A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

BACKGROUND: This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. METHODS: One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). RESULTS: On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). CONCLUSION: In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

A New Scoring Tool to Assess Overall Survival in Patients With Intracerebral Metastases From Gynecological Cancers.

OBJECTIVE: This study aimed to facilitate individualized treatment strategies for intracerebral metastases from gynecological cancers by creating a specific overall survival (OS) score. METHODS/MATERIALS: Fifty-six patients irradiated for cerebral metastases from gynecological cancers were included. Eleven factors were retrospectively analyzed for OS: age, Eastern Cooperative Oncology Group (ECOG) performance score, cancer type, histology, histologic grading, initial stage, number of lesions, extracerebral metastases, time between cancer diagnosis and brain metastases treatment, recursive partitioning analysis class, and type of treatment. Independent predictors of OS were incorporated in the score (better OS, 1 point; worse OS, 0 points). RESULTS: On Cox proportional hazards analysis, performance score (hazards ratio, 1.98; 95% confidence interval, 1.30-3.23; P = 0.001), no extracerebral metastases (3.34; 1.46-8.96; P = 0.003), and recursive partitioning analysis class 1 (3.27; 1.97-5.65; P < 0.001) were significant. The following points were assigned: ECOG score 1 to 2 = 1 point, ECOG score 3 to 4 = 0 points, no extracerebral metastases = 1 point, extracerebral metastases = 0 points. Sum scores were 0 (n = 32), 1 (n = 15), or 2 points (n = 9). Six-month OS rates were 6%, 67%, and 100%, respectively (P < 0.001). CONCLUSIONS: A predictive tool including 3 groups with significantly different OS probabilities was designed for patients with cerebral metastases from gynecological cancers. This tool will aid in choosing individual treatments.

A predictive tool particularly designed for elderly myeloma patients presenting with spinal cord compression.

BACKGROUND: This study was performed to design a predictive tool that allows the estimation of overall survival (OS) of elderly myeloma patients (aged ≥ 65 years) presenting with myeloma-induced spinal cord compression (SCC). METHODS: One-hundred-and-sixteen patients irradiated for motor deficits of the legs due to myeloma-induced spinal cord compression were retrospectively evaluated. Ten characteristics were analyzed for OS including age, interval between myeloma diagnosis and radiotherapy, other osseous myeloma lesions, myeloma type, gender, time developing motor deficits, number of affected vertebrae, ECOG-PS, pre-radiotherapy ambulatory status, and fractionation regimen. Characteristics that achieved significance on multivariate analysis were included in the predictive tool. The score for each characteristic was obtained from the 1-year OS rate divided by 10. The sum of these scores represented the prognostic score for each patient. RESULTS: On multivariate analysis, myeloma type (hazard ratio 3.31; 95%-confidence interval 1.75-6.49; p < 0.001), ECOG-PS (HR 5.33; 95%-CI 2.67-11.11; p < 0.001), ambulatory status (HR 2.71; 95% CI 1.65-4.57; p < 0.001), and age (HR 1.95; 95% CI 1.03-3.78; p = 0.040) were significantly associated with survival. Sum scores ranged from 18 to 32 points. Based on the sum scores, three prognostic groups were designed: 18-19, 21-28 and 29-32 points. The corresponding 1-year survival rates were 0, 43 and 96%, respectively (p < 0.001). CONCLUSIONS: This new predictive tool has been specifically designed for elderly myeloma patients with SCC. It allows estimating the survival prognosis of this patient group and supports the treating physicians when looking for the optimal treatment approach for an individual patient.

Metastatic spinal cord compression: a validated survival score for elderly patients.

BACKGROUND AND PURPOSE: This study aimed to develop a validated survival score for elderly patients with metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: In all, 1,128 patients were randomly assigned to the test (n = 564) or validation group (n = 564). In the test group, ten pretreatment factors (age, gender, performance status, primary tumor, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time to developing motor deficits) plus the radiation regimen were retrospectively evaluated. Factors significantly associated with survival on multivariate analysis were included in the survival score. The score for each factor was determined by dividing the 6-month survival rate (%) by 10. The prognostic score represented the sum of the scores for each factor. RESULTS: In the multivariate analysis of the test group, age, performance status, primary tumor type, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and time to developing motor deficits were significantly associated with survival. Total scores ranged from 25 to 57 points. In the test group, 6-month survival rates were 11 % for 25-39 points, 56 % for 40-48 points, and 97 % for 49-57 points (p < 0.001). In the validation group, 6-month survival rates were 10, 53, and 94 %, respectively (p < 0.001). CONCLUSION: Based on the survival scores of the test group, three prognostic groups were identified. The survival rates of the validation group were similar to the test group. This score appears reproducible and can help select the appropriate treatment for elderly patients with MSCC.

