Hypofractionated intensity-modulated radiotherapy for primary glioblastoma multiforme.
Floyd NS, Woo SY, Teh BS, Prado C, Mai WY, Trask T, Gildenberg PL, Holoye P, Augspurger ME, Carpenter LS, Lu HH, Chiu JK, Grant WH 3rd, Butler EB.
Department of Radiology, Section of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA.
PURPOSE: A pilot study was designed to evaluate the safety and efficacy of a novel regimen of hypofractionated intensity-modulated radiotherapy (RT) in the adjuvant treatment of primary glioblastoma multiforme (GBM). The rationale of the study was to combine the potential radiobiologic advantage of hypofractionation to GBM with a highly conformal radiotherapeutic technique. The study was designed to measure the acute and chronic morbidity of patients treated with this regimen, response of GBM to the treatment, overall survival, and time to disease progression after therapy completion. METHODS AND MATERIALS: Twenty eligible patients were accrued between February 1999 and May 2000 for the study. All patients had Karnofsky performance scores of >/=70. All patients were treated with intensity-modulated RT using the NOMOS Peacock system. A dose of 50 Gy was delivered in 5-Gy daily fractions within 2 weeks to enhancing primary disease, residual tumor, or surgical cavity. Simultaneously, 30 Gy was prescribed in 3-Gy daily fractions to surrounding edema. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicity was graded using Radiation Therapy Oncology Group neurotoxicity scores. RESULTS: Of the 20 patients, 18 were evaluated for outcome. The median time to disease progression was 6 months after RT completion. The median overall survival was 7 months after treatment completion. All recurrences were within 2 cm of the operative bed. Neurotoxicity during therapy was minimal, with all patients experiencing Grade 0 or 1 toxicity. Late toxicity included 10 patients with Grade 0, 2 patients with Grade 2, and 3 patients with Grade 4 toxicity, manifesting as brain necrosis requiring surgical reexcision. The survival of the 3 patients with brain necrosis was 23, 20, and 9 months. Mortality in all cases was the result of tumor recurrence, with no mortality resulting from brain necrosis. CONCLUSION: This regimen of hypofractionated intensity-modulated RT did not improve the time to disease progression or overall survival compared with historical experience using conventional fractionation. However, the treatment duration was reduced from 6 weeks to 2 weeks, which may be of palliative benefit in certain subsets of patients. This treatment regimen demonstrated a greater incidence of brain necrosis requiring surgical intervention; however, the 3 patients experiencing this toxicity had longer survival times. Future investigation may be useful to determine which fraction size may be optimal for GBM when highly conformal RT is used in the adjuvant setting.
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Stereotactic radiosurgery versus fractionated stereotactic radiotherapy boost for patients with glioblastoma multiforme.
Cho KH, Hall WA, Lo SS, Dusenbery KE.
Departments of Therapeutic Radiology and Radiation Oncology, Fairview University Medical Center, University of Minnesota, Minneapolis, MN, USA.
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
The aim of this study is to evaluate the efficacy of stereotactic radiotherapy boost (SRB) in patients with glioblastoma multiforme (GBM) by comparing two different regimens, single dose or fractionated treatment. Between December 1994 and January 2000, 24 patients with GBM were treated with SRB in conjunction with external beam radiotherapy (EBRT). Fourteen patients (58%) were treated with stereotactic radiosurgery (SRS) and 10 patients (42%) with fractionated stereotactic radiotherapy (FSRT). Median interval between EBRT and SRS or FSRT was 1.4 months (range -0.4-3.9 months). Actuarial survival rates of the entire 24 patients at one and two years following SRB were 63% and 34% respectively, with median survival time of 16 months. Variables predicting survival were age, extent of surgery, re-operation and the RTOG (Radiation Therapy Oncology Group) classes based on recursive partitioning analysis (RPA). In comparison to historical controls, improved survival benefit after SRB was observed. The median survival times for the RTOG classes 4, 5, and 6 were 28.3, 10.3, and 6.0 months following EBRT+SRB, respectively. Expected values for these classes after EBRT are 11.1, 8.9, and 4.6 months, respectively. This improvement in survival was seen predominantly for the RTOG class 4. There was no difference in survival between SRS and FSRT treated groups. Late complications developed in 4 patients in the SRS group and 1 patients in the FSRT group. Our retrospective data suggest that SRB in conjunction with EBRT may improve survival in patients with GBM with median survival time of 16 months, when compared to historical controls of the RTOG data following EBRT. The addition of SRB appeared to improve the median survival most demonstrably in RTOG RPA class 4 patients. SRS and FSRT are equally effective with similar median survival, but potentially less late complications associated with FSRT. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.
