Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. MATERIALS AND METHODS: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. RESULTS: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. CONCLUSIONS: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

Long-term outcomes and patterns of tumor progression after gamma knife radiosurgery for benign meningiomas.

OBJECT: To characterize the timing and patterns of long-term treatment failure after Gamma Knife radiosurgery (GKRS) for benign meningiomas. METHODS: Data were retrospectively reviewed in 116 patients who underwent 136 GKRS treatments for benign intracranial meningiomas from 1996 to 2004. Patients with atypical or malignant meningiomas were excluded. Surgical resection preceded GKRS in 72 patients (62%). The median tumor volume was 3.4 cm, and the median prescription dose to the 50% isodose line was 16 Gy. RESULTS: The median follow-up time was 75 months (range, 4-146 months). Overall tumor control was achieved in 128 of 136 lesions (94%), of which tumor size was stable in 68% and decreased in 26%. Seven patients experienced disease progression in 8 tumors, occurring at a mean time of 90 months. The overall 5-year and 10-year actuarial tumor control rate was 98.9% and 84%, respectively. Characteristics corresponding to tumor progression included insufficient tumor coverage (98% vs 93%, P = .007), cavernous sinus lesions, and meningiomatosis. Complications after GKRS developed in 8% of patients, in whom the mean tumor volume was nearly double that in patients with no adverse effects (11 vs 5.7 cm3, P = .003). CONCLUSIONS: GKRS demonstrates excellent long-term tumor control in the management of benign meningiomas. Tumor progression occurred at a mean time of 7.5 years after GKRS, reinforcing the need for long-term surveillance despite initial tumor control. Treatment failure was related to undercoverage of lesions in the majority of cases, with the remainder demonstrating evidence of abnormal tumor biology.

CyberKnife enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures.

INTRODUCTION: With conventional radiation technique alone, it is difficult to deliver radical treatment (>or= 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma. METHODS: Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide. RESULTS: During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients. CONCLUSION: We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.