Thymic Carcinoma Patients Research Articles

Narrative review of indication and management of induction therapy for thymic epithelial tumors.

Thymic epithelial tumors (TETs) are rare and originate from the thymus. Thymomas and thymic carcinomas are the most common types of TETs. Of the two, thymomas tend to have a better prognosis and are typically localized, while thymic carcinomas have a worse prognosis and are more likely to spread. The Masaoka-Koga staging system is commonly used to determine the stage of TETs. Complete resection is the preferred treatment option, but treating locally advanced TETs can be challenging due to the invasion of surrounding structures. In such cases, induction therapy is administered to downstage the tumors and enable complete resection. We conducted this narrative review to evaluate the current progress in induction treatment for locally advanced TETs. The literature search was performed using PubMed and Web of Science in June 2023. Prospective and retrospective published trials, systemic and narrative reviews, and meta-analyses were included. Induction chemotherapy is often used as a preoperative treatment for advanced TETs. Platinum and anthracycline-based chemotherapy regimens are commonly used for treating thymoma (response rate, 37-100%), and complete resection is highly common. Treatment with cisplatin and etoposide, carboplatin and paclitaxel, docetaxel and cisplatin have also demonstrated effectiveness, particularly in patients with thymic carcinoma or thymoma who cannot tolerate anthracycline regimens. The emergence of immunotherapy and targeted therapies may provide additional options for the treatment of TETs. Induction radiotherapy, as the sole treatment for TETs, is not widely practiced due to concerns about potential damage to surrounding tissues. However, combining modern radiation techniques with surgery has shown promising results in selected patients. Induction chemoradiotherapy, which combines chemotherapy and radiation, is an emerging approach for treating TETs. Despite the lack of randomized trials comparing chemotherapy with chemoradiotherapy, concurrent chemoradiation with radiation doses of 40-50 Gy is often considered the optimal induction therapy for thymic carcinoma patients or in more advanced special situations, such as great vessel invasion. Overall, the optimal treatment for locally advanced TETs remains controversial. Induction therapy, including chemotherapy, radiotherapy, or chemoradiotherapy, is administered to downstage tumors and improve resectability. The choice of treatment depends on individual factors such as tumor stage, histology, and overall patient condition. However, further research and well-designed studies are needed to determine the most effective treatment strategies for locally advanced TETs.

Rechallenge immunotherapy after immune resistance in patients with advanced thymic carcinoma.

Immunotherapy is effective for patients with advanced thymic carcinoma (TC). However, the effectiveness of rechallenge immunotherapy in patients who are resistant to immunotherapy has not been investigated. Thirty-five patients with advanced TC using immunotherapy between 2016 and 2023 at Zhejiang Cancer Hospital, The Second Affiliated Hospital of Nanchang University, and Fujian Cancer Hospital were evaluated in this study. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A total of 35 patients were included in this study. The median PFS (mPFS) for all patients was 5.43months and the median OS (mOS) was 16months. After rechallenge immunotherapy, only three patients achieved partial response, resulting in an overall response rate of 16.7%, and nine patients attained stable disease, resulting in a disease control rate of 66.7%. Patients who underwent rechallenge immunotherapy had shorter mPFS compared to chemotherapy (3.53months vs. 6.00months, P = 0.041). In addition, the incidence of Grade 3-4 treatment-related adverse events in these patients was 22.2%. Rechallenge immunotherapy has poor efficacy in immunotolerant TC patients.

Clinical features and prognostic factors in thymoma and thymic carcinoma.