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Fractionated stereotactic radiotherapy in low-grade astrocytomas: long-term outcome and prognostic factors.
Plathow C, Schulz-Ertner D, Thilman C, Zuna I, Lichy M, Weber MA, Schlemmer HP, Wannenmacher M, Debus J.
Division of Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
PURPOSE: To evaluate outcome after fractionated stereotactic radiotherapy (RT) of patients with World Health Organization Grade 2 astrocytoma in terms of progression-free survival, overall survival, toxicity, quality of life, and prognostic factors. METHODS AND MATERIALS: Between 1984 and 2000, 143 patients with histologically proven Grade 2 astrocytoma were treated with fractionated stereotactic RT at our institution. The evaluation of the quality of life and toxicity was based on neurologic examinations and the Karnofsky performance score. Univariate analysis was performed on seven potential prognosticators and multivariate analysis on four prognosticators. RESULTS: The median follow-up was 44 months. The actuarial overall survival and progression-free survival was 58% and 39% at 5 years, respectively. Out-of-field recurrences occurred in 1 patient (1.2%). We did not observe a dose-response relationship. Overall survival and progression-free survival were significantly correlated with the absence of contrast media enhancement before RT (p <0.01). Toxicity was mild and included severe side effects of European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 in only 4 patients (2.8%). The Karnofsky performance score improved in most patients. CONCLUSION: Fractionated stereotactic RT is effective and has low toxicity in the treatment of Grade 2 gliomas. The rate of field border recurrences was not increased compared with after conventional RT. Exceeding the tumor dose did not improve the tumor control rate but did enhance toxicity. Pretherapeutic contrast media enhancement should be interpreted as a sign of higher grade tumor elements.
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Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: outcome and prognostic factors.
Chang EL, Yi W, Allen PK, Levin VA, Sawaya RE, Maor MH.
Division of Radiation Oncology, Brain Tumor Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
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PURPOSE: To evaluate the outcome for elderly or younger poor prognosis glioblastoma patients treated with hypofractionated radiotherapy (HypoRT). METHODS AND MATERIALS: Retrospective review at The University of Texas M. D. Anderson Cancer Center identified 59 glioblastoma patients (median age 65 years) treated with HypoRT between 1988 and 2001 with 50 Gy given at 2.5 Gy/fraction/day in 20 fractions within 4 weeks. Classification was according to the Radiation Therapy Oncology Group recursive partitioning analysis and was Class IV in 11, V in 29, and VI in 19. Surgery consisted of gross total resection (n = 16), subtotal resection (n = 28), and biopsy only (n = 13). Two patients were treated presumptively on the basis of radiographic findings. Chemotherapy was given either as part of the initial treatment (n = 15) or for progression (n = 9). RESULTS: The median survival time for the entire study population was 7 months, and the median progression-free survival was 3.9 months. The median survival time for patients with Class IV, V, and VI was 11, 7, and 5 months, respectively. Concordance was found with Radiation Therapy Oncology Group-established recursive partitioning analysis class survival. Steroid requirements were not increased during RT compared with preoperatively and immediately postoperatively. Late complications of HypoRT were limited to 3 cases of radiation necrosis suggested by MRI, 2 of which were pathologically confirmed. CONCLUSION: HypoRT consisting of 50 Gy in 4 weeks can be used for selected GBM patients to reduce the overall treatment time of conventional RT by 33-39% without apparent increased toxicity or decrement in survival.
