Project description:The emergence of immunotherapy as a modern pillar of cancer treatment has changed the treatment landscape for various cancers. Immune checkpoint inhibitors directed at programed death-1 (PD-1) or its ligand (PD-L1), in particular, have found widespread clinical applications and have resulted in durable responses and an improvement in survival of patients with advanced or metastatic disease. Tumor cell PD-L1 expression and tumor mutation burden (TMB) are biomarkers of response and efforts are underway to identify other biomarkers that might predict benefit with these drugs. Most patients tolerate immunotherapy well, although a subset of patients develop immune-mediated toxicity due to excessive immune stimulation. Thymic epithelial tumors (TETs) have a unique biology which can predispose to development of autoimmune paraneoplastic disease, especially in patients with thymoma. Due to defects in immunological self-tolerance, the use of immunotherapy in TET patients is associated with an increased risk of immune-mediated adverse events, which can be potentially life-threatening. Development of biomarkers of response and toxicity is particularly important for the treatment of TETs since it is important to identify patients who might benefit from treatment and be at low risk for development of severe immune toxicity. The use of immunotherapy in patients with autoimmune disorders and those who have previously experienced immune-mediated toxicity is currently an area of active research. Various risk mitigation strategies are under evaluation in prospective clinical trials, including trials of immune checkpoint inhibitors in patients with thymic cancers.
Project description:Background and objectiveThymic epithelial tumors (TETs), including thymomas and thymic cancers, are relatively rare malignancies originating from the thymus. Although complete surgical resection is the cornerstone of treatment for these tumors, the optimal management strategy for locally advanced cases remains uncertain. Neoadjuvant therapies, with their potential to improve the likelihood of complete resection, are promising, particularly in marginally operable cases. However, the current evidence supporting this approach is lacking. This review of the existing literature on the efficacy of induction therapy followed by surgical resection for stage III or IV locally advanced TETs aimed to provide an up-to-date perspective and highlighting directions for future clinical research.MethodsPubMed was searched using the keywords "surgery," "survival", "thymoma", "thymic cancer", and "induction therapy". Relevant articles including case series, retrospective studies, prospective studies, and review articles were reviewed and selected for this comprehensive narrative review.Key content and findingsThis review included primarily revealed retrospective studies and a limited number of prospective phase II trials on induction therapy followed by surgery for stage III or IV locally advanced TETs. No randomized phase III studies were identified, indicating that a comprehensive evaluation of the benefits of induction therapy on overall survival (OS) has not yet been conducted. Induction therapies for both invasive thymoma and thymic cancer included chemotherapy, radiotherapy, and chemoradiotherapy, with anthracycline-based combination chemotherapies being the primary option. For exclusively invasive thymomas, the median rate of complete surgical resection and the 5-year OS rate were reported as 76% and 85%, respectively. Literature focusing on induction therapy for TETs, which includes both thymoma and thymic cancers, indicates that the rates of complete resection and 5-year OS are 76% and 70%, respectively.ConclusionsOur narrative review of retrospective and prospective studies highlighted promising long-term OS rates in patients with advanced TETs who underwent induction therapy followed by surgical resection. These findings support this multimodal treatment strategy in selected patients with stage III and IV TETs.
Project description:BackgroundHere, we investigated radiological responses following chemotherapy alone as compared to both radiation/chemotherapy (chemoRT) in patients with thymic epithelial tumors (TETs) who did not receive upfront surgery.MethodsTETs treated at a tertiary academic cancer center between January 2007 and July 2018 were identified. Patients received chemotherapy or chemoRT as initial therapy and pre- and post-treatment scans were available. Student's t-test, Wilcoxon rank-sum tests, and Cox proportional hazards method were used to compare clinical details and survival between groups. The primary outcome was change in tumor size, which was compared between groups using linear mixed-effects regression models, adjusting for baseline tumor size, age, and histology.ResultsA total of 24 of 114 patients with TETs identified met the inclusion criteria. The majority of patients had 67% thymoma (67%, n = 16) and AJCC8 III-IVA disease (58%, n = 14). Median age was 58.5 years (range: 33-76), median initial tumor volume was 187.1 cc (range: 28.7-653.6) and diameter was 8.5 cm (range: 4.5-14.3). Half of the patients received upfront chemotherapy (n = 12: 83% cisplatin/adriamycin/cyclophosphamide) or chemoRT (n = 12: 58% carboplatin/paclitaxel; median RT dose: 63 Gy [range: 60-70 Gy]). At a median imaging follow-up of 15 months (range: 0-86): ChemoRT was associated with increased average radiological response compared to chemotherapy alone (volume: -47.0 cc more, P < 0.001; diameter: -0.8 cm more, P = 0.03). In eight patients who received chemotherapy, 33% saw further tumor shrinkage (median volume: -42.3%, P = 0.03; diameter: -3.0%, P = 0.049) with additional radiation/chemoradiation. Median survival increased for patients ultimately receiving surgery versus those who did not (46 month, range: 16-127 vs. 14 month, range: 6-82; P < 0.01).ConclusionsChemoRT produced a greater radiologic response compared to chemotherapy alone in patients with TETs not suitable for upfront resection.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: We found that chemoRT was associated with a greater radiologic response compared to patients who received chemotherapy alone.What this study addsWhat this study adds: In patients with TET not amenable to upfront resection, chemoRT may be a feasible strategy for cytoreduction.
