A Case of Invasive Thymoma Complicated by Multiple Metastases.

Thymoma is a relatively uncommon thoracic solid tumor, and considered to possess malignant potential. Usually, the lung, pleura, and mediastinum are the most frequently affected sites for metastasis in thymoma. However, the thymoma presenting simultaneous intrathoracic and extrathoracic metastases are exceedingly rare. Herein, we present an exceptionally uncommon case of invasive thymoma with multiple metastases. Furthermore, our case underscores the indispensable role of multimodality imaging in confirming the primary diagnosis and guiding treatment decisions.

[Intraspinal Metastasis of Thymic Carcinoma:Report of One Case].

Intraspinal metastasis from malignant carcinomas in other body parts is rarely reported.Intraspinal metastases are often epidural,with primary tumors mostly from the lung and prostate.The extramedullary subdural metastasis of thymic carcinoma is particularly rare and prone to misdiagnosis due to overlapping imaging features with primary intraspinal tumors.This article reports one case of intraspinal metastasis of thymic carcinoma,with the main diagnostic clues including a history of thymic carcinoma,fast growth rate,and irregular shape.

Endobronchial Metastasis with Bloody Sputum 20 Years after Complete Resection of type A Non-Invasive Thymoma.

Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well.

The safety and efficacy of Cyberknife® for thymic malignancy.

PURPOSE: To evaluate the safety and efficacy of Cyberknife® (CK) for the treatment of primary or recurring thymic tumours. MATERIALS AND METHODS: We retrospectively reviewed 12 patients (16 tumour lesions) with primary or recurring thymic tumours who were treated with CK between March 2008 and October 2017. Their data was stored in prospectively collected database. Kaplan-Meier method was used to calculate survival curves. RESULTS: Five patients (41.7%), who had inoperable disease or refused surgery, were treated with CK initially, and 7 patients (58.3%) were treated with CK when they had recurrence diseases. The disease sites treated with CK were primary tumour site (5), regional lymph nodes (4), tumour bed (3), chest wall (2), pleura (1), and bone (1). The median target volume was 43.8 cm3 (range, 13.1-302.5cm3) for the 16 tumour lesions. The median follow-up time was 69.3 months (range, 9.7-124.8 months). The median survival time was 48.2 months, and the 5-year and 10-year OS rates were 68.2% and 45.5%, respectively. A high response rate for the tumour lesions irradiated with CK was obtained. Only one patient (8%) experienced in-field recurrence, and the 5-year local recurrence free survival was 90.9%. A case indicated that CK may induce the abscopal effect, which provides the potential to combine CK and immunotherapy. No severe radiation related toxicities were observed, and no treatment related death occurred. CONCLUSION: CK treatment resulted in good outcomes, particularly local control, with minimal side effects, in highly selected patients with primary and recurring thymic tumours. More studies with larger sample are needed.

Immunotherapy vs platinum for advanced or metastatic thymic carcinoma: A protocol for systematic review and meta analysis.

BACKGROUND: Thymic carcinoma is a rare malignancy, and platinum-based chemotherapy has not previously been established as a standard treatment for advanced or metastatic thymic carcinoma. With the breakthrough and progress of immunotherapy, the possibility of curing thymic carcinoma has greatly increased. Some clinical trials have reported that compared with traditional platinum-based chemotherapy, the use of programmed death 1 and programmed death ligand 1 inhibitors alone can benefit patients and effectively prolong their overall survival. We compare the efficacy of single immunotherapy with traditional platinum-based chemotherapy in a systematic review and meta-analysis to provide a reliable basis for clinicians. METHODS: Pubmed (Medline), Web of Science, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar will be searched for relevant randomised controlled trials, quasi- randomised controlled trials, and Hi-Q(high quality) prospective cohort trials published or unpublished in any language before March 1, 2021. Subgroup analysis will be performed in tumor pathological stage and ethnicity. INPLASY registration number: INPLASY2020110060. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The results of this systematic review and meta-analysis will provide a basis for clinicians to formulate the best chemotherapy regimen for patients, as well as a research clue for clinical researchers in this field. The results of this study will expand the treatment options for thymic carcinoma, but due to the nature of the disease and intervention, large sample clinical trials are not abundant, so we will include some high-quality small sample trials, which may cause high heterogeneity. INPLASY REGISTRATION NUMBER: INPLASY2020110060.

Single-center evaluation of prognostic factors for thymoma treated by surgery: a retrospective study.

