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.

Salvage stereotactic radiosurgery for recurrent gliomas with prior radiation therapy.

This study aims to assess the viability of salvage stereotactic radiosurgery (SRS) for recurrent malignant gliomas through assessing overall survival, local control and toxicity. We performed a retrospective review of 65 patients with 76 lesions (55 high-grade, 21 low-grade) treated with salvage SRS between 2002 and   2012. Median follow-up from salvage SRS was 14.9 months (IQR: 0.9-28.1), 8.3 months (IQR: 4.0-13.3) and 8.5 months (IQR: 3.9-15.8) for low-grade, high-grade, and combined, respectively. A 12-month overall survival from salvage SRS was 68.4, 38.7 and 47.3% for low-grade, high-grade and combined respectively. A total of 6-month local control was 86.2, 53.8 and 65.3% for low-grade, high-grade and combined, respectively. Our results indicate salvage SRS can provide acceptable survival and local control with minimal toxicity.

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.

Stereotactic body radiation therapy for adrenal metastases: a retrospective review of a noninvasive therapeutic strategy.

AIMS: The role of radiation therapy in the treatment of adrenal metastases has traditionally been a palliative one, achieving excellent pain control with very limited toxicity. Recent studies have focused on the potential role of stereotactic body radiation therapy (SBRT) with curative intent in limited metastatic disease, its potential to reduce tumor burden and to prevent symptomatic progression. This study reports the single-institution outcomes of SBRT utilizing both single fraction and hypofractionated regimens in the treatment of adrenal metastases. METHODS: A total of seven patients with nine adrenal metastases treated with SBRT at the University of Pittsburgh Cancer Institute were retrospectively studied. The primary malignancies consisted of non-small-cell lung cancer (n = 4), small-cell lung cancer (n = 1) and hepatocellular carcinoma (n = 2). RESULTS: Five lesions were treated in a single fraction to a median prescription dose of 16 Gy (range: 10-22 Gy) to the 80% isodose line. The remaining four lesions were treated over three fractions to a median prescription dose of 27 Gy (range: 24-36 Gy), with a median prescription isodose line of 94% (range: 80-94%). Median follow-up from the primary diagnosis was 38 months (range: 7-88 months) and from SBRT was 14 months (range: 1-60 months). Follow-up imaging for six patients, and eight metastatic lesions, revealed one complete response, two partial responses and five stable lesions. Five of the lesions eventually failed locally, with a median time to failure of 12 months and actuarial local control of 63% at 1 year. The median overall survival was 8 months from SBRT. CONCLUSION: SBRT can be safely delivered in single fraction, or hypofractionated, regimens for the treatment of adrenal metastases.

Stereotactic radiosurgery to the resection cavity of brain metastases: a retrospective analysis and literature review.

PURPOSE: The aim of this study was to analyze results of stereotactic radiosurgery (SRS) as adjuvant therapy for resected brain metastases. METHODS: Medical records of patients treated at a single institution with SRS to the postoperative cavity of brain metastases were retrospectively reviewed. Patients who completed the prescribed SRS regimen following gross-total resection and had no previous whole brain radiotherapy were included in the study. Kaplan-Meier analyses were used to estimate local (LC) and intracranial control (IC), and overall survival (OS) rates. RESULTS: Between April 2005 and July 2010, 77 patients (median age 63 years) with 89 metastases met the inclusion criteria. The median prescription dose was 18 Gy (12-27 Gy) delivered in 1-3 fractions for a median target volume of 7.6 cm(3) (0.5-59 cm(3)). The 6-month, 1-year, and 2-year LC rates were 76.1, 76.1, and 74.3%, respectively. The 6-month, 1-year, and 2-year IC rates were 75.2, 54, and 43.6%, respectively. With a median follow-up of 13.8 months, the median OS was 14.5 months (1.9-51.4 months) after SRS. The overall 6-month, 1-year, and 2-year OS rates were 91, 62.5, and 43.6%, respectively. Complications included 2 patients with radiation necrosis. CONCLUSION: Adjuvant radiosurgery to the tumor cavity of resected brain metastases is well-tolerated and achieves LC in the majority of patients.

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.

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.

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.

Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography-based treatment planning.

PURPOSE: The aim of this study was to assess the outcomes of patients treated with stereotactic body radiation therapy (SBRT) in patients with primary, recurrent, or metastatic lung lesions, with a focus on positron emission tomography (PET)/computed tomography (CT)-based management. PATIENTS AND METHODS: Fifty-one patients with primary stage I non-small-cell lung cancer (NSCLC; n = 26), recurrent lung cancer after definitive treatment (n = 12), or solitary lung metastases (n = 13) were treated with SBRT between 2005 and 2007. Patients were treated with the CyberKnife Robotic Radiosurgery System with Synchrony respiratory tracking. A dose of 60 Gy was delivered in 3 fractions. All patients had CT or PET/CT performed at approximately 3-month intervals after treatment. RESULTS: The median follow-up was 12 months. Local control at median follow-up was 85% in patients with stage I NSCLC, 92% in patients with recurrent lung cancer, and 62% in the patients with solitary lung metastasis. Analysis of the 28 patients with pre- and post-treatment PET/CT scans demonstrated that those with stable disease (n = 4) had a mean standardized uptake value (SUV) decrease of 28%, partial responders (n = 11) had a decrease of 48%, and patients with a complete response (n = 11) had a decrease of 94%. Patients with progressive disease (n = 2) had an SUV decrease of only 0.4%. Only 2 patients (7%) who had reduced fluorodeoxyglucose avidity later progressed locally. No correlations were found between pretreatment SUV and tumor response, disease progression, or survival. Overall 1-year survival rates were 81%, 67%, and 85% among the patients with primary NSCLC, recurrent lung cancer, and solitary lung metastases, respectively. CONCLUSION: Stereotactic body radiation therapy with CyberKnife is an effective treatment for patients with medically inoperable recurrent or metastatic lung cancer. Positron emission tomography/CT is valuable in staging, planning, and evaluating treatment response and might predict long-term outcome.

