Analysis of the Prognostic Factors of Extensive Disease Small-Cell Lung Cancer Patients in Tokushima University Hospital

Abstract

Small-cell lung cancer (SCLC) accounts for 15 -20% of lung cancer (1) and presents aggressive clinical behavior characterized by rapid growth, metastatic spread to the distant organs (2). Despite the high response rate to initial chemotherapy, most patients subsequently experience a relapse of the primary tumor or distant metastasis, and the prognosis is still poor. SCLC is clinically categorized as two stages, limited disease (LD) and extensive disease (ED). LD-SCLC is defined as to be confined to the ipsilateral hemithorax and regional nodes, and able to be included in a single tolerable radiotherapy port. LD-SCLC is primarily treated with a combination of chemotherapy and radiotherapy, and its prognosis is improved by the development novel effective radiation therapy, such as accelerated hyperfractionated thoracic radiotherapy (AHF-TRT) (3). On the other hands, for ED-SCLC which is beyond the boundaries of LD including distant metastases, malignant pericardial, or pleural effusion and contralateral supraclavicular and contralateral hilar involvement, platinum-based combination chemotherapy alone is used as the initial therapy (4 -6). Despite the several novel anticancer agents against non-small cell lung cancer were developed and shown to have favorable outcome, the chemotherapy regimens against SCLC were not making any progress in recent decade, which leads to the poor prognosis of ED-SCLC.In the past, several studies were performed to reveal the prognostic factors in SCLC (7 -19). In these studies, male, poor performance status (PS) and weight loss as the host factors, and the extent of disease, number of metastatic sites, brain metastasis, bone metastasis, liver metastasis, elevated white blood cell (WBC) counts, neutrophil counts, serum lactate dehydrogenase (LDH), alkaline phosphatase (ALP), decreased platelet (PLT) counts, albumin (ALB), sodium, and C -reactive protein (CRP) as the tumor -related factors were reported to be unfavorable prognostic factors in multivariate analysis. Among these factors, existence of distant organ metastasis become easily a major problem of treatment in clinics, and metastatic involvement of the central nervous system, the bone marrow, or the liver is usually unfavorable compared with other sites.For the brain metastasis of SCLC, whole brain radiotherapy (WBRT) was mainly performed currently in the combination with chemotherapy. Moreover, novel stereotactic irradiation (STI) techniques were developed recently, such as stereotactic radiosurgery (SRS) or volumetric-modulated arc therapy (VMAT), resulted in improving the management of adverse events and prognosis (20 -23). For the bone metastasis, not only palliative radiotherapy (24), but also novel bone modifying agents (BMAs), such as zoledronic acid or denosumab can be used in recent days (25)(26). On the other hands, we still have few treatment strategies against liver metastasis, and frequently faced lethal clinical courses of aggressive and uncontrollable liver metastasis.Given that most of data regarding the prognostic...

Prognostic effects of osteoclast inhibitors in extensive stage small cell lung cancer patients with bone metastases

“…However, this study showed no significant differences in OS between ES-SCLC patients with BM and metastasis in the brain, liver, adrenal glands and pleural cavities. Other studies suggest that liver metastases are the worst prognostic factor in patients with ES-SCLC (13,14), and that BM and brain metastases are similarly negative survival indicators. Specifically, one-year survival of SCLC patients with liver, brain and BM was 14.5, 25.1 and 23.9%, respectively (13), warranting consideration of BM as an important therapeutic target in SCLC patients.…”

DNAH10 mutation correlates with cisplatin sensitivity and tumor mutation burden in small-cell lung cancer

“…In the past three decades, limited progress has been achieved in treatment of extensive-stage SCLC (ES-SCLC), and standard chemotherapy has adopted a two-drug combination with etoposide and cisplatin (four to six cycles). Although ES-SCLC usually achieves good results in the initial stage of platinum-based chemotherapy, the clinical response rate is 50%-75%, and the median overall survival (OS) is about 10 months [1,4]. In addition, the majority of patients undergo relapse and develop chemoresistance within one year; some of them have primary resistance to cisplatin, and those with cisplatin sensitivity gradually develop resistance during the treatment [3,5].…”

Clinical factors associated with the therapeutic outcome of chemotherapy in very elderly cancer patients

“…Serum albumin level is known to be one of the indicators of nutritional status. In cancer patients, it has been reported that a low albumin level is related to serious blood toxicity [17] as well as non-blood toxicity [18] with chemotherapy, and that a low albumin level may be a factor indicative of a poor prognosis [19]. It is also related to mortality in certain cancers [20–23].…”