A Comprehensive Review of Spontaneous Pneumothorax Complicating Sarcoma

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A Comprehensive Review of Spontaneous Pneumothorax Complicating Sarcoma Jeffrey B. Hoag, MD, FCCP; Michael Sherman, MD; Quadeer Fasihuddin, MD; and Mark E. Lund, MD, FCCP

Background: Spontaneous pneumothorax (SPTX) is an uncommon phenomenon in the general population and is most commonly associated with prior bulbous emphysema, cystic parenchymal lung disease, and tuberculous lung disease. A rare cause of SPTX is malignant disease, either in the form of primary lung or pleural cancers, or in metastatic disease to the lungs. The purpose of this investigation was to compile patient characteristics, treatments received, and outcomes of patients with SPTX complicating sarcomatous cancer. Methods: Case reports and series published in the medical literature were identified through a MEDLINE search and compiled to determine similarities among patient characteristics, treatments received, and outcomes. Results: One hundred fifty-three cases representing 20 different sarcoma cell types were included; 126 (82.3%) had received some form of treatment prior to the development of pneumothorax, and 70 (45.7%) experienced recurrence of pneumothorax at an average of 61 (6 112) days. Patients had poor survival, with only seven of 81 subjects remaining alive 2 years after the initial diagnosis of SPTX. Conclusions: SPTX complicating sarcoma is associated with most cell types and is associated with increased mortality compared with patients without this complication. CHEST 2010; 138(3):510–518 Abbreviations: OR 5 odds ratio; SPTX 5 spontaneous pneumothorax

incidence of spontaneous pneumothorax (SPTX) Theis between five and 10 per 100,000 per year. 1

Primary SPTX occurs because of the rupture of subpleural blebs, whereas secondary SPTX refers to the development of pneumothorax due to the evolution of pulmonary pathology.1,2 Although secondary pneumothorax is most often associated with bulbous emphysema,1 other parenchymal lung diseases also

Manuscript received September 27, 2009; revision accepted March 20, 2010. Affiliations: From Drexel University College of Medicine (Drs Hoag, Sherman, Fasihuddin, and Lund); and the Cancer Treatment Centers of America, Eastern Regional Medical Center (Drs Hoag and Lund), Philadelphia, PA. Correspondence to: Jeffrey B. Hoag, MD, FCCP, Division of Pulmonary, Critical Care, and Sleep Medicine, Drexel University College of Medicine, 245 N 15th St, Mail Stop 107, NCB 12th Floor, Philadelphia, PA 19102; e-mail: JHoag@Drexel Med.edu © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.09-2292

lead to this complication. Malignancy involving the lung is one such disease process leading to secondary SPTX. Sarcoma represents a form of cancer originating from tissues of mesenchymal origin. The various tumor types are named for the type of tissue of origin according to the World Health Organization classification.3 The pooled incidence of sarcomas varies by type and is between 4.5 and 6.5 cases per 100,000 person-years in the general population.4 Sarcoma, when metastatic, most commonly leads to disease in the lungs, with . 20% of patients experiencing this complication.5 Complications of pulmonary spread of disease include symptomatic complaints, including cough, dyspnea, and chest pain. Other complications may include airway obstruction, hypoxemia with respiratory insufficiency, or SPTX. de Barrin6 was initially credited for the description of SPTX in a patient with metastatic cancer. Chemotherapeutic agents, including doxorubicin,7-9 have been implicated in case reports as a cause of

