Clinical Outcomes and Health-Related Quality of Life after Thoracoscopic Talc Pleurodesis

Abstract

Objectives:

Thoracoscopic pleurodesis is a safe and effective method of palliative care for patients suffering from malignant pleural effusion. Health-related quality of life (QOL) is an important factor in palliative therapy; however, we are not aware of any studies that have examined the QOL of patients following thoracoscopic pleurodesis.

Methods:

A total of 123 patients underwent thoracoscopic pleurodesis between January 2006 and February 2009. A total of 45 patients agreed to take part at the QOL assessment and were enrolled in our prospective study. In addition to clinical outcome, the patients' QOL data were assessed prior to thoracoscopic pleurodesis and for 12 months after surgery using the European Organization for Research and Treatment of Cancer (EORTC) QLQ C-30 questionnaire. We compared the patients' QOL scores at each time point with their preoperative scores and analyzed these data relative to the scores of a healthy age-matched population.

Results

: Due to the advanced clinical status of the patients in our study, the overall median survival time was 7.5 months versus 10.2 months for patients' QOL data. Following discharge from the hospital, most functional scales (with exception of emotional function, p=0.035) did not significantly differ from preoperative scores. Throughout the study period, patients experienced statistically and clinically significant improvements in functional scales. Global health values increased after surgery throughout the entire study period. There was a clear decline in dyspnea upon discharge, followed by a continuous remote increase throughout the subsequent months. QOL of the study population remained lower than that of the healthy cohort.

Conclusions:

Our data are consistent with clinical findings that pleurodesis decreases respiratory symptoms, but does not alleviate impairments in the patient's general condition.

Introduction

Malignant pleural effusion primarily affects patients with clinical advanced and disseminated neoplastic diseases. The median survival of patients with malignant pleural effusion after diagnosis ranges from 2.5 to 12 months.^1,2 Dyspnea and reduced physical capability can severely affect the quality of life (QOL) of these patients. Thoracoscopic talc pleurodesis is an effective and safe method of chemical pleurodesis.^3,4 The success of pleurodesis, in terms of postoperative morbidity and mortality, and recurrence rates of the pleural effusion, has been assessed in several studies. Secondary to clinical outcome, health-related QOL after pleurodesis is of primary interest to clinicians as well as patients receiving palliative care. To our knowledge, no study has examined the QOL of patients following thoracoscopic talc pleurodesis.

Thus, we performed a prospective, longitudinal outcome study to assess the QOL of patients with malignant pleural effusion prior to surgery and for up to 12 months after thoracoscopic pleurodesis. The QOL levels were assessed using the QLQ C-30 questionnaire developed by the European Organization for Research and Treatment of Cancer (EORTC). In addition, morbidity, mortality, and survival times were analyzed.

Materials and Methods

Patient populations and surgical procedures

This prospective study evaluated the clinical outcomes and QOL scores of patients suffering from malignant pleural effusion who underwent thoracoscopic talc pleurodesis between January 2006 and February 2009 at the Department of General and Thoracic Surgery of the University Hospital of Schleswig Holstein, Campus Kiel. The indications for a talc pleurodesis were recurrent pleural effusion after at least one pleuracentisis with full reexpansion of the lung. No bedside pleurodesis or catheters such as Pleurex^® (CareFusion Corp., San Diego, CA) were inserted beforehand. Patients who received bilateral talc pleurodesis as a treatment for bilateral pleural effusions were counted twice when discharged and readmitted for pleurodesis on the second lung. During the study period, thoracoscopic talc pleurodesis was performed 135 times on 123 patients. All patients were asked on admission to participate in the QOL assessment and 45 patients agreed. Informed consent was obtained from each patient prior to participation, and the study protocol was approved by the institutional ethics committee. We assessed QOL, clinical outcome, and survival before and after surgery. Pleurodesis was performed as a thoracoscopic procedure using 4 g of talcum powder after evacuation of the remaining pleural effusion and reexpansion of the lung. Postoperative complications were noted prospectively. “Major complications” were defined as death in the hospital, atelectasis following intervention, respiratory distress syndrome, long-term respiratory therapy, or other complications that extended the hospital stay by more than 14 days after the operation. Minor complications were defined as postoperative pneumothorax, pleural effusion without intervention, pneumonia, prolonged parenchyma fistula, and other complications.

