Single-fraction Stereotactic Body Research Articles

Linear accelerator-based single-fraction stereotactic body radiotherapy for symptomatic vertebral body hemangiomas: The Mayo Clinic experience

Symptomatic vertebral hemangiomas (SVHs) are rare benign tumors that when symptomatic require procedural intervention or radiotherapy (RT). Although conventionally-fractionated RT has been an alternative to surgical resection, there is very little data on stereotactic body radiotherapy (SBRT) for SVHs. Six consecutively treated patients with SVHs underwent definitive single-fraction SBRT from 2010 to 2018 at our institution. The RT planning parameters, treatment, outcome, and toxicities are reported for 6 patients with 6 total SVHs treated with single-fraction SBRT. Each patient presented with back pain and received single-fraction SBRT to a thoracic vertebral body hemangioma. One patient had received radiofrequency ablation prior to SBRT. The median SBRT dose was 18 Gy (range, 13–20). Following SBRT, 4 (67%) patients reported improvement in presenting symptoms and 2 patients (33%) were refractory. There were no acute or chronic toxicities associated with SBRT including esophagitis, vertebral compression fractures, or myelopathy. To date, this is the largest series of single-fraction SBRT for SVHs. Single fraction SBRT appears to be a feasible option for SVHs. Further studies are needed to confirm our preliminary findings and optimize dose fractionation.

A Pilot Trial Evaluating Stereotactic Body Radiation Therapy to Induce Hyperemia in Combination With Transarterial Chemoembolization for Hepatocellular Carcinoma

Despite the survival benefit of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), a majority of tumors recur, attributed to hypovascularity and treatment resistance. Preclinical studies show that moderate radiation doses induce changes in tumor permeability and perfusion, suggesting an opportunity for TACE sensitization by radiation. In this prospective phase 1 trial, we evaluated the feasibility, safety, tolerability, response, and functional magnetic resonance imaging (MRI) changes associated with single-fraction stereotactic body radiation therapy (SBRT) followed by TACE within 24 hours. Patients with HCC, 1 to 3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hours. Secondary endpoints included safety, tolerability, perfusional changes via functional MRI, overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression, progression-free survival, and overall survival. Sixteen patients were enrolled, and 13 received SBRT and TACE. Median follow-up was 15.3 months. Best overall ORR and CBR were 76.9% and 92.3%, respectively. The 1- and 3-month ORR was 76.9% and 69.2%, respectively, and 1- and 3-month CBR was 92.3% and 69.2%, respectively. Median overall survival, progression-free survival, and freedom from local progression were 14.0, 5.2, and 5.9 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity were 85% and 38%, respectively. No grade 3 to 4 toxicities were recorded. One grade 5 toxicity occurred due to hemorrhage 4 days after TACE. On dynamic contrast-enhanced MRI, the transfer rate constant from blood plasma to extracellular extravascular space (kpe) increased within 6 hours post-SBRT but decreased by 24 hours. We hypothesized a strategy of SBRT preceding TACE for the purpose of enhancing TACE delivery and efficacy and tested this strategy in a small pilot study. We found that single-dose SBRT followed by TACE within 24 hours is feasible and tolerable. Dynamic contrast-enhanced MRI revealed acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination and the effects of SBRT on the HCC microenvironment.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

BackgroundBone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic.MethodsThis is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24–48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode.DiscussionIf a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures.Trial registrationThe Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov (NCT03831243) on February 5th 2019.

Single Fraction Stereotactic Body Radiation Therapy After Surgery in Treating Patients With Non-small Cell Lung Cancer

Single Fraction Stereotactic Body Radiation Therapy After Surgery in Treating Patients With Non-small Cell Lung Cancer

Single-fraction radiotherapy for bone metastases.

New research suggests that in patients with mostly non-spine bone metastases, single-fraction stereotactic body radiotherapy (SBRT) could be non-inferior to standard multifraction radiotherapy (MFRT).

Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases

Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases. To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases. This prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions. The primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT. In this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT. Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival. ClinicalTrials.gov identifier: NCT02163226.

