Postoperative radiotherapy results in 192 epithelial thymic tumours patients with 10 years of follow-up.

PURPOSE: To assess the prognostic factors and patterns of failure of patients consecutively treated with surgery and postoperative radiation therapy (PORT) for thymic epithelial tumours (TET). PATIENTS AND METHODS: Data from 192 TET patients who were operated and received PORT at a single centre from 1990 to 2019 was retrospectively analysed. RESULTS: Most patients had thymoma (77 %, B247%), were classified Masaoka-Koga stage III (35 %) or IV (32 %) and had a R0 (75 %) resection. Radiotherapy was delivered at a median dose of 50.4 Gy (range, 42-66 Gy; ≥ 60 Gy in 17 %), 63 (33 %) patients were treated by intensity-modulated radiation therapy and elective nodal radiotherapy was used for 37 %. At a median follow-up of 10.9 years, the 10-year overall survival (OS) and progression-free survival (PFS) rates were 62 % (95 % CI: 54-70 %) and 47 % (95 % CI: 39-55 %), respectively. Locoregional recurrence (LRR) occurred in 72/192 (38 %) patients, distributed as 6 local, 45 regional and 21 both local and regional. LRR were mainly located to the pleura: 66/72 (92 %) and 16/72 (22 %; 16/192 in total, 8 %) were in-field. Distant relapse (DR) were observed in 30 patients (16 %), resulting in 10-year locoregional (LRC) and distant control rates of 58 % (95 % CI: 50-66 %) and 82 % (95 % CI: 77-88 %), respectively. In the multivariate analysis, Masaoka-Koga stage (HR [hazard ratio]: 1.9; p = 0.001), thymic carcinomas/neuroendocrine tumours (TC) (HR: 1.6; p = 0.045) and ECOG PS > 1 (HR: 1.9; p = 0.02) correlated with poorer OS. Higher Masaoka-Koga stage (HR: 2.6; p < 0.001) associated with a decreased LRC but not R1 status (HR: 1.2; p = 0.5) or WHO histology classification. TC (HR: 3.4; p < 0.001) and a younger age (HR: 2.5; p = 0.02) correlated with DR. CONCLUSION: Approximately one-third of the TET in our study experienced a LRR, mainly to the pleura, and 8% in total were in-field. The place of radiotherapy should be better defined in higher risk thymoma patients within prospective randomized studies.

The Prognostic Role of the Number of Involved Structures in Thymic Epithelial Tumors: Results from the ESTS Database.

BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.

Nomogram predict relapse-free survival of patients with thymic epithelial tumors after surgery.

BACKGROUND: Hematological indicators and clinical characteristics play an important role in the evaluation of the progression and prognosis of thymic epithelial tumors. Therefore, we aimed to combine these potential indicators to establish a prognostic nomogram to determine the relapse-free survival (RFS) of patients with thymic epithelial tumors undergoing thymectomy. METHODS: This retrospective study was conducted on 156 patients who underwent thymectomy between May 2004 and August 2015. Cox regression analysis were performed to determine the potential indicators related to prognosis and combine these indicators to create a nomogram for visual prediction. The prognostic predictive ability of the nomogram was evaluated using the consistency index (C-index), receiver operating characteristic (ROC) curve, and risk stratification. Decision curve analysis was used to evaluate the net benefits of the model. RESULTS: Preoperative albumin levels, neutrophil-to-lymphocyte ratio (NLR), T stage, and WHO histologic types were included in the nomogram. In the training cohort, the nomogram showed well prognostic ability (C index: 0.902). Calibration curves for the relapse-free survival (RFS) were in good agreement with the standard lines in training and validation cohorts. CONCLUSIONS: Combining clinical and hematologic factors, the nomogram performed well in predicting the prognosis and the relapse-free survival of this patient population. And it has potential to identify high-risk patients at an early stage. This is a relatively novel approach for the prediction of RFS in this patient population.

Significance of tumor mutation burden and immune infiltration in thymic epithelial tumors.

