Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma - A Report From the HIT 2000 Trial.

PURPOSE: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. METHODS AND MATERIALS: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. RESULTS: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P = .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%; P = .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49; P = .014) and time interval between surgery and irradiation (hazard ratio, 2.2; P = .018) were confirmed as independent risk factors. CONCLUSIONS: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.

A Survival Score for Patients Receiving Stereotactic Radiosurgery Alone for Brain Metastases from Breast Cancer.

AIM: To generate a survival score for patients with breast cancer treated with stereotactic radiosurgery (SRS) alone for brain metastases. PATIENTS AND METHODS: Seven factors were evaluated in 34 patients, namely age, performance score, number of brain metastases, maximum diameter of all brain metastases, location of brain metastases, extracerebral metastases and time between breast cancer diagnosis and SRS. The score was created from factors having a significant impact on survival. Points of 0 (worse survival) or 1 (better survival) were assigned. Factor scores were added to total prognostic scores for each patient. RESULTS: A significant impact on survival was found for performance score (p<0.001), maximum diameter of cerebral lesions (p=0.002), and extracerebral metastases (p=0.026). Three groups were designated by score: 0-1, 2 and 3 points. One-year survival rates were 48%, 71% and 100%, respectively (p<0.001). CONCLUSION: This score contributes to appropriate selection of personalized treatment in patients with breast cancer with few cerebral metastases.

Number of cerebral lesions predicts freedom from new brain metastases after radiosurgery alone in lung cancer patients.

Numerous patients with few brain metastases receive radiosurgery, either alone or in combination with whole-brain irradiation. The addition of whole-brain irradiation to radiosurgery reduces the rate of intracerebral failures, particularly the development of new cerebral lesions distant from those treated with radiosurgery. Less intracerebral failures mean less neurocognitive deficits. However, whole-brain irradiation itself may lead to a decline in neurocognitive functions. Therefore, a number of physicians have reservations with regard to adding whole-brain irradiation to radiosurgery. Prognostic factors that allow an estimation of the risk of developing new cerebral metastases can facilitate the decision regarding additional whole-brain irradiation. Since primary tumors show a different biology and clinical course, prognostic factors should be identified separately for each primary tumor leading to brain metastasis. The present study investigated 10 characteristics in a series of 98 patients receiving radiosurgery alone for 1-2 cerebral metastases from lung cancer, the most common primary tumor associated with brain metastasis. These characteristics included radiosurgery dose, age, gender, performance status, histology, number of cerebral lesions, maximum total diameter of cerebral lesions, main location of cerebral lesions, extracranial spread and interval from first diagnosis of lung cancer to administration of radiosurgery. On univariate analysis, the number of cerebral lesions prior to radiosurgery (1 vs. 2 lesions) was the only characteristic significantly associated with freedom from new brain metastases (P=0.002). In cases of 2 lesions, 73% of patients developed new cerebral lesions within 1 year. On multivariate analysis, the number of brain metastases remained significant (risk ratio, 2.46; 95% confidence interval, 1.34-4.58; P=0.004). Given the high rates of new cerebral lesions in patients with 2 brain metastases, these patients should be strongly considered for additional whole-brain irradiation.

Predicting the Risk of New Cerebral Lesions After Stereotactic Radiosurgery (SRS) for Brain Metastases from Breast Cancer.

AIM: To generate a tool that estimates the probability of developing new cerebral metastases after stereotactic radiosurgery (SRS) in breast cancer patients. PATIENTS AND METHODS: SRS dose plus seven characteristics (age, performance score, number of cerebral metastases, maximum diameter of all metastases, location of metastases, extra-cerebral spread and time from breast cancer diagnosis until SRS) were analyzed regarding their ability to predict the probability of new cerebral metastases development following SRS. For those characteristics deemed significant, points of 0 (higher risk of new lesions) or 1 (lower risk) were given. Scores were generated by adding the points of significant characteristics. RESULTS: Performance score (p=0.013) and maximum diameter of all metastases (p=0.022) were associated with development of subsequent brain metastases. Two groups were created, 0-1 and 2 points. Freedom from new cerebral metastases rates were 27% and 92%, respectively, at 15 months (p=0.003). CONCLUSION: This tool helps select breast cancer with few cerebral metastases receiving SRS who may benefit from additional whole-brain irradiation.

