Emerging treatment options for patients with recurrent advanced thymic epithelial tumors.
Ontology highlight
ABSTRACT:
SUBMITTER: Evans TL
PROVIDER: S-EPMC3439855 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Emerging treatment options for patients with recurrent advanced thymic epithelial tumors.
OncoTargets and therapy 20120907
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 tumo ...[more]
Similar Datasets
Project description:PurposeThymic epithelial tumors are rare malignancies, and there is no standard treatment for patients with advanced disease in whom chemotherapy has failed. Antitumor activity of histone deacetylase (HDAC) inhibitors in this disease has been documented, including one patient with thymoma treated with the pan-HDAC inhibitor belinostat.Patients and methodsPatients with advanced thymic epithelial malignancies in whom at least one line of platinum-containing chemotherapy had failed were eligible for this study. Other eligibility criteria included adequate organ function and good performance status. Belinostat was administered intravenously at 1 g/m(2) on days 1 to 5 of a 21-day cycle until disease progression or development of intolerance. The primary objective was response rate in patients with thymoma.ResultsOf the 41 patients enrolled, 25 had thymoma, and 16 had thymic carcinoma; patients had a median of two previous systemic regimens (range, one to 10 regimens). Treatment was well tolerated, with nausea, vomiting, and fatigue being the most frequent adverse effects. Two patients achieved partial response (both had thymoma; response rate, 8%; 95% CI, 2.2% to 25%), 25 had stable disease, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma (median not reached v 12.4 months; P = .001). Protein acetylation, regulatory T-cell numbers, and circulating angiogenic factors did not predict outcome.ConclusionBelinostat has modest antitumor activity in this group of heavily pretreated thymic malignancies. However, the duration of response and disease stabilization is intriguing, and additional testing of belinostat in this disease is warranted.
| S-EPMC3107761 | biostudies-literature
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.
| S-EPMC9121321 | biostudies-literature
Project description:Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare malignancies arising from the thymus gland. The optimal management requires a multidisciplinary approach. Standard first-line systemic treatment involves cytotoxic chemotherapeutic regimens; however, alternative options for systemic treatment are required. Current research focuses on the unique profile of immune-related pathogenic mechanisms of TETs, involving an overlap with certain autoimmune phenotypes, as well as on determining the landscape of oncogenic molecular alterations and the role of tumor angiogenesis. The aim of the present review is to summarize the current clinical investigation on immunotherapy and targeted agents in the management of TETs. Regarding immune checkpoint inhibitors, efficacy results are promising in certain subsets of patients; however, caution is required concerning their toxicity. Anti-angiogenic agents, mainly potent small-molecule inhibitors, have demonstrated antitumor activity in TETs, whereas other targeted agents, including KIT inhibitors and epigenetic agents, are associated with encouraging, yet still modest results for unselected populations, in the absence of predictive biomarkers. Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types.
| S-EPMC9877504 | biostudies-literature
Project description:Treatment options for neuroendocrine tumors (NETs) and carcinomas (NECs) are expanding. Early-phase studies have shown preliminary evidence of the antitumor activity of alpha-emitting peptide receptor radionuclide therapy (PRRT), and novel radiopeptides incorporating somatostatin receptor antagonists (rather than agonists) have been developed. Several tyrosine kinase inhibitors (TKIs) with antiangiogenic potential have been evaluated in patients with NETs, including lenvatinib, axitinib, cabozantinib and pazopanib. Recently, two phase 3 clinical trials have demonstrated the efficacy and safety of surufatinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, fibroblast growth factor receptor (FGFR)-1 and colony stimulating factor-1 receptor (CSF-1R), in patients with pancreatic and extra-pancreatic NETs. Multiple clinical trials of combination immunotherapy have been recently completed, but interpretation of the results is hampered by small samples sizes and discordant outcomes. This review summarizes recent data on emerging treatments for neuroendocrine neoplasms.
| S-EPMC7696369 | biostudies-literature
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.
