Outcome and prognostic factors in patients with brain metastases from small-cell lung cancer treated with whole brain radiotherapy

Abstract

The purpose of this study was to evaluate prognostic factors associated with overall survival (OS) and neurological progression free survival (nPFS) in small-cell lung cancer (SCLC) patients with brain metastases who received whole-brain radiotherapy (WBRT). From 2003 to 2015, 229 SCLC patients diagnosed with brain metastases who received WBRT were analyzed retrospectively. In this cohort 219 patients (95%) received a total photon dose of 30 Gy in 10 fractions. The prognostic factors evaluated for OS and nPFS were: age, Karnofsky Performance Status (KPS), number of brain metastases, synchronous versus metachronous disease, initial response to chemotherapy, the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class and thoracic radiation. Median OS after WBRT was 6 months and the median nPFS after WBRT was 11 months. Patients with synchronous cerebral metastases had a significantly better median OS with 8 months compared to patients with metachronous metastases with a median survival of 3 months (p < 0.0001; HR 0.46; 95% CI 0.31-0.67). Based on RPA classification median survival after WBRT was 17 months in RPA class I, 7 months in class II and 3 months in class III (p < 0.0001). Karnofsky performance status scale (KPS < 70%) was significantly associated with OS in both univariate (HR 2.84; p < 0.001) and multivariate analyses (HR 2.56; p = 0.011). Further, metachronous brain metastases (HR 1.8; p < 0.001), initial response to first-line chemotherapy (HR 0.51, p < 0.001) and RPA class III (HR 2.74; p < 0.001) were significantly associated with OS in univariate analysis. In multivariate analysis metachronous disease (HR 1.89; p < 0.001) and initial response to chemotherapy (HR 0.61; p < 0.001) were further identified as significant prognostic factors. NPFS was negatively significantly influenced by poor KPS (HR 2.56; p = 0.011), higher number of brain metastases (HR 1.97; p = 0.02), and higher RPA class (HR 2.26; p = 0.03) in univariate analysis. In this series, the main prognostic factors associated with OS were performance status, time of appearance of intracranial disease (synchronous vs. metachronous), initial response to chemotherapy and higher RPA class. NPFS was negatively influenced by poor KPS, multiplicity of brain metastases, and higher RPA class in univariate analysis. For patients with low performance status, metachronous disease or RPA class III, WBRT should be weighed against supportive therapy with steroids alone or palliative chemotherapy.

Stereotactic radiosurgery for brain metastases from newly diagnosed small cell lung cancer: practice patterns and outcomes

“…Given the diffuse nature of metastatic spread amongst patients with BM due to SCLC, and the high likelihood of clinically occult BM [3], whole brain radiation therapy (WBRT) is the primary treatment option for patients with intracranial metastatic disease. However, intracranial recurrence is still relatively common following WBRT, which also carries the risk of neurocognitive impairment [4,5]. Stereotactic radiosurgery (SRS) is a high-quality local therapy that is increasingly recommended for limited BM from other solid tumors, including non-small cell lung cancer (NSCLC).…”

Radiotherapy of brain metastases from small-cell lung cancer: standards and controversies

“…Apart from the factors included in the RTOG RPA score, the time of occurrence of BM in relation to the diagnosis of the primary (synchronous vs. metachronous BM) and initial response to chemotherapy had a significant impact on survival. Patients presenting with synchronous BM and initial good response to chemotherapy had improved overall survival compared with patients presenting with metachronous BM and non-/poor responders to initial chemotherapy [13] . The authors proposed a new BM from SCLC score (BMS-score), which included RTOG RPA class and synchronous vs. metachronous BM presentation.…”

“…The limited therapeutic options and poor survival after relapse determine the poor outcome of treatment of metachronous BM. Thus, a metachronous presentation, that is, occurrence after first-line treatment, appears as an adverse prognostic factor [13,14] . Treatment strategies for BM that occur at the relapse differ with regard to the earlier use or not of PCI.…”

Strategies for Improved Intra-arterial Treatments Targeting Brain Tumors: a Systematic Review

“…Skull and dura mater metastasis disappeared after repeatedly performed superselective intra-arterial administration of epirubicin into the right superficial temporal artery and the middle meningeal artery, combined with embolization of tumor-supplying vessels (196). Moreover, the median overall survival was effectively extended to 6 months in small-cell lung cancer patients with brain metastases receiving superselective intracranial arterial infusion chemotherapy (teniposide, ACNU, and carboplatin) (197) vs. 4-6 months of standard whole brain radiotherapy (198,199). Therefore, carefully weighing beneficial outcomes vs. potential risks and adverse events is required for different brain tumor types.…”