Thymic epithelial tumors represent the most common cause of anterior mediastinal masses in adults. Among these tumors, thymomas constitute the majority, whereas thymic carcinomas are less prevalent and associated with a poorer prognosis. This study seeks to investigate the clinical and prognostic factors of these rare entities, thymoma, and thymic carcinomas. We conducted a retrospective analysis on a cohort of 60 patients diagnosed with thymoma and thymic carcinoma, who were under follow-up at our clinic between January 1998 and February 2023. The clinical characteristics and prognostic factors of these patients were analyzed separately. Thymomas accounted for 75% of the cases. The median age at diagnosis was 46years in both patient groups. Masaoka stage 4 was observed in 28.9% of thymoma patients and 66.7% of thymic carcinoma patients. The median overall survival (mOS) for thymoma patients was 261.4months, while it was 9.23months for patients with thymic carcinoma. Curative surgery emerged as a prognostic factor significantly influencing overall survival in both thymoma and thymic carcinoma patients. Our study highlights the significance of Eastern Cooperative Oncology Group (ECOG) performance status and curative surgery as prognostic factors affecting overall survival in thymoma patients. In thymic carcinoma, only curative surgery was found as a prognostic factor. These findings may enhance patient care and guide personalized treatment strategies. Further investigations and prospective studies are warranted to corroborate and expand upon these results.

Incidence of second malignancies in patients with thymic carcinoma and thymic neuroendocrine tumor

ObjectivesThymic carcinoma and thymic neuroendocrine tumor (NET) are rare and are more likely to develop second malignancies. The purpose of this study was to explore the incidence and lifetime risk of second malignancies in thymic carcinoma and thymic NET.MethodsThe standardized incidence ratio (SIR) and the age-adjusted cancer incidence of the thymic carcinoma and thymic NET patients with second malignancies were retrospectively calculated by using the Surveillance, Epidemiology, and End Results (SEER) database. Prognosis results were also determined by Kaplan–Meier analysis and Cox regression.Results1130 patients with thymic carcinoma (73 patients had second malignancies) and 263 patients with thymic NET (19 patients had second malignancies) from 2000 to 2018 are included. Patients with thymic carcinoma (SIR: 1.36, 95% CI 1.08–1.69) and with thymic NET (SIR: 1.73, 95% CI 1.13–2.54) demonstrate an increased overall risk of developing second malignancies in various organ systems. The age-adjusted cancer incidence of second malignancies in patients with thymic carcinoma is 3058.48 per 100,000 persons (4178.46 per 100,000 persons in patients with thymic NET). Age at diagnosis is a significant risk factor for the development of second malignancies.ConclusionThe incidence of second malignancies in patients with thymic carcinoma and thymic NET is significantly higher than the patients in the normal population. The occurrence of second malignancies is not related to the use of different treatments. It is important to extend the follow-up period and add other screening methods.

Poor efficacy of immune checkpoint inhibitor treatment in advanced thymic carcinoma patients with liver metastases.

Although immune checkpoint inhibitor treatment for advanced thymic carcinoma exhibits promising efficacy, factors that affect the efficacy and prognosis, including metastases sites, remain uncertain. Our study aimed to investigate the determinants of survival among patients with advanced thymic carcinoma who underwent immunotherapy in real-world settings, with implications for clinical practice. Different therapy regimens of immunotherapy were produced to analyze the influence of liver metastases on survival and prognosis for advanced thymic carcinoma patients. Data for advanced thymic carcinoma patients receiving immunotherapy and their metastases sites were collected for analysis from seven different hospitals between January 2015 and January 2023. Progression-free survival (PFS) and overall survival (OS) analyses were performed using the Kaplan-Meier method. Cox analysis was used to evaluate factors influencing survival. The present study analyzed 136 advanced thymic carcinoma patients from seven different hospitals.The PFS for all patients receiving immunotherapy was 6.4 months, while the OS was 24.0 months. The objective response rate was different for patients with liver and non-liver metastases (11.9% versus 37.2%, p = 0.003). The disease control rate values were also different between the two groups (47.6% versus 80.9%, p = 0.037). The PFS for patients with liver metastases demonstrated poor immunotherapy efficacy compared to patients with non-liver metastases (3.0 versus 8.0 months, p < 0.0001). The OS was also significantly different between these two patient groups (16.1 versus 29.1 months, p = 0.009). Immunotherapy had poor efficacy in advanced thymic carcinoma patients with liver metastases.