Single-fraction Stereotactic Body Radiation Therapy versus Conventionally Fractionated Radiation Therapy for the Treatment of Prostate Cancer Bone Metastases

PurposeThis study aimed to compare outcomes of patients with prostate cancer with bone metastases treated with stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT). Methods and materialsAn institutional, retrospective review was conducted of patients with prostate cancer receiving radiation therapy to bone metastases. In-field failure (IFF) was the primary outcome of the study, and distant failure (DF) and biochemical failure (BF) were secondary outcomes. ResultsA total of 249 metastases (191 SBRT; 58 CFRT) in 201 patients with a median follow-up of 2.2 years were analyzed. The SBRT prescription dose was predominantly 18 Gy (45.5%) or 20 Gy (46.6%) in a single fraction. CFRT was given either as 8 Gy in 1 fraction (56.9%) or 20 Gy in 5 fractions (41.4%). Imaging follow up was performed most frequently with 11C-choline positron emission tomography/computed tomography (79%) or bone scan (10%). The median time to IFF was 1.6 years for CFRT-treated lesions and not met (>4.4 years) for SBRT. The 1- and 3-year IFF estimates were 34.4% (95% confidence interval [CI], 19.9-46.2) and 53.3% (95% CI, 34.3-66.8) for lesions treated with CFRT compared with 4.5% (95% CI, 1.4-7.5) and 12.9% (95% CI, 6.6-18-8) for those treated with SBRT (P < .01). On multivariate regression, the hazard ratio (HR) for IFF with CFRT compared with SBRT was 6.8 (95% CI, 3.7-12.5; P < .01). There were nonsignificant reduced rates of BF (HR, 1.4; 95% CI, 1.0-2.1; P = .05) and DF (HR, 1.3; 95% CI, 1.0-1.8; P = .08) in patients who received SBRT. The 3-year BF and DF estimates in these patients were 88.6% (95% CI, 82.0-92.8) and 82.2% (95% CI, 74.5-87.6), respectively. ConclusionsSBRT for the management of prostate cancer bone metastases significantly reduces radiographic IFF. However, the high rate of subsequent DF and BF highlights the challenges in selecting patients who may benefit from aggressive radiation therapy.

Effect of Tumor Location and Dosimetric Predictors for Chest Wall Toxicity in Single-Fraction Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer

PurposeDosimetric parameters to limit chest wall toxicity (CWT) are not well defined in single-fraction (SF) stereotactic body radiation therapy (SBRT) phase 2 trials. We sought to determine the relationship of tumor location and dosimetric parameters with CWT for SF-SBRT. Methods and MaterialsFrom a prospective registry of 1462 patients, we identified patients treated with 30 Gy or 34 Gy. Gross tumor volume was measured as abutting, ≤1 cm, 1 to 2 cm, or >2 cm from the chest wall. CWT was prospectively graded according to Common Terminology Criteria for Adverse Events version 3.0, with grade 2 requiring medical therapy, grade 3 requiring procedural intervention, and grade 4 being disabling pain. Grade 1 CWT or radiographic rib fracture was not included. Logistic regression analysis was used to identify the parameters associated with CWT and calculate the probability of CWT with dose. ResultsThis study included 146 lesions. The median follow-up time was 23.8 months. The 5-year local control, distant metastasis, and overall survival rates were 91.8%, 19.2%, and 28.7%, respectively. Grade 2 to 4 CWT was 30.6% for lesions abutting the chest wall, 8.2% for ≤1 cm from the chest wall, 3.8% for 1 to 2 cm from the chest wall, and 5.7% for >2 cm from the chest wall. Grade ≥3 CWT was 1.4%. Tumor abutment (odds ratio [OR]: 6.5; P = .0005), body mass index (OR: 1.1; P = .02), rib D1cc (OR: 1.01/Gy; P = .03), chest wall D1cc (OR: 1.08/Gy; P = .03), and chest wall D5cc (OR: 1.10/Gy; P = .01) were significant predictors for CWT on univariate analysis. Tumor abutment was significant for CWT (OR: 7.5; P = .007) on multivariate analysis. The probability of CWT was 15% with chest wall D5cc at 27.2 Gy and rib D1cc at 30.2 Gy. ConclusionsThe rate of CWT with SF-SBRT is similar to the rates published for fractionated SBRT, with most CWT being low grade. Tumor location relative to the chest wall is not a contraindication to SF-SBRT, but the rates increase significantly with abutment. Rib D1cc and chest wall D1cc and D5cc may be used as predictors of CWT.