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Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in patients with high-grade gliomas.
Baumert BG, Lutterbach J, Bernays R, Davis JB, Heppner FL.
Radiation-Oncology, University Hospital Zurich, Zurich, Switzerland.
PURPOSE: To determine the value and the toxicity of an additional fractionated stereotactic boost as used in the joint randomized EORTC-22972/MRC-BR10 study in patients with malignant gliomas. MATERIALS AND METHODS: Seventeen patients (11 male, six female) with a high-grade glioma (two WHO III, 15 WHO IV) < or =4 cm in maximum diameter, with a good performance status (WHO > or =2), were treated with a fractionated stereotactic radiotherapy (SRT) boost to 20 Gy in four fractions following partial brain irradiation to a dose of 60 Gy in 30 fractions. This patient group was compared with historical data in a matched-pair analysis. RESULTS: All patients were treated by conventional radiotherapy and a SRT boost (15 patients received 20 Gy and two patients 10 Gy). Acute side effects included fatigue (two), impairment of short-term memory (one) and worsening of pre-existing symptoms (one). No patient developed steroid dependence after SRT. One patient was re-operated for radiation necrosis. At a median follow-up of 25 months (9-50 months) 14 patients recurred locally. Survival was 77% at 1 year and 42% at 2 years; progression-free survival was 70% at 1 year and 35% at 2 years for all patients, respectively. Median survival for the whole patient group is 20 months. Comparison with a matched historical group showed a significantly better survival for the group treated with a stereotactic boost (P<0.0001). CONCLUSION: A fractionated stereotactic boost after standard external beam radiotherapy in selected patients with high-grade glioma is feasible and well tolerated with low toxicity. Compared to historical data survival is significantly better with an additional SRT boost. However, its effectiveness has to be proven in a randomized trial.
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Survival and prognostic factors of patients with unresectable glioblastoma multiforme.
Fazeny-Dorner B, Wenzel C, Veitl M, Piribauer M, Rossler K, Dieckmann K, Ungersbock K, Marosi C.
Ludwig Boltzmann Institute for Clinical Experimental Oncology, Department of Medicine I, University of Vienna, Wien, Australia.
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
The aim of this study was to assess survival and prognostic factors of 98 consecutive patients with unresectable glioblastoma multiforme (GBM) after stereotactic biopsy. Patients were diagnosed between 1993 and 1998, and the treatment modality subsequent to stereotactic biopsy was determined by the year of diagnosis. Before 1995, patients did not receive further specific therapy after stereotactic biopsy (n=36). In 1996, patients were administered radiotherapy starting within 6 weeks after stereotactic biopsy (n=24). >From 1997 to 1998, patients received combined radio-/chemotherapy (RCT; CCNU orally) starting within 2 weeks after stereotactic biopsy (n=38). Patients' age ranged from 21 to 84 (median 64) years and their median Karnofsky performance score 2 weeks after stereotactic biopsy was 80 (range 60-100). Survival and prognostic factors were analyzed with respect to administered treatment modalities (without specific therapy versus radiotherapy versus combined RCT), with respect to age (>or<or=50 years), gender, Karnofsky performance score (>or=or<80), tumor location (frontal, parieto-temporal, central, occipital) and tumor size (>or<or=5 cm; tumor multiplicity was considered as diameter >5 cm) by the Kaplan-Meier method, by log-rank test and multivariate Cox regression analysis. Post-biopsy treatment modality was the strongest predictor for survival. Median (range) survival was 9 (3-47) weeks in those without specific therapy, 13 (5-54) weeks in patients receiving radiotherapy and 31 (11-101) weeks in patients receiving combined RCT (p<or=0.001). Age<or=50 years (p<or=0.05) in addition to tumor size in multivariate Cox analysis were found to be of significant influence onto survival, too. Combined RCT could be performed on a complete outpatient basis. Toxicity consisted of mild asymptomatic thrombocytopenia. We conclude that the administration of combined RCT within a minimum interval after stereotactic biopsy yielded a significant increase in survival. Patients' acceptance was excellent. These results encourage us to treat even patients with unresectable GBM with combined RCT.