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SPTX during therapy of peripherally located tumors. In other reports, radiation therapy has been cited as a risk factor for SPTX in cancer,10 but the nature of this relationship is controversial. Necrosis of peripherally located pulmonary nodules in response to therapy is believed to be responsible. At this time, the peer-reviewed literature includes single-case reports and small case series describing this complication; however, a comprehensive analysis of symptoms, risk factors, complications, and treatments is lacking. The purpose of this investigation was to provide a comprehensive review of the published cases of SPTX in patients with sarcoma in an effort to describe patient characteristics, including primary sarcoma types, treatments received, rates of recurrence, and outcomes associated with the development of this complication. Materials and Methods To determine the factors associated with SPTX in sarcoma, an exhaustive search of the medical literature using MEDLINE was performed. Search terms included “pneumothorax,” “sarcoma,” and “cancer.” From this search, articles with patient descriptions that included age, type and location of sarcoma, descriptions of pneumothorax, treatment of sarcoma, and outcomes of pneumothoraces were analyzed. Subsequently, the reference list from each of these manuscripts was reviewed for cases that were not returned in the MEDLINE search. These articles were obtained through an Interlibrary Loan program, and they were included if adequate information was available. Data were extracted from each article (Table 1). Articles that included at least eight of the categories were included in the analysis. For those sections with missing data, percentages were based on the total number of included patients within that category. Statistical analysis for difference was performed using Student t test and x2 where appropriate, using the Statistical Package for Social Sciences, version 16.0 (SPSS Inc.; Chicago, IL). Bivariate logistic regression was performed for the evaluation of factors associated with (1) early mortality (within 1 month of presentation), and (2) recurrence of SPTX. P , .05 was considered statistically significant.

Results In total, 100 separate articles were included in the data compilation and analysis, with a total of 151 patients described.6-106 We included two patients from our own experience, for a total of 153 patients. Articles from 1937 through February 2008 were included in the analysis. Demographics and Patient Descriptions Overall, SPTX was more common in men, accounting for 65.8% of cases. There was a malesex predominance for all sarcoma cell types, except for leiomyosarcomas (men 2/7, 28.6%), which favored women, and Wilm tumor and rhabdomyosarcoma, www.chestpubs.org

which had an even distribution between men and women (Table 2) that mirrored the sex distribution of sarcoma in the general population. The patients described ranged in age from 1 to 86 years with a mean age of 30.6 (6 23.4) years, although the occurrence of the initial pneumothorax in these patients demonstrated a bimodal distribution similar to the distribution of sarcoma patients without pneumothorax. The first peak occurred in the second decade of life, with a smaller second peak in the seventh decade (Fig 1A). There was a definite influence of the type of sarcoma on the age of presentation of pneumothorax, as demonstrated in Figure 1B. SPTX in patients with bone tumors and rhabdomyosarcoma, as one would expect, were associated with younger age. Conversely, angiosarcoma (hemangioendothelioma), which is predominately seen in older individuals, was associated with initial pneumothorax in patients in their 70s. A total of 20 different cell types were reported in the literature as associated with SPTX in sarcoma (Table 3). The most commonly cited cell types were osteogenic sarcoma (n 5 48, 31.4%), angiosarcoma (hemangioendothelioma, n 5 28, 18.3%), and synovial cell sarcoma (n 5 13, 8.5%). The appearance of the initial chest radiograph was varied in these patients (Table 4). Multiple nodules (n 5 74, 48.4%) and cavitary or cystic lesions (n 5 39, 25.8%) were the most common radiographic findings, with pleural abnormalities seen in 18 (11.7%). Pneumothorax The majority of patients with secondary pneumothorax in sarcoma were symptomatic (n 5 126/153, 82.5%), and the most common symptoms included dyspnea (n 5 104, 82.7%), chest pain (n 5 45, 35.6%), cough (n 5 9, 6.7%), and hemoptysis (n 5 7, 5.8%). Unspecified pulmonary symptoms were reported in 26 patients (17.3%) with SPTX related to sarcoma. Twenty-two patients (15%) were asymptomatic and had pneumothoraces discovered by screening chest radiographs. Interestingly, SPTX was the initial presentation leading to the diagnosis of cancer in 24 patients (15.7%). Although a majority developed unilateral pneumothorax (n 5 87, 58.4%), a large proportion of patients had bilateral pneumothoraces (n 5 62, 41.6%) on initial presentation. Right-sided pneumothorax was more common (60.3%) than left-sided pneumothorax (39.7%). Recurrence of SPTX (n 5 58) was as common in patients with sarcoma as a single (n 5 56) episode (45.7% vs 44.1%, respectively), and 11 patients had persistent pneumothorax that was refractory to treatment. The incidence of recurrence was similar for each sarcoma cell type except for CHEST / 138 / 3 / SEPTEMBER, 2010

