Spine Stereotactic Radiosurgery Provides Long-Term Local Control and Overall Survival for Benign Intradural Tumors.

BACKGROUND AND OBJECTIVES: The role of radiosurgery in the treatment of benign intracranial tumors is well established. However, there are limited long-term follow-up studies on outcomes after stereotactic radiosurgery (SRS) for benign intradural spinal tumors. In this article, we report a large single-institution experience in using SRS to treat patients with benign intradural tumors of the spine. METHODS: Overall, 184 patients (55% female) and 207 benign intradural tumors were treated. The median patient age was 52 years (range: 19-93). Tumor histology included schwannoma (38%), meningioma (15%), neurofibroma (21%), hemangioma (9%), hemangioblastoma (8%), hemangiopericytoma (5%), and paraganglioma (4%). Thirty-four (16%) lesions underwent resection before radiosurgery. Twenty-three (11%) lesions were NF1-mutated. The median single-fraction margin dose was 14 Gy (range: 11-20), and the median multifraction margin dose was 21 Gy (range: 15-30). RESULTS: The median follow-up was 63 months (range: 1-258). At last follow-up, tumors volumetrically regressed (15%), remained stable (77%), or locally progressed (8%, median: 20 months [range: 3-161]) after SRS. The 1-, 5-, and 10-year local control rates were 97%, 92%, and 90%, respectively. On multivariable analysis, the absence of the NF1 mutation (P = .004, hazard ratio: 0.23, 95% CI: 0.08-0.63) and single-fraction SRS (P = .007, hazard ratio: 0.24, 95% CI: 0.08-0.68) correlated with improved local control. The median overall survival was 251 months (range: 1-258), and 1-, 5-, and 10-year overall survival rates were 95%, 85%, and 70%, respectively. For patients with pre-existing symptoms, tumor-associated pain and neurological deficits were noted to improve or remain stable in 85% and 87% of cases, respectively. Adverse radiation effects included delayed myelopathy (1%), acute pain flare (9%), dermatitis (0.5%), dysphagia (0.5%), and dysphonia (0.5%). CONCLUSION: With long-term follow-up, spine radiosurgery is a safe and effective treatment for benign intradural tumors. In carefully selected patients, even with an NF1 mutation, SRS is associated with a high likelihood of local tumor control.

Stereotactic radiosurgery for patients with spinal metastases from prostate cancer.

PURPOSE: Spinal metastases may result in intractable pain, neurological deficit, and vertebral body collapse. There are only a few studies describing outcomes following spine stereotactic radiosurgery (SRS) specifically for prostate cancer metastases. METHODS: A prospectively collected database of patients with prostate cancer spinal metastases treated at the University of Pittsburgh Medical Center from 2003 to 2023 was analyzed. The primary outcome was local control (LC). Secondary outcomes were overall survival (OS), pain resolution, and adverse radiation effects (AREs). RESULTS: Thirty-seven patients and 51 lesions were identified. Fifteen lesions (29%) were previously resected and 34 lesions (67%) were previously irradiated. The median tumor volume was 37.0 cc (range: 2.9-263.3). A majority of lesions (71%) were treated in a single fraction (median 20 Gy, range: 14-22.5); multi-fractionated treatment consisted of 21-30 Gy in 2-5 fractions. Median follow-up was 12 months (range: 1-146). The 6-month, 1-year, and 2-year LC rates were 97%, 91%, and 91%, respectively. No tested prognostic factors were associated with LC, including hormone sensitivity. The 6-month, 1-year, and 2-year OS rates were 71%, 56%, and 32%; age > 70 years (p = 0.048) and tumor volume > 30 cc (p = 0.03) were associated with inferior rates of OS. Complete or partial pain response was observed in 58% of patients. There were 8 instances (16%) of AREs, 2 of which were vertebral compression fractures (4%). CONCLUSION: Radiosurgery as a primary or adjuvant treatment modality for prostate cancer spinal metastases confers durable LC and moderate pain relief with minimal toxicity. Further studies are warranted to optimize management in this patient population.

Safety and Efficacy of Balloon-Assisted Kyphoplasty Followed by Stereotactic Body Radiation Therapy for Pathological Fractures.

