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The Consortium of Oligometastatic Research (CORE) database consists of 1033 patients who presented with either synchronous or metachronous oligometastatic disease and were treated with ablative therapy to all sites. Of this cohort, a subset of patients had subsequent extracranial oligometastatic recurrence. These patients represent a unique cohort and we aim to report their outcomes in an effort to appropriately select patients who would benefit from further ablative therapy. A retrospective review of patients in the CORE database was conducted. Oligorecurrent disease was defined as ≤5 new metastases after having previously received ablative treatment to all known sites of oligometastatic disease. Our primary endpoint was time to widespread progression (WSP), estimated using competing risk analysis where death was the competing risk. Widespread progression was defined as developing metastatic dissemination not amenable to further ablative treatment, inclusive of developing ≥6 new sites of extracranial metastases or a malignant effusion. WSP was measured from the date of initial diagnosis and from the date of first oligorecurrence. Secondary endpoint was estimated overall survival (OS) using Kaplan-Meier method. A total of 375 patients had oligorecurrent disease and 233 received further ablative therapy to all metastatic sites. Of the 233 patients, 83 had a subsequent oligorecurrent event and 57 received further ablative therapy to all metastases. Of the 375 patients, 161 developed widespread progression by last follow up. The median time to widespread progression from initial diagnosis was 80.7 months (95% CI: 68.2-90.9) and from first oligorecurrence was 55.1 months (95% CI: 33.3-not reached). The 2 year and 5-year WSP rates from initial diagnosis were 11.0% (95% CI: 7.6-14.3) and 40.6% (95% CI: 34.3-46.9) and from first oligorecurrence were 38.8% (95% CI: 33.6-43.9) and 52.5% (95% CI: 45.3-59.8). The median OS was 44.8 months (95% CI 37.0-51.0). The 1 year, 2 year and 5-year OS rates were 85.0% (95% CI: 81.9-89.1), 69.8% (95% CI: 64.9-74.6) and 33.3% (95% CI: 25.5-41.1) respectively. Individuals who develop recurrence in a limited number of sites appear to represent a favorable subgroup of metastatic patients. In this retrospective cohort, oligorecurrent patients demonstrate favorable natural histories with regards to time to widespread progression and overall survival that may benefit from further metastases directed ablative therapy. [ABSTRACT FROM AUTHOR]

To evaluate oncological and renal function outcomes of stereotactic body radiotherapy (SBRT) for medically inoperable patients with localised renal cell carcinoma. Consecutive patients treated with curative intent SBRT (30–45 Gy in five fractions or 42 Gy in three fractions) were included. Data on local control (Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), distant metastasis, impact on estimated glomerular filtration rate (eGFR) and proportional ipsilateral and contralateral renal functions (measured through renal scans) were collected. Univariate and multivariable analyses were conducted to determine association of variables with oncological and renal function outcomes. Seventy-four patients were analysed. The median follow-up was 27.8 months (interquartile range 17.6–41.7). Fifty-seven per cent had tumours ≥ T1b. One-, 2- and 4-year cumulative incidence of local failure was 5.85, 7.77 and 7.77%, respectively. The cumulative incidence of distant metastasis at 2 years was 4.24%. On multivariable analysis, a lower planning target volume (PTV) mean dose (P = 0.019) and a larger PTV (P = 0.005) were significantly associated with the risk of developing local failure. A lower PTV maximum dose (P = 0.039) was significantly associated with the risk of developing distant metastasis. The median change in global eGFR (ml/min) from pre-SBRT levels was –7.0 (interquartile range –14.5 to –1.0) at 1 year and –11.5 (interquartile range –19.5 to –4.0) at 2 years. The proportion of ipsilateral (differential) renal function decreased over time from 47% of overall renal function pre-SBRT to 36% at 2 years, whereas the proportion of contralateral renal function correspondingly improved. On multivariable analysis, a higher volume of uninvolved renal cortex (P < 0.0001) was significantly associated with a smaller decrease in eGFR over time. In this large institutional cohort, oncological outcomes of renal cell carcinoma treated with SBRT were favourable and a longitudinal decline in renal function in the ipsilateral kidney and compensatory increase in the contralateral kidney were observed. Clinical and dosimetric factors were significantly associated with oncological and renal function outcomes. • 2-year local failure after SBRT for non-operable RCC was 7.8%. • Higher risk of local failure associated with lower mean PTV dose, larger PTV volume. • Median change in eGFR was –7.0 and –11.5 at 1 and 2 years post-SBRT, respectively. • Higher volume of uninvolved renal cortex associated with smaller decrease in eGFR. [ABSTRACT FROM AUTHOR]

