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Survival Outcomes in Patients with Thymoma after Thymectomy in an Indian Scenario
Abstract
Thymomas are relatively slow growing with late presentation. Because of rarity and underreporting in India, there is an unmet need for evaluating the patient characteristics and assessing the factors affecting survival for standardizing the ideal modality of treatment in Indian population. A retrospective analysis of 96 patients with thymoma was done between 1998 and 2018. Patient characteristics, histopathological characteristics, operative outcomes, local recurrences, and survival outcomes were recorded. Survival analysis was done using Kaplan-Meier method, and statistical data were analyzed using SPSS version 25 (IBM). The incidence of thymoma was relatively high in 6th decade with no sex predilection. Common presenting symptoms were cough and dyspnea. Myasthenia gravis was noted in 30.2%, which resolved after thymectomy in 65.5% of patients. Most patients presented with Masaoka stages I and II, and predominant WHO histological types were B1 and AB. Complete resection was done in 69.8% cases, and local recurrence was noted in 15.6%. Median sternotomy was the most frequently used approach for thymectomy. The 5-year overall survival was 76%, with an excellent 5-year survival of 95% and 86% in stages I and II patients. Masaoka stage, WHO histologic type, completeness of surgery, and local recurrence did affect the survival significantly. Masaoka stages III and IV, histological type B3, incomplete resection during surgery, and presence of local recurrence did independently predict a worse overall survival.
... Long-term outcomes of thymoma-associated MG are variable, with some patients experiencing complete remission and others experiencing chronic disease with significant morbidity. Recurrence rates after thymectomy vary depending on the stage and histologic subtype of the thymoma, with higher rates observed in patients with more advanced disease (28,29). ...
Thymomas are rare tumors that can present with a wide range of clinical characteristics. The presence of symptoms and paraneoplastic syndromes, such as myasthenia gravis, along with the histological subtype and stage of the tumor, are important factors that guide the treatment approach and prognosis for patients with thymomas. The prognosis for thymoma varies depending on several factors, including the stage and type of the tumor, as well as the presence of associated autoimmune diseases. Generally, early-stage thymomas have a better prognosis compared to advanced-stage tumors. Regular follow-up with a multidisciplinary team, including oncologists and thoracic surgeons, is essential for long-term management and surveillance of patients.
Purpose
In recent years, the use of fluorodeoxyglucose PET-computed tomography (PET-CT) has become widespread to evaluate the diagnosis, metabolism, stage and distant metastases of thymoma. In this study, it was aimed to investigate the connection of malignancy potential, survival and maximum standardized uptake value (SUV max ) measured by PET-CT before surgery according to the histological classification of the WHO in patients operated for thymoma. In addition, the predictive value of the Glasgow prognostic score (GPS) generated by C-reactive protein (CRP) and albumin values on recurrence and survival was investigated and its potential as a prognostic biomarker was evaluated.
Methods
Forty-five patients who underwent surgical resection for thymoma and were examined with PET-CT in the preoperative period between January 2010 and January 2022 were included in the study. The relationship between WHO histological classification, tumor size and SUV max values on PET-CT according to TNM classification of retrospectively analyzed corticoafferents were evaluated. Preoperative albumin and CRP values were used to determine GPS.
Results
The cutoff value for SUV max was found to be 5.65 in the patients and the overall survival rate of low-risk (<5.65) and high-risk (>5.65) patients was compared according to the SUV max threshold value (5.65) and found to be statistically significant. In addition, the power of PET/CT SUV max value to predict mortality (according to receiver operating characteristics analysis) was statistically significant ( P = 0.048). Survival expectancy was 127.6 months in patients with mild GPS (O points), 96.7 months in patients with moderate GPS (1 point), and 25.9 months in patients with severe GPS (2 points).
Conclusion
PET/CT SUV max values can be used to predict histological sub-type in thymoma patients, and preoperative SUV max and GPS are parameters that can provide information about survival times and mortality in thymoma patients.