BACKGROUND AND OBJECTIVES: In patients experiencing pain secondary to pathological compression fractures, balloon-assisted kyphoplasty and subsequent stereotactic body radiation therapy (SBRT) may allow for restoration of vertebral height and irradiation of the underlying malignancy to control local disease progression. The aim of this study was to evaluate the safety and efficacy of kyphoplasty treatment before SBRT in patients with spinal metastases and benign tumors. METHODS: An analysis of a prospectively collected database of 70 patients and 75 metastatic and benign spinal lesions that underwent kyphoplasty before SBRT at a single institution (2002-2023) was conducted. Patient characteristics were recorded, including treatment history, dosimetry and fractionation schedule, pain outcomes, local control (LC), and overall survival. The Bilsky score and Spinal Instability Neoplastic Score were calculated to assess epidural involvement and spinal stability, respectively. RESULTS: The median time from kyphoplasty to SBRT was 29 days (range: 2-159). Seventy-two lesions (96%) were managed with single-fraction SBRT and 3 lesions (4%) with a multifraction regimen. The median single-fraction prescription dose was 20 Gy (range: 12-25) delivered to a median tumor volume of 35.1 cc (range: 2.2-160). After a median follow-up period of 9 months (range: 1-201), 6 lesions (8%) locally progressed. Pain was reported to improve or remain stable for most patients (88%). The LC rate was 88% at 6 months, 1 year, and 2 years. No prognostic factors were significantly associated with LC. The median overall survival was 11 months (range: 1-201) after radiosurgery. There were no reports of cement extravasation or radiation-induced neurological deficit. Two acute pain flares (3%) were reported 1 and 3 months after radiosurgery. CONCLUSION: The combined kyphoplasty and SBRT treatment paradigm can be used to treat patients with painful pathological compression fractures. Long-term LC and patient-reported improvement in pain were observed without the morbidity associated with open surgery.

Preoperative stereotactic radiosurgery for cerebral metastases: safe, effective, and decreases steroid dependency.

OBJECTIVE: Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm3) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score-matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions. METHODS: Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched. RESULTS: Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm3, p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38-6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38-3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04-1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02-0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02). CONCLUSIONS: Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.

Stereotactic Radiosurgery for Patients with Spinal Metastases from Thyroid Cancer: A 20-Year Experience.

OBJECTIVE: Primary thyroid cancer metastasizing to the spine portends poor survival and low quality of life. Current management strategies continue to evolve. This single-institution retrospective study analyzes outcomes after spinal stereotactic radiosurgery for patients with spinal metastases from thyroid cancer. METHODS: Nineteen patients (median age: 64.5 years) were treated with stereotactic radiosurgery (SRS) for spinal primary thyroid metastases (40 metastases, 47 vertebral levels) between 2003 and 2023. Nineteen (47.5%) lesions had epidural involvement and 20 (50%) lesions were classified as potentially unstable or unstable via the Spinal Instability Neoplastic Score. The median tumor volume per lesion was 33 cc (range: 1.5-153). The median single fraction prescription dose was 20 Gy (range: 12-23.5). RESULTS: The median follow-up period was 15 months (range: 2-40). Five (12.8%) lesions locally progressed at a median of 9 months (range: 4-26) after SRS. The 1-, 2-, and 3-year local tumor control rates per lesion were 90.4%, 83.5%, and 75.9%, respectively. On univariate analysis, age at SRS >70 years (P = 0.05, hazard ratio: 6.86, 95% confidence interval: 1.01-46.7) was significantly correlated with lower rates of local tumor control. The median overall survival was 35 months (range: 2-141). The 1-, 2-, and 3-year overall survival rates were 73.7%, 50.4%, and 43.2%, respectively. For 33 lesions initially associated with pain, patients reported pain improvement (22 lesions, 66.7%), stability (10 lesions, 30.3%), and worsening (1 lesion, 3.0%) after SRS. One patient developed dysphagia 4 months after SRS treatment. CONCLUSIONS: SRS can be utilized as an effective and safe primary and adjuvant treatment option for primary thyroid metastases to the spine.

The role of spine stereotactic radiosurgery for patients with breast cancer metastases.