BACKGROUND: Thymic epithelial tumors (TETs) are relatively rare malignant thoracic tumors. Tumor mutation burden (TMB) and immune infiltration play important roles in tumorigenesis. METHODS: Research data was obtained using the Cancer Genome Atlas (TCGA) database to evaluate the landscape of tumor mutations, related factors, and relationship of prognosis. The CIBERSORT algorithm was used to evaluate immune cell infiltration in TETs and its relationship with TMB. Immune-related differentially expressed genes (irDEGs) were identified. Hub irDEGs independently related to prognosis were analyzed using univariate and multivariate Cox proportional hazard models. A survival signature was constructed from hub irDEGs. RESULTS: A total of 122 patients were included in this study. GTF2I was the most common gene mutation. Higher TMB was significantly associated with the later stage, more advanced pathological type, and older age. The overall survival (OS) of patients in the low-TMB group was significantly better. There was no significant correlation between TMB levels and PD-L1 expression. Enrichment analysis showed that DEGs were mainly involved in the P13K-Akt signaling pathway. There were significant differences in macrophage and other types of immune cell infiltration between the high- and low-TMB groups. CCR5, FASLG, and CD79A independently relating to prognosis were screened from 391 irDEGs. The low-risk group had a significantly better prognosis than the high-risk group based on the signature, which has a good predictive effect on OS. CONCLUSIONS: In this study, TETs patients with high TMB had a significantly poor prognosis and an immune-related gene signature was found to effectively evaluate the long-term prognosis.

Mucin expression, epigenetic regulation and patient survival: A toolkit of prognostic biomarkers in epithelial cancers.

Twenty mucin genes have been identified and classified in two groups (encoding secreted and membrane-bound proteins). Secreted mucins participate in mucus formation by assembling a 3-dimensional network via oligomerization, whereas membrane-bound mucins are anchored to the outer membrane mediating extracellular interactions and cell signaling. Both groups have been associated with carcinogenesis progression in epithelial cancers, and are therefore considered as potential therapeutic targets. In the present review, we discuss the link between mucin expression patterns and patient survival and propose mucins as prognosis biomarkers of epithelial cancers (esophagus, gastric, pancreatic, colorectal, lung, breast or ovarian cancers). We also investigate the relationship between mucin expression and overall survival in the TCGA dataset. In particular, epigenetic mechanisms regulating mucin gene expression, such as aberrant DNA methylation and histone modification, are interesting as they are also associated with diagnosis or prognosis significance. Indeed, mucin hypomethylation has been shown to be associated with carcinogenesis progression and was linked to prognosis in colon cancer or pancreatic cancer patients. Finally we describe the relationship between mucin expression and non-coding RNAs that also may serve as biomarkers. Altogether the concomitant knowledge of specific mucin-pattern expression and epigenetic regulation could be translated as biomarkers with a better specificity/sensitivity performance in several epithelial cancers.

Thymic epithelial tumors: Do we know all the prognostic factors?

BACKGROUND: Thymic epithelial tumors constitute a morphologically and clinically diverse group of rare neoplasm of the anterior mediastinum. METHODS: Here, we present an analysis of 188 patients diagnosed with primary thymic tumors between 1995 and 2015. The prognostic value of selected clinical and morphological factors was assessed in relation to overall survival and recurrence-free survival. RESULTS: The risk of recurrence increased significantly in thymic carcinoma diagnosis (P = 0.0036), co-occurrence of other diseases, and weight loss (P = 0.0012 and 0.0348, respectively). Multivariate analysis showed that the most important independent risk factor for disease recurrence was clinical stage IV (P = 0.0036). A total of 63 patients (33.5%) died. In the univariate analysis, the following factors were considered as independent prognostic factors for overall survival: clinical stage (P < 0.0001), histological type (P < 0.0001), lymph node involvement (P < 0.001), WHO performance status 2 (P < 0.0001), anemia (Hb <9.5 g/dL; P = 0.0002), leucocytosis (>12.5 G/L; P = 0.0011), LDH level (>185 U/L; P < 0.0001), concomitant diseases (P = 0.0012) and weight loss (P < 0.0001).The strongest independent risk factor for death was stage IV disease (P < 0.001). CONCLUSIONS: The results confirmed a fairly good prognosis for patients with thymic epithelial tumors. Clinical stage was the most important prognostic factor, but, some additional clinical factors may also have prognostic value.

Different View on Tumor Size Dilemma in Tumor-Node-Metastasis Staging System for Thymoma.