Background & objectives: Thymomas are rare, but most common anterior mediastinal lesions. The histomorphologic spectrum of thymic epithelial tumours (TETs) in Indian population has not been explored in depth. This study was aimed to assess the histomorphology of TETs in the Indian patients and correlate clinical parameters with pathological features.
Methods: It was a retrospective study conducted in a tertiary referral hospital in north India. All morphologically confirmed cases of TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinicopathological correlation and survival analysis were done. A comparative review from other published Indian studies was performed.
Results: A total of 219 cases of TETs (138 resections and 81 biopsies) were identified. The most common histomorphologic type was B2, and the most frequent stage was I. Types A/AB were common in older age (P
Background
A thymoma is a common cancer within the anterior mediastinum; however, the prognostic characteristics have not been established. The aim of this study was to identify the prognostic factors and develop a nomogram for the prognostic prediction of patients with thymoma based on data from the Surveillance, Epidemiology, and End Results (SEER) database.
Methods
Patients with thymomas diagnosed between 1983 and 2014 were selected. Overall survival (OS) was estimated using the Kaplan–Meier method with the log‐rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors, from which a nomogram for thymomas was created. External validation of the nomogram was performed using data from our center.
Results
A total of 1312 patients with thymomas were enrolled. Age, tumor size, Masaoka–Koga stage, chemotherapy administered, and surgery type were independent prognostic factors for OS. A nomogram for OS was formulated based on the independent prognostic factors and validated using an internal bootstrap resampling approach, which showed that the nomogram exhibited a sufficient level of discrimination according to the C‐index in training (0.713, 95% confidence interval 0.685–0.741) and (0.746, 95% confidence interval 0.625–0.867) validation cohorts.
Conclusion
Several prognostic factors for thymomas were identified. The nomogram developed in this study accurately predicted the 5‐year and 10‐year OS rates of patients with thymomas based on individual characteristics. Risk stratification using the survival nomogram could optimize individual therapy and follow‐up.
Background
Thymoma, though a rare tumor disease, is the most common tumor of the anterior mediastinum. However, tumor size, as a critical factor, has been underestimated.
Results
Age, advanced tumor stage, and preoperative radiotherapy were poor prognostic factors of overall survival (OS) and disease specific survival (DSS) (P < 0.05 for all). Besides, tumor size was significantly related to survival. The larger tumor size indicated the less OS and DSS (P < 0.001 for all). Multivariate analysis revealed elder age, advanced stage, larger size were independent adverse predictors for survival (P < 0.05 for all). Logistic analysis revealed larger tumor size had greater rate of metastasis (P < 0.001). In the group with tumors smaller than 90mm, chemotherapy was a negative predictive factor of DSS (P < 0.05 for all), and it significantly decreased OS especially with tumor sizes between 50 and 90 mm (P < 0.001).
Materials and Methods
A total of 1,272 thymoma patients were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Survival based on thymoma size and other characteristics of tumors were analyzed by univariate and multivariate analysis. Correlation between thymoma size and thymoma metastatic status was contributed by logistic regression analysis. The efficiency of adjuvant therapy was analysis by stratification analysis.
Conclusions
Thymoma size could predict postoperative survival and guide chemotherapeutic regimens of patients. Larger tumor size indicated worse survival and higher metastatic rate. If thymoma is smaller than 90mm, traditional chemotherapy should be prohibited. While chemotherapy could be performed moderately when thymoma larger than 90 mm.
Background: Mediastinal masses are relatively uncommon lesions that sometimes pose an interesting diagnostic and therapeutic problem for the clinician. Thymomas are one of the common mediastinal neoplasms and exhibit a wide spectrum of morphologic features and an unrivalled frequency of other autoimmune diseases. The great morphologic variability and heterogeneity in thymomas has rendered their histological classification difficult and highly controversial. Methods: This retrospective and descriptive study on thymoma was done in the department of pathology, Kasturba Medical College Mangalore (Manipal University), India over a period of five years from January 2006 to June 2011. Histopathology sections taken were stained with routine Hematoxylin and Eosin stains in every case. Additional stains and immunohistochemistry were done as required. Results: Total number of mediastinal lesions studied was 66, with thymomas making up 15 cases. The age range of patients with thymomas was 22 to 65 years with a mean of 48 years. The most common histologic sub-type of thymoma was B2. Type AB thymoma was associated with bad prognosis. Five cases of thymomas were associated with Myasthenia Gravis. All thymomas showed cytokeratin positivity. Reticulin fibers were seen around individual tumor cells in Type A thymoma while Type B2 showed around tumor nests. Conclusion: Thymomas are rare & interesting neoplasm located in the mediastinum. A histomorphological analysis aided by immunohistochemistry and radiology permits an exact diagnosis and also allows for differentiation between benign and malignant neoplasms.
