Reappraisal of clinical outcome in adult medulloblastomas with emphasis on patterns of relapse.

BACKGROUND: Clinical outcome and prognostic factors were assessed in adult medulloblastoma patients, with emphasis on patterns of relapse. PATIENTS AND METHODS: Records of 36 consecutive adult patients with medulloblastoma were reviewed. Patients were classified into 2 prognostic groups according to the extent of disease and quality of surgical excision based on the early postoperative magnetic resonance imaging (MRI) findings. Standard-risk (SR) patients (n = 11) received postoperative craniospinal radiation therapy (RT) only, 36 Gy, 1.8 Gy per daily fraction, with a 18 Gy boost to the posterior cerebral fossa (PCF). High-risk (HR) patients (n = 25) received additional adjuvant chemotherapy. RESULTS: With a median follow-up of 46 months (range 5-155), 19 patients experienced tumour relapse. Sites of relapse(s) included tumour bed in 6 patients, resulting in a PCF control of 83.4%. Three-year overall survival (OS) and progression-free survival (PFS) were 67.3% and 57.4%, respectively. The comparison of the HR and SR populations demonstrated significant differences in OS (p = 0.005) and PFS (p = 0.001). Quality of surgical excision and extent of disease beyond the PCF were predictive factors for OS (p = 0.04, p = 0.001, respectively) and PFS (p = 0.004, and p = 0.02, respectively). CONCLUSION: The quality of resection was a significant prognostic factor, suggesting that surgery should be as extensive as possible. Systematic postoperative MRI allowed accurate selection of SR patients for whom RT alone was enough to obtain high local control. Every effort should be made to avoid RT disruption. Increased delay led to worse outcome.

Linac stereotactic radiosurgery: an effective and safe treatment for elderly patients with brain metastases.

PURPOSE: To evaluate the outcomes of radiosurgery for brain metastases in patients 65 years or older. PATIENTS AND METHODS: Between January 1994 and January 2003, 117 patients (47 women, 70 men), median age 71 years (range, 65-86 years), received radiosurgery for 227 metastases. Sixty-one patients (55%) presented symptoms in relation to the brain metastases. Thirty-eight patients (32%) received whole-brain radiotherapy. Median metastasis diameter and volume were 21 mm (range, 0.5-75 mm) and 1.7 cc (range, 0.02-71 cc), respectively. RESULTS: Median follow-up was 7 months (range, 1-45 months), 9.5 months for alive patients (range, 1-45 months). Median minimum and maximum doses were 14.5 Gy (6.5 Gy, 19.5 Gy), and 20.4 Gy (13.2 Gy, 41.9 Gy), respectively. Median survival was 8 months from the date of radiosurgery. Overall survival rates at 6 and 24 months were 58% +/- 5% and 13% +/- 4%, respectively. According to multivariate analysis, a low Karnofsky performance status was an independent unfavorable prognostic factor for overall survival (p = 0.003; odds ratio [OR] = 0.28; 95% confidence interval [CI], 0.14-0.56). Median brain disease-free survival was 10 months. Brain disease-free survival rates at 6 and 24 months were 67% +/- 6% and 40% +/- 7%, respectively. According to multivariate analysis, a radiosensitive lesion was an independent favorable factor (p = 0.038; OR = 0.42; 95% CI, 0.18-0.95); more than two metastases and a low Karnofsky performance status were independent unfavorable factors for brain disease-free survival (p = 0.046; OR = 2.15; 95% CI, 1.01-4.58 and p = 0.003; OR = 30.4; 95% CI, 3.1-296, respectively). Local control rates were 98% +/- 2% and 91% +/- 8.5% at 6 and 24 months. Out of the 61 patients presenting symptoms before radiosurgery, complete symptomatic response was achieved in 12 patients (20%), partial improvement in 25 (41%), stabilization in 7 (11%), and worsening in 4 (6%) related to a progression of the irradiated metastasis. Seven cases of radionecrosis were described and were related to the margin dose (p = 0.03). CONCLUSION: Radiosurgery for elderly patients was effective and safe. Age alone should not be a criterion for denying radiosurgery to any patient with brain metastases.

Brachytherapy of glioblastoma recurring in previously irradiated territory: predictive value of tumor volume.