Assessment of health-related quality of life

Health-related QOL was assessed using a cancer-specific, 30-item core questionnaire (QLQ-C30) developed by the EORTC. In total, 45 of the 123 patients completed at least one questionnaire. Patients were only counted once even when two operations were performed. The EORTC QLQ-C30 includes five functional scales (i.e., physical, role, cognitive, emotional, and social), four symptom-related scales (i.e., fatigue, pain, nausea, and vomiting), one scale to assess global health and general QOL, several questions regarding symptoms that are commonly reported by patients with cancer (e.g., dyspnea, loss of appetite, insomnia, constipation, and diarrhea), and additional questions regarding the perceived financial impact of the disease.⁵ Response categories for most questions spanned four levels, ranging from “not at all” to “very much.” Response categories for questions regarding general physical condition and overall QOL spanned seven levels, ranging from “very poor” to “excellent.” In general, high scores reflected high response levels. The EORTC QLQ is modular in design, with the core questionnaire (C30) accompanied by additional disease- or treatment-specific sections.

Questionnaires were distributed to patients before surgery to obtain baseline values, before discharge from the hospital, and at various intervals after surgery (i.e., 3, 6, and 12 months). A total of 45 patients completed at least one questionnaire; thus, a cross-sectional analysis was conducted to compare patients who provided QOL data before surgery with those who provided QOL data following surgery.

Statistical analyses

Data were analyzed using GraphPad Prism for Windows, version 4.0 (GraphPad Software, Inc., La Jolla, CA). Distributions and frequencies of medical data were compared using the χ² test. The EORTC QLQ-C30 core questionnaire was scored according to the EORTC-QLQ-C30 scoring manual,⁶ and raw scores were linearly transformed to yield a range of 0 to 100. Scales were calculated if at least half of the items had been completed by the patient. The QOL data were analyzed using nonparametric methods because the data were not normally distributed. However, as reference values were available only as mean scores, data were also plotted as means with standard error of mean. The different time points were compared using QOL analyses via the Wilcoxon signed-rank test. Survival curves were calculated according to the Kaplan-Meier method. Global p values lower than 0.05 were considered statistically significant, and mean differences of at least 10 points on the QOL scales were considered clinically relevant.⁷

Results

Descriptions of all patients and their underlying malignancies are shown in Table 1. Procedures were predominantly performed on patients with secondary pleural malignancy. The majority of the patients suffered from pleural effusion due to breast cancer (42 patients, 34.1%), followed by lung cancer (24 patients, 19.5%). Primary pleural malignancy (i.e., pleuralmesothelioma) was the underlying cause of pleural effusion in 13 patients (10.6%). Postoperative complications are listed in Table 2. The response rate of the QOL questionnaires is listed in Table 3.

Table 1.

Patient Characteristics

Variables	Total (n=123)	Median survival (month)	With QOL (n=45)	Median survival (month)
Male/Female	38/85		18/27
Mean age, years (SD)	65.39 (10.64)		61.26 (9.58)
Mean time in hospital, days	9.39		8.49
Primary pleural malignancy
Pleural mesothelioma	13 (10.5)	18.85	4 (8.8)	15.77
Secondary pleural malignancy
Breast cancer	51 (41.5)	7.58	18 (40)	9.3
Lung cancer	27 (22.0)	7.64	15 (33.3)	10.16
Gastrointestinal cancer	10 (8.1)	4.69	2 (4.4)	4.89
Ovarian cancer	6 (4.9)	6.72	2 (4.4)	11.75
CUP	6 (4.9)	13.03	0	0
Others	10 (8.1)	3.84	4 (8.8)	12.84

CUP, cancer of unknown primary; QOL, quality of life; SD, standard deviation.

Table 2.

Rates of Morbidity after Pleurodesis

	Total (n=135)	With QOL (n=45)	Without QOL (n=90)
Pleural effusion (%)	4 (2.9)	2 (4.4)	2 (2.2)
Prolonged parenchyma fistula (%)	1 (0.7)	0	1 (1.1)
Acute pulmonary distress	1 (0.7)	0	1 (1.1)
Pneumonia (%)	6 (4.3)	2 (4.4)	4 (4.4)
Dystelectasis (%)	7 (5.0)	0	7 (7.7)
Long-term respiratory therapy (%)	1 (0.7)	0	1 (1.1)
Cardial complication (%)	4 (2.9)	1 (2.2)	4 (4.4)
Pneumothorax (%)	10 (7.2)	4 (8.8)	10 (11.1)
Death in hospital (%)	5 (3.6)	2 (4.4)	3 (3.3)
Minor complications (%)	25 (17.9)	7 (15.5)	18 (20)
Major complications (%)	20 (14.4)	4 (8.8)	16 (17.8)
No complications (%)	83 (59.7)	34 (75.6)	49 (54.4)

Table 3.

