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.     

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.     

Survival following CyberKnife radiosurgery and hypofractionated radiotherapy for newly diagnosed glioblastoma multiforme

Current therapeutic goals for treatment of Glioblastoma Multiforme (GBM) involve gross total resection followed by multifractionated focal external beam radiation therapy (EBRT). Patients treated with optimal therapy have a median survival of approximately 12-15 months. In the present study, we sought to determine whether a hypofractionated dosing schedule using CyberKnife is at least as effective as multifractionated focal EBRT. A retrospective analysis was conducted on 20 histopathologically confirmed GBM patients treated with CyberKnife at Okayama Kyokuto Hospital in Japan after gross total resection (n=11), subtotal resection (n=8), or biopsy (n=1). Eight patients also received adjuvant ACNU and Vincrisitine chemotherapy according to local protocol; however, no patient received any other form of radiation besides post surgical/biopsy CyberKnife treatment. The treated tumor volumes ranged from 9.62 cm(3)-185.81 cm(3) (mean: 86.08 cm(3)). The marginal dose (D90) ranged from 19.99 Gy-41.47 Gy (mean: 34.58 Gy) with a maximum mean dose of 43.99 Gy (range: 23.33 Gy-56.89 Gy). The prescribed isodose line ranged from 50.38%-85.68% with a mean of 79.25%. Treatment was delivered in 1-8 fractions (mean: 5.65). Patients were followed from 2-36 months (mean: 16.45 months). Overall median survival was 16 months with 55% of patients alive at 12 months and 34% of patients alive at 24 months. Median survival of patients in Recursive Partitioning Analysis (RPA) classes III or IV was 32 months versus 12 months for those in RPA class V. Median survival for patients who received gross total resection was 36 months versus 8 months for those who underwent subtotal resection or biopsy. The results of this study using CyberKnife stereotactic radiosurgery (SRS) and hypofractionated radiotherapy compared favorably to historic data using focal EBRT in newly diagnosed post surgical GBM patients. A larger prospective analysis that compares CyberKnife SRS and hypofractionated radiotherapy to focal EBRT is warranted.     

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.     

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.     

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.     

Clinical outcomes of patients treated with a second course of stereotactic radiosurgery for locally or regionally recurrent brain metastases after prior stereotactic radiosurgery

Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan–Meier analysis and the multivariate proportional hazards model. The Kaplan–Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3–72.2 months) and 7.9 months (0.7–61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.     

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。     

Does stereotactic eligibility for the treatment of glioblastoma cause selection bias in randomized studies?

The purpose of this study was to evaluate the potential selection bias using stereotactic eligibility as a criteria for participation in studies of glioblastoma multiforme. Radiation Therapy Oncology Group (RTOG) 90-06 comparing 60 Gy in 30 fractions with BCNU and 72 Gy in 60 fractions with BCNU was analyzed based on eligibility criteria used to enter patients on RTOG 93-05 using a stereotactic boost for patients with glioblastoma. Five hundred nine patients with histopathologically confirmed glioblastoma multiforme were analyzed; of these, 137 met criteria for 93-05 and 372 did not. Recursive partitioning analysis (RPA) was used to evaluate for differences. The RPA distribution in stereotactic radiosurgery (SRS)-eligible and -ineligible patients was similar. The median survival for RPA class 3 SRS-eligible patients was 1.4 years and -ineligible patients 1.4 years. For RPA class 4, the median survival was 1.0 years for eligible patients and 0.9 years for ineligible patients (P = 0.0421). For class 5 patients, the median survival was 8.3 months versus 7.2 months (P = 0.09). RPA class 6 patients had a median survival of 1.7 months versus 2.7 months for ineligible patients (P = 0.199). By analyzing previously randomized patients in a study not using a stereotactic boost, there does not appear to be a survival benefit for those patients who fit the criteria for consideration of a stereotactic boost in patients with glioblastoma multiforme.     

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.     

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.     

Phase II radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme

PURPOSE: Fractionated external beam radiotherapy (EBRT) +/- carmustine (BCNU) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy between RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m(2)/3 h/week x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its MTD. PATIENTS AND METHODS: Sixty-two patients with histologic diagnosis of GBM were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m(2)/3 h (1-3 h before EBRT), administered the first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5 days per week. A smaller treatment field, to include gross disease plus a margin only, was used after 46 Gy. RESULTS: Sixty-one patients (98%) were evaluable. Median age was 55 years (range, 28-78). Seventy-four percent were > or = 50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3 or 4). Ninety-one percent of patients received treatment per protocol. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 patients with measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%. Seventeen percent demonstrated progression at first follow-up. Median potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10.2, 9.5, 2.5 months, respectively. Ten patients remain alive. CONCLUSION: Concurrent full-dose EBRT and weekly high-dose TAX is feasible in the majority of GBM patients. Acute toxicity is acceptable; myelosuppression and peripheral sensory neuropathy are surprisingly modest, despite considerably higher overall dose intensity, compared to that achievable in other disease sites. Median survival by RPA class without prolonged adjuvant therapy is comparable to RTOG controls treated with standard EBRT and BCNU (1 year of BCNU).     

