Search

Background: The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown., Objective: To examine these uncertainties., Methods: NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan-Meier method., Results: A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings (P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test-Revised Delayed Recognition [P = .048], Trail Making Test Part A [P = .035], and Controlled Oral Word Association [P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures., Conclusion: STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.

Background: Fractionated stereotactic radiotherapy (FSRT) is a noninvasive treatment for acoustic neuromas (ANs). Initial reports from our institution demonstrated that the reduction of treatment dose to 46.8 Gy resulted in improved preservation of functional hearing status., Objective: We now report the tumor control (TC), symptomatic outcome, and hearing preservation (HP) rate in patients treated with reduced-dose FSRT., Methods: We analyzed all patients with AN treated from 2002 to 2011. All patients received 46.8 Gy in 1.8-Gy fractions. Follow-up audiogram and magnetic resonance imaging were performed in ≤ 1-year intervals. TC and HP were calculated by the Kaplan-Meier method. Analysis of HP, defined as Gardner-Robertson value ≤ 2, was determined by audiometric data. Non-hearing-related symptoms were defined by Common Terminology Criteria for Adverse Events version 4., Results: In total, 154 patients were analyzed. At a median follow-up of 35 months (range, 4-108), TC was achieved in 96% of patients (n = 148/154) and at 3 and 5 years was 99% and 93%. Eighty-seven patients had serviceable hearing at the time of FSRT and evaluable audiometric follow-up. Overall HP was 67% and at 3 and 5 years was 66% and 54%. Pure tone average decreased by a median of 13 dB in all patients. Nineteen percent (n = 31) of patients experienced symptom improvement, and 8% (n = 13) had worsening of symptoms. Cranial nerve dysfunction occurred in 3.8% of patients (n = 6)., Conclusion: Reduced-dose FSRT to 46.8 Gy for AN achieves excellent functional HP rates and limited toxicity without compromising long-term TC. Based on these promising outcomes, further attempts at dose deescalation may be warranted.

Background: Data on radiotherapy for trigeminal schwannomas (TSs) and comparison of stereotactic radiosurgery (SRS) with fractionated stereotactic radiotherapy (FSRT) are limited., Objective: We present a large retrospective review of our institutional experience treating TSs with SRS and FSRT. We also describe a flare phenomenon experienced by some patients., Methods: The records of 23 consecutive TSs patients treated with radiotherapy between 1996 and 2011 were reviewed. We investigated radiographic response, tumor control, and toxicity., Results: Ten patients underwent SRS and 13 underwent FSRT, with median clinical follow-up of 32 months (range, 3-120 months). Tumor control at 5 and 10 years was 94% overall. Symptom control at 5 years was achieved in 48% of all patients, with nonsignificant improvement in more patients in the FSRT group than those in the SRS group (56% vs 40%, P = .37). Acute toxicity was higher in the FSRT group (38.5 vs 0%, P < .01), although lesions treated with FSRT were larger (mean, 9.5 mL vs 4.8 mL, P < .01). A symptomatic flare phenomenon occurred in 2 patients (8.7% overall) during FSRT, involving transient cystic formation and dramatic size increase. One lesion regressed in size and 1 remained stable on follow-up., Conclusion: Tumor control rates for TSs are excellent with SRS and FSRT with minimal toxicity. This represents the first documented report of a flare phenomenon after FSRT for TS treatment. Flare risk after FSRT in previously resected large lesions should be discussed with patients before treatment, and prophylactic oral steroids may be considered.

Objective: To review outcomes after fractionated stereotactic radiotherapy (FSR) and stereotactic radiosurgery (SRS) for nonacoustic cranial nerve schwannomas., Methods: We reviewed medical records of 39 patients who received FSR or SRS for nonacoustic cranial nerve schwannomas at our institution during the period from 1996 to 2007., Results: Tumors involved Cranial Nerves V (n = 19), III (n = 2), VI (n = 3), VII (n = 5), IX (n = 2), X (n = 5), and XII (n = 2) and the cavernous sinus (n = 1). Irradiation was performed after partial resection, biopsy, or no previous surgery in 16, 2, and 21 patients, respectively. Twenty-four patients received FSR, delivered in 1.8- to 2.0-Gy fractions to a median dose of 50.4 Gy (range, 45.0-54.0 Gy). Fifteen patients received SRS to a median dose of 12.0 Gy (range, 12-15 Gy). Mild acute toxicity occurred in 23% of the patients. The 2-year actuarial tumor control rate after FSR and SRS was 95%. The median follow-up period was 24 months. Changes in cranial nerve deficits after stereotactic irradiation were analyzed for patients with follow-up periods greater than 12 months (n = 26); cranial nerve deficits improved in 50%, were stable in 46%, and worsened in 4% of the patients. No significant difference was observed for FSR compared with SRS with regard to local control or to improvement of cranial nerve-related symptoms (P = 0.17)., Conclusion: SRS and FSR are both well-tolerated treatments for nonacoustic cranial nerve schwannomas, providing excellent tumor control and a high likelihood of symptomatic improvement.

