Postoperative radiation therapy after complete resection of thymoma has little impact on survival

BACKGROUND:

Postoperative radiation therapy for thymoma is widely used, although the clinical benefits are controversial. Furthermore, to the authors' knowledge, the relation between postoperative radiation therapy and cell type classified by the World Health Organization (WHO) is not known.

METHODS:

The records of 324 patients (ages 17‐83 years; mean, 51 years; 160 males and 164 females) who underwent complete resection of a thymoma between 1970 and 2005 were reviewed. Mediastinum postoperative radiation therapy was performed for 134 patients. Survival rates and patterns of recurrence were determined according to Masaoka stage and WHO cell type.

RESULTS:

The 10‐year disease‐specific survival rates for patients with and without postoperative radiation therapy were 92.8% and 94.4%, respectively (P = .22). Subset analyses after stratifying by Masaoka stage and WHO cell type demonstrated that the 10‐year disease‐specific survival rate for patients without postoperative radiation therapy with Masaoka stage I and II, as well as those with WHO cell types A, AB, or B1, was 100%, which was satisfactory. Furthermore, the rates for patients with Masaoka stage III/IV and those with WHO cell types B2/B3 with or without postoperative radiation therapy were not found to be significantly different. In 24 patients with disease recurrence, pleural dissemination was observed most often, followed by distant metastases; local disease recurrence without other recurrence occurred in 2.

CONCLUSIONS:

The authors concluded that surgical resection alone is sufficient for thymoma patients with Masaoka stage I and II, and those with WHO cell types A, AB, and B1. Furthermore, an optimal treatment strategy should be established for patients with Masaoka stage III/IV and WHO cell type B2/B3 thymomas. Cancer 2009. © 2009 American Cancer Society.     

Masaoka staging is of prognostic relevance in type B3 / C thymomas

BACKGROUND: The purpose of this study was to correlate the Ki67 labelling index (LI) with the Masaoka classification and the new WHO-classification in type B3 / C thymomas. PATIENTS AND METHODS: Fourteen patients with type B3 / C thymomas were evaluated, and archived specimens were histologically reclassified according to Masaoka staging, the new WHO classification and the Ki-67 LI in a retrospective analysis. RESULTS: Four patients presented with Masaoka stage II disease (all WHO-type B3), 1 patient had stage III (WHO-type C), 6 stage IVa (3 WHO-type B3 and 3 WHO-type C), and another 3 patients stage IVb (all WHO-type C). The statistical analysis revealed a significant correlation between Masaoka staging and Ki-67 LI (II, III vs. IV; p = 0.007). As well, WHO-classification correlated significantly with Ki-67 LI (B3 vs. C; p = 0.015). Masaoka staging (II, III vs. IV) correlated significantly with survival status (p = 0.0237) in patients with type B3 / C thymoma whereas WHO-classification did not (p = 0.3266). Between survivors and non-survivors there was no statistically significant correlation concerning Ki-67 LI (p = 0.075). CONCLUSION: Our study indicated that the Masaoka staging system is of prognostic relevance in type B3 / C thymomas.     

World Health Organization histologic classification: an independent prognostic factor in resected thymomas

The histologic classification of thymoma remained controversial since 1999, when the World Health Organization (WHO) Consensus Committee published a histologic typing system for tumours of thymus. Clinical features, postoperative relapsing rates, and survival of patients with thymoma were evaluated with reference to the WHO histologic classification, based on a series of 178 patients, submitted to surgery between 1988 and 2000.There were 21 type A, 49 type AB, 45 type B1, 50 type B2 and 13 type B3 tumours. The invasiveness of tumours was 23.8%, 51%, 73.3%, 82% and 100% for types A, AB, B1, B2 and B3 tumours, respectively. The frequency of invasion of the great vessels increased according to the tumour type in the order A (0%), AB (4%), B1 (6.6%), B2 (22%), and B3 (23%). The 10-year disease-free survival was 95%, 90%, 85%, 71% and 40% for types A, AB, B1, B2 and B3, respectively. According to the Masaoka staging system, the disease-free survival rates were 94%, 88% and 66% for stages I, II and III, respectively, at 10 years. No stage IVA thymomas reached 10 years follow-up. Overall survival at 10 years were 88% and 25% when complete and incomplete resection were considered. By multivariate analysis, Masaoka staging system, WHO histologic classification and complete resection were significant independent prognostic factors, whereas age- and sex-associated myasthenia gravis were not. The present study demonstrated the World Health Organization histologic classification a good prognostic factor, such as completeness of surgical resection and Masaoka staging system.     

