Coping Mechanisms Mitigate Psychological Stress in Patients With Rheumatologic Diseases During the COVID-19 Pandemic.

BACKGROUND: Coping with stress is part of self-managing systemic rheumatic diseases. Our objective was to assess stress and coping during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: During the pandemic in New York City, patients taking disease-modifying antirheumatic drugs answered open-ended questions about the pandemic's effects on daily life and their rheumatic condition. Themes of stress and coping were discerned from volunteered responses. Patients also completed the standard Generalized Anxiety Disorder (GAD-7) scale/PROMIS Anxiety surveys. Anxiety scores were independent variables in multivariable analyses with stress and coping themes as combined dependent variables. RESULTS: Of the 112 patients interviewed (86% women; mean age, 50 years), 72 volunteered COVID-19-related stress on their rheumatic condition, home, work, and finances. Patients volunteering stress were younger, had disease longer, were taking more than 1 medication, had worse GAD-7 scores and a positive anxiety screen, and had worse PROMIS scores that were significantly worse than population norms (all comparisons, p ≤ 0.01; all variables remained associated in multivariable analyses). Fourty-one patients volunteered coping mechanisms including support from others, engaging in activities, and resilience already establish in dealing with rheumatic diseases. Of these, 18 volunteered both coping and stress and 23 volunteered coping and no stress. Patients in the latter (coping-only) group were more likely to be older, taking only 1 medication, and had better GAD-7 and PROMIS scores (all comparisons, p ≤ 0.02). In multivariable analysis, older age (p = 0.02) and lower GAD-7 (p = 0.03) or PROMIS scores (p = 0.03) remained associated. CONCLUSIONS: Patients reported stress and coping due to the COVID-19 pandemic. Analyses with standard anxiety measures demonstrated lower anxiety in patients who volunteered coping mechanisms.

Psychological Stress Reported at the Start of the COVID-19 Pandemic and Subsequent Stress and Successful Coping in Patients With Rheumatic Diseases: A Longitudinal Analysis.

OBJECTIVE: In a cohort assembled during the height of mortality-associated coronavirus disease 2019 (COVID-19) in New York City, the objectives of this qualitative-quantitative mixed-methods study were to assess COVID-related stress at enrollment with subsequent stress and clinical and behavioral characteristics associated with successful coping during longitudinal follow-up. METHODS: Patients with rheumatologist-diagnosed rheumatic disease taking immunosuppressive medications were interviewed in April 2020 and were asked open-ended questions about the impact of COVID-19 on psychological well-being. Stress-related responses were grouped into categories. Patients were interviewed again in January-March 2021 and asked about interval and current disease status and how well they believed they coped. Patients also completed the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) measuring physical and emotional health during both interviews. RESULTS: Ninety-six patients had follow-ups; 83% were women, and mean age was 50 years. Patients who reported stress at enrollment had improved PROMIS-29 scores, particularly for the anxiety subscale. At the follow-up, patients reported persistent and new stresses as well as numerous self-identified coping strategies. Overall coping was rated as very well (30%), well (48%), and neutral-fair-poor (22%). Based on ordinal logistic regression, variables associated with worse overall coping were worse enrollment-to-follow-up PROMIS-29 anxiety (odds ratio [OR], 4.4; confidence interval [CI], 1.1-17.3; p = 0.03), not reporting excellent/very good disease status at follow-up (OR, 2.7; CI, 1.1-6.5; p = 0.03), pandemic-related persistent stress (OR, 5.7; CI, 1.6-20.1; p = 0.007), and pandemic-related adverse long-lasting effects on employment (OR, 6.1; CI, 1.9-20.0; p = 0.003) and health (OR, 3.0; CI, 1.0-9.0; p = 0.05). CONCLUSIONS: Our study reflects the evolving nature of COVID-related psychological stress and coping, with most patients reporting they coped well. For those not coping well, multidisciplinary health care providers are needed to address long-lasting pandemic-associated adverse consequences.

Improved setup and positioning accuracy using a three-point customized cushion/mask/bite-block immobilization system for stereotactic reirradiation of head and neck cancer.

