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Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival.

ABSTRACT:

Background

Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale.

Methods

The National Cancer Database was queried for patients undergoing resection for PM from 2006-2017. Patients were excluded if staging or survival data was incomplete. After propensity-score matching, patients who underwent HITHOC were compared to patients who did not (case-control study). Perioperative outcomes and survival were analyzed.

Results

The final cohort consisted of 3,232 patients; of these, 365 patients underwent HITHOC. After propensity-score matching, receipt of HITHOC was associated with increased length of stay (12 vs. 7 days, P<0.001) and increased 30-day readmissions (9.9% vs. 4.9%, P=0.007), but decreased 30-day mortality (3.2% vs. 6.0%, P=0.017) and 90-day mortality (7.5% vs. 10.9%). Kaplan-Meier modeling demonstrated that HITHOC was associated with improved survival in the overall cohort (median 20.5 vs. 16.8 months, P=0.001). In multivariable analysis, HITHOC remained associated with improved overall survival [hazard ratio (HR) =0.80; 95% confidence interval (CI): 0.69-0.92; P=0.002], and this persisted in the propensity-matched analysis (HR =0.73; 95% CI: 0.61-0.88; P=0.001).

Conclusions

Using a large national database, we describe the impact of HITHOC on survival in patients with PM. Despite observed increased short-term morbidity, in multivariable analysis HITHOC was associated with an overall survival advantage for patients undergoing surgical resection of PM.

SUBMITTER: Elliott IA

PROVIDER: S-EPMC10713319 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival.

Elliott Irmina A IA He Hao H Lui Natalie S NS Liou Douglas Z DZ Guenthart Brandon A BA Shrager Joseph B JB Berry Mark F MF Backhus Leah M LM

Journal of thoracic disease 20231103 11

<h4>Background</h4>Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale.<h4>Methods</h4>The National Cancer Database was ...[more]

PMID: 38090290

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Project description:BackgroundMalignant pleural mesothelioma (MPM) is primarily treated with a combination therapy based on lung pleurectomy in the early stage or pemetrexed combined with platinum-based chemotherapy in the late stage. However, these standard therapies do not significantly improve survival and are associated with significant adverse reactions.Case descriptionIn February 2017, a 63-year-old male patient was admitted to Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University coughing for 1 month and experienced chest tightness and chest pain for 2 days. After admission, the patient underwent thoracic puncture drainage and was diagnosed with stage IIIb (c-T4NxM0) MPM. The patient subsequently underwent left pleural biopsy under single-port thoracoscopy, followed by cytoreductive surgery plus hyperthermic intrathoracic chemotherapy as a local treatment for controlling pleural effusion. At a postoperative follow-up in October 2017, we found that he had recurrent MPM with multiple nodules on the left pleura. Despite this, the patient declined further antitumor treatment. In April 2020, the patient was readmitted to The Third Affiliated Hospital of Chongqing Medical University for left-sided chest pain and was observed to have an enlarged tumor in the left pleural according to further imaging examination. Fortunately, no further pleural effusion has been observed since then. Subsequently, the patient was administered a combination of immunotherapy and cisplatin-pemetrexed chemotherapy as systemic therapy for six cycles, along with subsequent mono immunotherapy as maintenance therapy for three additional cycles. Following this, the left pleural tumor shrank significantly, and the patient achieved partial remission. However, due to the patient's irregular treatment adherence, the patient returned for systemic immunotherapy therapy for four cycles in November 2021, and a slight reduction of the pleural tumor was achieved. Once again, the patient discontinued treatment until he experienced left-sided chest pain and partial tumor enlargement in February 2023. Another three cycles of immunotherapy were administered, but the pleural tumor continued to grow. In June 2023, the patient succumbed to respiratory failure caused by a pulmonary infection. Overall, the patient's survival time was 76 months.ConclusionsCytoreductive video-assisted thoracic surgery plus hyperthermic intrathoracic chemotherapy followed by systemic chemo-immunotherapy can effectively control pleural effusion, prolong patient survival, and improve the quality of life in patients with MPM.

Project description:ObjectiveWith 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.BackgroundThymomas 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.MethodsWe 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.ConclusionsHITHOC 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.KeywordsHypertermic intrathoracic chemotherapy (HITHOC); thymoma; intracavitary chemotherapy; hyperthermia; redo-surgery.

Project description:ObjectiveTo compare the pharmacokinetics and adverse effects of cisplatin administered via intravenous infusion for systemic chemotherapy (SC) versus injection into the perfusate during hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsTotal 60 patients who received SC, HITHOC, or HIPEC in the Department of Oncology, Tangdu Hospital, were enrolled into this study. After administering same dose of cisplatin (40 mg) via either intravenous infusion (SC group) or injection into the perfusate during the HITHOC or HIPEC procedure, concentration of cisplatin in the plasma as well as in the hyperthermic perfusate at various time points was quantified by HPLC analysis. The area under the plasma or perfusate concentration-time curve over the last 24h dosing interval (AUC0-24h), mean residence time over the 24 h (MRT0-24h), terminal elimination half-life (t1/2z), time to peak concentration (Tmax), apparent clearance (Clz/F), and peak concentration (Cmax) in the perfusate and plasma were compared.ResultsIn the perfusate, the AUC0-24h (64.32 ± 27.12 µg/mL·h) and Cmax (21.62 ± 5.88 µg/mL) were significantly higher in the HITHOC group compared to that in the HIPEC group (31.68 ± 13.29 µg/mL·h and 16.96 ± 5.54 µg/mL, respectively, p ≤ 0.01). In contrast, MRT0-∞, t1/2z, and Clz/F were significantly lower in the HITHOC group compared to that in the HIPEC group (p < 0.01). In the plasma, average AUC0-24h and Cmax of the HITHOC group were 2.57 ± 0.55 µg/mL·h and 0.26 ± 0.08 µg/mL, respectively, which were significantly lower than that of systemic chemotherapy (SC) group (3.26 ± 0.56 µg/mL·h and 0.69 ± 0.14 µg/mL, respectively, p < 0.01), but no difference compared to that of HIPEC group (3.02 ± 0.52 µg/mL·h and 0.40 ± 0.15 µg/mL, respectively, p > 0.05). In contrast, MRT0-24h and Tmax in the plasma of HITHOC group were significantly longer compared to that of SC group (p < 0.05), but no significant difference compared to that of HIPEC group (p > 0.05). Absolute bioavailability of cisplatin in the thoracic (HITHOC group) and abdominal (HIPEC group) cavities was 20 and 10 times higher than that in the blood administered intravenously (SC group), respectively. There was no significant difference in the incidence of adverse events among the three groups (p < 0.05).ConclusionThe current study demonstrated that, in the perfusate, AUC0-24h and Cmax of cisplatin was significantly higher in the group of HITHOC compared to that of HIPEC, and that, in the plasma, AUC0-24h and Cmax of cisplatin was lower in the group of HITHOC compared to that of HIPEC or SC group. This study provided pharmacokinetic evidence to further support the concept that topical application of chemotherapeutic drug through minimally invasive HITHOC or HIPEC may enhance local exposure compared to systemic chemotherapy for the patients with malignant pleural effusion or ascites.

Dataset Information

Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival.

Background

Methods

Results

Conclusions

Publications

Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival.

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