Hypertermic Intrathoracic Chemotherapy (HITHOC) for thymoma: a narrative review on indications and results

Abstract

Objective: With this narrative review, we retraced the history of hypertermic intrathoracic chemotherapy (HITHOC) since the beginning, analyzing literature on operative technique, feasibility and efficacy of this treatment. Moreover, we report the fifteen-year experience of our center in this relatively new technique, for what concerns both early postoperative results and long-term oncological outcomes.Background: Thymomas are frequently misdiagnosed and recognized in advanced stage, often with pleural dissemination, especially when not associated to Myasthenia Gravis that allows an early diagnosis during the initial assessment. Moreover, the natural history of locally advanced thymoma is characterized by a high rate of pleural or pericardial relapses. Surgery has always been considered a milestone in thymoma's treatment, even in case of serous dissemination or relapses, although his role as exclusive therapy does not guarantee an acceptable local disease control. In case of disseminated disease, different multidisciplinary protocols have been experimented, from chemotherapy to radiation therapy, alone or associated to surgery, in order to increase overall and disease-free survival, but the breakthrough happened in the early 90s with the introduction of HITHOC following surgery. Combination of surgery and HITHOC resulted in less toxic than systemic chemotherapy and providing a good local disease control in patients with stage IVa thymomas or thymoma's pleural recurrences.Methods: We searched PubMed for relevant literature, up to January 2020, on hypertermic intrapleural chemotherapy for thymomas (TPR or DNT), selecting only those reporting information about HITHOC protocol used, postoperative course and oncological outcomes.Conclusions: HITHOC is a safe and feasible procedure, with a very low complication rate and negligible systemic effects of chemotherapeutic agents, effective in controlling both TPR and DNT, in particular as regards local disease-free survival.

Subtotal Pleurectomy with Intrathoracic Chemo Hyperthermia (HITHOC) for IVa Thymomas: De Novo Versus Recurrent Pleural Disease

“…Secondly, we were able to demonstrate using the French database RYTHMIC that surgical excision of pleural nodules (including HITHOC cases) in stage IVa compared to systemic treatments reduced the risk of recurrence by 60% (HR = 0.4, 95 CI (0.25–062); p < 0.0001) [ 25 ]. These results were confirmed by the study of Aprile et al [ 26 ], who were able to demonstrate in a retrospective study that the HITHOC procedure coupled with a cytoreductive pleurectomy gave better results in DFI compared with cytoreduction alone: 88 ± 15 vs. 57 ± 19 months ( p = 0.046). Moreover, our results are fully comparable with those previously published showing a 5-year survival rate between 70–100% and a DFI of 61–87% [ 27 ].…”

Optimism with caution for patients with advanced thymoma and thymic carcinoma

“…To reinforce the data obtained by Ried et al [ 2 ], Chappuy et al [ 10 ] reported an important experience with 40 patients with T IVa pleural involvement treated with partial pleurectomy and HITHOC showing a median length of survival of 118 months and a median DFI of 70 months [ 10 ]. The group of Pisa in Italy had also similar results [ 11 ].…”

Hyperthermic intrathoracic extracorporeal chemotherapy for secondary malignant pleural disease

“…Aggressive trimodality treatment approach has been evaluated in patients with secondary pleural metastasis 15,16 . This combination has been effective in achieving local control and improved 5‐ and 10‐year survivals in selected patients with metastatic thymic malignancies 28–30 . All of our thymoma patients are alive after their P/D and HITEC at a median follow‐up of 24 months.…”

“…15,16 This combination has been effective in achieving local control and improved 5-and 10-year survivals in selected patients with metastatic thymic malignancies. [28][29][30] All of our thymoma patients are alive after their P/D and HITEC at a median follow-up of 24 months. Thymic metastases are usually more indolent than malignant mesothelioma or other secondary pleural metastasis.…”