Fractionated stereotactic radiotherapy in residual or recurrent nasopharyngeal carcinoma

The aim of this study was to evaluate results of fractionated stereotactic radiotherapy (FSRT) in patients with residual or recurrent nasopharyngeal carcinoma (NPC) in terms of local progression-free (LPFS) and overall survival (OS) rate and complications after treatment. There were 32 residual or recurrent NPC patients treated with FSRT using linac-based radiosurgery system. Time from the previous radiotherapy to FSRT was 1-165 months (median, 15). Two patients were treated for the second and one for the third recurrence. Thirteen patients (40.6%) also received chemotherapy with FSRT. Tumor volume ranged from 6.2-215 cc (median, 44.4). Average FSRT dose was 17-59.4 Gy (median, 34.6) in 4-25 fractions (median,6) in 1-5.5 weeks (median, 3). Median follow-up time was 25.5(3-67) months. LPFS rate at 1 and 3 years after FSRT was 67.8% and 37.9%. OS rate at 1 and 3 years was 89.7% and 71.2%. If all patients who had tumor progression with no further follow-up were assumed dead, the OS rate at 1 and 3 years would be 75.0% and 37.9%. Univariate analysis showed better local tumor control in patients with tumor volume ≤100 cc (p=0.04) or in those without chemotherapy (p=0.0005). Only chemotherapy retained significance in multivariate analysis (hazard ratio 5.47, 95%CI 1.86-16.04). Eight patients (25%) had complications after FSRT, all grade 2-3 except 1 grade 4 with complete recovery.     

Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution.

PURPOSE: To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) performed as reirradiation in 172 patients with recurrent low- and high-grade gliomas. PATIENTS AND METHODS: Between 1990 and 2004, 172 patients with recurrent gliomas were treated with FSRT as reirradiation in a single institution. Seventy-one patients suffered from WHO grade 2 gliomas. WHO grade 3 gliomas were diagnosed in 42 patients, and 59 patients were diagnosed with glioblastoma multiforme (GBM). The median time between primary radiotherapy and reirradiation was 10 months for GBM, 32 months for WHO grade 3 tumors, and 48 months for grade 2 astrocytomas. FSRT was performed with a median dose of 36 Gy in a median fractionation of 5 x 2 Gy/wk. RESULTS: Median overall survival after primary diagnosis was 21 months for patients with GBM, 50 months for patients with WHO grade 3 gliomas, and 111 months for patients with WHO grade 2 gliomas. Histologic grading was the strongest predictor for overall survival, together with the extent of neurosurgical resection and age at primary diagnosis. Median survival after reirradiation was 8 months for patients with GBM, 16 months for patients with grade 3 tumors, and 22 months for patients with low-grade gliomas. Only time to progression and histology were significant in influencing survival after reirradiation. Progression-free survival after FSRT was 5 months for GBM, 8 months for WHO grade 3 tumors, and 12 months for low-grade gliomas. CONCLUSION: FSRT is well tolerated and may be effective in patients with recurrent gliomas. Prospective studies are warranted for further evaluation.     

Fractionated stereotactic radiotherapy for craniopharyngiomas

PURPOSE: To investigate outcome and toxicity after fractionated stereotactic radiation therapy (FSRT) in patients with craniopharyngiomas. METHODS AND MATERIALS: Twenty-six patients with craniopharyngiomas were treated with FSRT between May 1989 and February 2001. Median age was 33.5 years (range: 5-57 years). Nine patients received FSRT after surgery as primary treatment, and 17 patients were irradiated for recurrent tumor or progressive growth after initial surgery. Median target dose was 52.2 Gy (range: 50.0-57.6 Gy) with conventional fractionation. Follow-up included MRI and neurologic, ophthalmologic, and endocrinologic examinations. RESULTS: The median follow-up was 43 months (range: 7-143 months). The actuarial local control rate and actuarial overall survival rates were 100% and 100%, respectively, at 5 years and 100% and 83%, respectively, at 10 years. Four patients showed complete response, 14 patients showed partial response, and 8 patients remained stable. In 5 patients, vision improved after radiation therapy. Acute toxicity was mild. One patient required cyst drainage 3 months after radiotherapy. Late toxicity after radiotherapy included impairment of hormone function in 3 out of 18 patients at risk. We did not observe any vision impairment, radionecrosis, or secondary malignancies. CONCLUSIONS: FSRT is effective and safe in the treatment of cystic craniopharyngiomas. Toxicity is extremely low using this conformal technique.     

Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution

PURPOSE: To assess the long-term outcome and toxicity of fractionated stereotactic radiotherapy for acoustic neuromas in 106 patients treated in a single institution. PATIENTS AND METHODS: Between October 1989 and January 2004, fractionated stereotactic radiotherapy (FSRT) was performed in 106 patients with acoustic neuroma (AN). The median total dose applied was 57.6 Gy in median single fractions of 1.8 Gy in five fractions per week. The median irradiated tumor volume was 3.9 mL (range, 2.7-30.7 mL). The median follow-up time was 48.5 months (range, 3-172 months). RESULTS: Fractionated stereotactic radiotherapy was well tolerated in all patients. Actuarial local tumor control rates at 3- and 5- years after FSRT were 94.3% and 93%, respectively. Actuarial useful hearing preservation was 94% at 5 years. The presence of neurofibromatosis (NF-2) significantly adversely influenced hearing preservation in patients that presented with useful hearing at the initiation of RT (p = 0.00062). Actuarial hearing preservation without the diagnosis of NF-2 was 98%. In cases with NF-2, the hearing preservation rate was 64%. Cranial nerve toxicity other than hearing impairment was rare. The rate of radiation induced toxicity to the trigeminal and facial nerve was 3.4% and 2.3%, respectively. CONCLUSION: Fractionated stereotactic radiotherapy is safe and efficacious for the treatment of AN, with mild toxicity with regard to hearing loss and cranial nerve function. FSRT might be considered as an equieffective treatment modality compared to neurosurgery and therefore represents an interesting alternative therapy for patients with AN.     

Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases

We retrospectively evaluated and compared the efficacy and the toxicity profile of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for the treatment of patients with brain metastases (BM). Between 2000 and 2009, 260 patients with 1-3 BM were treated using either SRS (median dose 20 Gy; n = 138) or two different FSRT dose concepts: 7 × 5 Gy (n = 61) or 10 × 4 Gy (n = 61). The median survival for SRS, 7 × 5 Gy and 10 × 4 Gy was 8, 7 and 10 months (p = 0.575), respectively, and the overall survival (OS) was 9 months. Follow-up imaging data were available in 214 of the 260 patients. The 1-year local progression-free survival (LPFS) was 73, 75 and 71 %, respectively (p = 0.191). After a mean follow-up of 28 months (range: 2.1-77 months), the rate of complete remission, partial remission, stable disease and progressive disease were 29, 40, 21 and 10 %, respectively. On multivariate analysis, RPA class I was associated with better OS and regional progression-free survival (both p < 0.001). SRS was associated with a higher toxicity rate (grade I-III) compared to the 7 × 5 Gy and 10 × 4 Gy groups (14 vs. 6 vs. 2 %, respectively; p = 0.01). Although FSRT was used for large lesions and/or lesions near critical structures, the LPFS was comparable to SRS. Importantly, FSRT presented low toxicity and appears to be an effective and safe treatment for BM not amenable to SRS. The 10 × 4 Gy fractionation scheme warrants further investigation due to its efficacy and safe toxicity profile.     