BACKGROUND: Although tumor size is included in the definition of T descriptor in the tumor-node-metastasis (TNM) classification of many solid tumors, it is not considered for thymomas. This study aimed to assess the relationship of tumor diameters (the largest tumor diameter [LTD] and the mean tumor diameter [MTD]) with survival in thymoma patients undergoing surgical resection in a single center. METHODS: The study included 127 thymoma patients (age, 49.2 ± 15.2 years; 65 males), who were evaluated based on pathological tumor sizes according to the LTD and MTD ([largest diameter + shortest diameter] / 2) and divided into three subgroups for each parameter as: patients with an LTD of ≤5 cm, 5.1 to 10 cm, and >10 cm and patients with an MTD of ≤5, 5.1 to 10, and >10 cm. RESULTS: In thymoma patients, survival significantly differed according to the presence of myasthenia gravis (p = 0.018), resection status (R0 or R1; p = 0.001), T status (p = 0.015), and the Masaoka-Koga stage (p = 0.003). In the LTD subgroups, the overall survival of those with R0 resection was lower in those with an LTD of 5.1 to 10 cm than in those with an LTD of ≤5 cm (p = 0.051) and significantly lower in those with an MTD of 5.1 to 10 cm than in those with an MTD of ≤5 cm (p = 0.027). In the MTD subgroups, survival decreased as the tumor size increased. CONCLUSION: Both smaller tumor size and complete resection are associated with better survival in thymoma patients. Therefore, the largest or the mean tumor size might be considered as a criterion in the TNM staging for thymoma.

Alcohol consumption, cigarette smoking and cancer of unknown primary risk: Results from the Netherlands Cohort Study.

Cancer of unknown primary (CUP) is a metastasised malignancy with no identifiable primary tumour origin. Despite the frequent occurrence and bleak prognosis of CUP, research into its aetiology is scarce. Our study investigates alcohol consumption, tobacco smoking and CUP risk. We used data from the Netherlands Cohort Study, a cohort that includes 120 852 participants aged 55 to 69 years, who completed a self-administered questionnaire on cancer risk factors at baseline. Cancer follow-up was established through record linkage to the Netherlands Cancer Registry and Dutch Pathology Registry. After 20.3 years of follow-up, 963 CUP cases and 4288 subcohort members were available for case-cohort analyses. Multivariable-adjusted hazard ratios (HRs) were calculated using proportional hazard models. In general, CUP risk increased with higher levels of alcohol intake (Ptrend = .02). The association was more pronounced in participants who drank ≥30 g of ethanol per day (HR: 1.57, 95% confidence interval [CI]: 1.20-2.05) compared to abstainers. Current smokers were at an increased CUP risk (HR: 1.59, 95% CI: 1.29-1.97) compared to never smokers. We observed that the more the cigarettes or the longer a participant smoked, the higher the CUP risk was (Ptrend = .003 and Ptrend = .02, respectively). Interaction on additive scale was found for participants with the highest exposure categories of alcohol consumption and cigarette smoking frequency and CUP risk. Our findings demonstrate that alcohol consumption and cigarette smoking are associated with increased CUP risk. Lifestyle recommendations for cancer prevention regarding not drinking alcohol and avoiding exposure to smoking are therefore also valid for CUP.

Role of modern neoadjuvant chemoradiotherapy in locally advanced thymic epithelial neoplasms.

PURPOSE: To improve resectability in patients with stage III-IVA thymic epithelial neoplasms, neoadjuvant chemotherapy and radiotherapy are considered. This retrospective study aimed to investigate the efficacy and safety of neoadjuvant therapies using modern techniques in thymic epithelial neoplasms. METHODS: We included 32 patients with Masaoka stage III-IV disease treated at our institution from January 2010 to December 2017. Data regarding clinicopathologic characteristics, treatment protocols, toxicities, and survival were collected. Response was evaluated according to the Response Evaluation Criteria in Solid Tumours 1.1. Survival was assessed using the Kaplan-Meier method. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Neoadjuvant radiotherapy alone, chemotherapy alone, sequence chemoradiotherapy, and concurrent chemoradiotherapy were administered to 10 (31.3%), 9 (28.1%), 3 (9.4%), and 10 (31.3%) patients, respectively. Twenty-nine patients (90.6%) underwent R0 resection. The median follow-up time was 38.0 months (3.3-109.5 months). After neoadjuvant therapy, 18 patients (56.3%) achieved partial response and 14 (43.8%) had stable disease. Pathologic complete response was achieved in 6 patients (18.8%), all of whom had thymic carcinoma. The 5-year overall and progression-free survival rates were 90.9% and 67.5%, respectively. For patients with thymic carcinoma, the 5-year overall and progression-free survival rates were 80.0% and 66.2%, respectively. Grade 3 toxicities were observed in only 1 patient (leukopenia). CONCLUSIONS: For patients with primary unresectable thymic neoplasms, neoadjuvant chemoradiotherapy is an efficient and safe choice, with favorable response and survival and moderate toxicities. Patients with thymic carcinoma might benefit more from neoadjuvant therapies.