Disseminated Thymic Carcinoma: Case Report and Discussion on Problems of Treatment

Thymic carcinoma (TC) is a rare epithelial malignancy often distinguished by significant local invasion and propensity for distant metastases. Representing approximately 20% of all thymic neoplasms, the primary therapeutic intervention for resectable tumors remains surgical resection. For those that are unresectable or metastatic, palliative platinum-based chemotherapy is standard. Despite these interventions, approximately 30% of these malignancies are already advanced upon initial presentation. The current 5-year survival rate for metastatic TC stands at approximately 38%, with a definitive optimal treatment regimen yet to be established. This case report delineates a comprehensive five-year clinical trajectory of a patient with advanced TC who exhibited resistance to systemic treatments but showed favorable response to stereotactic body radiation therapy (SBRT). Through this case, we underscore the potential of SBRT as a viable therapeutic alternative for select metastatic TC patients. In our case, SBRT exhibited reliable local tumor control in each treated site with minimal side effects. To better understand the possibility of treatment options for disseminated TC more cases should be collected.

Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways.

Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches. We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs. The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling. We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.

Investigation of the prognostic significance of CD5, CD117, EZH2, POU2F3, MTAP and BAP1 in thymic carcinoma.

e20646 Background: Thymic carcinomas tend to be aggressive malignancies with variable patterns of immunostaining. We aimed to assess whether the outcome of patients with thymic carcinomas was associated with immunoreactivity for conventional and emerging immunohistochemical markers of thymic carcinoma versus thymoma. Methods: Scoring of CD5, CD117, EZH2, POU2F3, BAP1, and MTAP immunohistochemistry on whole slide sections was compared to overall survival (OS) and progression free survival (PFS) for 36 thymic carcinoma patients, 28 of whom had complete tumor resection and 8 of whom had incomplete tumor resection. Results: Positive CD5 staining (defined as staining in ≥50% of tumor cells) was present in 13/36 cases (36%) and was significantly associated with longer OS (P = 0.005, hazard ratio = 0.18, CI 0.03-0.63) but not PFS (P = 0.14, hazard ratio = 0.48, CI 0.16-1.26), whereas the other markers were not significantly associated with OS or PFS. Positive CD5 staining remained significantly associated with OS in squamous cell carcinoma subgroup analysis (n = 23, HR = 0.17, CI 0.03-0.65, P = 0.009), patients who did not receive neo-adjuvant treatment (n = 24, HR = 0.21, CI 0.03-0.85, P = 0.03) and after adjusting for incomplete resection (HR = 0.20, CI0.03-0.73, P = 0.01), M1 stage (HR = 0.19, CI 0.03-0.71, P = 0.01) or neoadjuvant treatment (HR = 0.19, CI 0.03-0.71, P = 0.01) in bivariate models. Positive CD5 staining was also significantly associated with age ≥60 years, absence of neoadjuvant treatment, and positive POU2F3 staining. Conclusions: CD5 staining in ≥50% of tumor cells was significantly associated with longer OS for thymic carcinoma patients. Our study supports the notion that CD5 immunohistochemistry may have utility as a prognostic marker for thymic carcinomas.

An evaluation of cisplatin, doxorubicin, and cyclophosphamide (PAC) compared to other regimens for patients with unresectable or metastatic thymic carcinoma: A single-institution retrospective analysis.

