Achievement of long-term local control in patients with craniopharyngiomas using high precision stereotactic radiotherapy

BACKGROUND: The long-term outcome in patients with craniopharyngiomas treated with fractionated stereotactic radiotherapy (FSRT) was evaluated. METHODS: A total of 40 patients with craniopharyngiomas were treated between May 1989 and July 2006 with FSRT. Most patients were treated for tumor progression after surgery. A median target dose of 52.2 grays (Gy) (range, 50.4-56 Gy) was applied in a median conventional fractionation of 5 x 1.8 Gy per week. Follow-up examinations included thorough clinical assessment as well as contrast-enhanced magnetic resonance imaging scans. RESULTS: After a median follow-up of 98 months (range, 3-326 months), local control was 100% at both 5 years and 10 years. Overall survival rates at 5 years and 10 years were 97% and 89%, respectively. A complete response was observed in 4 patients and partial responses were noted in 25 patients. Eleven patients presented with stable disease during follow-up. Acute toxicity was mild in all patients. Long-term toxicity included enlargement of cysts requiring drainage 3 months after FSRT. No visual impairment, radionecrosis, or development of secondary malignancies were observed. CONCLUSIONS: The long-term outcome of FSRT for craniopharyngiomas is excellent with regard to local control as well as treatment-related side effects.     

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.     

389例脑胶质瘤立体定向放射治疗效果评价(英文)

目的探讨脑胶质瘤立体定向放射治疗的疗效及放疗副反应。方法从1995年6月到1998年12月,用立体定向放射治疗的方法共治疗脑胶质瘤病人389例,其中用立体定向放射外科(ster-eotactic radiosurgery,SYS)方法治疗151例,分次立体定向放射治疗(fractionated stereotatic radiotherapy,FSRT)方法治疗238例。SRS组单次周边剂量20～30Gy,靶点1～6个,平均2.48个,照射弧5～21个,平均8.45个;FSRT 组每日或隔日照射,每次周边剂量8～12Gy,共照射2～5次,靶点1～6个,平均2.53个,照射弧6～20个,平均8.25个。结果治疗结束后3个月,SRS 组完全缓解(CR)21例,占13.9%,部分缓解(PR)69例,占45.7%,稳定(SD)26例,占17.2%,进展(PD)35例,占23.2%,总有效率(PR+CR+SD)为76.8%;FSRT 组完全缓解(CR)47例,占19.7%,部分缓解(PR)114例,占47.9%,稳定(SD)49例,占20.6%,进展(PD)28例,占11.8%,总有效率(PR+CR+SD)为88.2%,两组差别有显著性(X~2=9.874,P=0.020)。全部病人的1、3、5年生存率分别为54.3%、29.3%、16.5%;SRS 组和 FSRT 组的1、3、5年生存率分别为52.3%、26.5%、11.9%和55.5%、31.1%、19.3%,两组差别没有显著性意义(X~2=2.16,P=0.1417);放射治疗的主要副反应为脑水肿,SRS组较 FSRT 组为重(X~2=4.916,P=0.027)。结论立体定向放射治疗对脑胶质瘤有较好的疗效,FSRT 与 SRS 相比,具有疗效好副作用小的优点。     

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.     

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。     

389例脑胶质瘤立体定向放射治疗效果评价

Objective： To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods： From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic radiotherapy, among which 151 cases were treated by stereotactic radiosurgery （SRS） and the other 238 cases, by fractionated stereotactic radiotherapy （FSRT）. In the SRS group, the marginal tumor dose was 20 to 30 Gy （median, 2.6 Gy）. One to 6 isocenters （median, 2.48） and 5 to 21 irradiation arcs （median, 8.45） were applied. In the FSRT group, the per-fraction marginal tumor dose was 8 to 12 Gy with 1 to 6 isocenters （median, 2.53）, 6 to 20 irradiation arcs （median, 8.25） and 2-5 fractions delivered everyday or every other day. Results： Three months after treatment, the complete and partial response rates were 13.9% and 45.7% in SRS group respectively. The stable disease rate was 17.2%. The total effective rate was 76.8%. In FSRT group, the complete and partial remission rates were 19.7% and 47.9% respectively. The stable disease rate was 20.6%. The total effective rate was 88.2%. The total effective rate of FSRT group was higher than that in SRS group （X^2=9.874, P=0.020）. The 1-year, 3-year and 5-year survival rate of all patients was 54.3%, 29.3%, 16.5% respectively. The 1-year, 3-year and 5-year survival rate in SRS group and FSRT group was 52.3% vs 26.5%, 11.9% vs 55.5%, and 31.1 vs 19.3% respectively. There was no significant difference between the two groups （X^2=2.16, P=0.1417）. The brain edema caused by the main radiation was more severe in the SRS group than in FSRT group （X^2=4.916, P=0.027）. Conclusion： It is effective for brain glioma to be treated by stereotactic radiotherapy. Compared with SRS, the FSRT has the advantage of good effect and less side response.     

