Role of Metastasis-Directed Therapy in Genitourinary Cancers.

OPINION STATEMENT: The treatment of oligometastatic genitourinary cancers is a rapidly advancing field with ablative radiotherapy as one of the critical treatment components. The oligometastatic disease state, which can be defined as 1-5 metastatic sites with a controlled primary, represents a distinct clinical state where comprehensive ablative local therapies may provide improved outcomes. Enhanced imaging has increased the number of patients identified with oligometastatic disease. Evidence for improved outcomes with metastasis-directed therapy (MDT) in oligometastatic genitourinary cancers is increasing, and previously published outcome data continues to mature with an increasing body of prospective data to inform the role of MDT in histology-specific settings or in the context of systemic therapy. In select patients, MDT can offer benefits beyond improved local control and allow for time off of systemic therapy, prolonged time until next therapy, or even the hope of cure. However, treatment decisions for locally ablative therapy must be balanced with consideration towards safety. There are exciting advances in technologies to target and adapt treatment in real-time which have expanded options for safer delivery and dose escalation to metastatic targets near critical organs at risk. The role of systemic therapies in conjunction with MDT and incorporation of tumor genetic information to further refine prognostication and treatment decision-making in the oligometastatic setting is actively being investigated. These developments highlight the evolving field of treatment of oligometastatic disease. Future prospective studies combining MDT with enhanced imaging and integrating MDT with evolving systemic therapies will enable the optimal selection of patients most likely to benefit from this "all-or-none" approach and reveal settings in which a combination of therapies could result in synergistic outcomes.

Multi-institutional Analysis of Metastasis-directed Therapy with or Without Androgen Deprivation Therapy in Oligometastatic Castration-sensitive Prostate Cancer.

BACKGROUND: Metastasis-directed therapy (MDT) is increasingly being used in oligometastatic castration-sensitive prostate cancer (omCSPC). However, it is currently unclear how to optimally integrate MDT with the standard of care of systemic hormonal therapy. OBJECTIVE: To report long-term outcomes of MDT alone versus MDT and a defined course of androgen deprivation therapy (ADT) in omCSPC. DESIGN, SETTING, AND PARTICIPANTS: Here, a multicenter, international retrospective cohort of omCSPC as defined by conventional imaging was reported. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical progression-free survival (bPFS), distant progression-free survival (dPFS), and combined biochemical or distant progression-free survival (cPFS) were evaluated with Kaplan-Meier and multivariable Cox proportional hazard regression models. RESULTS AND LIMITATIONS: A total of 263 patients were included, 105 with MDT + ADT and 158 with MDT alone. The majority of patients had metachronous disease (90.5%). Five-year bPFS, dPFS, and cPFS were, respectively, 24%, 41%, and 19% in patients treated with MDT + ADT and 11% (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.36-0.64), 29% (HR 0.56, 95% CI 0.40-0.78), and 9% (HR 0.50, 95% CI 0.38-0.67) in patients treated with MDT alone. On a multivariable analysis adjusting for pretreatment variables, the use of ADT was associated with improved bPFS (HR 0.43, p < 0.001), dPFS (HR 0.45, p = 0.002), and cPFS (HR 0.44, p < 0.001). CONCLUSIONS: In this large multi-institutional report, the addition of concurrent ADT to MDT appears to improve time to prostate-specific antigen progression and distant recurrence, noting that about 10% patients had durable control with MDT alone. Ongoing phase 3 studies will help further define treatment options for omCSPC. PATIENT SUMMARY: Here, we report a large retrospective review evaluating the outcomes of metastasis-directed therapy with or without a limited course of androgen deprivation for patients with oligometastatic castration-sensitive prostate cancer. This international multi-institutional review demonstrates that the addition of androgen deprivation therapy to metastasis-directed therapy (MDT) improves progression-free survival. While a proportion of patients appear to have long-term disease control with MDT alone, further work in biomarker discovery is required to better identify which patients would be appropriate for de-escalated therapy.

A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases.

Purpose: Stereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone because of its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess the efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. Methods and Materials: In this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at Brigham and Women's Hospital/Dana Farber Cancer Center and Beth Israel Deaconess Medical Center between December 2016 and May 2019. SBRT dose and fractionation regimen were not protocol mandated. Local progression-free survival, progression-free survival, prostatic specific antigen progression, and overall survival were reported. Treatment-related toxicity was also reported. Results: A total of 98 patients and 126 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (27.0%, 34/126), 30 Gy in 5 fractions (16.7%, 21/126), or 30/35 Gy in 5 fractions (16.7%, 21/126). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume and higher dose to the gross tumor volume. Four patients (4.1%, 4/98) experienced local progression at 1 site for each patient (3.2%, 4/126). Among the entire cohort, 2-year local progression-free survival (including death without local progression) was 84.8%, 2-year progression-free survival (including deaths as well as local, distant, and prostatic specific antigen progression) was 47.5%, and 2-year overall survival was 87.3%. Twenty-six patients (26.5%, 26/98) developed treatment-related toxicities. Conclusions: Our study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.

