Optimizing the study of tunneled intrapleural catheters for malignant pleural effusions

Abstract

The optimal therapy for malignant pleural effusions is relatively understudied considering half of patients with cancer develop them during their life span, yielding an annual US/European incidence of 750,000 cases. 1,2 The challenges studying this disease are numerous and discussed later in this article. Attempting to accelerate pleurodesis by a variety of sclerosis agents was the classic approach and remains popular today. Maintaining lung expansion by a tunneled intrapleural catheter (TIC) so that a pleurodesis could occur naturally began in approximately 1986 with the off-label use of a chemotherapy therapy infusion port and then a peritoneal dialysis catheter in 1994, which was modified to an intended-use device by adding a 1-way valve and popularized by Putnam and colleagues. 3 Interest in this technology has grown steadily and is preferred at many cancer centers because of the avoidance of inpatient hospitalization, as described in the AMPLE study by Thomas and colleagues. 4 Before discussing AMPLE, it is important to review briefly the relevant thoracic surgical contributions to cooperative group science that led up to the current study. In the early 1990s, visionary leaders at the Cancer and Leukemia Group B (CALGB) supported introduction of a National Institutes of Health U10 grant organized by Dr David Sugarbaker to both increase the ability of surgical oncologists to participate in clinical trials and enable study of then newly coined ''video-assisted thoracic surgery'' (VATS, now ''thoracoscopic surgery''). 5 CALGB 9334, which compared chest tube talc slurry with VATS poudrage for malignant pleural effusions, successfully accrued 501 randomized patients, the largest for the lung disease site. 6 The success of the then relatively novel accrual-based capitated model with payments made directly to its many participating surgeons did not go unnoticed and contributed to disrupting the traditional medical oncology-based cooperative group resource allocations.CALGB 9334 demonstrated equivalence between bedside talc slurry and VATS pleurodesis, and because there were more pneumonias for those who underwent a general anesthetic, the former became more popular. 6 However, surgeons today still will opt for a thoracoscopic approach to pleurodesis because of the option to free lung, more precisely apply sclerosant, and obtain tissue for diagnostic studies.There was naturally an interest in capitalizing on the success of 9334 because the infrastructure for accruing these patients was still in place. Comparing the then only TIC (PleurX, BD, Franklin Lakes, NJ) with the less-invasive talc slurry arm of 9334 seemed like an obvious choice, and CALGB 30102 was born. 7 In addition to Putnam and colleagues' randomized study, 3 experience was growing with the use of TIC, and single-institution reports compared its use with talc pleurodesis and suggested benefit for those with trapped lungs. 8,9 Supporting articles are described in comprehensive reviews and in the Appendix E1. 10 Unfortunately, CALGB 30102 failed to accrue...

Not all malignant pleural effusions are created equal

“…1,2 Such might be the initial response to a call for more careful study of this topic. 3 Given the high annual incidence of MPEs, studies focusing on their management are plentiful in the recent literature. Such studies pit talc pleurodesis against tunneled indwelling pleural catheters.…”

“…We are awaiting the results of newer randomized, controlled trials that have completed enrollment to determine whether these patients were captured. 4,5 In this issue of the Journal, Demmy 3 contends that not all MPEs are alike. He says that by clumping together various malignancies and degrees of trapped lung to facilitate recruitment, we inadvertently dull a study's ability to detect therapeutic nuances.…”

“…Demmy 3 provides a synopsis of trials that guide how we manage MPEs today, and expertly highlights the pending questions in the literature. Several of the randomized, controlled trials in this area had challenges with enrollment, and-perhaps as a result of clumping-they did not detect significant differences between the treatment arms.…”

“…The management of MPEs may not be a very controversial topic on its surface, but the aphorism still holds: the devil is in the details.of the study design. 3 Perhaps we should heed Demmy's call for a new detailed prospective registry that will help us design more meaningful trials.…”

Awakenings: From empiricism to an evidence-based management of malignant pleural effusions

“…The contribution in this issue of the Journal provided by Demmy 1 is particularly interesting because it suggests, among others, at least 3 considerations relevant to the current management of malignant pleural effusions that may foster new ideas. First, Demmy 1 emphasizes the results of the CALGB (Cancer and Leukemia Group B) 9334 trial, demonstrating a substantial equipoise between talc slurry and video-assisted thoracoscopic surgery (VATS) in effecting pleurodesis as well as an increased incidence of pneumonia in the thoracoscopic arm.…”