Aims To determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR). Materials and methods Patients were treated with lung SABR of 48–60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose–volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity. Results The median follow-up was 21.0 months (range 6.2–52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model ( P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis ( P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture. Conclusions None of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Stereotactic body radiation therapy (SBRT) is an increasingly important modality in the management of patients with oligometastatic disease (OMD). Though prospective clinical trials have demonstrated the benefits of SBRT in a variety of oligometastatic settings, there is currently limited data to guide patient selection and provide long-term prognostic information for OMD patients. The purpose of this study was to create a clinical prognostic model for overall survival (OS) for OMD patients treated with SBRT.Materials/methods: A large, retrospective multi-institutional database of OMD patients treated with SBRT provided the data for model construction. Recursive partitioning analysis (RPA) was used to generate a prognostic model for OS that could account for complex interactions between baseline patient characteristics. The model was generated using a training set (75% of all samples) and internally validated using the reserved testing set. Model performance in the training and test sets were evaluated using log-rank tests, Harrell's C-statistic and time-dependent area under the receiver operating characteristics curve (AUC). All analyses were carried out in R.Results: A total of 1,033 patients were included in the analysis. RPA for OS revealed three risk groups. The low-risk group consisted of younger (< 55) patients with favorable primary sites (hormone receptor/Her2-positive breast cancer, colorectal cancer or renal cell carcinoma) as well as any patient with a prostate cancer primary; the high-risk group consisted of patients with any other primary site who presented with non-pulmonary OMD within 24 months of the diagnosis of the primary disease; and the intermediate-risk group consisted of all other patients. The 5-year OS was 77.5 % (95% confidence interval: 63.1-91.9%), 32.3% (25.1-39.5%) and 12.1% (2.9-21.4%), respectively, for the low, intermediate and high-risk groups. Log-rank tests for difference in survival between the risk groups in both the training and test sets were highly significant (P < 0.0001). The model possessed good discriminative power with a C-statistic of 0.68 and time-dependent AUC of 0.72 in the training set, and there was an expected small reduction in these statistics in the test set (C-statistic: 0.65, AUC: 0.67).Conclusion: An internally validated prognostic model for OS with good ability to distinguish between low, intermediate and high-risk OMD patients was generated. Subsequent external validation will be undertaken to demonstrate the robustness of this model to new data. [ABSTRACT FROM AUTHOR]

We report on the first prospective series of patient-reported quality of life (QoL) following stereotactic body radiation therapy (SBRT) for primary kidney cancer. 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. 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. SBRT results in well-preserved QoL in the weeks to months following treatment for primary kidney cancer. • The first prospective assessment of QoL following SBRT for primary kidney cancer. • SBRT resulted in a transient reduction in global QoL at 1 week post-treatment. • Trends to improved symptom scores such as pain, nausea and appetite were observed in the months following SBRT. • Overall, there was a minimal influence of SBRT on QoL over time. • Comparative studies of SBRT to other ablative therapies and active surveillance are needed, with QoL as an important secondary end point. [ABSTRACT FROM AUTHOR]

Stereotactic Body Radiation Therapy (SBRT) is increasingly being utilized to treat non-spine bone metastases (NSBM) with both palliative and radical intent. There remains limited data on the long-term outcomes and toxicities and, therefore, we report mature results from our institutional database. Patients with NSBM who were treated with SBRT were identified from 2011 to 2021. The primary endpoint was radiographic local failure (LF). Secondary endpoints included rate of in-field pathologic fracture (PF), overall survival (OS), and late (>3 months post-SBRT) grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). Competing risks analysis was used to assess rates of LF and PF. OS was estimated using the Kaplan-Meier method. Univariable regression (UVR) and multivariable regression (MVR) were performed to investigate predictive factors for LF and PF. A total of 373 patients with 505 NSBM were included in this study. Primary indications for SBRT included oligometastatic disease (52.6%), pain relief (23.8%), and oligoprogression (19.7%). Median follow-up was 26.5 months (range: 3.0-128.3 months). The most common primary histologies included prostate (33.7%), RCC (20.7%), breast (16.9%), and lung (14.8%). The two most common NSBM sites were pelvic (42.3%) and rib (30.5%). Of all NSBM, 217 (42.7%) were lytic and 230 (45.3%) were symptomatic. The most common dose prescriptions were 35 Gy in 5 fractions (33.3%) and 24 Gy in 2 fractions (25.2%). 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. There were 3 instances of late grade ≥3 toxicity: 1 grade 3 osteonecrosis, 1 grade 3 peripheral neuropathy, and 1 grade 5 bowel fistula. Median OS was 53.9 months (95% confidence interval: 45.3-63.2 months). Lytic NSBM (HR=2.20; p<0.01), symptomatic NSBM (HR=2.15; p<0.01), and those with a larger PTV (HR=1.01; p=0.04) were at higher risk of LF on MVR. Lytic lesions (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) were at a higher risk of PF on MVR. SBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of fracture. We identify predictors of both LF and PF that can serve to inform practice. [ABSTRACT FROM AUTHOR]

