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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.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.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 V35In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Optimizing plans to lower the lung V35

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.

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.

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, Despite the increasing utilization of stereotactic body radiotherapy (SBRT) for patients with oligometastasic disease (OMD), prognostic and predictive factors for this treatment modality are not well understood. In this analysis of a large, multi‐institutional database of SBRT for OMD, the timing of metastatic presentation is a significant prognostic factor, as patients with late metastasis (>24 months from cancer diagnosis) have lower risk of widespread progression and death after SBRT.

To evaluate the cumulative incidence of fracture and local failure and associated risk factors after stereotactic body radiation therapy (SBRT) for long bone metastases.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.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).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.

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.

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.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.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 BEDThis 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 BED

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., The overall aim of this investigation was to study the psychological impact of working during the COVID‐19 pandemic among RTs in Canada and Norway. Work‐related stress and anxiety were prevalent among Canadian and Norwegian RTs, 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. The findings suggest that the COVID‐19 pandemic has led to similar stressors amongst Canadian and Norwegian RTs but relatively higher levels of psychological impact among Canadian RTs.

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.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.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.A clinical prognostic model for OS in patients with extracranial OMD treated with SBRT has been developed and validated.

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.

PURPOSE/OBJECTIVE(S) Treatment of oligometastatic disease with SBRT has shown the potential to improve disease control and survival in trials largely focused on lung and prostate cancer. Outcomes in other sites, such as head and neck cancers (HNC) are poorly defined. Here we report the results of a multi-institutional cohort of oligometastatic HNC patients receiving SBRT. MATERIALS/METHODS Data on HNC patients treated between 2008 and 2016 was extracted from an international consortium of six high volume SBRT centers. Patients were considered oligometastatic if they had 5 or fewer extracranial metastases. The risk of local recurrence (LR) and widespread progression (WSP, defined as 6 or more metastatic sites) was estimated with competing risks analysis. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method. Univariable and multivariable regression analysis (MVA) was used to determine the relationship between covariates and the main endpoints. RESULTS Forty-two patients harboring 84 metastases from mucosal head and neck cancer were included. The median age was 64 and most patients were male (83%). The median follow up was 18.2 months. The most common primary site was the oropharynx (43%). Most patients had 1 or 2 metastases (78.6%). Metastatic sites treated with SBRT were mostly lung (50%) and bone (35.7%). Presentation was synchronous in 11 patients (26.2%), early metachronous (within 24 months of diagnosis, 57%) and late metachronous in 7 patients (> 24 months from diagnosis, 16.7%). The majority of patients (88%) had no systemic therapy prior to SBRT. SBRT dose and fractionation ranged from 20-28 Gy/1fx to 50 Gy in 5-10fx. The median biologic equivalent dose (BED10) was 100 Gy. The local control rate was 80% at 1 year and 66% at 2 years. The median PFS was 4.7 months. The median overall survival (OS) was 23.3 months. Improved local control on MVA was seen with patients who had a maximum point BED greater than the median (HR = 0.31; 95% CI: 0.10-0.91, P = 0.03). Disease burden significantly correlated with PFS, with larger combined PTV volumes for all metastases greater than the median of 48cc having worse PFS on MVA (HR = 2.99; 95% CI: 1.58-5.66, P < 0.001). The risk of WSP at 12 and 24 months was 31.7% and 48.3%, respectively. There was a trend towards lower rates of WSP for patients who presented with late metachronous disease versus all others (HR = 0.22; 95% CI: 0.03-1.82, P = 0.16). Severe toxicity was rare, with one patient developing a grade 3 brachial plexus injury after spine SBRT and one patient with grade 3 pneumonitis after lung SBRT. CONCLUSION Patients undergoing SBRT for oligometastatic head and neck cancer have favorable local control and overall survival, however, PFS remains short. Patients with a late metachronous presentation may have more favorable biology. Future study should focus on whether subsets of patients such as those with synchronous or early metachronous disease may benefit from pre-SBRT systemic therapy.