Aims:
To explore the demographics and clinical outcome of patients with thymoma treated with a multimodality approach at our institute.
Methods:
A total of 71 patients with thymoma (Masaoka stage II-IV and WHO subtype AB-B3) treated from 1999-2013 were included in this retrospective analysis. Age, stage, WHO subtypes, details of surgery, radiotherapy, and chemotherapy were noted. Progression-free survival (PFS) was estimated using Kaplan-Meier method and SPSS (version 21.0) was used for statistical analysis.
Results:
Male:female ratio was 56:15 with median age at presentation of 41 years. Stage-wise distribution was 6:46:19 for stage II, stage III, and stage IV, respectively. A total of 31 patients (44%) had associated myasthenia gravis and 3 had pure red cell aplasia. A total of 57 patients (80%) underwent radical thymectomy and all of these patients received adjuvant radiotherapy. A total of 15 patients and 7 patients received adjuvant chemotherapy and neoadjuvant chemotherapy, respectively. At median follow-up of 19.3 months (range 7.9-72.3 months), 2-year and 3-year PFS rate for the entire cohort was 78.3% and 57.1%, respectively. On univariate analysis, surgery (hazard ratio [HR] 3.881; 95% confidence interval [CI] 1.784-19.220; p = 0.006) and stage (HR 5.457; 95% CI 1.567-18.996; p = 0.0001) were significant prognostic factors and association with myasthenia gravis (HR 0.404; 95% CI 0.151-1.078; p = 0.078) trended towards better PFS. Stage retained its prognostic significance (HR 5.501; 95% CI 2.076-14.573; p = 0.0006) on multivariate analysis.
Conclusions:
Multimodality management of locally advanced thymoma yields decent survival outcomes. Masaoka stage is an independent prognostic factor for survival and radical surgery should be contemplated in all cases of locoregionally limited thymoma.
The rarity of thymomas and lack of multi-institutional studies have hampered therapeutic progress for decades. To overcome this, the members of the International Thymic Malignancy Interest Group created a worldwide retrospective database. This database was analyzed regarding the demographic and geographic distribution of thymomas and the impact of different variables on survival and recurrence.
This study analyzed 4221 thymomas diagnosed between 1983 and 2012 with World Health Organization histotype information from the International Thymic Malignancy Interest Group database. Associations to survival and recurrence were studied by univariate and multivariate analyses.
Type B2 thymoma is the most common (28%) and type A the least common (12%) histotypes. They are significantly more frequent in Europe and the United States than Asia. Type A and AB occur at significantly higher age than other thymomas (64 and 57 years, respectively). There are no differences in gender distribution. Stage is lower in type A (90% in stages I-II) and AB than B1 to B3 thymomas (38% of type B3 in stage III). In univariate analysis, recurrence is significantly less frequent among stage I/II tumors, in type A and AB (recurrence rates, 1-2%) than B1 to B3 thymomas (2-7%). Multivariate analysis reveals an impact of age, stage, and resection status on survival and recurrence, whereas for histology there is only a significant impact on recurrence.
New findings are (1) geographic differences such as a lower incidence of type A and B2 thymoma in Asia; and (2) impact of stage and histology, the latter partially limited to early stage disease, on recurrence.
Background:
Thymomas are the most common tumors of the mediastinum. They have varied presentation ranging from asymptomatic incidental mediastinal masses to locally extensive tumor with compressive symptoms and distant metastases. The authors present our institute's experience in combined modality management of thymomas.