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1.68-103.57; P , .05), treatment of pneumothorax with chest tube (OR, 7.77; 95% CI, 2.56-23.6; P , .05) or CT surgical intervention (P , .03), and chest radiograph appearance of a cavitary (OR, 2.25; 95% CI, 1.03-4.95; P , .05) lesion. There was an 88.7% reduction in the odds of recurrent pneumothorax if patients were treated with a chest tube (OR for recurrent pneumothorax, 0.113; 95% CI, 0.04-0.36; P , .05) and an 87% reduction in odds of recurrent pneumothorax if the first pneumothorax was treated surgically (OR for recurrent pneumothorax, 0.13; 95% CI, 0.37-0.45; P , .05). By binary logistic regression, only pneumothorax management without a chest tube (OR, 7.0; 95% CI, 1.05-46.7; P , .05) and cavitary disease on chest radiograph (OR, 7.8; 95% CI, 0.95-64.3; P , .05) were significant predictors of recurrent pneumothorax.

Table 1—Variables Included in Analysis Age Gender Sarcoma type Smoking history Country of origin Symptoms of pneumothorax Location of primary tumor Treatment of primary cancer: Surgery Chemotherapy (specific agents) Radiation therapy (dose) Side of pneumothorax Recurrence of pneumothorax (timing) Relationship of diagnosis to pneumothorax (time) Treatment of pneumothorax: Aspiration Chest tube Pleurodesis Thoracic surgery Time to death from initial pneumothorax Radiographic appearance of lungs Suspected pathophysiology leading to pneumothorax

Treatment of Sarcoma

Ewing sarcoma, Wilm tumor, and rhabdomyosarcoma, which tended not to recur. The average time from initial pneumothorax to recurrence was just over 2 months (61.2 6 111.8 days) for the whole group, although there was a considerable variability (median 30, range 1-730 days) as demonstrated in Figure 2. Ewing, osteogenic, and angiosarcoma patients tended to have recurrence within the first month and earlier than other cell types. Smoking history was mentioned in only 15 (10%) of the reports. Of these reports, two of 15 patients had a positive history of smoking. Univariate analysis indicated that recurrent pneumothorax was associated with age (35.9 6 25.5 years vs 25.9 6 20.1 years for recurrent pneumothorax vs no recurrence, respectively, P , .01), location of primary tumor in the head and neck (odds ratio [OR], 2.89; 95% CI, 1.11-7.53; P , .05), presentation with pulmonary symptoms (OR, 3.03; 95% CI, 1.49-6.17; P , .05), prior treatment with chemotherapy (OR, 13.8; 95% CI,

Overall, the majority of patients (n 5 126, 82.3%) had some form of treatment of the primary sarcoma before the development of SPTX. Surgical resection of the primary tumor was performed in 47 patients (33%) with sarcoma before the development of SPTX. Radiation therapy was administered to 59 patients (42.4%) prior to the development of pneumothorax; however, only 10 of these patients (17%) received radiation to the thorax. All these subjects received radiation to the chest in the absence of concomitant chemotherapy. The average dose of radiation was 5,265 rads (62,981; median 6,000; range 1,300-13,000 rads). Chemotherapy was administered to 53 patients (38.1%) prior to the development of SPTX, whereas almost two-thirds of patients did not receive chemotherapy before they developed SPTX. Of patients treated with chemotherapy, the most commonly administered agents included doxorubicin (n 5 26, 49.1%), vincristine (n 5 19, 35.8%), cyclophosphamide (n 5 17, 32.1%), dactinomycin (n 5 14, 26.4%), and methotrexate (n 5 11, 20.8%). In 18 patients (34%) who received chemotherapy before

Table 2—Sex Predominance by Cell Type of Sarcoma Cases With Spontaneous Pneumothorax Male

Female

Cell Type

No.

%

Osteosarcoma Angiosarcoma Synovial sarcoma Ewing sarcoma Leiomyosarcoma Fibrosarcoma Wilm sarcoma Rhabdomyosarcoma Other sarcoma Total

33 20 10 7 2 6 4 4 12 98

70.2 71.4 76.9 70.0 22.2 66.7 50.0 50.0 70.6 65.8

No. 14 8 3 3 7 3 4 4 5 51

%

P Value

29.8 28.6 23.1 30.0 77.8 33.3 50.0 50.0 29.4 34.2

.001 .01 .01 .08 .02 .10 1.00 1.00 .02 .001

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Table 3—Cell Types of Sarcoma Cases and Percentage of Total Reported in Literature Cell Type Osteogenic sarcoma Angiosarcoma Synovial sarcoma Ewing sarcoma Leiomyosarcoma Fibrosarcoma Wilm tumor Rhabdomyosarcoma Sarcoma (unspecified) Lymphosarcoma