New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China

BACKGROUND: In 1999, a World Health Organization (WHO) committee published histologic criteria for distinct thymoma entities (labeled as Type A, AB, B1, B2, B3 thymomas) and for the heterogeneous group of thymic carcinomas, collectively called Type C thymomas. Whether WHO-defined histologic thymoma subtypes are of independent prognostic relevance has yet to be proved. METHODS: Two hundred thymomas from the Shanghai Chest Hospital with a mean follow-up time of 15 years (range, 1-246 months) were studied for the relevance of WHO histologic subtype and other factors (stage, therapy, and myasthenia gravis [MG]) for survival. RESULTS: In order of frequency, 68 patients (34.0%) had Type AB, 39 (19.5%) had Type B2, 36 (18.0%) had Type C, 27 (13.5%) had Type B3, 17 (8.5%) had Type B1, and 8 (4.0%) had Type A thymoma. Five cases (2.5%) were rare thymomas not mentioned in the WHO classification. Survival data showed significant differences among the histologic subtypes (log rank test: P < 0.001). Among patients with Type A and AB thymomas, none died of tumor; of the Type B1 thymoma patients, only one (5.9%) died at 22 months. Type B2, B3, and C thymomas had a significantly worse prognosis with 5-year survival rates of 75.0%, 70.0%, and 48.0%, respectively. Ninety-six patients (48.0%) were in Masaoka Stage I, 26 (13.0%) were in Stage II, 65 (32.5%) were in Stage III, and 13 (6.5%) were in Stage IV. Stage was highly significant in predicting survival (log rank, test P < 0.001). The association between histologic subtype and invasive behavior (stage) was statistically significant (P < 0.001). However, histology was an independent predictive factor of survival in Stage I and II thymomas: Type B2, B3, and C thymomas had a worse prognosis than Type A, AB, and B1 thymomas (log rank test: P < 0.003). Thirty patients (15.0%) presented with MG. MG was significantly more frequent in Type B2 and B3 than in Type A, AB, and B1 thymomas (P < 0.01). On multivariate analysis, MG had no adverse effect on survival (P = 0.17). Radiation or chemotherapy improved patients' survival at 5 and 10 years in Type B2, B3, and C thymomas (log rank test: P < 0.003). CONCLUSIONS: Tumor stage is the most important determinant of survival in thymoma patients, but the WHO histologic subtype is an independent prognostic factor in Stage I and II thymomas, among which WHO Type A, AB, and B1 thymomas form a low-risk group. Patients with high-risk thymomas might profit from novel adjuvant radiochemotherapy regimens.     

Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis.

PURPOSE: Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS: Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS: Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION: The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.     

Novel prognostic groups in thymic epithelial tumors: assessment of risk and therapeutic strategy selection

PURPOSE: To assess the role of multimodality treatment on patients with thymic epithelial tumors (TETs) (i.e., thymomas and thymic squamous cell carcinoma) and to define the prognostic classes according to the Masaoka and World Health Organization histologic classification systems. METHODS AND MATERIALS: Primary surgery was the mainstay of therapy. Extended thymectomy was performed in all cases. The cases were primarily staged according to the Masaoka system. Adjuvant radiotherapy was given to patients diagnosed with Masaoka Stage II, III, and IVA TET. Adjuvant chemotherapy was administered in selected cases. RESULTS: We reviewed the records of 120 patients with TETs, with a mean follow-up of 13.8 years. Of the 120 patients, 98 (81.6%) received adjuvant radiotherapy. Of these 98 patients, Grade 1-2 pulmonary or esophageal toxicity was acute in 12 (12.2%) and late in 8 (8.2%). The median overall survival was 21.6 years. Of the 120 patients, 106 were rediagnosed and reclassified according to the World Health Organization system, and the survival rate was correlated with it. Three different prognostic classes were defined: favorable, Masaoka Stage I and histologic grade A, AB, B1, B2 or Masaoka Stage II and histologic grade A, AB, B1; unfavorable, Stage IV disease or histologic grade C or Stage III and histologic grade B3; intermediate, all other combinations. The 10- and 20-year survival rate was 95% and 81% for the favorable group, 90% and 65% for the intermediate group, and 50% and 0% for the unfavorable group, respectively. Local recurrence, distant recurrence, and tumor-related deaths were also evaluated. CONCLUSION: The analysis of our experience singled out three novel prognostic classes and the assessment of risk identified treatment selection criteria.     

