Treatment Outcomes And Analysis Of Prognostic Factors For Locally Advanced Inoperable Non-Small Cell Lung Cancer

Part Ⅰ:Treatment Outcomes for Locally Advanced Inoperable Non-Small Cell Lung Cancer:A Single Center ReportPurposeTo retrospectively analyze the treatment results and investigate the prognostic factors for locally advanced non-small cell lung cancer (LA-NSCLC).Materials and MethodsWe retrospectively rewiewed the characteristics of patients with LA-NSCLC and treated with thoracic radiotherapy from January2007to December2010in our institution. The patients received surgery or radiation doses<50Gy were excluded. The survival (overall, progression-free, local progression-free, distant metastasis-free), patterns of failure and toxicities were evaluated. The prognostic factors of survival and toxicities were explored.ResultsTotal of438patients were analyzed. The median age of patients was61years old.82%of patients were male,58%were squamous cell carcinoma and63%were stage ⅢB.93%of patients were treated with IMRT.77%of patients were combined chemotherapy which including concurrent (43%) and sequential (34%). The median survival time and progression-free survival time was22.6and8.8months, respectively. The overall survival rate and progression-free rate at one, three and five years was75%,30%and17%and38%,20%and15%, respectively. A total of321patients (73%) experienced disease progression,127patients (29%) had local and/or regional recurrence,151patients (34%) had distant metastases, and43patients had (10%) local and/or regional recurrence and distant metastases. Multivariate analysis demonstrated that sex, KPS, N stage, radiation doses, chemotherapy and treatment response were independent prognostic factors of overall survival (p<0.05). For patients with combined chemotherapy, concurrent mode was slightly better than sequential, but the difference was not statistically significant (p=0.326). And the modality of combining concurrent and sequential chemotherapy was protect factor of survival (p<0.05). Lung V20and Dmean were independent prognostic factors of radiation pneumonitis (RP)(p<0.05), and esophagus V45, Dmean, concurrent chemotherapy, sex and smoking history were independent prognostic factors of radiation esophagitis (p<0.05).ConclusionsThe major modalities of treatment for LA-NSCLC were combined radiotherapy and chemotherapy. IMRT was the most widely used technology. The treatment outcomes were better than before with low accident rate of high grade radiation toxicity. Various factors were showed to be associated with prognosis. Dosimetry factors were related to radiation pneumonitis and esophagitis. Part II:Thoracic reirradiation for local recurrence of non-small cell lung cancerBackgroundTo analyze the efficacy and tolerance of thoracic reirradiation for local recurrent non-small cell lung carcinoma (NSCLC) after external beam radiotherapy.Materials and MethodsBetween January2007and December2010, twenty-seven patients with loco-regional recurrence of NSCLC after radiotherapy were retrospectively reviewed. Most reirradiation application (25/27) was performed using IMRT. The efficacy, toxicity and survival results after reirradiation and prognostic factors were analyzed.ResultsOf the27patients,23were men, and four were women (median age62years, range32-81years). The most common histology and stage was squamous cell carcinoma (63%) and stage Ⅲ (70%), respectively. The interval between the two courses of radiation varied from three to42months (median12.5months). The median BED of the initial radiation and reirradiation was72Gy (range59.6-91.2Gy) and70.2Gy (range51.7-90Gy), respectively. The median survival time from the second course of irradiation was16.4months (range1-44months) with a median follow-up of34.5months (range10-41). The overall survival rate and local progression-free rate at one, two and three years was58%,38%and28%and48%,21%and16%, respectively. For18patients (67%) with tumor-related symptoms before reirradiation, the overall symptom relief rate was72%(13/18) after the reirradiation. Grade2-3esophagitis occurred in3patients, and Grade2pneumonitis in three patients. No other Grade3or greater toxicity cases were recorded. Multivariate analysis demonstrated that longer interval to disease recurrence (<12months vs.>12months) from initial radiation was associated with longer survival after reirradiation (p=0.041; HR0.272). Patients with squamous cell carcinoma had longer progression-free survival time than patients with other pathological types (p=0.013; HR3.74). Patients with the total biologically effective dose (BED) of the two plans>142Gy had longer local progression-free time (p=0.05; HR0.369).Conclusions Thoracic reirradiation displayed favorable survival and acceptable toxicity. Long progression-free times of initial treatments were associated with improved retreatment survival. IMRT can be recommended for thoracic reirradiation. The radiation dose and normal tissue tolerance should be given individualized consideration, and according data are still unclear and require further investigation. Part Ⅲ:Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer with Definitive Chest RadiationPurposeWe intended to identify risk factors that affect brain metastasis (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy, which may guide the choice of selective prevention strategies.Materials and MethodsThe characteristics of346patients with stage Ⅲ NSCLC treated with thoracic radiotherapy from January2008to December2010in our institution were retrospectively reviewed. BM rates were analyzed using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM.ResultsThe median follow-up time was48.3months in surviving patients. A total of74(22%) patients developed BM at the time of analysis, and for40(12%) of them, the brain was the first site of failure. The1-year and3-year brain metastasis rates were15%and28%, respectively. In univariate analysis, female, age≤60years, non-squamous cell carcinoma, T3-4, N3,>3areas of lymph node metastasis, high LDH and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (p <0.05). In multivariate analysis, age≤60years (p=0.004, HR=2.037), non-squamous cell carcinoma (p=0.000, HR=3.726), NSE>18ng/ml (p=0.008, HR=1.968) and CA125≥35U/ml (p=0.002, HR=2.129) were independent risk factors for BM. For patients with0,1,2, and3-4risk factors, the3-year BM rates were7.3%,18.9%,35.8%and70.3%, respectively (p<0.001).ConclusionsAge≤60years, non-squamous cell carcinoma, serum NSE>18ng/ml and CA125≥35U/ml were independent risk factors for brain metastasis. Possibilities of selectively using PCI in higher risk patients with LA-NSCLC should be further explored in the future.