PURPOSE: Breast cancer that metastasizes to the spine is associated with low quality of life and poor survival. Radiosurgery has an increasing role in this patient population. This single-institution (2003-2023) study analyzes clinical outcomes and prognostic factors for patients who underwent spinal stereotactic radiosurgery (SSRS) for metastatic breast cancer. METHODS: Ninety patients (155 unique breast cancer spinal metastases) were treated with SSRS. The median age was 57 years (range: 35-88), and the median KPS was 80 (range: 40-100). Forty-two (27%) lesions were managed surgically prior to radiosurgery. At SSRS, 75 (48%) lesions impinged or compressed the spinal cord per the epidural spinal cord scale (ESCC). Seventy-nine (51%) lesions were categorized as potentially unstable or unstable by the Spinal Instability Neoplastic Score (SINS). RESULTS: The median follow-up was 15 months (range: 1-183). The median single-session tumor volume was 25.4 cc (range: 2-197), and the median single-fraction prescription dose was 17 Gy (range: 12-25). Seven (5%) lesions locally progressed. The 1-, 2-, and 5-year local control rates were 98%, 97%, and 92%, respectively. The median overall survival (OS) for the cohort was 32 months (range: 2-183). The 1-, 2-, and 5-year OS rates were 72%, 53%, and 30%, respectively. On univariate analysis, KPS ≥ 80 (p = 0.009, HR: 0.51, 95% CI: 0.31-0.84) was associated with improved OS. Patient-reported pain improved (68%), remained stable (29%), or worsened (3%) following radiosurgery. Fifteen (10%) radiation-induced toxicities were reported. CONCLUSIONS: Spinal radiosurgery is a safe and highly effective long-term treatment modality for metastases to the spine that originate from breast cancer.

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. Design, Setting, and Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. Interventions: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. Main Outcomes and Measures: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. Results: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. Conclusions and Relevance: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. Trial Registration: ClinicalTrials.gov Identifier: NCT00922974.

Long term outcomes with linear accelerator stereotactic radiosurgery for treatment of jugulotympanic paragangliomas.

BACKGROUND: Data supporting linear accelerator (linac) stereotactic radiosurgery (SRS) for jugulotympanic paragangliomas (JTPs) come from small series with minimal follow-up. Herein, we report a large series of JTPs with extended follow-up after frameless linac-based SRS. METHODS: JTPs treated with linac-based SRS from 2002 to 2019 with 1+ follow-up image were reviewed for treatment failure (radiographic or clinical progression, or persistent symptoms after SRS requiring intervention) and late toxicities (CTCAE v5.0). RESULTS: Forty JTPs were identified; 30 were treated with a multifraction regimen. Median clinical and radiographic follow-up was 79.7 (interquartile range [IQR] 31.7-156.9) and 54.4 months (IQR 17.9-105.1), respectively, with a median 4.5 follow-up scans (IQR 2-9). Seven-year progression-free survival (PFS) was 97.0% (95% confidence interval 91.1%-100.0%). PFS was similar between single- and multifraction regimens (log rank P = .99). Toxicity was seen in 7.7% (no grade III). CONCLUSIONS: With extended clinical and radiographic follow-up, frameless linac-based SRS provides excellent local control with mild toxicity <8%.

Patterns of Failure After Adjuvant Stereotactic Body Radiation Therapy for Pancreatic Cancer With Close or Positive Margins.

PURPOSE: There is no consensus on treatment volumes for adjuvant stereotactic body radiation therapy (SBRT) for pancreatic cancer. Herein, we report patterns of failure after pancreatic SBRT for close/positive margins, which may inform target volume design. METHODS AND MATERIALS: An institutional review board-approved retrospective review of patients with pancreatic adenocarcinoma treated with adjuvant SBRT for close/positive margins from 2009 to 2018 was conducted. Patterns of failure were defined as local (LF) within the tumor bed, regional (RF) within lymph nodes or anastomoses, or distant (DF). The cumulative incidence of locoregional failure was calculated using the cumulative incidence function accounting for the competing risk of death. LFs were mapped to the planning target volume (PTV) and classified as in-field (completely within the PTV), marginal (partially within the PTV), or out-of-field (completely outside the PTV). The location of LFs was compared with the Radiation Therapy Oncology Group 0848 contouring atlas to determine whether standard postoperative radiation therapy volumes would have included the LF. RESULTS: Seventy-six patients were treated with adjuvant SBRT for close (51.3%) or positive (48.7%) margins. Most (81.6%) received 36 Gy in 3 fractions, with a median PTV volume of 17.8 cc (interquartile range, 12.1-25.6). With a median follow-up of 17.0 months (interquartile range, 7.3-28.4), crude rates of first isolated LF, isolated RF, and DF +/- LF or RF were 9.2%, 6.6%, and 56.6%, respectively. Two-year cumulative incidences of LF, RF, locoregional failure, and DF were 34.9%, 30.8%, 49.2%, and 60.4%, respectively. Of 28 reviewable LFs, 21.4% were in-field while the remainder were completely outside (60.7%) or partially outside (17.9%) the PTV. Most LFs (92.9%) would have been encompassed by the Radiation Therapy Oncology Group consensus target volumes. CONCLUSIONS: After adjuvant pancreatic SBRT for close/positive margins, the majority of LFs were outside the PTV but within contemporary target volumes for conventional radiation therapy.

