Search Results (12)

Pleural malignancies represent a clinically devastating group of oncological disorders, most commonly arising from metastatic disease, with lung and breast cancers being the most frequent primary sites. Malignant pleural mesothelioma is a primary malignancy of the pleura and occurs less often than metastatic pleural disease. Pleural malignancies often present with malignant pleural effusion, which typically indicates advanced-stage disease and is associated with poor overall prognosis. Treatment of pleural malignancies includes both palliative and definitive approaches. Palliative interventions primarily aim to relieve symptoms and improve quality of life. Definitive treatments include systemic chemotherapy, targeted therapy, and immunotherapy, depending on the type and molecular profile of the underlying tumor. In mesothelioma, platinum-based chemotherapy in combination with pemetrexed remains the cornerstone of treatment, while the combination of nivolumab and ipilimumab is recommended as first-line therapy for unresectable disease. For metastatic disease, systemic therapy is typically tailored to the primary tumor’s characteristics. Intrapleural administration of chemotherapeutic agents is one of the therapeutic strategies and hyperthermic intrathoracic chemotherapy and pressurized intrathoracic aerosol chemotherapy are the most recent innovations that are under active investigation. This review provides an up-to-date synthesis of systemic chemotherapy strategies for pleural malignancies, their integration with targeted and immune-based therapies, and recent advances in intrapleural chemotherapy modalities. It also explores existing knowledge gaps and outlines directions for future research and potential changes in clinical practice. Full article

Background/Objectives: Thymic epithelial tumors with pleural metastasis require a multimodal treatment approach with the use of novel modalities such as hyperthermic intrathoracic chemotherapy (HITHOC). This systematic review and case report aims to summarize the existing evidence regarding HITHOC for these tumors and presents the first case of a robotic approach to HITHOC. Methods: A search in November 2023 yielded a total of 17 articles, including 281 patients who met the eligibility criteria (i.e., underwent HITHOC for treatment of a thymic epithelial tumor). Results: Variations existed among HITHOC regimens and surgical approaches. The most common complications observed were air leaks. Overall survival ranged 92–95% at 1 year, 83–91.7% at 3 years, 66.7–92% at 5 years, 40–83.3% at 10 years, and 27.8–58.2% at 15 years. Conclusions: While HITHOC for thymic epithelial tumors with pleural dissemination has been shown to yield successful outcomes in the literature, this procedure has historically been performed almost exclusively via an open thoracotomy. The robotic approach to HITHOC is feasible and affords several important benefits. Full article

Pleural mesothelioma (PM) is an aggressive cancer originating from the mesothelial lining of the pleura, with a rising global incidence since the mid-20th century due to asbestos and erionite exposure. PM accounts for 80–90% of all mesothelioma cases and is histologically classified into three subtypes—epithelioid, sarcomatoid, and biphasic— with epithelioid carrying the most favorable prognosis. Despite advances in surgery, chemotherapy, radiotherapy, and immunotherapy, PM prognosis remains poor, necessitating more effective, multimodal strategies. Hyperthermic intrathoracic chemoperfusion (HITHOC) has emerged as a promising adjunct to cytoreductive surgery by delivering heated chemotherapy directly to the pleural cavity, potentially improving survival—especially in patients with epithelioid PM. Combining HITHOC with post-surgical immunotherapy represents a novel approach to enhancing both local and systemic anti-tumor responses and targeting microscopic disease and distant metastases. This review explores surgical outcomes after surgery for PM, the therapeutic synergy of HITHOC and immunotherapy, ongoing clinical trials evaluating this multimodal strategy, and its implications for future patient care. Full article

Background: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive treatment option after surgical cytoreduction of pleural malignancies. Despite growing clinical experience and studies evaluating its feasibility, postoperative morbidity and mortality, as well as the effect on survival, there is still only little known about the local effects of HITOC on the lung parenchyma and tumour cells. The objective of this in vitro study was to evaluate the dose-dependent concentration and penetration depth of cisplatin in human lung tissue. Methods: In total, 40 patients were enrolled for elective lung resection, and wedge samples were taken to the laboratory. The visceral pleura was removed, and the decorticated lung tissue was incubated in cisplatin solutions of different concentrations (0.05, 0.075, and 0.1 mg/mL) at 42 °C over 60 min. Afterwards, platinum amounts in the lung tissue samples were measured using atomic absorption spectroscopy. Results: A strong decline of the cisplatin concentration was found until a depth of 3.5 mm, followed by a mild decline until a depth of 7.5 mm. In a depth of 0.5 mm, there was only a significant difference between 0.05 and 0.1 mg/mL (p = 0.03, Cohen’s d = 0.43). In a depth of 1.5 mm, there was an overall significant difference in cisplatin concentration dependent on dose (p = 0.027). In deeper tissue layers, no significant difference in cisplatin concentrations in the tissue was found. Conclusions: A dose-dependent increase of the cisplatin concentration was found for superficial tissue layers. This emphasises the relevance of sufficiently high intrathoracic concentrations of the chemotherapeutic agent. This study confirms that cisplatin penetrates lung tissue in therapeutically effective concentrations. Full article

