Recursive partitioning analysis is predictive of overall survival for patients undergoing spine stereotactic radiosurgery.

Spine stereotactic radiosurgery (SRS) offers excellent radiographic and pain control for patients with spine metastases. We created a prognostic index using recursive partitioning analysis (RPA) to allow better patient selection for spine SRS. Patients who underwent single-fraction spine SRS for spine metastases were included. Primary histologies were divided into favorable (breast/prostate), radioresistant (renal cell/sarcoma/melanoma) and other. Cox proportional hazards regression was done to identify factors associated with overall survival (OS). RPA was performed to identify factors to classify patients into distinct risk groups with respect to OS. A total of 444 patients were eligible. Median dose was 16 Gy (range 8-18) in 1 fraction and median follow-up was 11.7 months. At time of analysis, 103 (23.1%) patients were alive. Median OS was 12.9 months. RPA identified three distinct classes. Class 1 was defined as KPS > 70 with controlled systemic disease (n = 142); class 3 was defined as KPS ≤ 70 and age < 54 years or KPS ≤ 70 age ≥ 54 years and presence of visceral metastases (n = 95); all remaining patients comprise class 2 (n = 207). Median overall survival was 26.7 months for class 1, 13.4 months for class 2, and 4.5 months for class 3 (p < 0.01). Our analysis demonstrates that there is considerably variability in survival among patients undergoing spine SRS. We created an objective risk stratification via RPA for spine SRS. Given the safety and efficacy of spine SRS and good survival in class 1 and 2 patients, this RPA can help clinicians identify patients who may benefit from upfront spine SRS.

Intra- and inter-fractional liver and lung tumor motions treated with SBRT under active breathing control.

PURPOSE: To assess intra- and inter-fractional motions of liver and lung tumors using active breathing control (ABC). METHODS AND MATERIALS: Nineteen patients with liver cancer and 15 patients with lung cancer treated with stereotactic body radiotherapy (SBRT) were included in this retrospective study. All patients received a series of three CTs at simulation to test breath-hold reproducibility. The centroids of the whole livers and of the lung tumors from the three CTs were compared to assess intra-fraction variability. For 15 patients (8 liver, 7 lung), ABC-gated kilovoltage cone-beam CTs (kV-CBCTs) were acquired prior to each treatment, and the centroids of the whole livers and of the lung tumors were also compared to those in the planning CTs to assess inter-fraction variability. RESULTS: Liver intra-fractional systematic/random errors were 0.75/0.39 mm, 1.36/0.97 mm, and 1.55/1.41 mm at medial-lateral (ML), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. Lung intra-fractional systematic/random errors were 0.71/0.54 mm (ML), 1.45/1.10 mm (AP), and 3.95/1.93 mm (SI), respectively. Substantial intra-fraction motions (>3 mm) were observed in 26.3% of liver cancer patients and in 46.7% of lung cancer patients. For both liver and lung tumors, most inter-fractional systematic and random errors were larger than the corresponding intra-fractional errors. However, these inter-fractional errors were mostly corrected by the treatment team prior to each treatment based on kV CBCT-guided soft tissue alignment, thereby eliminating their effects on the treatment planning margins. CONCLUSIONS: Intra-fractional motion is the key to determine the planning margins since inter-fractional motion can be compensated based on daily gated soft tissue imaging guidance of CBCT. Patient-specific treatment planning margins instead of recipe-based margins were suggested, which can benefit mostly for the patients with small intra-fractional motions.

Volumetric-based image guidance is superior to marker-based alignments for stereotactic body radiotherapy of prostate cancer.

PURPOSES: The aim of this study was to evaluate a dual marker-based and soft-tissue based image guidance for inter-fractional corrections in stereotactic body radiotherapy (SBRT) of prostate cancer. METHODS/MATERIALS: We reviewed 18 patients treated with SBRT for prostate cancer. An endorectal balloon was inserted at simulation and each treatment. Planning margins were 3 mm/0 mm posteriorly. Prior to each treatment, a dual image guidance protocol was applied to align three makers using stereoscopic x ray images and then to the soft tissue using kilo-voltage cone beam CT (kV-CBCT). After treatment, prostate (CTV), rectal wall, and bladder were delineated on each kV-CBCT, and delivered dose was recalculated. Dosimetric endpoints were analyzed, including V36.25 Gy for prostate, and D0.03 cc for bladder and rectal wall. RESULTS: Following initial marker alignment, additional translational shifts were applied to 22 of 84 fractions after kV-CBCT. Among the 22 fractions, ten fractions exceeded 3 mm shifts in any direction, including one in the left-right direction, four in the superior-inferior direction, and five in the anterior-posterior direction. With and without the additional kV-CBCT shifts, the average V36.25 Gy of the prostate for the 22 fractions was 97.6 ± 2.6% with the kV x ray image alone, and was 98.1 ± 2.4% after applying the additional kV-CBCT shifts. The improvement was borderline statistical significance using Wilcoxon signed-rank test (P = 0.007). D0.03 cc was 45.8 ± 6.3 Gy vs. 45.1 ± 4.9 Gy for the rectal wall; and 49.5 ± 8.6 Gy vs. 49.3 ± 7.9 Gy for the bladder before and after applying kV-CBCT shifts. CONCLUSIONS: Marker-based alignment alone is not sufficient. Additional adjustments are needed for some patients based kV-CBCT.