Sparing the surgical area with stereotactic body radiotherapy for combined treatment of spinal metastases: a treatment planning study

Introduction: Decreasing the radiation dose in the surgical area is important to lower the risk of wound complications when surgery and radiotherapy are combined for the treatment of spinal metastases. The purpose of this study was to compare the radiation dose in the surgical area for spinal metastases between single fraction external beam radiotherapy (EBRT), single fraction stereotactic body radiotherapy (SBRT) and single fraction SBRT with active sparing (SBRT-AS) of the posterior surgical area.Methods: Radiotherapy treatment plans for EBRT, SBRT and SBRT-AS of the posterior surgical area were created for 13 patients with spinal metastases. A single fraction of 8Gy was prescribed to the spinal metastasis in the EBRT plan. For the SBRT treatment plans, a single fraction of 18Gy was prescribed to the metastasis and 8Gy to the rest of the vertebral body. For the SBRT plan with active sparing the dose in the designated surgical area was minimized without compromising the dose to the organs at risk.Results: The median dose in the surgical area was 2.6Gy (1.6–5.3Gy) in the SBRT plan with active sparing of the surgical area compared to a median dose of 3.7Gy (1.6–6.3Gy) in the SBRT plan without sparing and 6.5Gy (3.5–9.1Gy) in the EBRT plans (p < .001). The radiation doses to the spinal metastases and organs at risk were not significantly different between the SBRT plan with and without sparing the surgical area.Conclusions: The radiation dose to the surgical area is significantly decreased with the use of SBRT compared to EBRT. Active sparing of the surgical area further decreased the mean radiation dose in the surgical area without compromising the dose to the spinal metastasis and the organs at risk.

Stereotactic Body Versus Hypofractionated Radiation Therapy for Local Control of Prostate Cancer Bone Metastases

To compare the rate of radiographic in field failure (IFF) for prostate cancer bone metastases treated with single fraction stereotactic body radiation therapy (SBRT) and hypofractionated radiation therapy (HRT), and secondarily describe the rate of subsequent distant failure (DF). An institutional, retrospective review was conducted of all patients with prostate cancer receiving RT to bone metastases between January 2013 and May 2017. Patients were excluded if less than 6 months of clinical and imaging follow-up was available. IFF was defined as any increase in the size and/or radiotracer avidity of the treated lesion, subsequent use of a secondary local salvage therapy to the treated site, or the appearance of a new lesion within the initial 50% isodose line. DF, defined as new metastatic disease following RT, was a secondary outcome. The cumulative incidence of IFF and DF was determined using the Fine-Gray method with death as a competing risk. Hazard ratios (HR) for single variable associations with outcomes were calculated using the Cox model and a P value of 0.05 was set to determine significance. A total of 201 patients with 249 metastases (191 SBRT, 58 HRT) with a median follow-up of 2.2 (IQR 1.2-3.0) years were analyzed. Patients treated with SBRT more frequently had 1-3 metastases compared to those receiving HRT (85% vs 40%, P<0.0001). The presence of castrate resistant disease was not significantly different between the SBRT and HRT groups (41% vs 35%, P=0.39). The SBRT prescription dose ranged from 16 to 24 Gy in a single fraction, with most receiving 18 (46%) or 20 (47%) Gy. HRT was mainly 8 Gy in 1 fraction (57%) or 20 Gy in 5 fractions (41%). Imaging follow-up was primarily with 11C-choline PET/CT (79%), technetium 99m-MDP bone scan (10%), or CT scan (5%). The one and three-year IFF rates were 34% (95% CI 20-46) and 53% (34-67) for lesions treated with HRT compared to 5% (1.4-7.5) and 13% (7-19) in those treated with SBRT. On single variable regression, the HR for IFF with HRT compared to SBRT was 6.8 (3.7-12.5; P <.0001). No other variables assessed, including Gleason score, castrate resistant disease status, or anatomical location of metastasis were associated with an increased risk of IFF (P >0.05). There was no difference in DF for patients treated with HRT compared with SBRT [3-year cumulative incidence estimate 94% (77-98) vs. 82% (75-88); HR 1.33 (0.97-1.81), P=0.08]. Single fraction SBRT at doses ≥ 16 Gy is an effective means of local therapy and significantly improves radiographic IFF compared to HRT in prostate cancer patients with bone metastases. In this large cohort of patients, local control using SBRT was 95% and 87% at one and three years respectively. The subsequent risk of DF was high. Thus, optimizing patient selection and multidisciplinary management of local and systemic therapies remains essential.