e20650 Background: Thymic Epithelial Tumors (TETs) are uncommon tumors of the anterior mediastinum comprised of thymomas and Thymic Carcinomas (TC). Given the rarity of these tumors, little data exists regarding the comparative effectiveness of various combination therapies. Platinum-based treatment regimens in combination with anthracyclines (e.g., PAC), taxanes (e.g., carboplatin plus paclitaxel (CT)) or etoposide (PE) have demonstrated efficacy in TETs in the front-line setting (although current NCCN guidelines recommend only CT for the treatment previously untreated advanced TC). We sought to characterize the efficacy of these regimens for TCs in a real-world setting. Methods: We conducted a single-institution, retrospective database analysis of 164 TC patients seen at the IUSCCC from 1996 - 2020. Of those patients, 42 met the study criteria as having a de novo diagnosis of TC treated with front-line systemic chemotherapy and available outcome data. Chemotherapeutic intervention and demographic/clinical variables were evaluated in this study. Data was compiled and collected using descriptive statistics and the Kaplan Meier method for survival analysis via GraphPad Prism software. Results: Of the 42 patients identified to have sufficient data, the median age was 55.6 years (range, 21 - 82). The median follow-up for patients was 23 months. Metastatic sites of disease included the pleura (11%), lymph nodes (11%), bone (10%) and lungs (5%). Multi-site involvement accounted for 36% of cases. Squamous cell carcinoma (SCC) was found in 52.3% (n = 22) of the patients, while 26.2% (n = 11) had rare TC subtypes, including, SCC with basaloid features, SCC with neuroendocrine features, and neuroendocrine (21.4% of cases were classified as TC only). Most patients received first line treatment with PAC (n = 16), CT (n = 13) or PE (n = 9). There was no difference in progression free survival (PFS) for TC patients treated with PAC or CT (10.5 v. 7.5 months, respectively, NS). PE was associated with inferior outcomes compared to PAC (4.5 vs. 10.5 months, ***p = 0.0005) and CT (4.5 vs. 7.5 months, *p = 0.0158), respectively. A subgroup analysis of rarer histologic subtypes revealed a trend towards improved PFS for patients who received PAC compared to CT (9.5 v. 4.5 months, NS). Conclusions: The results of our study support PAC combination chemotherapy as a reasonable alternative for patients with previously untreated advanced TC. Further studies to correlate the genomic differences of common and uncommon TC subtypes will be crucial to optimize the role of conventional and targeted systemic therapies in this rare malignancy.

Racial and ethnic differences in thymic epithelial tumors: A single-institution retrospective analysis.

e20649 Background: Thymic epithelial tumors (TETs) are a rare, heterogeneous group of malignancies that arise from the thymus. While the etiology of TETs remains unknown, variation in incidence rates amongst racial/ethnic groups has raised the possibility of germline predispositions. Unfortunately, due to the rarity of this disease, there is a limited understanding of the impact of race/ethnicity on tumor characteristics and treatment outcomes for TET patients. We sought to characterize patient/tumor data and investigate treatment outcomes based on race and ethnicity. Methods: We conducted a single-institution, retrospective database analysis of TET patients evaluated at the IUSCCC from 1979 – 2021 from which clinical annotations were available for 477 thymoma and 164 thymic carcinoma (TC) patients. We identified 112 thymoma and 35 TC patients who were deemed to have sufficient data for evaluation of racial/ethnic characteristics. Demographic/clinical variables and therapeutic interventions, including treatment outcomes, were analyzed. Data was compiled and analyzed using descriptive statistics and the Kaplan Meier method for survival analysis via GraphPad Prism software. Results: Of the 112 thymoma patients, 29 thymoma patients presented with de novo metastatic disease at the time of diagnosis. The median age at the time of diagnosis of all patients revealed a statistically significant difference between White and Black TET patients (53.0 v. 42.0 years, *p = 0.0195). There was a trend towards significance when median age of diagnosis between White and Asian TET patients was compared (53.0 v. 48.0 years, p = 0.0633, NS). Advanced histologic subtypes, include B3 and TC, appeared predominantly in Asian and Black patients at 77.7% and 56.3%, respectively, compared to White patients (44.9%), though the finding was not statistically significant. No statistically significant differences between racial/ethnic groups regarding progression free survival for unresectable or metastatic disease were observed, regardless of histology. There was a non-significant difference in recurrence free survival for resectable thymoma in White (30.0 months) and Asian/Pacific Islander (47.0 months) patients compared to Black patients (24.0 months). Conclusions: Overall, this analysis suggests differences in the median age of diagnosis for patients with thymic malignancies based on race, raising the possibility of inherent biologic differences driving oncogenesis and symptoms at the time of presentation. While no statistically significant differences in treatment outcomes were found based on race and ethnicity, Black patients appeared to experience shorter times to recurrence after definitive surgery. Further studies to understand the mechanistic differences driving tumorigenesis and potential disparities in treatment outcomes are greatly needed in this rare tumor type.