Clinical Outcomes Among Patients Treated With Stereotactic Body Radiation Therapy to Femur Metastases for Oligometastatic Disease Control or Reirradiation: Results From a Large Single-Institution Experience.

Purpose: There are limited data regarding outcomes after stereotactic body radiation therapy (SBRT) for femur metastases, which was an exclusion criteria for the Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) trial. We aimed to characterize clinical outcomes from a large single institution experience. Methods and Materials: Forty-eight patients with 53 lesions were consecutively treated with femur SBRT from May 2017 to June 2022. The Kaplan-Meier method and Cox proportional hazard models were used to characterize time-to-event endpoints and associations between baseline factors and clinical outcomes, respectively. Local control and locoregional control were defined as the absence of tumor progression within the radiation treatment field or within the treated femur, respectively. Results: Most patients had Eastern Cooperative Oncology Group performance status 0 to 1 (90%), prostate (52%) or breast/lung (17%) cancer, and 1 to 3 lesions (100%), including 29 proximal and 5 distal. Fifty-seven percent of the lesions were treated with concurrent systemic therapy. Median planning target volume was 49.1 cc (range, 6.6-387 cc). Planning target volume V100 (%) was 99% (range, 90-100). Fractionation included 18 to 20 Gy/1F, 27 to 30 Gy/3F, and 28.5-40 Gy/5F. Forty-two percent had Mirels score ≥7 and most (94%) did not have extraosseous extension. Acute toxicities included grade 1 fatigue (15%), pain flare (7.5%), nausea (3.8%), and decreased blood counts (1.9%). Late toxicities included fracture (1.9%) at 1.5 years and osteonecrosis (4%) from dose of 40 Gy in 5F and 30 Gy in 5F (after prior 30 Gy/10F). One patient (2%) required fixation postradiation for progressive pain. With median follow-up 19.4 months, 1- and 2-year rates of local control were 94% and 89%, locoregional control was 83% and 67%, progression-free survival were 56% and 25%, and overall survival were 91% and 73%. Fifty percent of local regional recurrence events occurred within 5 cm of gross tumor volume. Conclusions: Femur SBRT for oligometastatic disease control in well-selected patients was associated with good outcomes with minimal rates of acute and late toxicity. Patterns of local regional recurrence warrant consideration of larger elective volume coverage. Additional prospective study is needed.

Prospective Evaluation of the Clinical Benefits of a Novel Tattoo-less Workflow for Nonspine Bone Stereotactic Body Radiation Therapy: Integrating Surface-Guidance With Triggered Imaging Reduces Treatment Time and Eliminates the Need for Tattoos.

PURPOSE: Oligometastatic disease has expanded the indications for nonspine bone stereotactic body radiation therapy (NSB SBRT). We investigated whether optical surface monitoring systems (OSMS) could enable tattoo-less setup and substitute for 2-dimensional/3-dimensional or cone beam computed tomography (CBCT)-based mid-imaging in NSB SBRT. METHODS AND MATERIALS: OSMS was incorporated in parallel with an existing workflow using pretreatment CBCT and 2-dimensional/3-dimensional kV/kV mid-imaging beginning November 2019. The ability of OSMS to detect out-of-tolerance (>2 mm/>2°) and commanded couch shifts was analyzed. A workflow incorporating OSMS reference captures, CBCT for pretreatment verification, and OSMS/triggered imaging (TI) for intrafraction monitoring was developed for rib/sternum SBRT beginning November 2021 and all NSB SBRT beginning February 2022. Treatment time and CBCT-related radiation dose between the OSMS and the non-OSMS intrafraction monitoring group was analyzed pre- and post-OSMS/TI workflow adoption. All fractions were analyzed through statistical process control with use of an XmR chart of treatment time per quarter from February 2019 to February 2023. Special cause rules were based on Institute for Healthcare Improvement criteria. RESULTS: From February 2019 to February 2023, 1993 NSB SBRT fractions were delivered, including 234 rib, 109 sternum, 214 ilium, and 682 multisite. Over 20 commanded shifts, OSMS could detect 2-mm shifts to within 0.4 mm 67% of the time and 0.8 mm 95% of the time. All NSB SBRT sites showed significant reductions in treatment time, including the greatest improvement in rib total treatment (21.6-13.4 minutes; P = 1.16 × 10-17) and beam time (7.9-3.2 minutes; P = 7.32 × 10-27). Significant reductions in CBCT-related radiation were also observed for several NSB sites. These process improvements were associated with OSMS adoption. CONCLUSIONS: Adoption of a novel NSB SBRT workflow incorporating OSMS/TI for bone intrafraction motion monitoring reduced treatment time and CBCT-related radiation exposure while also allowing for more continuous intrafraction motion monitoring for NSB SBRT. OSMS/TI enabled the transition to a tattoo-less workflow.