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. Full article

(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. Full article

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. Full article

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. Full article

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. Full article

In the context of quality assurance, the objectives were to describe the surgical treatment and postoperative morbidity (particularly renal insufficiency). A retrospective, multicentre study of patients who underwent cytoreductive surgery (CRS) with cisplatin-based HITOC was performed. The study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation (GZ: RI 2905/3-1)). Patients (n = 350) with malignant pleural mesothelioma (n = 261; 75%) and thymic tumours with pleural spread (n = 58; 17%) or pleural metastases (n = 31; 9%) were analyzed. CRS was accomplished by pleurectomy/decortication (P/D: n = 77; 22%), extended P/D (eP/D: n = 263; 75%) or extrapleural pneumonectomy (EPP: n = 10; 3%). Patients received cisplatin alone (n = 212; 61%) or cisplatin plus doxorubicin (n = 138; 39%). Low-dose cisplatin (≤125 mg/m² BSA) was given in 67% of patients (n = 234), and high-dose cisplatin (>125 mg/m² BSA) was given in 33% of patients (n = 116). Postoperative renal insufficiency appeared in 12% of the patients (n = 41), and 1.4% (n = 5) required temporary dialysis. Surgical revision was necessary in 51 patients (15%). In-hospital mortality was 3.7% (n = 13). Patients receiving high-dose cisplatin were 2.7 times more likely to suffer from renal insufficiency than patients receiving low-dose cisplatin (p = 0.006). The risk for postoperative renal failure is dependent on the intrathoracic cisplatin dosage but was within an acceptable range. Full article

A complete resection of thymic tumors is known to be the most important prognostic factor, but it is often difficult to perform, especially in advanced stages. In this study, 73 patients with advanced thymic tumors of UICC stages III and IV who underwent radical resection were examined retrospectively. The primary endpoint was defined as the postoperative resection status. Secondary endpoints included postoperative morbidity, mortality, recurrence/progression-free, and overall survival. In total, 31.5% of patients were assigned to stage IIIa, 9.6% to stage IIIb, 47.9% to stage IVa, and 11% to stage IVb. In stages III a R0 resection was achieved in 53.3% of patients. In stages IV a R0/R1 resection was documented in 76.7% of patients. Surgical revision was necessary in 17.8% of patients. In-hospital mortality was 2.7%. Median recurrence/progression-free interval was 43 months (p = 0.19) with an overall survival of 79 months. The 5-year survival rate was 61.3%, respectively. Median survival after R2 resection was 25 months, significantly shorter than after R0 or R1 resection (115 months; p = 0.004). Advanced thymic tumors can be resected with an acceptable risk of complications and low mortality. In stage III as well as in stage IV the promising survival rates are dependent on the resection-status. Full article

Introduction: Malignant Pleural Mesothelioma (MPM) is characterized by an aggressive behavior and an inevitably fatal prognosis, whose treatment is still far from being standardized. The role of surgery is questionable since a radical resection is unattainable in most cases. Hyperthermic IntraTHOracic Chemotherapy (HITHOC) combines the advantages of antitumoral effects together with those of high temperature on the exposed tissues with the aim to improve surgical radicality. Material and Methods: this is a narrative review on the role of HITHOC in the management of MPM patients. To provide data on the beginnings and the historical evolution of this technique, we searched the available literature by selecting the more exhaustive papers on this topic. Results: from 1994 to date different authors experimented HITHOC following a cytoreductive surgery in MPM, obtaining in most cases a good local control and a better overall survival associated to very low complication rate. Conclusions: HITHOC may be considered as a safe, feasible and effective procedure although there is a high heterogeneity between different protocols adopted worldwide. More structured studies are needed to reach a unanimous consensus on this technique. Full article