Chemoradiotherapy for untreated Masaoka-Koga stage IVB thymic carcinoma: asingle-center retrospective study.

Thymic carcinoma (TC) is arare type of amalignant tumor. The optimal treatment for Masaoka-Koga stage IVB TC patients is controversial due to the rarity of the disease. Chemotherapy is still the preferred option, but the outcomes are unsatisfactory. Whether radiotherapy combined with chemotherapy could improve prognosis remains unclear. Untreated stage IVB TC patients who have received first-line chemotherapy were included in the present study. The patients who have undergone surgery were excluded. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). Sixty-seven patients were included in the study. Atotal of 31patients received chemoradiotherapy (ChemoRT cohort), and the remaining 36patients only received chemotherapy (Chemo cohort). The median follow-up period was 40.3months. The ORR for the ChemoRT and Chemo cohorts was 61.3 and 27.8%, respectively (P = 0.006). Furthermore, PFS (P = 0.003) and OS (P = 0.046) were significantly superior in the ChemoRT cohort. Radiotherapy maintained asignificant favorable effect on PFS in multivariate analysis (P = 0.014), but the effect on OS was insignificant (P = 0.249). There was no advantage in PFS (P = 0.302) in the ChemoRT cohort in patients who received< 4cycles of chemotherapy. In contrast, radiotherapy significantly improved PFS (P = 0.005) in patients who received≥ 4cycles of chemotherapy. Chemoradiotherapy used as the first-line treatment improved ORR and PFS in Masaoka-Koga stage IVB TC patients. Patients receiving more cycles of chemotherapy may have abetter chance to benefit from chemoradiotherapy.

Evaluation of Chemotherapeutic Outcomes for Thymic Carcinoma Patients

Background and Hypothesis:Thymic Epithelial Tumors are uncommon tumors of the anterior mediastinum composed ofthymomas and thymic carcinomas (TC). TC’s are known to have worse disease outcomes andlower rates of survival in comparison to thymomas and are suspected to have lower responserates to chemotherapy as well. As these tumors are rare, little data exists assessing the trueefficacy of chemotherapeutic regimens for TC patients. Due to this lack of data, and that theIndiana University Health Simon Cancer Center treats a high percentage of TET patients, adatabase of these patients covering a variety different disease characteristics and treatmentshas been established. We hypothesize, upon evaluation of this database, response rates toanthracycline based regimens (PAC) will be superior to non-anthracycline based regimens (i.e.,PE, Carbo/Taxol) for TC patients.&#x0D; Methods:In this project, a collection of patients seen by Dr. Patrick Loehrer and/or Dr. Kenneth Keslerwas acquired, and a database was created using these patients in RedCap. Once established,we evaluated patient medical records in Cerner and entered data related to diseasecharacteristics and treatments. These patients were then analyzed accordingly to evaluatechemotherapy response rates.&#x0D; Results:The database yielded 123 instances of chemotherapy treatment for TC. Of which, the mostpopular treatments were PAC and Carbo/Taxol. The data suggests that PAC generates a higherresponse rate (65.5%) than other therapies (Carbo/Taxol: 27.6%, PE: 58.3%, etc.). Therefore,there is evidence that anthracycline based regimens may be more effective at generatingresponse rates in comparison to non-anthracycline based regimens.&#x0D; Conclusion and Potential Impact:This project will help elucidate the effectiveness of recommended systemic therapies for thymiccarcinoma patients from one of the largest TET databases constructed. Ultimately, we hope thatwith clarity of the effectiveness of treatment, this can serve as a reliable reference for evidencebasedmedicine for the care of TC patients.

The role of surgery in advanced thymic tumors: A retrospective cohort study.

