Hyperthermic Intrathoracic Chemotherapy Research Articles

EP.14A.20 Hyperthermic Intrathoracic Chemotherapy Following Cytoreductive Surgery in Patients with Pleural Mesothelioma

EP.14A.20 Hyperthermic Intrathoracic Chemotherapy Following Cytoreductive Surgery in Patients with Pleural Mesothelioma

Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study

AbstractMalignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. From March 2017 until August 2023, 55 patients with localized pleural mesothelioma underwent pleurectomy and decortication. Thirty patients performed only surgery while 25 consecutive patients had surgery followed by HITOC with cisplatin (125 mg/m2) infused for 70 min at a temp of 40–43 °C. We analyzed postoperative morbidity, HITOC-related complications, and the influence of HITOC on survival. The trial was registered on 19/08/2022 as NCT05508555. The HITOC group had a mean age of 53.1 ± 8.2 years while the surgery group (non-HITOC) had a mean age of 52.1 ± 8.6 years. The HITOC group had 17 (68%) men, whereas the surgery group included 18 (60%) males. The 30-day mortality in the HITOC group was 0% vs 1 case (3.3%) in the surgery group. HITOC-related transient complications occurred in 4/25 (16%) of the HITOC group (atrial fibrillation, renal impairment and transient hypotension). Progression-free survival in the HITOC group was 8 months (95% CI 4.3–11.6) vs 6 months (95% CI 2.5–9.9) in the surgery-only group (p = 0.79). The overall survival time in the HITOC group was 28 months (95% CI 21.5–34.5) vs 22 months (95% CI 17.5–26.5) in the surgery-only group (p = 0.75). Risk factors analysis for recurrence in the HITOC group confirmed a significant role for early stages (p = 0.03). HITOC following pleurectomy and decortication is a safe therapeutic option that may improve survival for selected patients with localized epithelial pleural mesothelioma. Patients with earlier-stage mesothelioma are more likely to benefit from radical surgery and HITOC.

Postoperative early laboratory changes and follow-up process of patients underwent hyperthermic intrathoracic chemotherapy

BackgroundThe aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30.MethodsThe study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure.ResultsOut of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery.ConclusionAlthough there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma.

The Role of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Thoracic Tumors.

Pleural mesothelioma (PM) is a rare but aggressive thoracic tumor with a poor prognosis. Multimodal treatment-including induction chemotherapy, aggressive surgical resection, radiotherapy and immunotherapy in selected cases-currently represents the best therapeutic option. Single-center studies advocate hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection as an additional therapeutic option, although its impact on post-operative morbidity and survival has not yet been evaluated on a larger scale. HITHOC can be applied not only in the case of mesothelioma, but also in the case of thymoma with pleural involvement or-in very selected cases-in patients with secondary pleural metastases. Despite favorable outcomes and reduced clinical risks, there is no uniform approach to HITHOC, and a wide variety of indications and technical applications are still reported. Based on available data, HITHOC seems to offer a clear benefit in regard to overall survival of all mesothelioma patients; however, multicenter randomized controlled trials are required to validate and standardize this approach. The aim of this review is to focus on the present role of HITHOC in thoracic tumors with pleural involvement as well as on future challenges, particularly in the light of possible combined therapy of thoracic tumors still presenting poor prognoses.

Hyperthermic Intrathoracic Chemotherapy (HITHOC) following decortication for pleural disseminated neoplastic disease: initial experience

Hyperthermic Intrathoracic Chemotherapy (HITHOC) following decortication for pleural disseminated neoplastic disease: initial experience

Association of Robotic Pleurectomy and Cytoreduction with Hyperthermic Intrathoracic Chemotherapy (HITHOC) for pleural recurrence of Type AB Thymoma

Association of Robotic Pleurectomy and Cytoreduction with Hyperthermic Intrathoracic Chemotherapy (HITHOC) for pleural recurrence of Type AB Thymoma

Update in the Treatment of Pleural Tumors: Robotic Surgery Combined with Hyperthermic Intrathoracic Chemotherapy.