A single institutional experience of thymic epithelial tumours over 11 years: clinical features and outcome and implications for future management

Thymic epithelial tumours (TETs), the most common tumour of the anterior mediastinum, are epithelial neoplasms of the thymus with a wide spectrum of morphologic features. We retrospectively analysed clinical features of TET and the correlation of World Health Organisation (WHO) histologic classification and Masaoka staging system with different treatment modalities in 195 patients, from 1995 to 2005. According to the Masaoka's staging system, there were 78 (40.0 %) patients with stage I, 38 (19.5%) with stage II, 41 (21.0%) with stage III, 38 (19.5%) with stage IV. All patients were reclassified according to the WHO criteria as follows: Type A (n=9, 4.6%), AB (n=37, 18.9%), B1 (n=29, 14.8%), B2 (n=48, 24.6%), B3 (n=40, 20.5%), C (n=32, 16.4%). There was a fairly good correlation between Masaoka staging and WHO histotype (P<0.05). However, in multivariate analysis, the tumour stage and WHO histotype were two independent factors separately for predicting overall survival (P<0.001, P<0.001, respectively). Thus, both Masaoka stage and WHO histotype should be considered in risk stratification of therapy for TET patients. Patients with completely resected types B2, B3 and C and adjuvant radiotherapy (n=57) had more favourable disease-free and overall survival as compared with those without adjuvant treatment (n=20) (P=0.015, 0.015, respectively). Given that the predominant sites of recurrence after surgery was pleura/pericardium and lung, and the fact that complete resection was a significant influential factor for survival at log-rank test, an active investigation of newer treatment strategies such as neoadjuvant treatment to improve the resectability and development of optimal adjuvant treatment modality is a high priority especially for those with high-risk for recurrence or in patients with advanced stage disease.     

A single institutional experience of surgically resected thymic epithelial tumors over 10 years: clinical outcomes and clinicopathologic features

Thymic epithelial tumors (TETs) consist of a series of neoplasm that differ morphologically and biologically. Due to its rarity and indolent natural history, large-scale prospective trials have been lacking. This study aimed to evaluate long-term clinical outcomes and clinicopathologic features for TET after surgical resection and adjuvant treatments. One hundred patients who received surgery plus adjuvant radiotherapy +/- chemotherapy for TET (Masaoka stage II-IVa) from 1995 to 2005 were retrospectively reviewed. Masaoka staging systems were adopted, and pathologic results were classified according to World health organization (WHO) histologic classification. After surgery, 55 patients were treated with radiotherapy alone, while 45 with radiotherapy and chemotherapy. The median radiation dose was 50.4 Gy (45-63 Gy) and six cycles of chemotherapy, consisting of doxorubicin, cisplatin, vincristine and cyclophosphamide, were applied every 3-4 weeks. Distributions according to Masaoka stage were as follows; stage II (58 patients), III (21) and IVa (21). According to WHO histology, there were A (3), AB (7), B1 (7), B2 (31), B3 (31) and C (21). With a median follow-up duration of 65 months (8-143 months), the 5-year overall survival (OS) and disease-free survival (DFS) rates were 75.7% (89.2, 67.9 and 52.1% in stage II, III and IVa, respectively) and 70.3% (83, 62.4 and 33.6% in stage II, III and IVa, respectively). In multivariate analysis, prognostic factors for OS were age, WHO histology, Masaoka stage, and recurrence, while pleural involvement, WHO histology, and Masaoka stage had significant impacts on DFS. Adjuvant chemotherapy did not alter survival outcomes and recurrence patterns. Pleura was the most common recurrence site (15 patients, 53.6%), and significantly associated with pleural recurrence-free survival. In conclusion, pleural involvement at diagnosis was the important prognostic factor, in addition to WHO histology and Masaoka stage. To prevent pleural recurrence and prolong survival, innovative therapeutic approaches warrant further investigations.     

Association of clinical and pathological variables with survival in thymoma

Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection.     

