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• W2898528034 abstract "Thymic malignancies represent a heterogeneous group of cancers, which are classified according to the World Health Organization (WHO) histopathologic classification, that distinguishes thymomas from thymic carcinomas; thymomas are further subdivided into different types (so-called A, AB, B1, B2, and B3) based upon the relative proportion of the non-tumoral lymphocytic component, and the resemblance to normal thymic architecture. Thymic carcinomas are similar to their extra-thymic counterpart, the most frequent subtype being squamous cell carcinoma. Neuroendocrine tumors may occur in the thymus, for which the management is similar to that of advanced neuroendocrine tumors originating from other anatomic locations. The management of thymic epithelial tumors is a paradigm of cooperation between clinicians, surgeons, and pathologists from establishing the diagnosis to organizing the multimodal therapeutic strategy. Data related to the systemic treatment of thymic malignancies are mostly based on non-randomized studies, retrospective data, and recommendations rely on expert opinion; this is related to the rarity of the disease, precluding large clinical trials to be developed. Systemic treatment may be delivered in a curative-intent approach, for patients presenting with locally-advanced tumor at time of diagnosis, with invasion of intra-thoracic neighboring structures, and/or dissemination to the pleura and the pericardium, precluding upfront complete resection to be achieved. In such cases, chemotherapy has been used both to reduce the tumor burden - possibly allowing subsequent surgery and/or radiotherapy- and to achieve prolonged disease control. In this setting, cisplatin-based combination regimens should be administered; combinations of cisplatin, adriamycin, and cyclophosphamide, and cisplatin and etoposide have been recommended, based on historical studies. When the patient is not deemed to be a surgical candidate - either because R0 resection is not thought to be achievable, or because of poor performance status or co-existent medical condition, definitive radiotherapy is recommended part of a sequential chemoradiotherapy strategy. Combination with chemotherapy may be considered as well. Chemotherapy is also a palliative-intent treatment of unresectable, metastatic, and recurrent tumors, which are more frequently thymic carcinomas than thymomas. Again, cisplatin-based combination regimens with anthracyclins and/or etoposide are standard. No randomized studies have been conducted, and it is unclear which regimens are best; multi-agent combination regimens and anthracycline-based regimens appear to have improved response rates compared to others, especially the etoposide, ifosfamide and cisplatin combination; however, the effect of corticosteroids to deplete the lymphocytic component of thymomas, without any antitumor effect, may significantly impact radiologic response assessment, and hamper comparisons between chemotherapy regimens. Combination of carboplatin and paclitaxel is an option for thymic carcinoma, based on results of recent phase II trials. Recurrences of thymic epithelial tumors should be managed according to the same strategy as newly diagnosed tumors. In non-resectable recurrences, several consecutive lines of chemotherapy may be administered when the patient presents with tumor progression. The re-administration of a previously effective regimen has to be considered, especially in case of previous response, late occurring recurrence. Preferred regimens for second-line treatment include carboplatin plus paclitaxel, and platin plus etoposide; capecitabine plus gemcitabine is an option. These regimens were evaluated in dedicated phase II trials. Options for subsequent lines include pemetrexed, oral etoposide. Sunitinib is an off-label option in the second-line setting, based on its antiangiogenic activity. Everolimus may be another option for refractory disease. Several trials assessing the efficacy of PD-1 checkpoint inhibitors are currently ongoing. Phase II studies of pembrolizumab were recently reported, collectively enrolling 63 patients, showing response rates of 24%, but occurrence of serious, autoimmune adverse events in 20% to 30% of patients. The off-label use of checkpoint inhibitors is currently not recommended. The management of patients requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. While access to innovative strategies represents a major challenge, as the rarity of the tumor precludes specific approval of drugs to be obtained, patient-centered initiatives, such as the establishment of dedicated networks to provide expertise for the actual management of patients, are warranted. In France, RYTHMIC (Réseau tumeurs THYMiques et Cancer; www.rythmic.org) is a nationwide network for thymic malignancies, which was appointed in 2012 by the French National Cancer Institute, as part of its rare cancer program. Since then, the management of all patients diagnosed with thymic tumors has been discussed on a real-time basis at a national multidisciplinary tumor board (MTB), which is organized twice a month basis using a web-based conferencing system. Decision-making is based on consensual recommendations, that were originally established based on available evidence, and are updated and approved each year by all members of the network. A prospective database of all patients is hosted by the French Thoracic Cancer Intergroup. Overall, more than 2,500 patients have been enrolled, demonstrating the feasibility of a national MTB for thymic malignancies, that, besides ensuring patients an equal access to highly specialized management, provides with a comprehensive tool to monitor dedicated actions to improve the management of patients, and enroll patients in clinical trials. Similar thymoma-dedicated and mesothelioma-dedicated networks are now being implemented in France and in other European countries, such as Spain and Italy (the TYME collaborative group). Within the European Reference Network EURACAN, the rare thoracic tumor domain – referred as to G8 domain - handles a network of 20+ healthcare providers; the objectives of EURACAN include the updating and the assessment of current guidelines, the development of educational programs, dissemination and communication with patients groups, and the establishment of research projects, from the diagnosis workup of the disease to the therapeutic strategies. Achieving the highest quality of patient care is the main objective of EURACAN, and the RYTHMIC model provides some practical tools to be implemented at the European level, including Clinical Patient Management System. The European network also provides an infrastructure for collaboration with diagnosis and pharmaceutical companies; one example may be the opening of dedicated cohorts in basket studies assessing new drugs, for which the network allows a better identification of patients and facilitates the recruitment in the trials. Network, multidisciplinary board, Thymoma" @default.
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• W2898528034 date "2018-10-01" @default.
• W2898528034 modified "2023-09-26" @default.
• W2898528034 title "GR01.04 Medical Oncology" @default.
• W2898528034 doi "https://doi.org/10.1016/j.jtho.2018.08.089" @default.
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