Stereotactic radiosurgery for early stage non-small cell lung cancer: rationale, patient selection, results, and complications.

Lung cancer is the most common cause of cancer-related mortality in the United States. Lobectomy is the current standard of care for early stage lung cancer. For nonoperative candidates, standard radiation has been offered but generally with little hope for cure. Advanced radiation techniques with three-dimensional planning, multiple beam paths, and respiratory-motion compensation have resulted in the ability to administer high-dose radiation or stereotactic radiosurgery to lung tumors. Stereotactic radiosurgery is likely to be more effective than standard external beam radiation and there is evidence that in appropriately selected medically inoperable patients such therapy may offer a chance for cure. Early results are encouraging but these results are not mature and, recently, severe late toxicity has been reported. Prospective trials are underway in our institution and others to evaluate stereotactic radiosurgery for early stage lung neoplasm. This article summarizes the role of stereotactic radiosurgery for the treatment of lung cancer.

Clinical assessment of stereotactic IGRT: spinal radiosurgery.

The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. Its use for the treatment of spinal lesions has been limited because of the availability of effective target immobilization devices. Recent advances in stereotactic IGRT have allowed for spinal applications. Large clinical experience with spinal radiosurgery to properly assess clinical outcomes has previously been limited. At our institution, we have developed a successful multidisciplinary spinal radiosurgery program in which 542 spinal lesions (486 malignant and 56 benign lesions) were treated with a single-fraction radiosurgery technique. Patient ages ranged from 18 to 85 years (mean 56 years). Lesion location included 92 cervical, 234 thoracic, 130 lumbar, and 86 sacral. The most common metastatic tumors were renal cell (89 cases), breast (74 cases), and lung (71 cases). The most common benign tumors were neurofibroma (24 cases), schwannoma (13 cases), and meningioma (7 cases). Eighty-nine cervical lesions were treated using skull tracking. Thoracic, lumbar, and sacral tumors were tracked relative to either gold or stainless steel fiducial markers. The maximum intratumoral dose ranged from 12.5 to 30 Gy (mean 20 Gy). Tumor volume ranged from 0.16 to 298 mL (mean 47 mL). Three hundred thirty-seven lesions had received prior external beam irradiation with spinal cord doses precluding further conventional irradiation. The primary indication for radiosurgery was pain in 326 cases, as a primary treatment modality in 70 cases, for tumor radiographic tumor progression in 65 cases, for post-surgical treatment in 38 cases, for progressive neurological deficit in 35 cases, and as a radiation boost in 8 cases. Follow-up period was at least 3 to 49 months. Axial and/or radicular pain improved in 300 of 326 cases (92%). Long-term tumor control was demonstrated in 90% of lesions treated with radiosurgery as a primary treatment modality and in 88% of lesions treated for radiographic tumor progression. Thirty of 35 patients (85%) with progressive neurological deficits experienced at least some improvement after treatment. Spinal stereotactic radiosurgery is now a feasible, safe, and clinically effective technique for the treatment of a variety of spinal lesions. The potential benefits of radiosurgical ablation of spinal lesions are short treatment time in an outpatient setting with essentially no recovery time and excellent symptomatic response. This technique offers a new therapeutic modality for the primary treatment of a variety of spinal lesions, including the treatment of neoplasms in medically inoperable patients, previously irradiated sites, for lesions not amenable to open surgical techniques, and as an adjunct to surgery.

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.

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.

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.

Long-Term Survivorship Following Stereotactic Radiosurgery Alone for Brain Metastases: Risk of Intracranial Failure and Implications for Surveillance and Counseling.

BACKGROUND: Historically, survival for even highly select cohorts of brain metastasis patients selected for SRS alone is <2 yr; thus, limited literature on risks of recurrence exists beyond 2 yr. OBJECTIVE: To investigate the possibility that for subsets of patients the risk of intracranial failure beyond 2 yr is less than the commonly quoted 50% to 60%, wherein less frequent screening may be appropriate. METHODS: As a part of our institutional radiosurgery database, we identified 132 patients treated initially with stereotactic radiosurgery (SRS) alone (± pre-SRS surgical resection) with at least 2 yr of survival and follow-up from SRS. Primary study endpoints were rates of actuarial intracranial progression beyond 2 yr, calculated using the Kaplan-Meier and Cox regression methods. RESULTS: The median follow-up from the first course of SRS was 3.5 yr. Significant predictors of intracranial failure beyond 2 yr included intracranial failure before 2 yr (52% vs 25%, P < .01) and total SRS tumor volume ≥5 cc (51% vs 25%, P < .01). On parsimonious multivariate analysis, failure before 2 yr (HR = 2.2, 95% CI: 1.2-4.3, P = .01) and total SRS tumor volume ≥5 cc (HR = 2.3, 95% CI: 1.2-4.3, P = .01) remained significant predictors of intracranial relapse beyond 2 yr. CONCLUSION: Relapse rates beyond 2 yr following SRS alone for brain metastases are low in patients who do not suffer intracranial relapse within the first 2 yr and with low-volume brain metastases, supporting a practice of less frequent screening beyond 2 yr. For remaining patients, frequent (every 3-4 mo) screening remains prudent, as the risk of intracranial failure after 2 yr remains high.

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.

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.