Materials and methods:
We retrospectively reviewed 36 patients of thymoma treated in our institute from January 2004 to December 2010. Clinical characteristics and treatment modality in form of surgery, radiotherapy (RT) and chemotherapy (CCT) were noted. Statistical analysis was done with regard to progression free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis.
Results:
A total of 17 patients had associated Myasthenia gravis and 3 patients had associated Cushing syndrome. Masaoka Stage 4a was the most common stage (13 patients) followed by stage 3 (10 patients), stage 2 (9 patients) and stage 1 (4 patients). Twenty seven patients underwent primary surgery, out of which 20 received adjuvant RT and five received both RT and CCT. Of nine non-surgical cases, four received only palliative RT whereas 5 received systemic CCT followed by local mediastinal RT. Overall, 23 patients had complete response while 13 had partial response. 1 patient had local recurrence. Three year PFS was 60% and 3 year OS was 83%.
Conclusions:
Most common presentation in our series was locally advanced tumors. Most of these patients require adjuvant mediastinal radiation, which helps in significant loco-regional control. Systemic CCT benefits in inoperable, advanced and high-risk tumors. Risk-adapted and multimodality approach is the need of the hour to achieve good control rates while minimizing treatment related toxicity.
To analyze the prognostic factors influencing the survival of patients with thymoma, clinical characteristics, treatment modalities and survival of patients were evaluated. The efficacy of chemotherapy was also determined.
Retrospective study was done on one hundred patients whose diagnosis was confirmed pathologically at Seoul National University Hospital from 1981 to 1994. The staging was carried out according to the Masaoka system. Survival rate was calculated by the Kaplan-Meier method and prognostic factors were analyzed by a multivariate analysis (Weibull model).
The stage of 100 patients was as follows: Stage I-50, II-6, III-27, IV A-10, IV B-7. The overall survival rates at 5 and 10 years after diagnosis were 73.1% and 58.7%, respectively. The 5-year survival differences, according to various prognostic factors, were as follows: 1) Stage: I-92.8%, II-100%, III-71.6%, IVA-25.9% and IVB-32.9% (p = 0.0029). 2) Age: < 60 years-79.5% and > or = 60 years-41.5% (p = 0.0489). 3) Extent of resection: Total patients: complete resection-87.6% and incomplete resection-50.5% (p > 0.05) Stage III: complete resection-66.7% and incomplete resection-75.5% (p > 0.05) 4) Myasthenia gravis: present-71.6% and absent-74.9% (p > 0.05) Seventeen patients were treated with a combination chemotherapy of Cyclophosphamide, Adriamycin and cisplatin(CAP). Two complete responses and seven partial responses (overall response rate of 53%) were observed with a median response duration of fourteen months. Combination chemotherapy with CAP was effective.
Stage and age were the independent prognostic factors in patients with thymoma. However, the presence of myasthenia gravis or the extent of resection in stage III patients was not associated with the survival time.
Background
The aim of this study was to evaluate the results of R0 resection of thymoma to identify prognostic factors for long-term outcomes.
Methods
Data of 62 patients (28 male, 34 female) with a mean age of 47.26 ± 14.42 years, who underwent R0 resection for thymoma and were followed-up between February 2004 and March 2016, were analyzed retrospectively.
Results
Eight patients had a video-assisted thoracoscopic thymectomy and 54 had a transsternal extended thymectomy. During a mean follow-up of 128.67 ± 7.95 months, regional recurrence of thymoma was observed in 9 (14.5%) patients. Overall 5- and 10-year survival rates were 85.36% and 78.20%, respectively. The 5- and 10-year survival rates in patients aged < 50 years were significantly better than in those aged ≥ 50 years (92% and 72% vs. 88% and 39%, p < 0.0001). The 10-year overall survival of patients in Masaoka stage I and II was better than those in stage III (88.9%, 78.4%, 69.8%, respectively, log-rank p < 0.001). The 10-year survival of patients with World Health Organization histological type A, AB, and B1 thymomas was better than those with type B2 and B3 (log-rank test p < 0.001). In multivariate analysis, age < 50 years ( p = 0.001), Masaoka stage ( p = 0.006), histological type ( p = 0.001), and recurrence ( p = 0.04) were independent prognostic factors for survival.
