Comparison of Survival Outcomes Based on Pre-treatment Pleural Effusion in Advanced Epithelial Ovarian Cancer

Patients and Methods

Patients. This study evaluated 313 patients diagnosed with primary epithelial ovarian cancer, tubal cancer, or peritoneal cancer after a permanent biopsy at the Kyungpook National University Chilgok Hospital (KNUCH) from February 2011 to February 2022. All medical records were collected from KNUCH and reviewed retrospectively.

Seventeen patients were excluded because they refused to complete chemotherapy after surgery. Twenty-two were excluded owing to insufficient follow-up data; some did not visit long enough to evaluate survival outcomes, and others were on chemotherapy. We included only stage IIIC and IVA according to FIGO guidelines to control the influence of tumor burden as much as possible (2). In all, 135 were excluded. Twenty-three were excluded as whole-body positron emission tomography/computed tomography (PET/CT) or chest CT scans before treatment were not available. Four patients were excluded because of unclear information with regard to chemotherapy. One was excluded because she received another round of chemotherapy owing to primary breast cancer during the follow-up period. Ultimately, 111 patients were included; however, some of them underwent pathological examination such as pleural fluid cytology or pleural biopsy to determine malignancy and the others did not. The flow diagram of the study is shown in Figure 1. The Institutional Review Board of the KNUCH approved of this study (KNUCH 2022-07-005).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1.

Flow diagram for patient selection. *¹Stage IVA was determined with whole-body PET/CT, chest CT, or cytology of pleural fluid; *²The patient received another chemotherapy in response to primary breast cancer after first-line treatment for epithelial ovarian cancer.

Diagnosis of pleural effusion and classification. To detect pleural effusions, we reviewed pre-treatment whole-body PET/CT, chest CT, or abdomen CT scans of all patients. If a pleural effusion could be observed on the abdominal CT, it was accepted as the presence of pleural effusion. If a patient who appeared not to have pleural effusion on her abdominal CT scan did not complete a chest CT scan, she was excluded. Stage IVA was determined when malignant pleural effusion was suspected based on the whole-body PET/CT or chest CT scans. Patients with pleural effusion, regardless of the amount of it or whether malignancy was suspected, were classified into the pleural effusion (PE) group, while the rest were classified into the no pleural effusion (NPE) group.

Surgery. Surgeries were performed by four experienced gynecologic oncologists at the KNUCH. Optimal surgery included total hysterectomy, bilateral salpingo-oophorectomy, lymphadenectomy from both pelvic sides to the infra-renal level, omentectomy, and resection of other metastatic lesions. We evaluated surgery as suboptimal when a residual tumor lesion was larger than 1 cm or if the surgeon did not perform any of the aforementioned surgeries (12).

Chemotherapy. Some patients were chosen to receive neoadjuvant chemotherapy (NAC) prior to debulking surgery depending on their medical condition. All patients in this study underwent at least four cycles of chemotherapy (13). They were administered a combination of taxane and carboplatin; the dose of taxane was 175 mg/m², and AUC5 was used to determine the dose of carboplatin. The delivered dose intensity (DDI), relative dose intensity (RDI), and duration over the course of treatment were reviewed in every patient. DDI is defined as the sum of the total ratio of chemotherapy agents administered over the course of therapy, including neoadjuvant and/or adjuvant. RDI is the ratio of the DDI divided by the planned dose intensity, 100% per cycle. The delay is defined as the number of days beyond the planned duration, i.e., 21 days between two cycles.

Additional treatment. To evaluate the influence of additional treatments such as hyperthermic intraperitoneal chemotherapy (HIPEC), bevacizumab, poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and pembrolizumab, we reviewed and analyzed the number of patients who received those treatments. The HIPEC group included patients who underwent HIPEC during the first operation. The bevacizumab-administered group included patients who used it either during first-line adjuvant chemotherapy or neoadjuvant chemotherapy. Patients who used PARP inhibitors or pembrolizumab for at least one month were included in the PARP inhibitor or pembrolizumab-administered group.

Evaluation of prognostic outcomes. Response to treatment was evaluated using either CT, magnetic resonance imaging (MRI), or PET/CT and evaluated as complete or partial resolution, stable disease, progressive disease (PD), or disease recurrence (14). Platinum resistance was defined when the PD or recurrence was confirmed within 6 months after the last administration of platinum-based chemotherapy (15). Overall survival (OS) and progression-free survival (PFS) were calculated from the first day of chemotherapy for patients who underwent neoadjuvant chemotherapy and interval debulking surgery; in primary debulking surgery (PDS), these values were calculated beginning from the operation day.

Statistical analysis. The Student’s t-test, Chi-squared test, and Fisher’s exact test were used to compare clinical factors and outcomes in both groups. A Kaplan–Meier survival analysis and a Cox regression were used to evaluate survival outcomes such as overall survival, progression-free survival, and hazard ratio (HR). All statistical analyses were performed using SPSS (version 26; IBM Corp., Armonk, NY, USA) and MedCalc (version 20.026; MedCalc Software Ltd., Ostend, Belgium).