Response Rates (i.e., QOL Questionnaire Return Rates) for All Patients (n=45) Who Underwent Thoracoscopic Pleurodeses

Time of assessment	Compliance (%)
Preoperative	40 of 45 (88.8)
At discharge	19 of 43 (44.1)
3 Months after surgery	21 of 33 (63.6)
6 Months after surgery	17 of 27 (62.9)
12 Months after surgery	8 of 16 (50.0)

Survival

During the 3-year study period, 95 of the 123 patients died. The overall median survival time was 7.54 months (Fig. 1A). Patients who were enrolled in the assessment of QOL data showed a median survival time of 10.2 month (Fig. 1B). Survival proportions depending of the underlying malignancy are shown in Table 1.

FIG. 1.

Kaplan-Meier survival analysis of patients who underwent thoracoscopic talc pleurodesis. (A) overall; (B) patients with QOL assessment.

Overall QOL

The core questionnaire consisted of numerous multi-item scales and single-item measures, including five functional scales, three symptom scales, a global health status/QOL scale, and six single items. Each of the multi-item scales includes a different set of items so that no item existed in more than one scale. The results of selected scales are shown in Figures 2, 3, and 4. Due to the median survival time of 6 months, the QOL analysis was only performed up to 12 months after the procedure. To allow comparison with a healthy cohort, reference QOL values from a previous analysis of an age-matched healthy German population⁸ are shown in the graphs.

FIG. 2.

QOL analysis (n=45), with regards to (A) physical function, (B) role function, (C) social function, and (D) emotional function before surgery, at the time of discharge, and 3, 6, and12 months after surgery. The p values refer to the differences in QOL levels at baseline (preoperatively) and at various postoperative time points. Symbols: *, p value<0.05.

FIG. 3.

QOL analysis (n=45), with regards to global health before surgery, at the time of discharge and 3, 6, and 12 months after surgery. The p values refer to the differences of QOL levels at baseline (preoperatively) and at various postoperative time points. Symbols: *, p value<0.05.

FIG. 4.

QOL analysis (n=45), with regards to dyspnea and before surgery, at the time of discharge, and 3, 6, and 12 months after surgery. The p values refer to the differences of QOL levels at baseline (preoperatively) and various postoperative time points. Symbols: *, p value<0.05.

After discharge from the hospital, there were no statistically significant differences in functional scales (with the exception of emotional function p=0.035) compared with preoperative baseline values (Fig. 2A–D). Slight increases in functional scales were observed for as long as 12 months after surgery. Functional scores at each time point (i.e., 3, 6, and 12 months) were not significantly different than baseline (pre-operative) scores (with the exception of emotional function at 3 months, p=0.031). However, a mean difference of more than 10 points was noted for physical function at 12 months (Fig. 2A), role function at 12 months (Fig. 2B), social function at 6 months (Fig. 2C), and emotional function at 6 and 12 months (Fig. 2D), indicating clinically significant improvements.⁷

Global health values increased throughout the study period. Relative to baseline values, a statistically significant increase was observed 3 months after the procedure (p=0.013) (Fig. 3). Similar to the results of the functional scales, clinically significant results (i.e., a mean difference of more than 10 points) were detected at 6 and 12 months after the procedure. The study population failed to reach the QOL scores exhibited by a healthy cohort, as shown in the graphs.⁸

Patients experienced a significant decrease in respiratory symptom-related scores upon discharge compared with preoperative scores (Fig. 4). In particular, dyspnea symptom scores declined significantly upon discharge then slightly but steadily increased over the following months. There was a statistically significant decrease in dyspnea score upon discharge (p=0.003) and at 3 months (p=0.048), compared with baseline values. There were no statistically significant or clinically relevant changes in fatigue or pain throughout the study period (Fig. 5A and 5B).

FIG. 5.

QOL analysis (n=45), with regards to (A) pain and (B) fatigue before surgery, at the time of discharge, and 3, 6, and 12 months after surgery. The p values refer to the differences of QOL levels at baseline (preoperatively) and at various postoperative time points. Symbols: *, p value<0.05.