BACKGROUND: This study aimed to retrospectively evaluate the clinical, pathological, and treatment-related factors associated with survival in patients with surgically treated thymomas. METHODS: Sixty patients with thymomas who underwent treatment at our institution between 2004 and 2015 were included. Survival analysis was performed based on curves that were obtained using the Kaplan-Meier method. The Wilcoxon test was used for all comparisons, and p < 0.05 was considered statistically significant. RESULTS: Forty-seven, four, three, four, and two patients presented tumor stages I, II, III, IVa, and IVb (according to the Masaoka classification), respectively, while six, 14, 11, 22, and seven patients had type A, AB, B1, B2, and B3 thymomas, respectively. Furthermore, 53 and eight patients underwent complete resection and required additional resection of adjacent organs, respectively, and no patients died from surgery-related complications. The five-year survival and recurrence-free survival (RFS) rates were 96 and 86%, respectively. The five-year survival rate for all stages was 100% except for those with stage IVb tumors (Masaoka classification); the survival rate for those patients was 0%. Separately, the five-year RFS rates for tumor stages I, II, III, IVa, and IVb were 100, 91, 91, 81, and 71%, respectively. Finally, the five-year survival rates in cases with complete and incomplete resections were 100 and 71%, respectively, indicating that the latter group had a significantly poorer prognosis (p < 0.001). CONCLUSIONS: These findings suggest that complete resection and the Masaoka pathological stage are significant predictors of prognosis in patients with thymomas. Surgery should aim to achieve complete resection; however, advanced cases may require multimodality therapy.

Intensity Modulated Radiation Therapy for Pleural Recurrence of Thymoma: A Prospective Phase 2 Study.

PURPOSE: This study aimed to evaluate the efficacy and safety of intensity modulated radiation therapy (IMRT) for pleural recurrence of thymoma that was not suitable for surgery and had progressed after chemotherapy. MATERIALS AND METHODS: From February 2012, consecutive patients with pleural recurrence of thymoma were prospectively enrolled. Due to dose restrictions to normal tissue (lung, liver, and kidney), 3 different levels of radiation doses (30 Gy, 40 Gy, and 50 Gy) were prescribed for pleural lesions of different sizes and locations, with a daily fraction dose of 2 Gy. The objective response rate, local control time (LCT), overall survival time, and toxicity were recorded, respectively. RESULTS: By August 2016, 31 patients had completed the IMRT treatment. There were 21 male and 10 female patients, with a median age of 49 (range, 22-70) years. B3 thymoma was the major (62%) tumor subtype observed. During the median follow-up of 48 (24-70) months, the objective response rate was 97%, and the median LCT was 49 (95% confidence interval, 40.4-58.1) months. However, 29 (93.5%) patients developed out-of-field recurrence, among whom 10 (32%; 30 Gy, n = 7; 40 Gy, n = 3) developed both out-of-field and in-field recurrence. The median progression-free survival was 19 months, and no in-field recurrence occurred in the 50 Gy group. Moreover, a higher dose was related to a longer LCT. No toxicities higher than a grade 4 occurred after IMRT within the normal-tissue dose limitation. The 5-year overall survival of the patients was 81%. CONCLUSIONS: IMRT for pleural recurrence may act as an alternative treatment when surgery is not feasible, with a higher dose resulting in a longer LCT. In this study, out-of-field recurrence was considerably common, but repeated IMRT for new recurrence should be cautiously carried out due to the high risk of radiation-induced pneumonitis.

Extended thymectomy with blood vessel resection and reconstruction improves therapeutic outcome for clinical stage III thymic carcinoma patients: a real-world research.

OBJECTIVES: We examine the therapeutic efficacy of extended thymectomy with blood vessel resection and reconstruction in thymic carcinoma patients with great vessel invasion. METHODS: In total 26 patients diagnosed as clinical stage III thymic carcinoma with severe great vessel invasion were enrolled in this retrospective study. Among these patients, 14 cases received adjuvant chemo- and radiotherapy (non-operation subgroup, NOG), the other 12 patients received extended thymectomy with vessel resection and reconstruction followed by the adjuvant treatment (operation subgroup, OG). RESULTS: All surgical procedures went smoothly with no perioperative death. R0 resection was obtained in all surgical cases, and we also observed a lymph node metastasis rate of 38.8%. The overall survival (OS) was 34 months for the whole cohort, 48 and 26 months for the OG and NOG respectively (p = 0.013). The median disease metastasis free survival (DMFS) was 47 months for the OG and 18 months for the NOG (p = 0.019). CONCLUSION: Extended thymectomy with vessel resection is feasible for patients with clinical stage III thymic carcinoma. Surgery significantly improves the overall survival and the prognosis of clinical stage III thymic carcinoma.