Salvage Curative-Intent Reirradiation Stereotactic Body Radiation Therapy for Isolated Pelvic and/or Paraortic Recurrences of Gynecologic Malignancies.

PURPOSE: To determine the feasibility of stereotactic body radiation therapy (SBRT) for isolated nodal recurrences of gynecologic malignancies within a previously irradiated area. METHODS AND MATERIALS: A retrospective review was performed on 20 patients who underwent 21 curative-intent reirradiation SBRT treatments for locoregional recurrences of gynecologic malignancies. Disease control and survival outcomes were analyzed with the Kaplan-Meier method and log-rank test. Treatment toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.03. RESULTS: All patients had an isolated pelvic, paraortic, or intra-abdominal nodal recurrence, with the exception of 1 patient who had a concurrent paraortic and right acetabulum metastasis, both of which were irradiated with SBRT. Primary sites included cervix (30.0%), uterus (55.0%), vulva (5.0%), vagina (5.0%), and ovary (5.0%). Median prior external beam radiation therapy dose was 45 Gy. Recurrences were in field in 14 (66.7%) and marginal in 7 (33.3%). SBRT was directed to the pelvis in 13 cases (61.9%) and to paraortic or celiac nodes in 8 (38.1%). The most common SBRT regimen was 40 to 45 Gy in 5 fractions (n = 12). At a median follow-up of 31.2 months, 3-year actuarial in-field local control, distant progression-free survival, and overall survival were 61.4%, 44.0%, and 51.9%, respectively. At the time of last follow-up, 9 (45.0%) patients remained alive without evidence of disease. Actuarial 3-year risk of grade ≥2 and grade ≥3 late toxicities was 38.1% and 14.3%, respectively. CONCLUSIONS: SBRT for isolated pelvic or intra-abdominal recurrences of gynecologic malignancies within a previously irradiated field is feasible with an acceptable toxicity rate. With this approach, about half of patients achieved durable disease-free survival.

Initial Results of a Prospective Study of Adjuvant Pancreatic Stereotactic Body Radiation Therapy for Close or Positive Margins.

PURPOSE: Patients with close or positive margins after surgery for pancreatic carcinoma are at a high risk for recurrence. Stereotactic body radiation therapy (SBRT) allows for safe dose escalation with great conformity and short duration of treatment. Herein, we report the initial results of a prospective observational study that evaluated the efficacy and safety of this treatment option. METHODS AND MATERIALS: Patients eligible for the study had pathologically proven T1-4N0-1M0 pancreatic adenocarcinoma with a positive margin (≤1 mm) or a close margin defined as <2.5 mm. Patients were treated with either neoadjuvant or adjuvant chemotherapy, if eligible for systemic therapy. All patients received 36 Gy in 3 fractions to the close or positive margin site. RESULTS: From February 2013 to January 2018, 50 patients were enrolled with 49 patients treated on protocol and included in the analysis. The median age was 71 years. The median clinical target volume was 11.3 cc and median planning target volume 22.0 cc. The median overall survival was 23.7 months (95% confidence interval, 13.6-33.8). Local progression-free survival at 1 and 2 years was 85% and 77%, respectively. Regional progression-free survival at 1 and 2 years was 73% and 73%, respectively. Distant metastases-free survival was 57% and 49% at 1 and 2 years, respectively. Grade 3+ radiation toxicity was only 4.1% and occurred in 2 patients. CONCLUSIONS: Adjuvant pancreatic SBRT was shown to be a safe and feasible treatment option for patients with high-risk pancreatic adenocarcinoma and close or positive margins. This is the first prospective study of SBRT in high-risk postoperative pancreatic cancer. Our results yielded significant local and regional control with low rates of acute toxicity. This technique does not interrupt the administration of systemically dosed multiagent chemotherapy and can be safely interdigitated between cycles because SBRT is only 1 week of treatment.

Stereotactic Ablative Radiation Therapy for Unresectable Colorectal Oligometastases.

