Double-Blind, Placebo-Controlled Pilot Study of Processed Ultra Emu Oil Versus Placebo in the Prevention of Radiation Dermatitis.

PURPOSE: The purpose of this single-institution pilot study was to evaluate the feasibility and safety of an oil-based skin agent, Ultra Emu Oil, on skin-related toxicity in patients undergoing radiation therapy to the breast or chest wall. METHODS AND MATERIALS: Patients were randomized 2:1 in a double-blind fashion and were instructed to apply processed Ultra Emu Oil or placebo (cottonseed oil) twice daily during the course of radiation therapy. The oils were applied before the third fraction and continued for 6 weeks after completion of treatment. The primary endpoint was the area under the curve (AUC) of Skindex-16 scale scores over time. Secondary outcomes included maximum grade of radiation dermatitis using the Common Terminology Criteria (CTC) for Adverse Events (CTCAE 3.0), the Skin Toxicity Assessment Tool, quality of life (QOL) measured by Linear Analogue Self-Assessment, and a symptom experience diary (SED). RESULTS: In all, 42 of 45 patients completed the study and were evaluable. The median times to peak rash, skin redness, peeling, and skin swelling were weeks 6, 6, 7, and 7, respectively as measured by the SED. The Skindex AUC scores tended to be lower in emu oil patients than in placebo patients (mean total AUC 7.2 vs 10.4, respectively). This trend was also seen in all the Skindex subdomains. The overall QOL was slightly better in the emu oil group but remained stable throughout the study for both arms. Peak CTC toxicity occurred at week 6. Patients using emu oil appeared slightly worse on maximum CTC grade, but the difference was not significant. CONCLUSIONS: This pilot study confirmed the safety of oil-based skin treatments during radiation therapy and suggests a trend for reduced skin toxicity for patients receiving emu oil. A larger study is needed to evaluate the efficacy of emu oil in reducing radiation dermatitis in patients receiving breast radiation.

Influence of patient's physiologic factors and immobilization choice with stereotactic body radiotherapy for upper lung tumors.

The purpose of the present study was to compare the impact of pulmonary function, body habitus, and stereotactic body radiation therapy (SBRT) immobilization on setup and reproducibility for upper lung tumor. From 2008 through 2011, our institution's prospective SBRT database was searched for patients with upper lung tumors. Two SBRT immobilization strategies were used: full-length BodyFIX and thermoplastic S-frame. At simulation, free-breathing, four-dimensional computed tomography was performed. For each treatment, patients were set up to isocenter with in-room lasers and skin tattoos. Shifts from initial and subsequent couch positions with cone-beam computed tomography (CBCT) were analyzed. Accounting for setup uncertainties, institutional tolerance of CBCT-based shifts for treatment was 2, 2, and 4 mm in left-right, anterior-posterior, and cranial-caudal directions, respectively; shifts exceeding these limits required reimaging. Each patient's pretreatment pulmonary function test was recorded. A multistep, multivariate linear regression model was performed to elucidate intervariable dependency for three-dimensional calculated couch shift parameters. BodyFIX was applied to 76 tumors and S-frame to 17 tumors. Of these tumors, 41 were non-small cell lung cancer and 15 were metastatic from other sites. Lesions measured < 1 (15%), 1.1 to 2 (50%), 2.1 to 3 (25%), and > 3 (11%) cm. Errors from first shifts of first fractions were significantly less with S-frame than BodyFIX (p < 0.001). No difference in local control (LC) was found between S-frame and BodyFIX (p = 0.35); two-year LC rate was 94%. Multivariate modeling confirmed that the ratio of forced expiratory volume in the first second of expiration to forced vital capacity, body habitus, and the immobilization device significantly impacted couch shift errors. For upper lung tumors, initial setup was more consistent with S-frame than BodyFIX, resulting in fewer CBCT scans. Patients with obese habitus and poor lung function had more SBRT setup uncertainty; however, outcome and probability for LC remained excellent.

Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone oligometastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) is being applied more widely for oligometastatic disease. This technique is now being used for non-spine bony metastases in addition to liver, spine, and lung. However, there are few studies examining the toxicity and outcomes of SBRT for non-spine bone metastases. METHODS AND MATERIALS: Between 2008 and 2012, 74 subjects with oligometastatic non-spine bony metastases of varying histologies were treated at the Mayo Clinic with SBRT. A total of 85 non-spine bony sites were treated. Median local control, overall survival, and progression-free survival were described. Acute toxicity (defined as toxicity <90 days) and late toxicity (defined as toxicity ≥90 days) were reported and graded as per standardized Common Toxicity Criteria for Adverse Events 4.0 criteria. RESULTS: The median age of patients treated was 60 years. The most common histology was prostate cancer (31%) and most patients had fewer than 3 sites of disease at the time of simulation (64%). Most of the non-spine bony sites lay within the pelvis (65%). Dose and fractionation varied but the most common prescription was 24 Gy/1 fraction. Local recurrence occurred in 7 patients with a median time to failure of 2.8 months. Local control was 91.8% at 1 year. With a median follow-up of 7.6 months, median SBRT specific overall survival and progression-free survival were 9.3 months and 9.7 months, respectively. Eighteen patients developed acute toxicity (mostly grade 1 and 2 fatigue and acute pain flare); 9 patients developed grade 1-2 late toxicities. Two patients developed pathologic fractures but both were asymptomatic. There were no late grade 3 or 4 toxicities. CONCLUSIONS: Stereotactic body radiation therapy is a feasible and tolerable treatment for non-spine bony metastases. Longer follow-up will be needed to accurately determine late effects.

Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGFI) after stereotactic body radiation therapy (SBRT).

PURPOSE: Gastrointestinal injury occurs rarely with agents that affect the vascular endothelial growth factor receptor and with abdominal stereotactic body radiation therapy (SBRT). We explored the incidence of serious bowel injury (SBI) in patients treated with SBRT with or without vascular endothelial growth factor inhibitor (VEGFI) therapy. METHODS AND MATERIALS: Seventy-six patients with 84 primary or metastatic intra-abdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Of the patients, 20 (26%) received VEGFI within 2 years after SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The incidence of SBI (Common Terminology Criteria for Adverse Events, version 4.0, grade 3-5 ulceration or perforation) after SBRT was obtained, and the relationship between SBI and VEGFI was examined. RESULTS: In the combined population, 7 patients (9%) had SBI at a median of 4.6 months (range, 3-17 months) from SBRT. All 7 had received VEGFI before SBI and within 13 months of completing SBRT, and 5 received VEGFI within 3 months of SBRT. The 6-month estimate of SBI in the 26 patients receiving VEGFI within 3 months of SBRT was 38%. No SBIs were noted in the 63 patients not receiving VEGFI. The log-rank test showed a significant correlation between SBI and VEGFI within 3 months of SBRT (P=.0006) but not between SBI and radiation therapy bowel dose (P=.20). CONCLUSIONS: The combination of SBRT and VEGFI results in a higher risk of SBI than would be expected with either treatment independently. Local therapies other than SBRT may be considered if a patient is likely to receive a VEGFI in the near future.

Lung stereotactic body radiotherapy using a coplanar versus a non-coplanar beam technique: a comparison of clinical outcomes.

OBJECTIVES: To determine if lung stereotactic body radiotherapy (SBRT) using a coplanar beam technique was associated with similar outcomes as lung SBRT using a non-coplanar beam technique. METHODS: A retrospective review was performed of patients undergoing lung SBRT between January 2008 and April 2011. SBRT was initially delivered with multiple non-coplanar, non-overlapping beams; however, starting in December 2009, SBRT was delivered predominantly with all coplanar beams in order to reduce treatment time and complexity. RESULTS: This analysis included 149 patients; the median follow-up was 21 months. SBRT was delivered for primary (n = 90) or recurrent (n = 17) non-small cell lung cancer, or lung oligometastasis (n = 42). The most common dose (Gy)/fraction (fx) regimens were 48 Gy/4 fx (39%), 54 Gy/3 fx (37%), and 50 Gy/5 fx (17%). The beam arrangement was coplanar in 61 patients (41%) and non-coplanar in 88 patients (59%). In patients treated with 54 Gy/3 fx, the mean treatment times per fraction for the coplanar and non-coplanar cohorts were 10 and 14 minutes (p < 0.0001). Kaplan-Meier 2-year estimates of overall survival (OS), progression-free survival, and local control (LC) for the coplanar and non-coplanar cohorts were 65% vs. 56% (p = 0.30), 47% vs. 39% (p = 0.71), and 92% and 92% (p = 0.94), respectively. The 1-year estimates of grade 2-5 pulmonary toxicity for the coplanar and non-coplanar cohorts were 11% and 17%, respectively (p = 0.30). On multivariate analysis, beam arrangement was not significantly associated with OS, LC or pulmonary toxicity. CONCLUSIONS: Patients treated with lung SBRT using a coplanar technique had similar outcomes as those treated with a non-coplanar technique.

Stereotactic body radiation therapy in spinal metastases.

PURPOSE: Based on reports of safety and efficacy, stereotactic body radiotherapy (SBRT) for treatment of malignant spinal tumors was initiated at our institution. We report prospective results of this population at Mayo Clinic. MATERIALS AND METHODS: Between April 2008 and December 2010, 85 lesions in 66 patients were treated with SBRT for spinal metastases. Twenty-two lesions (25.8%) were treated for recurrence after prior radiotherapy (RT). The mean age of patients was 56.8 ± 13.4 years. Patients were treated to a median dose of 24 Gy (range, 10-40 Gy) in a median of three fractions (range, 1-5). Radiation was delivered with intensity-modulated radiotherapy (IMRT) and prescribed to cover 80% of the planning target volume (PTV) with organs at risk such as the spinal cord taking priority over PTV coverage. RESULTS: Tumor sites included 48, 22, 12, and 3 in the thoracic, lumbar, cervical, and sacral spine, respectively. The mean actuarial survival at 12 months was 52.2%. A total of 7 patients had both local and marginal failure, 1 patient experienced marginal but not local failure, and 1 patient had local failure only. Actuarial local control at 1 year was 83.3% and 91.2% in patients with and without prior RT. The median dose delivered to patients who experienced local/marginal failure was 24 Gy (range, 18-30 Gy) in a median of three fractions (range, 1-5). No cases of Grade 4 toxicity were reported. In 1 of 2 patients experiencing Grade 3 toxicity, SBRT was given after previous radiation. CONCLUSION: The results indicate SBRT to be an effective measure to achieve local control in spinal metastases. Toxicity of treatment was rare, including those previously irradiated. Our results appear comparable to previous reports analyzing spine SBRT. Further research is needed to determine optimum dose and fractionation to further improve local control and prevent toxicity.

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions.

BACKGROUND AND PURPOSE: Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. MATERIAL AND METHODS: A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. RESULTS: With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. CONCLUSIONS: Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.