Impact of small MU/segment and dose rate on delivery accuracy of volumetric-modulated arc therapy (VMAT).

Volumetric-modulated arc therapy (VMAT) plans may require more control points (or segments) than some of fixed-beam IMRT plans that are created with a limited number of segments. Increasing number of control points in a VMAT plan for a given prescription dose could create a large portion of the total number of segments with small number monitor units (MUs) per segment. The purpose of this study is to investigate the impact of the small number MU/segment on the delivery accuracy of VMAT delivered with various dose rates. Ten patient datasets were planned for hippocampus sparing for whole brain irradiation. For each dataset, two VMAT plans were created with maximum dose rates of 600 MU/min (the maximum field size of 21 × 40 cm2) and 1000 MU/min (the maximum field size of 15 × 15 cm2) for a daily dose of 3 Gy. Without reoptimization, the daily dose of these plans was purposely reduced to 1.5 Gy and 1.0 Gy while keeping the same total dose. Using the two dose rates and three different daily doses, six VMAT plans for each dataset were delivered to a physical phantom to investigate how the changes of dose rate and daily doses impact on delivery accuracy. Using the gamma index, we directly compared the delivered planar dose profiles with the reduced daily doses (1.5 Gy and 1.0 Gy) to the delivered planar dose at 3 Gy daily dose, delivered at dose rate of 600 MU/min and 1000 MU/min, respectively. The average numbers of segments with MU/segment ≤ 1 were 35 ± 8, 87 ± 6 for VMAT-600 1.5 Gy, VMAT-600 1 Gy plans, and 30 ± 7 and 42 ± 6 for VMAT-1000 1.5 Gy and VMAT-1000 1 Gy plans, respectively. When delivered at 600 MU/min dose rate, the average gamma index passing rates (1%/1 mm criteria) of comparing delivered 1.5 Gy VMAT planar dose profiles to 3.0 Gy VMAT delivered planar dose profiles was 98.28% ± 1.66%, and the average gamma index passing rate of comparing delivered 1.0 Gy VMAT planar dose to 3.0 Gy VMAT delivered planar dose was 83.75% ± 4.86%. If using 2%/2mm and 3%/3 mm criteria, the gamma index passing rates were greater than 97% for both 1.5 Gy VMAT and 1.0 Gy VMAT delivered planar doses. At 1000MU/min dose rate, the average gamma index passing rates were 96.59% ± 2.70% for 1.5 Gy VMAT planar dose profiles and 79.37% ± 9.96% for 1.0 Gy VMAT planar dose profiles when compared to the 3.0 Gy VMAT planar delivered dose profile. When using 2%/2 mm and 3%/3 mm criteria, the gamma index passing rates were greater than 93% for both 1.5 Gy VMAT and 1.0 Gy VMAT planar delivered dose. Under a stricter gamma index criterion (1%/1 mm), significant differences in delivered planar dose profiles at different daily doses were detected, indicating that the known communication delay between the MU console and MLC console may affect VMAT delivery accuracy.

Dosimetric impact of orthopedic metal artifact reduction (O-MAR) on Spine SBRT patients.

The dosimetric impact of orthopedic metal artifact reduction (O-MAR) on spine SBRT patients has not been comprehensively studied, particularly with spinal prostheses in high-dose gradient regions. Using both phantom and patient datasets, we investigated dosimetric effects of O-MAR in combination of various metal locations and dose calculation algorithms. A physical phantom, with and without a titanium insert, was scanned. A clinical patient plan was applied to the artifact-free reference, non-O-MAR, and O-MAR phantom images with the titanium located either inside or outside of the tumor. Subsequently, five clinical patient plans were calculated with pencil beam and Monte Carlo (iPlan) on non-O-MAR and O-MAR patient images using an extended CT-density table. The dose differences for phantom plans and patient plans were analyzed using dose distributions, dose-volume histograms (DVHs), gamma index, and selected dosimetric endpoints. From both phantom plans and patient plans, O-MAR did not affect dose distributions and DVHs while minimizing metal artifacts. Among patient plans, we found that, when the same dose calculation method was used, the difference in the dosimetric endpoints between non-O-MAR and O-MAR datasets were small. In conclusion, for spine SBRT patients with spinal prostheses, O-MAR image reconstruction does not affect dose calculation accuracy while minimizing metal artifacts. Therefore, O-MAR images can be safely used for clinical spine SBRT treatment planning.