Discussion

Over the past few decades, several studies have investigated the best treatment for recurrent malignant pleural effusion in a palliative care setting.⁹,¹⁰,⁴,¹¹ Most research has focused on identifying the best chemical or biological agent and the best method of pleurodesis. Most recent studies, such as the 2006 study by Tan et al., are small and heterogeneous with few significant results. Tan et al. did not find any conclusive evidence to support the use of any particular sclerosant, and concluded that talcum powder is currently the favored chemical sclerosant.¹¹ The preferred method of applying talc (i.e., thoracoscopic or as slurry) also remains controversial,¹⁰,¹² Studies by our group and others showed that video assisted thoracic surgery (VATS) talc pleurodesis is an effective treatment for malignant pleural effusion and is associated with a low rate of recurrence.¹³ In his review, Tan et al. described a Cochrane review,⁴ which noted that a strong recommendation for thoracoscopic pleurodesis rather than a talc slurry cannot be made, even though thoracoscopic talc insufflation is associated with a lower rate of recurrence, owing to the scarcity of scientific studies on this topic. The side effects and complication rates of thoracoscopic talc pleurodesis in our study are consistent with those described in previous studies. There were five hospital deaths due to progression of the primary malignancy, cardiopulmonary failure in four cases, and acute renal failure in one case. None of the deaths seemed directly related to the use of talcum powder, in terms of the acute respiratory distress syndrome described in the literature.^3,14

Additional QOL studies would contribute important information to the ongoing debate about the best methods of palliative care. A review of the literature uncovered only one report of health-related QOL in patients who underwent pleurodesis. Dresler et al. performed a phase III intergroup study of talc poudrage versus talc slurry, and assessed changes in QOL after 30 days using the EORTC QLQ-C30 questionnaire. The two groups were not statistically different, with the exception of “fatigue.” Neither the actual QOL scores nor the baseline values were reported, preventing further evaluation and comparison of these data.¹⁰ To our knowledge, the present study is the first prospective study to examine changes in the QOL of patients before and for up to 12 months after thoracoscopic talc pleurodesis. The median survival rate was consistent with previous reports.^9,13 The respiratory-associated QOL decreased significantly after pleurodesis. Patients showed statistically significant lower scores for “dyspnea” at the time of discharge and 3 months after the procedure, compared with baseline preoperative levels. Symptoms such as pain and fatigue were not statistically or clinically different during the study period. Variations in physical function, role function, and social function did not significantly differ from baseline values; however, the mean values differed by more than 10 points, suggesting a clinically relevant increase in these QOL variables.⁷ Though the scores for “dyspnea” increase slightly over the study period the functional scales and global health increases slightly, too. This could reflect a so-called response shift, wherein patients adapt their standards and perceptions relative to their expectations and rate their personal situations better than would otherwise be expected, based on the parameters of QOL measurement.¹⁵ In comparison with the results of a healthy age-matched German cohort, patients showed significant higher scores (worse symptoms) at each time point with regards to the symptom scales, and lower scores for the functional scales (indicating impaired function).

Our findings are consistent with clinical findings that pleurodesis decreases respiratory symptoms but does not improve the patient's general condition.

The present study has some methodological limitations. Namely, we were unable to perform multivariate analysis owing to the comparatively small cohort size. Patients were free to choose to take part in the study, so it could not be ruled out that patients in better clinical condition were more likely to take part in this study. In addition, our use of an incomplete dataset introduces the possibility that our study population may not reflect the entire cohort of patients with malignant effusions. Incomplete data (due to death or disease progression) may have biased the results of this study and overemphasized the positive effects of treatment. In summary, our findings indicate that patients who undergo thoracoscopic pleurodesis for recurrent malignant effusion experience an improvement in respiratory symptoms that persists for as long as 3 months after surgery. Due to the progression of the underlying malignancy, this improvement decreases over time. In our opinion the option of a palliative thoracoscopic pleurodeses in patients with recurrent malignant effusion should be discussed early with patients. Our QOL data encourage the positive clinical effect and could be helpful in counseling patients.

Footnotes

Acknowledgments

Tobias Rose: data collection, manuscript preparation; Bodo Schniewind: statistical analysis of clinical data; Nikolas Woltmann: clinical data collection; Jessica Walter: clinical data collection; Peter Dohrmann: manuscript preparation; Thomas Küchler: QoL data collection and analysis; Roland Kurdow: manuscript preparation, data collection. The authors BS and TR contributed equally to this work.

Author Disclosure Statement

No competing financial interests exist.

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