In this study we sought to determine the time to improvement in symptoms of patients with thymomatous MG after thymectomy as evaluated by a 3 point decrease of QMGS, and factors associated with a lack of improvement in symptoms. The median time to achieve a 3 point decrease in QMGS was 6 months, and the median time to achieve another 3 point decrease was 30 months. Multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a 3 point decrease in QMGS (HR = 0.55 and 0.65, respectively). Likewise, multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a second 3 point decrease in QMGS (HR = 0.53 and 0.53, respectively).
Thymoma and thymomatous MG occur more frequently in the fourth decade of life, and the mean age of the patients in this study was 41.8 years. And overall, studies have indicated that MG associated with thymoma is more severe than MG without thymoma [16, 17]. Our results showed that age ≥ 42 years was associated with a lower probability of an initial 3 point reduction in QMGS, as well as a second 3 point reduction. López-Cano et al. [16] reported that age > 55 years was significantly associated with non-remission of thymomatous MG. Yu et al. [18] followed patients with MG for 8 years after thymectomy and reported that patients younger than 40 years of age achieved a higher clinical stable remission (CSR) rate (32% vs 9.1%) rate and a higher clinical remission rate (CMR) (60.4% vs 53%) compared with patients ≥ 41 years old; however, the difference in CMR did not reach statistical significance (P = 0.763). Siwachat et al. [1] reported that age < 40 years was a prognostic factor for CSR, but not an independent factor (HR = 2.1, 95% CI: 0.96–4.61, P = 0.062). Another study, however, showed that younger patients (< 45 years) had a relatively low remission rate (6.98 vs. 11.4%, HR = 0.601, 95% CI : 0.2–1.85, P = 0.3734) [17]. In our study, most of the patients presented with general myasthenic symptoms, only 0.8% patients of patients were MGFA class I, and the majority (66.7%) were treated with steroids.
The mean preoperative QMGS of patients with thymomatous MG in this study was 16.91, slightly higher of the reported value of 12.35 for patients generalized non-thymomatous MG [13]. Study has shown that the presence of thymoma is significantly associated with failure to achieve CSR over long-term follow-up [11]. Even though CSR is an important measure for the evaluation of treatment, it may not be an appropriate marker for patients with thymomatous MG. On the other hand, QMGs is a continuous variable and an objective measure which can minimize inter-observer discrepancies.
In 2000, a task force of the Medical Scientific Advisory Board of the MGFA recommended using QMGS for evaluating clinical change in all prospective MG treatment trials [19]. Barnett et al. [8] compared QMGS with clinical, electrophysiological, and laboratory markers and demonstrated that QMGS was a valid marker of MG severity, thus supporting the use of QMGS as a primary outcome measure in clinical trials of MG. In another study, Barnett et al. [9] compared the QMGS with other scales and showed there was fitness, but a threshold was not defined. Bedlack et al. [12] performed the first analysis of responsiveness and longitudinal construct validity of the QMGS, and showed that a reduction of 2.3 points correlated with improved MG clinical status. Sharshar et al. [20] showed that QMGS displays good inter-rater reliability, as well as construct validity, i.e., during a single visit there is agreement between QMG score, manual muscle testing score, functional score, and the patient’s own self-evaluation.
B1 and B2 thymomas were the most frequently observed histotypes in our study, and these have been confirmed as the most frequent histotypes by Evoli et al. [21], and the WHO [22]. However, Maggi et al. [17] reported AB and B2 histotypes as the most prevalent, and Shen et al. [23] reported that AB, B1, and B2-type thymomas were the most frequently associated with MG. This variability across studies may reflect variability in diagnostic procedures and the ethnic makeup of the patients in different studies [24]. In our study, most patients (about 90%) had early-stage thymomas (Masaoka stage I). Kondo et al. [25] reported that thymomas associated with MG were generally diagnosed at an early stage and had higher resectability than thymomas not associated with MG. Shen et al. [23] showed that MG was associated with early clinical stage thymomas, and WHO histological type AB, B1, and B2. The high prevalence of early-stage thymoma in patients with MG may be because of early diagnosis of thymoma as a result of MG symptoms.
Our results showed that Masaoka-Koga stage > I was associated with failure to achieve a 3 point decrease of QMGS, and thus worse prognosis and worse clinical outcome. A systematic review of prognostic factors predicting thymoma recurrence by Detterbeck et al. [26] reported significant factors were Masaoka stage and completeness of resection; whereas other factors such as age, sex, size of tumor, and MG were not statistically significant in multivariate analysis. De Rosa et al. [27] studied thymoma-associated MG and reported the risk of replase was associated with higher patient age and higher Masaoka-Koga stage.
The primary limitation of the study is the retrospective nature. However, the number of patients was large, and the follow-up period was long.