As far as we know, this is the first study to analyze the impact of prior cancer history on outcomes in thymoma. Our study indicated that a prior cancer history had a significant but heterogenous effect on the survival of thymoma patients. To some degree, the unadjusted survival analyses show the prior cancer was associated with worse survival compared to the first primary cancer (Fig. 1A). Prior cancer had an adverse effect on overall survival in patients younger than 65 years. Patients with a prior cancer history shown worse survival for stages II (Fig. 1C) but had no statistic difference survival in multivariate Cox proportional hazard model analysis. Patients may have competing priorities to make treatment decisions and treatment modalities may have implications for survival[7, 8]. The adjusted survival analyses were stratified by treatment modalities for further analysis. It revealed that the prior cancer cohort had significantly worse survival in the chemoradiotherapy subgroup.
The cancer survivor population is rapidly growing in the USA over the past 30 years, largely driven by the aging population, the improvement of treatment, and expanding cancer screening efforts[9]. These factors have led to an increased prevalence of multiple primary cancer[10]. In our study, 20% of older (age > 65 years) and more than 10% of younger adult (age ≤ 65 years) diagnosed with thymoma had prior cancer history. As shown in Fig. 2A, the patients with a history of prior cancer had significantly worse prognosis among younger adult subgroup. The study led by Andrew et al found that prior cancer did not adversely affect on clinical outcomes and suggested the prior cancer history subset should not be excluded from clinical trials among advanced lung cancer patients[11, 12]. Older patients were more likely to die of the progression of cancer and comorbidities, thus prior cancer had less impact relatively. Younger patients with thymoma tended to have a better prognosis and were more likely to be cured than older patients[13]. Prior cancer treatment could increase the risks of treatment intolerance thus worsen the survival of younger patients[14].
Although several staging systems exist, the Masaoka staging classification is the most extensive used and is a wonderful predictor for the prognosis of thymoma[15, 16]. The 5-year overall survival rate were approximately 85% in the stage I to III thymoma patients and 65% in the stage IV thymoma patients [15, 17, 18]. For stage I and stage II thymoma, complete surgical resection is the recommended standard treatment. What’s more, postoperative radiotherapy is suggested in incompletely resected or high-risk stage II thymomas[19]. Adjuvant radiotherapy can reduce local recurrence rates and completely resected stage II tumors may benefit from adjuvant radiotherapy but without impact on overall survival[20, 21]. It is not yet clear whether stage II thymoma patients with a prior cancer history could benefit from postoperative radiotherapy. We found that prior cancer didn’t display significantly worse survival to those without prior cancer in patients with stage II thymoma.
Thymomas are representative slow-growing tumors that can spread locally. Metastases are usually restricted to the pericardium, diaphragm, or pleura, whereas extrathoracic region metastases are uncommon[20]. Because of their rarity, various studies are necessary to expore and improve current therapeutic standards. Surgery is the cornerstone of the treatment of thymomas and primary treatment in multimodality strategies. Complete removal of the tumor and total thymectomy are recommended for most resectable tumors[6, 20–22]. Incompletely resected tumors or tumors with a positive resection margin are generally treated with radiotherapy. Chemotherapy combined with radiotherapy is recommended in unresectable thymomas or advanced thymomas[20, 21]. It can be seen from Fig. 3 that the “prior cancer history” cohort was associated with worse survival compared to the “first primary” cohort among patients received radiation and chemotherapy. Intriguingly, our results showed that the impact of a prior cancer history was not statistically significant for advanced thymomas. On one hand, the prior cancer treatment increased the toxicity and intolerance of chemoradiotherapy, and on the other hand unresectable thymoma patients with a prior cancer history had a more complex condition.
The current study suggested that prior cancer history may have a significant impact on the selection of retrospective study and clinical trial. We suggested that including prior cancer history as a stratification or covariate variable when prior cancer history was known to modify the effect of one or more independent variables. The relation between survival and prior cancer history most probably reflected an interaction between: (1) the recurrence or lethality of prior cancer, (2) the recurrence or lethality of the newly diagnosed thymoma, and (3) the personal circumstances of patients.
Undeniably, the present study has several limitations. Firstly, we confirmed a prior cancer history according to the sequence number only, without detailed prior cancer characteristics. Hence we could not distinguish whether the index thymoma was from local recurrence. Secondly, the current study focused on prior cancer history, without description of the specific prior cancer type. Prior cancer type could affect results, as the previously diagnosed cancer could be “likely lethal” or “likely irrelevant” to prognosis. Thirdly, the SEER database lacked detailed information on therapeutic regimens for chemotherapy and radiotherapy or toxicity. Comorbidities and adverse events were not captured in the database, either. In addition, the data which acquired from the SEER database cover approximately 34.6% of the population in the United States. Further studies are required to confirm the generality of our findings.