Objective: Despite the success of stereotactic radiosurgery, large inoperable arteriovenous malformations (AVMs) of 14 cm3 or more have remained largely refractory to stereotactic radiosurgery, with much lower obliteration rates. We review treatment of large AVMs either previously untreated or partially obliterated by embolization with fractionated stereotactic radiotherapy (FSR) regimens using a dedicated linear accelerator (LINAC)., Methods: Before treatment, all patients were discussed at a multidisciplinary radiosurgery board and found to be suitable for FSR. All patients were evaluated for pre-embolization. Those who had feeding pedicles amenable to glue embolization were treated. LINAC technique involved acquisition of a stereotactic angiogram in a relocatable frame that was also used for head localization during treatment. The FSR technique involved the use of six 7-Gy fractions delivered on alternate days over a 2-week period, and this was subsequently dropped to 5-Gy fractions after late complications in one of seven patients treated with 7-Gy fractions. Treatments were based exclusively on digitized biplanar stereotactic angiographic data. We used a Varian 600SR LINAC (Varian Medical Systems, Inc., Palo Alto, CA) and XKnife treatment planning software (Radionics, Inc., Burlington, MA). In most cases, one isocenter was used, and conformality was established by non-coplanar arc beam shaping and differential beam weighting., Results: Thirty patients with large AVMs were treated between January 1995 and August 1998. Seven patients were treated with 42-Gy/7-Gy fractions, with one patient lost to follow-up and the remaining six with previous partial embolization. Twenty-three patients were treated with 30-Gy/5-Gy fractions, with two patients lost to follow-up and three who died as a result of unrelated causes. Of 18 evaluable patients, 8 had previous partial embolization. MeanAVM volumes at FSR treatment were 23.8 and 14.5 cm3, respectively, for the 42-Gy/7-Gy fraction and 30-Gy/5-Gy fraction groups. After embolization, 18 patients still had AVM niduses of 14 cm3 or more: 6 in the 7-Gy cohort and 12 in the 5-Gy cohort. For patients with at least 5-year follow-up, angiographically documented AVM obliteration rates were 83%for the 42-Gy/7-Gy fraction group, with a mean latency of 108 weeks (5 of 6 evaluable patients), and 22% for the 30-Gy/5-Gy fraction group, with an average latency of 191 weeks (4 of 18 evaluable patients) (P = 0.018). For AVMs that remained at 14 cm3 or more after embolization (5 of 6 patients), the obliteration rate remained 80% (4 of 5 patients) for the 7-Gy cohort and dropped to 9% for the 5-Gy cohort. A cumulative hazard plot revealed a 7.2-fold greater likelihood of obliteration with the 42-Gy/7-Gy fraction protocol (P = 0.0001), which increased to a 17-fold greater likelihood for postembolization AVMs of 14 cm3 or more (P = 0.003)., Conclusion: FSR achieves obliteration for AVMs at a threshold dose, including large residual niduses after embolization. With significant treatment-related morbidities, further investigation warrants a need for better three-dimensional target definition with higher dose conformality.