Tumor size as a prognostic factor in limited-stage thymic epithelial tumors: A multicenter analysis.

OBJECTIVE: The prognostic significance of tumor size in thymic epithelial tumors (TETs) has not been fully evaluated. We aimed to clarify the prognostic value of tumor size in limited-stage and advanced-stage TETs. METHODS: Clinical records of patients with completely resected TETs were retrospectively collected from 4 tertiary centers between January 2000 and February 2013. Information on the Masaoka-Koga stage was available for 1215 patients (M-K group), and 433 patients were classified according to the eighth edition of the Tumor-Node-Metastasis staging system (TNM group). Limited-stage and advanced-stage TETs were defined according to whether they were confined within the surrounding fatty tissues without invasion. The optimal cutoff value was selected using a maximally selected log-rank statistic. RESULTS: The median tumor size was 6.0 ± 2.8 cm in the M-K group and 6.5 ± 3.0 cm in the TNM group. In the multivariable analysis, tumor size had a significant effect on both overall survival (P = .003) and recurrence-free survival (P < .001) for limited-stage tumors (M-K stage I or II or TNM stage I), but not for advanced-stage tumors (M-K stage III or IV or TNM stage II-IV; P = .349 for overall survival and P = .439 for recurrence-free survival). The optimal cutoff value for tumor size was >5.5 cm for both overall survival and recurrence-free survival in limited-stage TETs. CONCLUSIONS: Tumor size is an independent prognostic factor in patients with completely resected limited-stage TETs and a cutoff value >5.5 cm might help clinicians enact proper treatment strategies and surveillance.

Surgical outcomes of 215 patients with thymic epithelial tumors: A single-center experience.

OBJECTIVES: To evaluate the oncological prognosis and neurological outcomes for patients with thymic epithelial tumors (TETs) after thymectomy. METHODS: Consecutive patients with TETs who underwent thymectomy at Beijing Hospital from January 2011 to December 2018 were retrospectively enrolled into the study. Clinical, pathological, and perioperative data was collected. Patients were followed-up by telephone interview and outpatient records. Statistical analyses were performed using SPSS version 19.0. RESULTS: A total of 215 patients (115 men and 100 women) were included in this study of which 133 patients (61.9%) had TETs associated with myasthenia gravis (MG), and 82 patients (38.1%) had thymic tumors without MG. A total of 194 (90.2%) patients were successfully followed-up. The median follow-up period was 42 months. The five-year overall survival (OS) rate was 88.6%. MG was the first cause of death for patients with MG (6/10). Prognosis in MG patients was similar to those without MG. Multivariate Cox regression analysis demonstrated that TNM stage III + IV was an independent risk factor for OS. Incomplete resection and younger age were risk factors for tumor recurrence. For patients with MG, the cumulative complete stable remission (CSR) rate increased with the postoperative follow-up period, and the five-year CSR rate was 44.7%. Univariate Cox analysis indicated that age, preoperative MG duration and preoperative medication might correlate with CSR. Multivariate Cox analysis only indicated older age as a negative factor of achieving CSR. CONCLUSIONS: MG had little influence on OS and tumor recurrence of thymic tumors. The new TNM staging system was an independent prognostic factor. Incomplete resection and younger age were risk factors for tumor recurrence. Older age was a negative factor of achieving CSR for thymoma patients with MG after extended thymectomy. KEY POINTS: Significant findings of the study MG was not a prognostic factor for thymic tumors. The new TNM staging system was useful for prediction of prognosis. Incomplete resection and younger age were risk factors for tumor recurrence. Older age led to a lower probability of achieving CSR for thymomatous MG. What this study adds This study had a relatively large sample size of patients with thymic epithelial tumors in a single center. We evaluated not only the oncological prognosis, but also neurological outcomes after thymectomy, which was a more comprehensive assessment of surgical effect for thymic epithelial tumors.