There is no definitive and detailed treatment guideline for advanced thymic tumors, thus when lymph node and other organ metastasis are present, clinical guidelines recommend chemotherapy-based multidisciplinary treatment. A consensus has been reached that surgery has beneficial effects on partial patients with stage IVA whose metastatic lesions were isolated and resectable, but because of few cases of advanced thymic tumor s and the scarcity of reports, the role of surgery in stage IVB is still unknown. The current study aimed to systematically analyze the role of surgery in advanced thymic tumors based on the Surveillance, Epidemiology, and End Results (SEER) database, with a sufficient number of cases. A secondary aim was to clarify the prognostic value of surgery in advanced thymic tumors. Data derived from a total of 979 patients with advanced thymoma or advanced thymic carcinoma were collected from the SEER database. Propensity score matching was performed to eliminate confounding factors, and Cox regression analyses were conducted to assess prognoses. Patients were assigned to four groups based on pathology and whether surgery was performed; thymoma (surgery), thymoma (no surgery), thymic carcinom a (surgery), and thymic carcinoma (no surgery). Disease-specific survival differed significantly in the thymoma (surgery) and thymoma (no surgery) groups, both before and after propensity score matching (both p < 0.001). Similarly, disease-specific survival differed significantly in the thymic carcinoma (surgery) and the thymic carcinoma (no surgery) groups (p < 0.001 before and p = 0.003 after). No total resection, distant metastasis, and thymic carcinoma were all unfavorable prognostic factors. In the present study surgery had positive effects on advanced thymoma and advanced thymic carcinoma patients who could undergo surgical resection, significantly improving survival times. Total resection of the primary site was the most advantageous form of surgery. The study provides a reference for the clinical treatment of advanced thymic tumors.

The efficacy of small molecule anti-angiogenic drugs in previously treated Thymic carcinoma

BackgroundAntiangiogenic drugs have shown initial efficacy in the treatment of advanced thymic carcinomas (TCs); however, data are limited. In this study, we provide real-world data relating to the efficacy of antiangiogenic drugs for the treatment of patients with TCs.MethodsWe retrospectively collected data on clinical progress after first-line chemotherapy in TCs patients who were treated with small molecule antiangiogenic drugs at our institution between January 2010 and December 2021. Tumor response was evaluated according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Progression free survival and overall survival were calculated using the Kaplan-Meier method.ResultsOf the 17 patients enrolled, 13 (76.5%) received apatinib and four (23.5%) anlotinib monotherapy with an objective response rate of 23.5%. Eleven (64.7%) patients had stable disease. The median follow-up period was 46.0 months (95% confidence interval [CI], 33.0–59.0 months). The median progression survival and overall survival were 7.9 months (95% CI, 6.5–9.3) and 47.0 months (95% CI, 35.4–58.6), respectively. In the 13 patients receiving apatinib, the median PFS was 7.0 months (95% CI, 5.0–9.0), compared with 8.0 months (95% CI, 2.7–13.3 months) for patients in the anlotinib group (P = 0.945). The most common grade 3 adverse events (AEs) were hypertension (n = 3, 23.1%), followed by proteinuria and hand-foot syndrome (HFS, n = 2, 15.4%). There were no grade 4 AEs although eight patients (47.1%) required mid-course discontinuation.ConclusionFor refractory TCs, small molecule antiangiogenic drugs are efficacious as second- or post-line treatments. The toxicity of antiangiogenic therapy is manageable.

Genomic characterization of thymic epithelial tumors reveals critical genes underlying tumorigenesis and poor prognosis.