The role of salvage reirradiation for malignant gliomas that progress on bevacizumab

Bevacizumab and irinotecan are effective against recurrent malignant gliomas. However, at subsequent progression, patients rarely respond to a second bevacizumab-containing chemotherapeutic regimen. Salvage re-irradiation with bevacizumab for recurrent but bevacizumab naive malignant gliomas showed encouraging results. We performed a retrospective review of the medical records of 23 patients treated with either fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS) after progression on an initial bevacizumab regimen. Patients were treated after re-irradiation with bevacizumab but combined with a different chemotherapy. We then compared them to another 23 patients who progressed on an initial bevacizumab + chemotherapy regimen. These patients did not receive re-irradiation but bevacizumab was continued combined with a different chemotherapy. Patients treated with FSRT/SRS/bevacizumab had a longer median progression-free period (2.6 vs. 1. 7 months, P = 0.009), longer median post FSRT/SRS treatment survival (7.2 vs. 3.3 months, P = 0.03) and higher radiographic response rate (22 vs. 0%, P = 0.049). FSRT or SRS followed by bevacizumab + chemotherapy may have a role for patients who progress on bevacizumab.     

Bevacizumab and re-irradiation for recurrent high grade gliomas: does sequence matter?

Purpose/objectives

We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG.

Materials/methods

After Institutional Review Board approval, patients with pathologically confirmed WHO grade III anaplastic astrocytoma (AA) or IV glioblastoma multiforme (GBM) glioma who subsequently underwent re-irradiation at recurrence with FSRT were retrospectively reviewed. Patients from this group who had received BEV were also identified. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were analyzed as study endpoints. Date of recurrence was defined as the date of radiographic evidence of progressive/recurrent disease. Kaplan–Meier curves were generated utilizing a log-rank test with a p-value?≤?0.05 considered significant to compare treatment sequences in terms of survival outcomes.

Results

A total of 118 patients with recurrent/progressive HGG (GBM?=?87, AA?=?31) had received both BEV and FSRT. Patient characteristics were as follows: median KPS at recurrence was 80 (range 50–100); median age at recurrence was 57 years; median time to radiographic recurrence/progression was 10.8 months (mo) and 33.1% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months. For the entire cohort, median overall survival (OS) was 26.7 months and median survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months for GBM only). In patients that received BEV prior to FSRT (n?=?50), median OS and MST from recurrence were 25.2 and 13.3 months respectively. In patients receiving FSRT first (n?=?56), median OS and MST from recurrence were 28.8 months and 13.9 months, respectively. Sequencing of BEV and FSRT at recurrence was not significantly associated with OS (p?=?0.08) or median survival from recurrence (p?=?0.75).

Conclusions

The combination of FSRT and BEV for recurrent/progressive HGG provides promising results in terms of overall survival and survival from recurrence. Combining these treatment modalities appears to improve upon the historic outcomes of either treatment alone. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG.

     

Implant volume as a prognostic variable in brachytherapy decision-making for malignant gliomas stratified by the RTOG recursive partitioning analysis.

PURPOSE: When an initial retrospective review of malignant glioma patients (MG) undergoing brachytherapy was carried out using the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) criteria, it revealed that glioblastoma multiforme (GBM) cases benefit the most from implant. In the present study, we focused exclusively on these GBM patients stratified by RPA survival class and looked at the relationship between survival and implanted target volume, to distinguish the prognostic value of volume in general and for a given GBM class. METHODS AND MATERIALS: Between 1991 and 1998, 75 MG patients were treated with surgery, external beam radiation, and stereotactic iodine-125 (I-125) implant. Of these, 53 patients (70.7%) had GBMs, with 52 (98%) having target volume (TV) data for analysis. Stratification by RPA criteria showed 12, 26, 13, and 1 patients in classes III to VI, respectively. For analysis purposes, classes V and VI were merged. There were 27 (51.9%) male and 25 (48.1%) female patients. Mean age was 57.5 years (range 14-79). Median Karnofsky performance status (KPS) was 90 (range 50-100). Median follow-up time was 11 months (range 2-79). RESULTS: At analysis, 18 GBM patients (34.6%) were alive and 34 (65.4%) were dead. Two-year and 5-year survivals were 42% and 17.5%, respectively, with a median survival time (MST) of 16 months. Two-year survivals and MSTs for the implanted GBM patients compared to the RTOG database were as follows: 74% vs. 35% and 28 months vs. 17.9 months for class III; 32% vs. 15% and 16 months vs. 11.1 months for class IV; 29% vs. 6% and 11 months vs. 8.9 months for class V/VI. Mean implanted TV was 15.5 cc (range 0.8-78), which corresponds to a spherical implant diameter of 3.1 cm. Plotting survival as a function of 5-cc TV increments suggested a trend toward poorer survival as the implanted volume increases. The impact of incremental changes in TV on survival within a given RPA class of GBMs was compared to the RTOG database. Looking at absolute differences in MSTs: for classes III and IV, there was little effect of different TVs on survival; for class V/VI, a survival benefit to implantation was still seen at the target volume cutoff (TV > 25 cc). Within a given RPA class, no significant differences were found within class III; for class IV, the most significant difference was at 10 cc (p = 0.05); and for class V/VI, at 20 cc (p = 0.06). CONCLUSION: For all GBM patients, an inverse relationship between implanted TV size and median survival is suggested by this study. However, when GBM patients are stratified using the RTOG's RPA criteria, the prognostic effect of implant volume disappears within each RPA survival class. At the critical volume of 25 cc, which approximates an implant of 5-cm diameter (upper implantation limit of many CNS brachytherapy protocols), the "poorest" prognosis GBM patients stratified by RPA still demonstrate a survival benefit with implant. We suggest that any GBM patient meeting brachytherapy recognized size criteria be considered for I-125 implant.     

Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM)

BACKGROUND: This article describes the results of a study of stereotactic radiosurgery (SRS) in the treatment of patients with recurrent malignant glioma. METHODS: Thirty-two patients with recurrent glioblastoma multiforme (GBM) were treated for 36 lesions with SRS from 1993 to 2001. Nineteen patients were male and 13 were female. The median age at primary diagnosis of the tumor was 56 years (range, 33-76 yrs). At the time of initial diagnosis a total neurosurgical resection was performed in 7, a subtotal resection in 21, and a biopsy in 4 patients. Histology evaluations revealed glioblastoma multiforme (WHO Grade IV) in all 32 patients. In all patients radiotherapy was performed as the first-line therapy, applied as fractionated external beam radiotherapy. The median interval between primary irradiation and reirradiation was 10 months. The median dose applied was 15 Gy (range, 10-20 Gy) prescribed to the 80% isodose line that encompassed the target volume. No concomitant chemotherapy was applied. RESULTS: Treatment was well tolerated by all patients. No acute toxicities > CTC Grade II occurred. No severe long-term toxicities including radionecrosis were observed. The median follow-up time was 13 months (range, 1-89 mo). All patients died of tumor progression during follow-up. The median overall survival from primary diagnosis of the tumor was 22 months (range, 9-133 mo). The survival rate at 1 year was 90%, and 49% and 26% at 2 and 3 years, respectively. Median overall survival after SRS was 10 months. At 6 and 12 months after SRS, survival rates were 72% and 28%, respectively. Median progression-free survival after SRS was 7 months. CONCLUSIONS: SRS offers effective treatment as a salvage therapy for a subgroup of patients with smaller lesions of recurrent GBM.     

Stereotactic radiotherapy for patients who initially presented with brain metastases from non-small cell carcinoma

The purpose of this study was retrospectively to evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for patients who presented with intracranial metastases as the initial symptom of lung carcinoma. Fifteen patients with three or fewer brain metastases from lung carcinoma underwent FSRT receiving 42 Gy in 7 fractions or 40 Gy in 4 fractions from April 1999 to October 2002. Patients who developed new lesions were retreated with FSRT or whole brain radiotherapy (WBRT). Tumor control was obtained in 14 patients during a median period of 21.0 months (ranging from 11 to 34 months) with salvage radiotherapy whenever required. None died from brain metastasis. The median survival time was 7.0+/-3.0 months and 21.0+/-1.0 months for patients with or without extracranial metastases, respectively (p<0.01). Those who received treatment for the primary and mediastinal lymph nodes (22.0+/-1.4 months) survived longer than those who did not (8.0+/-2.5 months) (p<0.001). Overall high local control and high survival rates for the patients suggest that FSRT appears effective and safe in the treatment of patients who present with intracranial metastases as the initial symptom of lung carcinoma. After treatment of intracranial metastases, further therapy for the primary appears to improve survival rates.     

Outcomes for Pituitary Adenoma Patients Treated with Linac-Based Stereotactic Radiosurgery and Radiotherapy: a Long Term Experience in Thailand

Background: The study analyzed the long term clinical outcomes of pituitary adenoma cases treated withthe first Thailand installation of a dedicated Linac-based stereotactic radiation machine (X-Knife). Materialsand Methods: A retrospective review of 115 consecutive pituitary adenoma patients treated with X-Knife at theFaculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand from 1997 to 2003 was performed. Stereotacticradiosurgery (SRS) was selected for 21 patients (18%) including those with small tumors (≤3cm) located ≥ 5 mm.from the optic apparatus, whereas the remaining 94 patients (82%) were treated with fractionated stereotacticradiotherapy (FSRT). Results: With a median follow-up time of 62 months (range, 21-179), the six-year progressionfree survival was 95% (93% for SRS and 95% for FSRT). The overall hormone normalization at 3 and 5 yearswas 20% and 30%, respectively, with average time required for normalization of approximately 16 months forSRS and 20 months for FSRT. The incidence of new hypopituitarism was 10% in the SRS group and 9% in theFSRT group. Four patients (5%) developed optic neuropathy (1 in the SRS group and 3 in the FSRT group ).Conclusions: Linac-based SRS and FSRT achieved similar high local control rates with few complications inpituitary adenoma cases. However, further well designed, randomized comparative studies between SRS versusFSRT particularly focusing on hormone normalization rates are required.     

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.     

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.