PURPOSE: To evaluate the impact of tumor volume on survival of patients reirradiated with (192)Ir for recurrent glioblastoma. METHODS AND MATERIALS: Between 1993 and 1997, 42 patients with recurrent glioblastomas (29 males and 13 females, age 18-69 years, median age 49) were treated with (192)Ir implantation. Previous treatments included surgery, external beam radiotherapy, and chemotherapy. Maximum diameter of the recurrent tumor was 1.2-10.1 cm (median: 5.7 cm) and tumor volume was 1.6-122 cm(3) (median: 23 cm(3)). Karnofsky performance status score was 50-100 (median: 80). Brachytherapy dose was 40-60 Gy. RESULTS: Probability of overall survival was 80% at 6 months, 48% at 1 year, and 11% at 2 years. Median survival was 50 weeks. Univariate analysis showed that both tumor volume (T < or T > or = 30 cm(3)) and Karnofsky performance status score were significant predictors of survival. Multivariate analysis showed that smaller tumor volumes were associated with a higher probability of survival (p < 0.001). CONCLUSION: Tumor volume less than 30 cm(3) was associated with a higher probability of, and quality of, survival than larger lesions for patients reirradiated by brachytherapy for recurrent glioblastoma.

Radiosurgery for brain metastasis: impact of CTV on local control.

PURPOSE: The purpose of the present analysis was to assess whether adding a 1 mm margin to the gross tumour volume (GTV) improves the control rate of brain metastasis treated with radiosurgery (RS). PATIENTS AND METHODS: All the patients had one or two brain metastases, 30 mm or less in diameter, and only one isocentre was used for RS. There were 23 females and 38 males. The median age was 54 years (34-76). The median Karnofsky performance status was 80 (60-100). At the time of RS, 23 patients had no evidence of extracranial disease and 38 had a progressive systemic disease. Thirty-eight patients were treated up-front with only RS. Twenty-three patients were treated for relapse or progression more than 2 months after whole brain radiotherapy. From January 1994 to July 1995, clinical target volume (CTV) was equal to GTV without any margin (33 metastases). From August 1995 to August 2000, CTV was defined as GTV plus a 1 mm margin (45 metastases). A dose of 20Gy was prescribed to the isocentre and 14Gy at the margin of CTV. RESULTS: The median follow-up was 10.5 months (1-45). The mean minimum dose delivered to GTV was 14.6Gy in the group without a margin and 16.8Gy in the group with a 1 mm margin (P<0.0001). The response of 11 metastases was never assessed because patients died before the first follow-up. Ten metastases recurred, eight in the group treated without a margin and two in the group treated with a 1 mm margin (P=0.01). Two-year local control rates were 50.7+/-12.7% and 89.7+/-7.4% (P=0.008), respectively. Univariate analysis showed that the treatment group (P=0.008) and the tumour volume (P=0.009) were prognostic factors for local control. In multivariate analysis, only the treatment group with a 1 mm margin was an independent prognostic factor for local control (P=0.04, RR: 5.8, 95% CI [1.08-31.13]). There were no significant differences, either in overall survival rate or in early and late side effects, between the two groups. CONCLUSION: Adding a 1 mm margin to the GTV in patients treated with RS significantly improves the probability of metastasis control without increasing the side effects.

Three irradiation treatment options including radiosurgery for brain metastases from primary lung cancer.