Single brain metastasis: radiosurgery alone compared with radiosurgery plus up-front whole-brain radiotherapy.

BACKGROUND: Neurosurgical resection is considered the standard treatment for most patients with a single brain metastasis. However, radiosurgery (RS) is a reasonable alternative. It was demonstrated that whole-brain radiotherapy (WBRT) in addition to RS improves local control of 1-3 brain metastases. Little information is available regarding WBRT in addition to RS for a single lesion. METHODS: Data of 63 patients who received RS alone for a single brain metastasis were retrospectively compared with 39 patients treated with WBRT+RS for local control of the treated metastasis, distant intracerebral control, and survival. Seven additional potential prognostic factors were investigated including age, sex, Karnofsky performance score, tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. RESULTS: The 1-year local control rates were 49% after RS and 77% after WBRT+RS (P = .040). The 1-year distant control rates were 70% and 90%, respectively (P = .08). The 1-year survival rates were 57% and 61%, respectively (P = .47). On multivariate analysis, improved local control was associated with WBRT+RS (risk ratio [RR], 1.95; P = .033) and interval from tumor diagnosis to irradiation >15 months (RR, 1.88; P = .042). Improved distant control was almost associated with WBRT+RS (RR, 2.24; P = .05) and age (RR, 2.20; P = .05). Improved survival was associated with KPS 90-100 (RR, 1.73; P = .040), no extracerebral metastases (RR, 1.88; P = .013), RPA class 1 (RR, 2.06; P = .005), and interval from tumor diagnosis to irradiation >15 months (RR, 1.98; P = .009). CONCLUSION: The addition of WBRT to RS was associated with improved local control and distant intracerebral control but not survival.

Single brain metastasis: whole-brain irradiation plus either radiosurgery or neurosurgical resection.

BACKGROUND: The current study was conducted to compare neurosurgical resection (NR) followed by whole-brain irradiation (WBI) (NR + WBI) with WBI followed by radiosurgery (WBI + RS) in patients with a single brain metastasis. METHODS: The outcome of 41 patients treated with WBI + RS was retrospectively compared with 111 patients who received NR ;+ WBI with respect to local control of the treated metastasis and survival. Eleven additional potential prognostic factors were investigated, including WBI schedule, patient age, patient gender, Karnofsky performance score (KPS), primary tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, interval between the first diagnosis of cancer to the treatment of brain metastasis, metastatic site, maximum diameter of the metastasis, and graded prognostic assessment (GPA) score. RESULTS: The 1-year local control rates were 87% after WBI + RS and 56% after NR + WBI (P = .001). Using the Cox proportional hazards model, the treatment regimen remained significant (risk ratio [RR], 2.46; 95% confidence interval [95% CI], 1.29-5.17 [P = .005]). On the multivariate analysis, local control was also found to be associated with the maximum diameter of the metastasis. The 1-year survival rates were 61% after WBI + RS and 53% after NR + WBI (P = .16). Acute and late toxicities were similar in both groups. On the multivariate analysis, KPS, extracerebral metastases, RPA class, and the GPA score were found to be independent predictors of survival. CONCLUSIONS: The use of WBI + RS resulted in significantly better local control of the treated metastasis than NR + WBI. Survival was not found to be significantly different in either group. Because WBI + RS is less invasive than NR + WBI, it appears to be preferable for many patients with a single brain metastasis. These results should be confirmed in a randomized trial.

A validated survival score for patients with metastatic spinal cord compression from non-small cell lung cancer.

