Yi-Ting Yen, MD,* Wu-Wei Lai, MD,* Kai-Wei Chang, MD, Kung-Chao Chang, MD, PhD, Shang-Chi Lee, MsD, Sheng-Hsiang Lin, PhD, Ming-Ho Wu, MD, and Yau-Lin Tseng, MD, PhD Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medical College, National Cheng Kung University, Department of Pathology, National Cheng Kung University Hospital, College of Medical College, National Cheng Kung University, Biostatistics Consulting Center, National Cheng Kung University Hospital, Institute of Clinical Medicine, National Cheng Kung University, and Division of Thoracic Surgery, Department of Surgery, Tainan Municipal Hospital, Tainan, Taiwan

Background. There are few data on factors predicting recurrence of completely resected thymic carcinoma. This study analyzed prognosticators for recurrence and postrecurrence survival. Methods. Eighty-two patients with surgically treated thymic carcinoma were reviewed between June 1988 and March 2013, and 54 who underwent complete resection were enrolled. Sex, age, myasthenia gravis, tumor histologic classification, Masaoka staging, characteristics of locoregional invasion and recurrence, and the treatment for recurrence were collected. Continuous variables between groups were compared using Student’s t test, and categorical variables were compared using the c2 test, Fisher’s exact test, or Spearman rank correlation. Survival analysis was performed using the Kaplan-Meier and logrank test. Statistical significance was set at a probability value of less than 0.05. Results. A total of 54 patients underwent complete resection for thymic carcinoma, 21 of whom had recurrent diseases and 33 of whom remained disease-free. Patients without recurrent disease had a significantly better 5-year

overall survival of 79% than 26% of those who had recurrent disease (p [ 0.000). Masaoka staging and tumor invasion of the superior vena cava were significantly associated with recurrence-free survival in the univariate analysis (p [ 0.047 and 0.019, respectively). In the multivariate analysis for survival, tumor invasion into the superior vena cava was the only prognostic variable for recurrence-free survival (p [ 0.047). Patients who underwent surgical intervention followed by chemotherapy for recurrent diseases had the best progression-free survival after recurrence (p [ 0.000). Conclusions. Superior vena cava invasion as well as Masaoka staging was significantly associated with recurrence-free survival in patients with completely resected thymic carcinoma. In patients with recurrent disease, surgical resection should be attempted for localized disease because it might provide some benefit for progression-free survival.

S

carcinoma and thymoma as separate and distinct histologic entities [5], they tend to be treated fairly similarly. Factors predicting recurrence and the optimal treatment for recurrent disease have been investigated; however, the number of patients with surgically treated thymic carcinoma was small, and patients who underwent incomplete resection were included [2, 4, 6–8]. Before this study, we reported that involvement of the great vessels indicated poor prognosis in patients with surgically treated thymic carcinoma [9], and over the years we have had a substantial number of surgically treated patients in our institution, especially those treated with complete resection. Prognostic statements can therefore be made on the basis of greater patient collectives. Given that longterm survival is achievable with resection and recurrence may provide a more clinically relevant end point [10], the present study used the latest classification of thymic carcinoma, inclusive of carcinoid and exclusive of type B3 thymoma, to retrospectively analyze the prognostic factor in patients with completely resected thymic carcinoma.

urgical resection is considered the mainstay of treatment for thymic epithelial tumors [1–3]. Despite the fact that complete resection provides the best survival and opportunity of cure, approximately 10% to 30% of patients with thymic epithelial tumors undergoing surgical resection had recurrent diseases [2–4]. Thymic carcinoma is relatively uncommon among thymic neoplasms, traditionally considered together with thymoma and comprising approximately 10% of these lesions [3], and it presents frequently with locally advanced or distant metastatic disease. Although the recent update of the World Health Organization classification in 2004 officially recognizes the distinction between thymic

Accepted for publication Dec 18, 2013. *Yi-Ting Yen and Wu-Wei Lai contributed equally to this manuscript. Address correspondence to Dr Tseng, Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, 138 Sheng-Li Rd, Tainan 704, Taiwan; e-mail: [email protected]

Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc

(Ann Thorac Surg 2014;97:1169–75) Ó 2014 by The Society of Thoracic Surgeons

0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2013.12.024

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Factors Predicting Recurrence and Postrecurrence Survival in Completely Resected Thymic Carcinoma

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Material and Methods Patient Enrollment A retrospective review of medical records between June 1988 and March 2013 was conducted among 82 patients who underwent intent-to-treat surgery for thymic carcinoma. Informed consent was waived because the study was retrospective, and the review of medical records was approved by the institutional review board of National Cheng Kung University Hospital (B-ER-101-347). The surgical pathologic diagnoses, including the tumor histology and resection margin, were microscopically confirmed by an experienced pathologist, who was blind to the clinical data, and the tumors were classified according to the newly published World Health Organization classification. Clinical information was collected on sex, age, myasthenia gravis, tumor histology, Masaoka staging, characteristics of locoregional invasion, sites of recurrence, and the treatment modalities for recurrent disease. Tumor histology, Masaoka stage, and characteristics of tumor invasion were included in the analysis of prognostic factors for survival.