(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien-Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusions: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM.

Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy.

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

Extensive surgical resections for rare pleural neoplasms: a single-center experience with a yolk sac tumor and synovial sarcoma

BackgroundPleural neoplasms are rare and can be subdivided into pleural metastasis and primary pleural neoplasms. Non-mesothelioma primary pleural neoplasms are a diverse group of extremely rare pathologies.Case presentationIn this case series, we describe the presentation and management of two rare primary pleural neoplasms. A first case describes a primary pleural yolk sac tumor treated with neoadjuvant chemotherapy, extended pleurectomy decortication, and hyperthermic intrathoracic chemotherapy. In a second case we describe the management of a primary pleural synovial sarcoma by neoadjuvant chemotherapy and extrapleural pneumonectomy. A complete resection was obtained in both cases and the post-operative course was uncomplicated. No signs of tumor recurrence were noted during follow-up in the first patient. In the second patient a local recurrence was diagnosed 6 months after surgery.ConclusionNeo-adjuvant chemotherapy followed by extensive thoracic surgery, including hyperthermic intrathoracic chemotherapy, is a feasible treatment strategy for non-mesothelioma primary pleural neoplasms, but careful follow-up is required.

Successful Implementation of HITOC and HIPEC in the Management of Advanced Ovarian Carcinoma with Pleural and Peritoneal Carcinomatosis.

This case report details the application and outcomes of a novel therapeutic approach involving hyperthermic intraperitoneal chemotherapy (HIPEC) and hyperthermic intrathoracic chemotherapy (HITOC) in a single patient diagnosed with advanced ovarian neoplasm. The treatment protocol included pleural cytoreductive surgery (CRS) and HITOC followed by a second surgical intervention consisting of peritoneal CRS and HIPEC. HIPEC targeted the intraperitoneal space with heated chemotherapy, while HITOC extended the thermal perfusion to the thoracic cavity. The patient has shown significant progression in disease-free survival over one year and eight months of observation, demonstrating lower recurrence rates and an overall survival outcome exceeding expectations based on conventional therapy outcomes. The combined modality demonstrated a manageable toxicity profile, with no significant increase in peri- or postoperative complications observed.

Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy for the treatment of thymic epithelial malignancies with pleural spread or recurrence (CHOICE): a study protocol for a prospective, open, single-arm study.

Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (S-HITHOC) may be effective in treating thymic epithelial tumors (TETs) with pleural spread or recurrence. This study will evaluate the safety and efficacy of S-HITHOC in the treatment of TETs with pleural spread or recurrence. This study is an open, single-arm, prospective trial. Approximately 37 patients diagnosed with TETs with pleural spread or recurrence at the Zhongshan Hospital of Fudan University will be recruited and treated with S-HITHOC. The co-primary outcomes of the study are the length of postoperative hospital stay, complications, and overall quality of life (QoL). The secondary outcomes include drainage duration, volume, and cumulative pain scores. This trial was approved by the Zhongshan Hospital Research Ethics Committee. The study findings will be actively disseminated through manuscript publications and conference presentations. Information sheets will be provided to each participant, and informed written consent will be obtained for each evaluation. This prospective study will evaluate the effectiveness of a surgical resection combined with the HITHOC procedure in treating TETs with pleural spread or recurrence in China and will support the standardization of the procedure. This trial was registered on Clinialtrial.gov (No. NCT05446935).

Anesthetic Aspects of Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Treatment of Pleural Malignancies - Experiences from IORS