The purpose of this study was to investigate the setup and positioning uncertainty of a custom cushion/mask/bite-block (CMB) immobilization system and determine PTV margin for image-guided head and neck stereotactic ablative radiotherapy (HN-SABR). We analyzed 105 treatment sessions among 21 patients treated with HN-SABR for recurrent head and neck cancers using a custom CMB immobilization system. Initial patient setup was performed using the ExacTrac infrared (IR) tracking system and initial setup errors were based on comparison of ExacTrac IR tracking system to corrected online ExacTrac X-rays images registered to treatment plans. Residual setup errors were determined using repeat verification X-ray. The online ExacTrac corrections were compared to cone-beam CT (CBCT) before treatment to assess agreement. Intrafractional positioning errors were determined using prebeam X-rays. The systematic and random errors were analyzed. The initial translational setup errors were -0.8 ± 1.3 mm, -0.8 ± 1.6 mm, and 0.3 ± 1.9 mm in AP, CC, and LR directions, respectively, with a three-dimensional (3D) vector of 2.7 ± 1.4 mm. The initial rotational errors were up to 2.4° if 6D couch is not available. CBCT agreed with ExacTrac X-ray images to within 2 mm and 2.5°. The intrafractional uncertainties were 0.1 ± 0.6 mm, 0.1 ± 0.6 mm, and 0.2 ± 0.5 mm in AP, CC, and LR directions, respectively, and 0.0° ± 0.5°, 0.0° ± 0.6°, and -0.1° ± 0.4° in yaw, roll, and pitch direction, respectively. The translational vector was 0.9 ± 0.6 mm. The calculated PTV margins mPTV(90,95) were within 1.6 mm when using image guidance for online setup correction. The use of image guidance for online setup correction, in combination with our customized CMB device, highly restricted target motion during treatments and provided robust immobilization to ensure minimum dose of 95% to target volume with 2.0 mm PTV margin for HN-SABR.

Accuracy and sources of error of out-of field dose calculations by a commercial treatment planning system for intensity-modulated radiation therapy treatments.

Although treatment planning systems are generally thought to have poor accuracy for out-of-field dose calculations, little work has been done to quantify this dose calculation inaccuracy for modern treatment techniques, such as intensity-modulated radiation therapy (IMRT), or to understand the sources of this inaccuracy. The aim of this work is to evaluate the accuracy of out-of-field dose calculations by a commercial treatment planning system (TPS), Pinnacle3 v.9.0, for IMRT treatment plans. Three IMRT plans were delivered to anthropomorphic phantoms, and out-of-field doses were measured using thermoluminescent detectors (TLDs). The TLD-measured dose was then compared to the TPS-calculated dose to quantify the accuracy of TPS calculations at various distances from the field edge and out-of-field anatomical locations of interest (i.e., radiosensitive organs). The individual components of out-of-field dose (patient scatter, collimator scatter, and head leakage) were also calculated in Pinnacle and compared to Monte Carlo simulations for a 10 × 10 cm2 field. Our results show that the treatment planning system generally underestimated the out-of-field dose and that this underestimation worsened (accuracy decreased) for increasing distances from the field edge. For the three IMRT treatment plans investigated, the TPS underestimated the dose by an average of 50%. Our results also showed that collimator scatter was underestimated by the TPS near the treatment field, while all components of out-of-field dose were severely underestimated at greater distances from the field edge. This study highlights the limitations of commercial treatment planning systems in calculating out-of-field dose and provides data about the level of accuracy, or rather inaccuracy, that can be expected for modern IMRT treatments. Based on our results, use of the TPS-reported dose could lead to an underestimation of secondary cancer induction risk, as well as poor clinical decision-making for pregnant patients or patients with implantable cardiac pacemakers and defibrillators.

Visual outcome and ocular complications in patients with lacrimal gland carcinoma after eye-sparing surgery and adjuvant radiation therapy.

BACKGROUND: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy. METHODS: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed. RESULTS: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months (range: 8-83), 13 patients (57%) had best-corrected visual acuity 20/40 or better, 3 (13%) had moderate vision loss (between 20/40 and 20/200) and 7 (30%) had severe vision loss (20/200 or worse). The most common ocular complications were dry eye disease (21 patients; 91%), radiation retinopathy (16; 70%) and cataract progression (11; 49%). Tumour crossing the orbital midline (p=0.014) and Hispanic ethnicity (p=0.014) were associated with increased risk of severe vision loss. The risk of radiation retinopathy was significantly different among the three racial groups; Hispanic patients (n=3) had the highest rate of retinopathy (p<0.001). Tumour size, initial T category and total prescribed radiation dose were not significantly associated with severe vision loss. CONCLUSION: Eye-sparing surgery followed by adjuvant radiotherapy in patients with lacrimal gland carcinoma has a reasonable overall visual prognosis. Patients with tumours crossing the orbital midline and Hispanic patients have a higher risk of severe vision loss.

