| Objective:Thymoma is an uncommon tumor without a widely accepted standard care in the literature to date.Since the rarity of thymoma,the information regarding its long-term outcomes and possible prognostic factors is limited.In this study,we aimed to investigate the clinicopathological variables of thymoma and estimate possible predictors of survival in primary thymoma and recurrent disease after initial resection.Method:We retrospectively enrolled 307 patients with thymoma who underwent complete resection at Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between January 2003 and December 2014.The Kaplan-Meier method was used to calculate overall survival(OS),disease-free survival(DFS)and post-recurrence survival(PRS),and the log-rank test was used to evaluate the statistical significance of the differences.The Cox proportional regression analysis was used to determine the significance of the associations between each variable with OS,DFS and PRS.Results:A total of 307 thymoma patients who underwent complete resection were analyzed in the study.Among them,disease recurred in 52(16.9%)patients after initially complete resection of thymoma.The median recurrence time was 71 months(range,4-160 months).The WHO histological classification was highly associated with the Masaoka-Koga stage(P<0.001).Postoperative radiotherapy was significantly associated with the WHO histological classification(P<0.001)and the Masaoka-Koga stage(P<0.001).During follow-up(median,86 months;range,24-160 months),the 5-and 10-year disease-free survival(DFS)rates were 84.0%and 73.0%,respectively,and those for overall survival(OS)were 91.0%and 74.0%,respectively.The Masaoka-Koga stage(P<0.001),WHO histological classification(P<0.001),and postoperative radiotherapy after initial resection(P = 0.006)were associated with recurrence rates(16.9%).Multivariate analysis revealed that after initial resection,the WHO histological classification and the Masaoka stage were independent predictors of DFS and OS.Subsequently,in the patients with non-aggressive thymoma(Masaoka-Koga stage ?),there was no significant difference between DFS of patients underwent postoperative radiotherapy and that of those without postoperative radiotherapy(P = 0.403).For patients with aggressive thymoma(including Masaoka-Koga stage ?,stage ? and stage ?a),patients underwent postoperative radiotherapy had higher DFS than those without postoperative radiotherapy(P ?0.028).Meanwhile,in the patients with type A and AB,there was no significant difference between DFS of patients underwent postoperative radiotherapy and that of those without postoperative radiotherapy(P = P = 0.895).For patients with type B thymoma,patients underwent postoperative radiotherapy had higher DFS than those without postoperative radiotherapy(P = 0.022).Among 52 recurrent thymomas after initial resection,14(27.0%),25(48.0%),12(23.0%),and 1(2.0%)were detected in the mediastinum,pleura,lung,and diaphragm,respectively.The recurrence patterns included 41(79.0%)locoregional recurrences and 11(21.0%)intrathoracic disseminations.Sixteen(31.0%)recurrent patients underwent surgical resection combined with adjuvant therapy(13 locoregional recurrences via complete resection plus radiotherapy and three patients with intrathoracic dissemination via debulking surgery plus radiochemotherapy).The other thirty-six(69.0%)patients did not undergo surgery(20 locoregional recurrences and 2 intrathoracic disseminations via radiotherapy therapy,4 locoregional recurrences and 4 intrathoracic disseminations via chemotherapy,and 4 locoregional recurrences and 2 intrathoracic disseminations via radiochemotherapy).The median PRS was 35.5 months(range,2-124 months).The 1-,3-,and 5-year PRS rates were 76.0%,61.0%and 56.0%,respectively.Patients with recurrent thymoma who underwent repeated surgical resection had improved PRS compared with those administered therapies other than surgery(P ?0.017).Multivariate analysis revealed that the recurrence pattern was an independent predictor of PRS.Conclusion:The Masaoka-Koga stage and the WHO histological classification were independent prognostic factors after initially complete resection of thymoma.Postoperative radiotherapy could reduce the incidence of recurrence after initially complete resection and was significantly associated with DFS.Furthermore,Postoperative radiotherapy can increase DFS of thymoma patients with type B and aggressive disease.The relapse pattern was an independent predictor of PRS.Locoregional recurrence and repeated surgical resection