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Stereotactic radiosurgery in the management of intracranial gliomas.
Roberge D, Souhami L.
Division of Radiation Oncology, McGill University, Montreal General Hospital, 1650 Cedar Ave., Montreal, QC, Canada H3G 1A4.
Glial neoplasms are the most common primary intracranial malignancies. Treatment of high-grade gliomas has been frustrating, with less than 5% of patients surviving 5 years after a diagnosis of glioblastoma multiforme (GBM). Stereotactic radiosurgery (SRS) and fractionated strereotactic radiotherapy (F-SRT) provide means to either escalate the dose in primary treatment or to palliate recurrences. Because of their lower alpha/beta ratios and more focal nature, low-grade gliomas (LGG) are more attractive targets for stereotactically focused radiation. Results of available phase I-II data are reviewed for both low and high-grade gliomas. In the case of high-grade gliomas disappointing preliminary phase III data from RTOG 93-05 are discussed. Toxicity of SRS is discussed. Acute treatment toxicity of significance is unusual and generally self-limited. Occasionally an exacerbation of existing symptoms occurs. Late complications attributable to SRS are usually defined as necrosis within the treatment volume. The rate of necrosis can be hard to define in high-grade gliomas as tumor cells are often present in surgical specimens. New strategies in the application of stereotactic radiation are touched upon, these include: changes in planning and fractionation, concurrent use of chemotherapy, use of radiation modifiers and biologic agents. After reviewing the current data for high-grade gliomas, it appears that any apparent improvement in outcome seen in phase I-II trials is attributable to patient selection. The best evidence available does not support the use of SRS for primary high-grade gliomas. The somewhat limited experience in LGG also indicates a lack of benefit for patients treated with stereotactic radiosurgery or F-SRT. For a very select group of patients with small recurrent lesions, F-SRT may represent a safe, reasonable treatment.
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High-dose-rate stereotactic brachytherapy for patients with newly diagnosed glioblastoma multiformes.
Chang CN, Chen WC, Wei KC, Ng SH, Ho YS, Huang DY, Lee SP, Hong JH.
Department of Neurosurgery, Chang Gung Memorial Hospital, LinKou, Taiwan, ROC.
PURPOSE: To evaluate high-dose-rate (HDR) stereotactic brachytherapy (STBT) for glioblastoma multiforme (GBM). MATERIALS AND METHODS: Between August 1994 and December 1998, 28 patients with newly diagnosed GBM underwent surgery, external-beam radiotherapy (EBRT) and HDR STBT. STBT eligibility criteria included unifocal lesions, residual tumor < or = 6 cm in maximum diameter, supratentorial lesions, tumors not crossing the midline, tumors without subependymal spread and Karnofsky performance status (KPS) > 60. STBT was delivered over five consecutive days with two fractions per day for a total median dose of 30 Gy. Twenty-eight STBT eligible GBM patients treated with surgery and EBRT only over the same period were matched controls. RESULTS: Median survival times for the STBT group and controls were 19.5 versus 12.5 months; one and two year survival rates were 89% versus 42% and 61% versus 28%, respectively (p = 0.12). Using multivariate analysis, age, KPS and HDR STBT were significant factors predicting survival. By RPA class, 2-year survival rates for STBT and controls were: III--78% versus 50%; IV--40% versus 0%; V--21% versus 15%, respectively. Corresponding median survival times in months were: 41.6 versus 21.2 (p = 0.39); 16.7 versus 12.1 (p = 0.36); 18.7 versus 10.6 (p = 0.02). No major complications were found in the STBT arm. CONCLUSIONS: Because of small patient numbers, median survival time increases were only statistically significant in the RPA Class V patients, but a strong survival time trend emerged favoring patients undergoing HDR STBT. Further prospective study is warranted to fully assess the merits of this technique for GBM management.