Stereotactic body ablative radiotherapy for reirradiation of small volume head and neck cancers is associated with prolonged survival: Large, single-institution, modern cohort study.

BACKGROUND: Recurrent head and neck cancer has poor prognosis. Stereotactic body radiotherapy (SBRT) may improve outcomes by delivering ablative radiation doses. METHODS: We reviewed patients who received definitive-intent SBRT reirradiation at our institution from 2013 to 2020. Patterns of failure, overall survival (OS), and toxicities were analyzed. RESULTS: One hundred and thirty-seven patients were evaluated. The median OS was 44.3 months. The median SBRT dose was 45 Gy and median target volume 16.9 cc. The 1-year local, regional, and distant control was 78%, 66%, and 83%, respectively. Systemic therapy improved regional (p = 0.004) and distant control (p = 0.04) in nonmetastatic patients. Grade 3+ toxicities were more common at mucosal sites (p = 0.001) and with concurrent systemic therapy (p = 0.02). CONCLUSIONS: In a large cohort of SBRT reirradiation for recurrent, small volume head and neck cancers, a median OS of 44.3 months was observed. Systemic therapy improved regional and distant control. Toxicities were modulated by anatomic site and systemic therapy.

Our Experience Leading a Large Medical Physics Practice During the COVID-19 Pandemic.

PURPOSE: To provide a series of suggestions for other Medical Physics practices to follow in order to provide effective radiation therapy treatments during the COVID-19 pandemic. METHODS AND MATERIALS: We reviewed our entire Radiation Oncology infrastructure to identify a series of workflows and policy changes that we implemented during the pandemic that yielded more effective practices during this time. RESULTS: We identified a structured list of several suggestions that can help other Medical Physics practices overcome the challenges involved in delivering high quality radiotherapy services during this pandemic. CONCLUSIONS: Our facility encompasses 4 smaller Houston Area Locations (HALs), a main campus with 8 distinct services based on treatment site (ie. Thoracic, Head and Neck, Breast, Gastrointestinal, Gynecology, Genitourinary, Hematologic Malignancies, Melanoma and Sarcoma and Central Nervous System/Pediatrics), a Proton Center facility, an MR-Linac, a Gamma Knife clinic and an array of brachytherapy services. Due to the scope of our services, we have gained experience in dealing with the rapidly changing pandemic effects on our clinical practice. Our paper provides a resource to other Medical Physics practices in search of workflows that have been resilient during these challenging times.

Decreased heart dose with deep inspiration breath hold for the treatment of gastric lymphoma with IMRT.

We hypothesized that deep inspiration breath-hold (DIBH) and computed-tomography image-guided radiotherapy (CT-IGRT) may be beneficial to decrease dose to organs at risk (OARs), when treating the stomach with radiotherapy for lymphoma. We compared dosimetric parameters of OARs from plans generated using free-breathing (FB) versus DIBH for 10 patients with non-Hodgkin lymphoma involving the stomach treated with involved site radiotherapy. All patients had 4DCT and DIBH scans. Planning was performed with intensity modulated radiotherapy (IMRT) to 30.6 Gy in 17 fractions. Differences in target volume and dosimetric parameters were assessed using a paired two-sided t-test. All heart and left ventricle parameters including mean dose, V30, V20, V10, and V5 were statistically significantly lower with DIBH. For IMRT-FB plans the average mean heart dose was 4.9 Gy compared to 2.6 Gy for the IMRT-DIBH group (p < 0.001). There was a statistically significant decrease in right kidney dose with DIBH. For lymphoma patients treated to the stomach with IMRT, DIBH provides superior OAR sparing compared to FB-based planning, most notably reducing dose to the heart and left ventricle. This strategy could be considered when treating other gastric malignancies.

Spine stereotactic radiosurgery for metastatic thyroid cancer: a single-institution experience.