Treatment strategy and prognostic analysis of spinal metastases from thymomas: A retrospective study from a single center.

OBJECTIVE: Thymomas are rare in clinical practice, and cases of metastatic spinal thymoma are extremely scarce, with only a few case reports or case series described in the literature. In this study, we characterized the clinical features, treatment options and prognostic analysis of patients with metastatic spinal thymomas. PATIENTS AND METHODS: This study included seven patients with metastatic spinal thymoma who underwent open surgery or minimally invasive surgery, and adjuvant treatment in a single center of Peking Union Medical College Hospital from 2010 to 2019. The basic clinical data of the patients were analyzed retrospectively. The possible prognostic factors of progression-free survival (PFS) and overall survival (OS) were studied using the Kaplan-Meier method. RESULTS: This retrospective study included six male patients and one female patient, with a median age of 58.4 (47-75) years. The time from initial diagnosis to detection of spinal metastasis was 54.2 (30-108) months. Kaplan-Meier survival analysis showed the number of spinal metastasis and adjuvant therapies were favorable factors for improving OS and PFS in patients with metastatic spinal thymomas. CONCLUSION: Radiation therapy after the primary operation is an efficient adjuvant therapy, since patients who received postoperative radiation treatment have longer OS and PFS than those who receive chemoradiotherapy. The number of spinal metastases seems to be an effective prognostic factor for longer OS and PFS of patients with spinal metastasis of thymoma.

Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial.

BACKGROUND: Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma. METHODS: This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777. FINDINGS: Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1-17·5). The objective response rate was 38% (90% CI 25·6-52·0, p<0·0001). 16 (38%) of 42 patients had a partial response and 24 (57%) had stable disease. The most frequent grade 3 treatment-related adverse events were hypertension (27 [64%]) and palmar-plantar erythrodysaesthesia syndrome (three [7%]). No patient died from adverse events. INTERPRETATION: The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma. FUNDING: Center for Clinical Trials, Japan Medical Association.

Persistent type 2 respiratory failure on background of advanced thymoma with lung metastases.

We report a patient in her 60s with history of end-stage thymoma with bilateral lung metastases on palliative chemotherapy presented to the hospital with sudden shortness of breath initially treated for probable pulmonary embolism (PE) pending CT of the pulmonary arteries which was subsequently negative for PE. During this admission, she developed transient right-sided facial droop and slurred speech which resolved spontaneously; however, the patient became unresponsive and desaturated with severe decompensated type 2 respiratory failure. Patient was supported with non-invasive ventilation (biphasic positive airway pressure) for few days. Myasthenia gravis was suspected due to clinical features and confirmed by the high titre of acetylcholine receptor antibody titre.

Cytoreductive Pleurectomy and Intrathoracic Chemohyperthermia for Pleural Relapse of Thymomas.

Several surgical procedures, from debulking to extrapleural pneumonectomy, may be applied for stage IVa Masaoka thymomas, but their efficiency is still controversial. Case studies have favored R0 resection as the cornerstone of multimodal therapy for locoregional metastatic extension. This report describes a standardized procedure combining a cytoreductive surgical procedure and intrathoracic chemohyperthermia on a 46-year-old patient presenting with B2 thymoma and synchronous unilateral pleural metastasis.

Successful treatment of malignant thymoma with sacrum metastases: A case report and review of literature.

RATIONALE: Malignant thymoma in the spine is a rare disease without standard curative managements so far. The objective of this article is to report a very rare case of recurrent malignant thymoma with sacrum metastases causing severe lumbosacral pain, which was presented with acute radiculopathy and treated with 2 operations combined with stabilization and cement augmentation. The management of these unique cases is not well-documented. PATIENT CONCERNS: A 75-year-old man presented with lumbosacral pain, radiating pain and numbness of the left extremity. The patient underwent thymectomy in 2008, and posterior spinal cord decompression, tumor resection and a stabilization procedure in 2011. Pathologic results confirmed malignant thymomas of the spine. Imaging studies revealed the density of soft tissues, obvious bony destruction in the sacrum, and significant spinal cord obstruction. DIAGNOSES: We believe this is a less-documented case of metastatic thymoma of the sacral spine presenting with back pain and radiculopathy, and presenting as a giant solid tumor. INTERVENTIONS: The patient underwent osteoplasty via a posterior approach. Pathologic results confirmed malignant thymomas of the sacral spine. OUTCOMES: The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 6-month and 1-year follow-up visit. There were no other complications associated with the operation during the follow-up period. LESSONS: This article emphasizes metastatic thymoma of the spine, although rare, should be part of the differential when the patient presents with back pain and radiculopathy. We recommend the posterior approach for spinal decompression of the metastatic thymoma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation is also a good choice for surgical treatment.