Widening the therapeutic window for central and ultra-central thoracic oligometastatic disease with stereotactic MR-guided adaptive radiation therapy (SMART).

BACKGROUND/PURPOSE: Central/ultra-central thoracic tumors are challenging to treat with stereotactic radiotherapy due potential high-grade toxicity. Stereotactic MR-guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath-hold gating and real-time MR-imaging as well as the option for daily online adaptive replanning to account for changes in target and/or organ-at-risk (OAR) location. MATERIALS/METHODS: 26 central (19 ultra-central) thoracic oligoprogressive/oligometastatic tumors treated with isotoxic (OAR constraints-driven) 5-fraction SMART (median 50 Gy, range 35-60) between 10/2019-10/2022 were reviewed. Central tumor was defined as tumor within or touching 2 cm around proximal tracheobronchial tree (PBT) or adjacent to mediastinal/pericardial pleura. Ultra-central was defined as tumor abutting the PBT, esophagus, or great vessel. Hard OAR constraints observed were ≤ 0.03 cc for PBT V40, great vessel V52.5, and esophagus V35. Local failure was defined as tumor progression/recurrence within the planning target volume. RESULTS: Tumor abutted the PBT in 31 %, esophagus in 31 %, great vessel in 65 %, and heart in 42 % of cases. 96 % of fractions were treated with reoptimized plan, necessary to meet OAR constraints (80 %) and/or target coverage (20 %). Median follow-up was 19 months (27 months among surviving patients). Local control (LC) was 96 % at 1-year and 90 % at 2-years (total 2/26 local failure). 23 % had G2 acute toxicities (esophagitis, dysphagia, anorexia, nausea) and one (4 %) had G3 acute radiation dermatitis. There were no G4-5 acute toxicities. There was no symptomatic pneumonitis and no G2 + late toxicities. CONCLUSION: Isotoxic 5-fraction SMART resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk oligoprogressive/oligometastatic thoracic tumors.

Spinal Cord Delineation Based on Computed Tomography Myelogram Versus T2 Magnetic Resonance Imaging in Spinal Stereotactic Body Radiation Therapy.

Purpose: Spinal cord delineation is critical to the delivery of stereotactic body radiation therapy (SBRT). Although underestimating the spinal cord can lead to irreversible myelopathy, overestimating the spinal cord may compromise the planning target volume coverage. We compare spinal cord contours based on computed tomography (CT) simulation with a myelogram to spinal cord contours based on fused axial T2 magnetic resonance imaging (MRI). Methods and Materials: Eight patients with 9 spinal metastases treated with spinal SBRT were contoured by 8 radiation oncologists, neurosurgeons, and physicists, with spinal cord definition based on (1) fused axial T2 MRI and (2) CT-myelogram simulation images, yielding 72 sets of spinal cord contours. The spinal cord volume was contoured at the target vertebral body volume based on both images. The mixed-effect model assessed comparisons of T2 MRI- to myelogram-defined spinal cord in centroid deviations (deviations in the center point of the cord) through the vertebral body target volume, spinal cord volumes, and maximum doses (0.035 cc point) to the spinal cord applying the patient's SBRT treatment plan, in addition to in-between and within-subject variabilities. Results: The estimate for the fixed effect from the mixed model showed that the mean difference between 72 CT volumes and 72 MRI volumes was 0.06 cc and was not statistically significant (95% confidence interval, -0.034, 0.153; P = .1832). The mixed model showed that the mean dose at 0.035 cc for CT-defined spinal cord contours was 1.24 Gy lower than that of MRI-defined spinal cord contours and was statistically significant (95% confidence interval, -2.292, -0.180; P = .0271). Also, the mixed model indicated no statistical significance for deviations in any of the axes between MRI-defined spinal cord contours and CT-defined spinal cord contours. Conclusions: CT myelogram may not be required when MRI imaging is feasible, although uncertainty at the cord-to-treatment volume interface may result in overcontouring and hence higher estimated cord dose-maximums with axial T2 MRI-based cord definition.

Comparison of MR-soft tissue based versus biliary stent based alignment for image guidance in pancreatic SBRT.