Dose differences in intensity-modulated radiotherapy plans calculated with pencil beam and Monte Carlo for lung SBRT.

For patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy, early treatment plans were based on a simpler dose calculation algorithm, the pencil beam (PB) calculation. Because these patients had the longest treatment follow-up, identifying dose differences between the PB calculated dose and Monte Carlo calculated dose is clinically important for understanding of treatment outcomes. Previous studies found significant dose differences between the PB dose calculation and more accurate dose calculation algorithms, such as convolution-based or Monte Carlo (MC), mostly for three-dimensional conformal radiotherapy (3D CRT) plans. The aim of this study is to investigate whether these observed dose differences also exist for intensity-modulated radiotherapy (IMRT) plans for both centrally and peripherally located tumors. Seventy patients (35 central and 35 peripheral) were retrospectively selected for this study. The clinical IMRT plans that were initially calculated with the PB algorithm were recalculated with the MC algorithm. Among these paired plans, dosimetric parameters were compared for the targets and critical organs. When compared to MC calculation, PB calculation overestimated doses to the planning target volumes (PTVs) of central and peripheral tumors with different magnitudes. The doses to 95% of the central and peripheral PTVs were overestimated by 9.7% ± 5.6% and 12.0% ± 7.3%, respectively. This dose overestimation did not affect doses to the critical organs, such as the spinal cord and lung. In conclusion, for NSCLC treated with IMRT, dose differences between the PB and MC calculations were different from that of 3D CRT. No significant dose differences in critical organs were observed between the two calculations.

Dose calculation differences between Monte Carlo and pencil beam depend on the tumor locations and volumes for lung stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) has been increasingly used as an efficacious treatment modality for early-stage non-small cell lung cancer. The accuracy of dose calculations is compromised due to the presence of inhomogeneity. For the purpose of a consistent prescription, radiation doses were calculated without heterogeneity correction in several RTOG trials. For patients participating in these trials, recalculations of the planned doses with more accurate dose methods could provide better correlations between the treatment outcomes and the planned doses. Using a Monte Carlo (MC) dose calculation algorithm as a gold standard, we compared the recalculated doses with the MC algorithm to the original pencil beam (PB) calculations for our institutional clinical lung SBRT plans. The focus of this comparison is to investigate the volume and location dependence on the differences between the two dose calculations. Thirty-one clinical plans that followed RTOG and other protocol guidelines were retrospectively investigated in this study. Dosimetric parameters, such as D1, D95, and D99 for the PTV and D1 for organs at risk, were compared between two calculations. Correlations of mean lung dose and V20 of lungs between two calculations were investigated. Significant dependence on tumor size and location was observed from the comparisons between the two dose calculation methods. When comparing the PB calculations without heterogeneity correction to the MC calculations with heterogeneity correction, we found that in terms of D95 of PTV: (1) the two calculations resulted in similar D95 for edge tumors with volumes greater than 25.1 cc; (2) an average overestimation of 5% in PB calculations for edge tumors with volumes less than 25.1 cc; and (3) an average overestimation of 9% or underestimation of 3% in PB calculations for island tumors with volumes smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the PB calculations resulted in an average reduction of 23.8% and 15.3% in the D95 for the PTV for island and edge lesions, respectively, when compared to the MC calculations. For organs at risks, very small differences were found among all the comparisons. Excellent correlations for mean dose and V20 of lungs were observed between the two calculations. This study demonstrated that using a single scaling factor may be overly simplified when accounting for the effects of heterogeneity correction. Accurate dose calculations, such as the Monte Carlo algorithms, are highly recommended to understand dose responses in lung SBRT.

Treatment plan quality and delivery accuracy assessments on 3 IMRT delivery methods of stereotactic body radiotherapy for spine tumors.