A New Predictive Tool for Optimization of the Treatment of Brain Metastases from Colorectal Cancer After Stereotactic Radiosurgery.

AIM: To develop a predictive tool for survival after stereotactic radiosurgery of brain metastases from colorectal cancer. PATIENTS AND METHODS: Out of nine factors analyzed for survival, those showing significance (p<0.05) or a trend (p≤0.06) were included. For each factor, 0 (worse survival) or 1 (better survival) point was assigned. Total scores represented the sum of the factor scores. RESULTS: Performance status (p=0.010) and interval from diagnosis of colorectal cancer until radiosurgery (p=0.026) achieved significance, extracranial metastases showed a trend (p=0.06). These factors were included in the tool. Total scores were 0-3 points. Six-month survival rates were 17% for patients with 0, 25% for those with 1, 67% for those with 2 and 100% for those with 3 points; 12-month rates were 0%, 0%, 33% and 67%, respectively. Two groups were created: 0-1 and 2-3 points. Six- and 12-month survival rates were 20% vs. 78% and 0% vs. 44% (p=0.002), respectively. CONCLUSION: This tool helps optimize the treatment of patients after stereotactic radiosurgery for brain metastases from colorectal cancer.

Impact of stereotactic radiosurgery dose on control of cerebral metastases from renal cell carcinoma.

AIM: Renal cell carcinoma (RCC) is a relatively radioresistant tumor and may require for higher radiation doses than other tumor types. PATIENTS AND METHODS: Nineteen patients treated with 20 Gy of stereotactic radiosurgery (SRS) alone for one to three cerebral metastases were compared to nine patients treated with 16-18 Gy. RESULTS: SRS with 20 Gy led to significantly better local control than did 16-18 Gy (81% vs. 50% at 12 months; p<0.001). Results were also significant on multivariate analysis (risk ratio: 6.30; p=0.033). SRS dose did not associate with freedom from new cerebral metastases (75% vs. 62% at 12 months; p=0.42) or survival (16% vs. 56% at 12 months; p=0.46). On multivariate analyses, better survival was associated with higher Karnofsky performance score (p<0.001) and absence of extracranial metastatic disease (p=0.006). CONCLUSION: In patients treated with SRS alone, local control of cerebral metastases from RCC was better after 20 Gy than after 16-18 Gy.

A new tool to predict survival after radiosurgery alone for newly diagnosed cerebral metastases.

Many patients with few cerebral metastases receive radiosurgery alone. The goal of this study was to create a tool to estimate the survival of such patients. To identify characteristics associated with survival, nine variables including radiosurgery dose, age, gender, Eastern cooperative oncology group performance score (ECOG-PS), primary tumor type, number/size of cerebral metastases, location of cerebral metastases, extra-cerebral metastases and time between cancer diagnosis and radiosurgery were analyzed in 214 patients. On multivariate analysis, age (p=0.03), ECOG-PS (p=0.02) and extra-cerebral metastases (p<0.01) had significant impacts on survival. Scoring points for each patient were obtained from 12-month survival rates (in %) related to the significant variables divided by 10. Addition of the scoring points of the three variables resulted in a patient's total predictive score. Two groups were designed, A (10-14 points) and B (16-17 points). Twelve-month survival rates were 33% and 77%, respectively (p<0.001). Median survival times were 8 and 20 months, respectively. Because most patients of group A died from extra-cerebral disease and/or new cerebral lesions, early systemic treatment and additional WBI should be considered. As cause of death in group B was mostly new cerebral metastases, additional WBI appears even more important for this group.

Radiosurgery with 20 Gy provides better local contol of 1-3 brain metastases from breast cancer than with lower doses.

AIM: To determine the optimal dose of radiosurgery-alone for patients with 1-3 cerebral metastases from breast cancer. PATIENTS AND METHODS: Patients receiving 20 Gy (n=20) were compared to those receiving 16-18.5 Gy (n=10) for local control, distant brain control and overall survival. Seven other variables were also evaluated. RESULTS: Radiosurgery dose achieved significance on univariate (p=0.002; log-rank and Wilcoxon test) and multivariate analysis (p=0.004) of local control. Twelve-month local control rates were 94% after 20 Gy and 48% after 16-18.5 Gy. On univariate analysis of distant brain control, radiosurgery dose was not a significant factor, with 12-month rates of 73% and 60%, respectively. Regarding overall survival, radiosurgery dose was of borderline significance (p=0.059; Wilcoxon test). Twelve-month overall survival rates were 75% and 40%, respectively. On Cox regression analysis, radiosurgery dose exhibited a trend for improving survival (p=0.10). CONCLUSION: Radiosurgery with 20 Gy resulted in significantly better local control and led to a trend towards improved overall survival compared to treatment with 16-18.5 Gy.

