Garces, Yolanda I.

Objectives: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. Materials and Methods: Eligible patients included stage II-IIIB non–small cell lung cancer, stage I central non–small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. Results: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients’ refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. Conclusions: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.

OBJECTIVE Successful stereotactic radiosurgery (SRS) for the treatment of arteriovenous malformations (AVMs) results in nidus obliteration without new neurological deficits related to either intracranial hemorrhage (ICH) or radiation-induced complications (RICs). In this study the authors compared 5 AVM grading scales (Spetzler-Martin grading scale, radiosurgery-based AVM score [RBAS], Heidelberg score, Virginia Radiosurgery AVM Scale [VRAS], and proton radiosurgery AVM scale [PRAS]) at predicting outcomes after SRS. METHODS The study group consisted of 381 patients with sporadic AVMs who underwent Gamma Knife SRS between January 1990 and December 2009; none of the patients underwent prior radiation therapy. The primary end point was AVM obliteration without a decline in modified Rankin Scale (mRS) score (excellent outcome). Comparison of the area under the receiver operating characteristic curve (AUC) and accuracy was performed between the AVM grading scales and the best linear regression model (generalized linear model, elastic net [GLMnet]). RESULTS The median radiological follow-up after initial SRS was 77 months; the median clinical follow-up was 93 months. AVM obliteration was documented in 297 patients (78.0%). Obliteration was 59% at 4 years and 85% at 8 years. Fifty-five patients (14.4%) had a decline in mRS score secondary to RICs (n = 29, 7.6%) or ICH (n = 26, 6.8%). The mRS score declined by 10% at 4 years and 15% at 8 years. Overall, 274 patients (71.9%) had excellent outcomes. There was no difference between the AUC for the GLMnet (0.69 [95% CI 0.64–0.75]), RBAS (0.68 [95% CI 0.62–0.74]), or PRAS (0.69 [95% CI 0.62–0.74]). Pairwise comparison for accuracy showed no difference between the GLMnet and the RBAS (p = 0.08) or PRAS (p = 0.16), but it did show a significant difference between the GLMnet and the Spetzler-Martin grading system (p < 0.001), Heidelberg score (p < 0.001), and the VRAS (p < 0.001). The RBAS and the PRAS were more accurate when compared with the Spetzler-Martin grading scale (p = 0.03 and p = 0.01), Heidelberg score (p = 0.02 and p = 0.02), and VRAS (p = 0.03 and p = 0.02). CONCLUSIONS SRS provides AVM obliteration without functional decline in the majority of treated patients. AVM grading scales having continuous scores (RBAS and PRAS) outperformed integer-based grading systems in the prediction of AVM obliteration without mRS score decline after SRS.

AbstractBackgroundTo assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy.MethodsA cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed.ResultsMedian follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26–23.03; P < .001); male sex (HR, 3.67; 95% CI, 2.03–6.84; P < .001), and reirradiation (HR, 3.41; 95% CI, 1.05–9.68; P = .04) were associated with worse CVA-free survival. In multivariate analysis, only age > 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8–6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient).ConclusionCVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality.

Object Stereotactic radiosurgery (SRS) is an important treatment option for patients with cavernous sinus meningiomas (CSM). To analyze factors associated with local tumor control and complications after single-fraction SRS, the authors reviewed cases involving patients treated with Gamma Knife SRS between 1990 and 2008. Methods Excluded were patients with WHO Grade II or III tumors, radiation-induced tumors, multiple meningiomas, neurofibromatosis Type 2, and prior or concurrent radiotherapy. Five patients were lost to follow-up and 3 patients refused research authorization. The remaining 115 patients (29 men, 86 women) had either histologically confirmed WHO Grade I (n = 46, 40%) or presumed (n = 69, 60%) CSM. The median treatment volume was 9.3 cm3 (range 1.3–42.2 cm3). The median margin dose was 16 Gy (range 12–20 Gy). The median follow-up after SRS was 89 months (range 12–251 months). Thirty-nine patients (34%) had 10 or more years of follow-up after SRS. Results Six patients (5%) had tumor progression (in field, n = 3; marginal, n = 3) at a median of 74 months (range 42–145 months) after SRS. The local tumor control rate was 99% at 5 years and 93% at 10 years after SRS. No analyzed factor was associated with local control after SRS. Fourteen patients (12%) had permanent complications at a median onset of 23 months (range 2–146 months) including trigeminal dysfunction (n = 9), diplopia (n = 2), ischemic stroke (n = 2), and hypopituitarism (n = 1). The 2-year, 5-year, and 10-year rates of complications were 7%, 10%, and 15%, respectively. Multivariate analysis found larger treatment volume (HR 1.1, 95% CI 1.02–1.2, p = 0.01) to be associated with complications after SRS. The complication rate for patients with a treatment volume of 9.3 cm3 or less was 3% (2 of 58 cases) compared with 21% (12 of 57 cases) for patients with a treatment volume greater than 9.4 cm3. Conclusions Single-fraction SRS at the radiation doses used in this series provided durable tumor control for patients with benign CSM. Larger tumor volume remains the primary factor associated with complications after single-fraction SRS of benign CSM despite advancements in SRS technique.

Fatigue is the problematic symptom identified by patients with cancer. However, fatigue has not been widely examined in caregivers of patients with cancer. In this study, 131 caregivers of patients diagnosed with advanced stage cancer and actively receiving radiotherapy reported experiencing the most difficulties with fatigue (mean 46.9; on a 0-100 scale, with a 10-point difference having clinical meaning) at baseline and at a 6-month follow-up (mean 48.3). This is in sharp contrast to other domains of quality of life and functioning being rated in the 60s, 70s and 80s by the caregivers of patients with cancer. Given the level of fatigue reported by the caregivers of patients with cancer, if confirmed by other investigators in larger and more diverse samples, interventions targeting caregiver fatigue should be explored.

The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.