Objective: Despite the success of stereotactic radiosurgery, large inoperable arteriovenous malformations (AVMs) of 14 cm(3) or more have remained largely refractory to stereotactic radiosurgery, with much lower obliteration rates. We review treatment of large AVMs either previously untreated or partially obliterated by embolization with fractionated stereotactic radiotherapy (FSR) regimens using a dedicated linear accelerator (LINAC)., Methods: Before treatment, all patients were discussed at a multidisciplinary radiosurgery board and found to be suitable for FSR. All patients were evaluated for pre-embolization. Those who had feeding pedicles amenable to glue embolization were treated. LINAC technique involved acquisition of a stereotactic angiogram in a relocatable frame that was also used for head localization during treatment. The FSR technique involved the use of six 7-Gy fractions delivered on alternate days over a 2-week period, and this was subsequently dropped to 5-Gy fractions after late complications in one of seven patients treated with 7-Gy fractions. Treatments were based exclusively on digitized biplanar stereotactic angiographic data. We used a Varian 600SR LINAC (Varian Medical Systems, Inc., Palo Alto, CA) and XKnife treatment planning software (Radionics, Inc., Burlington, MA). In most cases, one isocenter was used, and conformality was established by non-coplanar arc beam shaping and differential beam weighting., Results: Thirty patients with large AVMs were treated between January 1995 and August 1998. Seven patients were treated with 42-Gy/7-Gy fractions, with one patient lost to follow-up and the remaining six with previous partial embolization. Twenty-three patients were treated with 30-Gy/5-Gy fractions, with two patients lost to follow-up and three who died as a result of unrelated causes. Of 18 evaluable patients, 8 had previous partial embolization. Mean AVM volumes at FSR treatment were 23.8 and 14.5 cm(3), respectively, for the 42-Gy/7-Gy fraction and 30-Gy/5-Gy fraction groups. After embolization, 18 patients still had AVM niduses of 14 cm(3) or more: 6 in the 7-Gy cohort and 12 in the 5-Gy cohort. For patients with at least 5-year follow-up, angiographically documented AVM obliteration rates were 83% for the 42-Gy/7-Gy fraction group, with a mean latency of 108 weeks (5 of 6 evaluable patients), and 22% for the 30-Gy/5-Gy fraction group, with an average latency of 191 weeks (4 of 18 evaluable patients) (P = 0.018). For AVMs that remained at 14 cm(3) or more after embolization (5 of 6 patients), the obliteration rate remained 80% (4 of 5 patients) for the 7-Gy cohort and dropped to 9% for the 5-Gy cohort. A cumulative hazard plot revealed a 7.2-fold greater likelihood of obliteration with the 42-Gy/7-Gy fraction protocol (P = 0.0001), which increased to a 17-fold greater likelihood for postembolization AVMs of 14 cm(3) or more (P = 0.003)., Conclusion: FSR achieves obliteration for AVMs at a threshold dose, including large residual niduses after embolization. With significant treatment-related morbidities, further investigation warrants a need for better three-dimensional target definition with higher dose conformality.

Objective: We investigated the safety and efficacy of stereotactic radiotherapy as an alternative therapy to surgical resection for optic nerve sheath meningiomas (ONSMs)., Methods: Thirty patients and 33 optic nerves with ONSMs were treated with conventional fractionated stereotactic radiotherapy treatment (CF-SRT) between July 1996 and May 2001 with the use of a 6-MeV LINAC designed for and dedicated to radiosurgery. The LINAC technique involved daily CF-SRT involving a relocatable frame, an average of three isocenters, and high-radiation dose conformality established by noncoplanar arc beam shaping and differential beam weighting. The patients who were treated with CF-SRT were followed clinically with serial visual fields and radiographically with both magnetic resonance imaging and functional (111)In-octreotide single-photon emission computed tomography. The results of treatment were compared with a historical control group of ONSM patients who were either observed or treated surgically and then observed., Results: Our study population comprised 18 women and 12 men with a median age of 44 years (age range, 20-76 yr). The median isosurface radiation dose was 51 Gy (dose range, 50-54.0 Gy), and the median clinical follow-up time was 89 weeks (range, 9-284 wk). Of 22 optic nerves with vision before CF-SRT, 20 nerves (92%) demonstrated preserved vision, and 42% manifested improvement in visual acuity and/or visual field at follow-up. Comparison of our patients with a historical control group revealed preserved vision in only 16% of patients in a comparable period of observation, along with a 150% greater probability of visual improvement. Four patients (13%) had posttreatment morbidities, including visual loss (two patients), optic neuritis (one patient), and transient orbital pain (one patient). On magnetic resonance imaging studies, there was no evidence of tumor progression or recurrence in all patients, including tumor volume reductions noted in four patients. All six patients monitored with (111)In-octreotide scintigraphy demonstrated significant decreases in tumor activity after CF-SRT., Conclusion: To date, this article describes the largest reported series of ONSMs. Although longer follow-up is necessary, we think that CF-SRT represents a safe alternative to surgery and offers a higher likelihood of preserved or improved vision in patients with ONSM. Our analysis suggests that CF-SRT is also preferable to observation. Functional (111)In-octreotide single-photon emission computed tomographic scintigraphy provides a useful technique for the assessment of tumor control that complements serial posttreatment magnetic resonance imaging in patients with ONSMs.