BACKGROUND: This multicenter study aimed to create and validate a scoring system for survival of patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC). METHODS: The entire cohort of 356 patients was divided in a test group (N = 178) and a validation group (N = 178). In the test group, nine pre-treatment factors including age, gender, Eastern Cooperative Oncology Group performance status (ECOG-PS), number of involved vertebrae, pre-radiotherapy ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and the time developing motor were retrospectively analyzed. RESULTS: On multivariate analysis, survival was significantly associated with ECOG-PS, pre-radiotherapy ambulatory status, visceral metastases, and the time developing motor deficits. These factors were included in the scoring system; the score for each factor was determined by dividing the 6-month survival rate (in %) by 10. The risk score represented the sum of the scores for each factor. According to the risk scores, which ranged from 6 to 19 points, three prognostic groups were designed. The 6-month survival rates were 6% for 6-10 points, 29% for 11-15 points, and 78% for 16-19 points (p < 0.001). In the validation group, the 6-month survival rates were 4%, 24%, and 76%, respectively (p < 0.001). CONCLUSIONS: Since the survival rates of the validation group were similar to those of the test group, this score can be considered reproducible. The scoring system can help when selecting the individual treatment for patients with MSCC from NSCLC. A prospective confirmatory study is warranted.

Identifying patients with malignant spinal cord compression (MSCC) near end of life who can benefit from palliative radiotherapy.

BACKGROUND: A previous score predicted death ≤ 2 months following radiotherapy for MSCC. For patients with a high probability of early death, best supportive care was recommended. However, some of these patients may benefit from radiotherapy regarding preservation or improvement of motor function. To identify these patients, an additional score was developed. METHODS: Pre-treatment factors plus radiotherapy regimen were retrospectively evaluated for successful treatment (improved motor function or remaining ambulatory without aid) and post-treatment ambulatory status in 545 patients who died ≤ 2 months. Factors included age, interval from tumor diagnosis until MSCC, visceral metastases, further bone metastases, primary tumor type, sex, time developing motor deficits, pre-treatment ambulatory status, and number of affected vertebrae. Factors significant on both multivariable analyses were included in the score (worse outcomes 0 points, better outcomes 1 point). RESULTS: On multivariable analyses, myeloma/lymphoma, time developing motor deficits > 14 days, and pre-treatment ambulatory status were significantly associated with both successful treatment and ambulatory status, affection of 1-2 vertebrae with successful treatment only. On univariable analyses, 1 × 8 and 5 × 4 Gy were not inferior to 5 × 5 Gy and longer-course regimens. Considering the three factors significant for both endpoints, three groups were designed (0, 1, 2-3 points) with treatment success rates of 4%, 15% and 39%, respectively (p < 0.0001), and post-treatment ambulatory rates of 4%, 43% and 86%, respectively (p < 0.0001). CONCLUSION: This score helps identify patients with MSCC who appear to benefit from palliative radiotherapy in terms of improved motor function or remaining ambulatory in spite of being near end of life.

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis.

BACKGROUND: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. METHODS: Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA) class. RESULTS: Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038), KPS ≥70 (p < 0.001), only 1-3 brain metastases (p = 0.007), no extracerebral metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved survival. Local control rates at 6 and 12 months were 37% and 15%, respectively. In the multivariate analyses, KPS ≥70 (p < 0.001), only 1-3 brain metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved local control. In RPA class 3 patients, survival rates at 6 months were 10% (35 of 39 patients) after 10 × 3 Gy and 9% (2 of 23 patients) after greater doses, respectively (p = 0.98). CONCLUSIONS: Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

Prognostic factors for survival and intracerebral control after irradiation for brain metastases from gynecological cancer.

OBJECTIVE: The most appropriate treatment for the individual patient with brain metastases from gynecological cancer is unclear. Most of these patients receive whole-brain radiotherapy (WBRT) alone. Prognostic factors predicting the outcomes of these patients may guide the physician to select the appropriate treatment regimen for the individual patient. METHODS: The data of 42 patients with brain metastases from gynecological cancer treated with WBRT alone were retrospectively analyzed. Six potential prognostic factors were evaluated for survival and intracerebral control including WBRT regimen, age, Karnofsky performance score (KPS), primary tumor type, number of brain metastases, and extracranial metastases at the time of WBRT. RESULTS: On univariate analysis, improved survival was associated with KPS > or = 70 (P<0.001), <4 brain metastases (P=0.033), and lack of extracranial metastases (P=0.008). On multivariate analysis, KPS maintained significance (P<0.001). On univariate analysis, improved intracerebral control was associated with KPS > or = 70 (P=0.003). KPS was also significant in the multivariate analysis (P=0.007). CONCLUSIONS: KPS was the most important predictor for both survival and intracerebral control. For patients with a KPS <70, a short-course of WBRT appears appropriate. For patients with a KPS > or = 70, more aggressive treatment regimens including longer courses of WBRT, resection or radiosurgery should be seriously considered.