PURPOSE: Patients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clinical trial. METHODS AND MATERIALS: Patients with a pathologically proven diagnosis of oligometastatic colorectal cancer were enrolled as part of a prospective study. SABR dose and fractionation schedules were dependent on the lesion location and size. Patient follow-up occurred 6 weeks after completion of SABR and at 3-month intervals for the following 3 years. Patients received the Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up visit to assess PR-QoL. The total Functional Assessment of Cancer Therapy-General questionnaire scores were compared with those from baseline using the Wilcoxon signed rank test. Overall survival, local progression-free survival (PFS), and distant PFS were calculated using the Kaplan-Meier estimation to the date of the last follow-up visit/death or local/distant failure. RESULTS: A total of 31 patients with oligometastatic colorectal cancer with 1 (71.0%), 2 (16.1%), 3 (3.2%), 4 (3.2%), or 5 (6.5%) metastatic lesions were identified. After a median follow-up time of 50.1 months, the median OS from the time of completion of the SABR was 53.9 months (95% confidence interval, 23.2-84.6), and the 5-year OS, local PFS, and distant PFS were 45%, 83%, and 27%, respectively. Acute grade 2+ toxicity was 9.7% (pain, nausea, fatigue) and late grade 3+ toxicity (small bowel obstruction) was 3.2% with no significant change in PR-QoL in the year after SABR. CONCLUSIONS: This subset analysis of a prospective phase 2 study demonstrates that SABR is a safe and effective treatment option for patients with unresectable oligometastic colorectal cancer. In addition, SABR of oligometastatic disease preserves PR-QoL.

Initial Results of a Multicenter Phase 2 Trial of Stereotactic Ablative Radiation Therapy for Oligometastatic Cancer.

PURPOSE: Oligometastatic disease has emerged as a potentially curable state in the spectrum of cancer progression. Aggressive local therapy such as stereotactic ablative radiation therapy (SABR) may improve oncologic outcomes. Herein, we report the initial oncologic outcomes and patient-reported quality of life (PR-QoL) from a phase 2 multicenter trial for patients with oliogmetastatic disease. METHODS AND MATERIALS: Patients with oligometastatic disease (1-5 metastases) were prospectively recruited between 2011 and 2017. SABR dose and fractionation was dependent on the lesion size and location. Patient follow-up occurred within 6 weeks of completion of SABR and at 3-month intervals. Patients received a Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up to assess for PR-QoL. Median follow-up was calculated by reverse Kaplan-Meier method. Overall survival (OS), local progression-free survival, and distant progression-free survival were calculated using the Kaplan-Meier method. RESULTS: We enrolled 147 patients with oligometastatic cancer with a median age of 66.4 years (interquartile range, 59.9-74.6). The most common primary tumors included lung (21.8%, non-small cell: n = 29, small cell: n = 3), colorectal adenocarcinoma (21.1%), and head and neck (10.9%, squamous cell carcinoma: n = 11). In a median follow-up of 41.3 months (interquartile range: 14.6-59.0), the median OS was 42.3 months (95% confidence interval: 27.4-∞) with 5-year OS of 43%. Five-year local progression-free survival and distant progression-free survival were 74% and 17%, respectively. Acute grade 2+ and 3+ toxicity were 7.5% and 2.0%, respectively, and late grade 2+ and 3+ toxicity were both 1.4%. There was no significant change in quality of life at completion and 6 weeks, 3 months, and 9 months after treatment. At 6 and 12 months, patients were found to have statistically significant improvement in PR-QoL. CONCLUSIONS: This multicenter prospective phase 2 study demonstrates that SABR for recurrent oligometastatic cancer is a feasible and tolerable treatment option with minimal acute and late grade 3 toxicity. Additionally, PR-QoL was not adversely affected.

Thoracic reirradiation with SBRT for residual/recurrent and new primary NSCLC within or immediately adjacent to a prior high-dose radiation field.