Background: Cytoreductive surgery (CRS) with hyperthermic intrathoracic chemotherapy (HITHOC) is a procedure that includes surgical removal of all visible tumor implants and intrathoracic application of gradually heated cytostatic solution. Numerous changes in hemodynamic, respiratory, core body temperature and metabolic parameters are possible during this complex procedure. The aim of this retrospective study was to analyze pathophysiological changes which occur during CRS + HITHOC procedure, and to suggest efficient strategies for perioperative patient care that might reduce complication rate. Methods: The study included 7 patients who underwent CRS + HITHOC in our cancer center. Enhanced Recovery After Surgery (ERAS) guideline for Thoracic Surgery was applied to all patients. Data on intraoperative hemodynamics (mean arterial pressure, stroke volume, heart rate, cardiac output) and temperature variations were collected from medical records and analyzed in three timelines: during the CRS phase, at the beginning, and the end of cytostatic perfusion. Occurrence of respiratory, renal, and cardiac complications was monitored. Results: All patients were respiratory stable during one-lung ventilation, with adequate gas exchange. Hemodynamic stability was compromised at the beginning of cytostatic perfusion, with significant decrease of mean arterial pressure and stroke volume. Two patients required vasopressor support. Average core body temperature was satisfactory in all patients. Coagulation disorders and acute renal failure were not recorded in postoperative period. One patient developed atrial fibrillation which was successfully pharmacologically restored. Conclusion: Our results indicate that goal directed fluid management following ERAS protocol, with maintaining hemodynamic stability and normothermia, could prevent perioperative complications during HITHOC procedure.

Outcome after cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy in patients with secondary pleural metastases

BackgroundThe role of cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (CRS+HITOC) for patients with secondary pleural metastases has scarcely been investigated.Patients and MethodsWe conducted a retrospective, multicentre study investigating the outcome of CRS+HITOC for 31 patients with pleural metastases from different primary tumours in four high-volume departments of thoracic surgery in Germany. The primary endpoint was overall survival (OS). Secondary endpoints included postoperative complications and recurrence/progression-free survival (RFS/PFS).ResultsThe primary tumour was non-small cell lung cancer in 12 (39%), ovarian cancer in 5 (16%), sarcoma in 3 (10%), pseudomyxoma peritonei in 3 (10%), and others in 8 (26%) patients. A macroscopic complete resection (R/1) could be achieved in 28 (90%) patients. Major postoperative complications as classified by Clavien-Dindo (III-V) were observed in 11 (35%) patients. The postoperative mortality rate was 10% (n=3). A total of 13 patients received additive chemotherapy (42%). The median time of follow up was 30 months (95% CI = 17– 43). The median OS was 39 months (95% CI: 34-44 months) with 1-month, 3-month, 1-, 3-, and 5-year survival estimates of 97%, 89%, 77%, 66%, and 41%. There was a significantly prolonged OS in patients who received additive chemotherapy compared to patients with only CRS+HITOC (median OS 69 vs 38 months; p= 0.048). The median RFS was 14 months (95% CI: 7-21 months).ConclusionsWe observed that CRS+HITOC is a feasible approach with reasonable complications and prolonged survival as a part of multimodal concept for highly selected patients with secondary pleural metastases.

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

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

The Excretion of Cisplatin after Hyperthermic Intrathoracic Chemotherapy.

Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.

Hyperthermic intrapleural chemotherapy: an update.

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.

Hyperthermic intrathoracic/intraperitoneal chemotherapy versus conventional intrapleural/intraperitoneal chemotherapy for the malignant effusion: a multi-center randomized clinical trial

Objective To compare the efficacy and safety of hyperthermic intrathoracic/intraperitoneal chemotherapy versus conventional intrapleural/intraperitoneal chemotherapy in the treatment of malignant pleural or peritoneal effusion. Methods A randomized clinical trial was carried out in 8 cancer centers across China. Patients with malignant pleural or peritoneal effusion were randomly assigned to the study group or control group. Patients in the study group were treated with cisplatin-based hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC), while the control group was treated with conventional intrapleural or intraperitoneal chemotherapy using same chemotherapeutic regime as the study group. The objective response rate (ORR) was analyzed as primary outcome. Quality-of-life (QOL) score was recorded as secondary outcome using the questionnaire 30 (QLQ-C30) of the European Organization for Research and Treatment of Cancer (EORTC). The efficacy and safety of the two treatments were compared. Results Total 135 patients were recruited and randomized in this study, with 67 patients in the study group and 68 patients in the control group. The ORR in the study group (80.70%) was significantly higher than that in the control group (31.03%, p < 0.001). However, neither changes of QOL scores, nor incidence rates of adverse events were significantly different between the two groups (p = 0.076 and 0.197, respectively). Conclusion Efficacy of HITHOC or HIPEC is superior to that of conventional modality for the treatment of malignant effusion with comparable side effects.

