Multimodality Treatment Of Locally Advanced Thymic Malignancies

Part I: Safety and Effectiveness of Surgical Resection for Thymic Malignancies after Neoadjuvant Concurrent ChemoradiotherapyObjective: To explore the therapeutic effect of operation on locally advanced thymic malignancies after induction of concurrent chemoradiotherapy.Methods: From Nov.2008 to Mar.2018,37 patients with thymic malignancies were enrolled in the Shanghai Chest Hospital.All the subjects were thymic malignancies patients with locally advanced stage T3-4 confirmed by pathological biopsy and imaging.The tumor remission rate,surgical complete resection rate(R0 resection rate),complication rate,long-term survival rate,and the progression free and long-term survival rate of the patients without surgical resection after consolidation treatment were analyzed.Result: Among the 37 eligible patients included in this study,all patients completed at least one course of induction concurrent chemoradiotherapy,of which 14 patients completed two courses of induction chemotherapy.Among 37 patients,2 achieved complete response(CR),28 achieved partial response(PR),and 7 achieved stable disease(SD).The main adverse effect of induction of concurrent chemoradiotherapy was myelosuppression with leucopenia as the main side effect.Among the 30 patients who achieved remission,25 received surgical treatment,of which 18 underwent complete tumor resection(R0 resection),with the R0 resection rate of 72.0%.Postoperative pathology showed that 7 patients(28.0%)achieved complete pathological remission(PCR).The 3-year and 5-year survival rates of 37 patients were 72% and 63%,respectively.Compared with the surgical group and the non-surgical group,the 3-year DFS was(78.0% vs.19.0%,P <0.05),and the difference was statistically significant.Conclusion: Concurrent chemoradiotherapy as induction therapy for locally advanced stage T3-4 thymic malignanciess can achieve higher tumor remission rate and lower complication rate,and create the possibility of complete resection for surgical treatment.After induction therapy,the resection rate of R0 is higher and the longterm survival rate is better.Part II: Safety and Effectiveness of Surgical Resection for Thymic Malignancies after Neoadjuvant Sequential ChemoradiotherapyObjective: To evaluate the effect of radiotherapy and chemotherapy in the process of induction Sequential therapy and the overall therapeutic effect.Methods: From Sep.2015 to Aug.2019,29 patients with thymic malignancies were included prospectively.All the subjects were thymic malignancies patients with locally advanced stage T3-4 confirmed by pathological biopsy and imaging.After two courses of induction chemotherapy and one course of induction radiotherapy,the remission rate of chemotherapy,the remission rate of radiotherapy,the total remission rate of tumor,the complete resection rate of surgery(R0 resection rate),the incidence of complications,the long-term survival rate and the progress of disease were analyzed.Result: Of the 29 patients included in the study,all patients completed 2 courses of paclitaxel + carboplatin(TC).In the case of chemotherapy,2 patients achieved partial response(PR)after chemotherapy and received direct surgical treatment,and the remaining 27 patients received induced radiation therapy.Of the 29 patients,4 received PR for chemotherapy and 19 received PR for radiotherapy.A total of 21 patients achieved PR and 8 had stable disease(SD).The main adverse effect of sequential chemoradiotherapy is myelosuppression,which is mainly caused by leukopenia.Twenty-four patients underwent surgical treatment after induction therapy,of which 16 patients had complete tumor resection(R0 resection),and the R0 resection rate was 66.7%.Postoperative pathology showed that 7(29.2%)patients achieved major pathological response(MPR).The 3-year disease-free survival(DFS)of 24 surgical patients was 81%,and 3-year overall survival(OS)was 87%.Conclusion: Sequential chemoradiotherapy as an induction treatment for locally advanced stage T3-4 thymic tumors can achieve a higher tumor response rate,which is superior to chemotherapy.No serious complications occurred after sequential chemoradiotherapy,and most patients underwent surgery to obtain a complete and complete resection.The long-term disease-free survival rate of patients after surgery is higher.Part III: Is Minimally Invasive Thymectomy An Acceptable Approach For Locally Advanced Thymic Malignancies: A Propensity-matched StudyObjective: To evaluate whether the minimally invasive thymectomy(MIT) is an acceptable approach for locally advanced thymic malignancies in terms of perioperative and oncology outcomes,when compared to standard median sternotomy thymectomy(MST).Methods: The clinical data of 128 patients between January 2008 to December 2019,with UICC 8th edition staging T2-3Nx M0 who underwent surgery for thymic malignancies,via two different approaches MIT & MST were retrospectively analysed.The effect of the surgical approach on perioperative complications and survival in patients was assessed using multivariable logistic regression,Cox proportional hazards analysis,and propensity-score matching.Result: During this study period,128 patients met the inclusion criteria and underwent thymectomy for locally advanced thymic tumors;50(31.3%)of them were performed by MIT,70(62.5%)were performed by MST,and 8(13.8%)were converted to open during surgery.There were no perioperative mortality occurred in either group.There was no significant difference in the perioperative morbidity between the two groups before(10.0% vs.17.1%,P=0.302)or after propensity-score matched analysis(11.6% vs.14.0%,P=0.419).MIT showed similar 5-year RFS when compared with MST in unadjusted analysis(87.3% vs 83.3%,P =0.874),even after multivariable adjustment(hazard ratio,1.136;95% CI,0.284-4.542;P=0.856).In a propensity score–matched analysis that balanced patient characteristics,there was no significant differences found in recurrence-free survival between the 2 groups(85.8% vs 86.2%,P=0.781).Conclusion: The current study suggests that MIT for locally advanced thymic tumors is safe to perform,with at least equivalent oncologic outcomes when compared to standard median sternotomy approach.