PURPOSE: Local failure following concurrent chemoradiation and in-lobe failures following stereotactic body radiation therapy (SBRT) are common. We evaluated our institutional experience using SBRT as salvage in this setting. METHODS AND MATERIALS: Seventy-two patients were reirradiated with SBRT for residual, locally recurrent, or new primary non-small cell lung cancer within or adjacent to a high-dose external beam radiation therapy or SBRT field. Kaplan-Meier analysis with log-rank test were used to estimate endpoints and differentiate cohorts. RESULTS: Median follow-up was 17.9 months. Patients had residual or recurrent disease (54.2%); 45.8% had new lung primaries. Median reirradiated T size was 2.5 cm (range, 0.8-7.8 cm). Median pre-retreatment maximum standardized uptake value (SUVmax) was 7.15 (range, 1.2-37.6). The most common SBRT reirradiation regimen was 48 Gy in 4 fractions (range, 17-60 Gy in 1-5 fractions). Median progression-free survival was 15.2 months, and median overall survival was 20.8 months. Two-year local failure was 21.6%. Patients with SUVmax at reirradiation <7.0 had a 2-year local control of 93.1% versus 61.1% above the median (P < .001). The 2-year rate of distant metastases was 10.4% versus 54.1% in patients treated for a new primary versus residual or recurrent disease (P < .001). Median progression-free survival was 31.9 months versus 8.4 months, respectively (P = .037). Median survival of patients treated for new primary was 25.2 months versus 16.2 months with residual or recurrent disease (P = .049), and median survival for patients with reirradiation SUVmax below the median was 42.0 months versus 9.8 months above the median (P < .001). Acute any-grade toxicity was seen in 29.2% of patients, acute grade 3 toxicity in 11.1%, and late grade 3 toxicity in 1.4% with no treatment-related deaths. CONCLUSIONS: SBRT appears to be a safe and effective means of salvaging recurrent, residual, or new primary NSCLC in or adjacent to a previous high-dose radiation field.

Stereotactic body radiation therapy for benign spine tumors: is dose de-escalation appropriate?

OBJECTIVE Akin to the nonoperative management of benign intracranial tumors, stereotactic body radiation therapy (SBRT) has emerged as a nonoperative treatment option for noninfiltrative primary spine tumors such as meningioma and schwannoma. The majority of initial series used higher doses of 16-24 Gy in 1-3 fractions. The authors hypothesized that lower doses (such as 12-13 Gy in 1 fraction) might provide an efficacy similar to that found with the dose de-escalation commonly used for intracranial radiosurgery to treat acoustic neuroma or meningioma and with a lower risk of toxicity. METHODS The authors identified 38 patients in a prospectively maintained institutional radiosurgery database who were treated with definitive SBRT for a total of 47 benign primary spine tumors between 2004 and 2016. SBRT consisted of 9-21 Gy in 1-3 fractions using the CyberKnife (n = 11 [23%]), Synergy S (n = 21 [45%]), or TrueBeam (n = 15 [32%]) radiosurgery platform. For a comparison of SBRT doses, patients were dichotomized into 1 of 2 groups (low-dose or high-dose SBRT) using a cutoff biologically effective dose (BED10Gy) of 30 Gy. Tumor control was calculated from the date of SBRT to the last follow-up using Kaplan-Meier survival analysis, with comparisons between groups completed using a log-rank method. To account for potential indication bias, a propensity score analysis was completed based on the conditional probabilities of SBRT dose selection. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0 with a focus on grade 3+ toxicity and the incidence of pain flare. RESULTS For the 38 patients, the most common histological findings were meningioma (15 patients), schwannoma (13 patients), and hemangioblastoma (7 patients). The median age at SBRT was 58 years (range 25-91 years). The 47 treated lesions were located in the cervical (n = 18), thoracic (n = 19), or lumbosacral (n = 10) spine. Five (11%) lesions were lost to follow-up after SBRT. The median follow-up duration for the remaining 42 lesions was 54 months (range 1.2-133 months). Six (16%) patients (with a total of 8 lesions) experienced pain flare after SBRT; no significant predictor of pain flare was identified. No grade 3+ acute- or late-onset complication was noted. The 5-year local control rate was 76% (95% CI 61%-91%). No significant difference in local control according to dose, fractionation, previous radiation, surgery, tumor histology, age, treatment platform, planning target volume, or spine level treated was found. The 5-year local control rates for low- and high-dose treatments were 73% (95% CI 53%-93%) and 83% (95% CI 61%-100%) (p = 0.52). In propensity score-adjusted multivariable analysis, no difference in local control was identified (HR 0.30, 95% CI 0.02-5.40; p = 0.41). CONCLUSIONS Long-term follow-up of patients treated with SBRT for benign spinal lesions revealed no significant difference between low-dose (BED10Gy ≤ 30) and high-dose SBRT in local control, pain-flare rate, or long-term toxicity.