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Hypofractionated intensity-modulated radiotherapy for primary glioblastoma multiforme.
Floyd NS, Woo SY, Teh BS, Prado C, Mai WY, Trask T, Gildenberg PL, Holoye P, Augspurger ME, Carpenter LS, Lu HH, Chiu JK, Grant WH 3rd, Butler EB.
Department of Radiology, Section of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA.
PURPOSE: A pilot study was designed to evaluate the safety and efficacy of a novel regimen of hypofractionated intensity-modulated radiotherapy (RT) in the adjuvant treatment of primary glioblastoma multiforme (GBM). The rationale of the study was to combine the potential radiobiologic advantage of hypofractionation to GBM with a highly conformal radiotherapeutic technique. The study was designed to measure the acute and chronic morbidity of patients treated with this regimen, response of GBM to the treatment, overall survival, and time to disease progression after therapy completion. METHODS AND MATERIALS: Twenty eligible patients were accrued between February 1999 and May 2000 for the study. All patients had Karnofsky performance scores of >/=70. All patients were treated with intensity-modulated RT using the NOMOS Peacock system. A dose of 50 Gy was delivered in 5-Gy daily fractions within 2 weeks to enhancing primary disease, residual tumor, or surgical cavity. Simultaneously, 30 Gy was prescribed in 3-Gy daily fractions to surrounding edema. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicity was graded using Radiation Therapy Oncology Group neurotoxicity scores. RESULTS: Of the 20 patients, 18 were evaluated for outcome. The median time to disease progression was 6 months after RT completion. The median overall survival was 7 months after treatment completion. All recurrences were within 2 cm of the operative bed. Neurotoxicity during therapy was minimal, with all patients experiencing Grade 0 or 1 toxicity. Late toxicity included 10 patients with Grade 0, 2 patients with Grade 2, and 3 patients with Grade 4 toxicity, manifesting as brain necrosis requiring surgical reexcision. The survival of the 3 patients with brain necrosis was 23, 20, and 9 months. Mortality in all cases was the result of tumor recurrence, with no mortality resulting from brain necrosis. CONCLUSION: This regimen of hypofractionated intensity-modulated RT did not improve the time to disease progression or overall survival compared with historical experience using conventional fractionation. However, the treatment duration was reduced from 6 weeks to 2 weeks, which may be of palliative benefit in certain subsets of patients. This treatment regimen demonstrated a greater incidence of brain necrosis requiring surgical intervention; however, the 3 patients experiencing this toxicity had longer survival times. Future investigation may be useful to determine which fraction size may be optimal for GBM when highly conformal RT is used in the adjuvant setting.
-
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Stereotactic radiosurgery versus fractionated stereotactic radiotherapy boost for patients with glioblastoma multiforme.
Cho KH, Hall WA, Lo SS, Dusenbery KE.
Departments of Therapeutic Radiology and Radiation Oncology, Fairview University Medical Center, University of Minnesota, Minneapolis, MN, USA.
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
The aim of this study is to evaluate the efficacy of stereotactic radiotherapy boost (SRB) in patients with glioblastoma multiforme (GBM) by comparing two different regimens, single dose or fractionated treatment. Between December 1994 and January 2000, 24 patients with GBM were treated with SRB in conjunction with external beam radiotherapy (EBRT). Fourteen patients (58%) were treated with stereotactic radiosurgery (SRS) and 10 patients (42%) with fractionated stereotactic radiotherapy (FSRT). Median interval between EBRT and SRS or FSRT was 1.4 months (range -0.4-3.9 months). Actuarial survival rates of the entire 24 patients at one and two years following SRB were 63% and 34% respectively, with median survival time of 16 months. Variables predicting survival were age, extent of surgery, re-operation and the RTOG (Radiation Therapy Oncology Group) classes based on recursive partitioning analysis (RPA). In comparison to historical controls, improved survival benefit after SRB was observed. The median survival times for the RTOG classes 4, 5, and 6 were 28.3, 10.3, and 6.0 months following EBRT+SRB, respectively. Expected values for these classes after EBRT are 11.1, 8.9, and 4.6 months, respectively. This improvement in survival was seen predominantly for the RTOG class 4. There was no difference in survival between SRS and FSRT treated groups. Late complications developed in 4 patients in the SRS group and 1 patients in the FSRT group. Our retrospective data suggest that SRB in conjunction with EBRT may improve survival in patients with GBM with median survival time of 16 months, when compared to historical controls of the RTOG data following EBRT. The addition of SRB appeared to improve the median survival most demonstrably in RTOG RPA class 4 patients. SRS and FSRT are equally effective with similar median survival, but potentially less late complications associated with FSRT. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.
