Zongmei Zhou

Randomized phase II study of concurrent cisplatin/etoposide or paclitaxel/carboplatin and thoracic radiotherapy in patients with stage III non-small cell lung cancer

OBJECTIVE To evaluate the activity and safety of concurrent thoracic radiotherapy (TRT) plus weekly paclitaxel/carboplatin (PC) regimen compared with widely used cisplatin/etoposide (PE) regimen in patients with unresectable stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Patients were randomly assigned to receive the following treatments: PE arm, cisplatin (50mg/m(2)) on days 1, 8, 29, and 36 and etoposide (50 mg/m(2)) on days 1-5 and 29-33 plus 60 Gy of TRT; PC arm, weekly concurrent carboplatin (AUC = 2) and paclitaxel (45 mg/m(2)) plus 60 Gy of TRT. RESULTS A total of 65 patients were randomized (PE arm, n = 33; PC arm, n = 32). The 3-year overall survival (OS) was significantly better in the PE arm than in the PC arm (33.1% vs. 13%, P = .04). The incidence of Grade 3/4 neutropenia was 78.1% in the PE arm and 51.5% in the PC arm (P = .05). The rate of Grade 2 or greater radiation pneumonitis was 25% in the PE arm and 48.5% in the PC arm (P = .09). CONCLUSIONS Compared to PE regimen, weekly PC regimen cannot be recommended since it failed to achieve an improvement in either OS or PFS.

Postoperative Radiotherapy for Resected Pathological Stage IIIA–N2 Non-Small Cell Lung Cancer: A Retrospective Study of 221 Cases from a Single Institution

BACKGROUND For patients with resected pathological stage IIIA-N2 non-small cell lung cancer (NSCLC), the role of postoperative radiotherapy (PORT) is not well defined. In this single-institutional study, we re-evaluated the effect of PORT on overall survival (OS) as well as tumor control in this subgroup of patients. METHODS In 2003-2005, 221 consecutive patients with resected pathological stage IIIA-N2 NSCLC at our institution were retrospectively analyzed in an institutional review board-approved study. The effect of PORT on OS, cancer-specific survival (CSS), and disease-free survival (DFS) was evaluated using the Kaplan-Meier method and log-rank tests. The impact of PORT on locoregional control and distant metastasis was also analyzed. Results. Compared with the control, patients treated with PORT had a significantly longer OS time (χ2, 3.966; p = .046) and DFS interval (χ2, 6.891; p = .009), as well as a trend toward a longer CSS duration (χ2, 3.486; p = .062). Patients treated with PORT also had a significantly higher locoregional recurrence-free survival rate (χ2, 5.048; p = .025) as well as distant metastasis-free survival rate (χ2, 11.248; p = .001). Multivariate analyses showed that PORT was significantly associated with a longer OS duration (p = .000). CONCLUSIONS PORT can significantly improve the survival of patients with resected pathological stage IIIA-N2 NSCLC. A prospective randomized multicenter clinical trial is ongoing.

Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

PURPOSE To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. METHODS AND MATERIALS A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. RESULTS Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. CONCLUSIONS Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

Thoracic radiation therapy improves the overall survival of patients with extensive-stage small cell lung cancer with distant metastasis.

The authors conducted a retrospective study to evaluate the effects of thoracic radiation therapy (TRT) for patients with extensive‐stage small cell lung cancer (ED‐SCLC).

Epidermal Growth Factor Receptor Is a Prognosis Predictor in Patients With Esophageal Squamous Cell Carcinoma

BACKGROUND Our previous study indicated the survival rate for esophageal squamous cell cancer (ESCC) patients in stage III and positive lymph node groups with postoperative radiation therapy was significantly increased compared with surgery alone. But a predictive biomarker was needed to identify the patients who would benefit from postoperative radiotherapy. This study aims to evaluate epidermal growth factor receptor (EGFR) as an indicator to predict the prognosis of ESCC and to identify the patients who would benefit from postoperative radiotherapy. METHODS Tissue samples were collected from our previous randomized study: 243 in the surgery alone group and 198 in the surgery plus radiotherapy group. Expression of EGFR was analyzed by immunohistochemical staining. RESULTS The expression of EGFR is correlated with depth of tumor invasion (p=0.005), lymph node metastasis (p<0.001), and pathologic stage (p<0.001). The survival rate of patients with high EGFR expression is significantly lower than that of patients with low EGFR expression (p=0.000). Notably, in stage IIA cases, the 5-year survival rate is 57.6% in the low EGFR expression group and 36.6% in the high expression group (p=0.020). EGFR is one of the independent variants that influence the prognosis. Moreover, for high EGFR expression patients the survival rate of the surgery plus radiotherapy group is higher than that of the surgery alone group (p=0.034). CONCLUSIONS Expression of EGFR can be a prognostic predictor for ESCC. Patients with high expression of EGFR may benefit from postoperative radiation therapy.

Changes of Circulating Transforming Growth Factor-²1 Level During Radiation Therapy Are Correlated with the Prognosis of Locally Advanced Non-small Cell Lung Cancer

Introduction: We hypothesized that plasma transforming growth factor-&bgr;1 (TGF-&bgr;1) level and its dynamic change are correlated with the prognosis of locally advanced non-small cell lung cancer (NSCLC) treated with radiation therapy (RT). Methods: Patients with stage IIIA or IIIB NSCLC treated with RT with or without chemotherapy were eligible for this study. Platelet poor plasma was collected from each patient within 1 week before RT (pre-RT) and at the 4th week during RT (during-RT). TGF-&bgr;1 level was measured with enzyme-linked immunosorbent assay. The primary end point was overall survival (OS) and the secondary end point was progression-free survival (PFS). Kaplan-Meier and Cox regression were used for risk factor evaluation. Results: A total of 65 patients were eligible for the study. The median OS and PFS were 17.7 and 13.7 months, respectively. In univariate analysis, performance status, weight loss, radiation dose, and TGF-&bgr;1 ratio (during-RT/pre-RT TGF-&bgr;1 level) were all significantly correlated with OS. In the multivariate analysis, performance status, radiation dose, and TGF-&bgr;1 ratio were still significantly correlated with OS. The median OS was 30.7 months for patients with TGF-&bgr;1 ratio ≤1 versus 13.3 months for those with TGF-&bgr;1 ratio more than 1 (p = 0.0029); and the median PFS was 16.8 months versus 7.2 months, respectively (p = 0.010). Conclusions: In locally advanced NSCLC, the decrease of TGF-&bgr;1 level during RT is correlated with favorable prognosis.

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.

Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

PURPOSE We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. METHODS AND MATERIALS The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. RESULTS The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). CONCLUSIONS Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

BackgroundBrain metastases (BM) is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC) after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2) NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset.MethodsBetween 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM.ResultsFifty-three (24.4 %) patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001) and the ratio of metastatic to examined nodes or lymph node ratio (LNR) ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000) were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %.ConclusionsIn NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

Selection of proper candidates with resected pathological stage IIIA-N2 non-small cell lung cancer for postoperative radiotherapy

To establish a prediction model in selecting fit patients with resected pIIIA‐N2 non‐small cell lung cancer (NSCLC) for postoperative radiotherapy (PORT), and evaluate the model in clinical practice.