Purpose/Objective(s) In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective local treatment for oligometastatic cancers. However, it has been suggested that colorectal cancers may represent a more radioresistant histology, even to the high doses used in SBRT. Here, we report local recurrence rates, progression free-survival, and overall survival of patients with oligometastatic CRC treated with SBRT using a large multi-institutional data-base. Materials/Methods We collected data retrospectively from six cancer centers with a high volume of SBRT treatments from Jan 1 2008 to December 31, 2016. Our primary outcome was local recurrence while secondary outcomes included overall survival (OS), local recurrence free survival, progression free survival, oligo-progression, and widespread progression. Time-to event outcomes were estimated using the Kaplan-Meier method. Univariable regression analysis was performed to determine the relationship between patient, tumor and treatment variables and outcomes. Variables significant on univariable screen were entered into a multivariable model. All analysis was performed in R (R Foundation for Statistical Computing, version 4.0.2) Results We identified 235 patients with a total of 381 oligometastatic CRC lesions that were treated with SBRT. The mean age was 70.7 ± 12.2 years, 58% of patients were male with a median follow-up of 25.5 months. The most common site of metastasis was the lung (n = 133, 56.6%) with a total of 239 (62.7%) lesions. The median time to local recurrence was not reached with 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 probability of 76.1% and 35.9% respectively. On multivariable analysis, a BED10 of ≥100 Gy (HR 0.67, 95% CI 0.45-0.99) and the presence of lung (HR 0.53, 95% CI 0.34-0.82) or lymph node metastasis as opposed to liver metastasis (HR 0.31, 95% CI 0.13-0.74) were associated with improved local control. Larger total PTV size (≥17.5cc) was associated with worse overall survival (HR 2.62, 95% CI 1.45-4.72), progression free survival (HR 2.01, 95% CI 1.39-2.90) and widespread progression (HR = 2.82, 95% CI: 1.63-4.88). Use of prior systemic therapy before SBRT was also adversely associated with widespread progression (HR = 1.90, 95% CI: 1.22-2.95). 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 appreciably lower than what has historically been demonstrated in other cancer primary sites. These results suggest that an increase in BED should be considered if feasible and safe, in order to optimize local control. Increased overall PTV size may also be an indicator for the need for systemic therapy in addition to SBRT.

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, This large international, multi‐institutional series of SBRT to extracranial oligometastases demonstrates total volume of metastatic lesions as a strong, independent prognostic factor for cancer outcomes. This metric can redefine oligometastatic disease beyond number of lesions and refine patient selection for an increasingly important treatment paradigm.

Aims We report on the first prospective series of patient-reported quality of life (QoL) following stereotactic body radiation therapy (SBRT) for primary kidney cancer. Materials and methods Patients were treated on a multi-institutional prospective cohort study with 30–42 Gy SBRT in three or five fractions. QoL assessments were carried out using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15 Palliative (EORTC-QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FACT FKSI-19) and the EuroQol-5D-3L tools at baseline, 1 week, and 1, 3 and 6 months post-treatment. QoL over time was analysed using linear mixed modelling, pairwise and anchor-based analyses. Results Twenty-eight patients were included. No significant reduction in any QoL metric was observed on repeated measures. However, a trend to reduced EORTC global QoL and fatigue was observed at 1 week, with improvement over time in other symptom scores such as pain, appetite and nausea. On pairwise analysis, there were statistically significant reductions in global QoL at 1 week (with subsequent recovery) and dyspnoea at 6 months post-SBRT. Trends to improved pain, appetite and nausea were observed following SBRT. Less than half of patients reported stable or better EORTC global QoL at 1 week. For all other QoL and symptom scales, most patients had reported stable or better scores at all times, with a slight proportional improvement in emotional functioning, nausea, fatigue, pain and appetite, and a slight worsening of physical functioning and dyspnoea over time. Conclusions SBRT results in well-preserved QoL in the weeks to months following treatment for primary kidney cancer.

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.

Background and purpose Recent studies have postulated that patients undergoing lung stereotactic body radiotherapy (SBRT) for ultracentral tumors have higher toxicity and mortality rates than those with central tumors. Our aim was to compare the outcomes after lung SBRT for central versus ultracentral tumors in our own series. Material and methods This was a retrospective review of patients with primary and metastatic lung tumors treated with SBRT from 1 September 2009 to 30 June 2015. Patients were included if they were treated with five-fraction SBRT to central or ultracentral tumors. Central tumors were defined as tumors where the closest point was within 2 cm of (but not abutting) the proximal bronchial tree, or within 2 cm of (whether abutting or not) mediastinal structures. Ultracentral tumors were defined as tumors abutting the proximal bronchial tree. The 2-year overall survival (OS), 2-year local failure (LF), and 2-year grade ≥3 toxicity rates were compared between patients with central and ultracentral tumors. Results A total of 107 patients were included in this study. There were no significant differences in 2-year OS between the two groups, with 2-year OS 57.7% for central tumors, and 50.4% for ultracentral tumors (p = 0.10). There were no significant differences in 2-year LF between the two groups, with 2-year LF 3.4% for central tumors and 4.3% for ultracentral tumors (p = 0.92). There were no significant differences in 2-year grade ≥3 toxicity rate for the two groups, with 3.5% with central tumors and 8.7% with ultracentral tumors (p = 0.23). Conclusions There were no significant differences in OS, LF, or grade ≥3 toxicity between patients with central and ultracentral lung tumors. Although these results indicate that SBRT for ultracentral tumors may be safe, caution should be applied in selecting and treating these patients until the completion of large prospective trials.