Impact of Lymph Node Dissection on Thymic Malignancies: Multi-Institutional Propensity Score Matched Analysis.

INTRODUCTION: Surgical resection is a standard treatment for thymic malignancies. However, prognostic significance of nodal metastases and lymph node dissection remains unclear. The aim of this study is to determine prognostic significance of nodal metastases and the role of lymph node dissection (LND) in thymic malignancies. METHODS: Between 2000 and 2013, 1597 patients who underwent thymectomy due to thymic malignancy were included. Predictive factors for nodal metastasis and prognostic significance of LND were evaluated. Patients were divided into two groups: (1) LND+ group, with intentional LND (446 patients, 27.9%); and (2) LND- group, without intentional LND (1151 patients, 72.1%). Propensity score matching was performed between the two groups. RESULTS: Lymph node metastasis was identified in 20 (6.7%) of 298 patients with thymoma and 47 (31.7%) of 148 patients with thymic carcinoma. In multivariable analysis, thymic carcinoma (hazard ratio: 19.2, p < 0.001) and tumor size (hazard ratio: 1.09, p = 0.02) were significant predictive factors for lymph node metastasis. The 10-year freedom from recurrence rate of pN1 and pN2 was significantly worse than that of pN0 (p < 0.001). LND did not increase operative mortality or complication. There was no significant difference in 10-year freedom from recurrence rate between LND+ and LND- groups (82.4% versus 80.9%, p = 0.46 in thymoma; 45.7% versus 44.0%, p = 0.42 in thymic carcinoma). CONCLUSIONS: Lymph node metastasis was a significant prognostic factor in thymic malignancies. Although LND did not improve long-term outcomes in thymic malignancies, LND played a role in accurate staging, and improved prediction of prognosis.

Metastatic thymoma in the liver of a dog.

A 12-y-old neutered male Portuguese Water dog was presented because of a 1-y history of persistent hyporexia, diarrhea, and recurrent pyelonephritis. Abdominal ultrasound revealed hepatic nodules and diffuse splenomegaly, and radiographs revealed a mediastinal mass. Fine-needle aspirates of the liver, spleen, and mediastinal mass were suspicious for lymphoma. Flow cytometry identified small T cells that co-expressed CD4 and CD8 at all sites, most suspicious for thymoma, but lymphoma could not be ruled out. PCR for antigen receptor rearrangements analysis identified polyclonal amplification of the T-cell receptor genes, more consistent with thymoma than lymphoma. Histopathology of the liver and thymic mass confirmed thymoma with hepatic metastasis.

A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma.

INTRODUCTION: Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC. METHODS: A total of 27 previously treated patients (16 with thymoma and 11 with TC) with advanced, unresectable disease were treated with pemetrexed, 500 mg/m2, intravenously every 3 weeks for a maximum of six cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12, and steroid prophylaxis. RESULTS: The median number of cycles administered was 6 (range 1-6). Nine patients with a total of 14 events had grade 3 toxicities; no grade 4 toxicities were noted. In 26 fully evaluable patients, two complete and three partial responses (according to the Response Evaluation Criteria in Solid Tumors) were documented (all in patients with stage IVA thymoma, except for one partial response with stage IVA TC). A total of 14 patients completed the full six cycles of treatment, 7 patients progressed while undergoing therapy, 5 patients discontinued therapy because of intolerance, and 1 patient discontinued therapy because of progressive Morvan syndrome. The median progression-free survival time for all patients was 10.6 months (12.1 months for those with thymoma versus 2.9 months for those with TC). With 23 deaths at data cutoff, the median overall survival time was 28.7 months (46.4 months for those with thymoma versus 9.8 months for those with TC). CONCLUSIONS: Pemetrexed is an active agent in this heavily pretreated population of patients with recurrent thymic malignancies, especially thymoma.

Recurrent sternal thymoma after thymectomy by video-assisted thoracic surgery.

An 81-year-old man underwent thymectomy by video-assisted thoracic surgery for a mediastinal tumor. The pathological diagnosis was Masaoka stage II type B3 thymoma. Thirty-six months later, he presented with a growing mass on his anterior chest wall. Computed tomography showed a lobulated tumor in the sternum with bone destruction. Positron-emission tomography-computed tomography showed a maximal standardized uptake of 12.3 in the tumor. Core needle biopsy confirmed a metastatic sternal tumor from a type B3 thymoma. We partially resected the sternum and reconstructed the defect using an expanded polytetrafluoroethylene sheet. The patient has remained recurrence-free for 3 years after the second surgery.