Predictors of Outcomes and a Scoring System for Estimating Survival in Patients Treated With Radiotherapy for Metastatic Spinal Cord Compression From Small-Cell Lung Cancer.

PURPOSE: To identify prognostic factors and create a survival score to facilitate individualized care of patients with metastatic spinal cord compression (MSCC) from small-cell lung cancer (SCLC). PATIENTS AND METHODS: Radiation regimen plus 9 factors were retrospectively evaluated in 120 patients irradiated for MSCC from SCLC for overall response, improvement of motor deficits, postradiotherapy ambulatory status, local control of MSCC, and overall survival (OS). Factors included age, interval diagnosis of SCLC to radiotherapy (RT) of MSCC, visceral metastases, further bone metastases, gender, time developing motor deficits, pre-RT ambulatory status, number of affected vertebrae, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Improvement of motor deficits showed significant associations with ECOG PS 1-2 (P = .018); time developing motor deficits achieved borderline significance (P = .059). Post-RT ambulatory status was significantly associated with slower development of motor dysfunction (P = .003), ambulatory status (P < .001), and ECOG PS 1-2 (P < .001). No factor was significantly associated with overall response and local control. On multivariate analysis, OS was significantly associated with interval from SCLC diagnosis to RT of MSCC (P = .004), visceral metastases (P < .001), ambulatory status (P = .002), and ECOG PS (P = .002). For the survival score, 6-month OS rates related to each of these factors were divided by 10. Patient scores were obtained by adding these factors' scores. Three groups were defined (5, 7-13, and 15-17 points) with 6-month OS rates of 0, 18%, and 77%, respectively (P < .001). CONCLUSION: Predictors of various outcomes were identified and a survival score was created that can support physicians aiming to create personalized treatments to patients with MSCC from SCLC.

Atypical and malignant meningioma: outcome and prognostic factors in 119 irradiated patients. A multicenter, retrospective study of the Rare Cancer Network.

PURPOSE: To retrospectively analyze and assess the outcomes and prognostic factors in a large number of patients with atypical and malignant meningiomas. METHODS AND MATERIALS: Ten academic medical centers participating in this Rare Cancer Network contributed 119 cases of patients with atypical or malignant meningiomas treated with external beam radiotherapy (EBRT) after surgery or for recurrence. Eligibility criteria were histologically proven atypical or anaplastic (malignant) meningioma (World Health Organization Grade 2 and 3) treated with fractionated EBRT after initial resection or for recurrence, and age >18 years. Sex ratio (male/female) was 1.3, and mean (+/-SD) age was 57.6 +/- 12 years. Surgery was macroscopically complete (Simpson Grades 1-3) in 71% of patients; histology was atypical and malignant in 69% and 31%, respectively. Mean dose of EBRT was 54.6 +/- 5.1 Gy (range, 40-66 Gy). Median follow-up was 4.1 years. RESULTS: The 5- and 10-year actuarial overall survival rates were 65% and 51%, respectively, and were significantly influenced by age >60 years (p = 0.005), Karnofsky performance status (KPS) (p = 0.01), and high mitotic rate (p = 0.047) on univariate analysis. On multivariate analysis age >60 years (p = 0.001) and high mitotic rate (p = 0.02) remained significant adverse prognostic factors. The 5- and 10-year disease-free survival rates were 58% and 48%, respectively, and were significantly influenced by KPS (p = 0.04) and high mitotic rate (p = 0.003) on univariate analysis. On multivariate analysis only high mitotic rate (p = 0.003) remained a significant prognostic factor. CONCLUSIONS: In this multicenter retrospective study, age, KPS, and mitotic rate influenced outcome. Multicenter prospective studies are necessary to clarify the management and prognostic factors of such a rare disease.

Outcomes After Radiotherapy Alone for Metastatic Spinal Cord Compression in Patients with Oligo-metastatic Breast Cancer.