Objectives The purpose of this study was to review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic non-small-cell lung cancer (NSCLC) from a large academic institution. Materials and methods Metastatic NSCLC patients treated with extracranial SBRT were identified from an institutional database. Treatment indications were: (1) oligometastases, (2) oligoprogression, and (3) local control of dominant tumors. Endpoints included overall survival (OS), progression-free survival (PFS), time to starting/changing systemic therapy (SCST), and local failure (LF). Univariate and multivariable analyses were performed to look for predictive factors. Results 108 patients with 165 tumors were treated. SBRT was delivered for oligometastases in 66 patents, for oligoprogression in 20 patients, and for local control in 22 patients. Median OS and PFS for all patients were 27.3 months and 4.4 months, respectively, with treatment indication being the only predictive factor on multivariable analysis (patients with oligometastases having the highest median OS and PFS of 39.3 months and 7.6 months respectively). Cumulative incidence of SCST was only 21.5% at 1 year after SBRT, with larger tumor size and positivity for EGFR/ALK mutation being predictive of higher rates of SCST on multivariable analysis. LF was 15.6% at 1 year, with larger tumor size and exposure to previous systemic therapy being predictive of higher rates of LF on multivariable analysis. Conclusion Patients treated with SBRT for oligometastases have better OS and PFS than those treated for oligoprogression or for local control of dominant tumors. Use of SBRT may delay the need for SCST. Larger tumors and previous exposure to systemic therapy were predictive of higher rates of LF.

Purpose/objective(s) Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment approach in oligometastatic patients with adrenal gland metastases (AGM). Nevertheless, most of the literature reporting SBRT outcomes for AGM comes from published single institutional experience, and no specific guidelines are yet established to guide patients' inclusion and dosimetric planning. Materials/methods The Consortium for Oligometastases Research (CORE) is currently the largest retrospective series of patients with oligometastases (OM). Among CORE patients, those treated with SBRT for AGM were included. Adrenal metastatic burden (AMB) was defined as the sum of all adrenal GTV if more than one OM is present. BED10 was calculated with tumor alpha/beta ratio of 10. Competing risk analysis was used to estimate the risk of local recurrence (LR) and widespread progression (WP) over time, using death from any cause as a competing risk factor. Kaplan-Meier method was used to estimate the overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). Univariable and multivariable regression was used to quantify the relationship between potential predictors and the main endpoints. A P-value threshold of 0.05 was used for statistical significance. Results 46 patients with 57 adrenal lesions were included. Median follow-up was 18.2 months. The most common primary malignancy was NSCLC. The mean (standard deviation) age at diagnosis was 65.84 (10.84) years, with 25 (53.2%) male patients and 22 (46.8%) female patients. 8 out of the 46 patients had developed more than one AGM. The most used fractionation scheme was 30 - 35 Gy in 3 - 5 fractions, and the mean prescribed BED10 was 69.37 Gy10. Median LRFS, PFS, and OS were 15.3, 5.29, and 19.1 months, respectively. The 1-year and 5-year LRFS were 65% and 25.4%, respectively. The 1-year and 5-year OS were 70% and 33%, respectively. Only 1 patient developed a Grade 3 GI toxicity. On multivariable regression, a minimum received PTV dose > 46 Gy10 was associated with an improved OS (HR 0.42, 95% CI [0.20 - 0.89], P = 0.024) and LRFS (HR 0.37, [0.18 - 0.76], P = 0.006), after adjusting for primary site. A prescribed BED10 more than 70 Gy10 was an independent prognostic factor of a lower LR rate (HR 0.31, [0.102-0.94], P = 0.039). Interestingly, AMB greater than 10 cc was an independent predictor of a lower risk WP (HR 0.29, [0.11 - 0.80], P = 0.017), after adjusting for primary histology and number of OM. Conclusion SBRT to AGM is a safe procedure that achieves a satisfactory local control and survival in oligometastatic patients. The current results suggest that patients should be treated with a prescription BED10 dose of at least 70 Gy10, and a minimum PTV dose > 46 Gy10, if safely achievable. Paradoxically, AMB > 10cc was favorable, and a high AMB should not preclude the administration of a definitive course of SBRT. Prospective studies are needed to determine comprehensive criteria for patients SBRT eligibility and dosimetric planning.