General Management Principles for Thymic Carcinoma Computed tomography or magnetic resonance imaging was used to evaluate whether the lesions were resectable. Abdominal sonography and whole-body bone scan were routine preoperative metastatic evaluation modalities. Biopsy was performed by mediastinotomy, mediastinoscopy, or thoracoscopy for unresectable lesions. Preoperative cisplatin-based chemotherapy along with radiation therapy (3,000 to 5,000 cGy) were administered to patients whose imaging studies showed locally advanced and unresectable diseases, including superior vena cava syndrome or pericardial effusion with encasement of the pulmonary vessels or aorta. The chemotherapy consisted of three cycles of cisplatin (60 mg/m2, day 1), and etoposide (120 mg/m2, day 1) every 3 weeks. Postoperative chemotherapy was given to patients who had residual or recurrent disease. The regimen was composed of three cycles of cisplatin (50 mg/m2, day 1), doxorubicin (50 mg/m2, day 1), and cyclophosphamide (500 mg/m2, day 1) every 3 weeks. Operative procedures were subsequently performed if the tumor had been downstaged radiographically and evaluated as resectable. Postoperative radiation therapy with a full dose (5,000 to 6,000 cGy) was routinely performed at the tumor bed and mediastinum for patients undergoing complete resection if they were not preoperatively irradiated. For those with residual, recurrent disease or who were previously irradiated, the dose of radiotherapy was tailored accordingly so that it was limited to a total dose of 6,000 cGy in the mediastinum.

Surgery for Thymic Carcinoma Radical resection, including extended thymectomy and thymomectomy, was the goal of surgery. The phrenic or recurrent laryngeal nerve was preserved under the condition that the tumor capsule was not violated. Resection of the nerve was otherwise performed if it was

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severely adherent or encased by the tumor. The lung parenchyma was resected using surgical staples instead of dissection if adhesion between the tumor and lung parenchyma was identified. For tumors involving more than half the circumference of the superior vena cava (SVC), we performed a total excision followed by prostheses (ringed GoreTex, woven Dacron, and pericardial tube graft) interposition as in our previous report [11]. Direct resection and repair was done if less than half of the circumference was involved and the blood flow was not compromised, and patched repair with equine pericardium was done instead if the lumen would have been compromised.

Follow-Up and Evaluation of Recurrence All the patients were followed up for at least 6 months or until the time of their death. For patients with clinical appearance of new diseases on follow-up imaging after a complete resection, thoracoscopy was the option of diagnostic and therapeutic modality for intrathoracic lesions. Extrathoracic lesions were determined by biopsy and tissue proof whenever possible, or the consensus of a multidisciplinary panel discussion based on the RECIST guideline [12, 13]. Recurrence was divided into three categories according to the definition of the International Thymic Malignancy Interest Group [14]. A local recurrence was defined as disease appearing in the anterior mediastinum or tissues immediately contiguous with the resected thymus or thymic carcinoma. A regional recurrence was defined as intrathoracic recurrence that is not contiguous with the thymus or previous resected thymic carcinoma. A distant recurrence included extrathoracic recurrence and intraparenchymal pulmonary nodules. The overall survival was computed from the date of resection of primary thymic carcinoma to the date of the last follow-up or death. The recurrence-free survival was calculated from the date of resection of the primary thymic carcinoma to the date of the last follow-up or recurrence diagnosis. Recurrent disease was treated with surgery followed by chemotherapy if it was localized, and with chemoradiation therapy if not surgically feasible. Patients who died of cancers other than thymic carcinoma were defined to have nonthymic tumor–related death, whereas mortality resulting from adverse effect or complication of treatment was defined as treatmentrelated death. The survival period after recurrence was computed from the date of recurrence diagnosis to the date of the last follow-up or death. The progression-free survival after recurrence was computed from the date of treatment initiation for recurrence to the date of documentation of disease worsening.

