Efficacy of pleurodesis for malignant pleural effusions in breast cancer patients

Patients

We retrieved data for 230 consecutive breast cancer patients who had been treated for MPE between 1997 and 2008 from the National Cancer Center Hospital (Tokyo, Japan) database. Inclusion in the study required: 1) documentation of MPE through a cytological examination of pleural fluid or through a pleural biopsy by video-assisted thoracic surgery (VATS); and 2) treatment with ST (i.e. chemotherapy or endocrine therapy). 24 patients who could not receive ST because of their condition due to disease progression and 26 patients who showed evidence of trapped lung were excluded. Trapped lung was defined as failed re-expansion of the lung after pleural fluid drainage, as confirmed by chest radiography. The remaining 180 patients had received ST or P-ST as an initial treatment for MPE. All clinical information was collected from the patients’ charts. Performance status (PS) was evaluated according to the criteria of the Eastern Cooperative Oncology Group [8]. The study was approved by the Institutional Review Board of the National Cancer Center Hospital (approval number 21-013).

Pleurodesis agents

The indication for pleurodesis was determined based on a review of the following factors by a medical oncology tumour board: degree of dyspnoea, including need for oxygen; MPE size; expected response rate to ST; expected survival; and the patient’s preference. The expected response rate to ST for breast cancer patients was estimated based on factors including: number of previous STs, response to previous ST (e.g. evaluation by the Response Evaluation Criteria in Solid Tumors and disease control interval), hormone status, and human epidermal growth factor receptor (HER)2 status. All the patients who received talc poudrage required pleural biopsy, and they underwent talc poudrage after VATS-assisted biopsy. Other patients underwent instillation of minocycline or OK-432. The decision to opt for instillation of either minocycline or OK-432 was made on the basis of the treating physician’s preference.

Patients received a pleural sclerosant (i.e. minocycline or OK-432) through a chest tube (18F–24F in size) that had been inserted under local anaesthesia. OK-432 is a purified preparation derived from Streptococcus pyogenes type A3 that contains 0.1 mg dried streptococci, which is equivalent to a dose of 1 Klinische Einheit (KE). OK-432 scleroses by promoting pleural fibrosis in the pleural cavity [9–11]. Intrapleural therapy was performed by instillation of either minocycline (7 mg·kg⁻¹, up to a maximum of 400 mg) or OK-432 (0.2 KE·kg⁻¹, up to a maximum of 10 KE) diluted in 100 mL saline. The tube was then clamped for 3 h. The decision to rotate the position of the patient was based on the treating physician’s preferences. Talc poudrage was performed by VATS under general anaesthesia and selective one-lung ventilation. Residual fluid was aspirated, loculi were divided when present, pleural biopsies were taken and lung re-expansion was confirmed. 5 g talc was insufflated. The chest tubes were removed when pleural effusion had decreased to ≤150 mL·day⁻¹.

Evaluation of response and size of MPE

Each patient underwent a pre-drainage, baseline chest radiograph. Sizes of MPE were classified into three groups on the basis of the initial chest radiographs: 1) small-to-moderate MPE was defined as occupying less than one-quarter of the hemithorax; 2) moderate-to-large was defined as occupying greater than one-quarter, but less than the entire hemithorax; and 3) massive was defined as those effusions occupying the entire hemithorax. All patients received a full drainage; that is, the P-ST group underwent drainage through a chest tube and the ST group underwent therapeutic thoracentesis. The treatment response of MPE to pleurodesis was evaluated according to the following criteria: 1) complete response was defined as long-term relief of symptoms related to the effusion, with absence of fluid re-accumulation on chest radiographs until death; 2) partial response was defined as diminution of dyspnoea related to the effusion with only partial re-accumulation of fluid (<50% of the initial radiographic evidence of fluid), with no further therapeutic thoracenteses required for the remainder of the patient’s life; and 3) lack of response was defined as lack of either a complete or partial response [4].

Statistical analysis

The frequencies and descriptive statistics of the demographic and clinical variables from the two groups were compared using t-tests and Fisher’s exact test. Pleural progression-free survival (PPFS) was defined as the time from ST in the ST group and from pleurodesis in the P-ST group to the first observation of pleural progression or to death resulting from any cause. The definition of pleural progression was the same as that for lack of response in that pleural progression occurred when neither a complete nor a partial response occurred. Progression-free survival (PFS) was defined as the time from ST in the ST group and from pleurodesis in the P-ST group to disease progression or to death due to any cause. Overall survival (OS) was defined as the time from ST in the ST group and from pleurodesis in the P-ST group to death due to any cause. PPFS, PFS and OS were estimated using the Kaplan–Meier method, and the survival curves were compared using the log-rank test. Multivariate Cox regression analysis was used to estimate the hazard ratio (HR), 95% confidence interval and effects of clinical variables. A two-sided p-value of <0.05 was considered to be statistically significant. All the analyses were performed using the SAS software program (version 9.1; SAS Institute Inc., Cary, NC, USA).