OBJECTIVE: Patients with metastatic thyroid cancer have prolonged survival compared to those with other primary tumors. The spine is the most common site of osseous involvement in cases of metastatic thyroid cancer. As a result, obtaining durable local control (LC) in the spine is crucial. This study aimed to evaluate the efficacy of spine stereotactic radiosurgery (SSRS) in patients with metastatic thyroid cancer. METHODS: Information on patients with metastatic thyroid cancer treated with SSRS for spinal metastases was retrospectively evaluated. SSRS was delivered with a simultaneous integrated boost technique using single- or multiple-fraction treatments. LC, defined as stable or reduced disease volume, was evaluated by examining posttreatment MRI, CT, and PET studies. RESULTS: A total of 133 lesions were treated in 67 patients. The median follow-up duration was 31 months. Dose regimens for SSRS included 18 Gy in 1 fraction, 27 Gy in 3 fractions, and 30 Gy in 5 fractions. The histology distribution was 36% follicular, 33% papillary, 15% medullary, 13% Hurthle cell, and 3% anaplastic. The 1-, 2-, and 5-year LC rates were 96%, 89%, and 82%, respectively. The median overall survival (OS) was 43 months, with 1-, 2-, and 5-year survival rates of 86%, 74%, and 44%, respectively. There was no correlation between the absolute biological equivalent dose (BED) and OS or LC. Patients with effective LC had a trend toward improved OS when compared to patients who had local failure: 68 versus 28 months (p = 0.07). In terms of toxicity, 5 vertebral compression fractures (2.8%) occurred, and only 1 case (0.6%) of greater than or equal to grade 3 toxicity (esophageal stenosis) was reported. CONCLUSIONS: SSRS is a safe and effective treatment option with excellent LC and minimal toxicity for patients with metastatic thyroid cancer. No association with increased radiation dose or BED was found, suggesting that such patients can be effectively treated with reduced dose regimens.

Outcomes After Hypofractionated Dose-Escalation using a Simultaneous Integrated Boost Technique for Treatment of Spine Metastases Not Amenable to Stereotactic Radiosurgery.

PURPOSE: Spine stereotactic radiosurgery delivers an ablative dose of radiation therapy (RT) with high conformity relative to standard fractionated RT. This technique is suboptimal for extended targets (>3 vertebral levels) owing to treatment alignment concerns or for patients with marked epidural extension. In these patients, we hypothesized that use of hypofractionated intensity modulated RT/volumetric modulated arc therapy to dose escalate the gross tumor volume (GTV) to 40 Gy as a spinal simultaneous integrated boost (SSIB) would allow for durable local control and palliation. METHODS AND MATERIALS: We retrospectively analyzed 15 separate spinal sites (12 patients) that were treated with the SSIB technique between 2012 and 2016. The GTV and clinical target volume were prescribed at 40 Gy and 30 Gy, respectively, in 10 fractions. The spinal cord was allowed a maximum point dose of 34 Gy. The GTV was defined as gross tumor. The clinical target volume encompassed the GTV in addition to the involved vertebral bodies, at-risk paraspinal space, and spinal canal, followed by a planning target volume expansion of 3 to 5 mm. RESULTS: The median follow-up for patients in our cohort was 17 months. At 1 year, local control was 93%, and overall survival was 58%, with a median time to death after treatment of 7 months. No grade ≥2 neurologic toxicities were reported for any of the patients. Nine of 12 patients had pain at presentation, of which 7 patients (78%) reported improvement and/or complete resolution of their pain after treatment. CONCLUSIONS: Our early experience using a dose of 40 Gy to the GTV delivered via an SSIB technique, in lieu of spine stereotactic radiation surgery but more aggressive than conventional palliative doses, provides durable local control and pain relief. This technique may allow for improved local control and palliation in patients with radioresistant disease compared with conventional 3-dimensional conformal fractionated RT.

Spine Stereotactic Radiosurgery for Metastatic Pheochromocytoma.

