS. CONCLUSION: Late metastatic presentation is associated with improved survival and delayed progression in patients with OMD treated with SBRT.

Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis.

Importance: The outcomes and factors that influence survival in patients with oligometastasis (OM) are not well understood and have not been well described in large-scale studies. Objective: To evaluate overall progression-free survival (PFS), widespread progression (WSP) outcomes, and survival factors from a pooled data set of 1033 patients with OM treated with stereotactic body radiotherapy (SBRT). Design, Setting, and Participants: Case series from January 1, 2008, to December 31, 2016. The dates of analysis were April 2019 to May 2020. The setting was multi-institutional tertiary care hospitals. Participants were consecutive patients with 5 or fewer extracranial OMs whose primary tumor was treated curatively. Exposure: Definitive SBRT. Main Outcomes and Measures: Overall survival (OS), progression-free survival, rate of WSP, patterns of failure, and factors altering OS. Results: In the largest international OM case series to date (1033 participants) (mean age, 68.0 years [range, 18.0-94.3 years]; 601 [58.2%] men), 1416 SBRT courses were delivered to patients with 1 OM (596 [57.7%]), 2 OMs (245 [23.7%]), 3 OMs (105 [10.2%]), 4 OMs (55 [5.3%]), and 5 OMs (32 [3.1%]). The median follow-up was 24.1 months (range, 0.3-104.7 months), and the median OS was 44.2 months (95% CI, 39.2-48.8 months). The median PFS was 12.9 months (95% CI, 11.6-14.2 months), and the median time to WSP was 42.5 months (95% CI, 36.8-53.5 months). The OS rates were 84.1% (95% CI, 81.7%-86.2%) at 1 year, 56.7% (95% CI, 53.0%-60.2%) at 3 years, and 35.2% (95% CI, 30.1%-40.3%) at 5 years. The 3-year OS, PFS, and WSP rates were 56.7% (95% CI, 53.0%-60.2%), 23.0% (95% CI, 20.2%-25.9%), and 45.2% (95% CI, 41.4%-48.9%), respectively. The 5-year OS, PFS, and WSP rates were 35.2% (95% CI, 30.1%-40.3%), 14.8% (95% CI, 11.9%-17.9%), and 54.5% (95% CI, 49.8%-59.2%), respectively. At the time of first progression, 342 patients (33.1%) had recurrence of OM disease, and 230 patients (22.3%) underwent subsequent ablative therapies to all known metastatic sites. Multivariable analyses identified primary tumor type (hazard ratio [HR], 3.73; 95% CI, 1.75-7.94; P < .001 for breast; 5.75; 95% CI, 2.88-11.46; P < .001 for colorectal; 4.67; 95% CI, 2.12-10.31; P < .001 for kidney; 10.61; 95% CI, 5.36-20.99; P < .001 for lung; and 12.00; 95% CI, 6.06-23.76; P < .001 for other [with prostate being the reference group]), metachronous OM presentation more than 24 months since initial diagnosis (HR, 0.63; 95% CI, 0.49-0.80; P < .001), metastases confined to the lung only (HR, 0.58; 95% CI, 0.48-0.72; P < .001), and nodal or soft-tissue metastases only (HR, 0.49; 95% CI, 0.26-0.90; P = .02) as survival factors. Sixty-six (6.4%) grade 3 or higher toxic effects were observed, including 1 (0.1%) grade 5 event. Conclusions and Relevance: This study found favorable long-term OS and WSP rates associated with extracranial OM ablated with SBRT; however, modest PFS rates were observed. A substantial proportion of patients with OM developed progressive disease and were treated with local ablation. Factors that can inform clinical decision-making and clinical trial design include primary tumor type, a metachronous presentation more than 24 months since diagnosis, and the site of OM presentation.

Stereotactic Radiotherapy for Pancreatic Cancer: A Single-Institution Experience.