胸腺瘤组织学分型与重症肌无力及临床分期关系

目的探讨胸腺瘤最新WHO病理分型与重症肌无力(MG)及临床分期之间的关系。方法回顾分析1980-2004年间74例因胸腺瘤行胸腺切除的患者,运用最新WHO分型标准(1999)对胸腺瘤进行重新分类,并运用统计软件对新的WHO组织学分型与MG的发生率及Masaoka临床分期之间的关系做进一步分析。结果(1)胸腺瘤A型2例,AB型23例,B1型4例,B2型27例,B3型16例,C型2例。其中B2型较AB、B1及B3型易合并MG(P<0.05),A型两例均合并MG,而C型则均未合并MG。(2)临床I期:1例,Ⅱ期:30例,Ⅲ期:38例,Ⅳ期:5例。新的WHO组织学分型与Masaoka分期之间关系密切(P<0.01)。结论新WHO组织学分型与胸腺瘤合并MG的发生率之间有一定关系,同时能反映其临床分期及评价患者的预后。     

Thymoma--the usefulness of some prognostic factors for diagnosis and surgical treatment.

AIMS: The aim of the study was to identify prognostic factors which could help evaluate both the treatment offered to patients with thymoma and late results. METHODS: Forty patients were treated for mediastinal thymoma. The patients were staged clinico-pathologically (according to Masaoka) on the basis of the retrospective analysis of their operation protocols as follows: seven (17.5%)-stage I, 19 (22. 5%)-stage II, 17 (42.5%)-stage III, seven (17.5%)-stage IV. Analysis of DNA contents in cell nuclei of 23 thymomas was performed by the flow cytofluorometric method. RESULTS: From the whole group of patients, 65% survived for 5 years, 55% survived for 10 years and 43% survived for 15 years. We noted significant differences in survival time between stage I and stage IV (P<0.0012); stage II and stage IV (P<0.0006), as well as between stage III and stage IV (P<0. 005). Significantly worse prognosis was observed in the case of cortical thymomas as compared with medullary or mixed types (P<0. 0001 P<0.002). Analysis of DNA content showed signficantly higher probability of survival for the patients who had DI=1.0 (diploid), as compared with DNA >1.0 (aneuploid) (P<0.006). Of the 11 patients with diploid tumours, 91% survived for 5 years, but of the 12 aneuploid, only 23% survived. CONCLUSION: The most important positive prognostic factors influencing survival rate in patients with thymoma are: lower stage, medullary type (according to Muller-Hermelink classification), possibility of performing complete resection, diploidal nature of the tumour. Multivariate analysis of survival revealed clinico-pathological stage (according to Masaoka) and histological type (according to Salyer) as significantly independent prognostic factors.     

82例胸腺瘤新组织学分型与患者临床特征和预后的相关性分析

背景与目的:世界卫生组织(WHO)于1999年制定了新的胸腺瘤组织学分型标准。本研究探讨胸腺瘤WHO组织学分型与临床特征和预后的相关性。方法:回顾性分析82例经外科治疗的胸腺瘤患者的临床资料,经有经验的病理科医生按WHO组织学分型标准重新做出诊断,并结合患者的临床特征和预后进行分析。结果:胸腺瘤A型5例(6.1%),AB型21例(25.6%),B1型14例(17.1%),B2型12例(14.6%),B3型14例(17.1%),C型16例(19.5%)。根据Masaoka临床分期,Ⅰ期29例(35.4%),Ⅱ期13例(15.8%),Ⅲ期32例(39.0%),Ⅳa期8例(9.8%)。临床分期与组织学分型的相关性有显著性意义(χ2=47.29,P<0.001)。肿瘤外侵的程度与组织学分型的相关性也有显著性意义(χ2=30.78,P<0.001)。A﹑AB﹑B1和B2型胸腺瘤合计切除率较B3和C型胸腺瘤合计切除率高(84.6%vs.50.0%,χ2=11.29,P=0.002)。临床Ⅰ、Ⅱ、Ⅲ、Ⅳa期胸腺瘤切除术后5年生存率分别为100%、100%、69.5%和37.5%;10年生存率分别为88.1%、57.1%、47.5%和0。不同临床分期患者生存率的差异(log-rank=40.31,P<0.001)与组织学分型间生存率的差异(log-rank=16.0,P=0.007)均有统计学意义。结论:WHO组织学分型可在一定程度上反映胸腺瘤的生物学行为和临床特征,对临床诊断和治疗胸腺瘤有指导意义。     