PURPOSE:  Despite aggressive primary treatment, up to 13.5% of patients diagnosed with pheochromocytoma may develop metastases, most often affecting the axial skeleton. Given that systemic therapy options are often inadequate, local therapy remains the cornerstone of palliation for these patients. Historically poor responses to standard fractionated radiotherapy have led to the consideration of stereotactic radiosurgery as an option to overcome potential radioresistance and provide durable local control of these tumors. Here we report our institutional experience in treating spine metastases from pheochromocytoma with spine stereotactic radiosurgery (SSRS). METHODS AND MATERIALS: Our clinical databases were retrospectively reviewed for patients with metastatic pheochromocytoma treated with SSRS from 2000-2017. Seven patients with 16 treated metastatic spinal lesions were identified. Local control was evaluated using magnetic resonance imaging (MRI). Pain and symptom data were assessed to evaluate toxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The Kaplan-Meier method was used to assess local control and overall survival (OS). RESULTS: Median follow-up for treated lesions was 11 months (range 2.2 - 70.8). Most lesions were treated to a dose of 27 Gy in three fractions (62.5%). Other fractionation schemes included 24 Gy in one fraction (25%), 16 Gy in one fraction (6.3%), and 18 Gy in three fractions (6.3%). Treatment sites included the cervical spine (18.8%), thoracic spine (37.5%), lumbar spine (31.3%), and sacrum (12.5%). The crude local control rate was 93.7%, with one thoracic spine lesion progressing 20.7 months after treatment with 24 Gy in one fraction. Kaplan-Meier OS rates at 1 and 2 years after SSRS were 71.4% and 42.9%, respectively. Most common toxicities included acute grade 1-2 pain and fatigue. There was one case of vertebral fracture in a cervical spine lesion treated to 27 Gy in three fractions, which was managed non-surgically. CONCLUSION: Very few studies have explored the use of SSRS in metastatic pheochromocytoma. Our data suggest this modern radiation modality is effective, safe, and provides durable local control to palliate symptoms and potentially limit further metastatic seeding. Larger patient numbers and longer follow-up will further define the role of SSRS as a treatment option in these patients.

Low incidence of late failure and toxicity after spine stereotactic radiosurgery: Secondary analysis of phase I/II trials with long-term follow-up.

BACKGROUND AND PURPOSE: To characterize local control and late toxicity in long-term survivors prospectively-treated with spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: From 2002 to 2011, 228 patients were prospectively-treated on protocol for metastatic disease of 261 vertebral sites. A subset of 52 patients surviving >4 years following treatment were collectively treated for 58 sites (encompassing 69 vertebrae) and underwent secondary analysis. Of all sites, 9% received prior radiation, and 16% encompassed multiple contiguous vertebrae. Radiation prescriptions were most commonly 24 Gy in 1 and 27 Gy in 3 fractions. Outcomes were evaluated via Kaplan-Meier, and associations analyzed via logistic regression. RESULTS: Median follow-up was 6.7 years (range: 49-142 months). Five-year local control by site was 91%, with late failures (>2 years) occurring in 3%. Overall and Grade ≥3 late toxicities (>2 years) were observed in 5% and 2% of sites. The last known neurologic event (grade 2 radiculopathy) was noted 2.1 years post-treatment, while the last documented fracture occurred at 4.1 years. No Grade ≥3 events were witnessed after 3.1 years post-SSRS, and no toxicities were noted after 4.1 years through end of follow-up. Re-irradiation, number of segments treated per site (1 vs. 2-3), and fractionation (1 vs. 3-5) were not associated with failure or toxicity. CONCLUSION: SSRS maintains excellent disease control and a favorable late toxicity profile even among long-term survivors, with very few failures or toxicities after 2 years in this prospectively-treated population. Overall, these data support the durable control and long-term safety of SSRS with extended follow-up.

The influence of non-rigid anatomy and patient positioning on endoscopy-CT image registration in the head and neck.

PURPOSE: To assess the influence of non-rigid anatomy and differences in patient positioning between CT acquisition and endoscopic examination on endoscopy-CT image registration in the head and neck. METHODS: Radiotherapy planning CTs and 31-35 daily treatment-room CTs were acquired for nineteen patients. Diagnostic CTs were acquired for thirteen of the patients. The surfaces of the airways were segmented on all scans and triangular meshes were created to render virtual endoscopic images with a calibrated pinhole model of an endoscope. The virtual images were used to take projective measurements throughout the meshes, with reference measurements defined as those taken on the planning CTs and test measurements defined as those taken on the daily or diagnostic CTs. The influence of non-rigid anatomy was quantified by 3D distance errors between reference and test measurements on the daily CTs, and the influence of patient positioning was quantified by 3D distance errors between reference and test measurements on the diagnostic CTs. The daily CT measurements were also used to investigate the influences of camera-to-surface distance, surface angle, and the interval of time between scans. RESULTS: Average errors in the daily CTs were 0.36 ± 0.61 cm in the nasal cavity, 0.58 ± 0.83 cm in the naso- and oropharynx, and 0.47 ± 0.73 cm in the hypopharynx and larynx. Average errors in the diagnostic CTs in those regions were 0.52 ± 0.69 cm, 0.65 ± 0.84 cm, and 0.69 ± 0.90 cm, respectively. All CTs had errors heavily skewed towards 0, albeit with large outliers. Large camera-to-surface distances were found to increase the errors, but the angle at which the camera viewed the surface had no effect. The errors in the Day 1 and Day 15 CTs were found to be significantly smaller than those in the Day 30 CTs (P < 0.05). CONCLUSIONS: Inconsistencies of patient positioning have a larger influence than non-rigid anatomy on projective measurement errors. In general, these errors are largest when the camera is in the superior pharynx, where it sees large distances and a lot of muscle motion. The errors are larger when the interval of time between CT acquisitions is longer, which suggests that the interval of time between the CT acquisition and the endoscopic examination should be kept short. The median errors found in this study are comparable to acceptable levels of uncertainty in deformable CT registration. Large errors are possible even when image alignment is very good, indicating that projective measurements must be made carefully to avoid these outliers.