Efficacy of hyperthermic intrathoracic chemotherapy for initially diagnosed lung cancer with symptomatic malignant pleural effusion

Initially diagnosed malignant pleural effusion (MPE) has different systematic treatments, and defining the best drainage regimen according to the responsiveness of MPE to different systematic treatments is important. This study compared the efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) and pleural catheter drainage (IPCD) for initially diagnosed lung cancer with symptomatic MPE. We retrospectively reviewed the medical records of initially diagnosed lung cancer patients with symptomatic MPE between January 2018 and May 2022. The patients were treated with IPCD or HITHOC for local control of MPE after diagnosis. Systematic regimens were conducted during 1 month according to guidelines after local treatment. Intrathoracic MPE progression-free survival (iPFS) and overall survival (OS) were calculated, Univariate and multivariable Cox-regression were used to identify factors associated with iPFS and OS. A total of 33 patients were evaluated; 10 (30.3%) patients received IPCD, and 23 (69.7%) patients received HITHOC. No difference in the MPE control rate at 1 month was found between the IPCD group (90%) and HITHOC group (95.7%). However, this control rate was significantly higher in the HITHOC group (69.6%) than in the IPCD group (30%) at 3 months (P = 0.035). Multivariate analysis showed that receiving tyrosine kinase inhibitors (TKIs) or chemotherapy was a significant protective factor for iPFS (HR = 0.376, 95% CI 0.214–0.659, P = 0.007) and OS (HR = 0.321, 95% CI 0.174–0.594, P < 0.001). According to subgroup analysis, among patients treated with TKIs, those who received HITHOC had longer iPFS and OS than those who received IPCD (P = 0.011 and P = 0.002, respectively), but this difference was not found in the palliative care subgroup. Moreover, no patients treated with chemotherapy showed reaccumulation of MPE. Systematic TKIs or chemotherapy prolonged iPFS and OS for those initially diagnosed with lung cancer with symptomatic MPE. HITHOC prolonged iPFS and OS for those treated with systematic TKIs.

Hyperthermic intrathoracic extracorporeal chemotherapy for secondary malignant pleural disease.

Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in selected patients. We evaluated the safety and efficacy of hyperthermic intrathoracic extracorporeal chemotherapy (HITEC) in patients who underwent pleurectomy/decortication (P/D) for secondary malignant pleural disease (SPD). A total of 101 patients were evaluated over 72 months, with 35 patients electing to proceed with P/D and 60 minutes of HITEC with cisplatin at 42°C. Inclusion criteria were adults 18-79 years with unilateral pleural dissemination. Exclusion criteria were patients without control of primary site, extrathoracic metastatic disease, significant comorbidities, and a history of adverse reaction to cisplatin. Median age was 56 years (36-73); 60% were women. SPD was thymoma in 13, breast cancer in 9, lung cancer in 6, colon cancer in 2, renal cell in 2, and esophageal, anal, and thymic cancers in one each. There was no operative mortality. Postoperative complications occurred in 18 patients (51%). No patient developed renal failure. Median follow-up was 24 months (4-60). The overall survival rate was 61%; 17 patients (49%) developed recurrent disease at a median of 12 months (6-36). There were no recurrences after 36 months Eleven patients (31%) died of metastatic disease at a median of 17 months (7-25). Surgical cytoreduction of SPD followed by HITEC with cisplatin was well tolerated. No patient developed cisplatin-related toxicities. Long-term follow-up is warranted to determine survival advantage and refinement of inclusion criteria.

Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study

Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6–80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12–25) in Group A and 28 months (95% CI 0–56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0–34) in Group A and 45 months (95% CI 0–107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.