-
-
Fractionated stereotactic radiotherapy in low-grade astrocytomas: long-term outcome and prognostic factors.
Plathow C, Schulz-Ertner D, Thilman C, Zuna I, Lichy M, Weber MA, Schlemmer HP, Wannenmacher M, Debus J.
Division of Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
PURPOSE: To evaluate outcome after fractionated stereotactic radiotherapy (RT) of patients with World Health Organization Grade 2 astrocytoma in terms of progression-free survival, overall survival, toxicity, quality of life, and prognostic factors. METHODS AND MATERIALS: Between 1984 and 2000, 143 patients with histologically proven Grade 2 astrocytoma were treated with fractionated stereotactic RT at our institution. The evaluation of the quality of life and toxicity was based on neurologic examinations and the Karnofsky performance score. Univariate analysis was performed on seven potential prognosticators and multivariate analysis on four prognosticators. RESULTS: The median follow-up was 44 months. The actuarial overall survival and progression-free survival was 58% and 39% at 5 years, respectively. Out-of-field recurrences occurred in 1 patient (1.2%). We did not observe a dose-response relationship. Overall survival and progression-free survival were significantly correlated with the absence of contrast media enhancement before RT (p <0.01). Toxicity was mild and included severe side effects of European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 in only 4 patients (2.8%). The Karnofsky performance score improved in most patients. CONCLUSION: Fractionated stereotactic RT is effective and has low toxicity in the treatment of Grade 2 gliomas. The rate of field border recurrences was not increased compared with after conventional RT. Exceeding the tumor dose did not improve the tumor control rate but did enhance toxicity. Pretherapeutic contrast media enhancement should be interpreted as a sign of higher grade tumor elements.
-
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Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: outcome and prognostic factors.
Chang EL, Yi W, Allen PK, Levin VA, Sawaya RE, Maor MH.
Division of Radiation Oncology, Brain Tumor Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
PURPOSE: To evaluate the outcome for elderly or younger poor prognosis glioblastoma patients treated with hypofractionated radiotherapy (HypoRT). METHODS AND MATERIALS: Retrospective review at The University of Texas M. D. Anderson Cancer Center identified 59 glioblastoma patients (median age 65 years) treated with HypoRT between 1988 and 2001 with 50 Gy given at 2.5 Gy/fraction/day in 20 fractions within 4 weeks. Classification was according to the Radiation Therapy Oncology Group recursive partitioning analysis and was Class IV in 11, V in 29, and VI in 19. Surgery consisted of gross total resection (n = 16), subtotal resection (n = 28), and biopsy only (n = 13). Two patients were treated presumptively on the basis of radiographic findings. Chemotherapy was given either as part of the initial treatment (n = 15) or for progression (n = 9). RESULTS: The median survival time for the entire study population was 7 months, and the median progression-free survival was 3.9 months. The median survival time for patients with Class IV, V, and VI was 11, 7, and 5 months, respectively. Concordance was found with Radiation Therapy Oncology Group-established recursive partitioning analysis class survival. Steroid requirements were not increased during RT compared with preoperatively and immediately postoperatively. Late complications of HypoRT were limited to 3 cases of radiation necrosis suggested by MRI, 2 of which were pathologically confirmed. CONCLUSION: HypoRT consisting of 50 Gy in 4 weeks can be used for selected GBM patients to reduce the overall treatment time of conventional RT by 33-39% without apparent increased toxicity or decrement in survival.