A new tool predicting survival after radiosurgery alone for one or two cerebral metastases from lung cancer.

Radiosurgery is frequently used for patients with few cerebral metastases. Decisions regarding personalized treatment should include the patient's survival prognosis. Prognostic tools should be available for estimating the remaining lifetime for each primary tumor and treatment. We designed such a tool for patients receiving radiosurgery alone for cerebral metastases from lung cancer. Ten variables were analyzed in 98 patients. On multivariate analysis, extra-cranial spread was significantly associated with worse survival (p < 0.001). A trend was observed for poorer performance status (p = 0.08) and greater diameter of cerebral lesions (p = 0.07). Points for the tool were derived from 12-month survival rates of these variables and added, resulting in sum scores of 10-16 points. Three groups were built, 10-12, 14-15, and 16 points with 12-month survival rates of 22, 52, and 79% (p < 0.001). This new tool enables physicians to estimate the survival of lung cancer patients with few cerebral metastases which should impact individualized treatment choices.

Comparison of two dose levels of stereotactic radiosurgery for 1-3 brain metastases from non-small cell lung cancer.

AIM: Two dose groups of patients treated with stereotactic radiosurgery (SRS) alone for 1-3 brain metastases from non-small cell lung cancer (NSCLC) were compared for outcomes. PATIENTS AND METHODS: Based on the SRS dose administered to the margins of the brain lesions, 46 patients were assigned to groups treated with 15-18 Gy (n=13) or with 20 Gy (n=33). Seven additional factors were investigated: age (≤ 58 vs. ≥ 59 years), gender, Karnofsky performance score (KPS 70-80 vs. 90-100), number of brain metastases (1 vs. 2-3), histology (adenocarcinoma vs. other) extracerebral metastases and interval from NSCLC diagnosis to SRS (≤ 6 vs. >6 months). RESULTS: Local control rates for 15-18-Gy and 20-Gy groups were 75% and 92% at one year (p=0.043). SRS dose was significant on multivariate analysis (p=0.030). SRS dose was not associated with freedom from new brain metastases (p=0.24) or survival (p=0.37). CONCLUSION: SRS with 20 Gy resulted in better control of the irradiated metastases than 15-18 Gy did.

Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

BACKGROUND: An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. METHODS: Fifty-eight patients with 1-3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. RESULTS: The treatment regimen had no significant impact on local control in the univariate analysis (p=0.59). Age ≤59 years showed a trend towards improved local control on univariate (p=0.066) and multivariate analysis (p=0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p=0.040) and ECOG 0-1 (p=0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p=0.039) and performance status (p=0.028) maintained significance on multivariate analysis. ECOG 0-1 was positively correlated with survival on univariate analysis (p<0.001); age ≤59 years showed a strong trend (p=0.054). On multivariate analysis, performance status (p<0.001) and age (p=0.041) were significant. CONCLUSIONS: In breast cancer patients with few brain metastases, radiosurgery plus whole-brain radiotherapy resulted in significantly better freedom from new brain metastases than radiosurgery alone. However, this advantage did not lead to significantly better survival.

Radiosurgery alone versus radiosurgery plus whole-brain irradiation for very few cerebral metastases from lung cancer.