Stereotactic body radiotherapy (SBRT) for spine tumors has demonstrated clinical effectiveness. The treatment planning and delivery techniques have evolved from dynamic conformal arc therapy, to fixed gantry angle intensity modulated radiotherapy (IMRT), and most recently to volumetric modulated arc therapy (VMAT). A hybrid-arc (HARC) planning and delivery method combining dynamic conformal arc therapy delivery with a number of equally spaced IMRT beams is proposed. In this study we investigated plan quality, delivery accuracy, and efficiency of 3 delivery techniques: IMRT, HARC, and VMAT. Patients who underwent spine SBRT treatments were randomly selected from an Institutional Review Board-approved registry. For each patient, the prescription dose was 14 to 16 Gy in a single fraction to cover >90% of the tumor (without planning margin) while constraining V10Gy ≤ 10% of the spinal cord and the maximum point dose (MPD) of the spinal cord ≤ 14 Gy. All cases were clinically treated with fixed gantry step-shoot IMRT plans and then re-planned with VMAT using Pinnacle 9.0 and with HARC using Brainlab iPlan 4.5. Student t-test was used to compare the dosimetric end points, including V16Gy to the planning target volume, homogeneity index, MPDPTV, the conformity index, V10Gy of the spinal cord, and MPDcord. To compare the accuracy of delivery, we delivered all plans on a phantom and conducted gamma index (GI) comparisons with 3 mm/3% and 2 mm/2% criteria. All plans met our clinical requirements. Among 3 techniques, there were no differences on dose coverage to the tumor volume, maximum dose to the spinal cord, and plan homogeneity index (p > 0.05). The average V10Gy of the spinal cord was 6.66 ± 0.03%, 5.49 ± 0.03%, and 4.76 ± 0.02% for IMRT, HARC, and VMAT plans, respectively. Accordingly, the conformity indices were 1.30 ± 0.11 and 1.29 ± 0.20, 1.53 ± 0.29, respectively. VMAT plans were significantly (p < 0.05) less conformal but significantly (p < 0.05) lower V10Gy of the spinal cord than those from HARC and IMRT plans. With delivery accuracy measured by GIs, the average GIs of 3%/3 mm were 92.6 ± 1.1%, 96.5 ± 2.7%, 99.0 ± 1.1% for IMRT, HARC, and VMAT plans, respectively. The differences were significant (p < 0.05). Accordingly, the average monitor units were 9238 ± 2242, 9853 ± 2548 and 5091 ± 910. The plan quality created from the 3 planning techniques can meet the clinical requirement. Adding arc beams in delivery such as in HARC and VMAT plans improves the delivery accuracy. VMAT is the most efficient delivery method.

Dosimetric differences between local failure and local controlled non-small cell lung cancer patients treated with stereotactic body radiotherapy: A matched-pair study.

INTRODUCTION: Concerns were raised about the accuracy of pencil beam (PB) calculation and potential underdosing of medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). From our institutional series, we designed a matched-pair study where each local failure and controlled patient was matched based upon several clinical factors, to investigate the dose difference between the matched-pair. METHODS: Eighteen pairs of NSCLC patients, treated with 50 Gy in five fractions, were selected. These patients were matched based on treatment intent, tumour size, histology and clinical follow-up. All PB calculated clinical plans were retrospectively recalculated with a MC algorithm. The D99 and DMean of the gross tumour volume (GTV) and D95 and DMean of the planning tumour volume (PTV) from PB and Monte Carlo (MC) calculation were compared between local failures and controls using the Mann-Whitney test. RESULTS: The mean PB calculated D95 of PTV was 50.4 Gy for both failures and controls (P = 0.85), indicating no planning differences between the groups. From MC calculations, the mean (±SD) of GTV D99 , GTV DMean , PTV D95 , PTV DMean were 47.6 ± 2.6/46.3 ± 2.4, 50.4 ± 2.1/49.8 ± 1.6, 44.4 ± 2.7/43.6 ± 3.1, 48.7 ± 2.4/48.2 ± 2.4 Gy for failure/controlled groups, respectively, and there was no significant difference between two groups (all P > 0.1). The dose differences between MC and PB calculations were in agreement with other literatures and there was no significant difference between two groups. CONCLUSIONS: While PB algorithms may overestimate tumour doses relative to MC algorithms, our matched-pair study did not find dose differences between local failure and local controlled cases.

Pain flare after stereotactic radiosurgery for spine metastases.