82例脑胶质瘤立体定向放射治疗的疗效观察

目的探讨立体定向放射治疗（SRT）对于脑胶质瘤患者的治疗效果。方法采用SRT治疗82例脑胶质瘤，其中初治63例，复治19例。所有患者均采用分次立体定向放射治疗（FSRT）。中位照射剂量46Gy，中位随访期为25个月（12-36个月）。结果全组局部病灶控制率为68．3％（56／82），中位生存期（MST）为12．5个月。初治和复治者MST分别为19．5和9．5个月。1年生存率为58．5％（48／82）。结论SRT可有效控制局部病灶，可作为瘤体较小、边界较清楚胶质瘤的一种安全有效治疗手段。     

Low-dose fractionated radiotherapy and concomitant chemotherapy in glioblastoma multiforme with poor prognosis: a feasibility study

We explored the feasibility of concurrent palliative chemotherapy and low-dose fractionated radiotherapy (LD-FRT) in glioblastoma multiforme (GBM). Patients with recurrent/progressive GBM at least 3 months after the end of primary radiotherapy received 0.3 Gy twice daily with cisplatin and fotemustine if progressing on temozolomide, or 0.4 Gy twice daily with temozolomide if recurrent 4-6 months later (retreatment group). Newly diagnosed GBM with gross residual mass received 30 Gy with concomitant and adjuvant temozolomide and 0.4 Gy twice daily from the second adjuvant cycle (naive group) for 2-4 cycles. Twenty-six patients were enrolled. In the retreatment group (n = 17; median LD-FRT total dose 7.2 Gy [range 2.4-11.6]), grade 3 or 4 hematological toxicity was observed in 5.9% of patients. Median follow-up time was 20 months (range 4-35). Median progression-free survival (PFS) and overall survival (OS) from the time of recurrence or progression were 4 and 8 months, respectively (OS at 6 months, 69%; at 12 months, 16.7%). In the naive group (n = 9; median LD-FRT total dose 8 Gy [range 3.2-16]), grade 3 or 4 hematological toxicity was observed in 11.1% of patients. Median follow-up time was 17 months (range 8-20)-median PFS was 9 months, with PFS at 6 months and at 1 year of 66.7% and 26.7%, respectively; and median OS was 12 months, with OS at 6 months and at 1 year of 77.8% and 34.6%, respectively. LD-FRT with concurrent chemotherapy was well tolerated.     

Stereotactic conformal radiotherapy in patients with growth hormone-secreting pituitary adenoma

PURPOSE: To evaluate the reduction of hormonal overproduction and side effects as well as survival rates after fractionated stereotactic conformal radiotherapy (FSRT) and radiosurgery in patients with growth hormone (GH)-secreting pituitary adenoma. METHODS AND MATERIALS: Between January 1989 and May 2001, 25 consecutive patients were treated with FSRT (n = 20) or radiosurgery (n = 5) for GH-secreting pituitary adenoma. Nine patients were treated for recurrent disease after primary surgery. One patient had primary radiotherapy because of inoperability, and 15 patients received radiotherapy after subtotal resection due to increased GH level. Median total dose was 52.2 Gy for FSRT and 15 Gy for radiosurgery. RESULTS: Radiologic local tumor control was 100% after a median follow-up of 59.8 months (range, 20.3-168.2 months). Seventeen patients had stable disease on CT/MRI, and eight showed a reduction of tumor volume on MRI scans. Endocrinologic control was 92% (23 of 25 patients). Two patients had an endocrinologic recurrence 21 and 54 months after FSRT. A normalization of preexisting acromegalic symptoms was seen in 1 patient, 4.5 years after FSRT. GH level normalized in 21 of 25 patients after 26 months median. Five of these patients underwent concurrent Octreotid therapy because of increased insulin-like growth factor I levels. Improvement of visual acuity was seen in 1 patient. New onset of clinically evident hypopituitarism as an adverse reaction of stereotactic radiotherapy was only infrequently observed in this series. CONCLUSION: Stereotactic conformal radiotherapy is effective and safe in the treatment of GH-secreting pituitary adenoma to reduce hormonal overproduction and to improve local control. It is an alternative option to surgery especially for patients at high risk of surgical complications due to comorbidity.     

Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas

Background To reduce this complication and to enhance the radiation effect to hypoxic cells of high-grade gliomas, the authors performed noninvasive fractionated stereotactic radiotherapy (FSRT) using a Gamma unit combined with hyperbaric oxygen (HBO) therapy for the treatment of recurrent disease. Patients and methods Twenty-five consecutive patients who had previously received radiotherapy with chemotherapy for recurrent high-grade gliomas, including 14 patients with anaplastic astrocytoma (AA) and 11 with glioblastoma multiforme (GBM), underwent Gamma FSRT immediately after HBO therapy (2.5 atmospheres absolute for 60 min). The Gamma FSRT was repeatedly performed using a relocatable head cast. Median tumor volume was 8.7 cc (range, 1.7–159.3 cc), and the median total radiation dose was 22 Gy (range, 18–27 Gy) to the tumor margin in 8 fractions. Results Actuarial median survival time after FSRT was 19 months for patients with AA and 11 months for patients with GBM, which was significantly different (P = 0.012, log-rank test). Two patients underwent subsequent second FSRT for regional or remote recurrence. Seven patients (28%) underwent subsequent craniotomies and resections at a mean of 8.4 months after FSRT treatment, and 4 of them had radiation effects without viable cells and remained alive for 50–78 months. Conclusion Gamma FSRT after HBO therapy appears to confer a survival benefit for patients with recurrent high-grade gliomas and warrants further investigation.     

Fractionated stereotactic conformal radiation therapy of brain stem gliomas: outcome and prognostic factors.

BACKGROUND AND PURPOSE: Evaluation of outcome and prognostic factors in patients with brain stem glioma (BSG) following fractionated stereotactic radiotherapy (FSRT). MATERIALS AND METHODS: Between 1990 and 1997, we treated 41 patients with FSRT in a phase I/II trial. Median age was 24 years. Out of 36 patients with histologically proven glioma, ten had a partial tumour resection. Histology revealed low grade gliomas in 30 patients and anaplastic gliomas in six patients. A mean total dose of 54 Gy was given in daily fractions of 1.8 Gy. Median follow-up was 12 months. RESULTS: Three patients died during FSRT. Neurological improvement was achieved in 19/38 patients. Reduction of tumour size was reported in 12/38, in 16 patients the lesion was unchanged, ten showed progression. Median time to progression was 23 months, median overall survival 40 months with an actuarial survival of 83% at 1 year, 55% at 3 years and 33% at 5 years. In 20 of 22 patients with recurrence progression was inside the target volume. Significant prognostic factors for survival were clinical and radiological response 6 weeks after FSRT. Treatment toxicity was mild. Ototoxicity occurred in one patient. CONCLUSIONS: FSRT is a feasible treatment modality for BSG with tolerable toxicity. The risk of marginal failure is low.     

Salvage fractionated stereotactic re-irradiation (FSRT) for patients with recurrent high grade gliomas progressed after bevacizumab treatment

Bevacizumab failure is a major clinical problem in the management of high grade gliomas (HGG), with a median overall survival (OS) of <?4 months. This study evaluated the feasibility and efficacy of fractionated stereotactic re-irradiation (FSRT) for patients progressed after Bevacizumab treatment. Retrospective review was conducted of 36 patients treated with FSRT after progression on bevacizumab. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. The median time from initial bevacizumab treatment to FSRT was 8.5 months. The median plan target volume for FSRT was 27.5 cc. The median OS from FSRT was 4.8 months. FSRT treatment was well tolerated with no grade 3 or higher toxicity. Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment.     

Fractionated stereotactic conformal radiotherapy in the management of large chemodectomas of the skull base