PURPOSE: To determine local control and survival rates in 92 patients with 145 brain metastases treated with three options of radiotherapy including stereotactic radiosurgery (SR). METHODS: Between July 1994 and August 2002, 92 consecutive patients with 145 metastases were treated with a SR, 34 with initially SR alone, 22 initially with an association of whole-brain radiotherapy (WBRT) and 36 with SR alone for recurrent new brain metastasis after WBRT. At time of treatment, extracranial disease was controlled in 46 (50%) and uncontrolled in 46 (50%). Pathologies were adenocarcinoma in 54 cases (59%), squamous cell carcinoma in 14 cases (15%), small cell carcinoma in 10 cases (11%) and miscellaneous in 14 cases (15%). All patients underwent only one treatment fraction for 1 or 2 metastases in 73 cases (83%) and for more than 2 metastases for the others. RESULTS: The characteristics of patients and metastases in the group treated initially with SR alone and in the group treated initially with WBRT+SR were comparable. Median follow-up was 29 months (18-36). Overall, the median and the 1- and 2-year rates of overall survival were, respectively, 9 months, 37 and 20%. A controlled extracranial disease, a high Karnofsky index and a low number of metastasis were independent prognostic factor of overall survival, respectively, HR 0.53 (95% CI 0.31-0.90, P=0.01), HR 0.95 (95% CI 0.92-0.97, P=0.0002), and HR 0.48 (95% CI 0.25-0.90, P=0.02). Thirteen metastases were not controlled (9%). Six-month and 1-year local control rate were, respectively, 93 and 86%. High delivered dose was an independent prognostic factor of local control, HR 0.41 (95% CI 0.18-0.95, P=0.03). A controlled extracranial disease was favourable independent prognostic factor of brain free-disease free survival, HR 0.47 (95% CI 0.2-0.98, P=0.04). Although there was a trend of a better local control, overall and brain disease free survivals rates in the WBRT+SR group compared to SR alone one, the difference were not statistically different. CONCLUSION: Local control and survival rates are acceptable for a palliative treatment for the three option of treatment. In this series, the number of patients is not enough great to conclude to the necessity of the association of WBRT to SR. Re-irradiation is a safe treatment after new metastases appeared in previously irradiated area.

LINAC radiosurgery for brain metastasis of renal cell carcinoma.

The purpose of the study was to evaluate the efficacy and toxicity of stereotactic radiotherapy in the treatment of the brain metastasis of renal cell carcinoma. From 1994 to 2001, 28 patients presenting with 65 metastases of renal cell cancer were treated by radiosurgery. Median age was 55 years (35-75), and median Karnofski performance status ranges between 50 and 100. Seven patients had received whole brain radiotherapy (WBRT) before radiosurgery. Twelve patients were treated by radiosurgery for 1 metastasis, 5 patients for two metastases and 6 for three, and 5 for more than three metastases. One procedure was performed in 22 patients and, 2 or 3 procedures for 6 patients. Median metastasis diameter was 19 mm (5-55 mm). Median metastasis volume was 1.28 cc (0.02-28 cc). Irradiation was delivered by linear accelerator. Median minimal dose (on the 70% isodose) was 14.7 Gy (10.8 Gy, 19.5 Gy), median maximal dose (at the isocenter) 20.5 Gy (14.3 Gy, 39.6 Gy). Median follow-up was 14 months (1-33). Two metastases progressed (3%), 2 and 12 months after radiosurgery. Overall, crude local control rate was 97% and 3-, 6- and 12-month local control rates were 98% +/- 2%, 98% +/- 2%, and 93% +/- 5%, respectively. In univariate analysis, no prognostic factor of local control was retrieved. Median brain disease-free survival was 25 months after RS. the 3-, 6- and 12-month distant brain control rates were 91% +/- 4%, 91% +/- 4%, and 70% +/- 12%, respectively. Median survival duration was 11 months. The 3-, 6-, 12- and 24-month overall survival rates were 82% +/- 7%, 67% +/- 9%, 48% +/- 10%, and 33% +/- 10%, respectively. According to univariate analysis, only site of metastasis was overall survival prognostic factor. Radiosurgery for brain metastasis of renal cell carcinoma is an effective and accurate treatment. The use of radiosurgery alone is an appropriate management strategy for many patients with brain metastasis of renal cell carcinoma. Radiosurgery is efficient even after development of new metastasis appearing after WBRT.

[Stereotaxic irradiation of brain metastasis in elderly patients]. / Irradiation en conditions stéréotaxiques des métastases cérébrales chez les patients âgés.