Figure 1. Distribution of age at presentation of spontaneous pneumothorax (SPTX) in sarcoma patients across all cell types (A). Mean age in years (6 SD) of initial pneumothorax in sarcoma patients based on sarcoma cell type (B).

the development of pneumothorax, “cytotoxic chemotherapy” was listed as the treatment; thus, differentiation of specific medications was not possible (Table 5). For those who received any cancer therapy before developing a SPTX, including chemotherapy, radiation therapy, or surgery, the median time from therapy to the development of pneumothorax was 90 days, although the range was huge (1 day to 16 years; mean 317 6 672 days). Patients receiving chemotherapy alone or in conjunction with surgery and/or radiation therapy developed pneumothorax earlier (Table 6). There was considerable variability by cell type within specific groups with regard to the time from therapy to the development of SPTX, and no trends were noted. Treatment of SPTX The majority of patients required treatment of pneumothorax, with 121 (78.9%) receiving at least one form of treatment, although in 24 of these reports, therapy for the pneumothorax was not specified. Of those receiving specific therapy for pneumothorax, chest tube placement was performed most commonly (n 5 71, 73.2%), followed by thoracic surgery (n 5 35, 36.1%), pleurodesis (n 5 21, 21.6%), and aspiration (n 5 13, 13.4%). Supportive care without direct intervention for pneumothorax, or conservative therapy, was used for 26 patients (21.1%). Specific treatment of the pneumothorax was necessary in virtually all patients with angiosarcoma and synovial sarcoma, whereas only two-thirds of patients with pneumothorax associated with Wilm tumor and fibrosarcoma required intervention. Because of the high rate of recurrence of SPTX overall, multiple modalities were used in many of these patients. www.chestpubs.org

%

Cell Type

%

31.4 18.3 8.5 6.5 5.9

Choriosarcoma Epithelioid sarcoma Fibrous histiocytoma Mesenchymoma Endometrial stromal sarcoma Liposarcoma Kaposi sarcoma Giant cell sarcoma Reticulosarcoma Pleomorphic sarcoma

2.0 1.3 0.7 0.7 0.7

5.9 5.2 5.2 2.6 2.0

0.7 0.7 0.7 0.7 0.7

Outcome of Patients Overall, the 50% mortality was between 4 and 5 months after SPTX; the 1-year mortality was 75% (n 5 133/153). Although not solely attributed to the SPTX, a significant percentage of patients died within the first 30 days of developing the pneumothorax. Figure 3 depicts the percentage of patients alive over the duration of follow-up. More than one-quarter of patients died within the first month (n 5 28/108, 25.9%), and by 2 years, only seven of 81 patients (8.6%) remained alive. Osteosarcoma (n 5 13/30) and angiosarcoma (n 5 11/23) had the lowest survival, with 3-month mortality rates post pneumothorax of 57.7% (n 5 17/30) and 52.2% (n 5 12/23), respectively. Univariate analysis indicated that early, 1-month mortality was associated with age (age 40.1 6 28.3 years vs 28.0 6 21.1 years for 1-month mortality vs survivors, respectively, P , .02) and presentation with pulmonary symptoms (OR, 7.54; 95% CI, 1.0-60.4; P , .05). There was an 82.6% reduction in the odds of dying in the first month in patients treated with chesttube drainage, compared with patients treated with observation or aspiration (OR for 1-month mortality, 0.174; 95% CI, 0.04-0.77; P , .05). Binary logistic regression showed that patients presenting with pulmonary symptoms (OR, 9.4; 95% CI, 1.1-18.6; P , .05) or pneumothorax treatment without a chest tube (OR, 7.8; 95% CI, 1.1-16.4; P , .05) were more likely to die within 1 month of pneumothorax. Table 4—Chest Radiograph Findings in Sarcoma Patients With Spontaneous Pneumothorax Radiographic Findings

No.