Conclusion
Our study indicates that age < 50 years, Masaoka stage, histological type, and recurrence are the determinants of survival in surgically resected cases of thymoma.
Background:
It is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG.
Methods:
The Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, patients were followed and their survival status were analyzed.
Results:
There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5- and 10-year overall survival (OS) rates were both higher in MG group (93% vs. 88%; 83% vs. 81%, P=0.034) respectively. The survival rate was significantly higher in patients with MG when the Masaoka staging was 3/4 (P=0.003). Among patients with advanced stage thymoma (stage 3, 4a, 4b), the constituent ratios of 3, 4a, 4b were similar between MG and non-MG group. Histologically, however, there were significantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classification, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were significant factors, and multivariate analysis showed WHO classification, Masaoka stage, and resectability were strong independent prognostic indicators.
Conclusions:
Although MG is not an independent prognostic factor, the survival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.
Objective:
To evaluate the different pathological and clinical characteristics of thymomas with and without myasthenia gravis (MG) and to determine whether the presence of MG influences the prognosis in thymoma patients.
Methods:
The clinical data from 228 consecutive patients (median sternotomy were used in 153, video-assisted thoracoscopic themectomy were used in 75) operated on from January 1992 to December 2007 was analyzed retrospectively. These thymoma patients had been subdivided into two groups: thymoma with MG (n = 125) and thymoma without MG (n = 103). All thymic epithelial tumors were classified according to the WHO histologic classification and the Masaoka clinical staging system. The result was evaluated according to the Myasthenia Gravis Foundation of America's criterion. The clinical features of the 2 test was compared between the two groups by χ(2) test, and the survival were compared between the two groups by Cox analysis.
Results:
There were no peri-operative deaths. 19 cases were inoperable (6 in the group with MG, 13 without MG (χ(2) = 4.52, P = 0.035)). The proportions of type A and thymic carcinoma were 0 in the group with MG, 10.5% (11/103) and 11.6% (12/103) respectively in the group without MG. According to the Masaoka's clinical staging, in the group MG, 24.8% (31/125) patients were stage III and IV; in the group without MG, 33.0% (34/103) patients were stage III and IV. There was a significant difference between hyperplastic paraneoplastic thymus coexisting in 28.8% (36/125) patients with MG and only 5.8% (6/103) in patients without MG (χ(2) = 20.91, P = 0.000) Microthymoma was identified in the paraneoplastic thymus of 3 patients with MG. There were 198 patients followed up, the rate was 86.8% (198/228). There was no recurrence in patients with type A and a few patients with type AB, B1, B2, B3 thymoma and thymic carcinoma recurred. The actuarial 5- and 10-year survival rates were 89.3% and 81.2% for patients with MG respectively, and 90.0% and 78.9% for patients without MG respectively. Within 5 years postoperatively, 6 of 9 patients with MG died of myasthenia crisis, while 6 out of 7 deaths in patients without MG were attributable to inoperable tumors (stage IV) and thymic carcinoma.
Conclusions:
The existence of myasthenia gravis has little influence on the prognosis of thymomas, but it is good for early diagnosis and treatment. Extended thymectomy should be performed to all patients with thymoma, no matter they have myasthenia gravis or not. The main cause of death is myasthenia crisis for thymoma patients with MG and stage IV and (or) thymic carcinoma for patients without MG.
This meta-analysis was designed to determine the effect of induction therapy and surgical resection on overall survival in patients with advanced thymic epithelial tumors. PubMed and Scopus databases were queried, and 12 studies comprising 266 patients were analyzed. Meta-analysis using a random effect model revealed a pooled rate of response to induction therapy of 59%, a pooled rate of complete resection of 73%, and pooled 5-year and 10-year overall survival of 87% and 76% after induction therapy, respectively. Surgical resection after induction therapy for advanced thymic epithelial tumors can be undertaken with favorable outcomes.
Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
The prognostic value of histopathologic classifications of thymoma is debated. Problematic reproducibility might cause this controversy. We studied the prognostic significance of three histopathologic classifications of thymomas after three thoracic pathologists agreed upon thymoma subtype and invasion. We also compared the outcome to established prognostic parameters.
Patients, surgically treated for thymic epithelial neoplasm at Mayo Clinic (1942-2008), were staged according to the modified Masaoka staging and the recently proposed staging by Moran. Three thoracic pathologists independently classified all cases according to the World Health Organization (WHO), Bernatz and proposed Suster and Moran (S&M) classification. Only thymoma that all three pathologists diagnosed as the same histopathologic subtype and extent of invasion were included in outcome analysis.
In 214 (S&M classification), 145 (WHO classification) and 120 (Bernatz classification) cases reviewers agreed upon subtype of thymoma and invasion and follow up was available. Median follow up time was 7.5-7.7 years (range between classifications). All histopathologic classifications were associated with OS and DFS (p≤0.0001 to p=0.048); only Bernatz classification was independent of modified Masaoka staging associated with OS (p=0.04). Modified Masaoka stage predicted outcome independent of all histopathologic classifications and resection status and strongly correlated with the proposed Moran stage (correlation coefficient, 0.95). Thymoma size and age were prognostic parameters for OS independent of any histopathologic classification.
Histopathologic classifications of thymomas are associated with prognosis but are in general not independent predictors of outcome. Modified Masaoka stage and proposed Moran staging are independent prognostic parameters for thymoma and superior to histopathologic classifications.
Background:
Thymoma is the most common tumor of the anterior mediastinum. Surgery is mainstay of treatment, with adjuvant radiation recommended for invasive thymoma. Because of rarity, prospective randomized trials may not be feasible even in multicentric settings hence the best possible evidence can be large series. Till date Thymoma has not been studied in Indian settings.
Materials and methods:
All patients presenting to Thoracic disease management group at our Centre during 2006-2011 were screened. Sixty two patients' with histo-pathological confirmation of thymoma medical records could be retrieved and are presented in this study. Mosaoka staging and WHO classification was used. The clinical, therapeutic factors and follow up parameters were recorded and survival was calculated. Effects of prognostic factors were compared.
Results:
Sixty two patients were identified (36M, 26F; age 22-84, median 51.5 years) and majorities (57%) of thymoma were stage I-II. WHO pathological subtype B was most common 30 (49%). Mean tumor size was smaller in patients with myasthenia (5.3cm) than the entire group (7.6cm). Neoadjuvant therapy was offered to five unresectable stages III or IV a patient's with 40% resectability rates. Median overall survival was 60 months (Inter quartile-range 3-44 months) with overall survival rate (OS) at three year being 90%. Resectable tumors had better outcomes (94%) than non resectable (81%) at three years. Mosaoka Stage was the only significant (P = 0.03) prognostic factor on multivariate analysis.
Conclusion:
This is first thymoma series from India with large number of patients where staging is an important prognostic factor and surgery is the mainstay of therapy. In Indian context aggressive multimodality treatment should be offered to advanced stage patients and which yields good survival rates and comparable.
Thymoma and thymic carcinoma are an extremely heterogeneous group of neoplastic lesions with an exceedingly wide spectrum of morphologic appearances. They show different presentations with a variable and unpredictable evolution ranging from an indolent non-invasive attitude to a highly infiltrative and metastasising one. Prognosis can be predicted on the basis of a number of variables, mainly staging, the WHO histological pattern and diameter of the tumour. Complete surgical resection is certainly the gold standard to achieve cure. However, especially in patients with lesions at advanced stage, complete resection may be difficult and recurrence often occurs; at these stages, disease-free long-term survival may be difficult to be accomplished. Chemo- and radiotherapy protocols have been designed to complete surgical treatment and improve results in inoperable patients as well, based on the reported sensitivity of thymic tumours to these treatment modalities. The integration of clinical staging and histology, with the new histogenetic morphological classification, has contributed to design multimodality treatment protocols that help to improve prognosis. Induction therapy can now be applied before surgery in patients with tumours considered inoperable, improving resectability and outcome without adding morbidity and mortality to the surgical procedure. This newly developed approach helps to reduce the recurrence rate and to ameliorate disease-free survival. New therapies are now being evaluated as for many other tumours; however, they still need confirmation in prospective randomised studies. In the future, integrated treatment modality should be incorporated in a standardised approach that goes from a careful assessment of histology, staging and lymph node status, and a constructive and non-empirical co-operation between medical and radiation oncologists, pathologists and thoracic surgeons.