-
-
Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in patients with high-grade gliomas.
Baumert BG, Lutterbach J, Bernays R, Davis JB, Heppner FL.
Radiation-Oncology, University Hospital Zurich, Zurich, Switzerland.
PURPOSE: To determine the value and the toxicity of an additional fractionated stereotactic boost as used in the joint randomized EORTC-22972/MRC-BR10 study in patients with malignant gliomas. MATERIALS AND METHODS: Seventeen patients (11 male, six female) with a high-grade glioma (two WHO III, 15 WHO IV) < or =4 cm in maximum diameter, with a good performance status (WHO > or =2), were treated with a fractionated stereotactic radiotherapy (SRT) boost to 20 Gy in four fractions following partial brain irradiation to a dose of 60 Gy in 30 fractions. This patient group was compared with historical data in a matched-pair analysis. RESULTS: All patients were treated by conventional radiotherapy and a SRT boost (15 patients received 20 Gy and two patients 10 Gy). Acute side effects included fatigue (two), impairment of short-term memory (one) and worsening of pre-existing symptoms (one). No patient developed steroid dependence after SRT. One patient was re-operated for radiation necrosis. At a median follow-up of 25 months (9-50 months) 14 patients recurred locally. Survival was 77% at 1 year and 42% at 2 years; progression-free survival was 70% at 1 year and 35% at 2 years for all patients, respectively. Median survival for the whole patient group is 20 months. Comparison with a matched historical group showed a significantly better survival for the group treated with a stereotactic boost (P<0.0001). CONCLUSION: A fractionated stereotactic boost after standard external beam radiotherapy in selected patients with high-grade glioma is feasible and well tolerated with low toxicity. Compared to historical data survival is significantly better with an additional SRT boost. However, its effectiveness has to be proven in a randomized trial.
-
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Survival and prognostic factors of patients with unresectable glioblastoma multiforme.
Fazeny-Dorner B, Wenzel C, Veitl M, Piribauer M, Rossler K, Dieckmann K, Ungersbock K, Marosi C.
Ludwig Boltzmann Institute for Clinical Experimental Oncology, Department of Medicine I, University of Vienna, Wien, Australia.
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
The aim of this study was to assess survival and prognostic factors of 98 consecutive patients with unresectable glioblastoma multiforme (GBM) after stereotactic biopsy. Patients were diagnosed between 1993 and 1998, and the treatment modality subsequent to stereotactic biopsy was determined by the year of diagnosis. Before 1995, patients did not receive further specific therapy after stereotactic biopsy (n=36). In 1996, patients were administered radiotherapy starting within 6 weeks after stereotactic biopsy (n=24). >From 1997 to 1998, patients received combined radio-/chemotherapy (RCT; CCNU orally) starting within 2 weeks after stereotactic biopsy (n=38). Patients' age ranged from 21 to 84 (median 64) years and their median Karnofsky performance score 2 weeks after stereotactic biopsy was 80 (range 60-100). Survival and prognostic factors were analyzed with respect to administered treatment modalities (without specific therapy versus radiotherapy versus combined RCT), with respect to age (>or<or=50 years), gender, Karnofsky performance score (>or=or<80), tumor location (frontal, parieto-temporal, central, occipital) and tumor size (>or<or=5 cm; tumor multiplicity was considered as diameter >5 cm) by the Kaplan-Meier method, by log-rank test and multivariate Cox regression analysis. Post-biopsy treatment modality was the strongest predictor for survival. Median (range) survival was 9 (3-47) weeks in those without specific therapy, 13 (5-54) weeks in patients receiving radiotherapy and 31 (11-101) weeks in patients receiving combined RCT (p<or=0.001). Age<or=50 years (p<or=0.05) in addition to tumor size in multivariate Cox analysis were found to be of significant influence onto survival, too. Combined RCT could be performed on a complete outpatient basis. Toxicity consisted of mild asymptomatic thrombocytopenia. We conclude that the administration of combined RCT within a minimum interval after stereotactic biopsy yielded a significant increase in survival. Patients' acceptance was excellent. These results encourage us to treat even patients with unresectable GBM with combined RCT.
