Hyperthermic Intrathoracic Chemotherapy Research Articles

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.

Bilateral Thoracic Cytoreductive Surgery for Pseudomyxoma Peritonei of Appendiceal Origin.

Pleural spread occurs in pseudomyxoma peritonei (PMP) in less than 10% of the patients and is treated by thoracic cytoreductive surgery with or without hyperthermic intrathoracic chemotherapy (HITOC). It is performed both for symptom palliation and disease control and includes pleurectomy and decortication and wedge and segmental lung resections. So far, only unilateral spread treated with a thoracic cytoreductive surgery (CRS) has been reported in literature. We report a patient with bilateral thoracic PMP following a complete abdominal CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) who was treated with bilateral staged thoracic CRS and subsequently had a 4th CRS for abdominal disease. The staged procedure was performed as she was symptomatic due to the thoracic disease and there was disease on all pleural surfaces. HITOC was not performed. Both procedures were uneventful with no major morbidity. The patient is currently disease free nearly 84months after the first abdominal CRS and 60months after the second thoracic CRS. Thus, an aggressive CRS in the thorax in patients with PMP can result in a prolongation of survival while preserving the quality of life if the abdominal disease is controlled. A thorough understanding of the disease biology and surgical expertise are both essential for selecting the right patients for these complex procedures and achieving good short- and long-term outcomes.

Abstract 6399: Hyperthermic intrathoracic chemotherapy (HITOC) improves malignant pleural mesothelioma control through a tumor specific cytotoxic immune response

Abstract Introduction: The management of malignant pleural mesothelioma (MPM) remains challenging with poor patient survival. Local therapies such as hyperthermic intrathoracic cisplatin (HITOC) have shown good tumor control in selected patients. HITOC was shown to increase MPM drug exposure while limiting systemic side effects but alternative mechanisms for HITOC are still lacking. Here, we hypothesized that HITOC induces an immune response directed against MPM which decreases cancer related mortality. Methods: We implanted AB12-luc MPM cells in the pleural cavity of BALB/c mice. A chemotherapy perfusion circuit was downsized to administer cisplatin (80mg/m2 equivalent dose) in the thoracic cavity at normo (37°C, ITOC) or hyperthermic (39°C, HITOC) conditions for 30 minutes. Tumor growth (visualized by bioluminescence) and mouse survival were then assessed. We determined tumor platinum content and distribution by inductively coupled plasma mass spectrometry (ICP-MS) and by laser ablation ICP-MS (LA-ICP-MS) respectively. We also questioned the impact of (H)ITOC on the MPM immune microenvironment (innate and adaptive immune cells, activity and checkpoint expression) by 16-colour flow cytometry and immunohistochemistry. Finally, tumor response to (H)ITOC was assessed in BALB/c athymic mice implanted with AB12-luc cells. Results: MPM tumor control and mouse survival were significantly improved by HITOC compared to controls (ITOC, saline 37 and 39°C). Tumor platinum content was significantly higher in HITOC compared to ITOC but was majorly located at the surface of tumors. HITOC enhanced MPM infiltration by CD8+Granzyme B+ T-cells and decreased the levels of MCHII−/CD80− (M2-like) macrophages compared to controls at day 7. Interestingly, immune checkpoint expression of PD1 and CTLA4 was significantly enhanced in CD8+ lymphocytes in HITOC treated MPM compared to controls at day 7. Finally, the lack of T lymphocytes (BALB/c athymic mice) abrogated the impact of HITOC on MPM control and mouse survival. Conclusion: HITOC improves MPM control through a T lymphocyte immune mediated response. The enhanced immune checkpoint (PD1/CTLA4) expression in CD8+ lymphocytes opens perspectives for the combination of HITOC with immune checkpoint inhibitors. Citation Format: Yameng Hao, Aspasia Gkasti, Louis-Emmanuel Chriqui, Damien Marie, Michel Gonzalez, Thorsten Krueger, Solange Peters, Paul J. Dyson, Etienne Meylan, Johanna Joyce, Sabrina Cavin, Jean Y. Perentes. Hyperthermic intrathoracic chemotherapy (HITOC) improves malignant pleural mesothelioma control through a tumor specific cytotoxic immune response. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6399.

Surgical cytoreduction and hyperthermic intrathoracic chemotherapy for thymic tumours with pleural spread is effective on survival: results from the multicentre German hyperthermic intrathoracic chemotherapy study.