PURPOSE: To evaluate the role of fractionated stereotactic conformal radiotherapy (FSRT) as a noninvasive method in the management of large chemodectomas of the skull base. METHODS AND MATERIALS: Twenty-two patients with chemodectomas of the skull base were treated with FSRT at our institution. Ten patients received primary RT, and 12 patients were treated for recurrent or progressive disease after primary surgery (8 patients) or embolization (4 patients). The median total dose was 57.6 Gy, with a median of 1.8 Gy/fraction. The median target volume was 71.8 cm3 (range, 10.5-212.2 cm3). The most common symptoms at the initial diagnosis were pulsatile tinnitus (16 patients), hearing loss (14 patients), and balance disturbance (14 patients). Twelve patients had additional cranial nerve deficits. RESULTS: The median follow-up was 5.7 years (range, 19-177 months). The actuarial overall survival rate was 89.5% at 5 and 10 years. The actuarial local control rate was 90.4% at 5 and 10 years. Seven patients (32%) had a partial response and 13 (59%) had stable disease of the irradiated chemodectoma. Two symptomatic patients developed recurrence after 19 and 32 months. Neurologic dysfunction improved or completely resolved in 59% and stabilized in 32%; 9% of patients experienced impairment of preexisting neurologic dysfunction. No patient developed new neurologic deficits after FSRT. RT was interrupted in 1 patient because of a maxillary bone abscess. In all other patients, no acute or late adverse reactions greater than Common Toxicity Criteria Grade 2 were seen. CONCLUSION: Fractionated stereotactic conformal radiotherapy is an effective and well-tolerated noninvasive treatment for chemodectomas, with excellent tumor control rates and a low risk of morbidity. It is an option for patients at greater risk of microsurgical resection or with residual and recurrent tumors.     

FSRT联合替莫唑胺治疗大体积脑转移瘤的对照研究

目的 回顾比较应用分次立体定向放疗(FSRT)±替莫唑胺治疗大体积脑转移瘤患者疗效及安全性。方法 2009—2017年间共84例脑转移瘤患者(体积≥ 6 cm³)纳入分析,其中同步放化疗组(CRT组) 与单纯放疗组(RT组)各42例。放疗方案为52.0~52.5 Gy分13~15次,3.5~4.0 Gy/次。疗中复查脑MRI,如病灶体积明显缩小则行疗中缩野。疗后2~3个月评估疗效。主要研究终点为LRFS,次要研究终点为IPFS、PFS、OS、BMSS及不良反应。采用Kaplan-Meier法计算生存率并Logrank法检验和单因素预后分析。结果 CRT、RT组的中位GTV体积分别为16.9、15.7 cm³,疗中缩野率分别为75%、34%(P=0.000)。CRT、RT组LC率分别为100%、98%。中位随访时间为16.1个月(2.1~105.7个月),CRT组LRFS、IPFS、PFS、OS、BMSS均显著优于RT组(P=0.040、0.022、0.045、0.013、0.006)。1—2级消化道不良反应CRT组高于RT组(33%∶26%,P=0.006),两组均无4— 5级不良反应发生。结论 FSRT联合替莫唑胺进一步提高了大体积脑转移瘤患者的LC率及生存率且未增加严重不良反应。     

Fractionated stereotactic radiotherapy of optic pathway gliomas: tolerance and long-term outcome

PURPOSE: To evaluate the effectiveness and toxicity of fractionated stereotactically guided radiotherapy (FSRT) in the management of optic glioma. METHODS AND MATERIALS: Fifteen patients with optic pathway gliomas were treated with FSRT at our institution between 1990 and 2003. A median target dose of 52.2 Gy (range, 45.2-57.6 Gy) was applied using a median fractionation of 5 fractions of 1.8 Gy weekly using a linear accelerator. RESULTS: The median follow-up time was 97 months (range, 8-151 months). Of the 15 patients, 1 died of tumor progression during the follow-up period. The progression-free survival rate at 3 and 5 years was 92% and 72%, respectively. The median overall survival after FSRT was 90 months (range, 8-151 months). The 5-year survival rate after FSRT was 90%. We did not observe secondary malignancies. CONCLUSION: Fractionated stereotactic radiotherapy was safe and well tolerated in all patients. The good tumor control and the potential of sparing normal brain tissue, especially the pituitary gland in lesions involving the optic chiasm, permit effective treatment of patients with optic nerve gliomas. Longer follow-up is needed to assess the incidence of late effects fully.     

Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival

Purpose To determine the radiographic and clinical efficacy of stereotactic single dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) as salvage therapy for glioblastoma (GBM) at recurrence. Methods Thirty-six patients with pathologically proven recurrent GBM were treated with salvage reirradiation by either SRS or FSRT between March of 2001 and August of 2006. Thirty-one patients had an initial diagnosis of GBM. Five patients had a malignant transformation. All patients had received radiotherapy with a dose of 50–60 Gy, a median 13.6 months prior to reirradiation (range: 0.8–119 months). At the time of recurrence, 26 patients were treated with SRS with a median dose of 18 Gy (range: 12–20 Gy). FSRT was performed in ten patients with a dose of 36 Gy in six fractions, twice weekly. Follow-up included MRI and clinical examination every 2 months. Results Median survival time after SRS was 8.5 months, compared to 7.4 months after FSRT (P = 0.81). Of 26 patients treated with SRS, radiographic tumor response or stable disease was observed in eight (35%) patients and tumor progression was seen in 18 (65%) patients. Of 10 patients treated by FSRT, radiographic tumor response or stable disease was observed in four (40%) patients and tumor progression was observed in four (40%) patients (two lost to follow-up). Patients who responded to treatment had statistically improved survival compared to non-responders, with median survival of 15.8 vs. 7.3 months (P < 0.05). Conclusion Salvage reirradiation with SRS or FSRT for recurrent GBM results in radiographic response in a proportion of patients. Survival was significantly improved among patients who either responded or had stable disease after salvage reirradiation, compared to non-responders. Further study is warranted to investigate the method and time of reirradiation for recurrent GBM.     

Fractionated stereotactic radiotherapy for the treatment of vestibular schwannomas: combined experience of the Toronto-Sunnybrook Regional Cancer Centre and the Princess Margaret Hospital

PURPOSE: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for vestibular schwannomas in patients treated at two university-affiliated hospitals. METHODS AND MATERIALS: Thirty-nine patients were treated between April 1996 and September 2000. The median age was 56 years (range: 29-80), and median maximal tumor diameter was 20 mm (range: 9-40). A total of 11 patients had fifth and/or seventh cranial nerve dysfunction before irradiation; 2 patients had only facial weakness, 5 patients had only facial numbness, and 4 patients had both facial weakness and numbness. Thirty-three patients were treated with primary FSRT, and 6 patients were treated for recurrent or persistent disease after previous surgery. All patients were treated with 6-MV photons using a stereotactic system with a relocatable frame. The 39 patients received 50 Gy in 25 fractions over 5 weeks. Median follow-up was 21.8 months (range: 4.4-49.6). RESULTS: Local control was achieved in 37 patients (95%). Two patients experienced deterioration of their symptoms at 3 and 20 months as a result of clinical progression in one case and tumor progression in the other and underwent surgery post FSRT. A total of 19/28 (67.9%) patients preserved serviceable hearing after FSRT. Deterioration of the facial and trigeminal nerves was observed in only 2 patients who were treated with surgery post FSRT. CONCLUSION: FSRT provided excellent tumor control with minimal morbidity and good hearing preservation in this cohort of patients. Longer follow-up is required to confirm long-term control rates.     

Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma

The aim of this paper is to evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) and concomitant temozolomide (TMZ) as a salvage treatment option in patients with recurrent glioblastoma (GBM). Between May 2006 and December 2009, 36 patients with recurrent GBM received FSRT plus concomitant TMZ at University of Rome La Sapienza, Sant’ Andrea Hospital. All patients had Karnofsky performance score ≥60 and were previously treated with standard conformal radiotherapy (RT) (60 Gy) with concomitant and adjuvant TMZ for 6–12 cycles. The median time interval between primary RT and reirradiation was 14 months. At the time of recurrence, all patients received FSRT plus concomitant daily TMZ at the dose of 75 mg/m², given 7 days per week from the first day of RT. Radiation dose was 37.5 Gy delivered in 15 fractions over 3 weeks. Median overall survival after FSRT was 9.7 months, and the 6- and 12-month survival rates were 84 and 33%, respectively. The median progression-free survival (PFS) was 5 months, and 6- and 12-month PFS rates were 42 and 8%, respectively. In univariate analysis, KPS (P = 0.04), the interval between primary RT and reirradiation (P = 0.02), and O6-methylguanine-DNA-methyltransferase (MGMT) methylation status at the time of diagnosis (P = 0.009) had an effect on survival; however, in multivariate analysis, only MGMT methylation was statistically significant (P = 0.03). In general, FSRT was well tolerated and the treatment was completed in all patients. Neurological deterioration due to radiation-induced necrosis occurred in three patients (8%). FSRT plus concomitant TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent GBM. The potential advantages of combined chemoradiation schedules in patients with recurrent GBM need to be explored in future studies.     

Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas

Purpose: To evaluate the efficacy of stereotactic radiotherapy (SRT) in patients with recurrent high-grade gliomas by comparing two different treatment regimens, single dose or fractionated radiotherapy.

Methods and Materials: Between April 1991 and January 1998, 71 patients with recurrent high-grade gliomas were treated with SRT. Forty-six patients (65%) were treated with single dose radiosurgery (SRS) and 25 patients (35%) with fractionated stereotactic radiotherapy (FSRT). For the SRS group, the median radiosurgical dose of 17 Gy was delivered to the median of 50% isodose surface (IDS) encompassing the target. For the FSRT group, the median dose of 37.5 Gy in 15 fractions was delivered to the median of 85% IDS.

Results: Actuarial median survival time was 11 months for the SRS group and 12 months for the FSRT group (p = 0.3, log-rank test). Variables predicting longer survival were younger age (p = 0.006), lower grade (p = 0.0006), higher Karnofsky Performance Scale (KPS) (p = 0.0005), and smaller tumor volume (p = 0.02). Patients in the SRS group had more favorable prognostic factors, with median age of 48 years, KPS of 70, and tumor volume of 10 ml versus median age of 53 years, KPS of 60, and tumor volume of 25 ml in the FSRT group. Late complications developed in 14 patients in the SRS group and 2 patients in the FSRT group (p < 0.05).

Conclusion: Given that FSRT patients had comparable survival to SRS patients, despite having poorer pretreatment prognostic factors and a lower risk of late complications, FSRT may be a better option for patients with larger tumors or tumors in eloquent structures. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.     

Integration of surgery with fractionated stereotactic radiotherapy for treatment of nonfunctioning pituitary macroadenomas

OBJECTIVE: To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) after surgery in the management of residual or recurrent nonfunctioning pituitary adenomas with respect to tumor control and the development of complications. METHODS AND MATERIALS: The clinical records of patients with nonfunctioning pituitary adenomas who underwent FSRT were retrospectively analyzed. For newly diagnosed tumors, transsphenoidal surgery was performed, and, if residual tumor was identified at 3 months, FSRT was performed. If significant tumor volume persisted, transcranial surgery was performed before FSRT. We originally initiated FSRT with 2-Gy fractions to 46 Gy. We escalated the dose to 50.4 Gy thereafter. As a final modification, we dropped the daily dose to 1.8-Gy fractions delivered within 6 weeks. High-dose conformality and homogeneity was achieved with arc beam shaping and differential beam weighting. The radiographic, endocrinologic, and visual outcomes after FSRT were evaluated. RESULTS: The 68 patients included 36 males and 32 females with an age range of 15-81 years. The median follow-up was 30 months (range, 2-82 months), and the median tumor volume was 6.2 cm(3). Of the 68 patients, 20 were treated to 46 Gy and 48 to 50-52.2 Gy. Most were treated to 50.4 Gy. Eleven patients had recurrent tumors, 54 had residual tumors, and no surgery was performed in 3 patients before FSRT. We noted no radiation-induced acute or late toxicities, except for radiation-induced optic neuropathy in 2 patients. At latest follow-up, the tumor had decreased in size in 26 patients and remained stable in 41 of the 42 remaining patients. Of the 68 patients, 4 (6%) developed hypopituitarism at 6, 11, 12, and 17 months after FSRT. Reviewing available serial Humphrey visual fields, visual fields were objectively improved in 28 patients, and remained stable in 24 patients, and worsened in 2 patients. CONCLUSION: The findings of this analysis support the use of surgery followed by FSRT as a safe, effective, and integrated treatment for nonfunctioning pituitary adenomas. Additional follow-up is needed to document the long-term tumor control rates, preservation rates for vision and pituitary function, and neurocognitive outcomes.