of the recurrent tumor are associated with favorable prognosis.Objective:esophageal cancer has become the sixth leading cause of death and the eighth most frequently diagnosed cancer worldwide.Esophageal squamous cell carcinoma(ESCC)is predominant in most parts of the world,especially in high risk regions such as China where it accounts for over 90%of the total cases of esophageal cancer.Despite significant advances in the diagnosis,treatment and pathogenesis of ESCC in recent decades,few significant improvements in overall survival have been achieved:the 5-year overall survival rate remains around 30%.Local recurrences and distant metastases are the leading causes of treatment failure and poor prognosis.Current studies have confirmed that circulating tumor cells(CTCs)can be detected in cancer at early stages and even in precancerosis.Therefore,it is potentially valuable for early diagnosis and dynamically monitoring therapeutic response by using techniques of high sensitivity to detect CTCs in esophageal cancer.Intratumor heterogeneity is an important hallmark of cancer,which makes the significant differences in therapeutic sensitivity and prognosis in clinical practice.We screened the relevant genes in patients with ESCC based on Oncomine database and compared their expression levels in multiple regions.We analyzed the intratumor heterogeneity in ESCC and explored the novel therapeutic targets that would provide clues for novel targeted drugs development and subsequent clinical trials.Method:We collected whole blood of 130 patients with ESCC who underwent complete resection at Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between May 2016 and April 2017.The Celsee Diagnostics,PREP 100 system was used in our study to detect CTCs in patients with ESCC.The Mann-Whitney U test and Kruskal-Wallis test were used to determine the significance of the associations between each variable with CTCs counts.Of them,ten patients' tumor tissues were selected randomly to be tested based on Oncomine database by using DNA-seq and RNA-seq techniques in multiple regions to find ESCC-related genes,analyze Intratumor heterogeneity and explore novel molecular targets by bioinformatics.Results:one hundred and thirty patients with ESCC were enrolled into the study.In addition,peripheral blood samples were obtained from 10 healthy donors who exhibited no evidence of any clinically detectable disease after health checkups.Our results showed that the median CTC counts were 2[1,3]per 4mL,and no CTCs was detected in healthy donors.Our results showed that the median CTC counts in patients with intravascular cancer embolus was higher than those without intravascular cancer embolus(P=0.006).The median CTC counts in patients with neural invasion were higher than those without neural invasion(P=0.001).The CTCs levels were significantly higher in patients with tumors in lower thorax than those with ones in upper and middle thorax(P=0.032).However,there was no significant difference between those with tumors in upper thorax and ones in middle thorax.The CTCs levels of ESCC patients with lymph nodes metastasis were higher than those without lymph node metastasis(P=0.001).We also found that the CTCs levels of patients with advanced-stage diseases(stage ?/?)were higher than those with early-stage diseases(stage ?)(P<0.001).Furthermore,there was no significant difference between patients at stage ? and those at stage ?.Postoperative blood samples were obtained in twelve patients with ESCC and CTCs counts ?5/4mL.Our results showed that CTCs levels in postoperative blood samples were 3[2-5]/4mL,which were lower than those in preoperative blood samples of 5[5-6]/4mL(p =0.0496).Based on Oncomine OCP143 panel,we found that there were differences among types of mutant genes,copy number variation(CNV),single nucleotide variation(SNV)and INDEL in multiple regions of ESCC.Additionally,we found a novel molecular event-EGFRv?,which is deletion of exons 2-7 of the EGFR gene.Conclusion:Higher CTCs counts in peripheral blood in ESCC patients were associated with tumors located in lower thorax,intravascular cancer embolus,neural invasion,lymph nodes metastasis and advanced-stage diseases.The CTCs levels of patients with ESCC would decline after the tumor load was removed.Based on Oncomine database,intratumor heterogeneity was found among multiple regions of ESCC.In addition,we found a novel molecular event—EGFRv?,which may be involved in oncogenesis and progression in ESCC. |
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