PURPOSE: The role of biliary stents in image-guided localization for pancreatic cancer has been inconclusive. To date, stent accuracy has been largely evaluated against implanted fiducials on cone beam computed tomography. We aim to use magnetic resonance (MR) soft tissue as a direct reference to examine the geometric and dosimetric impacts of stent-based localization on the newly available MR linear accelerator. METHODS: Thirty pancreatic cancer patients (132 fractions) treated on our MR linear accelerator were identified to have a biliary stent. In our standard adaptive workflow, patients were set up to the target using soft tissue for image registration and structures were re-contoured on daily MR images. The original plan was then projected on treatment anatomy and dose predicted, followed by plan re-optimization and treatment delivery. These online predicted plans were soft tissue-based and served as reference plans. Retrospective image registration to the stent was performed offline to simulate stent-based localization and the magnitude of shifts was taken as the geometric accuracy of stent localization. New predicted plans were generated based on stent-alignment for dosimetric comparison. RESULTS: Shifts were within 3 mm for 90% of the cases (mean = 1.5 mm); however, larger shifts up to 7.2 mm were observed. Average PTV coverage dropped by 1.1% with a maximum drop of 26.8%. The mean increase in V35Gy was 0.15, 0.05, 0.02, and 0.02 cc for duodenum, stomach, small bowel and large bowel, respectively. Stent alignment was significantly worse for all metrics except for small bowel (p = 0.07). CONCLUSIONS: Overall discrepancy between stent- and soft tissue-alignment was modest; however, large discrepancies were observed for select cases. While PTV coverage loss may be compensated for by using a larger margin, the increase in dose to gastrointestinal organs at risk may limit the role of biliary stents in image-guided localization.

Review of Prospective Trials Assessing the Role of Stereotactic Body Radiation Therapy for Metastasis-directed Treatment in Oligometastatic Genitourinary Cancers.

CONTEXT: Emerging evidence supports the use of stereotactic body radiation therapy (SBRT) as metastatic-directed therapy (MDT) for oligometastatic genitourinary cancers; however, the prospective data to guide its application as an alternative standard of care remain limited. OBJECTIVE: To review prospective trials that assess the role of SBRT for patients with genitourinary cancers within a modern framework of oligometastatic disease (OMD) and to highlight clinical scenarios where SBRT may offer a benefit to patients with metastatic cancer. EVIDENCE ACQUISITION: We performed a critical review of PubMed and clinicaltrials.gov in April 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, combined with expert input to identify prospective studies investigating the role of SBRT for oligometastatic prostate, renal, or bladder cancer. EVIDENCE SYNTHESIS: The most commonly studied application of SBRT has been for metachronous oligorecurrent hormone-sensitive prostate cancer (HSPC). Further prospective study is needed to define the role of SBRT in delaying time to next therapy or inducing synergy with other systemic therapies. CONCLUSIONS: SBRT has been associated with high rates of local control and minimal risk of toxicity with multiple trials assessing an MDT-alone approach for oligorecurrent HSPC. From a tumor-agnostic perspective, the clinical benefit of SBRT for OMD has been associated with the ability to extend overall survival. As methods of cancer detection and treatment evolve, expansion of studies that prospectively evaluate SBRT MDT, stratifying by tumor histology and oligometastatic state, is needed to inform optimal patient selection and treatment strategy. PATIENT SUMMARY: We review outcomes from prospective trials assessing the role of stereotactic body radiation therapy (SBRT) for oligometastatic genitourinary cancers, which have predominantly investigated SBRT for oligorecurrent prostate cancer. Much work remains to define how SBRT alone compares with other standard of care treatments for prostate cancer or the role of SBRT in tumor control or delaying time to next therapy in oligometastatic renal and bladder cancer.

Less Time Is Less Motion: Analysis of Practical Efficiencies Gained With a Modified Workflow Integrating Planar kV Midimaging With CBCT for Spine Stereotactic Body Radiation Therapy.

Purpose: Our purpose was to optimize an image guided radiation therapy (IGRT) workflow to achieve practical setup accuracy in spine stereotactic body radiation therapy (SBRT). We assessed the time-saving efficiencies gained from incorporating planar kV midimaging as a surrogate for cone beam computed tomography (CBCT) for intrafraction motion monitoring. Methods and Materials: We selected 5 thoracic spine SBRT patients treated in 5 fractions and analyzed patient shifts captured by a modified IGRT workflow using planar kV midimaging integrated with CBCT to maintain a tolerance of 1 mm and 1°. We determined the frequency at which kV midimaging captured intrafraction motion as validated on repeat CBCT and assessed the potential time and dosimetric advantages of our modified IGRT workflow. Results: Patient motion, detected as out-of-tolerance shifts on planar kV midimaging, occurred during 6 of 25 fractions (24%) and were validated on repeat CBCT 100% of the time. Observed intrafraction absolute shifts (mean ± standard deviation) for the 25 fractions were 0.39 ± 0.21, 0.56 ± 0.22, and 0.45 ± 0.21 mm for lateral-longitude-vertical translations and 0.38 ± 0.12°, 0.32 ± 0.09°, and 0.47 ± 0.14° for pitch-roll-yaw rotation, which if uncorrected, could have significantly affected target coverage and increased spinal cord dose. The average times for pretreatment imaging, midtreatment verification, and total treatment time were 8.94, 2.81, and 16.21 minutes. Our modified IGRT workflow reduced the total number of CBCTs required from 120 to 35 (70%) and imaging dose from 126.2 to 43.4 cGy (65.6%) while maintaining high fidelity for our patient population. Conclusions: Accurate patient positioning was effectively achieved with use of multiple 2-dimensional-3-dimensional kV images and an average of 1 verification CBCT scan per fraction. Integration of planar kV midimaging can effectively reduce treatment time associated with spine SBRT delivery and minimize the potential dosimetric effect of intrafraction motion on target coverage and spinal cord dose.