BACKGROUND/AIM: Patients with oligo-metastatic breast cancer are a unique patient subgroup with more favourable outlook than most patients with metastatic disease. Prognostic factors in these patients with metastatic spinal cord compression (MSCC) were evaluated. PATIENTS AND METHODS: In 159 patients irradiated for MSCC from oligo-metastatic breast cancer, seven characteristics were retrospectively analyzed including age, interval between breast cancer diagnosis and irradiation of MSCC, time developing motor deficits, ambulatory status, involved vertebrae, performance score (ECOG-PS) and radiotherapy regimen. RESULTS: Improvement of motor function was significantly associated with time developing motor deficits (p=0.017), post-radiotherapy ambulatory status with pre-radiotherapy ambulation (p=0.012) and ECOG-PS 1-2 (p=0.029). Radiation doses of 39-40 Gy (equivalent doses) resulted in 1- and 2-year local control of 100% and 95%. On multivariate analyses, higher doses were associated with local control (p=0.011). Pre-radiotherapy ambulatory status (p=0.001) and ECOG-PS 1-2 (p=0.002) were associated with survival. CONCLUSION: Significant prognostic factors were identified for patients with MSCC from oligo-metastatic breast cancer. Higher radiation doses improved local control.

1x8 Gy versus 5x4 Gy for metastatic epidural spinal cord compression: a matched-pair study of three prognostic patient subgroups.

BACKGROUND: This study provides separate comparisons of 1 × 8 Gy to 5 × 4 Gy for metastatic epidural spinal cord compression (MESCC) in patients with poor, intermediate and favorable survival prognoses. METHODS: Patients receiving 1 × 8 Gy were matched to patients receiving 5 × 4 Gy for age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, ambulatory status and time developing motor deficits. From a study including patients with poor (N = 156) or intermediate (N = 86) survival prognoses, subgroup analyses were performed. Furthermore, 232 new patients with favorable prognoses matched the same way were included. RESULTS: In poor prognoses patients, 6-month survival rates were 10% after 1 × 8 Gy and 6% after 5 × 4 Gy (p = 0.38); in-field reRT rates in few patients alive at 6 months were 15 and 2% (p = 0.16). In intermediate prognoses patients, 6-month survival rates were 49% after 1 × 8 Gy and 58% after 5 × 4 Gy (p = 0.30). ReRT rates at 6 months were 23 and 13% (p = 0.25). In favorable prognoses patients, 6-month survival rates were 89% after 1 × 8 Gy and 91% after 5 × 4 Gy. ReRT rates at 6 months were 14 and 3% (p = 0.007). In no subgroup, RT regimen had a significant impact on motor function. CONCLUSIONS: Since in patients with poor prognoses, outcomes after 1 × 8 Gy and 5 × 4 Gy were not significantly different, 1 × 8 Gy may be an option. In patients with intermediate prognoses, a trend was found in favor of 5 × 4 Gy. In patients with favorable prognoses, need for in-field reRT was greater after 1 × 8 Gy.

A scoring system to predict local progression-free survival in patients irradiated with 20 Gy in 5 fractions for malignant spinal cord compression.

BACKGROUND: Local progression-free survival (LPFS = stable or improved motor function/resolution of paraplegia during RT without in-field recurrence following RT) is important when treating metastatic spinal cord compression (MSCC). An instrument to estimate LPFS was created to identify patients appropriately treated with short-course RT instead of longer-course RT plus/minus decompressive surgery. METHODS: In 686 patients treated with 20 Gy in 5 fractions alone, ten characteristics were retrospectively analyzed for LPFS including age, interval between tumor diagnosis and RT of MSCC, visceral metastases, other bone metastases, primary tumor type, gender, time developing motor deficits, pre-RT gait function, number of vertebrae affected by MSCC, and performance score. Characteristics significantly (p < 0.05) associated with LPFS on multivariate analyses were incorporated in the scoring system. Six-month LPFS rates for significant characteristics were divided by 10, and corresponding points were added. RESULTS: On multivariate analyses, visceral metastases (p < 0.001), tumor type (p = 0.009), time developing motor deficits (p < 0.001) and performance score (p = 0.009) were associated with LPFS and used for the scoring system. Scores for patients ranged between 24 and 35 points. Three groups were designed: 24-28 (A), 29-31 (B) and 32-35 (C) points. Six-month LPFS rates were 46, 69 and 92%, 12-month LPFS rates 46, 63 and 83%. Median survival times were 2 months (61% died within 2 months), 4 months and ≥ 11 months (median not reached). CONCLUSIONS: Most group A patients appeared sub-optimally treated with 20 Gy in 5 fractions. Patients with survival prognoses ≤2 months may be considered for best supportive care or single-fraction RT, those with prognoses ≥3 months for longer-course RT plus/minus upfront decompressive surgery. Many group B and most group C patients achieved long-time LPFS and appeared sufficiently treated with 20 Gy in 5 fractions. However, based on previous data, long-term survivors may benefit from longer-course RT.

