Y.R. Zhai

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.

Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial.

Objective To determine the safety and therapeutic effects of nimotuzumab (h-R3) combined with radiotherapy in esophageal cancer. Methods This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery) to stage IV (supraclavicular lymph node metastasis only) esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy. Results There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50–70 Gy radiation; 37 patients (88.1%) received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events) included esophagitis and gastrointestinal, dermatological and hematological toxicities. Complete response, partial response, stable disease, and progressive disease were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients at 1 month after the treatment. The epidermal growth factor receptor (EGFR) overexpression rate was 95.2%. After a median follow-up of 37 months, the median survival time (MST) was 14 months. The 2 year and 3 year overall survival (OS) rates were 33.3% and 26.2%, respectively. The median progression-free survival (PFS) time was 10 months. The 2 year and 3 year PFS rates were 24.5% and 22.1%, respectively. The MST in the 13 patients with (+++) EGFR expression (group A) and 7 patients with (++) EGFR expression (group B) was 15 and 11 months, respectively. The 2 year and 3 year OS rates were 46.2% and 38.5% in group A and 28.6% and 28.6% in group B, respectively (P = 0.405). Conclusion Although concurrent chemoradiotherapy was the standard care for locally advanced esophageal cancer, radiotherapy was the choice for those who were refused or could not tolerate chemoradiotherapy. Our study shows that nimotuzumab combined with radiotherapy was well tolerated in patients with esophageal cancer. EGFR overexpression was more common than previously reported. OS was higher after combined therapy than after historical control radiotherapy alone. Further studies are required to confirm the therapeutic efficacy of nimotuzumab in esophageal cancer.

Patterns and predictors of recurrence after radical resection of thymoma

BACKGROUND Recurrence of thymomas even after complete resection is common, but the relapse patterns remain controversial. This study aimed to define the patterns and predictors of relapse after complete resection of thymoma. METHODS A single-institution retrospective study was performed with 331 patients who underwent radical resection of thymoma between 1991 and 2012. RESULTS After a median follow-up of 59 months, the recurrence rate was 6.9% (23/331). Relapse occurred in 23 patients with the pleura (14) and tumor bed (6) as the most common sites of recurrence. According to the definitions of the International Thymic Malignancy Interest Group, 10 (43.5%) patients had local relapse, 15 (65.2%) had regional relapse, 10 (43.5%) had distant relapse. The difference in survival following relapse between lung and regional relapse was statistically significant (P=0.027) but that between lung and distant relapse was not (P=0.808). The recurrence rates correlated with the initial Masaoka stage. Further, recurrence also correlated with World Health Organization (WHO) tumor type. The recurrence-free survival rates in patients with tumor size ⩾8 cm were worse than those of patients with tumor size <8 cm (P=0.007). Tumor size was also correlated with stage (r=0.110). As tumor becomes larger, the stage is more advanced (P=0.023). Multivariate analysis showed that Masaoka stage (P=0.005), tumor size (P=0.033), and WHO histological type (P=0.046) were predictive factors of relapse. CONCLUSION Regional recurrence is the most common relapse pattern but local and distant relapse are also common. Advanced Masaoka stage, larger tumor size, and type B3 are risk factors of recurrence. Lung relapse should be considered distant relapse. Further, tumor size was correlated with Masaoka stage and therefore should be considered in the staging system.

The role of postoperative radiotherapy (PORT) in combined small cell lung cancer (C-SCLC)

Purpose To explore the value of radiotherapy in C-SCLC patients, especially in those receiving a radical resection. Results The differences of survivals between the postoperative radiotherapy (PORT) and non-PORT groups were not statistically significant. But analyzing the benefits in subgroups, PORT significantly improved OS (p = 0.015), DFS (p = 0.026), LRFS (p = 0.008) and DMFS (p = 0.030) in stage III patients. For the patients with N2 stage, all survivals of the PORT group were also statistically significantly higher than non-PORT group (p = 0.018, 0.032, 0.008, 0.042). Patients with more than 10% of metastatic lymph nodes could get a significant benefit survivals by receiving PORT (p = 0.033, 0.030, 0.025, 0.031). Having a systematic dissection of more than 17 lymph nodes was a subset which could get better OS and LRFS by receiving PORT (p = 0.045, 0.048). Methods Between Jan. 2004 to Dec. 2012, fifty-five patients diagnosed as C-SCLC after complete surgical resection in our center were retrospectively analyzed. The overall survival (OS), disease free survival (DFS), loco-regional recurrence free survival (LRFS), and distant metastasis free survival (DMFS) were calculated by Kaplan-Meier method. Conclusions PORT can significantly improve the survival of C-SCLC patients with resected pathological pN2 stage. For the patients with a large percent of metastatic lymph nodes, PORT can also improve survivals.

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.

Long-Term Outcomes of Recurrent Thymoma

Background: This study sought to analyze the results and prognosis of recurrent thymoma. Methods: Between 1991 and 2012, 32 patients that developed recurring thymoma after radical resection at initial treatment were reviewed. Results: The median follow-up duration after initial treatment and recurrence was 89 and 49.5 months, respectively. The median recurrence free internal (RFI) was 42 months, and the 5-year overall survival (OS) rates following recurrence was 65.5% for recurrent thymoma. Among 32 patients that relapsed, 7 underwent reoperation, 18 experienced nonsurgical management, 5 failed to receive treatment, and 2 remain unknown. The 5-year OS rates after recurrence of the surgery plus adjuvant chemotherapy/radiotherapy group and the non-surgery group were 100% and 73.1%, respectively (P=0.210). Histological WHO upgrading was frequently observed (57.1%) in patients with recurrent thymoma who received reoperation. In univariate analysis, age (<55 years, P=0.009), local and regional recurrence (P=0.022), and late recurrence (RFI ≥ 20 months, P=0.038) indicated good prognostic factors of recurrent thymoma. Conclusions: Reoperation plus adjuvant chemotherapy/radiotherapy may result in good outcomes for patients who can tolerate surgery when complete resection is possible, and may get better results than non-surgery treatment. Histological WHO upgrade was frequently observed in recurrent thymoma. Age <55 years, local and regional recurrence, and longer RFI (RFI ≥ 20 months) were associated with a positive prognosis.