Aims To report the outcomes of a cohort of patients with renal cell carcinoma (RCC) treated using stereotactic ablative body radiotherapy (SABR). Materials and methods Patients treated with SABR for primary RCC from 1 January 2012 to 1 April 2015 were retrospectively reviewed. Patients were non-surgical candidates treated with doses ranging from 30 to 40 Gy in five fractions. The tumour sizes and serum creatinine were compared between the pre-treatment assessment and subsequent follow-up assessments. The worst acute and late grade ≥2 toxicity rates were recorded. Results In total, 16 patients were included in this study. The median follow-up was 19 months (range 7–30). Eleven patients had stable disease, four had partial responses and none had progressive disease, indicating a local control rate of 100%. One patient had grade 2 acute nausea and two patients had grade 4 renal toxicities (two patients with pre-existing stage 4–5 chronic kidney disease required dialysis following SABR). Four of four patients with pre-SABR symptoms (pain and/or haematuria) had symptomatic relief after SABR. Conclusion SABR for RCC is safe, the toxicities are minimal, and the local control is excellent at early follow-up. This technique should be further evaluated in prospective clinical trials. [ABSTRACT FROM AUTHOR]

To report clinical outcomes for patients with metastatic disease to the head and neck (HN) treated with stereotactic body radiation therapy (SBRT) at a large academic center. A retrospective review of SBRT patients treated to the HN from 2012 to 2020 was conducted. Treatment indications included: oligometastases, oligoprogression, and local control of 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 to determine the relationship between clinical characteristics and outcomes. Grade 3—4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. Fifty-six patients (58 lesions) were analyzed with a median follow-up of 16 months. Primary cancer sites included lung (25%), kidney (19.6%), breast (19.6%) and other (35.8%). SBRT indications were: oligometastases (n = 24, 42.9%), oligoprogression (n = 11, 19.6%), and local control of a DAP (n = 21, 37.5%). Most patients received SBRT to a single neck node (n = 48, 82.8%). Median SBRT dose was 40 Gy (range: 25-50 Gy) in 5 fractions, with a median biologically effective dose (BED 10) of 72 Gy (range: 37.5-100 Gy). One- and 2-year LC rates were 97.6% and 72.7%. One- and 2-year RC rates were 100% and 86.7%, respectively. Median OS was 19.2 months (95% confidence interval [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), and 56.5%, 27.3% and 19.1% (p = 0.0004), respectively. On MVA, treatment indication and histology were found to be predictive for OS and treatment indication and prior systemic therapy were the predictive factors for PFS. Ten patients (18%) developed acute grade ≥ 3 treatment-related toxicity and six patients (11%) experienced late grade ≥ 3 toxicity. The use of SBRT for metastatic disease to the HN provided excellent LC rates with low rates of regional failure. Patients with oligometastatic disease had better OS and PFS than others. This treatment resulted in an acceptable toxicity profile. [ABSTRACT FROM AUTHOR]

With the increasing utilization of stereotactic body radiation therapy (SBRT) for primary and metastatic cancer, use of multi-target thoracic (MTT) SBRT is rising. Given the limited safety and efficacy data on MTT, the purpose of this study was to report the experience of this strategy from a large academic center. Between 2012 and 2021, patients who received SBRT for ≥2 thoracic targets within 1 year were retrospectively reviewed. The primary endpoint was clinically significant radiation pneumonitis (CSRP) requiring steroids, oxygen, or intubation. Secondary endpoints included late grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0) apart from pneumonitis, local failure (LF), initiation or change of systemic therapy (ICST), progression-free survival (PFS), and overall survival (OS). Competing risk analysis was used to evaluate the cumulative incidence (CI) of CSRP, LF, and ICST. PFS and OS were estimated using the Kaplan-Meier method. Univariate analyses (UVA) and multivariable analyses (MVA) were performed to look for clinical and dosimetric predictive factors of CSRP. One-hundred and ninety patients (481 lesions) were treated with MTT SBRT with a median follow-up of 19.7 months. Primary histologies included colorectal (29.9%), lung (28.1%), kidney (17.5%), and breast (6.0%). Indications for SBRT were oligoprogression (n=180; 37.4%), oligometastases (n=164; 34.1%), curative intent (n=81; 16.9%), and control of dominant areas of progression (n=56; 11.6%). Thirty-two patients (16.8%) had systemic therapy within 3 months of SBRT. Number of irradiated tumors ranged from 2-7 and the majority of SBRT courses were delivered concurrently (88.2%). Of concurrent courses, 157 (62.3%) used multiple isocenters and 95 (37.7%) used a single isocenter. Median SBRT dose was 50 Gy (range: 25-60 Gy) delivered in 1-8 fractions, with a median biological effective dose of 105.6 Gy (range: 37.5-150 Gy). Overall, 14 patients (7.4%) had CSRP, with 5 cases requiring oxygen. The CI of CSRP at 6 and 12 months was 5.3% and 7.7%, respectively. Two other patients had late grade ≥3 toxicity: 1 grade 3 rib fracture and 1 grade 4 esophageal perforation. The CI of LF at 2 years was 10.5%. The CI of ICST at 2 years was 44.0%. Median PFS was 9.9 months and median OS was 47.4 months. On UVA, shorter time between SBRT treatments (HR=62.50; p<0.01), ≥3 tumor targets (HR=2.96; p=0.04), and a higher V35Gy (HR=2.60; p=0.02) were predictive for a higher risk of CSRP. On MVA, shorter time between SBRT treatments (HR=55.56; p<0.01) and a higher V35Gy (HR=2.58; p=0.02) remained as statistically significant predictors. In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Increasing the time between SBRT treatments and optimizing plans to lower the V35Gy may decrease the risk of CSRP. [ABSTRACT FROM AUTHOR]