Impact of Tumor Location & Dosimetric Predictors for Chest Wall Toxicity in Single Fraction SBRT for Stage I Non-Small Cell Lung Cancer

Single fraction stereotactic body radiation therapy (SF-SBRT) is an acceptable regimen for the treatment of peripheral Stage I Non-Small Cell Lung Cancer (NSCLC). Rates of chest wall toxicity (CWT) reported by phase II trials did not stratify by distance of tumor to chest wall (CW) and dosimetric parameters to limit CWT are not well defined. We sought to determine the relationship of tumor location and dosimetric parameters with CWT in SF-SBRT for peripheral Stage I NSCLC. An institutional review board-approved prospective SBRT registry of 1,462 patients (pts) was used to identify pts treated with 30 Gy or 34 Gy in one fraction, on or off relevant protocols. Tumors were ≤ 5 cm, node-negative, and ≥ 2 cm from the proximal tracheo-bronchial tree. The ribs and CW were retrospectively contoured (CW as a 3 cm soft-tissue structure between the sternum and vertebral body). Gross tumor volume was measured as abutting, ≤ 1 cm, 1-2 cm or > 2 cm from the CW. CWT was graded according to CTCAE 3.0 criteria. Rates of CWT were compared using unpaired t-test. Logistic regression analysis was used to identify tumor and dosimetric parameters associated with CWT. This study included 138 pts treated with SF-SBRT to 146 lesions. Median follow-up was 23.8 months (34.7 months for living pts). There were 80 pts (55%) treated with 30 Gy and 66 pts (45%) treated with 34 Gy. The rate of CWT was 30.6% for lesions abutting CW, 8.2% for lesions ≤ 1 cm from CW, 3.8% for lesions 1-2 cm from CW, and 5.7% for lesions > 2 cm from CW. Grade ≥ 3 CWT for the whole cohort was modest (1.4%). Tumor abutment (OR 6.5; p=0.0005), BMI (OR 1.1; p= 0.02), rib D1cc (defined as dose to 1 cc) (OR 1.01 per Gy; p= 0.03), CW D1cc (OR= 1.08 per Gy; p=0.03), and CW D5cc (OR 1.10 per Gy; p= 0.01) were significant predictors for CWT on univariate analysis. Tumor abutment was the only significant predictor for CWT (OR 7.5; p= 0.007) on multivariate analysis. CWT remained low until a dose threshold and then increased more rapidly. CWT occurred in only 1 out of 40 pts with CW D5cc < 18 Gy (defined as dose to 5 cc less than 18 Gy), while our model suggested a 15% risk of CWT with D5cc of 27.2 Gy to the CW. CWT occurred in only 1 out of 39 pts with rib D1cc < 19 Gy, while our model suggested a 15% risk of CWT with D1cc of 30.2 Gy to the rib. The rate of CWT is significantly associated with distance from the CW. When considering only lesions adjacent to the CW, the rate of CWT in this series (30.6%) does not appear to exceed rates in the published fractionated SBRT literature (20-33%). This suggests location adjacent to the CW should not be a contraindication to SF-SBRT. Rib D1cc and CW D1cc and D5cc may be used as predictors of CWT rates, as noted in this model. As most CWT is low-grade and self-limited, these dosimetric parameters should be utilized as a guideline, rather than an absolute constraint.

Single-Fraction Stereotactic Ablative Body Radiation Therapy as an Effective Management of Oligometastasis: Results From 133 Consecutive Patients

Single-Fraction Stereotactic Ablative Body Radiation Therapy as an Effective Management of Oligometastasis: Results From 133 Consecutive Patients

Single-fraction flattening filter–free volumetric modulated arc therapy for lung cancer: Dosimetric results and comparison with flattened beams technique

PurposeTo report on single-fraction stereotactic body radiotherapy (RT) (SBRT) with flattening filter (FF)–free (FFF) volumetric modulated arc therapy (VMAT) for lung cancer and to compare dosimetric results with VMAT with FF. Methods and materialsOverall, 25 patients were treated with 6-MV FFF VMAT (Varian TrueBeam STx LINAC) to a prescribed dose of 24Gy in a single fraction. Treatment plans were recreated using FF VMAT. Dose-volume indices, monitor units (MU), and treatment times were compared between FFF and FF VMAT techniques. ResultsDose constraints to PTV, spinal cord, and lungs were reached in FFF and FF plans. In FFF plans, average conformity index was 1.13 (95% CI: 1.07 to1.38). Maximum doses to spinal cord, heart, esophagus, and trachea were 2.9Gy (95% CI: 0.4 to 6.7Gy), 0.8Gy (95% CI: 0 to 3.6Gy), 3.3Gy (95% CI: 0.02 to 13.9Gy), and 1.5Gy (95% CI: 0 to 4.9Gy), respectively. Average V7Gy, V7.4Gy, and mean dose to the healthy lung were 126.5cc (95% CI: 41.3 to 248.9cc), 107.3cc (95% CI: 18.7 to 232.8cc), and 1.1Gy (95% CI: 0.3 to 2.2Gy), respectively. No statistically significant differences were found in dosimetric results and MU between FF and FFF treatments. Treatment time was reduced by an average factor of 2.31 (95% CI: 2.15 to 2.43) from FF treatments to FFF, and the difference was statistically significant. ConclusionsFFF VMAT for lung SBRT provides equivalent dosimetric results to the target and organs at risk as FF VMAT while significantly reducing treatment time.