术后放疗在I期/II期/III期胸腺肿瘤中的作用--ChART回顾性数据库研究结果

背景与目的胸腺肿瘤术后放疗尚存在争议,此研究目的为评价术后放疗在I期-III期胸腺肿瘤中的作用。方法搜索中国胸腺瘤研究协作组（Chinese Alliance of Research for hTymomas, ChART）数据库中1994年至2012年接受手术切除未行新辅助治疗的I期-III期胸腺肿瘤患者的资料。对临床病理资料进行单因素、多因素分析,Cox比例风险模型用于决定死亡风险比。结果 ChART数据库中I期-III期胸腺肿瘤共1,546例。其中649例（41.98%）接受术后放疗。术后放疗与性别、组织学类型（World Health Organization, WHO）、胸腺切除程度、是否完全切除、Masaoka-Koga分期及辅助化疗相关。手术后辅助放疗患者5年、10年总生存和无瘤生存分别为90%和80%、81%和63%,而单纯手术者5年、10年总生存和无瘤生存分别为96%和95%、92%和90%,两组生存有统计学差异（P=0.001, P<0.001）。单因素表明年龄、组织学分类（WHO）、Masaoka-Koga分期、是否完全切除和术后放疗与总生存相关。多因素分析提示组织学分类（WHO）（P=0.001）、Masaoka-Koga分期（P=0.029）和是否完全切除（P=0.003）是总生存的独立预后因素。单因素分析表明性别、重症肌无力、组织学分类、Masaoka-Koga分期、手术方式、术后放疗和是否完全切除与无瘤生存相关。多因素分析表明组织学类型（P<0.001）、Masaoka-Koga分期（P=0.005）和是否完全切除（P=0.006）是无瘤生存的独立预后因素。亚组分析表明不完全切除患者接受术后放疗可以提高总生存和无瘤生存（P=0.010, P=0.017）。然而,完全切除者接受术后放疗则会降低总生存和无瘤生存（P<0.001, P<0.001）。结论此回顾性研究表明不完全切除I期-III期胸腺肿瘤患者术后放疗可以提高总生存和无瘤生存。但是,对于完全切除患者,术后放疗总体上并未显示出生存获益。     

The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients

BACKGROUND: Although the histologic classification of thymic epithelial tumors has been confusing and controversial, an agreement on the universal classification system for thymic epithelial tumors was achieved by the World Health Organization (WHO) in 1999. The authors previously reported that the WHO histologic classification system reflects invasiveness and immunologic function of thymic epithelial tumors. In this subsequent study, they examined the prognostic significance of this classification system. METHODS: Clinical features as well as postoperative survival of patients with thymoma, but not thymic carcinoma, were examined with reference to WHO histologic classification based on an experience with 273 patients over a 44-year period. RESULTS: There were 18 type A tumors, 77 type AB tumors, 55 type B1 tumors, 97 type B2 tumors, and 26 type B3 tumors. In patients with type A, AB, B1, B2, and B3 tumors, the respective proportions of invasive tumor were 11.1%, 41.6%, 47.3%, 69.1%, and 84.6%; the respective proportions of tumors with involvement of the great vessels were 0%, 3.9%, 7.3%, 17.5%, and 19.2%; and the respective 20-year survival rates were 100%, 87%, 91%, 59%, and 36%. According to the Masaoka staging system, the 20-year survival rates were 89%, 91%, 49%, 0%, and 0% in patients with Stage I, II, III, IVa, and IVb disease, respectively. By multivariate analysis, the Masaoka staging system and the WHO histologic classification system were significant independent prognostic factors, whereas age, gender, association with myasthenia gravis, completeness of resection, or involvement of the great vessels were not significant independent prognostic factors. CONCLUSIONS: This study showed that histologic appearance reflects the oncologic behavior of thymoma when the WHO classification system is adopted. The WHO classification system may be helpful in clinical practice for the assessment and treatment of patients with thymoma.     

