Good Doctor·Hyperthermic Intrathoracic Chemotherapy | Multidisciplinary Treatment of Malignant Pleural Effusion: HITHOC Is Superior to Traditional Methods in Controlling Effusion

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“Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Malignant Pleural Effusion Associated with Ovarian Cancer (2026 Edition)” – Chinese Journal of Practical Gynecology and Obstetrics (Original by Zhang Guonan, Xiang Yang, et al.)

[Abstract]

Malignant pleural effusion (MPE) refers to pleural effusion caused by primary malignant tumors of the pleura or by metastasis of malignant tumors from other sites to the pleura. Epithelial ovarian cancer (EOC), commonly referred to as ovarian cancer, is highly heterogeneous, prone to metastasis and recurrence, and represents the gynecologic malignancy with the highest mortality rate [1]. Ovarian cancer–associated MPE occurs when ovarian cancer spreads via the peritoneum, lymphatic system, or hematogenous route to the pleura, or when malignant cells are drained through diaphragmatic lymphatics into the pleural cavity (hereafter referred to as the thoracic cavity), leading to increased capillary permeability of the pleura or obstruction of lymphatic drainage and resulting in a pleural effusion containing malignant tumor cells. DOI: 10.19538/j.fk2026030110
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[Key Summary]

 

 

1). The pleura is one of the most common extra-abdominal sites of metastasis in advanced ovarian cancer, with malignant pleural effusion (MPE) occurring in approximately 33% to 53% of stage IV patients. MPE often represents the initial or concurrent manifestation of distant metastasis in ovarian cancer, typically presenting as moderate to large, rapidly accumulating bilateral or unilateral (more commonly right-sided) pleural effusions that coexist with ascites and pelvic/abdominal masses.

2). Treatment strategies for ovarian cancer–associated malignant pleural effusion should shift from a symptom-relief–focused approach to early intervention and aggressive management of pleural effusion to improve oncologic outcomes.

3). Chest ultrasound and CT imaging are essential tools for the detection, localization, and quantification of pleural effusion, and they play a critical role in the diagnosis of ovarian cancer–associated malignant pleural effusion. (Recommendation grade: 2A.)

4). Cytological examination of pleural effusion is a simple and practical method for determining whether the effusion is benign or malignant and for identifying the origin of tumor cells. Commonly used techniques include cytological smear (CS), liquid-based cytology (LBC), and cell block (CB) examination—where all cellular sediment obtained after centrifugation of the pleural effusion specimen is fixed and embedded in paraffin to form a cell block. H&E staining of pleural effusion cell blocks (CB) combined with immunocytochemical staining (ICC) is the routinely recommended approach for definitive diagnosis of malignant pleural effusion (MPE) (recommendation grade: 2A).

5) Compared with other malignant tumors, patients with ovarian cancer–associated malignant pleural effusion have a relatively better prognosis and longer survival. The therapeutic goal should not be limited to transient symptom relief; rather, the aim should be to achieve long-term, stable control of pleural effusion, thereby improving quality of life and prolonging survival. The treatment principle is to prioritize standard ovarian cancer therapy, supplemented by active local interventions (recommendation grade: 2A).

6). For newly diagnosed ovarian cancer patients with malignant pleural effusion (MPE), either primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) may be considered. The ability to achieve safe, complete cytoreduction—defined as no visible residual disease (R0)—is the critical factor in determining the initial treatment strategy. MPE is not a contraindication to PDS; rather, the decision should be based on a multidisciplinary team (MDT) assessment of the patient’s performance status and the resectability of the tumor burden. If the MDT estimates a high likelihood of achieving R0, PDS should be prioritized; if satisfactory cytoreduction is unlikely or the patient cannot tolerate surgery, NACT should be administered first (recommendation grade: Level 1).

