Prophylactic cranial irradiation in patients with small cell lung cancer. A retrospective study of recurrence, survival and morbidity
ABSTRACT Prophylactic cerebral irradiation (PCI) is a standard treatment for all small cell lung cancer (SCLC) patients with response to chemotherapy. The aims of this study were: to evaluate patients undergoing PCI with regard to cerebral recurrence rate, site of recurrence, and overall survival (OS) and to investigate the influence of steroid dose on acute toxicity.
From 2007 to 2010 a total of 118 consecutive patients underwent PCI (25 Gray in 10 fractions). In total, 114/118 received full PCI dose, all 118 were included in the study. Data were analyzed retrospectively with regard to disease stage, treatment, date of PCI, steroid dose during PCI, toxicity, time to recurrence, site of recurrence and time of death. The median follow up time was 16.6 months (range 3-54 months).
Of the 118 patients undergoing PCI, 74 had limited disease (LD-SCLC) and 44 had extensive disease (ED-SCLC). The median age was 65 years (range 46-80 years). The median overall survival of all patients from the time of diagnosis was 16.0 months (CI 95% 13.0-19.0), in LD-SCLC it was 24.0 months (CI 95% 19.6-28.3), and in ED-SCLC it was 12.0 months (CI 95% 9.6-14.4). Twenty-one patients (17.8%) were diagnosed with cerebral recurrence. Five of these presented with metastatic disease within the limbic system. Of these five patients, four had miliary cerebral disease and one had non-oligometastatic disease. The time from PCI to cerebral recurrence ranged from 4 to 27 months. Prednisolone administration varied from 0 to 100 mg/day. Forty-eight patients were not treated with steroids, 64.6% of these patients reported acute toxicity. Of the 36 patients receiving 50 mg prednisolone, only 22.2% had side effects. The most common symptoms during PCI were nausea and headache.
Twenty-one patients out of 118 developed brain metastases after PCI: five of the twenty-one had metastases located in the limbic system. The study showed that prophylactic steroid use might reduce acute toxicity to PCI. Survival data and recurrence rates are comparable to other clinical studies.
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ABSTRACT: Lung cancer remains the leading cause of cancer-related mortality worldwide. The propensity for metastasis to the central nervous system (CNS) is a major clinical hurdle contributing to the low five-year survival rate of advanced disease. CNS metastases significantly outnumber primary brain tumors and carry a dismal prognosis in part due to the inability of therapeutic agents to cross the blood brain barrier. Standard treatment using radiation has been largely ineffective in improving mortality, suggesting the need for new agents targeting the critical metastatic drivers. The genetic and molecular events governing CNS metastasis from the lung are poorly understood at this time. This review highlights genetic events associated with CNS dissemination from the lung and molecular mechanisms associated with CNS metastasis. In vivo model systems that faithfully recapitulate escape from the lung and colonization of the CNS are described as tools for understanding the metastatic phenotype and for testing new therapeutic agents. A deeper understanding of the mechanisms of lung cancer metastasis to the CNS is needed to elucidate novel therapeutic avenues towards the improvement of the mortality associated with advanced stage lung cancer.08/2013; 2(4):273-83. DOI:10.3978/j.issn.2218-6751.2013.03.12
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ABSTRACT: Objective: We investigated the correlation between circulating tumor cells and the incidence of brain metastases as a first site of recurrence among patients with small-cell lung cancer after systemic chemoradiotherapy and prophylactic cranial irradiation. In addition, we assessed the contribution of circulating tumor cells for planning the appropriate total dose of prophylactic cranial irradiation for small-cell lung cancer. Methods: Patients (n = 112) with diagnosed Stage III small-cell lung cancer were treated with four cycles of platinum-based regimen and concurrent chest irradiation, and then prophylactic cranial irradiation. Blood samples for circulating tumor cell analysis were obtained before the initiation of chemotherapy and after the first and fourth cycle of chemotherapy. Results: Circulating tumor cells after the first cycle of chemotherapy correlated with tumor response after completion of chemotherapy (P = 0.012). Patients with brain as the first site suffered a higher rate of further metastases to other organs, and local recurrence, compared with those whose first site was the other organs (P < 0.001), and their survival rates were worse. Circulating tumor cells at baseline were the sole independent prognostic factor for specific progression-free survival. Receiver operating characteristic curves based on median specific progression-free survival revealed a circulating tumor cell cutoff at baseline of 218, and circulating tumor cells <= 218 at baseline correlated with significantly higher progression-free survival (P = 0.007), specific progression-free survival (P = 0.001) and overall survival (P = 0.001). Conclusions: Circulating tumor cells prior to the initiation of chemotherapy are a valuable predictor of specific progression-free survival in Stage III small-cell lung cancer. For patients with circulating tumor cells >218, prophylactic cranial irradiation at a total dose of 30 Gy in 15 fractions is insufficient.Japanese Journal of Clinical Oncology 08/2014; 44(10). DOI:10.1093/jjco/hyu109 · 1.75 Impact Factor
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ABSTRACT: Because of the high likelihood of multiple brain metastases (BM) from small cell lung cancer (SCLC), the role of focal treatment using stereotactic radiosurgery (SRS) has yet to be determined. We aimed to evaluate the efficacy and limitations of upfront and salvage SRS for patients with BM from SCLC. This was a retrospective and observational study analyzing 70 consecutive patients with BM from SCLC who received SRS. The median age was 68 years, and the median Karnofsky performance status (KPS) was 90. Forty-six (66%) and 24 (34%) patients underwent SRS as the upfront and salvage treatment after prophylactic or therapeutic whole brain radiotherapy (WBRT), respectively. Overall survival (OS), neurological death-free survival, remote and local tumor recurrence rates were analyzed. None of our patients were lost to follow-up and the median follow-up was 7.8 months. One-and 2-year OS rates were 43% and 15%, respectively. The median OS time was 7.8 months. One-and 2-year neurological death-free survival rates were 94% and 84%, respectively. In total, 219/292 tumors (75%) in 60 patients (86 %) with sufficient radiological follow-up data were evaluated. Six-and 12-month rates of remote BM relapse were 25% and 47%, respectively. Six-and 12-month rates of local control failure were 4% and 23%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 30, 8 and one patient, respectively. Symptomatic radiation injury, treated conservatively, developed in 3 patients. The present study suggested SRS to be a potentially effective and minimally invasive treatment option for BM from SCLC either alone or after failed WBRT. Although repeat salvage treatment was needed in nearly half of patients to achieve control of distant BM, such continuation of radiotherapeutic management might contribute to reducing the rate of neurological death.BMC Cancer 12/2015; 15(1):1103. DOI:10.1186/s12885-015-1103-6 · 3.32 Impact Factor