Follow-up data were obtained for 96 cases of thymoma. The one-year survival rate was 84.3%, the three-year 77.1%, the five-year 74.1%, and the ten-year 57.1%. The five-year survival rate of total resection group was 88.9%; that of non-radically treated group was 44.4%. Clinical stages were defined: Stage I--macroscopically encapsulated and microscopically no capsular invasion; Stage II--1. macroscopic invasion into surrounding fatty tissue of mediastinal pleura, or 2. microscopic invasion into capsule; Stage III--macroscopic invasion into neighboring organ; Stage IVa--pleural or pericardial dissemination; Stage IVb--lymphogenous or hematogenous metastasis. Five-year survival rates of each clinical stage were 92.6% in Stage I, 85.7% in Stage II, 69.6% in Stage III, and 50% in Stage IV. Recurrence after total resection was found in six of 69 cases. Seven of 13 patients treated by subtotal resection survived more than five years with postoperative radiotherapy.
To assess the change in clinical status of patients with generalized myasthenia gravis treated with thymectomy and to identify prognostic variables that may be of significance in optimizing patient selection.
Retrospective review. Mean follow-up period was 41 months.
Large community hospital.
Thirty-seven patients (11 male and 26 female) with generalized myasthenia gravis who were referred for thymectomy if they were refractory to medical treatment or had a thymoma. This represents all patients undergoing thymectomy for myasthenia gravis between January 1982 and December 1991.
Each patient underwent staging before and after thymectomy using a modified Osserman classification. Medication requirements were also recorded. All patients underwent transsternal thymectomy and complete mediastinal dissection.
Changes in clinical stage and medication requirement before and after thymectomy; effect of patient age, sex, duration of disease, stage of disease, antibody status, histologic characteristics of the thymus, and duration of follow-up on outcome.
Improvement after thymectomy was noted in all 37 patients. Complete remission was achieved in three patients (8%) and pharmacologic remission in 23 (62%). The remainder improved in stage, medication requirement, or both. Patients in preoperative stages IIb and IIc showed the greatest improvement. Age, sex, duration of disease, antibody status, histologic characteristics of the thymus, and duration of follow-up were not significant factors in assessing improvement.
Transsternal thymectomy was found to be beneficial to all patients with generalized myasthenia gravis. Complete or pharmacologic remission was achieved in most patients (70%) following the procedure. Patients in preoperative stages IIb and IIc showed the greatest degree of postoperative improvement.
The objective of this study was to establish prognostic factors for thymoma and determine the impact of surgery with or without postoperative radiotherapy.
Seventy patients treated at the University Hospital Düsseldorf during the period 1954-1991 were retrospectively studied. All thymoma patients underwent surgery, 22 received postoperative radiotherapy, and 3 also received chemotherapy. According to thymoma staging as described previously by Masaoka et al., 21% were Stage I, 26% Stage II, 43% Stage III, 7% Stage IVA, and 3% Stage IVB. Lymphocytic type disease was found in 36% of patients, lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in 9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia gravis, histology, tumor size, and stage to survival was determined by univariate analysis, and their independent significance was tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log rank test.