Cytoreductive surgery and hyperthermic intrathoracic chemotherapy (HITOC) is effective on survival for patients with pleural metastatic thymic tumours. Multicentre, retrospective analysis of patients with stage IVa thymic tumours treated with surgical resection and HITOC. Primary end point was overall survival, secondary end points were recurrence-/progression-free survival and morbidity/mortality. A total of n = 58 patients (thymoma, n = 42; thymic carcinoma, n = 15; atypical carcinoid of the thymus, n = 1) were included, who had primary pleural metastases (n = 50; 86%) or pleural recurrence (n = 8; 14%). Lung-preserving resection (n = 56; 97%) was the preferred approach. Macroscopically complete tumour resection was achieved in n = 49 patients (85%). HITOC was performed with cisplatin alone (n = 38; 66%) or in combination with doxorubicin (n = 20; 34%). Almost half of the patients (n = 28; 48%) received high-dose cisplatin > 125 mg/m2 body surface area. Surgical revision was required in 8 (14%) patients. In-hospital mortality rate was 2%. During follow-up, tumour recurrence/progression was evident in n = 31 (53%) patients. Median follow-up time was 59 months. The 1-, 3- and 5-year survival rates were 95%, 83% and 77%, respectively. Recurrence/progression-free survival rates were 89%, 54% and 44%, respectively. Patients with thymoma had significantly better survival compared to patients with thymic carcinoma (P-value ≤0.001). Promising survival rates in patients with pleural metastatic stage IVa in thymoma (94%) and even in thymic carcinoma (41%) were achieved. Surgical resection and HITOC is safe and effective for treatment of patients with pleural metastatic thymic tumours stage IVa.

A glimpse into the role of debulking surgery and hyperthermic intrathoracic chemotherapy (HITHOC) in the management of malignant pleural mesothelioma

A glimpse into the role of debulking surgery and hyperthermic intrathoracic chemotherapy (HITHOC) in the management of malignant pleural mesothelioma

Hyperthermic Intrathoracic Chemotherapy (HITHOC) for Pleural Disseminated Thymoma: A Systematic Literature Review.

Optimal treatment for thymoma with pleural dissemination (TPD) remains unclear. Extended radical resection is the cornerstone for local treatment but the need for pleuro-pneumonectomy is debatable. Cytoreductive surgery with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) provides an alternative strategy to reduce tumor load and prevent pleural recurrence. The aim of this review was to provide an overview of current literature regarding HITHOC for TPD. A systematic literature review (PRISMA) was performed in the EMBASE, MEDLINE, Cochrane and Web of Science databases, resulting in 154 papers selected for screening (PROSPERO: CRD42020208242). Title, abstract, and full-text screening resulted in 13 papers subjected to structured data extraction and methodological quality assessment. One additional case from our department was included. Inclusion criteria were original research reporting on patients diagnosed with TPD; oncological outcome reporting; intraoperative HITHOC; and papers written in English, Dutch or German. Methodological quality was assessed using the Risk-of-Bias (RoB)-2 Tool and the Newcastle-Ottawa scale. HITHOC for TPD was reported in 171 cases. HITHOC-related mortality was absent and morbidity was reported in three cases. Intrathoracic perfusion of a platinum-derivative, often combined with other chemotherapeutic drugs at >40°C for 60min or longer was always used. Post-HITHOC recurrence was reported in 37/120 cases (31%). In patients with a minimal 1-year follow-up, average time to recurrence was 68.5 months. Combining cytoreductive surgery and HITHOC is feasible and safe for TPD. The strong heterogeneity in the literature impedes proper outcome analysis. More research is needed to better understand the additional benefit of HITHOC in the TPD setting.

Pleural decortication and hyperthermic intrathoracic chemotherapy for pseudomyxoma

Aim: Pleural dissemination of pseudomyxoma peritonei (PMP) is an extremely rare diagnosis, for which no standard therapy is available. Methods: We describe the successful treatment of a 67-year-old male diagnosed with left-sided intrapleural dissemination of PMP (low-grade appendiceal mucinous neoplasm), 2 years after treatment of abdominal PMP with cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy. Treatment consisted of extended pleural decortication (ePD) and oxaliplatin-based hyperthermic intrathoracic chemotherapy (HITHOC). The patient is doing well without complications or signs of recurrence, 26 months after thoracic surgery. Conclusion: ePD in combination with HITHOC is a valuable treatment for thoracic PMP.