PURPOSE: Understanding of pain flare (PF) following spine stereotactic radiosurgery (sSRS) is lacking. This study sought to determine the incidence and risk factors associated with PF following single fraction sSRS. MATERIALS/METHODS: An IRB-approved database was compiled to include patients who underwent sSRS. Patient and disease characteristics as well as treatment and dosimetric details were collected retrospectively. Pain relief post-sSRS was prospectively collected using the Brief Pain Inventory (BPI). These factors were correlated to the development of PF (defined as an increase in pain within 7 days of treatment which resolved with steroids). Survival was calculated using Kaplan-Meier analysis and logistic regression was utilized to evaluate the association between the clinical and treatment factors and occurrence of PF. RESULTS: A total of 348 patients with 507 treatments were included. Median age and prescription dose were 59 years and 15 Gy (range: 7-18), respectively, and 62% of patients were male. Renal cell carcinoma (24%), lung cancer (14%), and breast cancer (11%) were the most common histologies, and 74% had epidural disease and 43% had thecal sac compression. The most common location of metastases was in the cervical/thoracic spine (59%), followed by lumbar spine (32%), and sacral spine (9%). Most common reason for treatment was pain (73%), followed by pain and neurological deficit (13%), asymptomatic disease (10%), and neurologic deficit only (3%). Median time to pain relief was 1.8 months. Median overall survival, time to radiographic failure, and time to pain progression were 13.6 months, 26.5 months, and 56.6 months, respectively. Only 14.4% of treatments resulted in the development of PF. Univariate analysis showed that higher Karnofsky performance score (KPS) (OR=1.03, p=0.03), female gender (OR=1.80, p=0.02), higher prescription dose (OR=1.30, p=0.008), and tumor location of cervical/thoracic spine vs lumbar spine (OR=1.81, p=0.047) were predictors for the development of PF. On multivariate analysis, higher consult KPS (OR=1.03, p=0.04), female gender (OR=1.93, p=0.01), higher prescription dose (OR=1.27, p=0.02), and tumor location of cervical/thoracic spine vs lumbar spine (OR=1.81, p=0.05) remained predictors of PF. No other dosimetric parameters were associated with the development of PF. CONCLUSION: PF is an infrequent complication of sSRS. Predictors for the development of PF include higher consult KPS, female gender, higher prescription dose, and cervical/thoracic tumor location. Dose to the spinal cord was not a predictor of PF. Since a minority (14.4%) of treatments result in PF, we do not routinely utilize prophylactic steroid treatment; however, prophylactic steroids may be considered in female patients with cervical/thoracic metastases receiving higher dose sSRS.

Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy.

PURPOSE: To report the clinical experience with an electromagnetic treatment target positioning and continuous monitoring system in patients with localized prostate cancer receiving external beam radiotherapy. METHODS AND MATERIALS: The Calypso System is a target positioning device that continuously monitors the location of three implanted electromagnetic transponders at a rate of 10 Hz. The system was used at five centers to position 41 patients over a full course of therapy. Electromagnetic positioning was compared to setup using skin marks and to stereoscopic X-ray localization of the transponders. Continuous monitoring was performed in 35 patients. RESULTS: The difference between skin mark vs. the Calypso System alignment was found to be >5 mm in vector length in more than 75% of fractions. Comparisons between the Calypso System and X-ray localization showed good agreement. Qualitatively, the continuous motion was unpredictable and varied from persistent drift to transient rapid movements. Displacements > or =3 and > or =5 mm for cumulative durations of at least 30 s were observed during 41% and 15% of sessions. In individual patients, the number of fractions with displacements > or =3 mm ranged from 3% to 87%; whereas the number of fractions with displacements > or =5 mm ranged from 0% to 56%. CONCLUSION: The Calypso System is a clinically efficient and objective localization method for positioning prostate patients undergoing radiotherapy. Initial treatment setup can be performed rapidly, accurately, and objectively before radiation delivery. The extent and frequency of prostate motion during radiotherapy delivery can be easily monitored and used for motion management.

Dosimetric effect of multileaf collimator leaf width on volumetric modulated arc stereotactic radiotherapy for spine tumors.