Survival outcomes of patients with high-grade and poorly differentiated thymic neuroendocrine carcinoma.

High-grade and poorly differentiated thymic neuroendocrine carcinoma is the rarest entity in thymic epithelial tumours. The aim of this study is to report survival data in a multi-institutional database in comparison to data in the literature. Retrospective chart review was performed on the basis of our multi-institutional database to identify patients undergoing the resection of poorly differentiated thymic neuroendocrine carcinoma between 1991 and 2018. Relevant factors were extracted, and survival analysis was performed using the Kaplan-Meier method. Twenty-one patients were identified. Five-year overall survival and recurrence-free survival were 64.6% and 51.8%, respectively. Twelve (57.1%) patients had recurrences. Due to the scarcity of data reported in the literature, our data may be used as a standard in high-grade and poorly differentiated thymic neuroendocrine carcinoma.

Definitive-intent radiotherapy for sinonasal carcinoma in cats: A multicenter retrospective assessment.

Treatment of epithelial sinonasal tumours in cats is not commonly reported. In the newer reports, palliative radiation protocols have been described more often than definitive-intent protocols. In this multi-institutional retrospective study, we included 27 cats treated with single-modality radiotherapy. Cats were irradiated using 10 daily fractions of 4.2 Gy. Three cats (11.1%) experienced a complete clinical response and 17 (63%) had a partial clinical response. Stable clinical disease was noted in three cats (11.1%). Four cats (14.8%) showed progression within 3 months following treatment. The median time to progression for all cases was 269 days (95 % confidence intervals [CI]: 225; 314). The proportion of cats free of progression at 1 and 2 years was 24% (95% CI: 22%; 26%) and 5% (95% CI: 5%; 6%), respectively. None of the prognostic factors evaluated were predictive of outcome (anaemia, tumour volume at the time of staging, modified Adams stage, intracranial involvement, facial deformity, epistaxis, inappetence or weight loss). Median overall survival (OS) for all deaths was 452 days (95% CI: 334; 571). The proportion of cats alive at 1 and 2 years was 57% (95% CI: 37%; 77%) and 27% (95% CI: 25%; 29%), respectively. Surprisingly, cats with epistaxis had a longer median OS of 828 days (95% CI: 356; 1301) compared to 296 days (95% CI: 85; 508) in cats without epistaxis, (P = .04, Breslow). Radiation therapy used as a single modality for the treatment of feline sinonasal carcinoma improved clinical signs and was well tolerated but progression within a year was common.

Thymic Epithelial Tumors: Prognostic Significance and Relationship between Histology and the New TNM Staging System.

BACKGROUND: This study aims to describe the relationship between the new tumor nodes metastasis (TNM) staging and World Health Organization (WHO) classification and to identify how these two variables relate to each other and whether they possess a prognostic value in predicting survival and recurrence of disease. METHODS: Medical records of 54 patients who underwent surgery for thymic epithelial tumors between 1996 and 2015 were reviewed.The histologic type of neoplasm was classified according to the criteria of WHO and staging was evaluated using the new TNM classification system. RESULTS: A significant correlation between the TNM stages and the histological classification was found (p < 0.001). Complete resection is related to both TNM stage and histological grading (p < 0.001). Evaluation of the 5- and 10-year survival curves shows how these are significantly correlated only at the stage (p = 0.03 and = 0.04, respectively). The risk of death at 5 and 10 years for stages III to IV is six and three times higher than in stages I to II, respectively. Regarding the disease-free survival, there is significant correlation with both staging and histology (p = 0.001 and = 0.02, respectively). CONCLUSIONS: There is a significant correlation between the new TNM staging and the histological grade WHO. The ability to implement a complete resection, the overall and disease-free survival is closely related to the thymoma stage. Furthermore, both histotype and stage correlate with disease-free survival. In fact, the least aggressive stages, both WHO and TNM, have a free time out of disease superior to advanced stages.

Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative.