Magnetic Resonance-Guided Prostate Stereotactic Body Radiation Therapy With Daily Online Plan Adaptation: Results of a Prospective Phase 1 Trial and Supplemental Cohort.

Purpose: Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for prostate cancer allows for MR-based contouring, real-time MR motion management, and daily plan adaptation. The clinical and dosimetric benefits associated with prostate SMART remain largely unknown. Methods and Materials: A phase 1 trial of prostate SMART was conducted with primary endpoints of safety and feasibility. An additional cohort of patients similarly treated with prostate SMART were included in the analysis. SMART was delivered to 36.25 Gy in 5 fractions to the prostate ± seminal vesicles using the MRIdian linear accelerator system (ViewRay, Inc). Rates of urinary and gastrointestinal toxic effects and patient-reported outcome measures were assessed. Dosimetric analyses were conducted to evaluate the specific benefits of daily plan adaptation. Results: The cohort included 22 patients (n = 10 phase 1, n = 12 supplemental) treated in 110 fractions. Median follow-up was 7.9 months. Acute grade 2 urinary and gastrointestinal toxic effects were observed in 22.7% and 4.5%, respectively, and 4.5% and 0%, respectively, at last follow-up. No grade 3+ events were observed. Expanded Prostate Cancer Index-26 urinary obstructive scores decreased during SMART (mean, 9.3 points; P = .03) and returned to baseline by 3 months. No other significant changes in patient-reported outcome measures were observed. One-hundred percent of fractions required plan adaptation owing to exceeding organ-at-risk metrics (68%) or suboptimal target coverage (33%) resulting from anatomic changes. Minimum acceptable planning target volume, rectal, bladder, and urethra/bladder neck metrics were violated in 24%, 20%, 24%, and 33% of predicted plans, respectively; 0% of reoptimized plans violated metrics. Underlying causes for deficient dosimetry before reoptimization included changes in bladder filling, seminal vesicle position, prostate volume (median 4.7% increase by fraction 3; range, 0%-56%), and hotspots shifting into urethra/bladder neck. Conclusions: Prostate SMART results in low risk of acute toxic effects with improvements in target and organ-at-risk dosimetry. The clinical benefits resulting from daily plan adaptation, including urethra/bladder neck protection, warrant further investigation.

Longitudinal symptoms and temporal trends in palliative care, palliative radiotherapy, and anti-cancer treatment near end of life among patients with metastatic cancer.

BACKGROUND: Early specialty palliative care (PC) integration improves oncologic outcomes. We aimed to examine longitudinal relationships between specialty PC and palliative radiotherapy (RT), temporal distribution of symptoms, and predictors of earlier specialty PC. METHODS: We retrospectively reviewed 135 patients with metastatic cancer who received palliative RT at our institution (7/2017-2/2018) and who had died by final study follow-up (6/2021). Descriptive statistics summarized frequencies of clinical visits and symptoms over relative survival time (quartiles 1-3: first 75% of life remaining from metastatic diagnosis to death versus quartile 4: last 25% of life remaining from metastatic diagnosis to death). Logistic regression analyses revealed predictors of receiving earlier (quartiles 1-3) versus later (quartile 4) specialty PC. RESULTS: There were 16.3%, 10.4%, 26.7%, and 46.7% of palliative RT consultations, compared to 4.7%, 7.6%, 14.0%, and 73.7% of specialty PC visits, that occurred in quartiles 1, 2, 3, and 4, respectively. On multivariable analysis, pain significantly predicted for receiving earlier specialty PC [odds ratios (OR) =15.34; 95% confidence interval (CI): 2.16-324.23; P=0.020], while patients with ≥2 prior chemotherapy regimens were less likely to have received earlier specialty PC (OR =0.16; 95% CI: 0.04-0.58; P=0.009). The most common reasons for first specialty PC visit were addressing pain (61.0%) and goals of care (19.5%). Overall, 73.3% (99/135) of patients were referred to hospice and 9.6% (13/135) received either palliative RT, chemotherapy, or surgery within 30 days of death. CONCLUSIONS: Nearly 47% of palliative RT visits compared with 74% of specialty PC visits occurred in the last quarter of life from metastatic diagnosis to death. Multidisciplinary efforts are needed to manage longitudinal symptoms and offer goal-concordant care.