Stereotactic Body Radiation Therapy for Pulmonary Oligometastases Arising from Non-lung Primaries in Patients Without Extrapulmonary Disease.

Purpose Stereotactic body radiation therapy (SBRT) is increasingly used in the management of patients with oligometastatic cancers and is under prospective evaluation by the Radiation Therapy Oncology Group (RTOG). Here we report outcomes from a high-volume institution of patients treated with SBRT for pulmonary oligometastases. Materials and methods We conducted a retrospective review of 105 patients who had one to five pulmonary oligometastases (185 lesions) without extrapulmonary disease treated with SBRT from 2002-2014. Target failure-free survival (TFFS), progression-free survival (PFS), and overall survival (OS) were calculated. Univariate and multivariate Cox regression analyses were performed on factors predictive of outcomes. Results The median age at first SBRT was 68 years and the median follow-up was 29.5 months. The median time from initial diagnosis of primary to SBRT was 42.7 months; 14.3% had synchronous oligometastases and 76.7% had one to two pulmonary lesions at first SBRT. The distribution of primaries was as follows: 36.2% colorectal, 16.2% head/neck, 9.5% genitourinary, 9.5% sarcoma, 7.6% gynecologic, 6.7% other, 5.7% breast, 5% melanoma, and 4% esophageal. The median lesion size was 1.6 cm and the most common regimen was 60 Gy in three fractions (range: 12-60 Gy in one to five fractions). TFFS was 94.4% and 90.8% at two and three years, respectively. Two and three year OS were 87.9% and 60.2%, respectively. Median PFS and OS were 16.2 and 45.3 months, respectively. In multivariate analysis, age at primary cancer diagnosis and biologically effective dose with an alpha-beta ratio of 10 (BED10) were identified as factors significantly affecting OS (p<0.05). Conclusions Comprehensive treatment of pulmonary oligometastases with SBRT in the absence of extrapulmonary disease results in excellent target control and modest survival outcomes.

Long-Term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose-Response for Late Toxicity.

PURPOSE: To document the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. METHODS AND MATERIALS: A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16 Gy (range, 12-24 Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. RESULTS: Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range, 4.2-59.0 months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED3) > 200 Gy (or EQD22Gy [2-Gy equivalent dose calculated using an α/ß ratio of 2] > 130 Gy) was associated with grade ≥2 late toxicity (P = .036). Maximum point BED3 > 110 Gy (or EQD22Gy > 70 Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P = .017). Nine VCFs (18%) occurred at a median time of 10.2 months (range, 3.2-57.2 months), with 5- and 10-year VCF rates of 17% and 17%, respectively. CONCLUSION: Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 > 200 Gy and spinal cord or cauda equina point BED3 > 110 Gy. Patients remain at moderate risk of VCF up to 5 years after treatment, with a plateau in incidence thereafter up to 10 years.

Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation.

INTRODUCTION: Pancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT) is a promising modality capable of delivering high dose to the tumor while limiting dose to critical structures. We aimed to determine the feasibility and tolerability of SBRT for recurrent or local pancreatic cancer in patients previously treated with external beam radiation therapy (EBRT). MATERIALS AND METHODS: Patients treated with EBRT who developed recurrent or local pancreatic ductal adenocarcinoma treated with SBRT reirradiation at our institution, from 2004 to 2014 were reviewed. Our primary endpoints included overall survival (OS), local control, regional control, and late grade 3+ radiation toxicity. Endpoints were analyzed with the Kaplan-Meier method. The association of these survival endpoints with risk factors was studied with univariate Cox proportional hazards models. RESULTS: We identified 38 patients with recurrent/progressive pancreatic cancer treated with SBRT following prior radiation therapy. Prior radiation was delivered to a median dose of 50.4 Gy in 28 fractions. SBRT was delivered to a median dose of 24.5 Gy in 1-3 fractions. Surgical resection was performed on 55.3% of all patients. Within a median follow-up of 24.4 months (inter-quartile range, 14.9-32.7 months), the median OS from diagnosis for the entire cohort was 26.6 months (95% CI: 20.3-29.8) with 2-year OS of 53.0%. Median survival from SBRT was 9.7 months (95% CI, 5.5-13.8). The 2-year freedom from local progression and regional progression was 58 and 82%, respectively. For the entire cohort, 18.4 and 10.5% experienced late grade 2+ and grade 3+ toxicity, respectively. CONCLUSION: This single institution retrospective review identified SBRT reirradiation to be a feasible and tolerable treatment strategy for patients with previous locally progressive or recurrent pancreatic adenocarcinoma.