Adjuvant postoperative high-dose radiotherapy for atypical and malignant meningioma: A phase-II parallel non-randomized and observation study (EORTC 22042-26042).

PURPOSE: The therapeutic strategy for non-benign meningiomas is controversial. The objective of this study was to prospectively investigate the impact of high dose radiation therapy (RT) on the progression-free survival (PFS) rate at 3 years in WHO grade II and III meningioma patients. MATERIALS AND METHODS: In this multi-cohorts non-randomized phase II and observational study, non-benign meningioma patients were treated according to their WHO grade and Simpson's grade. Patients with atypical meningioma (WHO grade II) and Simpson's grade 1-3 [Arm 1] entered the non-randomized phase II study designed to show a 3-year PFS > 70% (primary endpoint). All other patients entered the 3 observational cohorts: WHO grade II Simpson grade 4-5 [Arm 2] and Grade III Simpson grade 1-3 or 4-5 [Arm 3&4] in which few patients were expected. RESULTS: Between 02/2008 and 06/2013, 78 patients were enrolled into the study. This report focuses on the 56 (median age, 54 years) eligible patients with WHO grade II Simpson's grade 1-3 meningioma who received RT (60 Gy). At a median follow up of 5.1 years, the estimated 3-year PFS is 88.7%, hence significantly greater than 70%. Eight (14.3%) treatment failures were observed. The 3-year overall survival was 98.2%. The rate of late signs and symptoms grade 3 or more was 14.3%. CONCLUSIONS: These data show that 3-year PFS for WHO grade II meningioma patients undergoing a complete resection (Simpson I-III) is superior to 70% when treated with high-dose (60 Gy) RT.

Reduction of overall treatment time in patients irradiated for more than three brain metastases.

PURPOSE: Patients with multiple brain metastases usually receive whole brain radiotherapy (WBRT). A dose of 30 Gy in 10 fractions (10 x 3 Gy) in 2 weeks is the standard treatment in many centers. Regarding the poor survival of these patients, a shorter RT regimen would be preferable if it provides a similar outcome as that with 10 x 3 Gy. This study compared 20 Gy in five fractions (5 x 4 Gy) within 5 days to 10 x 3 Gy. METHODS AND MATERIALS: Data from 442 patients treated with WBRT for multiple brain metastases were retrospectively analyzed. Survival and local control within the brain of 232 patients treated with 5 x 4 Gy were compared with the survival and local control within the brain of 210 patients treated with 10 x 3 Gy. Seven additional potential prognostic factors were investigated: age, gender, Karnofsky performance score, tumor type, interval from tumor diagnosis to RT, extracranial metastases, and recursive partitioning analysis class. RESULTS: On univariate analysis, the WBRT program was not associated with survival (p = 0.29) or local control (p = 0.07). On multivariate analyses, improved survival was associated with a lower recursive partitioning analysis class (p < 0.001), age or=70 (p = 0.015), and the absence of extracranial metastases (p = 0.005). Improved local control was associated with a lower recursive partitioning analysis class (p < 0.001), Karnofsky performance score >or=70 (p < 0.001), and breast cancer (p = 0.043). Grade 3 acute toxicity rates were not significantly different between 5 x 4 Gy and 10 x 3 Gy. CONCLUSIONS: Shorter course WBRT with 5 x 4 Gy was associated with similar survival and local control as "standard" WBRT with 10 x 3 Gy in patients with more than three brain metastases. The 5 x 4-Gy regimen appears preferable for most of these patients, because it is less time consuming and more convenient for patients than the 10 x 3-Gy regimen.

Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression.