The feasibility of endoscopy-CT image registration in the head and neck without prospective endoscope tracking.

PURPOSE: Endoscopic examinations are frequently-used procedures for patients with head and neck cancer undergoing radiotherapy, but radiation treatment plans are created on computed tomography (CT) scans. Image registration between endoscopic video and CT could be used to improve treatment planning and analysis of radiation-related normal tissue toxicity. The purpose of this study was to explore the feasibility of endoscopy-CT image registration without prospective physical tracking of the endoscope during the examination. METHODS: A novel registration technique called Location Search was developed. This technique uses physical constraints on the endoscope's view direction to search for the virtual endoscope coordinates that maximize the similarity between the endoscopic video frame and the virtual endoscopic image. Its performance was tested on phantom and patient images and compared to an established registration technique, Frame-To-Frame Tracking. RESULTS: In phantoms, Location Search had average registration errors of 0.55 ± 0.60 cm for point measurements and 0.29 ± 0.15 cm for object surface measurements. Frame-To-Frame Tracking achieved similar results on some frames, but it failed on others due to the virtual endoscope becoming lost. This weakness was more pronounced in patients, where Frame-To-Frame tracking could not make it through the nasal cavity. On successful patient video frames, Location Search was able to find endoscope positions with an average distance of 0.98 ± 0.53 cm away from the ground truth positions. However, it failed on many frames due to false similarity matches caused by anatomical structural differences between the endoscopic video and the virtual endoscopic images. CONCLUSIONS: Endoscopy-CT image registration without prospective physical tracking of the endoscope is possible, but more development is required to achieve an accuracy suitable for clinical translation.

Heterogeneity in Treatment Response of Spine Metastases to Spine Stereotactic Radiosurgery Within "Radiosensitive" Subtypes.

PURPOSE: To characterize outcomes of metastatic colorectal and non-small cell lung cancer (NSCLC) histologies, compared with other radiosensitive histologies, treated with spine stereotactic radiosurgery with regard to local control, overall survival, and predictors of response. METHODS AND MATERIALS: A total of 127 patients with 148 spine stereotactic radiosurgery-treated metastatic lesions at our institution between 2003 and 2013 were reviewed. We assessed clinical endpoints in relation to histologic type, including local control (LC) and overall survival (OS), using univariate and multivariate analyses. RESULTS: For all patients, the 1- and 2-year actuarial rates for LC were 82.6% and 75.8%, and rates for OS were 72.9% and 51.5% respectively. Among tumor histologies, 1-year cumulative incidence rates of local failure for thyroid, breast, lung, and colon cancer were 8.7%, 7.0%, 26.6%, and 39.6%, respectively. When analyzed together, NSCLC and colorectal cancers had significantly greater cumulative incidence rates at 1 and 2 years (30.4% and 38.7%, respectively) than other histologies (8.0% and 14.1% respectively, P=.0008). Non-small cell lung cancer/colorectal tumor status was a significant predictor of local failure in a competing risk univariate model (hazard ratio 2.12, 95% confidence interval 1.07-4.17, P=.03) and multivariate model (hazard ratio 2.35, 95% confidence interval 1.12-4.92, P=.024). CONCLUSIONS: Spine stereotactic radiosurgery is an effective strategy in achieving local control of spine metastases, particularly among radiosensitive histologies. However, a subset of these classically defined histologies (NSCLC and colorectal) has a propensity toward local failure. In addition to resulting in poorer OS outcomes, the poor LC rates seen in NSCLC and colorectal cancers in this study are more consistent with a radioresistant phenotype, suggesting the need for optimized dosing regimens in this subgroup.