7). Local treatment recommendations for ovarian cancer–associated malignant pleural effusion: The preferred approach is chest tube placement and indwelling pleural catheter drainage (IPC). When pleural effusion is difficult to control, intrapleural chemotherapy is often administered following drainage to inhibit the rapid accumulation of pleural fluid (Recommendation 11; Recommendation Level: Grade 2A). Next is pleurodesis; if pleurodesis fails, placement of a chest drainage tube is recommended (Recommendation 12; Recommendation Level: Grade 2B). Finally, hyperthermic intrathoracic chemotherapy (HITHOC) may be considered (Recommendation 15; Recommendation Level: Grade 3).

[Expert Commentary on Local Treatment Methods for MPE]

Since the Dutch van Driel team published the results of a phase III randomized controlled trial in the New England Journal of Medicine (NEJM, 2018; 378(3):230–40), hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) or interval cytoreductive surgery (ICS) has become an expert consensus for the treatment of peritoneal metastases from ovarian cancer.

Although there is currently no unified standard, expert consensus, or guideline for the clinical application of HITHOC, since Matsuzaki in Japan first reported the use of hyperthermic intrathoracic chemotherapy for treating malignant pleural effusion secondary to lung cancer metastasis in 1995 (Ann Thoracic Surg. 1995;59(1):127–31), the HITHOC technique has drawn on the principles and methods of HIPEC, has continued to evolve and improve, and has gradually become a common and effective treatment modality for malignant pleural mesothelioma, thymic tumor with pleural metastases, and pleural metastatic cancers arising from lung or ovarian cancer.

This “Consensus” represents the most recent expert consensus on the treatment of “ovarian cancer–associated malignant pleural effusion” issued by gynecologic oncology specialists. The Consensus cites the results of a multicenter clinical study reported by the team led by Professor Li-li Liu from the Department of Oncology at Tangdu Hospital, Air Force Medical University (formerly the Fourth Military Medical University) (Liu et al., Int J Hyperthermia, 2023; 40(1):2241689), which demonstrate that the objective response rate (ORR) of HITHOC in the treatment of MPE is significantly higher than that of conventional intrapleural chemotherapy (80.70% vs. 31.03%, p<0.001); it also references the findings of a meta-analysis (Zhou et al., Medicine [Baltimore], 2017; 96(1):e5532), which indicate that HITHOC can markedly prolong the median overall survival of patients with ovarian cancer–associated pleural metastases following cytoreductive surgery (meta-analysis, Hedges’ g = 0.763, p<0.001).

However, in this consensus document, HITHOC is assigned a recommendation grade of 3, indicating that there is substantial disagreement among expert opinions regardless of the level of evidence. In contrast, chest tube drainage (IPC) with or without intrapleural chemotherapy is recommended as the first-line treatment for managing pleural effusion (recommendation grade: 2A, based on high-level clinical research evidence with near-unanimous expert agreement, or low-level clinical research evidence with highly consistent expert opinion); secondly, pleurodesis is recommended (recommendation grade: 2B, based on low-level clinical research evidence with generally consistent expert opinion). This suggests that awareness of the clinical utility of HITHOC in the field of gynecologic oncology still needs to be enhanced.

Placing hope in the future:

1). Strengthen the promotion of the clinical value of HITHOC (benefits versus harms).

2). Initiate multi-center, randomized, controlled Phase III clinical trials in the relevant fields as soon as possible.

3) Promptly publish the “Standardization of HITHOC Clinical Application Methods,” along with expert consensus statements and clinical guidelines, jointly developed by specialists from relevant departments such as respiratory medicine, thoracic surgery, obstetrics and gynecology, and oncology, based on a unified understanding.
Expert Profile

Dr. Liu, M.D., Ph.D.
Professional Society Membership: American Society for Cell Biology (2006–present)
American Heart Association (2006–present)
American Thoracic Society (1997–present)
2023–2025.5 Associate Professor, Department of Cardiovascular Medicine, University of Miami, USA
1999–2023 Assistant/Associate Professor, Division of Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, USA
1996–1999 Postdoctoral Fellow, Department of Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, USA
1992–1995: Master of Medicine, Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University (under Professor Sun Bin)
1986–1992: Clinical Physician, Department of Respiratory Medicine, General Hospital of the Shenyang Military Region
1981–1986: Bachelor of Medicine, Department of Clinical Medicine, Fourth Military Medical University

Original text