Introduction Despite treatment advances, the prognosis of locally advanced pancreatic cancer is poor. Treatment remains varied and includes systemic and radiotherapy (RT). Stereotactic body radiotherapy (SBRT), highly conformal high-dose RT per fraction, is an emerging treatment option. Materials and methods We performed a single-institution retrospective review of patients with pancreatic adenocarcinoma treated with SBRT from 2015-2017. The median dose was 27 Gy (range: 21-36 Gy) in three fractions. Endpoints included local progression (RECIST 1.1; Response Evaluation Criteria in Solid Tumors 1.1), distant metastasis, overall survival, and toxicity. Results Forty-one patients were treated, with a median follow-up of eight months. Patients who received SBRT had unresectable (49%), metastatic (17%), or borderline resectable (7%) disease, declined surgery (17%), medically inoperable (7%), or developed local recurrence following the Whipple procedure (2%). The six-month and one-year rates of local progression-free survival, distant metastasis-free survival, and overall survival were 62% and 55%, 44% and 32%, and 70% and 49%, respectively. Five patients (12%) experienced seven late gastrointestinal (GI) grade 3 events. Conclusion  SBRT may be considered a treatment option to achieve local control of pancreatic cancer and is associated with a modest risk of severe late GI toxicities. Systemic therapies remain important, given the proportion of patients who develop distant metastases.

Stereotactic body radiotherapy for medically unfit patients with cancers to the head and neck.

BACKGROUND: A single institutional experience of stereotactic body radiation therapy (SBRT) to medically unfit patients with unresectable head and neck cancers (HNCs). METHODS: A retrospective review of HNC patients undergoing SBRT was undertaken from 2011 to 2016 for fractionation ranges between 35 and 50 Gy in 4 to 6 fractions. RESULTS: One hundred and fourteen patients with 117 SBRT courses were included with mean follow-up of 10.5 months. The cohort consisted of previously untreated primary HNC (n = 48), recurrent never irradiated HNC (n = 19), oligometastatic (n = 17) non-HNC primaries and previously irradiated HNC (n = 33). Local control (LC) at 12 months and median progression free survival was 85.8%, 78.2%, 85%, 78.9% (P = .86) and 23.7, 14.8, 10.5 and 7.8 months (P = .04) respectively. Only one patient had an acute grade 4 toxicity, two patients had grade 4 late toxicities. CONCLUSIONS: HNC SBRT is an effective treatment for frail patients where longer LC is relevant but are unable to tolerate protracted radiation schedules.

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic colorectal cancer: Dose and site of metastases matter.

BACKGROUND AND PURPOSE: To review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic colorectal cancer (mCRC) from a large academic institution. MATERIALS AND METHODS: Patients with mCRC treated with extracranial SBRT between 2008 and 2016 were identified from an institutional database. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. Endpoints included local progression (LP), overall survival (OS), progression-free survival (PFS), and cumulative incidence of starting or changing systemic therapy (SCST). Univariate and multivariable analyses (MVA) were performed to identify predictive factors. RESULTS: One hundred and sixty-five patients (262 lesions treated) were included. The 2-year cumulative incidence of LP was 23.8%. Lower SBRT doses and tumor location in the liver were significant predictors of LP on MVA. Median OS was 49.3 months, 19.3 months, and 9.0 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. Primary tumor not in situ, smaller tumors, fewer lines of previous systemic therapy, lower CEA, and oligometastases treatment indications were significant predictors of higher OS on MVA. For the entire cohort, median PFS was 9.9 months, while oligometastatic patients had a median PFS of 12.4 months. 2-year cumulative incidence of SCST was 41.7%. CONCLUSIONS: Survival outcomes are favorable after SBRT for mCRC patients. A significant proportion of patients did not have a change in systemic therapy after SBRT. Higher doses are required to obtain the best local control. Efforts should be made to better optimize SBRT delivery for liver metastases given their higher local failure rate.