%

No visible lesion Multiple nodules (unilateral or bilateral) Cystic or cavitary nodules Pleural nodules, masses, thickening Lung or chest wall masses Bullae Infiltrates

7 62 33 15 7 2 1

5.5 48.4 25.8 11.7 5.5 2.3 0.8

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Figure 2. Time to recurrence of pneumothorax complicating sarcoma for all cell types.

Discussion SPTX is a devastating complication associated with sarcoma of virtually every cell type and, once present, it frequently recurs. SPTX is associated with poor outcome, because , 10% of reported patients lived more than 2 years after the initial pneumothorax diagnosis. The incidence of SPTX is difficult to ascertain from the literature reviewed, but several case series of specific cell types report a low prevalence overall. Kitagawa et al51 reported a series of 95 patients with angiosarcoma with only a single case of SPTX (1.05%). Moskovic et al107 described a case series of 76 patients with uterine sarcoma; two patients in this series developed SPTX (2.63%). D’Angio and Iannocone24 reported a prevalence of 1.94% of SPTX in a mixed series of sarcoma types in children. Coley et al108 reported a series of 91 patients with Ewing’s sarcoma, with a single case of SPTX. Approximately 50% of these patients had lung metastases. Bergin109 reported a 5% prevalence of SPTX in osteogenic sarcoma. Overall, from the case series reported in the literature, the prevalence of SPTX in sarcoma is 1.9%. Table 5—Chemotherapeutic Agents Administered Before the Development of Spontaneous Pneumothorax in Sarcoma Patients Chemotherapeutic Agent

No.

% Total Patients

% Receiving Chemotherapy

Doxorubicin Cyclophosphamide Vincristine Cytotoxic agent Dactinomycin Methotrexate Platinum Dacarbazine Bleomycin Vinblastine Ifosfamide Othera

26 20 19 18 14 11 7 7 6 4 3 11

17.0 13.1 12.4 11.8 9.2 7.2 4.6 4.6 3.9 2.6 2.0 7.4

49.1 37.6 35.8 34.0 26.4 20.8 13.2 13.2 11.3 7.5 5.7 20.9

aOther includes interleukin-2, melphalan, gemcitabine, a-interferon, hydroxyurea, 5-flourouracil, Bacillus Calmette-Guerin, and mitomycin C.

Although most patients with SPTX were symptomatic, almost one in seven patients had pneumothoraces indentified in the absence of symptoms with routine screening chest radiographs, and 60% (15/25) of these received treatment of pneumothorax. Moreover, a similar percentage of patients had SPTX as the initial manifestation leading to the diagnosis of sarcoma. Recurrence of SPTX is also common in patients with sarcoma-associated pneumothorax, with almost one-half of patients experiencing more than one pneumothorax. Patients presenting with cavitary disease on chest radiographs and patients presenting with a pneumothorax that required chest-tube management were at higher risk for recurrent pneumothoraces. It should be noted that the wide variability in timing of recurrence likely represents differences in cell types, patient ages, and treatments received. Patients with Ewing sarcoma, Wilm tumor, and rhabdomyosarcoma tended not to have recurrence, although these findings were not statistically significant. Several potential mechanisms have been postulated for the development of SPTX in patients with sarcoma. Many of these are related to the location of the tumor, characteristics of the tumor in the lung, treatments received for the sarcoma, and effects of the tumor on local physiology. Direct involvement of tumor within the pleura, or extension of cavitary tumor lesions into the pleural space, were cited most commonly as the mechanism leading to the development of SPTX. The use of chemotherapy has also been reported as a risk factor for the development of SPTX. Smevik and Klepp92 reported a relative risk of SPTX of 7% in his series, that increased to 14% after the introduction of chemotherapy in patients with osteogenic sarcoma. Rimondi et al110 reported five cases of osteogenic sarcoma that developed SPTX after receiving chemotherapy despite chest radiographs without evidence of pulmonary involvement. Our pooled data showed that one-half of the patients with SPTX associated with sarcoma received doxorubicin-based chemotherapy prior to the development of SPTX. However, this is not surprising given that many of the chemotherapeutic regimens used for treatment of sarcoma include this medication. Necrosis of peripherally located pulmonary or pleural lesions in response to chemotherapy is likely to be responsible for pneumothorax, as opposed to any direct toxicity of doxorubicin. Of note, the development of SPTX in sarcoma patients occurred in a significant number of subjects in the absence of treatment likely to affect the pulmonary parenchyma. Treatment of pneumothorax in patients with sarcoma included typical therapies for other causes of pneumothorax and ranged in invasiveness from supportive care to aspiration or chest tube placement to