PURPOSE: In many centers worldwide, radiotherapy for metastatic spinal cord compression (MSCC) is performed with 30 Gy in 10 fractions. This study investigated the potential benefit of dose escalation. METHODS AND MATERIALS: Data from 922 patients with carcinomas causing MSCC were retrospectively evaluated. The outcome of 345 patients treated with 10 fractions of 3 Gy in 2 weeks was compared with the outcomes of 577 patients treated with 37.5 Gy in 15 fractions within 3 weeks or 40 Gy in 20 fractions within 4 weeks. Additionally, 10 potential prognostic factors were investigated: age, gender, performance status, tumor type, interval between cancer diagnosis and MSCC, number of involved vertebrae, other bone and visceral metastases, ambulatory status, and the interval to the development of motor deficits before radiotherapy. RESULTS: Motor function improved in 19% of patients after 30 Gy in 10 fractions and in 22% after greater doses (p = 0.31). The local control (p = 0.28) and survival (p = 0.85) rates were not significantly different with doses >30 Gy. Better functional outcome was associated with the absence of visceral metastases, an interval between tumor diagnosis and MSCC of >12 months, ambulatory status, and an interval to the development of motor deficits of >7 days. Improved local control was significantly associated with no visceral metastases, improved survival with favorable histologic features (breast or prostate cancer), no visceral metastases, ambulatory status, an interval between cancer diagnosis and MSCC of >12 months, and an interval to the development of motor deficits of >7days. CONCLUSION: Escalation of the radiation dose to >30 Gy in 10 fractions did not improve the outcomes in terms of motor function, local control, or survival but did increase the treatment time for these frequently debilitated patients. Therefore, doses >30 Gy in 10 fractions are not recommended.

Functional outcome and survival after radiotherapy of metastatic spinal cord compression in patients with cancer of unknown primary.

PURPOSE: Patients with cancer of unknown primary (CUP) account for about 10% of patients with metastatic spinal cord compression (MSCC). This study aims to define the appropriate radiation regimen for these patients. METHODS AND MATERIALS: Data of 143 CUP patients irradiated for MSCC were retrospectively evaluated. Short-course radiotherapy (RT) (1x8 Gy, 5x4 Gy, n = 68) and long-course RT (10x3 Gy, 15x2.5 Gy, 20x2 Gy, n = 75) plus 8 further potential prognostic factors (age, gender, performance status, visceral metastases, other bone metastases, number of involved vertebrae, ambulatory status, time of developing motor deficits before RT) were compared for functional outcome and survival. RESULTS: Improvement of motor function occurred in 10% of patients, no further progression of motor deficits in 57%, and deterioration in 33%. On multivariate analysis, functional outcome was positively associated with slower development of motor deficits (p < 0.001), absence of visceral metastases (p = 0.008) and other bone metastases (p = 0.027), and ambulatory status (p = 0.054), not with the radiation regimen (p = 0.74). Recurrence of MSCC in the irradiated region occurred in 7 patients after median 6 months. Median survival was 4 months. On multivariate analysis, better survival was significantly associated with absence of visceral metastases (p < 0.001), absence of other bone metastases (p = 0.005), ambulatory status (p = 0.001), and slower development of motor deficits (p = 0.030). CONCLUSIONS: For MSCC treatment in patients with CUP, no significant difference was observed between short-course and long-course RT regarding functional outcome and survival. Short-course RT appears preferable, at least for patients with a poor predicted survival, as it is more patient convenient and more cost-effective.

Improved posttreatment functional outcome is associated with better survival in patients irradiated for metastatic spinal cord compression.

PURPOSE: To evaluate the potential prognostic impact of the effect of radiotherapy (RT) on motor function and of the post-RT ambulatory status on survival in metastatic spinal cord compression (MSCC) patients. METHODS AND MATERIALS: Of 1,852 patients irradiated for MSCC, 778 patients (42%) received short-course RT and 1,074 (58%) received long-course RT. The effect of RT on motor function (improvement vs. no change vs. deterioration) and the ambulatory status after RT (ambulatory vs. nonambulatory) were evaluated with respect to survival. RESULTS: The actuarial survival rate of the entire cohort was 56% at 6 months, 43% at 12 months, and 32% at 24 months. The patients in whom motor function improved after RT had a significantly better 1-year survival rate than those who had no change or deterioration of motor function (75% vs. 40% and 3%, p < 0.001). The 1-year survival rate of the patients who were ambulatory after RT was significantly better than for those who were not ambulatory (63% vs. 4%, p < 0.001). The results were confirmed in multivariate analysis. CONCLUSIONS: The response to RT and the post-RT ambulatory status are important predictors for survival in MSCC patients. This finding can be used by physicians to stratify future studies, plan further therapy, and improve follow-up strategy in these patients.