In univariate analysis, KPS (P < 0.001), histologic type (P=0.0093), and stage (P=0.0001) proved to be significant predictors of overall survival. Spindle cell type was associated with the best and epithelial type the worst prognosis; patients with the latter type had a 5-year survival rate of 30%. Multivariate analysis revealed that stage, histology, and KPS were predictive of overall survival. In Stages III and IV, relapses were reduced by postoperative radiotherapy from 50% to 20%. The site of relapse was outside the irradiated area in 80% of patients. Disease free survival (P=0.36) and median survival (P=0.72) of patients with completely resected advanced thymomas did not differ from that for patients with incompletely resected tumors who received radiotherapy.
Postoperative radiotherapy can improve local control in patients with advanced thymoma. Survival after incomplete resection is not compromised when postoperative radiotherapy is employed. KPS should be considered an important prognostic factor in future studies.
To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG).
Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients.
CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR.
In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up.
Thymoma is the most common primary tumor of anterior superior mediastinum. Sixty cases of thymomas over a 12 year period were analysed and the histologic subtype, according to Marino and Muller-Hermilink, classification was correlated with presence or absence of myasthenia gravis (MG) and capsular invasion. Thirty four patients had myasthenia gravis associated with thymoma and there was one case of pure red cell aplasia. There were 3 (1) predominantly cortical, 28 (20) cortical, 12 (9) mixed, 16 (4) medullary thymomas and 1 (0) thymic carcinoma (Figures in parenthesis indicate number of cases associated with MG). Capsular invasion was seen in 25 cases. Association with myasthenia gravis and capsular invasion were seen predominantly in cortical and mixed thymomas which were also associated with aggressive behaviour.
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.
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.
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).
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.
A combination of epithelial cells and lymphocytes results in a varied histomorphology of thymomas and consequent varied classification systems.
To correlate the Marino and Muller-Hermelink (MMH) classification with the invasive behaviour of thymomas.
Retrospective analysis.
Thymomas encountered in the past 21 years were re-classified with the MMH classification and correlated with Masaoka's staging and clinical presentation.
The thymomas formed 91% of the primary thymic epithelial tumours. Predominantly cortical thymomas (n=21) and cortical thymomas (n=22) were the common subtypes and 60% and 77% of these, respectively, were in stages II or III. Cystic change, necrosis or haemorrhage played no role in predicting invasive behaviour. Cortical epithelium correlated well with the presence of para-thymic syndromes, especially myasthenia gravis.
MMH classification is easy to apply. Cortical thymomas in stage I should be followed up for possible recurrence.
To assess the factors that predict local control and survival in patients with thymoma treated with adjuvant radiotherapy (RT) and suggest strategies for optimizing adjuvant RT.
The study population comprised 47 patients with noninvasive thymoma and 128 patients with invasive thymoma. Treatment was surgery in 175 patients and radiotherapy in 169 patients; 25 patients also received adjuvant chemotherapy. The clinical factors (age, histologic features, stage, presence of myasthenia gravis) and therapeutic factors (extent of operation, irradiation dose, and field size) were retrospectively recorded and accessed using multivariate analysis.
The overall survival rate at 5 and 10 years was 86.4% and 80.6%, respectively. Only 2 patients had a relapse in the noninvasive group. None died of thymoma during the study period. The patients with invasive disease had a 5- and 10-year disease-free survival rate of 64.4% and 55.6%, respectively, with 24 intrathoracic failures, 14 extrathoracic failures, and 8 combined failures. The univariate and multivariate analyses showed that Mosaoka stage and extent of resection were the important prognostic factors for patient with invasive thymoma. The 5-year survival rate and local control rate was 96% and 96% for Stage II, 77.8% and 56.4% for Stage III, 56.6% and 42.7% for Stage lVa, and 35.6% and 21.6% for Stage IVb (p < 0.0001 among different stage groups), respectively. The 5-year local control rate in patients with the tumor bed irradiated was 68.2%, comparable to the group treated with an extended RT field (66.6%). Age, histopathologic findings, radiation dose, and presence of myasthenia gravis were not statistically significant prognostic factors.
Disease stage and extent of resection affected the prognosis of invasive thymoma patients. Extending the radiation field prophylactically was not associated with greater local control and is of questionable value for patients with invasive thymoma.