This work aimed to study the dosimetric effect of multileaf collimator (MLC) leaf widths in treatment plans for patients receiving volumetric modulated arc therapy (VMAT) for spine stereotactic body radiation therapy (SBRT). Thirteen patients treated with spine SBRT were retrospectively selected for this study. The patients were treated following the protocol of the Radiation Therapy Oncology Group 0631 (RTOG 0631) for spine metastasis. The prescription dose was 16 Gy in 1 fraction to 90% of the target volume (V16 > 90%). The maximum spinal cord dose of 14 Gy and 10% of the spinal cord receiving < 10 Gy (V10) were the acceptable tolerance doses. For the purpose of this study, 2 dual-arc VMAT plans were created for each patient using 3 different MLC leaf widths: 2.5 mm, 4 mm, and 5 mm. The compliance with the RTOG 0631 protocol, conformity index (CI), dose gradient index (DGI), and number of monitor units (MUs) were compared. The average V16Gy of the targets was 91.8 ± 1.2%, 92.2 ± 2.1%, and 91.7 ± 2.3% for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively (p = 0.78). Accordingly, the average CI was 1.45 ± 0.4, 1.47 ± 0.29, and 1.47 ± 0.31 (p = 0.98), respectively. The average DGI was 0.22 ± 0.04, 0.20 ± 0.06, and 0.22 ± 0.05, respectively (p = 0.77). The average maximum dose to the spinal cord was 12.45 ± 1.0 Gy, 12.80 ± 1.0 Gy, and 12.48 ± 1.1 (p = 0.62) and V10% of the spinal cord was 3.6 ± 2.1%, 5.6 ± 2.8%, and 5.5 ± 3.0% (p = 0.11) for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively. Accordingly, the average number of MUs was 4341 ± 500 MU, 5019 ± 834 MU, and 4606 ± 691 MU, respectively (p = 0.053). The use of 2.5-mm, 4-mm, and 5-mm MLCs achieved similar VMAT plan quality as recommended by the RTOG 0631. The dosimetric parameters were also comparable for the 3 MLCs. In general, any of these leaf widths can be used for spine SBRT using VMAT.

Spine stereotactic radiosurgery for the treatment of multiple myeloma.

OBJECTIVE The objective of this study was to define symptomatic and radiographic outcomes following spine stereotactic radiosurgery (SRS) for the treatment of multiple myeloma. METHODS All patients with pathological diagnoses of myeloma undergoing spine SRS at a single institution were included. Patients with less than 1 month of follow-up were excluded. The primary outcome measure was the cumulative incidence of pain relief after spine SRS, while secondary outcomes included the cumulative incidences of radiographic failure and vertebral fracture. Pain scores before and after treatment were prospectively collected using the Brief Pain Inventory (BPI), a validated questionnaire used to assess severity and impact of pain upon daily functions. RESULTS Fifty-six treatments (in 38 patients) were eligible for inclusion. Epidural disease was present in nearly all treatment sites (77%). Moreover, preexisting vertebral fracture (63%), thecal sac compression (55%), and neural foraminal involvement (48%) were common. Many treatment sites had undergone prior local therapy, including external beam radiation therapy (EBRT; 30%), surgery (23%), and kyphoplasty (21%). At the time of consultation for SRS, the worst, current, and average BPI pain scores at these treatment sites were 6, 4, and 4, respectively. The median prescription dose was 16 Gy in a single fraction. The median clinical follow-up duration after SRS was 26 months. The 6- and 12-month cumulative incidences of radiographic failure were 6% and 9%, respectively. Among painful treatment sites, 41% achieved pain relief adjusted for narcotic usage, with a median time to relief of 1.6 months. The 6- and 12-month cumulative incidences of adjusted pain progression were 13% and 15%, respectively. After SRS, 1-month and 3-month worst, current, and average BPI scores all significantly decreased (p < 0.01). Vertebral fracture occurred following 12 treatments (21%), with an 18% cumulative incidence of fracture at 6 and 12 months. Two patients (4%) developed pain flare following spine SRS. CONCLUSIONS This study reports the largest series of myeloma lesions treated with spine SRS. A rapid and durable symptomatic response was observed, with a median time to pain relief of 1.6 months. This response was durable among 85% of patients at 12 months following treatment, with 91% local control. The efficacy and minimal toxicity of spine SRS is likely related to the delivery of ablative and conformal radiation doses to the target. SRS should be considered with doses of 14-16 Gy in a single fraction for patients with multiple myeloma and limited spinal disease, myelosuppression requiring "marrow-sparing" radiation therapy, or recurrent disease after EBRT.

Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Spinal Sarcomas.

