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Purpose Stereotactic body radiation therapy (SBRT) is an emerging option for localized prostate cancer. However, there are no standard dosimetric guidelines, and normal tissue tolerances for extreme hypofractionation are not well defined. We analyzed dosimetric correlations with patient-reported urinary and bowel quality of life (QOL) on a prospective trial. Methods and Materials Patients with low- or intermediate-risk prostate cancer from 18 institutions were enrolled on a phase 2 trial from 2007 to 2012 and treated using robotic SBRT to 38 Gy in 4 fractions on consecutive days. No androgen deprivation was used. Patients received simulation with Foley catheter for urethral delineation. The clinical target volume was prostate (low-risk patients) or prostate plus 1 cm of proximal seminal vesicles (intermediate-risk patients). Multiple dosimetric measures for urethra, bladder, and rectum were prospectively recorded. QOL using the Expanded Prostate Cancer Index Composite was assessed before and after treatment at protocol-specific time points. Linear regression was used to assess factors associated with QOL at 1 month and 2 years. Results A total of 259 patients were enrolled. QOL data were available for 98%, 96%, and 84% at baseline, 1 month, and 2 years, respectively. Median age was 69 years. Prior transurethral resection of the prostate and clinical target volume size were associated with 2-year urinary incontinence. There was a trend toward worse 2-year obstruction/irritation in older patients on multivariable analysis. Bladder and urethral doses were not associated with either 1-month or 2-year urinary QOL. In contrast, rectum maximum dose was associated with both 1-month and 2-year bowel QOL. At 2 years, the proportion with moderate or big overall bowel problems (as defined by Expanded Prostate Cancer Index Composite-26) was significantly higher in patients with rectum maximum dose greater than versus less than the median 37.4 Gy (11% vs 2%, Fisher's exact test P = .008). Conclusions These results provide novel data that contribute to a better understanding of patient and dosimetric factors associated with adverse QOL effects from prostate SBRT.

Background Stereotactic body radiation therapy is an emerging treatment for prostate cancer (PC), with potential biological and oncologic advantages. A well-established radiation dosing schedule (38Gy in 4 fractions) has shown excellent long-term efficacy in high-dose-rate (HDR) brachytherapy. Objective To report 5-yr efficacy, toxicity, and quality-of-life (QOL) outcomes of a novel 4-d SBRT regimen. Design, setting, and participants This was a single-arm prospective phase 2 trial involving 259 patients with low- or intermediate-risk PC treated at 18 US centers from December 2007 to February 2012. The median follow-up was 5yr (interquartile range 37–85mo). Intervention SBRT with 38Gy in four fractions; radiation plans mimicked HDR brachytherapy dosimetry. Outcome measurements and statistical analysis We measured freedom from biochemical recurrence (BCR) and assessed toxicities using the Common Terminology Criteria for Adverse Events v3.0 and QOL using the Expanded Prostate Cancer Index Composite. Results and limitations The 5-yr BCR-free rates were 100% and 88.5% for patients with low- and intermediate-risk PC, respectively. The cumulative 5-yr grade 2, 3, and 4 toxicity rates were 12.4%, 1.9%, and 0.4% for urinary, and 3.4%, 0%, and 0% for gastrointestinal toxicities, respectively. The median baseline prostate-specific antigen (PSA) level of 5.12ng/ml decreased to 0.1ng/ml by ≥42mo. QOL scores decreased at 1mo but returned to baseline by 6mo, with a later decline (≥24mo) in the urinary continence domain (pad use was 2% at baseline and 10% at 5yr), and lower sexual potency over time. Comparative outcomes versus other types of radiotherapy are difficult because the trial was not randomized. Conclusions This regimen yields a high rate of BCR-free survival, with a very low median PSA nadir suggesting prostate ablation. For properly selected patients with low- or intermediate-risk PC who choose SBRT, this treatment regimen is effective. Patient summary This potent four-treatment stereotactic body radiotherapy regimen appears to be effective for patients with early prostate cancer.