Patient and Treatment Factors Associated With Improved Local Control and Survival in Oligometastatic Bone Disease: Results From a Large Single-Institution Experience Using Stereotactic Body Radiation Therapy.

PURPOSE: Limited data exist to guide optimal patient selection and treatment of bone metastases with curative intent despite the increasing application of stereotactic body radiation therapy (SBRT) for oligometastatic (OM) disease control and reirradiation (Re-RT). METHODS AND MATERIALS: Clinical characteristics for 434 patients consecutively treated with bone SBRT at a single institution from March 2011 to June 2020 were analyzed by OM, spine, and nonspine bone using Cox regression to determine association with local control (LC), progression-free survival (PFS), and overall survival (OS), and the Kaplan-Meier method to estimate PFS and OS. RESULTS: Most patients had prostate (39%) or breast/lung (21%) cancer and 1 to 3 lesions (96%), with 651 lesions (spine 63%) treated for Re-RT (12%) or OMD (88%), including synchronous (10%), metachronous (28%), repeat (27%), or induced (23%) states as defined by The European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer criteria. Biologically effective dose (BED10) ≥50 (hazard ratio, 0.68; 95% confidence interval, 0.48-0.96; P < .03) predicted improved LC among OM lesions and planning target volume (PTV) ≥150 cc (hazard ratio, 1.94; 95% confidence interval, 1.02-3.70; P < .04) predicted worse LC for nonspine bone. Prostate histology, performance status (PS) 0 to 1, and metastasis-free interval ≥2 year predicted improved PFS and OS (P < .05). Metachronous, synchronous, or repeat OM had higher PFS and OS (P ≤ .001) than induced OM. With median follow-up 25.7 months, 1- and 2-year PFS was 63% and 47% for OM and 36% and 25% for Re-RT; 1- and 2-year OS was 87% and 73% for OM and 58% and 43% for Re-RT. Acute toxicities included grade 1 to 2 pain flare (9%) and fatigue (14%). Late toxicities included fracture (1%) for OM and myelopathy (2.5%) or nerve pain (1.2%) for Re-RT. CONCLUSIONS: BED10 ≥50 for OM and PTV <150 cc for nonspine bone lesions was associated with improved LC. Prostate histology, PS 0 to 1, metastasis-free interval ≥2 years, and metachronous, synchronous, or repeat presentations per The European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer criteria predicted improved PFS and OS among OM patients treated with bone SBRT.

Retrospective Review of Outcomes After Radiation Therapy for Oligoprogressive Disease on Immune Checkpoint Blockade.

PURPOSE: We retrospectively evaluated outcomes after radiation therapy for patients with oligoprogression on immune checkpoint inhibitors (ICI). METHODS AND MATERIALS: We identified patients irradiated to ≤5 progressive lesions while receiving ICI between 2010 and 2020. We excluded patients whose systemic therapy was switched after radiation but before progression. We evaluated predictors of local control (LC), progression-free survival (PFS) and overall survival (OS). RESULTS: We screened 1423 patients and identified 120 who were eligible; the most common histologies were lung cancer (n = 59) and melanoma (n = 36). The median number of oligoprogressive lesions was 1. For the median LC of irradiated oligoprogressive lesions, PFS and OS were not reached at 6.41 (4.67-7.66) and 29.80 (22.54-43.33) months, respectively. Tumor histology, radiated site, or radiation modality were not associated with LC, PFS, or OS. Local response to radiation (P < .0001) and radiation of newly developed lesions (P = .02) were associated with LC. Predictors of PFS on univariate and multivariate analyses were best response to radiation (P = .006) and high programmed death ligand 1 tumor proportion score (P = .02). On multivariate analyses, OS was associated with cumulative oligoprogressive lesion volumes (P = .02) and duration of ICI before oligoprogression (P = .03). CONCLUSIONS: Promising outcomes were observed among patients irradiated for oligoprogression on ICI, especially those with a favorable local response, high tumor programmed death ligand 1 expression, and those receiving ICI for longer periods before oligoprogression. These data can help identify patients well suited for radiation therapy versus those who should switch systemic treatment.

Stereotactic Magnetic Resonance-Guided Adaptive Radiation Therapy (SMART) for Abdominopelvic Oligometastases.