Project description:Currently, adjunctive therapy for gastric cancer is not standardized worldwide and the most effective combination of different modalities has not been clearly determined. The aim of the present study was to retrospectively analyze the efficacy and toxicity of the combination of perioperative epirubicin, capecitabine and oxaliplatin (EOX) chemotherapy and postoperative concurrent chemoradiotherapy in the treatment of locally advanced gastric cancer. A total of 41 patients with locally advanced gastric cancer who had undergone perioperative EOX chemotherapy and surgical resection followed by chemoradiotherapy, were assessed. The perioperative EOX regimen consisted of 50 mg/m2 epirubicin and 130 mg/m2 oxaliplatin on day 1, with 625 mg/m2 capecitabine administered twice daily on days 1-21. The perioperative regimen was repeated 2-3 times every 3 weeks. After complete resection following the perioperative EOX regimen, concurrent chemoradiotherapy with capecitabine (4,500 cGy in daily fractions of 180 cGy administered 5 days per week for 5 weeks, with 625 mg/m2 capecitabine twice daily during radiotherapy) and 2 cycles of the EOX regimen 4 weeks after radiotherapy, were performed. In total, 30/41 patients (73.2%) completed all the planned treatments, including perioperative chemotherapy, surgical resection and chemoradiotherapy. The effective rate of preoperative chemotherapy (partial and complete response) was 56.1%; 30/41 patients received R0 resection, and the overall 3-year survival rate was 57.7%. Grade 3/4 gastrointestinal toxicity (nausea/vomiting) occurred in 22% of the patients, while 18 patients (43.9%) developed grade 3/4 hematological toxicity (granulocytopenia). The results of the present study indicated that the combination of perioperative EOX chemotherapy and postoperative concurrent chemoradiotherapy is feasible and effective for locally advanced gastric cancer.
Project description:IntroductionParaneoplastic autoimmune diseases (ADs) are a hallmark of thymic epithelial tumors (TETs) and affect treatment management in patients with advanced-stage tumors, yet the risk factors for development of AD in advanced TET remain poorly understood.MethodsAll patients with advanced TET treated at Stanford University between 2006 and 2020 were included. Charts were retrospectively reviewed for the presence of AD, demographic information, and treatment history. Next-generation sequencing was performed on available TET tissue. Multivariate regression was used to evaluate variables associated with AD.ResultsA total of 48 patients were included in the analysis with a median follow-up of 5.4 years. One-third (n = 16, 33%) were diagnosed with having ADs, with 28 distinct ADs identified. The only significant difference observed in the AD cohort compared with the non-AD cohort was a higher proportion of thymoma histotype (81% versus 47%, p = 0.013). The most common AD events were myasthenia gravis (n = 7, 44%) followed by pure red cell aplasia (n = 5, 31%). In the multivariate models, there were no independent factors associated with AD, either at TET diagnosis or subsequent to TET diagnosis. Genomic data were available on 18 patients, and there were no overlapping mutations identified in the nine patients with AD.ConclusionsADs are common in patients with advanced TETs. Prior total thymectomy does not affect the development of subsequent AD. Patients who developed AD other than myasthenia gravis were more likely to do so several years after TET diagnosis. Additional work, including multiomic analyses, is needed to develop predictive markers for AD in advanced TET.
Project description:IntroductionAlthough thymic epithelial tumors (TETs) commonly infiltrate mediastinal structures, cardiac involvement is uncommon and has not been systematically studied. The purpose of this study was to describe our single-institution experience of the clinical presentation, treatment, and follow-up of cardiac involvement in patients with TETs.MethodsA single-institution retrospective review of cardiac involvement among patients with TETs from 2008 to 2012.ResultsThe frequency of cardiac involvement was 4%. All five patients with confirmed cardiac disease had left heart involvement. Only one patient was symptomatic. Myocardial invasion was the most common mode of involvement followed by transvenous spread. Surgical resection of the involved area was attempted in three patients: in one, surgery was aborted because of extensive myocardial involvement; in the other two patients, resection was incomplete. Surgery averted a potentially catastrophic hemodynamic complication in one patient. However, cardiac tumor recurred in both patients who underwent incomplete resection. One patient underwent radiation therapy resulting in complete regression of an aortic root mass.ConclusionsThis study represents the most comprehensive review of cardiac involvement in patients with TETs. In contrast to previous single-case reports, we found a preponderance of asymptomatic presentation, left heart involvement, and myocardial invasion. Dynamic cardiovascular magnetic resonance imaging should be considered in cases when cardiac involvement is suspected. Although immediate surgical resection is indicated for impending hemodynamic compromise, long-term palliation with surgery for myocardial involvement seems poor, especially when complete resection cannot be performed. Radiation therapy should be considered in selected patients.
Project description:The purpose of this review article is to review recent advances in the treatment of advanced thymic epithelial tumors. These tumors are generally responsive to cytotoxic combination chemotherapy in the first-line setting. While newer agents have shown efficacy in the salvage setting, there is no one standard approach. A multitude of targeted agents have shown promise generally in case reports, though as of yet, nothing has shown consistent benefit. Because of the rarity of thymic epithelial tumors, clinical trial enrollment is difficult but nevertheless essential.