PURPOSE/OBJECTIVE(S) The definition of oligometastatic (OM) disease has largely focused on the number of metastatic lesions. Here, we investigate the total volumetric burden of metastases at initial OM presentation as an independent prognostic factor for distant progression free survival (DPFS), widespread progression (WSP, i.e., > 5 new lesions), and overall survival (OS) in patients treated with SBRT. MATERIALS/METHODS Patients with oligometastatic cancer treated with SBRT at 6 international institutions from 2007 - 2016 were retrospectively reviewed. Patients were included if they had 1) five or fewer metastases, 2) no history of brain metastases, 3) curative treatment for primary disease, and 4) SBRT to all known metastases. Multivariable Cox regression models were used to determine the relationship between DPFS and OS with the total planning target volume (PTV) at initial OM presentation. The relationship between WSP and total PTV was determined using multivariable competing risks regression. All models were adjusted for the potential confounders of histology, pre-SBRT systemic therapy, osseous-only vs. visceral lesions, and number of metastases. RESULTS In total, 961 OM patients were included. The median follow-up was 24.4mo (IQR: 13.8-37.5). The most common primary histologies were NSCLC (25.9%), colorectal (22.0%), prostate (13.3%), and breast (7.9%). The majority of patients (59.4%) had a solitary oligometastasis, while 22.6%, 9.6%, 5.5%, and 2.9% had 2, 3, 4, or 5 lesions, respectively. Two-thirds (65.8%) did not have pre-SBRT systemic therapy, and 28.3% had only osseous lesions. The median total PTV was 40.0cc (IQR: 19.7-85.0). The median DPFS, time to WSP, and OS were 15.1, 43.5, and 44.7mo, respectively. Modeling total PTV using restricted cubic splines revealed significant non-linear effects, and log-transformation was optimal to account for this non-linearity. Total PTV had a significant effect on DPFS in the first 18mo after SBRT and this was most profound in the first 6mo, when each doubling of total PTV conferred a 40.6% increased risk of distant progression (P < 0.001). Similarly, each total PTV doubling increased the risk of WSP by 45.4% in the first 6mo (P < 0.001). Total PTV had a significant effect on OS in the first 2yrs after SBRT, with each PTV doubling increasing the risk of death by 60.7% during the first 6mo (P < 0.001) and by 34.6 % thereafter (P < 0.001). Exploratory GTV analysis, where complete data was available for 76.1% of patients due to variability in contouring GTV vs. CTV, confirmed the PTV-based observations. CONCLUSION This large multi-institutional series demonstrates the strong impact of total volumetric burden of metastases at initial OM presentation on the risk of distant and widespread progression and OS. We propose that total volume of metastatic lesions may have prognostic merit beyond number of metastases in identifying OM patients who would benefit most from systemic therapy in addition to local metastasis-directed therapy.