合并重症肌无力的胸腺瘤患者术后生存的初步分析--ChART数据库回顾性结果

背景与目的重症肌无力（myasthenia gravis, MG）对胸腺瘤患者预后的影响至今尚不明确,本文旨在比较单纯胸腺瘤与合并肌无力胸腺瘤患者的手术预后。方法1992年至2012年中国胸腺协作组（Chinese Alliance for Research in hTymomas, ChART）数据库录入的18个胸外科中心诊断胸腺瘤并接受相关手术的患者分为合并重症肌无力组（合并组）和单纯胸腺瘤组（对照组）。收集两组患者的人口学资料及临床资料,比较两组患者生存率。结果共1,850例患者纳入研究,其中合并肌无力组及单纯胸腺瘤组分别421人和1429人,行胸腺全切的比例分别是91.2%和71.0%（P<0.05）;肌无力组患者的WHO病理类型多分布于AB、B1和B2型,优于单纯胸腺瘤组（P<0.05）;合并肌无力组的Masaoka分期较早（I和II期）的比例高于单纯胸腺瘤组。5年和10年的总体生存率在MG组和非MG组中分别为93%和88%;83%和81%（P=0.034）;在Masaoka III、IVa和IVb期胸腺瘤患者中,合并肌无力患者的生存曲线高于单纯胸腺瘤患者（P=0.003）。在进展型胸腺瘤患者中,MG组和非MG组患者的Masaoka III、IVa、IVb的构成比相似,组织学结果中,MG组的AB/B1/B2/B3型的比例高于C型比例更高的非MG组（P<0.001）。整体的单因素分析结果提示,MG、WHO分型、Masaoka分期、手术方式、化疗、放疗和临床切除状况均为预后的影响因素。而在多因素分析中,WHO分型、Masaoka分期和临床切除状况是独立的预后预测指标。结论虽然重症肌无力不是独立的预后影响因素,但是在胸腺瘤患者中,合并MG的患者预后较优,尤其是Masaoka分期晚期的患者,可能与疾病的早期发现、病理类型分布相对较好、整体R0切除率较高以及复发率较低有关。     

Assessment of the ITMIG Statement on the WHO Histological Classification and of the Eighth TNM Staging of Thymic Epithelial Tumors of a Series of 188 Thymic Epithelial Tumors

IntroductionThymic epithelial tumors (TETs) are rare intrathoracic malignancies that are categorized histologically according to the WHO classification, which was recently updated in 2015 on the basis of a consensus statement of the International Thymic Malignancy Interest Group (ITMIG); at the same time, the standard Masaoka-Koga staging system is scheduled to be replaced by the eighth edition of the TNM staging classification by the American Joint Committee on Cancer/Union for International Cancer Control consortium. Our objectives were to analyze the feasibility of assessing ITMIG consensus major and minor morphological and immunohistochemical criteria and the eighth edition of the TNM staging classification in a routine practice setting.MethodsThis is a single-center study conducted at the Louis-Pradel Hospital of Lyon University, one of the largest centers for TETs in France. Overall, a large surgical series of 188 TETs diagnosed in 181 patients between 2000 and 2014 at our center were analyzed.ResultsThere were 89 men (49%) and 92 women (51%); 57 patients (31%) presented with myasthenia gravis at time of diagnosis. According to the WHO classification, there were nine type A thymomas (5%), 67 type AB thymomas (36%), 19 type B1 thymomas (10%), 46 type B2 thymomas (24%), 27 type B3 thymomas (14%), and 20 thymic carcinomas (11%). ITMIG consensus major criteria were identified in 100% of type A, AB, B1, and B2 thymomas. After restaging according to the eighth edition of the TNM staging classification, there were 127 stage I (84%), three stage II (2%), 17 stage IIIa (11%), no stage IIIb, two stage IVa (1%), and three stage IVb (2%) thymomas. Significant correlation between histological type and stage at diagnosis was maintained after restaging according the TNM classification.ConclusionComprehensive analysis of our well-characterized surgical series of 188 TETs indicates the feasibility and the diagnostic value of the ITMIG consensus statement on WHO histological classification and highlights the major switch in staging when the eighth edition of the TNM staging classification is applied.     

Three cases of multiple thymoma with a review of the literature

Three cases of patients with synchronous multiple thymoma are reported. Two patients had two thymomas each and the remaining patient had three. The thymomas in each patient all displayed similar histological findings, of which the WHO histological classification were type B2, A and B1, respectively. With a modified Masaoka staging system, the thymomas were determined to be stages II-1 and I in patient 1, one of stage III and two of stage I in patient 2, and two of stage II-1 in patient 3. We reviewed nine reported cases of multiple thymoma in which histological findings were provided and discuss whether they developed from multi-centric origin or from intra-thymic metastasis.     

