Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the two major histological categories of lung cancers. Drug resistance is a great challenge for cancer treatment, and histological transformation from NSCLC to SCLC is one of the mechanisms underlying drug resistance in NSCLC patients. SCLC-transformed patients show combined characteristics of NSCLC and SCLC; however, they lack timely diagnoses and effective treatment strategies. Thus, we reviewed the clinical characteristics of SCLC transformation patients with a literature search to enhance clinical consciousness, diagnosis, and personalized treatment for patients with it.

Background: Histone deacetylase inhibitors (HDACi) have shown pre-clinical promise in estrogen receptor(ER)-modulation and restoring sensitivity to endocrine manipulation, suggesting potential clinical benefit (Sabnis 2011) (Huang 2000) in ER+ breast cancer. Vorinostat is an FDA-approved HDACi for CTCL, and could have a beneficial role in restoring ER-signaling in endocrine-resistant tumors (Munster 2011) (Yardley 2011). [F-18]fluoroestradiol (FES) PET imaging may be used to monitor regional tumor ER expression in patients with breast cancer (Linden 2011). Methods: Patients with metastatic breast cancer with prior clinical benefit from endocrine manipulation who progressed on an AI therapy are eligible for this ongoing trial. In part A, patients were given vorinostat for 2 weeks, then resumed AI for 6 W. In part B (reflecting results of prior HDACi trials) patients are given vorinostat 400mg po daily 5/7 days 3/4 weeks while AI is given continuously. Paired FES and FDG PET are performed at baseline, week 2 and 8; clinical/radiologic assessment of disease is also performed at week 8. Patients with clinical benefit (response or stable disease) may continue on treatment until progressive disease or study withdrawal. Lesion-level analysis of the association between baseline FES uptake (logged) and FES/FDG ratio used generalized estimating equations (GEE) with small-sample adjustments to standard errors. Results: 12/ 20 planned patients have accrued, and the treatment is well tolerated. Enrolled women were postmenopausal, the majority with primary infiltrating ductal tumors, bone/soft tissue dominant with longstanding metastatic disease, exposed to multiple endocrine and chemotherapy regimens. Five patients have had clinical benefit (2/4 on part B with greater HDACi exposure). One patient withdrew from the study due to toxicity. FES and FDG uptake was analyzed in 42 lesions in 11 patients. Average FES uptake was 2.0 (SULmean) for patients with clinical benefit, and 1.2 in patients with progressive disease by 8 weeks (p = 0.09). FES/FDG ratio at baseline was also associated with response (p = 0.04). Conclusions: HDACi therapy is promising in relapsed ER+ breast cancer. Imaging of metabolic pathways in parallel with clinical trials may accelerate understanding of the underlying tumor biology and refine treatment selection. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-03.