The potential of oligometastasis (OM)-directed therapy to translate to survival benefit has been shown in randomized trials, but typically in small or histology-specific cohorts (i.e., prostate or NSCLC). We investigated the impact of local control (LC) on widespread progression (WSP) and overall survival (OS) in a large, multi-institutional cohort of patients across heterogeneous histologies treated with SBRT to OMs. Patients treated at 6 international centers from 2007 – 2016 were retrospectively reviewed and included if they had 1) five or fewer lesions, 2) no history of brain metastases, 3) curative treatment for primary disease, and 4) SBRT to all known OMs at initial presentation. The relationship between LC at certain time points and OS and WSP (>5 active/untreated lesions) were explored using Cox and Fine-Gray regression models. The relative strength of association between LC and dosimetric predictors was analyzed with competing risk regression using death as a competing risk. In total, 1033 patients treated to 1700 OMs were analyzed. The median follow up was 24.1 mo (range: 0.3-104.7). Most patients (57.1%) had solitary OM, 24.0% had 2 OMs, 10.3% had 3 OMs, and 8.6% had 4-5 OMs. The most common histologies were NSCLC (25.2%), colorectal (22.8%), prostate (12.8%), and breast (8.1%). The median prescription dose was 48 Gy (range: 10-60) in a median of 5 fractions (range: 1-15). Median OS was 44.2 mo. Cumulative incidence of local failure at 6m, 1y, 2y and 3y was 3.3%, 10.0%, 19.6% and 23.9% respectively. As detailed below, patients who fail locally in any or all SBRT-targeted OMs have significantly increased risk of WSP and death compared to those with no failure. These risks may be greater with shorter duration of LC. Patients who failed in only a subset of treated OMs and those who failed in all OMs did not have significantly different WSP and OS outcomes. Minimum BED to the GTV or ITV was most predictive of LC when compared to prescription dose, PTV Dmin, and PTV Dmax, across a range of simulated a/b ratios. This large multi-institutional series demonstrates that duration of LC in SBRT-targeted OMs translates strongly to WSP and OS outcomes in an all or nothing manner, where failure in a subset of treated OMs appears no different in risk compared to failing in all OMs. This highlights the importance of maximizing LC to each OM in this treatment paradigm, where GTV or ITV Dmin may be a key dosimetric parameter. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims We report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control. Materials and methods In total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48–60 Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses. Results Of the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control. Conclusions Lung SABR of 48–60 Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim Stereotactic body radiation therapy (SBRT) is increasingly used as an option for those with liver metastases. In order to facilitate future economic impact of health technologies, health utility scores may be used. The EuroQOL-5D-3L (EQ-5D) preference-based healthy utility instrument was used to evaluate the impact of treatment with SBRT on health utility scores. Materials and methods Between August 2013 and October 2014, 31 patients treated with 3–5 fractions of SBRT for liver metastases were enrolled in this study. The EQ-5D instrument was administered at baseline, during and up to 6 months post-SBRT. Results Mean EQ-5D score at baseline was 0.857, which remained stable across the entire study time period. Transient increases in difficulties with mobility (9.7% reported at baseline to 16.1% on the last day of treatment) and usual activities (3.2% reported at baseline to 34.5% on day two) were found during the course of treatment; these returned to baseline levels subsequently. The mean visual analogue score at baseline was 65.8 and remained unchanged throughout treatment and follow-up. Conclusions The stability of health utility scores and problems reported by patients undergoing treatment indicate that SBRT for liver metastases does not impart a significant adverse effect on quality of life. These results may be used for future economic evaluation of SBRT. [ABSTRACT FROM AUTHOR]