Spine stereotactic radiosurgery for metastatic sarcoma: patterns of failure and radiation treatment volume considerations.

OBJECTIVE Given the relatively lower radiosensitivity of sarcomas and the locally infiltrative patterns of spread, the authors sought to investigate spine stereotactic radiosurgery (SSRS) outcomes for metastatic sarcomas and to analyze patterns of failure. METHODS The records of 48 patients with 66 sarcoma spinal metastases consecutively treated with SSRS between 2002 and 2013 were reviewed. The Kaplan-Meier method was used to estimate rates of overall survival (OS) and local control (LC). Local recurrences were categorized as occurring infield (within the 95% isodose line [IDL]), marginally (between the 20% and 95% IDLs), or out of field. RESULTS Median follow-up time was 19 months (range 1-121 months), and median age was 53 years (range 17-85 years). The most commonly treated histology was leiomyosarcoma (42%). Approximately two-thirds of the patients were treated with definitive SSRS (44 [67%]) versus postoperatively (22 [33%]). The actuarial 1-year OS and LC rates were 67% and 81%, respectively. Eighteen patients had a local relapse, which was more significantly associated with postoperative SSRS (p = 0.04). On multivariate modeling, receipt of postoperative SSRS neared significance for poorer LC (p = 0.06, subhazard ratio [SHR] 2.33), while only 2 covariates emerged as significantly correlated with LC: 1) biological equivalent dose (BED) > 48 Gy (vs BED ≤ 48 Gy, p = 0.006, SHR 0.21) and 2) single vertebral body involvement (vs multiple bodies, p = 0.03, SHR 0.27). Of the 18 local recurrences, 14 (78%) occurred at the margin, and while the majority of these cases relapsed within the epidural space, 4 relapsed within the paraspinal soft tissue. In addition, 1 relapse occurred out of field. Finally, the most common acute toxicity was fatigue (15 cases), with few late toxicities (4 insufficiency fractures, 3 neuropathies). CONCLUSIONS For metastatic sarcomas, SSRS provides durable tumor control with minimal toxicity. High-dose single-fraction regimens offer optimal LC, and given the infiltrative nature of sarcomas, when paraspinal soft tissues are involved, larger treatment volumes may be warranted.

Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTLA-4 treatment is associated with improved intracranial control.

BACKGROUND: Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. MATERIAL AND METHODS: Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy. All patients had complete blood count acquired before SRS. Primary outcomes were intracranial disease control and overall survival (OS). RESULTS: The median follow-up time was 15.5months. In the MD Anderson cohort, patients who received SRS after 5.5months (n=20) of their last dose of ipilimumab had significantly worse intracranial control than patients who received SRS within 5.5months (n=51) (median 3.63 vs. 8.09months; hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.03-4.16, p=0.041). OS was not different between the two arms. The improvement in intracranial control was confirmed in an independent validation cohort of 28 patients treated at Yale-New Haven Hospital. Circulating absolute lymphocyte count before SRS predicted for treatment response as those with baseline counts >1000/µL had reduced risk of intracranial recurrence compared with those with ≤1000/µL (HR 0.46, 95% CI 0.0.23-0.94, p=0.03). CONCLUSIONS: In this multi-institutional study, patients who received SRS for new brain metastases within 5.5months after ipilimumab therapy had better intracranial disease control than those who received SRS later. Moreover, higher circulating lymphocyte count was associated with improved intracranial disease control.

The use of spine stereotactic radiosurgery for oligometastatic disease.

OBJECTIVE The authors investigated the outcomes following spine stereotactic radiosurgery (SSRS) for patients with oligometastatic disease of the spine. METHODS The study was a secondary analysis of 38 of 209 patients enrolled in 2 separate institutional Phase I/II prospective protocols and treated with SSRS between 2002 and 2011. Of these 38 patients, 33 (87%) were treated for a solitary spine metastasis, with no other history of metastatic disease. SSRS was prescribed to 24 Gy in 1 fraction (8%), 18 Gy in 1 fraction (18%), 16 Gy in 1 fraction (11%), 27 Gy in 3 fractions (53%), 30 Gy in 5 fractions (8%), or 20 Gy in 5 fractions (3%). Seventeen patients (45%) received prior conventional external beam radiation therapy. RESULTS The median overall survival (OS) was 75.7 months, and the 2- and 5-year OS rates were 84% and 60%, respectively. In multivariate analysis, patients who had prior spine surgery and a better Karnofsky Performance Scale score had an improved OS (HR 0.16, 95% CI 0.05-0.52, p < 0.01, and HR 0.33, 95% CI 0.13%-0.84%, p = 0.02, respectively), and those who had undergone prior radiation therapy had a worse OS (HR 3.6, 95% CI 1.2%-10%, p = 0.02). The 1-, 2-, and 5-year local progression-free survival rates were 85%, 82%, and 78%, respectively. The median time to systemic therapy modification was 41 months. Two patients (5%) experienced late Grade 3-4 toxicity. CONCLUSIONS Patients with oligometastatic disease of the spine treated with SSRS can experience long-term survival and a long time before needing a modification in systemic therapy. In addition, SSRS leads to excellent local control and minimal late toxicity.