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.     

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.     

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.     

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.     

Fractionated stereotactic radiotherapy (FSRT) for optic glioma

PURPOSE: To determine efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with optic glioma. METHODS AND MATERIALS: Ten patients suffering from optic glioma were treated by FSRT between December 1990 and December 1995 at the German Cancer Research Center (DKFZ) in Heidelberg. Eight patients were treated for progressive recurrent tumor following partial tumor resection and 2 patients were treated postoperatively. Dose distributions were calculated by a 3D treatment planning system (Voxelplan, Heidelberg). Patients were treated with a noninvasive repeatable stereotactic fixation system using a manually driven midsize multileaf collimator attached to a linear accelerator. We applied a median prescribed total dose to the isocenter of 52.4 Gy with a median daily fraction size of 1.8 Gy. RESULTS: All patients treated by definitive radiotherapy remained free from local tumor progression during the follow-up period (range 12-72 months) except the 1 patient treated for recurrence after previous radiotherapy. A complete remission was achieved in 3 patients with subsequent improvement of visual acuity. None of the patients with locally controlled tumor experienced any further impairment of vision. One patient developed new ACTH deficiency. No other clinically significant late effects attributable to radiotherapy were observed. CONCLUSION: FSRT permits treatment of optic glioma with excellent tumor control and without clinically relevant morbidity. Compared to conventional techniques there is the potential of sparing the pituitary gland in chiasmatic lesions.     

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.     

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.     

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 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.     

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.     

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 of brain metastases from renal cell carcinoma

Purpose: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for brain metastases from renal cell carcinoma (RCC).

Methods and Materials: From May 1983 to September 1998, 35 patients with brain metastases from RCC underwent radiotherapy at the National Cancer Center Hospital, Tokyo; 10 patients treated initially with FSRT (FSRT group); 11 with surgery followed by conventional radiotherapy (S/CR group); and 14 with conventional radiotherapy (CR group). Survival and local control rates were determined for patients who had an ECOG performance status of 0–2.

Results: Overall median survival rate was 18 months, and actuarial 1- and 2-year survival rates were 57.6% and 31.0%, respectively. Median survival rates were 25.6 months for the FSRT group, 18.7 months for the S/CR group, and 4.3 months for the CR group. Significant prognostic factors associated with survival were age less than 60 years and good performance status. In patients treated with FSRT, imaging studies revealed that 21 of 24 tumors (88%) were locally controlled during a median follow-up time of 5.2 months (range 0.5–68). Actuarial 1- and 2-year local control rates were 89.6% and 55.2%, respectively. No patient suffered from acute or late complications during and following FSRT.

Conclusions: FSRT offers better tumor control and prolonged survival over the S/CR or CR groups, and should be considered as primary treatment for brain metastases from RCC. Patients under 60-years-old and those with a good performance status at the beginning of radiotherapy had a better prognosis.     

A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023

PURPOSE: This phase II trial was performed to assess the feasibility, toxicity, and efficacy of dose-intense accelerated radiation therapy using weekly fractionated stereotactic radiotherapy (FSRT) boost for patients with glioblastoma multiforme (GBM). METHODS AND MATERIALS: Patients with histologically confirmed GBM with postoperative enhancing tumor plus tumor cavity diameter <60 mm were enrolled. A 50-Gy dose of standard radiation therapy (RT) was given in daily 2-Gy fractions. In addition, patients received four FSRT treatments, once weekly, during Weeks 3 to 6. FSRT dosing of either 5 Gy or 7 Gy per fraction was given for a cumulative dose of 70 or 78 Gy in 29 (25 standard RT + 4 FSRT) treatments over 6 weeks. After the RT course, carmustine (BCNU) at 80 mg/m(2) was given for 3 days, every 8 weeks, for 6 cycles. RESULTS: A total of 76 patients were analyzed. Toxicity included: 3 Grade 4 chemotherapy, 3 acute Grade 4 radiotherapy, and 1 Grade 3 late. The median survival time was 12.5 months. No survival difference is seen when compared with the RTOG historical database. Patients with gross total resection (41%) had a median survival time of 16.6 months vs. 12.0 months for historic controls with gross total resection (p = 0.14). CONCLUSION: This first, multi-institutional FSRT boost trial for GBM was feasible and well tolerated. There is no significant survival benefit using this dose-intense RT regimen. Subset analysis revealed a trend toward improved outcome for GTR patients suggesting that patients with minimal disease burden may benefit from this form of accelerated RT.