AIMS: Analysis of results of stereotactic irradiation for brain metastases for patients older than 70 years. PATIENTS AND METHODS: From January 1994 to January 2002, 53 patients received stereotactic irradiation for a total of 105 brain metastases. There were 26 females and 27 males. Median age was 73 years (70-86). Median interval between cancer diagnosis and brain metastases was 18 months (0-216). Metastases were diagnosed after development of related clinical symptoms in 34 patients (64.1%). Patients were irradiated for one to 6 metastases. Twenty-nine patients (54.7%) were treated for only one metastasis. Median metastasis diameter and volume were respectively 24 mm (5-74.9 mm) and 2.1 cc (0.02-71.3). Eighty-three metastases were supratentorial (79%), and 22 subtentorial (21%). Forty-five underwent only one procedure (85%) and 8 patients underwent a second procedure for one or several new metastases. Three patients were irradiated with whole brain radiotherapy (WBRT) concomitantly of radiosurgery and three patients received WBRT after radiosurgery for development of more than four metastases or for carcinomatous meningitis. RESULTS: The median follow-up was 8 months (1-33). Median minimum and maximum doses delivered to the metastases were respectively, 16.42 Gy (6.5-20.5) and 20.36 Gy (13.2-41.9). The median overall survival duration was 9 months. Three-, 6-, 12- and 18-month overall survival rates were respectively, 85.6% +/- 5, 65.2% +/- 7.1, 35.5% +/- 7.8 and 26.6% +/- 8. According to unifactorial analysis, two prognostic factors of overall survival were retrieved, extra-cranial disease status and RPAa (Recursive Partitioning Analysis for aged patients) separated in three classes including Karnofsky index performance status and extra-cranial disease status, respectively p = 0.043 et p = 0.016. According to multifactorial analysis only RPAa was an independent prognostic factor of overall survival (p = 0.019, RR: 0.89, 95% confidence interval [0.017-0.47]). Median brain disease-free survival was 12 months. Three-, 6-, 12- and 18-month free-brain disease survival rates were, 81.5% +/- 6.4, 68.7% +/- 8, 47.2% +/- 9.9 and 35.4% +/- 12.6, respectively. No prognostic factor of free-brain disease survival was retrieved. Crude local control rate was 97%. Only three metastases relapsed. Six and 12-month local control rates were 98.6% +/- 1.4 and 88.5% +/- 7.6. Among 34 patients with initial clinical symptoms, one patient presented an aggravation, 9 improved up to complete response (26.5%), 13 patients presented a partial remission (38.2%) and 5 were stabilized (14.7%). For 6 patients, data were not available. We observed 3 radionecroses and 1 hemorrhage of the metastases. CONCLUSION: Radiosurgery in the elderly was efficient and well tolerated. Age alone should not be used to deny potentially beneficial radiosurgery to any patient with brain metastases.

Linac radiosurgery for brain metastasis of melanoma.

PURPOSE: To evaluate the efficacy and toxicity of stereotactic radiotherapy in the treatment of brain metastases of melanoma. PATIENTS AND METHODS: From 1994 to 2001, 25 patients presenting with 61 metastases of cutaneous melanoma were treated with radiosurgery. Median age was 47 years (range: 25-73 years) and median Karnofski performance status 80 (range: 50-100). Twenty patients had one radiosurgery, 5 had two or three. Median metastasis diameter was 21 mm (range: 6-54.4 mm), and median metastasis volume was 1.7 cm(3) (range: 0.4-25.6 cm(3)). Irradiation was delivered by a linear accelerator. Median minimal dose was 14.1 Gy (range: 10-19.4 Gy), and median maximal dose was 20.5 Gy (range: 16-48 Gy). RESULTS: Mean follow-up was 12.6 months (range: 1-85 months). Five metastases progressed (9.8%), 2-12 months after radiosurgery. Three-, 6- and 12-month local control rates were 95 +/- 3, 90 +/- 5 and 84 +/- 7%, respectively. By univariate analysis, only absence of extracranial tumor was a prognostic factor of local control. Three-, 6- and 12-month brain-disease-free survival rates were 75 +/- 9, 68 +/- 11 and 38 +/- 13%, respectively. According to univariate analysis, only the Score Index for Radiosurgery in brain metastases (SIR) was a prognostic factor of brain-event-free survival (p = 0.03). Median survival was 8 months. Three-, 6- and 12-month overall survival rates were 75 +/- 9, 53 +/- 10, and 29 +/- 10%, respectively. According to univariate analysis, extracranial controlled disease status (p = 0.03), and SIR (p = 0.04) were prognostic factors for overall survival. According to multivariate analysis, none was an independent prognosticator for overall survival. Complications were minimal. CONCLUSION: Radiosurgical treatment of brain metastases of melanoma is effective and accurate. The use of radiosurgery alone is an appropriate management strategy for many patients with brain metastases of melanoma.