PURPOSE: Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation is frequently limited by the proximity of mobile organs sensitive to high radiation doses. The goal of this study was to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases. METHODS AND MATERIALS: We identified 101 patients with abdominopelvic oligometastases, including 20 patients enrolled on phase 1 protocols, who were consecutively treated with SMART on a 0.35T magnetic resonance linear accelerator (MR linac) at a single institution from October 2019 to September 2021. Local control and overall survival were analyzed using the Kaplan-Meier method. RESULTS: Overall, 114 tumors were treated. The most common histology was prostate adenocarcinoma (60 tumors [53.5%]), and 65 sites (57.0%) were centered in the pelvis. Ninety-one sites (79.8%) were treated to 8 Gy × 5, and 49 (43.0%) were treated with breath-hold respiratory gating. Online adaptation resulted in a clinically significant improvement in coverage or organ sparing in 86.6% of delivered fractions. The median time required for adaptation was 24 minutes, and the median time in the treatment room was 58 minutes. With median follow-up of 11.4 months, the 12-month local control was 93% and was higher for prostate adenocarcinoma versus other histologies (100% vs 84%; P = .009). The 12-month overall survival was 96% and was higher for prostate adenocarcinoma versus other histologies (100% vs 91%; P = .046). Three patients (3.0%) developed grade 3 toxic effects (colonic hemorrhage at 3.4 months and urinary tract obstructions at 10.1 and 18.4 months, respectively). CONCLUSIONS: In this study, SMART was feasible, safe, and effective for delivering ablative radiation therapy to abdominopelvic metastases. Adaptive planning was necessary in the large majority of cases. The advantages of SMART warrant its further investigation as a standard option for the treatment of abdominopelvic oligometastases.

Evaluating the Role of Stereotactic Body Radiation Therapy With Respect to Androgen Receptor Signaling Inhibitors for Oligometastatic Prostate Cancer.

PURPOSE: Outcomes of stereotactic body radiation therapy (SBRT) with respect to androgen receptor signaling inhibitors (ARSI) have not been characterized for oligometastatic prostate cancer. We sought to characterize prostate specific antigen (PSA) response and progression-free survival (PFS) after SBRT among men who have progressed on ARSI therapy in the oligometastatic castration-resistant setting. METHODS AND MATERIALS: A single-institution retrospective analysis was performed for men with ARSI-resistant, oligometastatic, castrate-resistant prostate cancer (omCRPC). Intervention consisted of SBRT. PSA reduction greater than 50% and median PFS (PSA or radiographic progression) as determined by routine care comprised outcome measurements. Cox regression analysis was used to determine factors influencing PFS. RESULTS: Thirty-five men with ARSI-resistant omCRPC and 65 lesions treated with SBRT were followed for a median of 17.2 months. In 63% of men PSA reduction greater than 50% was achieved. Median PFS was 9.0 months. Incomplete ablation (defined as the presence of untreated lesions after SBRT or receipt of prior palliative radiation therapy doses) was associated with worse PFS (hazard ratio 4.21 [1.74-10.19]; P < .01). For a subgroup of 22 men with complete ablation of metastatic sites with SBRT, the median PFS was 13.1 months. One-year overall survival was 93.1% (95% confidence interval, 84.4-100). CONCLUSIONS: SBRT may augment the efficacy of ARSI in omCRPC, provided that all lesions receive ablative radiation doses. Future prospective study of SBRT for men receiving ARSI is warranted.

Oligometastatic adenoid cystic carcinoma: Correlating tumor burden and time to treatment with outcomes.

BACKGROUND: There is limited information on the management and outcomes of oligometastases (OM) in adenoid cystic carcinoma (ACC). METHODS: Retrospective study of 42 patients with metastatic ACC of the head and neck. Imaging studies were analyzed to identify patients with OM (1-5 lesions) at any point during follow-up. RESULTS: There was radiographic evidence of OM in 33/42 (79%) patients. Eighteen patients had OM when treated for metastases, with median overall survival (OS) of 36.0 versus 9.2 years for patients with polymetastases (6+ lesions, HR 0.38, 95%CI 0.14-0.89). Earlier locally ablative treatment, but not systemic treatment, of patients with OM predicted improved survival 3 years after metastasis (HR 0.15, 95%CI 0.02-0.63) and postponed systemic treatment by 80 more months (HR 0.22, 95%CI 0.07-0.71). CONCLUSIONS: There is a considerable population of ACC patients with detectable oligometastases, and early locally ablative treatment of oligometastases may be associated with improved outcomes.

Characteristics and Predictors of Radiographic Local Failure in Patients With Spinal Metastases Treated With Palliative Conventional Radiation Therapy.