Stereotactic Body Radiotherapy for Pancreatic Adenocarcinoma: Single versus Multi-Fraction

We have previously reported excellent local control of single-fraction stereotactic body radiotherapy (SBRT) for unresectable pancreatic adenocarcinoma, although with associated GI toxicity. In order to reduce toxicity rates, we transitioned to a multi-fraction treatment. We report updated outcomes of single versus multi-fraction SBRT for patients with unresectable pancreatic adenocarcinoma.

PTV Margin Determination for Single-Fraction Stereotactic Body Radiation Therapy (SBRT) Boost for Intermediate-Risk Adenocarcinoma of the Prostate

PTV Margin Determination for Single-Fraction Stereotactic Body Radiation Therapy (SBRT) Boost for Intermediate-Risk Adenocarcinoma of the Prostate

A Phase 2 Multi-institutional Study to Evaluate Gemcitabine and Fractionated Stereotactic Radiotherapy for Unresectable, Locally Advanced Pancreatic Adenocarcinoma

4045 Background: Phase I/II studies with single-fraction (25 Gy) stereotactic body radiotherapy (SBRT) for pancreatic ductal adenocarcinoma (PDA) have shown local progression free survival (LPFS) r...

Single-fraction stereotactic body radiotherapy for spinal metastases from renal cell carcinoma

Stereotactic body radiotherapy (SBRT) has emerged as an important treatment option for spinal metastases from renal cell carcinoma (RCC) as a means to overcome RCC's inherent radioresistance. The authors reviewed the outcomes of SBRT for the treatment of RCC metastases to the spine at their institution, and they identified factors associated with treatment failure. Fifty-seven patients (88 treatment sites) with RCC metastases to the spine received single-fraction SBRT. Pain relief was based on the Brief Pain Inventory and was adjusted for narcotic use according to the Radiation Therapy Oncology Group protocol 0631. Toxicity was scored according to Common Toxicity Criteria for Adverse Events version 4.0. Radiographic failure was defined as infield or adjacent (within 1 vertebral body [VB]) failure on follow-up MRI. Multivariate analyses were performed to correlate outcomes with the following variables: epidural, paraspinal, single-level, or multilevel disease (2-5 sites); neural foramen involvement; and VB fracture prior to SBRT. Kaplan-Meier analysis and Cox proportional hazards modeling were used for statistical analysis. The median follow-up and survival periods were 5.4 months (range 0.3-38 months) and 8.3 months (range 1.5-38 months), respectively. The median time to radiographic failure and unadjusted pain progression were 26.5 and 26.0 months, respectively. The median time to pain relief (from date of simulation) and duration of pain relief (from date of treatment) were 0.9 months (range 0.1-4.4 months) and 5.4 months (range 0.1-37.4 months), respectively. Multivariate analyses demonstrated that multilevel disease (hazard ratio [HR] 3.5, p = 0.02) and neural foramen involvement (HR 3.4, p = 0.02) were correlated with radiographic failure; multilevel disease (HR 2.3, p = 0.056) and VB fracture (HR 2.4, p = 0.046) were correlated with unadjusted pain progression. One patient experienced Grade 3 nausea and vomiting; no other Grade 3 or 4 toxicities were observed. Twelve treatment sites (14%) were complicated by subsequent vertebral fractures. Stereotactic body radiotherapy for RCC metastases to the spine offers fast and durable pain relief with minimal toxicity. Stereotactic body radiotherapy seems optimal for patients who have solitary or few spinal metastases. Patients with neural foramen involvement are at an increased risk for failure.

A phase II multi-institutional study to evaluate gemcitabine and fractionated stereotactic body radiotherapy for unresectable, locally advanced pancreatic adenocarcinoma.