PURPOSE/OBJECTIVE(S) Multiparametric magnetic resonance imaging (mpMRI) is increasingly being used in high dose rate (HDR) brachytherapy treatment planning. Its enhanced soft tissue contrast over conventional computed tomography increases the ability to identify the dominant intraprostatic lesion (DIL) and enables focal boosting using HDR brachytherapy. This can have important implications for adjacent organs at risk. We therefore investigated the acute and late toxicities reported within our institutional experience with this approach. MATERIALS/METHODS We compiled 4 cohorts of prostate cancer patients treated with mpMRI dose painted HDR brachytherapy (either as a boost or as monotherapy on clinical trial) between December 2014 and October 2018. Salvage brachytherapy was excluded. Three of the cohorts were from prospective clinical trials (MARS, HDR monotherapy and SPARE). For the MR-HDR boost cohort, pertinent demographic, clinical and dosimetric information were extracted from patients' medical records. Descriptive statistics were used to summarize baseline data. Toxicities experienced were coded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The Nelson-Aalen estimator method using 95% confidence intervals was used to assess the cumulative incidence of biochemical failure (BCF; using the Phoenix Failure definition) and the cumulative incidences of grade 2 or higher toxicity. RESULTS 144 patients with a mean age (65.6 ± 6.7 years), follow-up (55.7 ± 15.0 months) and baseline PSA (9.7 ± 8.3 ng/mL), with predominantly cT2a (32.6%) and Gleason 7 (3+4; 62.0%) disease, were included in the final analysis. Fifteen patients treated with MR-HDR boost were followed elsewhere so no toxicity data were available at time of analysis. All risk groups were represented: low (10.4%), favorable (27.8%) and unfavorable intermediate (36.8%), and high (25.0%). 25/137 (18%) experienced BCF with cumulative incidence rates of 20.6% at 5-years. A total of 41/129 (32%) patients experienced any grade 2+ GU (1 G3) and 7/129 patients (5.4%) experienced any grade 2+ GI (0 G3) toxicity. The cumulative incidence rates at 5-years were 33.2% for GU and 5.7% for GI, respectively. Neither BCF or toxicity (GU or GI) was significantly different between treatment groups. CONCLUSION Dose escalation to the DIL using mp-MRI dose painted HDR brachytherapy appears to be feasible, safe and well-tolerated. Further follow-up and investigation are warranted to determine whether MR-HDR improves outcomes compared to standard non-MR-HDR brachytherapy.

To assess the association between colorectal cancer (CRC) histology, dose, and local failure (LF) after stereotactic ablative radiation therapy (SABR) for pulmonary metastases, and to describe subsequent cancer progression, change of systemic therapy (CST), survival, and their association with treatment indications.From a prospective SABR cohort, 180 pulmonary metastases in 120 patients were identified. Treatment indications were single metastasis, oligometastases, oligoprogression, and dominant areas of progression. Doses of 48 to 52 Gy/4 to 5 fractions were delivered. Since 2010 the dose for peripheral CRC metastases was increased to 60 Gy/4 fractions. Cumulative incidence function (CIF) was used to report LF, progression probability, and CST. The Kaplan-Meier method estimated overall survival (OS). Univariate and multivariable analyses to assess variable associations were conducted.Median follow-up was 22 months (interquartile range, 14-33 months). At 24 months, the CIF of LF was 23.6% (95% confidence interval [CI] 15.1%-33.3%) and 8.3% (95% CI 2.6%-18.6%), respectively, for CRC and non-CRC metastases (P.001). This association remained significant after adjusting for confounders (subdistribution hazard ratio [SHR] 13.6, 95% CI 4.2-44.1, P.001). Among CRC metastases, 56 and 45 received60 Gy and 60 Gy, respectively. Delivering 60 Gy was independently associated with a lower hazard of LF (SHR 0.271, 95% CI 0.078-0.940, P=.040). At 12 months the CIF of progression was 41.67% (95% CI 21.69%-60.56%), 42.51% (95% CI 29.09%-55.29%), 62.96% (95% CI 41.25%-78.53%), and 78.57% (95% CI 42.20%-93.48%), respectively, for patients treated for single metastasis, oligometastases, oligoprogression, and dominant area of progression (P.001). A CST was observed, respectively, in 4 (17%), 17 (31%), 12 (44%), and 10 (71%) patients with a median time of 13.1, 11.1, 8.4, and 8.4 months.Colorectal cancer lung metastases are associated with a higher hazard of LF and require higher SABR doses. Outcomes for patients with oligometastases and oligoprogression treated with SABR seem favorable. Prospective clinical trials are needed to confirm these benefits.

This case series reports overall progression-free survival, widespread progression outcomes, and prognostic survival factors from a pooled data set of 1033 patients with oligometastasis treated with stereotactic body radiotherapy., Key Points Question What are survival outcomes and factors specific to patients with oligometastasis (OM) treated with stereotactic body radiotherapy? Findings In the largest international OM case series to date (1033 participants), the median overall survival was prolonged at 44.2 months and statistically significantly associated predominantly with primary tumor type and a metachronous presentation more than 24 months since initial OM diagnosis. The median progression-free survival was 12.9 months; however, a substantial proportion of patients relapsed in an oligoprogressive pattern that was amenable to repeat local therapy. Meaning Findings of this study suggest that patients with OM disease have long-term overall survival and modest progression-free survival; a metachronous presentation more than 24 months since diagnosis is favorable., 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