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Stereotactic radiosurgery in the management of intracranial gliomas.
Roberge D, Souhami L.
Division of Radiation Oncology, McGill University, Montreal General Hospital, 1650 Cedar Ave., Montreal, QC, Canada H3G 1A4.
Glial neoplasms are the most common primary intracranial malignancies. Treatment of high-grade gliomas has been frustrating, with less than 5% of patients surviving 5 years after a diagnosis of glioblastoma multiforme (GBM). Stereotactic radiosurgery (SRS) and fractionated strereotactic radiotherapy (F-SRT) provide means to either escalate the dose in primary treatment or to palliate recurrences. Because of their lower alpha/beta ratios and more focal nature, low-grade gliomas (LGG) are more attractive targets for stereotactically focused radiation. Results of available phase I-II data are reviewed for both low and high-grade gliomas. In the case of high-grade gliomas disappointing preliminary phase III data from RTOG 93-05 are discussed. Toxicity of SRS is discussed. Acute treatment toxicity of significance is unusual and generally self-limited. Occasionally an exacerbation of existing symptoms occurs. Late complications attributable to SRS are usually defined as necrosis within the treatment volume. The rate of necrosis can be hard to define in high-grade gliomas as tumor cells are often present in surgical specimens. New strategies in the application of stereotactic radiation are touched upon, these include: changes in planning and fractionation, concurrent use of chemotherapy, use of radiation modifiers and biologic agents. After reviewing the current data for high-grade gliomas, it appears that any apparent improvement in outcome seen in phase I-II trials is attributable to patient selection. The best evidence available does not support the use of SRS for primary high-grade gliomas. The somewhat limited experience in LGG also indicates a lack of benefit for patients treated with stereotactic radiosurgery or F-SRT. For a very select group of patients with small recurrent lesions, F-SRT may represent a safe, reasonable treatment.
-
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High-dose-rate stereotactic brachytherapy for patients with newly diagnosed glioblastoma multiformes.
Chang CN, Chen WC, Wei KC, Ng SH, Ho YS, Huang DY, Lee SP, Hong JH.
Department of Neurosurgery, Chang Gung Memorial Hospital, LinKou, Taiwan, ROC.
PURPOSE: To evaluate high-dose-rate (HDR) stereotactic brachytherapy (STBT) for glioblastoma multiforme (GBM). MATERIALS AND METHODS: Between August 1994 and December 1998, 28 patients with newly diagnosed GBM underwent surgery, external-beam radiotherapy (EBRT) and HDR STBT. STBT eligibility criteria included unifocal lesions, residual tumor < or = 6 cm in maximum diameter, supratentorial lesions, tumors not crossing the midline, tumors without subependymal spread and Karnofsky performance status (KPS) > 60. STBT was delivered over five consecutive days with two fractions per day for a total median dose of 30 Gy. Twenty-eight STBT eligible GBM patients treated with surgery and EBRT only over the same period were matched controls. RESULTS: Median survival times for the STBT group and controls were 19.5 versus 12.5 months; one and two year survival rates were 89% versus 42% and 61% versus 28%, respectively (p = 0.12). Using multivariate analysis, age, KPS and HDR STBT were significant factors predicting survival. By RPA class, 2-year survival rates for STBT and controls were: III--78% versus 50%; IV--40% versus 0%; V--21% versus 15%, respectively. Corresponding median survival times in months were: 41.6 versus 21.2 (p = 0.39); 16.7 versus 12.1 (p = 0.36); 18.7 versus 10.6 (p = 0.02). No major complications were found in the STBT arm. CONCLUSIONS: Because of small patient numbers, median survival time increases were only statistically significant in the RPA Class V patients, but a strong survival time trend emerged favoring patients undergoing HDR STBT. Further prospective study is warranted to fully assess the merits of this technique for GBM management.
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