35 Background: SBRT is an emerging treatment for prostate cancer, but long-term reporting remains sparse. We present a prospective Phase II trial with 90% treated in community facilities. Methods: 14 institutions enrolled 259 patients - 112 low-risk; 147 intermediate-risk. The regimen emulated a high-dose rate brachytherapy (HDR) regimen - 38 Gy/4 fractions delivered by robotic SBRT. Androgen deprivation therapy was not allowed. HDR-like heterogeneous prostate dosing was used (Dmax >57 Gy). Toxicities were assessed by CTCAE v3.0 and quality of life assessed by Expanded Prostate Cancer Index Composite (EPIC). Biochemical recurrence was defined by Phoenix criteria. Results: Median follow-up is 5 years. 5-yr Grade 2 GU toxicity was 13.7% and GI toxicity 4.5%, with Grade 3 rates of 3% (GU) and 0% (GI) (one Gd 4 GU event). 5-yr median PSA was 0.1 ng/mL with further subsequent decrease (7 y = 0.035 ng/mL). 5-yr biochemical disease-free survival (bDFS) = 100% for low-risk and 88.5% for int-risk. 6 patients developed distant metastasis and one died of disease. Median EPIC GU obstruction and GI scores were similar at baseline vs. 5 years. 2% of patients had baseline GU incontinence requiring pad use vs 10% at 5 yrs. Of baseline potent men, 46% remained so at 5 yrs (66.7% for those age ≤65 vs. 37.1% age >65 at treatment). Conclusions: This is the first report of 5-year median follow-up outcomes post heterogeneous dosing SBRT for early prostate cancer. This treatment produces a low PSA nadir vs other forms of radiotherapy, with a favorable long-term result that appears reproducible in the community. Clinical trial information: 00643617. [Table: see text]

The use of the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) for radiosurgical treatment of lung tumors [1] typically requires placement of one or more gold fiducials for tracking during treatment. Possible exceptions to this requirement are tumors involving the posterior chest wall, which may be localized with Xsightℳ (Accuray Incorporated, Sunnyvale, CA) based on spinal anatomy. Placement of gold fiducial seeds has been associated with post-placement pneumothorax at rates of 25–40% [1]. Some of these patients will require treatment by chest tube placement, and all of them will require repeated physician exams and radiological follow-up. In addition, some patients are refused consideration for radiosurgery for fear they will be unable to tolerate a potential pneumothorax. Pneumothorax prevention, therefore, has become a major priority in CyberKnife radiosurgery for lung cancer.

Low-grade astrocytomas in adults are uncommon malignant neoplasms of the central nervous system which are fatal in the great majority of patients despite a lack of aggressive histologic features. Several series of such patients have been previously reported, but prognostic factors have not been fully identified. Between 1960 and 1986, 50 patients with low-grade astrocytomas have been treated with megavoltage radiation at the Naval Hospital, Bethesda, MD, following surgical biopsy or excision. Overall actuarial survival at 10 years for the entire treated group was 32%, similar to other series. The most significant prognostic factor was patient age, with decreasing survival for each age decade and a highly significant difference in survival between patients less than age 40 compared to older patients (p = .0017). The era of treatment (before or after 1978) was also an important prognostic indicator (p = .057), largely due to an effect of dose, although better tumor localization in the CT era may also have played a role. There was a trend toward increasing survival with increasing dose of radiation, although not reaching statistical significance at the p = .05 level on multivariate analysis. Patient sex, extent of surgical resection, use of whole brain irradiation, and tumor grade did not significantly affect survival. In comparison, in a separate group of 10 patients who received surgery without radiation during the same period, all patients who were completely resected were long-term survivors, whereas none of those with incomplete resections survived longer than 6 years.

• A 58-year-old man was initially seen with fatigue and weight loss. Laboratory examination detected hypercalcemia, elevated 1,25-dihydroxycholecalciferol levels, low parathyroid hormone (PTH) concentrations, and subperiosteal bone resorption. The patient underwent subtotal parathyroidectomy for presumed hyperparathyroidism, but serum calcium and 1,25-dihydroxycholecalciferol levels remained elevated following surgery. Search for another cause of the hypercalcemia disclosed enlarged para-aortic lymph nodes, biopsy specimens of which demonstrated Hodgkin's disease. After treatment of the patient with two cycles of chemotherapy with mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone, serum calcium, 1,25-dihydroxycholecalciferol, and PTH levels normalized. We speculate that the humoral hypercalcemia in this patient resulted from tumor production of 1,25-dihydroxycholecalciferol. (Arch Intern Med1985;145:155-157)