4045 Background: Phase I/II studies with single-fraction (25 Gy) stereotactic body radiotherapy (SBRT) for pancreatic ductal adenocarcinoma (PDA) have shown local progression free survival (LPFS) rates of &gt;90%, but are limited by late GI toxicity and minimal tumor response. We performed a phase II multi-center trial of gemcitabine (GEM) and fractionated SBRT to determine if a high rate of LPFS with reduced toxicity could be achieved. Methods: After multidisciplinary review, 32 pts with locally advanced PDA received GEM in sequence with SBRT (6.6 Gy in 5 consecutive daily fractions, 33 Gy total). LPFS, metastasis free survival (MFS), and overall survival (OS) were measured from date of tissue diagnosis. Objective tumor response (OTR) was assessed by RECIST/PERCIST. EORTC QLQ-C30/PAN26 questionnaires were used to measure QOL. Results: Median f-up was 12 mos (range, 2-23). Mean age was 69.9 yrs (SD, 9.8) and 62% were male. Pts received a mean of 2.2 (SD, 1.0) GEM doses prior to SBRT and 8.3 (SD, 5.6) doses total. All pts completed SBRT. Median OS was 15.9 months (95% CI, 12.7-18.8). Stratification by CA19-9 &gt; or &lt; 90 at diagnosis yielded a hazard ratio of 6.2 for &gt; 90 (p=0.021). Median LPFS has not been reached and median MFS was 10.2 mos (95% CI, 2.9-17.5). LPFS rate at 1 year was 87%. OTR on CT was seen in 41%, while 41% had stable disease and 18% progressed. Tumor metabolic activity decreased in 17/18 patients with pre/post-SBRT PET available. Mean peak SUV was 4.0 pre-SBRT versus 2.4 post-SBRT (p=0.002). Median CA19-9 was reduced from 124.7 prior to SBRT to 43.9 afterwards. Acute toxicity included: grade 2 anorexia (37%), fatigue (28%), nausea (22%), abd pain (19%), weight loss (9%), diarrhea (3%); gr 3 nausea (9%); and gr 4 nausea (6%). Late gr ≥3 GI toxicity was seen in 9%. Mean QOL score 4 wks post-SBRT was similar to baseline (p=0.38). At 6 mos there was a trend towards improved QOL (p=0.07). Conclusions: Fractionated SBRT with GEM achieves high rates of LPFS and tumor response. Minimal grade ≥3 acute and late toxicity was observed. SBRT is more likely to benefit patients with Ca-19-9 &lt;90. A combination of SBRT with more aggressive chemotherapy may further improve outcomes.

Phase 1/2 trial of single‐session stereotactic body radiotherapy for previously unirradiated spinal metastases

In this phase 1/2 study, the authors tested the hypothesis that single-fraction stereotactic body radiotherapy (SBRT) for previously unirradiated spinal metastases is a safe, feasible, and efficacious treatment approach. All patients were evaluated by a multidisciplinary team. Spinal magnetic resonance imaging studies were obtained before treatment and at regular intervals to define both target volume and response to treatment. SBRT was delivered to a peripheral dose of 16 to 24 grays in a single fraction while limiting the dose to the spinal cord. Higher doses were used for renal cell histology. The National Cancer Institute Common Toxicity Criteria 2.0 and McCormick neurologic function score were used as toxicity assessment tools. In total, 61 patients who had 63 tumors of the noncervical spine were enrolled and received SBRT between 2005 and 2010 on a prospective, phase 1/2 trial at The University of Texas M. D. Anderson Cancer Center. The mean follow-up was 20 months. The actuarial 18-month imaging local control rate for all patients was 88%, the actuarial 18-month overall survival rate for all patients was 64%, and the median survival for all patients was 30 months. No significant differences in outcomes were noted with respect to tumor histology or SBRT dose. Two patients experienced radiation adverse events (grade 3 or higher). The actuarial rate of 18-month freedom from neurologic deterioration from any cause was 82%. Data from this phase 1/2 trial supported an expanded indication for SBRT as first-line treatment of spinal metastases in selected patients. The authors concluded that additional studies that can prospectively identify predictive factors for spinal cord toxicity after SBRT are warranted to minimize the incidence of this serious yet rare complication.

Phase I/II Trial of Single Fraction Stereotactic Body Radiotherapy for Previously Un-irradiated Spinal or Paraspinal Metastases

To report on the results from a completed Phase I/II study designed to test the hypothesis that single-fraction SBRT for previously un-irradiated spinal and paraspinal metastases is a safe, feasible, and efficacious treatment approach.