Statistical Analysis Continuous variables between groups were compared using Student’s t test, and categorical variables were compared using the c2 test. When the numbers in a cell of the comparison table were smaller than 5, Fisher’s exact test was used for comparison between two groups, and Spearman rank correlation test was used for comparison among three groups. Survival analysis was performed

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using the Kaplan-Meier method, and the statistical difference was determined using the log-rank test. Cox proportional hazards model was used for univariate and multivariate analyses of prognostic factors. Statistical significance was set at a probability value of less than 0.05. All statistical analysis was performed using SPSS version 20.0 for Windows (IBM Corp, Armonk, NY).

Results There were a total of 82 patients with thymic carcinoma undergoing intent-to-treat surgery. Fifty-four of the 82 patients had microscopically complete (R0) resection, whereas 5 had grossly complete resection with microscopically positive margin (R1 resection), and 23 underwent resection with grossly residual tumor (R2 resection). Ten of the 82 patients were administered neoadjuvant therapy; 2 of whom received chemotherapy, 7 received chemoradiotherapy, and 1 received radiotherapy. One patient who had chemotherapy and 4 patients who had chemoradiotherapy were successfully downstaged and the tumors were completely resected, whereas the remaining 5 patients underwent R2 resection despite having radiographically reduced the tumor size. Significant differences were found among patients undergoing R0, R1, and R2 resection in the Masaoka staging, invasion of pericardium, innominate vein, SVC, aorta, and pulmonary artery (p ¼ 0.000, 0.001, 0.007, 0.016, 0.000, and 0.000, respectively; Table 1). Among the 54 patients who underwent complete resection for thymic carcinoma, 52

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were operated on with median sternotomy, 1 was approached with thoracotomy, and another 1 with videoassisted thoracoscopic surgery. Fourteen of the 54 patients with complete resection had tumor invasion into the SVC, and 7 of them underwent partial resection and direct repair, whereas the other 7 underwent patch repair or reconstruction with prosthesis. Twenty-one of the 54 patients with complete resection had recurrent diseases, whereas the remaining 33 were disease-free (Table 2). Patients without recurrent disease had a significantly better 5-year overall survival of 79% (95% confidence interval, 127 to 196 months) than 26% (95% confidence interval, 33 to 67 months) of those who had recurrent disease (p ¼ 0.000). In the univariate analysis of prognostic factors for survival, Masaoka staging and tumor invasion of the SVC were significantly associated with recurrence-free survival but not overall survival (p ¼ 0.047 and 0.019, respectively; Table 3, Fig 1). The tumor histology and locoregional invasion into the lung, pericardium, phrenic nerve, recurrent laryngeal nerve, and innominate vein were not associated with recurrence-free survival (p ¼ 0.692, 0.684, 0.560, 0.800, 0.277, and 0.499, respectively). In the multivariate analysis for survival, tumor invasion into the SVC was the only prognostic factor significantly associated with recurrencefree survival (p ¼ 0.047). Among the recurrent diseases in 21 patients with complete resection, there were 4 local recurrences, 10 regional recurrences, and 18 distant recurrences. Nine recurrences occurred in the pulmonary parenchyma, 5 in

Table 1. Comparison of Patients With Thymic Carcinoma Undergoing R0, R1, and R2 Resection Variable Sex (F:M) Age (y) Histology Squamous cell carcinoma Lymphoepithelioma-like carcinoma Others Masaoka stage I II III IV Myasthenia gravis (Y:N) Locoregional invasion (Y:N) Lung Pericardium Phrenic nerve Recurrent laryngeal nerve Innominate vein Superior vena cava Aorta Pulmonary artery Preoperative treatment (Y:N) Chemotherapy Radiotherapy

R0 Resection (n ¼ 54)

R1 Resection (n ¼ 5)

R2 Resection (n ¼ 23)

p Value

26:28 52.8  12.0

4:1 60.4  14.3

16:7 55.8  7.4

0.056 0.243 0.487

39 8 7

4 1 0

15 2 6

1 5 40 8 1:53

0 0 4 1 0:5

0 0 8 15 1:22

0.579

34:20 27:27 15:39 5:49 19:35 14:40 0:54 0:54

4:1 3:2 3:2 0:5 4:1 3:2 1:4 0:55

18:5 21:2 11:12 2:21 15:8 12:11 9:14 7:16

0.162 0.001 0.060 0.828 0.007 0.016 0.000 0.000

5:49 4:50

0:5 0:5

4:19 4:19

0.395 0.247

0.000

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Table 2. Characteristics of Patients With and Without Disease Recurrence of Completely Resected Thymic Carcinoma Variable Sex (F:M) Age (y) Histology Squamous cell carcinoma Lymphoepithelioma-like carcinoma Others Masaoka stage I II III IV Myasthenia gravis (Y:N) Locoregional invasion (Y:N) Lung Pericardium Phrenic nerve Recurrent laryngeal nerve Innominate vein Superior vena cava Preoperative treatment (Y:N) Chemotherapy Radiotherapy