Thymic epithelial tumors (TETs) are rare mediastinal tumors whose tumorigenesis mechanism is poorly understood. Characterization of molecular alterations in TETs may contribute to a better understanding of tumorigenesis and prognosis. Hybrid capture-based next-generation sequencing was performed on tumor tissues from 47 TETs (39 thymomas and 8 thymic carcinomas) to detect mutations in 315 tumor-associated genes. In total, 178 nonsynonymous mutations were identified, with a median of 3.79 per tumor in 47 TETs. Higher tumor mutation burden (TMB) level was more common in older TET patients, and significantly associated with the more advanced pathological type, especially in thymic carcinomas (TC) patients. The gene mutation profiles of B1-3, A/AB, and TC patients varied greatly. In the actionable mutations analysis, we found 32 actionable mutations in 24 genes. Among them, NFKBIA and TP53 mutations was the most frequently, which were only identified in TCs. Additionally, TCGA database analysis found that the expression of NFKBIA mRNA in the TCs were significantly higher than thymomas. TET patients with high NFKBIA expression had shorter overall survival compared with patients with low/medium NFKBIA expression, thus providing insights to consider NFKBIA as a potential prognosis biomarker and therapeutic target in TETs.

Anlotinib in patients with relapsed or refractory thymic epithelial tumors: a study of 50 cases.

The optimal pharmaceutical regimen for advanced thymic epithelial tumors (TETs) remains controversial when first-line chemotherapy fails. This retrospective study aims to evaluate the efficacy and safety of anlotinib treatment for patients with relapsed and refractory TETs. Patients with progressive disease after failure of platinum-based chemotherapy were enrolled in this study. Anlotinib was orally taken once a day at an initial dose of 12 mg (10 mg when body weight <60 kg). The cycle was repeated every 3 weeks (2 weeks of treatment followed by 1-week rest). Objective response rate (ORR) and progression-free survival (PFS) were recorded as primary endpoints. There were 50 patients enrolled in this study from October 2018 to June 2021 at a median age of 50 (range 23-79) years old. Patients with thymoma and thymic carcinoma were 33 (66%) and 17 (34%), respectively. The ORR in thymoma and thymic carcinoma patients were 33% (11/33) and 41% (7/17), respectively. The median PFS (mPFS) was 7 (95% CI, 5.9-10.2) months in thymoma patients and 6 (95% CI, 4.6-9.3) months in the thymic carcinoma group. Eleven patients experienced dose reduction due to toxicities, among whom, eight patients discontinued treatment even after dose reduction. Six patients with thymoma showed myasthenia gravis deterioration during treatment, and two of them died of myasthenia gravis crisis. Anlotinib is active in patients with advanced TETs refractory to routine chemotherapy. Prescription of anlotinib to patients with myasthenia gravis should be made cautiously.

Analysis of the efficacy and safety of immunotherapy in advanced thymoma patients.

Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of immunotherapy also remains to be determined. The efficacy and safety of immunotherapy were analyzed in 11 thymoma patients who received PD-1 inhibitors according to a range of relevant indexes including the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immunotherapy-related adverse events. The PFS and OS rates for all patients were 12.8 and 56.5 months, respectively. No difference in efficacy was detected between monotherapy and combination therapy (PFS: 12.8 vs 2.2 months, P = 0.787; OS: 73.8 vs 56.5 months, P = 0.367). The ORRs and DCRs for all patients were 27.3% and 90.9%, respectively. The incidence of adverse events was 45.5% among the 11 thymoma patients, including immune-related myocarditis (36.4%), immune-related liver damage (18.2%), and myasthenia gravis (18.2%). In the whole cohort of patients, the rate of adverse events of grade 3 or higher was 36.4%. The rates of adverse events of grade 3 or 4 in B3-type and non-B3-type thymoma patients were 0% and 62.5%, respectively. Immunotherapy elicited a response in thymoma patients; however, more attention should be paid to the immune-related adverse events.