PURPOSE: Although local control is an important issue for longer-term survivors of spinal metastases treated with conventional external beam radiation therapy (EBRT), the literature on radiographic local failure (LF) in these patients is sparse. To inform clinical decision-making, we evaluated rates, consequences, and predictors of radiographic LF in patients with spinal metastases managed with palliative conventional EBRT alone. METHODS AND MATERIALS: We retrospectively reviewed 296 patients with spinal metastases who received palliative EBRT at a single institution (2006-2013). Radiographic LF was defined as radiologic progression within the treatment field, with death considered a competing risk. Kaplan-Meier, cumulative incidence, and Cox regression analyses determined overall survival estimates, LF rates, and predictors of LF, respectively. RESULTS: There were 182 patients with follow-up computed tomography or magnetic resonance imaging; median overall survival for these patients was 7.7 months. Patients received a median of 30 Gy in 10 fractions to a median of 4 vertebral bodies. Overall, 74 of 182 patients (40.7%) experienced LF. The 6-, 12-, and 18-month LF rates were 26.5%, 33.1%, and 36.5%, respectively, while corresponding rates of death were 24.3%, 38.1%, and 45.9%. Median time to LF was 3.8 months. Of those with LF, 51.4% had new compression fractures, 39.2% were admitted for pain control, and 35.1% received reirradiation; median time from radiation therapy (RT) to each of these events was 3.0, 5.7, and 9.2 months, respectively. Independent predictors of LF included single-fraction RT (8 Gy) (hazard ratio [HR], 2.592; 95% confidence interval [CI], 1.437-4.675; P = .002), lung histology (HR, 3.568; 95% CI, 1.532-8.309; P = .003), and kidney histology (HR, 4.937; 95% CI, 1.529-15.935; P = .008). CONCLUSIONS: Patients experienced a >30% rate of radiographic LF by 1 year after EBRT. Single-fraction RT and lung or kidney histology predicted LF. Given the high rates of LF for patients with favorable prognosis, assessing the risk of death versus LF is important for clinical decision-making.

Quantitative-qualitative analyses of patient-reported pain response after palliative radiation therapy.

PURPOSE: While the 0-10 pain scale is often used to assess treatment response, it may not accurately reflect change in pain over time. The purpose of this study is to correlate pain improvement using the 0-10 pain scale to patients' perceived improvement in pain following palliative radiation therapy (RT), and to qualitatively characterize themes of pain assessment. METHODS: Patients age ≥ 20 receiving RT for spinal metastases were enrolled. Patients rated their pain (0-10) at the treatment site at RT start, and 1 and 4 weeks post-RT completion. At 1 and 4 weeks post-RT, patients reported their perceived percent improvement in pain (pPIP) (0-100%), which was compared to calculated percent improvement in pain (cPIP) based on the 0-10 pain scores. At 4 weeks post-RT, 20 randomly selected patients participated in a qualitative pain assessment. RESULTS: Sixty-four patients treated at 1-2 sites were analyzed. At 1 week post-RT completion, 53.7% (36/67) reported pPIP within 10 percentage points of cPIP, 32.8% (22/67) reported pPIP > 10 percentage points higher than cPIP, and 13.4% (9/67) reported pPIP > 10 percentage points lower than cPIP. Similar degrees of discordance were seen at 4 weeks post-RT. Qualitative analysis revealed five themes: pain quality (n = 19), activities (n = 9), function (n = 7), medication use (n = 2), and radiation side effects (n = 1). CONCLUSIONS: About half of patients reported a pPIP substantially disparate from their cPIP, and the change in pain measured by the 0-10 scale tended to underestimate the degree of perceived pain improvement. Multiple themes were identified in qualitative analysis of pain response.

Patterns of Specialty Palliative Care Utilization Among Patients Receiving Palliative Radiation Therapy.

CONTEXT: Palliative radiation therapy (RT) is frequently used to ameliorate cancer-associated symptoms and improve quality of life. OBJECTIVES: To examine how palliative care (PC) as a specialty is integrated at the time of RT consultation for patients with advanced cancer. METHODS: We retrospectively reviewed 162 patients with metastatic cancer who received palliative RT at our institution (7/2017-2/2018). Fisher's exact test identified differences in incidence of receiving any specialty PC. Logistic regression analyses determined predictors of receiving PC. RESULTS: Of the 74 patients (46%) who received any specialty PC, 24 (32%) initiated PC within four weeks of RT consultation. The most common reasons for specialty PC initiation were pain (64%) and goals of care/end-of-life care management (23%). Referrals to specialty PC were made by inpatient care teams (48.6%), medical oncologists (48.6%), radiation oncologists (1.4%), and self-referring patients (1.4%). Patients with pain at RT consultation had a higher incidence of receiving specialty PC (58.7% vs. 37.4%, P = 0.0097). There was a trend toward decreased PC among patients presenting with neurological symptoms (34.8% vs. 50%, P = 0.084). On multivariable analysis, receiving specialty PC significantly differed by race (non-white vs. white, odds ratio [OR] = 6.295 [95% CI 1.951-20.313], P = 0.002), cancer type (lung vs. other histology, OR = 0.174 [95% CI 0.071-0.426], P = 0.0006), and RT consultation setting (inpatient vs. outpatient, OR = 3.453 [95% CI 1.427-8.361], P = 0.006). CONCLUSION: Fewer than half of patients receiving palliative RT utilized specialty PC. Initiatives are needed to increase PC, especially for patients with lung cancer and neurological symptoms, and to empower radiation oncologists to refer patients to specialty PC.