BACKGROUND: It is unclear whether patients with few cerebral metastases benefit from whole-brain irradiation added to radiosurgery. Since primary tumors disseminating to the brain show different behavior, this question should be answered separately for each tumor type. This study compared both treatments in patients with 1-3 cerebral metastases from lung cancer. METHODS: Ninety-eight patients receiving radiosurgery alone were retrospectively compared to 50 patients receiving radiosurgery plus whole-brain irradiation for local control, distant cerebral control and overall survival. Ten other characteristics were additionally considered including radiosurgery dose, age, gender, Eastern Cooperative Oncology Group (ECOG) performance score, histology, number of cerebral metastases, maximum diameter of all cerebral metastases, site of cerebral metastases, extra-cerebral metastases, and interval from lung cancer diagnosis to irradiation. RESULTS: The treatment approach had no significant impact on local control (p = 0.61). On multivariate analysis of local control, ECOG performance score was significant (risk ratio [RR]: 2.10; p < 0.001). The multivariate analysis of distant brain control revealed significant positive associations with radiosurgery plus whole-brain irradiation (RR: 4.67; p < 0.001) and one cerebral metastasis (RR: 2.62; p < 0.001). Treatment approach was not significantly associated with overall survival (p = 0.32). On multivariate analysis, significant associations with overall survival were found for maximum diameter of all cerebral metastases (RR: 1.81; p = 0.008), extra-cerebral metastases (RR: 2.98; p < 0.001), and interval from lung cancer diagnosis to irradiation (RR: 1.19; p < 0.001). CONCLUSION: Addition of whole-brain irradiation to radiosurgery significantly improved distant brain control in patients with few cerebral metastases from lung cancer. This improvement did not translate into better overall survival.

Identifying melanoma patients with 1-3 brain metastases who may benefit from whole-brain irradiation in addition to radiosurgery.

BACKGROUND/AIM: To develop a tool for estimating the risk of developing new cerebral lesions in 69 melanoma patients receiving radiosurgery for 1-3 cerebral metastases. PATIENTS AND METHODS: Ten factors were investigated: lactate dehydrogenase (LDH), radiosurgery dose, age, gender, performance status, maximum diameter, location and number of cerebral lesions, extra-cranial spread, time between melanoma diagnosis and radiosurgery. Two factors, number of lesions and extra-cranial spread, were included in the tool. Scoring points were achieved by dividing the 6-month rate of freedom from new cerebral lesions by 10. RESULTS: Sum scores were 9, 11, 12 or 14 points. Six-month rates of freedom from new brain metastases were 28%, 63%, 59% and 92% (p=0.002). Three prognostic groups were designed: A (9 points), B (11-12 points) and C (14 points). Freedom from new cerebral lesion rates were 28%, 60% and 92% (p<0.001). CONCLUSION: Group A and B patients should be considered for additional whole-brain radiotherapy (WBRT).

A new prognostic instrument to predict the probability of developing new cerebral metastases after radiosurgery alone.

BACKGROUND: Addition of whole-brain irradiation (WBI) to radiosurgery for treatment of few cerebral metastases is controversial. This study aimed to create an instrument that estimates the probability of developing new cerebral metastases after radiosurgery to facilitate the decision regarding additional WBI. METHODS: Nine characteristics were investigated for associations with the development of new cerebral metastases including radiosurgery dose (dose equivalent to <20 Gy vs. 20 Gy vs. >20 Gy for tumor cell kill, prescribed to the 73-90% isodose level), age (≤60 vs. ≥61 years), gender, Eastern Cooperative Oncology Group performance score (0-1 vs. 2), primary tumor type (breast cancer vs. non-small lung cancer vs. malignant melanoma vs. others), number/size of cerebral metastases (1 lesion <15 mm vs. 1 lesion ≥15 mm vs. 2 or 3 lesions), location of the cerebral metastases (supratentorial alone vs. infratentorial ± supratentorial), extra-cerebra metastases (no vs. yes) and time between first diagnosis of the primary tumor and radiosurgery (≤15 vs. >15 months). RESULTS: Number of cerebral metastases (p = 0.002), primary tumor type (p = 0.10) and extra-cerebral metastases (p = 0.06) showed significant associations with development of new cerebral metastases or a trend, and were integrated into the predictive instrument. Scoring points were calculated from 6-months freedom from new cerebral metastases rates. Three groups were formed, group I (16-17 points, N = 47), group II (18-20 points, N = 120) and group III (21-22 points, N = 47). Six-month rates of freedom from new cerebral metastases were 36%, 65% and 80%, respectively (p < 0.001). Corresponding rates at 12 months were 27%, 44% and 71%, respectively. CONCLUSION: This new instrument enables the physician to estimate the probability of developing new cerebral metastases after radiosurgery alone. Patients of groups I and II appear good candidates for additional WBI in addition to radiosurgery, whereas patients of group III may not require WBI in addition to radiosurgery.

