Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.
ABSTRACT Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG).
Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements.
From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121).
WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.
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ABSTRACT: Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC). The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs) were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group), and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%-57.8%) and 75.7% (95% CI: 70.3%-80.5%), respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%); a similar trend was observed for the DCR (94.6% vs 71.3%). The pooled median PFS and OS were 7.4 months (95% CI, 4.9-9.9) and 11.9 months (95% CI, 7.7-16.2), respectively, with longer PFS (12.3 months vs 5.9 months) and OS (16.2 months vs 10.3 months) in the EGFR mutation group than in the unselected group. This pooled analysis strongly suggests that EGFR-TKIs are an effective treatment for NSCLC patients with brain metastases, particularly in those patients harboring EGFR mutations. Larger prospective randomized clinical trials are warranted to confirm our conclusion and identify the most appropriate treatment model.OncoTargets and Therapy 01/2014; 7:2075-2084. · 1.34 Impact Factor
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ABSTRACT: To evaluate the feasibility of whole-brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) by forward intensity-modulated radiation therapy (IMRT) in patients with 1-3 brain metastases. Two forward IMRT plans were implemented among 18 patients. In plan A, the prescribed dose was 30 Gy to the whole brain (PTVWBRT) and 50 Gy to individual brain metastases (PTVboost) delivered simultaneously in 10 fractions. In plan B, the prescribed dose was 30 Gy to the PTVWBRT and 40 Gy to the PTVboost. Plans were evaluated with regard to conformation number (CN), prescription isodose volume to target volume ratio (PITV), target coverage (TC), homogeneity index (HI), and the volume receiving at least 95% of the prescribed dose (V95). Plan A was implemented for 5 of these patients, and plan B was used for the remaining patients. The mean values of CN, PITV, TC, and HI for the PTVboost were 0.71, 1.32, 0.97, and 0.07, respectively, for plan A and 0.65, 1.47, 0.97, and 0.05, respectively, for plan B. The mean values of TC, HI, and V95 for the PTVWBRT were 0.98, 0.45, and 99.71%, respectively, for plan A and 0.97, 0.27, and 99.61%, respectively, for plan B. All patients completed the planned radiotherapy (RT) schedule with no acute and late RT-related toxicity greater than grade 2. It is feasible to deliver WBRT with a SIB via forward IMRT for patients with 1-3 brain metastases with good dose conformity and acceptable toxicity.Contemporary Oncology / Wspólczesna Onkologia 01/2014; 18(3):187-91. · 0.22 Impact Factor
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ABSTRACT: Patients with non-small cell lung cancer (NSCLC) and simultaneously having brain metastases at the initial diagnosis, presenting symptoms related brain metastasis, survived shorter duration and showed poor quality of life. We analyzed our experiences on surgical treatment of brain metastasis in patients with NSCLC. We performed a single-center, retrospective review of 36 patients with NSCLC and synchronous brain metastases between April 2006 and December 2011. Patients were categorized according to the presence of neurological symptoms and having a brain surgery. As a result, 14 patients did not show neurological symptoms and 22 patients presented neurological symptoms. Symptomatic 22 patients were divided into two groups according to undergoing brain surgery (neurosurgery group; n=11, non-neurosurgery group; n=11). We analyzed overall surgery (OS), intracranial progression-free survival (PFS), and quality of life. Survival analysis showed there was no difference between patients with neurosurgery (OS, 12.1 months) and non-neurosurgery (OS, 10.2 months; p=0.550). Likewise for intracranial PFS, there was no significant difference between patients with neurosurgery (PFS, 6.3 months) and non-neurosurgery (PFS, 5.3 months; p=0.666). Reliable neurological one month follow up by the Medical Research Council neurological function evaluation scale were performed in symptomatic 22 patients. The scale improved in eight (73%) patients in the neurosurgery group, but only in three (27%) patients in the non-neurosurgery group (p=0.0495). Patients with NSCLC and synchronous brain metastases, presenting neurological symptoms showed no survival benefit from neurosurgical resection, although quality of life was improved due to early control of neurological symptoms.Yonsei medical journal. 01/2015; 56(1):103-11.