| S-EPMC7529575 | biostudies-literature
Project description:Desmoid tumors describe a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Although histologically benign, desmoids are locally invasive and associated with a high local recurrence rate, but lack metastatic potential. On the molecular level, desmoids are characterized by mutations in the β-catenin gene, CTNNB1, or the adenomatous polyposis coli gene, APC. Proof of a CTNNB1 mutation may be useful when the pathological differential diagnosis is difficult and location might be predictive for disease recurrence. Many issues regarding the optimal treatment of patients with desmoids remain controversial; however, surgery is the therapeutic mainstay, except if mutilating and associated with considerable function loss. Postoperative radiotherapy reduces the local recurrence rate, in cases of involved surgical margins. Because of the heterogeneity of the biological behavior of desmoids, including long periods of stable disease or even spontaneous regression, treatment needs to be individualized to optimize local tumor control and preserve patients' quality of life. Therefore, the application of a multidisciplinary assessment with multimodality treatment forms the basis of care for these patients. Watchful waiting may be the most appropriate management in selected asymptomatic patients. Patients with desmoids located at the mesentery or in the head and neck region could present with life-threatening complications and often need more aggressive treatment. This review describes treatment options and management strategies for patients with desmoid tumors with a focus on advanced disease.
| S-EPMC3228186 | biostudies-literature
Project description:Several inflammation-based prognostic scores emerged in various types of cancer to predict clinical outcomes. So far, no accurate pre-treatment scoring systems exist for patients with thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas (TCs). Therefore, we sought to test the prognostic value of different clinical composite scores and their components, identify optimal cut-off values for TETs as well as combine predictive components to new suitable prognostic scores. One hundred eighty-four patients with TETs undergoing surgical tumor resection were analyzed. A significant advantage in Freedom-from-Recurrence and/or Cause-specific survival (CSS) was evident for patients with high Advanced-Lung- Cancer-Inflammation-Index, low CRP-Fibrinogen-Score (CFS), low Glasgow-Prognostic-Score (GPS), low high-sensitivity-modified GPS, low TET-adapted GPS (TET-aGPS) and low Systemic-Immune-Inflammation Index. On multivariable analysis high TET-aGPS (HR = 14.9;p = 0.001), incomplete resection status (HR = 13.5;p = 0.001) and TC (HR = 26.0;p = 0.001) were significant independent prognostic factors for worse CSS. The CFS had the highest coefficient of determination (R2 = 0.188) to predict tumor recurrence of all composite scores, comprising CRP (R2 = 0.141) and fibrinogen (R2 = 0.158), the best single factor predictors. Inflammation-based prognostic scores and selected components are suitable to predict survival and/or tumor recurrence in TET patients undergoing primary surgery. Due to excellent long-term survival and frequent tumor recurrence, cut-off values were tailored to increase prognostic power.
| S-EPMC6901461 | biostudies-literature
Project description:Olaparib has shown promising anticancer activity as a single agent in the treatment and maintenance of recurrent ovarian cancer in early clinical trials, but it is far from standard therapy. This article outlines the problem of relapsed ovarian cancer and the mechanisms of poly(ADP-ribose) polymerase inhibitors and reviews the recent literature pertaining to olaparib in ovarian cancer.
| S-EPMC3772750 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma is a devastating disease with a poor prognosis regardless of stage. To date the mainstay of therapy for advanced disease has been chemotherapy with little incremental improvements in outcome. Despite extensive research investigating new treatment options the current practices continue to utilise fluorouracil or gemcitabine containing combinations. The need for novel therapeutic approaches is mandated by the ongoing poor survival rates associated with this disease. One such approach may include manipulation of ribosome biogenesis and the nucleolar stress response, which has recently been applied to haematological malignancies such as lymphoma and prostate cancer with promising results. This review will focus on the current therapeutic options for pancreatic ductal adenocarcinoma and the complexities associated with developing novel treatments, with a particular emphasis on the role of the nucleolus as a treatment strategy.
| S-EPMC5385394 | biostudies-literature
Project description:BackgroundNo standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy.MethodsBetween Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with ClinicalTrials.gov, number NCT00965250.Findings49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24·0 months (IQR 17·3-36·9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3-4 adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune conditions during treatment (five were new-onset disorders), the most common of which was pure red-cell aplasia. Two (4%) patients died; one was attributed to disease progression and the other to disease-related complications (respiratory failure, myositis, and an acute coronary event), which could have been precipitated by treatment with cixutumumab.InterpretationCixutumumab monotherapy is well-tolerated and active in relapsed thymoma. Development of autoimmunity during treatment needs further investigation.FundingDivision of Cancer Treatment and Diagnosis at the National Cancer Institute (National Institutes of Health), ImClone Systems.
| S-EPMC3954701 | biostudies-literature