A 25-year thymoma treatment review

Most thymomas are stage I or II at presentation, and they have a good prognosis with surgical treatment. Higher stage thymomas are less common and their treatment is more problematic. Our center tends to attract patients with higher stage thymomas for treatment. We reviewed our experience and contrasted it with other published series. A 25-year retrospective record review of thymomas was done. 38 patients were treated. Median age was 49 years. Four had myasthenia gravis. Masaoka staging was: stage I--9; stage II--6; stage III--15; stage IVa--4; stage IVb--4. Resection was done in 25 patients (21 had R0 resection), chemotherapy was given to 15 patients, and 27 patients received radiotherapy. Overall median survival was 55 months. Overall 5 and 10-year survivals were 30% and 18%. 5-year survival by stage was: stage I--75%; stage II--50%; stage III/IV--23%. Negative prognostic factors on univariate analysis included presence of symptoms at presentation (p = 0.02), unresectable tumor (p = 0.06), stage III/IV (p = 0.04), and disease recurrence after resection (p = 0.0001). On multivariate analysis, only stage (p = 0.04) and recurrence (p = 0.0001) were independent predictors of survival. All patients who recurred after resection eventually died of disease. Our overall treatment results are disappointing, but we had higher stage patients than reported by most other centers. Early stage thymomas are suitable for complete surgical resection, and the prognosis is favorable. However, higher stage thymomas (stage III and higher) pose problems for complete surgical resection and their prognosis is poor. Newer multimodality treatment approaches are indicated for higher stage thymomas.     

A Recurrence Predictive Model for Thymic Tumors and Its Implication for Postoperative Management: a Chinese Alliance for Research in Thymomas Database Study

ObjectiveOur aim was to investigate appropriate postoperative management based on the risk of disease recurrence in thymic epithelial tumors after complete resection.MethodsThe Chinese Alliance for Research in Thymomas retrospective database was reviewed. Patients having stage I to IIIa tumors without pretreatment and with complete resection were included. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram for building a recurrence predictive model.ResultsA total of 907 cases, including 802 thymomas, 88 thymic carcinomas, and 17 neuroendocrine tumors, were retrieved between 1994 and 2012. With a median follow-up of 52 months, the 10-year overall survival rate was 89.5%. Distant and/or locoregional recurrences were noted in 53 patients (5.8%). The nomogram model revealed histologic type and T stage as independent predictive factors for recurrence, with a bootstrap-corrected C-index of 0.86. On the basis of this model, patients with T1 thymomas or T2 or T3 type A, AB, or B1 thymomas had a significantly lower incidence of recurrence (low-risk group) than those with T2 or T3 type B2 or B3 thymomas and all thymic carcinomas and neuroendocrine tumors (high-risk group) (2.7% versus 20.1% [p < 0.001]). In the high-risk group, more than half of the recurrences (55.2% [16 of 29]) were seen within the first 3 postoperative years, whereas all recurrences but one were recorded within 6 years after surgery. Recurrence occurred quite evenly over 10 postoperative years in the low-risk group.ConclusionsA 6-year active surveillance should be considered in high-risk patients regardless of adjuvant therapy. For low-risk patients, annual follow-up may be sufficient. Studies examining postoperative adjuvant therapies would be plausible in high-risk patients.     

Diagnostic and clinical significance of KIT(CD117) expression in thymic epithelial tumors in China

Aims: To study KIT (CD117) expression in thymic epithelial tumors in China, and investigate diagnosticand clinical significance. Material and Methods: Thymic epithelial tumors (TETs) from 102 patients (3 type A,29 type AB, 5 type B1, 22 type B2, 29 typeB3 and 16 thymic carcinomas) were examined. Immunohistochemicalstaining with an antic-kit monoclonal antibody was performed on a tissue microarray. Relationships betweenKIT positive expression and the TET clinical characteristics (WHO histologic classification and Masaoka stagesystem) were analysed. Results: The KIT positive expression rate was significantly higher in thymic carcinoma(60%, 9/16) than in thymoma (8%, 7/86), a strong correlation being found with the WHO classification, but notthe Masaoka tumor stage. The overall survival for patients with KIT positive lesions was significantly worse.Conclusions: KIT is a good molecule marker to differentially diagnose thymic carcinoma from thymoma, whilealso serving as a predictor of prognosis for TETs. Further research into KIT mutations in Chinese TETs shouldbe conducted to assess the efficacy of targeted therapy.