Radiosurgery alone for 1-3 newly-diagnosed brain metastases from melanoma: impact of dose on treatment outcomes.

BACKGROUND/AIM: To compare different doses of stereotactic radiosurgery (SRS) for 1-3 newly-diagnosed cerebral metastases from melanoma. PATIENTS AND METHODS: Fifty-four patients were assigned to dose groups of 20 Gy (N=36) and 21-22.5 Gy (N=18). Variables additionally analyzed were age, gender, Karnofsky Performance Score (KPS), lactate dehydrogenase (LDH) before SRS, number of cerebral lesions, extracranial lesions, time from melanoma diagnosis to SRS. RESULTS: The 12-month local control was 72% after 20 Gy and 100% after 21-22.5 Gy (p=0.020). Freedom from new cerebral metastases (p=0.13) and survival (p=0.13) showed no association with SRS dose. On multivariate analyses, improved local control showed significant associations with SRS doses of 21-22.5 Gy (p=0.007) and normal lactate dehydrogenase levels (p=0.018). Improved survival was associated with normal LDH levels (p=0.006) and KPS 90-100 (p=0.046). CONCLUSION: SRS doses of 21-22.5 Gy resulted in better local control than 20 Gy. Freedom from new brain metastases and survival were not significantly different.

Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy.

PURPOSE: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. METHODS AND MATERIALS: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). RESULTS: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (± standard error [SE]) were each 58% (± 10%) for the entire cohort: CNS-PNET was 53% (± 13); pinealoblastoma was 64% (± 15%; P=.524 and P=.627, respectively). CONCLUSIONS: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

Stereotactic radiosurgery for newly diagnosed brain metastases: comparison of three dose levels.

BACKGROUND AND PURPOSE: Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases. PATIENTS AND METHODS: In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size (< 15 vs. ≥ 15 mm), extracranial metastases (no vs. yes), RPA class (1 vs. 2), and interval of cancer diagnosis to SRS (≤ 24 vs. > 24 months). RESULTS: For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79%, respectively (p < 0.001). The SRS dose maintained significance on multivariate analysis (risk ratio: 2.25; 95% confidence interval: 1.56-3.29; p < 0.001). On intergroup comparisons of local control, 20 Gy was superior to 13-16 Gy (p < 0.001) but not to 18 Gy (p = 0.12); 18 Gy showed a strong trend toward better local control when compared with 13-16 Gy (p = 0.059). Freedom from new brain metastases (p = 0.57) and survival (p = 0.15) were not associated with SRS dose in the univariate analysis. CONCLUSION: SRS doses of 18 Gy and 20 Gy resulted in better local control than 13-16 Gy. However, 20 Gy and 18 Gy must be compared again in a larger cohort of patients. Freedom from new brain metastases and survival were not associated with SRS dose.

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.

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.

Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT+SRS) for one to three brain metastases.

BACKGROUND: The best available treatment of patients with one to three brain metastases is still unclear. This study compared the results of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT+SRS). PATIENTS AND METHODS: Survival (OS), intracerebral control (IC), and local control of treated metastases (LC) were retrospectively analyzed in 144 patients receiving SRS alone (n=93) or WBRT+SRS (n=51). Eight additional potential prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. Subgroup analyses were performed for RPA class I and II patients. RESULTS: 1-year-OS was 53% after SRS and 56% after WBRT+SRS (p=0.24). 1-year-IC rates were 51% and 66% (p=0.015), respectively. 1-year-LC rates were 66% and 87% (p=0.003), respectively. On multivariate analyses, OS was associated with age (p=0.004), ECOG-PS (p=0.005), extracerebral metastases (p<0.001), RPA class (p<0.001), and interval from tumor diagnosis to irradiation (p<0.001). IC was associated with interval from tumor diagnosis to irradiation (p=0.004) and almost with treatment (p=0.09), and LC with treatment (p=0.026) and almost with interval (p=0.08). The results of the subgroup analyses were similar to those of the entire cohort. The increase in IC was stronger in RPA class I patients. CONCLUSION: WBRT+SRS resulted in better IC and LC but not better OS than SRS alone. Because also IC and LC are important end-points, additional WBRT appears justified in patients with one to three brain metastases, in particular in RPA class I patients.