Investigational drugs for the treatment of thymic cancer: a focus on phase 1 and 2 clinical trials

Introduction Thymic epithelial tumors (TETs) are rare tumors of thymic epithelial cells. Treatment options for advanced disease patients who failed standard platinum-based chemotherapy are limited. Areas covered Phase I and II trials published in the last five years testing new systemic treatments for advanced TET patients are discussed, as well as ongoing trials. A PubMed database literature review was conducted for articles published between January 2016 and December 2021, and ongoing clinical trials were retrieved from ClinicalTrials.gov database. Expert opinion The most promising classes of new drugs in TET patients are angiogenesis inhibitors and immune checkpoint antibodies (ICIs). Sunitinib and Lenvatinib showed response rates of 26% and 38%, respectively, and ICIs showed durable responses in 20-25% in thymic carcinoma patients (TCs). Both approaches are mainly active in TCs, therefore new treatment options for thymomas is an unmet medical need. Two major new therapeutic strategies are ICIs combinations with other drugs and drugs that target pathways that are dysregulated in TETs. Future challenges include the development of preclinical models to help identify novel targets and test new treatment strategies, and randomized clinical trials to provide reliable evidence based on survival endpoints.

1632P Analysis of penpulimab plus anlotinib in pleural mesothelioma or thymic carcinoma patients who have received at least one line of chemotherapy

Pleural mesothelioma and thymic carcinoma have low morbidity and few treatment options available. Penpulimab is an IgG1 PD-1 antibody, which features point mutations in the antibody Fc region to eliminate all Fc gamma receptor binding and associated effector function. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit，Preclinical research has confirmed that penpulimab and anlotinib can significantly reduce the proportion of TIM3+PD1+CD8+ T cells，improving anti-tumor efficacy. This study aimed to evaluate the efficacy and safety of anlotinib in combination with penpulimab in patients with pleural mesothelioma or thymic carcinoma who have received at least one line of chemotherapy. This study is a single-arm phase II study. Eligible patients had recurrent/metastatic pleural mesothelioma and thymic carcinoma who were inoperable or intolerant to radical radiotherapy and had failed at least first-line chemotherapy, were over 18 years old, with ECOG PS of 0-1. The primary endpoint was ORR, and secondary endpoints were DCR, PFS, DOR, OS and safety. Patients received anlotinib (12mg QD from day 1 to 14 of a 21-day cycle) plus penpulimab (200mg Q3W) until disease progression or intolerance. Between Nov 13, 2020, and May 12,2021, 12 patients were enrolled and treated, including 5 cases of thymic carcinoma and 7 cases of pleural mesothelioma. The data cutoff date was on Apr 19, 2022. There were 10 males and 2 females. All patients had ECOG PS of 1. Four patients received only one prior line of chemotherapy. 11 patients were available for tumor assessment, ORR was 18.2%, and DCR was 81.8%. The data on PFS and OS were not mature. The common TEAE were hypoalbuminemia (75%), hypertension (75%), anemia (75%), and hypertriglyceridemia(62.5%). The incidence of grade 3 or higher treatment-related AEs was 62.5%, and there was one immune-related AE of grade 3 or higher which was hypocalcemia. Penpulimab plus annlotinib demonstrated preliminary antitumor efficacy and acceptable toxicity in pleural mesothelioma or thymic carcinoma patients who have received at least one line of chemotherapy.

A single-center analysis of 71 patients with thymic carcinoma: the chronological changes in the surgical procedure and prognosis.

BackgroundEffective treatments for thymic carcinoma (TC) have not been established due to its rarity and the prognosis has not yet been improved. In the present study, data of patients who underwent treatment for TC at our single institution were retrospectively reviewed to investigate the chronological changes in the clinical characteristics, surgical procedure, and prognosis.MethodsA total of 71 patients were included in this study. To investigate the chronological changes, the patients were divided into two groups at January 2009, when minimally invasive surgery (MIS) for thymic epithelial tumors (TETs) was introduced.ResultsAmong the 71 TC patients, 24 patients underwent surgery through December 2008 (earlier period), and 21 underwent surgery from January 2009 (later period). The patients in the later group were more likely to be diagnosed by chest computed tomography (CT) scan without subjective symptom. The rates of MIS and complete resection were significantly higher and the number of the patients at the early stage were significantly greater in the later group. The 5-year overall survival (OS) rate of the patients who underwent surgery at earlier and later groups were 58.7% and 92.8% respectively (P<0.01).ConclusionsThe prognosis of TC has improved over time, thanks to early detection by CT screening and complete surgical resection.