Present and future of hyperthermic intrathoracic chemotherapy (HITHOC) in thoracic surgical oncology.
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ABSTRACT:
SUBMITTER: Migliore M
PROVIDER: S-EPMC8263878 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Present and future of hyperthermic intrathoracic chemotherapy (HITHOC) in thoracic surgical oncology.
Annals of translational medicine 20210601 11
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Project description:Although the method of hyperthermic intrathoracic chemotherapy (HITHOC) after cytoreductive surgery is known for more than 20 years now, the interest of the scientific community has been growing especially in recent years with annually increasing numbers of publications. The feasibility and safety of HITHOC has already been demonstrated. The primary objective now is to reach a consent about the optimal implementation and standardization of the procedure. In the international clinical practice of HITHOC the parameters of temperature, duration, type and number of chemotherapeutic agents vary, making a comparison of the short- and long-term results difficult. For about ten years, the combination of surgical cytoreduction and HITHOC has been performed more routinely in several departments of thoracic surgery in Germany, especially in university hospitals. Recently, a group of experts for thoracic surgery of five departments of thoracic surgery elaborated recommendations for the HITHOC procedure in Germany. These recommendations represent a standardized and consistent implementation of HITHOC. Through this, postoperative complications associated to HITHOC should be reduced and a better comparison of the results should be enabled. This article is intended to give a brief overview of the literature, current recommendations in the implementation of HITHOC and also aims to show future perspectives of this procedure.
| S-EPMC8263861 | biostudies-literature
Project description: Not available
| S-EPMC8263862 | biostudies-literature
Project description:BackgroundPleural 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.MethodsThe 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.ResultsThe 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).ConclusionsUsing 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.
| S-EPMC10713319 | biostudies-literature
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.
| S-EPMC11635204 | biostudies-literature
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.
| S-EPMC8263885 | biostudies-literature
Project description:Hyperthermic intraperitoneal chemotherapy (HIPEC), along with optimal cytoreductive surgery, has been debated to be a viable option for the treatment of advanced epithelial ovarian cancer with peritoneal carcinomatosis. HIPEC is associated with a direct and improved penetration of chemotherapy drugs into the affected tissue and is associated with fewer systemic side effects. There is no standard protocol for the use of HIPEC in advanced ovarian cancer. Hence, there is controversy over the timing, dose, duration, and efficacy of HIPEC. In this review, the history, technique, current evidence, recommendations, and future directions of HIPEC are discussed.
| S-EPMC8272440 | biostudies-literature
Project description:The traditional treatment of stage IV lung cancer is predominantly supportive or palliative. No current standardized guidelines promote the use of hyperthermic intrathoracic chemotherapy (HITHOC) in the treatment of advanced lung cancer with pleural involvement. Several small studies have examined the safety and utilization of HITHOC for this population, though the data is extremely limited. A review of the literature is presented in accordance with the Narrative Review checklist. The MEDLINE electronic database was searched for articles published in English from January 1999 - August 2020 using relevant keywords such as "hyperthermic intrathoracic chemotherapy", "hyperthermic intrapleural chemotherapy" and "HITHOC". This was supplemented by review and hand search of the reference lists. While data suggest a potential though controversial role for HITHOC for certain intrathoracic tumors such as malignant pleural mesothelioma and thymoma, there is insufficient evidence to confidently promote a role for hyperthermic intrathoracic chemotherapy in the treatment of advanced lung cancers. Existing studies are small, nonrandomized, and prone to bias. Hyperthermic intrathoracic chemotherapy is not a standardized treatment for advanced lung cancer, and is characterized by potentially serious side effects with little clinical benefit. Recent developments in targeted therapy and immunotherapy are unlikely to leave room for the development of large randomized controlled trials.
| S-EPMC8263853 | biostudies-literature
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.
| S-EPMC11671569 | biostudies-literature
Project description:IntroductionObjective of the 'German hyperthermic intrathoracic chemotherapy (HITOC) study' is to evaluate the HITOC as additional treatment after surgical cytoreduction for malignant pleural tumours. Even though HITOC is applied with increasing frequency, there is no standardised therapy protocol concerning the technique of HITOC, the selection as well as dosage of chemotherapeutic agents and perioperative management in order to provide a safe and comparable, standardised treatment regime.Methods and analysisThis trial is a retrospective, multicentre observational study, which is funded by the German Research Foundation. Approximately 300 patients will be included. Four departments of thoracic surgery, which are performing the most HITOC procedures in Germany, are contributing to this study: Center for Thoracic Surgery at the University Hospital Regensburg, Thoracic Clinic Heidelberg of the University of Heidelberg, Center for Thoracic Surgery of the Hospital University of Munich and the Department of Thoracic Surgery at the University Hospital Freiburg. All patients who underwent surgical cytoreduction and subsequent HITOC at one of the four centres between starting the HITOC programme in 2008 and December 2019 will be included. Information on the performed HITOC will be obtained, focusing on the technique as well as the applied perfusion solution including the chemotherapeutic agent. Furthermore, parameters of the patient's postoperative recovery will be analysed to determine 30-day morbidity and mortality.Ethics and disseminationThe approvals by the local ethics committee of the respective clinic and the three participating clinics have been obtained. The results will be presented in conferences and published in a peer-reviewed journal.Trial registration numberGerman Clinical Trials Registry (DRKS00015012; Pre-results).
| S-EPMC7375498 | biostudies-literature
Project description:Although cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) have not been shown to be effective by themselves, as a combined treatment they are now standard of care for peritoneal metastases from appendiceal cancer and from colorectal cancer as well as peritoneal mesothelioma. The timing of the HIPEC in relation to the CRS is crucial in that the HIPEC is to destroy minimal residual disease that remains following the CRS and prevent microscopic tumor emboli within the abdomen and pelvis from implanting within the resection site, within fibrinous clot, or within blood clot. Proper selection of chemotherapy agents is crucial to the long-term benefit of CRS and HIPEC. One must consider the response expected with the cancer chemotherapy agent, its area under the curve (AUC) ratio indicating the amount of dose intensity within the peritoneal space, and the drug retention within the peritoneal space for a prolonged exposure. Hyperthermia will augment the cytotoxicity of the cancer chemotherapy agents and improve drug penetration. Irrigation techniques should not be overlooked as an important means of reducing the cancer cell burden within the abdomen and pelvis. Multiple technologies for HIPEC exist and these have advantages and disadvantages. The techniques vary from a totally open technique with a vapor barrier over the open abdominal space to a totally closed technique whereby the HIPEC is administered at the completion of the surgical procedure. The open techniques depend on a table-mounted retractor for suspension of the skin edges allowing a reservoir to occur within the abdomen and pelvis. There are nearly a dozen commercially available hyperthermia pumps, all of which seem to perform adequately for HIPEC although there is a variable degree of convenience and documentation of the HIPEC procedure. As the management of peritoneal metastases has progressed over three decades, early cases are now seen in which a laparoscopic CRS and HIPEC may be appropriate. Also, prophylactic use of laparoscopic HIPEC with perforated appendiceal malignancies and T4 colon cancers may be appropriate.
| S-EPMC4754302 | biostudies-other