Abstract
Purpose
The aim of this study is to investigate the impact of chemotherapy and/or radiotherapy on disease-free survival and overall survival for patients with stage II thymic carcinoma.
Methods
We retrospectively evaluated the outcome of 31 patients with Masaoka stage II thymic carcinoma who were treated between 1995 and 2009 in Zhejiang Cancer Hospital. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis.
Results
Thirty-one patients were included in current study. The most common histological subtypes were squamous cell carcinoma (48.4 %), followed by undifferentiated carcinoma (19.4 %) and neuroendocrine tumor (19.4 %).The 5-year disease-free survival and overall survival rate was 74.6 and 89.5 %, respectively. Univariate and multivariate analysis revealed that radiotherapy and/or chemotherapy did not statistically associated with disease-free survival and overall survival.
Conclusion
Our result indicated that adjuvant therapy after complete resection could not impact the disease-free survival and overall survival of patients with stage II thymic carcinoma.
Keywords: Thymic carcinoma, Early stage, Treatment, Prognosis
Introduction
Thymic carcinoma is a rare mediastinal tumor (Wick et al.1982). Surgery is the standard treatment for early stage thymic carcinoma (including Masaoka stage I or stage II), and complete resection is the most important prognostic factor for survival (Lee et al. 2009; Kondo and Monden 2003a, b). Some previous studies have shown approximately survival rates of 70–90 % in patients with early stage thymic carcinoma who were treated with complete resection (Yano et al. 2008a; Kim et al. 2005). Although chemotherapy and radiation are widely applied in locally and advanced thymic carcinoma, the role of adjuvant chemotherapy and/or radiotherapy in these stages remains controversial.
According to the guidelines of the National Comprehensive Cancer Network (NCCN), systemic chemotherapy and radiotherapy are not recommended in stage I of thymic carcinoma. Radiotherapy was recommended after complete tumor resection in stage II of thymic carcinoma; however, the recommended category is 2B.
In the present study, we retrospectively evaluated the efficacy of adjuvant therapy including radiotherapy and/or chemotherapy in patients with Masaoka II thymic carcinoma and explore the role of radiotherapy and/or chemotherapy in this setting.
Methods and patients
Methods
A total of 75 patients had surgical resection for thymic carcinoma between January 1995 and December 2009 in Zhejiang Cancer Hospital. Thirty-one patients were diagnosed as pathologically stage II in this period. All of the 31 patients with complete tumor resected had pathologically confirmed thymic carcinoma. Histological typing was determined according to the 2004 World Health Organization classification. The staging was performed for all patients according to the Masaoka–Koga system. The recurrence or metastases were confirmed using chest CT, as well as ultrasound and/or CT of the abdomen.
Follow-up
Surviving patients were followed every 3–6 months for the first 5 years, than annually. The history, physical examination, and chest computer tomographic scan were recorded during the follow-up time. Survival case was recorded from the first day of operation to the date of death or last follow-up visit. July 2013 was the last censoring date for survival. The median time from surgery to the last censoring date was 65 months, ranging from 25 to 187 months.
Statistical analysis
The Kaplan–Meier method was used to estimate survival curves. Disease-free survival encompassed the time from the surgery to documented progression or death from any cause. The definition of overall survival was determined from the date of surgery and the last known follow-up or date of death. P value of <0.05 was regarded as statistically significant. All statistical tests were analyzed using the computer software SPSS version 16.0 (SPSS Inc, Chicago, IL, USA).
Results
Patient characteristics
The total number of patients in this analysis was 31. Table 1 showed the patient clinical characteristics. The median age was 48 years (range 24–71 years). Fifteen patients were diagnosed with squamous cell carcinoma, and 6 patients were undifferentiated carcinoma. Six patients were diagnosed as having neuroendocrine tumors and four patients with other histologic classification.
Table 1.
Demographic characteristics of the study population
| Gender | Number (%) |
|---|---|
| Male | 14 (45.2) |
| Female | 17 (54.8) |
| Age | |
| Range | 24–71 |
| Median | 48 |
| <50 | 21 (67.7) |
| ≥50 | 10 (32.3) |
| Histology | |
| Squamous cell carcinoma | 15 (48.4) |
| Undifferentiated carcinoma | 6 (19.4) |
| Neuroendocrine tumor | 6 (19.4) |
| Others | 4 (12.8) |
| Treatment after surgery | |
| Only radiotherapy | 12 (38.7) |
| Only chemotherapy | 1 (3.1) |
| Radiotherapy + chemotherapy | 9 (29.0) |
| No | 9 (29.0) |
Treatment after operation
All patients underwent complete surgical resection. Twenty-two patients received radiotherapy and/or chemotherapy. Twenty-one patients were treated with radiation therapy (12 with only radiotherapy and 9 with radiotherapy and chemotherapy). Ten patients received chemotherapy (one with only chemotherapy and 9 with radiotherapy and chemotherapy), regimen containing carboplatin and paclitaxel (n = 2), CAP (cyclophosphamide + doxorubicin + cisplatin, n = 5), and VIP (ifosfamide + cisplatin + etoposide, n = 3).