PURPOSE: Despite advancements in local and systemic therapy, metastasis remains common in the natural history of sarcomas. Unfortunately, such metastases are the most significant source of morbidity and mortality in this heterogeneous disease. As a classically radioresistant histology, stereotactic radiosurgery has emerged to control spinal sarcomas and provide palliation. However, there is a lack of data regarding pain relief and relapse following stereotactic radiosurgery. METHODS: We queried a retrospective institutional database of patients who underwent spine stereotactic radiosurgery for primary and metastatic sarcomas. The primary outcome was pain relief following stereotactic radiosurgery. Secondary outcomes included progression of pain, radiographic failure, and development of toxicities following treatment. RESULTS: Forty treatment sites were eligible for inclusion; the median prescription dose was 16 Gy in a single fraction. Median time to radiographic failure was 14 months. At 6 and 12 months, radiographic control was 63% and 51%, respectively. Among patients presenting with pain, median time to pain relief was 1 month. Actuarial pain relief at 6 months was 82%. Median time to pain progression was 10 months; at 12 months, actuarial pain progression was 51%. Following multivariate analysis, presence of neurologic deficit at consult (hazard ratio: 2.48, P < .01) and presence of extraspinal bone metastases (hazard ratio: 2.83, P < .01) were associated with pain relief. Greater pain at consult (hazard ratio: 1.92, P < .01), prior radiotherapy (hazard ratio: 4.65, P = .02), and greater number of irradiated vertebral levels were associated with pain progression. CONCLUSIONS: Local treatment of spinal sarcomas has remained a challenge for decades, with poor rates of local control and limited pain relief following conventional radiotherapy. In this series, pain relief was achieved in 82% of treatments at 6 months, with half of patients experiencing pain progression by 12 months. Given minimal toxicity and suboptimal pain control at 12 months, dose escalation beyond 16 Gy is warranted.

Single-Fraction Spine Stereotactic Body Radiation Therapy for the Treatment of Chordoma.

PURPOSE: Chordoma is a radioresistant tumor that presents a therapeutic challenge with spine involvement, as high doses of radiation are needed for local control while limiting dose to the spinal cord. The purpose of this study is to determine the efficacy and safety of single-fraction spine stereotactic body radiation therapy for the treatment of spine chordoma. METHODS: A retrospective review of our institutional database from 2006 to 2013 identified 8 patients (12 cases) with chordoma of the spine who were treated with spine stereotactic body radiation therapy. Surgical resection was performed in 7 of the 12 cases. The treatment volume was defined by the bony vertebral level of the tumor along with soft tissue extension appreciated on magnetic resonance imaging fusion. Medical records and imaging were assessed for pain relief and local control. Treatment toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Median age was 59 years (range, 17-91). Median target volume was 48 cm3 (1-304), and median prescription dose was 16 Gy (11-16). Median conformality index was 1.44 (1.14-3.21), and homogeneity index was 1.12 (1.05-1.19). With a median follow-up time of 9.7 months (.5-84), local control was achieved in 75% of the cases treated. One patient developed limited grade 2 spinal cord myelopathy that resolved with steroids. There were no other treatment toxicities from spine stereotactic body radiation therapy. CONCLUSION: Single-fraction spine stereotactic body radiation therapy can be safely delivered to treat chordoma of the spine with the potential to improve pain symptoms. Although the early data are suggestive, long-term follow-up with more patients is necessary to determine the efficacy of spine stereotactic body radiation therapy in the treatment of chordoma of the spine.

Stereotactic Body Radiotherapy for T3N0 Lung Cancer With Chest Wall Invasion.

INTRODUCTION: The role of stereotactic body radiotherapy (SBRT) for tumors involving the chest wall (CW) remains ill-defined. The Radiation Therapy Oncology Group 0236 trial allowed inclusion of T3N0 non-small-cell lung cancer (NSCLC) < 5 cm, although ultimately none were enrolled. No published data set investigating this population is available. MATERIALS AND METHODS: We queried an institutional review board-approved prospective SBRT registry to identify patients with tumors involving the CW, defined as radiographic evidence of frank soft tissue invasion or bony destruction. All patients underwent SBRT to a median dose of 50 Gy in 5 fractions and were followed up for tumor control, pain response, and toxicity. RESULTS: Of 820 NSCLC patients reviewed, 13 with CW involvement were identified. Of these 13 patients, 10 had primary T3N0 NSCLC and 3 had recurrent NSCLC. Their median age was 78 years, the Karnofsky performance status was 80, the Charlson score was 3, and the tumor diameter was 4.0 cm. The 1-year local, locoregional, and distant control rates were 89%, 62%, 80%, respectively. Of 9 patients with pretreatment tumor-related CW pain, 7 (78%) reported improvement after treatment. Regarding toxicity, 2 of 13 (15%) experienced new or worsening CW pain (both grade ≤ 2); 3 cases (23%) of grade 1-2 radiation pneumonitis developed. No patient exhibited late skin changes or fibrosis. CONCLUSION: SBRT for NSCLC involving the CW was well tolerated, with promising early rates of tumor control and no grade ≥ 3 toxicity. Tumor-related CW pain was relieved in most patients, and the treatment-related toxicity rates appeared acceptable. Further investigation in this subset of patients with NSCLC is warranted.

