Xiaozhen Wang

ELEVATION OF PLASMA TGF-β1 DURING RADIATION THERAPY PREDICTS RADIATION-INDUCED LUNG TOXICITY IN PATIENTS WITH NON-SMALL-CELL LUNG CANCER: A COMBINED ANALYSIS FROM BEIJING AND MICHIGAN

PURPOSE To test whether radiation-induced elevations of transforming growth factor-beta1 (TGF-beta1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power. METHODS AND MATERIALS Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-beta1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was > or = Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. RESULTS A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-beta1 ratio > 1 vs. 7.9% in patients with a TGF-beta1 ratio < or = 1 (p < 0.001), and it was 42.9% if MLD > 20 Gy vs. 17.4% if MLD < or = 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-beta1 ratio < or = 1 and MLD < or = 20 Gy, 47.4% in those with a TGF-beta1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-beta1 ratio >1 and MLD > 20 Gy (p < 0.001). CONCLUSIONS Radiation-induced elevation of plasma TGF-beta1 level during RT is predictive of RILT. The combination of TGF- beta1 and MLD may help stratify the patients for their risk of RILT.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial

Background The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients and methods Patients were randomly received 60–66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1–5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. Results A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%–28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55–1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). Conclusion EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. Trial registration ID NCT01494558.

Radical thoracic radiotherapy may provide favorable outcomes for stage IV non‐small cell lung cancer

This study investigates the outcome of synchronous stage IV non‐small cell lung cancer (NSCLC) patients who received radical thoracic radiotherapy (TRT).

Role of radiotherapy in treating patients with primary malignant mediastinal non-seminomatous germ cell tumor: A 21-year experience at a single institution.

The aim of this study was to investigate the clinical characteristics and outcomes of patients with primary malignant mediastinal non‐seminomatous germ cell tumor (MMNSGCT) by comparing the efficacies of different treatment modalities.

Hypofractionated radiotherapy for medically inoperable stage I non‐small cell lung cancer

To investigate the clinical outcomes and toxicity of hypofractionated radiotherapy for medically inoperable stage I non‐small cell lung cancer (NSCLC).

A Single-Center Analysis of the Treatment and Prognosis of Patients With Thymic Carcinoma

BACKGROUND The low incidence of thymic carcinoma has precluded the development of randomized clinical trials, and present knowledge is based on small retrospective studies. We performed this single-center retrospective analysis to evaluate the clinical characteristics, treatments, and prognosis in patients with pathologically confirmed thymic carcinoma. METHODS Data regarding clinicopathologic characteristics, treatment protocols, toxicities, and survival were collected from 135 patients who attended our institution between January 1980 and January 2010. Survival was assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional hazards model. RESULTS The 135 patients (88 men) were with a median age of 48 years, and 123 patients were diagnosed with Masaoka stage III to IV disease. R0 resection was performed in 35 patients. Treatment comprised radiotherapy in 121 patients and chemotherapy in 60. The median follow-up time was 12.5 years. At 5 and 10 years, local-regional relapse free survivals were 81.4% and 54.4%, overall survivals were 42.2% and 15.4%, progression-free survivals were 29.7% and 8.0%, and distant metastasis-free survivals were 35.9% and 25.6%, respectively. R0 resection was the only independent prognosticator of overall survival, progression-free survival, and distant metastasis-free survival in univariate and multivariate analyses. CONCLUSIONS Thymic carcinoma was frequently diagnosed at Masaoka stage III to IV with a poor prognosis. Surgical resection is still the predominant treatment. Radiotherapy may increase local-regional relapse free survival with mild toxicities in advanced-stage patients.

Continuous intravenous infusion of recombinant human endostatin combined with concurrent etoposide plus cisplatin and radiotherapy for treatment of unresectable stage III non-small-cell lung cancer (HELPER): a phase 2, multicentre study

Abstract Background Concurrent chemoradiotherapy is the standard treatment for unresectable stage III non-small lung cancer, with frequently unsatisfactory results. We aimed to evaluate the efficacy and safety of the addition of continuous intravenous infusion of recombinant human endostatin (Endostar) to concurrent chemoradiotherapy. Methods We did this prospective, phase 2 study (HELPER) in patients with inoperable stage III non-small-cell lung cancer (defined by the American Joint Committee on Cancer 7th edn staging system) with an E performance score of 0–2; diagnoses were made on the basis of pathology or cytology results. All enrolled patients received thoracic radiation at doses of 60–66 Gy and continuous intravenous infusions of Endostar (7·5 mg/m 2 per 24h, 120 h continuously, 120 h per cycle; from day −5 to day −1, days 10–13, days 24–28, and days 38–42). Additionally, patients received two cycles of etoposide (50 mg/m 2 ; days 1–5 and days 29–33) plus cisplatin (50 mg/m 2 ; day 1, 8, 29, and 36). The primary endpoint was progression-free survival and the secondary endpoints were objective response, overall survival, local recurrence-free survival, and toxicities. Findings From November, 2012, to June, 2015, 73 patients were enrolled and 67 patients were evaluable. 56 patients were male and 11 patients were female. The median age was 59 years (range 31–69). Most patients (44, 66%) had squamous cell carcinoma. 27 patients (40%) had stage IIIa disease, and 40 (60%) had stage IIIb disease. Severe adverse events were observed in two patients (one had massive haemoptysis and one had pneumonia). The most common adverse event was leucopenia (96%; 45% were grade 3–4). The complete response was 12% and partial response was 64%. The median follow-up time was 37·1 months (range 20·1–52·1). The median overall survival was 34·7 months (21·9–47·4), progression-free survival was 13·3 months (5·5–21·0), and local recurrence-free survival was 27·1 months. Progression-free survival was 51% at 1 year, 35% at 2 years, and 28% at 3 years, overall survival was 82% at 1 year, 60% at 2 years, and 48% at 3 years, and local recurrence-free survival was 73% at 1 year, 55% at 2 years, and 50% at 3 years. Interpretation For patients with unresectable stage III non-small-cell lung cancer, continuous intravenous human recombinant endostatin in combination with concurrent chemoradiotherapy is an effective treatment with tolerable toxicities. A phase 3 study is warranted. Funding None.