Factors affecting overall survival by univariate and multivariate analysis
Univariate analyses were performed by the Kaplan–Meier method to assess the predictive capability of each variable assessed. These data are summarized in Table 2. Age, gender, radiotherapy, chemotherapy, and chemoradiotherapy were not found to be statistically associated with DFS and OS (Fig. 1a, b). Histology (undifferentiated carcinoma versus other histology) was predictive of DFS, but not OS.
Table 2.
Univariate analysis of the patient survival according to the clinicopathologic characteristics
| 5-year DFS rate (%) | P | 5-year OS rate (%) | P | |
|---|---|---|---|---|
| Gender | 0.086 | 0.079 | ||
| Male | 57.5 | 80.0 | ||
| Female | 90.9 | 100 | ||
| Age | 0.904 | 0.309 | ||
| <50 | 78.4 | 85.7 | ||
| ≥50 | 60.0 | 75.0 | ||
| Histology | 0.039 | 0.127 | ||
| Undifferentiated | 44.4 | 93.3 | ||
| Others | 83.1 | 75.0 | ||
| Treatment | 0.068 | 0.708 | ||
| Yes | 84.0 | 87.5 | ||
| No | 44.4 | 50.0 | ||
| Adjuvant chemotherapy | 0.362 | 0.420 | ||
| Yes | 75.0 | 85.7 | ||
| No | 74.7 | 91.7 | ||
| Adjuvant radiotherapy | 0.101 | 0.985 | ||
| Yes | 83.0 | 86.7 | ||
| No | 54.0 | 66.7 | ||
| Radiotherapy and chemotherapy | 0.395 | 0.212 | ||
| Yes | 71.1 | 83.3 | ||
| No | 76.3 | 92.3 |
Fig. 1.
a DFS in treatment group and observation group (P = 0.068), b OS in treatment group and observation group (P = 0.708)
The variables included in the final model are presented in Table 3 and include age, gender, and treatment (radiotherapy and/or chemotherapy) and histology; none factors have significantly influenced on survival in multivariate analysis.
Table 3.
Multivariate survival analysis for disease-free survival and overall survival
| DFS | OS | |||||
|---|---|---|---|---|---|---|
| HR | 95 % CI | P | HR | 95 % CI | P | |
| Gender (male vs. female) | 2.570 | 0.454–14.552 | 0.286 | 168.479 | 0.001–1.26 | 0.957 |
| Age (≥50 vs. <50) | 0.952 | 0.157–5.761 | 0.957 | 0.655 | 0.086–5.005 | 0.686 |
| Adjuvant treatment (yes vs. no) | 1.997 | 0.397–10.041 | 0.401 | 0.528 | 0.043–6.497 | 0.618 |
| Histologic subtype (undifferentiated vs. other types) | 2.346 | 0.462–11.914 | 0.304 | 2.828 | 0.353–22.652 | 0.327 |
Discussion
To our knowledge, this is one of the largest studies to evaluate the value of radiotherapy and/or chemotherapy in stage II thymic carcinoma. Our results suggest that adjuvant radiotherapy and/or chemotherapy after complete resection could not impact the disease-free survival and overall survival of patients with stage II thymic carcinoma.
Whether postoperative radiation and chemotherapy reduce the rate of local recurrence and distant metastasis in completely resected thymic carcinoma is controversial (Yano et al. 2008b; Kitami et al. 2001; Sakai et al. 2013). A multicenter retrospective study by the Japanese Association for Chest Surgery demonstrated that neither adjuvant radiation nor chemotherapy improves overall survival in patients with completely resected thymic carcinoma (Kondo and Monden 2003a, b). However, some studies showed postoperative mediastinal radiation therapy in terms of reducing local recurrence and prolonging survival time (Nonaka et al. 2004; Latz et al. 1997). Similarly, adjuvant chemotherapy in some studies showed a benefit of reduce distant metastasis rate and prolonging overall survival and other did not indicated any role (Sakai et al. 2013; Kondo and Monden 2003a, b). Our series also revealed that adjuvant treatment could not be found to be of significant effect in completely resected thymic carcinoma. However, considering selection bias and small number, no conclusion can be set on the efficacy of adjuvant treatment.
Our study is limited by its retrospective design over a long period and its small number of patients. In addition, there were only 8 patients with recurrence in the current study, of which 4 were dead. Therefore, the influence of radiotherapy and/or chemotherapy on DFS and OS might be viable for a longer time follow-up. However, with few cases in previous clinical studies, our retrospective study may also be considered to be meaningful.
In summary, adjuvant radiotherapy and/or chemotherapy after complete resection in stage II thymic carcinoma could not impact the DFS and OS. Multicenter prospective trials should be performed to elucidate the effect and survival benefit of adjuvant chemotherapy and radiation.
Conflict of interest
The authors declare no conflict of interest.
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