No Recurrence (n ¼ 33)

Recurrence (n ¼ 21)

16:17 51.9  12.5

10:11 51.7  11.7

23 4

16 4

6

1

1 4 26 2 1:32

0 1 14 6 0:21

21:12 15:18 9:24 2:31 10:23 5:28

13:8 12:9 6:15 3:18 9:12 9:12

1:32 0:33

4:17 4:17

the bone, and 2 in the adrenal gland. There was also 1 recurrence in the liver, 1 in the brain, and another 1 in the neck lymph node. All the recurrences but 5 in the bone and 1 in the brain were documented with tissue proof. In total, 7 patients underwent surgical resection followed by chemotherapy for recurrent diseases, and 8 patients were treated with chemoradiation therapy. Nonetheless, 6 patients who had recurrent diseases did not receive further treatment (Table 4). The progression-free survival of 21 patients with recurrent diseases was further analyzed to

evaluate the efficacy of different treatment modalities. Patients treated with surgical resection followed by chemotherapy for recurrence had a significantly better progression-free survival than those undergoing chemoradiation therapy and those without treatment (p ¼ 0.000; Fig 2). In our series the longest postrecurrence survival was 67 months, which occurred in a patient undergoing extended thymectomy and thymomectomy, partial pericardiectomy, and innominate vein ligation for the primary thymic carcinoma. He had lung resection for pulmonary recurrence 41 months after the primary surgery. One patient underwent repeat surgical resection for adrenal gland recurrence 16 months after radical resection for the primary thymic carcinoma. Adrenal gland relapse also occurred in another patient 19 months after the primary surgery of extended thymectomy and thymomectomy, partial pericardiectomy, and reconstruction of the SVC and innominate vein. The adrenal lesion was resected. This patient had retroperitoneal recurrence 48 months after the primary surgery, which was also resected, and had a postrecurrence survival of 47 months. A total number of 26 patient deaths were documented, including 18 cancer-related deaths, 3 non–thymic cancer-related deaths, 1 treatment-related death, and 4 non–cancer-related deaths. Two patients died of lung cancer and 1 of hepatoma, and they were disease-free of thymic carcinoma. One patient died of radiation-induced myocarditis and subsequent heart failure 20 months after resection; he received a total dose of 5,400 cGy and was also free of thymic carcinoma. Spontaneous esophageal bleeding occurred in 1 patient 4 months after resection, who also received a total dose of 5,400 cGy postoperatively. Among those 4 non–cancer-related deaths, 1 patient, who was free of thymic carcinoma, died of cerebrovascular disease and central failure. One patient who had surgery for adrenal gland recurrence died of perforated peptic ulcer because of multiple organ failure 4 months after the adrenectomy. Deep neck infection occurred in 1 patient and resulted in death 1 month after complete resection for thymic carcinoma. One patient died of respiratory failure because of acute exacerbation

Table 3. Univariate and Multivariate Analysis of Recurrence-Free Survival of Patients With Completely Resected Thymic Carcinoma Characteristics

Numbers

Sex (F:M) Age Histology (SqCC:LE:other) Masaoka stage (IþII:III:IV) Locoregional invasion (Y:N) Lung Pericardium Phrenic nerve Recurrent laryngeal nerve Innominate vein Superior vena cava CI ¼ confidence interval;

26:28

Univariate HR (95% CI)

p Value

Multivariate HR (95% CI)

p Value

49:8:7 1þ5:40:8

0.981 1.02 0.867 2.22

(0.42–2.31) (0.98–1.06) (0.43–1.76) (1.01–4.88)

0.965 0.290 0.692 0.047

0.869 (0.43–1.75) 1.983 (0.90–4.33)

0.694 0.086

34:20 27:27 15:39 5:49 19:35 14:40

0.833 1.294 1.131 1.974 1.348 2.867

(0.34–2.01) (0.54–3.08) (0.44–2.92) (0.58–6.73) (0.57–3.20) (1.19–6.93)

0.684 0.560 0.800 0.277 0.499 0.019

0.673 (0.23–1.98) 3.071 (1.02–9.27)

0.472 0.047

HR ¼ hazard ratio;

LE ¼ lymphoepithelioma-like carcinoma;

SqCC ¼ squamous cell carcinoma.