Results of a prospective phase 2 clinical trial of induction gemcitabine/capecitabine followed by stereotactic ablative radiation therapy in borderline resectable or locally advanced pancreatic adenocarcinoma.

PURPOSE: Stereotactic ablative radiation therapy's (SABR's) great conformity and short duration has become an attractive treatment modality. We report a phase 2 clinical trial to evaluate efficacy and safety of induction chemotherapy (ICT) followed by SABR in patient with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). METHODS AND MATERIALS: Patients with biopsy-proven BR or LA PDAC were treated with four 21-day cycles of intravenous gemcitabine and oral capecitabine. Patients were restaged within 4 weeks after ICT by computed tomography and treated by 3-fraction SABR if no metastasis or progressive disease was identified. Patients were restaged 4 weeks following SABR to determine resectability. Tumor response was assessed with carbohydrate antigen 19-9. RESULTS: Thirty-five patients (19 BR/16 LA) were enrolled. The median age was 71.8 years (range, 50.6-81.1). ICT was completed in 91.4% (n = 32) of patients. All patients who completed ICT completed SABR. Of those 32 patients, 34.3% (n = 12: 10 BR, 2 LA) underwent pancreaticoduodenectomy and 11 of 12 (91.7%) received R0 resection. Median overall survival was 18.8, 28.3, and 14.3 months for the entire cohort, BR, and LA, respectively. The 2-year local progression-free survival (LPFS) was 44.9%, 40%, and 52% for the entire cohort, BR, and LA, respectively. For BR patients, multivariate analysis showed surgery was associated with better overall survival and LPFS. One-year LPFS for patients with surgery was 80% and 44% without surgery. Within the 15.4-month follow-up, no grade 3+ toxicity from SABR was observed. No significant quality of life change was observed before and after ICT, SABR, or surgery for BR or LA patients. CONCLUSIONS: This is the first prospective phase 2 study to investigate the feasibility and efficacy of a 12-week gemcitabine/capecitabine ICT followed by SABR for BR or LA PDAC. The results suggest excellent tolerability, high R0 resection rates, and acceptable posttreatment complications.

Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers.

OBJECTIVES: The seminal phase II trial for pulmonary stereotactic body radiation therapy (SBRT) suggested that SBRT to central lesions resulted in unacceptable toxicity. Alternative dose-fractionation schemes have been proposed which may improve safety without compromise of efficacy. We report our institutional outcomes of SBRT for hilar/mediastinal non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A retrospective review was conducted of patients with NSCLC in a hilar or mediastinal nodal station which was treated with SBRT. Patients presented with a lesion involving the hilum or mediastinum from primary or oligorecurrent NSCLC. Kaplan-Meier with log-rank testing and Cox analysis were utilized for outcomes analysis. RESULTS: From 2008-2015, 40 patients with median age of 70 were treated with SBRT for primary/oligorecurrent hilar/mediastinal NSCLC with median follow-up of 16.4 months. 85% presented with oligorecurrent disease at a median of 22.4 months following definitive therapy. The aortico-pulmonary window was the target in 40%, the hilum in 25%, lower paratracheal in 20%, subcarinal in 10%, and prevascular in 5%. The median dose was 48Gy in 4 fractions (range: 35-48Gy in 4-5 fractions). Median overall (OS) and progression-free (PFS) survivals were 22.7 and 13.1 months, respectively. Two-year local control was 87.7% and not significantly different between hilar and mediastinal targets. Median PFS was significantly improved in patients with hilar vs mediastinal nodal targets: 33.3 vs 8.4 months, respectively (p=0.031). OS was not statistically different between hilar and mediastinal targets (p=0.359). On multivariable analysis, hilar vs mediastinal target predicted for PFS (HR 3.045 95%CI [1.044-8.833], p=0.042), as did shorter time to presentation in patients with oligorecurrence (HR 0.983 [95%CI 0.967-1.000], p=0.049). Acute grade 3+ morbidity was seen in 3 patients (hemoptysis, pericardial/pleural effusion, heart failure) and late grade 3+ morbidity (hemoptysis) in 1 patient. CONCLUSION: Hilar/mediastinal SBRT appears to be a safe technique for the local control of isolated nodal disease with limited toxicity from the fractionation schemes utilized.