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Table 6—Time From Treatment of Sarcoma to Development of Spontaneous Pneumothorax Sarcoma Treatment Chemotherapy Radiation Surgery Any

Mean

SD

Median

Range

224 275 459 317

370 413 1,125 672

90 75 221 65

0-2,170 0-2,190 0-5,840 0-5,840

Data are presented in days.

thoracic surgery interventions. Many of the patients reported required multiple modalities because of the severity of the symptoms or recurrence of SPTX. Our pooled data suggest that patients treated with chest tubes had a lower likelihood of recurrent pneumothorax and a lower likelihood of dying within a month of treatment than those treated more conservatively. Although this may be due to a pleurodesis effect of the chest tube protecting against recurrent pneumothorax, this finding may also be explained by the most severe patients electing to avoid aggressive care at the end of life. Outcomes of patients with sarcoma-associated pneumothorax are not good. From our review, survival rates at 1 year are about 20% depending on the particular cell type examined. When compared with existing data regarding outcomes of sarcoma patients with particular cell types, the outcomes of patients with SPTX were universally worse. Based on information from several collaborative sarcoma databases, the overall 5-year survival is widely variable, from 33% to 85%, depending on the particular cell type.45,111-113 When comparing with the outcomes of patients from this investigation, there is a dramatic decrease in longevity of patients with sarcoma-associated pneumothorax when compared with general population studies of specific cell types of sarcoma. It is

Figure 3. Outcomes of patients with SPTX by cell type after the development of SPTX. The points represent the proportion of reported subjects remaining alive. The connecting lines are included for visualization of downward trends. The thick line represents compiled data. See Figure 1 legend for expansion of abbreviation. www.chestpubs.org

difficult to ascertain from the present investigation if the decrease in survival was specifically related to the pneumothorax itself or, more likely, if the presence of pneumothorax represented a subset of patients with more aggressive or more advanced disease. Interestingly, patients experiencing pneumothorax as the presenting feature of sarcoma similarly had shortened survival compared with historic controls. Unfortunately, however, the data did not lend themselves to a direct comparison of patients with and without SPTX. This investigation suffers from several limitations, and thus the results should be interpreted and generalizations inferred with caution. First, the data collected were a compilation of case reports and case series published over nearly three-quarters of a century. Reports did not all include uniform presentations, treatments, and outcomes of patients, which made averaging and comparisons difficult. Moreover, the cell types were categorized according to the original source documents, possibly leading to misclassification of histologic type because criteria may have changed over the study period. Also, because the data included described particular cases, there was not a uniform comparison group to determine the direct effects of sarcoma-specific therapies with the development of SPTX. Moreover, the outcomes of many of the patients included were not followed for uniform durations or to death, making evaluation of mortality rates difficult. To fully appreciate the outcomes of patients with SPTX complicating sarcoma, a prospective database may be useful; however, because of the rarity of this complication, coordination of data collection from many centers would be required. Conclusions SPTX is an uncommon complication of sarcoma that is associated with frequent recurrence and increased mortality. Symptoms of dyspnea, chest pain, and cough should prompt evaluation for SPTX in patients with sarcoma. We report significant numbers of asymptomatic patients with SPTX; however, the usefulness of routine radiographic screening for asymptomatic patients has yet to be determined. Patients presenting with cavitary disease on chest radiograph and those presenting with a pneumothorax that required chest tube management were at higher risk for recurrent pneumothoraces and thus may warrant closer observation. We found decreased longevity in patients with SPTX complicating sarcoma, with a worse prognosis in those who were symptomatic and in those who did not have chest tube placement for management of their pneumothorax. The presence of this complication may herald more aggressive or advanced disease and may provide prognostic information. CHEST / 138 / 3 / SEPTEMBER, 2010

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Acknowledgments Author contributions: Dr Hoag: contributed to the study design, data collection, analysis, and writing. Dr Sherman: contributed to the study design, data analysis, and editing. Dr Fasihuddin: contributed to the data collection and reference checking. Dr Lund: contributed to the study design, data analysis, and editing. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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