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Fig 1. The Masaoka staging of thymic carcinoma was significantly associated with (A) a better recurrence-free survival but not (B) overall survival. Likewise, the presence of superior vena cava (SVC) invasion predicted significantly better (C) recurrence-free survival, but not (D) overall survival. (CI ¼ confidence interval.)

Table 4. Classification and Treatment for 21 Patients With Recurrent Thymic Carcinoma Classification of Recurrence Local recurrence (n ¼ 4) Regional recurrence (n ¼ 10) Distant recurrence (n ¼ 18) Lung Liver Bone Brain Adrenal gland Extrathoracic lymph node Treatment modality Surgery with chemotherapy Chemoradiation therapy No treatment

Numbers

9 1 5 1 2 1 7 8 6

Fig 2. Patients who underwent surgical intervention followed by chemotherapy for recurrent diseases had the best progression-free survival. (CI ¼ confidence interval.)

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of chronic obstructive pulmonary disease, aggravated by preexisting radiation pneumonitis. This patient remained free of thymic carcinoma for 168 months.

Comment This study enrolled a substantial number of patients undergoing complete resection for thymic carcinoma in a 20-year span of a single institution and analyzed the prognostic factors for recurrence-free survival as well as the progression-free survival after recurrence. Unlike thymoma, which is usually comorbid with myasthenia gravis [15], the rare occurrence of myasthenia gravis with thymic carcinoma portends its invasiveness before diagnosis. Factors predicting recurrence in patients with thymic carcinoma, however, have been analyzed along with those in patients with thymoma, or including patients undergoing incomplete resection [2, 4, 6–8]. It is generally agreed that complete resection should always be attempted for thymic carcinoma, although it is achieved only in 35% to 50% of the cases [1, 16, 17]. Although selected patients with locally advanced disease undergoing complete resection can experience long-term survival [9, 18, 19], it is reported that recurrence is often earlier and more distant, with lower progression-free survival in patients with thymic carcinoma [6]. The pattern of recurrence also differed significantly in patients with thymoma and thymic carcinoma [6]. Viewed as a histologically distinct entity, prognostic factors of thymic carcinoma should therefore be focused on its own patient cohort. On the other hand, older reports of risk factors must be cautiously interpreted because of lack of prolonged follow-up and use of overall survival instead of the more accurate tumor-related and recurrence-free survival. Death is inevitable if there is recurrent disease, and recurrence might precede death by many years. In addition, thymoma and neuroendocrine carcinoma are both associated with increased risk of extrathymic malignancy [20]. It is likely that patients who had non– cancer-related deaths or who died of cancer other than thymic carcinoma also had asymptomatic recurrent disease at the time of death. These undiagnosed recurrences would be responsible for the overestimated recurrencefree survival and underestimated overall survival. Moreover, treatment for recurrent disease may shed some light on the postrecurrence survival. Our study analyzed recurrence-free survival and progression-free survival after recurrence instead of overall survival so that prognostic factors predicting recurrence and postrecurrence survival could be clarified. Quite a few reports regarding treatment for recurrent thymic epithelial tumor have been published [4, 7], yet their results on thymic carcinoma were not conclusive. Given the presence of residual thymic epithelial tumor in patients undergoing incomplete resection, we believe that the clinical course and factors influencing disease progression should not be considered as those predicting recurrence after complete resection. Contradictory results have been reported about whether Masaoka staging predicts the surgical outcome of thymic carcinoma