Spine Stereotactic Radiosurgery for Patients with Metastatic Thyroid Cancer: Secondary Analysis of Phase I/II Trials.

BACKGROUND: Metastatic deposits to the spine in thyroid cancer patients represent the most common site of bone involvement and can contribute to pain, neurologic deficits, and death. This study sought to determine the efficacy and safety of spine stereotactic radiosurgery (SSRS) for thyroid cancer patients. METHODS: Thyroid cancer patients with spine metastases were selected and analyzed from a cohort of patients who were prospectively enrolled in two single-institution Phase I/II studies. SSRS was delivered in single or multi-fraction schedules. Dose regimens ranged from 16-18 Gy in one fraction to 27-30 Gy in three to five fractions. Toxicity was graded according to the NCI-CTC toxicity scale. Local control was determined by serial post-treatment magnetic resonance imaging scans showing no evidence of progressive disease. Patients were followed until date of death or date of last known visit for survival analyses. Local control and overall survival rates were carried out using Kaplan-Meier estimates. The log-rank test was used to assess the equality of the survivor function across groups. A p-value of ≤0.05 was considered to be statistically significant. RESULTS: A total of 27 spine lesions were treated in 23 patients over a six-year period. Median follow-up was 28.9 months (range 5-93 months). Local control was 88% at two years and 79% at three years. In patients with progressive disease following conventional radiation therapy, local control for salvage SSRS remained at 88% at three years. Patients requiring upfront surgical intervention and treated with adjuvant SSRS achieved sustained control rates of 86% at three years. Overall survival rates were 85% and 67% at one and two years, respectively. In patients classified with oligoprogression and controlled extra-spinal disease, overall survival was significantly higher than those with evidence of systemic progression (81% vs. 45% at two years; p = 0.01). Univariate analysis did not show significant correlations between local control and age, systemic disease status, prior (131)I therapy, SSRS fraction regimen, spine location, histological subtype, or time from initial diagnosis to evidence of spinal metastasis. No patient experienced any grade 3-5 toxicity. Pain flare was reported in 30% of patients, with only three patients (13%) requiring narcotics or short-course steroids. There was no evidence of vertebral body fracture in any patient that achieved local control in the treated area. CONCLUSIONS: SSRS for thyroid metastases as a primary or adjuvant/salvage therapy is well tolerated and yields high rates of local control.

Prospective validation of treatment accuracy using implanted fiducial markers for spinal stereotactic body radiation therapy.

In order to accurately assess positioning errors in spinal SBRT, many institutions employ bony-fusion based imaging techniques, such as the ExacTrac™ (Brain Lab) system, in conjunction with 3D verification (performed via CT-on-rails in our practice). We hypothesized that the use of implanted gold fiducial markers could improve the accuracy of patient positioning over bony fusion alone. We addressed this question prospectively, enrolling patients on an IRB-approved protocol. Gold seeds were implanted in the vertebral pedicles flanking the target level. At treatment, setup error was calculated using two methods-standard kV image fusion, and geometric fiducial-based projection, with independent CT-on-rails verification. Analyses of residual set-up error showed that fiducial-based setup agreed with fusion-based determination, but did not significantly reduce error. Offline 6D fusion of the treatment and planning CT illustrated residual rotational error using standard or fiducial based setup. We conclude that the ExacTrac and CT-on-rails platform yields highly accurate results for spinal SBRT setup, with reduced residual error than previously reported. While the addition of fiducials did not further reduce error, the bony fusion approach is now prospectively validated in comparison to implanted fiducials. Both bony fusion and fiducial marker methods are associated with residual rotational error, thus 3D verification remains an important component of spinal SBRT treatment.