BACKGROUND: For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. METHODS: All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). RESULTS: Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. CONCLUSION: The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

Treatments and outcomes of spinal metastasis from thymic epithelial tumors: 10-year experience with 15 patients in a single center.

PURPOSE: Although thymic epithelial tumors (TETs) are rare, their spinal metastases are even rarer, and they have only been described in a few case reports. The aim of the present study is to discuss the possible treatments and outcomes of patients with spinal metastasis from TETs. METHODS: Included in this retrospective study were 15 patients with metastasis of TETs who received either radical or debulking surgery plus radiochemotherapy as adjuvant therapy in our center between 2007 and 2017. Possible prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed by log-rank analysis. RESULTS: Our series comprised seven men and eight women, with a median age of 52 years. The period from the primary diagnosis to spinal metastasis varied from 0 to 16 months. The metastatic lesions were mainly located in the thoracic spine (n = 11; 73.3%), followed by the cervical and lumbar spine (n = 2; 13.3%, respectively). The median follow-up period was 28 months. Local tumor progression was detected in four patients (26.7%), and seven patients (46.7%) died of the disease during the follow-up period. Log-rank analysis indicated that radical resection was associated with longer PFS, whereas PFS, response to systemic chemotherapy and WHO B1-B2 were favorable factors of OS for patients with spinal metastatic TETs. CONCLUSIONS: Radical surgery is associated with longer PFS, while PFS is associated with better OS. Postoperative radiotherapy seems to be a useful supplementary treatment after debulking surgery, and patients who respond to postoperative chemotherapy were demonstrated with greater OS. WHO type B3-C seemed to be an adverse factor for spinal metastasis from TETs. These slides can be retrieved under Electronic Supplementary Material.

High expression level of SOX2 is significantly associated with shorter survival in patients with thymic epithelial tumors.

OBJECTIVES: Thymic epithelial tumors (TET) are heterogenous tumors which are composed of thymoma (TM) and thymic carcinoma (TC). We attempted to determine differences in gene expression between TM and TC, and to determine the effect of such genes on the prognosis of patients with TET. MATERIALS AND METHODS: Gene expression profiles of SOX2, OCT-4, IGF-1, IGF-1R and IR mRNA transcripts in tumor tissues of TM and TC were determined using real-time PCR (RT-PCR). We constructed tissue microarray with 140 paraffin-embedded tumor tissues and performed immunohistochemistry (IHC) for IGF-1R-related signaling molecules, including SOX2, IGF-1, IGF-1R and pAKT. RESULTS: SOX2 mRNA expression was notably higher (216-fold) in TCs than in TMs. However, there was no significant difference in expression of IGF-1, IGF-1R, OCT-4 or IR between the two tumor types. In IHC results, SOX2 (HR: 7.57, P = 0.001) and IGF-1 (HR: 9.43, P = 0.001) expression levels in TC were significantly higher than those in TM. There was a significant correlation in expression of SOX2 with IGF-1 (P = 0.021) and pAKT (P = 0.026). In univariate analysis, clinical TNM stage, WHO classification, serum LDH, expression of SOX2, IGF-1R, IGF-1 and pAKT, were significantly correlated with overall survival (OS). Multivariate analysis using a forward-selection procedure revealed that clinical N stage (HR: 4.08, P < 0.001), M stage (HR: 3.37, P = 0.001) and SOX2 expression (HR: 4.53, P = 0.010) were significantly associated with OS. CONCLUSIONS: SOX2 is expressed significantly higher in TC than in TM. SOX2 expression is also closely related to IGF-1 and pAKT expression. The higher expression of SOX2 is significantly associated with shorter survival in patients with TET.

Discovery and validation of DNA methylation markers for overall survival prognosis in patients with thymic epithelial tumors.