Quantitative Evaluation of Local Control and Wound Healing Following Surgery and Stereotactic Spine Radiosurgery for Spine Tumors.

OBJECTIVE: The present study evaluated the optimal measuring criteria to assess spinal tumor response to surgery followed by stereotactic spine radiosurgery (SRS) and reports the local control and wound complication rates following combined multimodality treatment. METHODS AND MATERIALS: Prospectively collected patient information was retrospectively reviewed to identify patients treated with spine surgery followed by SRS. Tumor sizes and volumetric assessment were formally measured. Local control status was defined according to World Health Organization (WHO, bidimensional), RECIST (unidimensional), or volumetric size change. Statistical comparative assessments of tumor measurements were performed. RESULTS: Twenty-two patients were eligible for evaluation after having undergone surgery followed by single-fraction SRS within a 2-month period. Seventeen had follow-up magnetic resonance imaging (MRI) with a mean patient follow-up of 12.59 months (range 3-36 months). None developed wound complication after radiation therapy (95% lower confidence bound 13%). Two patients had clinical recurrence while 15 of 17 achieved local control (88.3%). A test of marginal homogeneity for RECIST versus WHO was not statistically significant, P = 1.0 suggesting similar response classifications with both systems. Spearman correlations among 1) volumetric assessment, 2) bidimensional size, and 3) unidimensional size were significant for all groups (P < 0.05). CONCLUSION: High local control rates can be achieved with surgery followed by SRS. Further, adjuvant SRS following spine tumor surgery delivers less radiation to the wound than conventional radiation and thus potentially reduces wound complications. Unidimensional, bidimensional, and volumetric tumor assessments demonstrate similar results. Hence the use of the simpler RECIST criteria is suitable and appropriate for evaluating the response to treatment after spine radiosurgery.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes.

PURPOSE: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. RESULTS: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. CONCLUSIONS: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer Tumors Greater Than 5 cm: Safety and Efficacy.

PURPOSE: The purpose of this study was to determine outcomes of patients with node-negative medically inoperable non-small cell lung cancer (NSCLC) whose primary tumors exceeded 5 cm and were treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: We surveyed our institutional prospective lung SBRT registry to identify treated patients with tumors >5 cm. Treatment outcomes for local control (LC), locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were assessed by Kaplan-Meier estimates. Toxicities were graded according to Common Terminology Criteria for Adverse Events version 4. Mean pretreatment pulmonary function test values were compared to mean posttreatment values. RESULTS: From December 2003 to July 2014, 40 patients met study criteria. Median follow-up was 10.8 months (range: 0.4-70.3 months). Median age was 76 years (range: 56-90 years), median body mass index was 24.3 (range: 17.7-37.2), median Karnofsky performance score was 80 (range: 60-90), and median Charlson comorbidity index score was 2 (range: 0-5). Median forced expiratory volume in 1 second (FEV1) was 1.41 L (range: 0.47-3.67 L), and median diffusion capacity (DLCO) was 47% of predicted (range: 29%-80%). All patients were staged by fluorodeoxyglucose-positron emission tomography/computed tomography staging, and 47.5% underwent mediastinal staging by endobronchial ultrasonography. Median tumor size was 5.6 cm (range: 5.1-10 cm), median SBRT dose was 50 Gy (range: 30-60 Gy) in 5 fractions (range: 3-10 fractions). Eighteen-month LC, LRC, DFS, and OS rates were 91.2%, 64.4%, 34.6%, and 59.7%, respectively. Distant failure was the predominant pattern of failure (32.5%). Three patients (7.5%) experienced grade 3 or higher toxicity. Mean posttreatment FEV1 was not significantly reduced (P=.51), but a statistically significant absolute 6.5% (P=.03) reduction in DLCO was observed. CONCLUSIONS: Lung SBRT for medically inoperable node-negative NSCLC with primary tumors larger than 5 cm is safe and provides excellent local control with limited toxicity. The predominant pattern of failure in this population was distant failure.

Stereotactic body radiotherapy for a large arteriovenous malformation of the head and neck.

Large arteriovenous malformations (AVMs) of the head and neck present a treatment challenge. A 38-year-old woman presented with a large intraoral bleed from longstanding AVMs of the left infratemporal fossa and the right tongue, despite 10 prior surgeries and embolizations. She was treated with stereotactic body radiotherapy with a dose of 24 Gy in three weekly fractions. Four years later, she has had dramatic shrinkage of her AVM, no recurrent bleeding episodes, no further treatment required, and no significant late effects. Level of evidence: NA.