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[21, 22]. Our results demonstrated that Masaoka staging was significantly associated with recurrence-free survival but not with overall survival of patients with completely resected thymic carcinoma. In fact, the number of patients with stage I and II thymic carcinoma was limited and outweighed by that of patients with stage III and IV because of its natural course as an indolent disease. As a result, delineation of locoregional invasion could facilitate our understanding of the tumor behavior, the impact on tumor recurrence and survival, and tailoring the adjuvant therapy in addition to surgical resection. The tumor histology has been identified as one of the prognosticators of recurrent thymic epithelial tumors [2, 4, 8]. In most of the studies, thymic carcinoma was categorized and analyzed along with thymoma, and few studies focused on the association of tumor relapse with subtyping of thymic carcinoma [21]. It is reported that the surgical outcome of patients with thymic carcinoma depends on histologic grade [21]. We demonstrated that histologic subtyping did not affect recurrence-free survival in patients with completely resected thymic carcinoma. Despite the fact that neuroendocrine and undifferentiated carcinoma were classified as intermediate and high grade, respectively [21], only 1 patient in our series had recurrent disease in this category. This observation implies that the tumor behavior is different between recurrent and progressive disease, and complete resection provides the only opportunity of long-term survival whatever the tumor histology is. Locoregional invasion of nearby organs by thymic carcinoma is common, with the lung being the organ most often involved. It is a common belief that invasion of the aorta or pulmonary vessels by thymic carcinoma precludes complete resection because of extensive encasement, and our surgical results validated that involvement of the great vessels was associated with incomplete resection and hence poor prognosis, compatible with our previous report [9]. Specifically, invasion of the SVC did not preclude surgery, and long-term survival could be anticipated if the tumor was radically resected. Our results showed tumor invasion of the SVC was associated with an inferior recurrence-free survival after complete resection, suggestive of occult metastasis arising from penetration and spread of tumor cells. Despite routine performance of postoperative radiotherapy as an adjunct for completely resected thymic carcinoma, still recurrence developed in 21 of 54 patients. The administration of preoperative chemoradiation in our series did not seem to reduce the likelihood of recurrence. In fact, preoperative chemoradiation was intended to reduce the extent of tumor invasion when vascular invasion precluded direct and complete resection. Even though complete resection could be achieved after neoadjuvant therapy, tumor invasion into the SVC was often the case. This may explain the finding that occult metastasis, which occurred mostly along with great vessel invasion, accounts for the recurrent disease after complete resection. The administration of adjuvant chemotherapy after surgical resection should therefore be taken into account for SVC-invading thymic carcinoma.

The optimal treatment for recurrent disease in patients with thymic carcinoma mainly relies on the lesion site. Although surgical resection has been advocated as the preferred treatment modality for recurrent thymoma, it is not yet validated for thymic carcinoma. We found that SVC invasion was significantly associated with an inferior recurrence-free survival. The overall survival, however, was not affected by the presence of SVC invasion, indicating that certain factors might have influenced the survival after recurrence. In addition, recurrence in the pleural space and lung parenchyma was the most common in our series, different from some published literature that reported disease relapse tended to be distant in patients with thymic carcinoma [6]. We believe this is because our population includes patients undergoing complete resection for thymic carcinoma, whose recurrent diseases result from occult metastasis instead of residual or existing tumor. Incompletely resected thymic carcinoma, on the contrary, contributes to the earlier and more distant relapse with an evident tumor burden rather than circulating tumor cells. Surgical resection, in our experience, should therefore be performed not only for the recurrent disease localized in the thorax but also for a single solitary extrathoracic metastatic lesion. Repeat recurrence after surgical resection for recurrent disease could also be attributed to the circulating tumor cells as in patients undergoing complete resection for primary thymic carcinoma. In fact, 1 patient experienced repeated surgical resection for his recurrence in the adrenal gland and then retroperitoneum, and achieved long-term survival. Of note, patients who underwent surgical resection for recurrent disease were administered chemotherapy, which might play some role in the postrecurrence survival by eliminating the circulating tumor cells. For those whose recurrent disease is not amenable to surgery, alternative modalities such as chemoradiation therapy should be attempted as they might still provide survival benefit. This study has certain limitations because of its retrospective nature. Although the number of patients undergoing complete resection was substantial, a study on a larger scale is mandatory to further validate our conclusion. Selection bias could also exist because surgery for recurrent diseases was mostly reserved for the physically fit patients. Besides, patients who were amenable to surgical intervention might have an intuitively better survival because the disease extent was limited. Patients who died of causes other than thymic carcinoma remained free of recurrent disease, which might contribute to a shorter overall survival. More research into the impact of adjuvant chemotherapy on the prevention of recurrence is necessary so that the effect of occult metastasis from vascular invasion can be defined. In conclusion, our study revealed that SVC invasion as well as Masaoka staging was significantly associated with recurrence-free survival in patients with completely resected thymic carcinoma. In patients with recurrent disease, surgical resection should be attempted whenever feasible, especially for those with localized disease, as it might provide some benefit for progression-free survival.

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Factors predicting recurrence and postrecurrence survival in completely resected thymic carcinoma.

There are few data on factors predicting recurrence of completely resected thymic carcinoma. This study analyzed prognosticators for recurrence and po...
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