BACKGROUND: The current prognosis of thymic epithelial tumors (TETs) is according to the World Health Organization (WHO) histologic classification and the Masaoka staging system. These methods of prognosis have certain limitations in clinical application and there is a need to seek new method for determining the prognosis of patients with TETs. To date, there have been no studies done on the use of DNA methylation biomarkers for prognosis of TETs. The present study was therefore carried out to identify DNA methylation biomarkers that can determine the overall survival in patients with TETs. METHODS: Bioinformatic analysis of TCGA 450 K methylation array data, transcriptome sequencing data, WHO histologic classification and Masaoka staging system was performed to identify differentially expressed methylation sites between thymoma and thymic carcinoma as well as the different DNA methylation sites associated with the overall survival in patients with TETs. Using pyrosequencing, 4 different methylation sites (cg05784862, cg07154254, cg02543462, and cg06288355) were sequenced from tumor tissues of 100 Chinese patients with TETs. A prognostic model for TETs was constructed using these four methylation sites. RESULTS: The TCGA dataset showed 5155 and 6967 hyper- and hypomethylated CpG sites in type A-B3 group and type C group, respectively, of which 3600 were located within the gene promoter regions. One hundred thirty-four genes were silenced by promoter hypermethylation and 174 mRNAs were upregulated. Analysis of univariate and multivariate Cox regression showed significant association between the methylation levels of 187 sites and the overall survival in patients with TETs. cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) were identified as independent prognostic factors for overall survival in patients with TETs after adjusting for Masaoka staging in 100 Chinese patients. The prognostic model which consists of the four abovementioned genes had higher accuracy for predicting the 5-year overall survival in patients with TETs as compared to the Masaoka clinical staging. (Time-dependent ROC analysis AUC 1.000 vs 0.742, P = 2.7 × 10-6). CONCLUSIONS: The methylation levels of cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) sites are associated with the progression of TETs and may serve as new biomarkers for predicting the overall survival in patients with TETs.

Increased Galectin-1 Expression in Thymic Epithelial Tumors.

INTRODUCTION: Thymic epithelial tumors (TET) are rare malignancies with a paucity of data on biology and therapeutics. Galectin-1 is a member of the ß-galactoside binding protein family and has been shown to mediate tumor growth via modulation of immune cell function. This study examined galectin-1 expression in TET. PATIENTS AND METHODS: A tissue microarray of 68 patients with TET and 8 benign thymus controls were stained for galectin-1 expression and scored by a pathologist blinded to patient clinical and pathologic data. Galectin-1 expression +1 or greater staining intensity was considered positive. Clinical and pathologic data were abstracted from institutional databases. Expression of galectin-1 in thymic tumor was compared to benign thymus controls and correlated with pertinent clinical and pathologic data. RESULTS: Galectin-1 expression was higher in TET compared to benign thymus controls (65% vs. 0%). No significant association between galectin-1 expression and the development of recurrent disease, paraneoplastic syndromes, or overall survival was noted. CONCLUSION: Galectin-1 is overexpressed in the majority of TET. Detection of galectin-1 may differentiate benign from neoplastic thymic processes. Additional studies are needed to assess the role of galectin-1 in the development of TET.

Clinical outcomes of endoscopic treatment for gastric epithelial neoplasm in remnant stomach after distal gastrectomy.

BACKGROUNDS/AIM: We aimed to evaluate the feasibility of endoscopic treatment for gastric epithelial neoplasm in the remnant stomach after distal gastrectomy and compared the clinical outcomes by tumor location and endoscopic treatment modality. METHODS: We reviewed the data of patients who underwent endoscopic treatment for gastric epithelial neoplasms in the remnant stomach after distal gastrectomy between January 1996 and August 2013. The treatments included endoscopic resection or argon plasma coagulation. RESULTS: Herein, 107 patients (median age, 65.1 years; 92 men) encompassing 117 cases of gastric neoplasms in the remnant stomach after distal gastrectomy were endoscopically treated. Forty of these lesions were located at anastomotic sites; they were treated with endoscopic resection in 29 cases (72.5%) and argon plasma coagulation in 11 cases (27.5%). For 77 lesions located on the non-anastomotic site, endoscopic resection was performed in 68 cases (88.4%) and argon plasma coagulation was performed in nine cases (11.7%; p = 0.031). The mean endoscopic resection duration was significantly longer in the anastomotic site group than in the non-anastomotic site group (43.6 vs. 26.3 min, p = 0.018). Recurrence was observed in five (12.8%) patients in the former and in one (1.3%) in the latter (p = 0.015); all the patients were successfully retreated with endoscopic resection or APC. CONCLUSIONS: Endoscopic treatment for gastric epithelial neoplasm in a remnant stomach after distal gastrectomy is effective and safe. However, closely monitoring for recurrence should be conducted, particularly when the tumor is located at the anastomotic site.