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Thoracic Oncology
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Clinicopathologic Characteristics of Malignant Mesotheliomas Arising in Patients With a History of Radiation for Hodgkin and Non-Hodgkin Lymphoma
Abstract
Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established.
We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival.
We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P < .001), age ≤ 65 years (P = .005), cytoreductive surgery (P < .001), and epithelioid histology (P < .001).
Pleural diffuse malignant mesothelioma (PDMM) is a highly aggressive tumor increasing in incidence throughout most of the world that was expected to reach a peak in the United States in 2010.1–5 Although the majority of cases of PDMM are attributable to asbestos, other causes have been identified, including man-made fibers and chemicals.6,7 Mesothelioma is a known complication of therapeutic radiation for lymphoma, breast cancer, lung cancer, and other malignancies.8–11 Patients with Hodgkin lymphoma have a 20-fold increased risk of mesothelioma after radiotherapy.12 Typically, this occurs as a late complication after a latency period of approximately 20 years after irradiation.13 Several recent studies have reported an association between malignant mesothelioma and chest radiation for Hodgkin lymphoma.9,12,13 However, the clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established.
In this study, we evaluated a large series of consecutive patients diagnosed with PDMM at a single institution and identified patients who had a prior history of radiation to the chest for lymphoma. We determined the clinicopathologic characteristics, including the histologies identified in the resection specimens of patients with lymphoma-associated mesotheliomas, and correlated the findings with overall survival.
The study group includes 1,618 consecutive patients with PDMM who were diagnosed between July 1993 and February 2008 at Brigham and Women's Hospital in Boston, Massachusetts. The group was identified through a search of the Division of Thoracic Surgery Registry database, which includes location and histologic type of the primary tumor, along with patient demographic data. We identified patients who were diagnosed with PDMM who also had a reported history of therapeutic radiation for both Hodgkin and non-Hodgkin lymphoma. The study was approved by the institutional review board.
The hematoxylin and eosin–stained slides of lymphoma-associated PDMM were reviewed by two pathologists (J.A.B. and L.R.C.), and tumors were classified into epithelioid, sarcomatoid, and biphasic types according to WHO criteria.7 We reviewed an average of 13 hematoxylin and eosin slides (range, two to 32 slides) from each tumor and recorded the presence of rhabdoid, clear cell, signet ring cell, and myxoid histologies, as well as pleomorphism, necrosis, and mitoses. When tumor tissue was available, the number and type of cytogenetic and molecular alterations were investigated as part of the initial work-up of malignant mesotheliomas. The pathology reports of the biopsy samples and resection specimens from all patients included in the study were reviewed to record the histologic type of each case of malignant mesothelioma at the time of diagnosis.
Asbestos body counts were performed as part of the pathologic assessment of mesotheliomas in the Department of Pathology. Methodology used has been previously described.14 An additional 15 samples from lung specimens from totally separate patients without a history of PDMM or lymphoma were used as the unexposed control group as reference for asbestos body count.
χ2 or unpaired t tests were used to compare categorical data. Overall survival was calculated from time of surgery to time of death from any cause or to time of last follow-up, at which point the data were censored. Overall survival curves were constructed using the Kaplan-Meier method, and the log-rank test was used to evaluate the statistical significance of differences.
The prognostic significance of clinical and pathologic characteristics was determined using univariate Cox regression analysis. Cox proportional hazards models were fitted for multivariate analysis. After interactions between variables were examined, a backward stepwise procedure was used to derive the best-fitting model.
Statistical analysis was performed using GraphPad InStat (version 3.10 for Windows 95; GraphPad Software, San Diego, CA, www.graphpad.com) and Systat (version 13.1 for Windows; Systat, Chicago, IL). Kaplan-Meier survival curves were drawn with GraphPad Prism (version 6.02 for Windows; GraphPad Software).
Patient characteristics are listed in Table 1. Among the entire cohort of patients with PDMM, there were 1,282 men and 336 women. The median age was 64 years (range, 17 to 93 years). Of the 1,596 patients, 659 (41%) had left-sided disease and 937 (59%) had right-sided disease. The majority of patients (n = 990; 61%) had epithelioid mesothelioma, 507 patients (31%) had biphasic mesothelioma, and 121 patients (8%) had sarcomatoid mesothelioma. After the initial biopsy, 80% of patients underwent complete macroscopic cytoreductive surgery (extrapleural pneumonectomy or pleurectomy/decortication), and 20% of patients underwent only biopsy or debulking (Table 1). Patients with lymphoma-associated PDMM were treated with similar surgical modalities as patients with asbestos-associated PDMM (P = .77).
|
| Demographic or Clinical Characteristic | Lymphoma-Associated PDMM (n = 22) | Asbestos-Associated PDMM (n = 1,596) | P | ||
|---|---|---|---|---|---|
| No. of Patients | % | No. of Patients | % | ||
| Sex | .82 | ||||
| Female | 5 | 22.7 | 331 | 20.7 | |
| Male | 17 | 77.93 | 1,265 | 79.3 | |
| Age, years | < .001 | ||||
| Mean | 46.7 | 63.3 | |||
| Median | 45 | 64 | |||
| Range | 27-79 | 17-93 | |||
| Asbestos bodies,* bodies/g | < .001 | ||||
| Mean | 21 | 5,850 | |||
| Median | 15 | 325 | |||
| Range | 0-56 | 0-1,400,000 | |||
| Histology | .21 | ||||
| Epithelioid | 17 | 77.3 | 973 | 60.9 | |
| Biphasic | 5 | 22.7 | 502 | 31.5 | |
| Sarcomatoid | 0 | 0 | 121 | 7.6 | |
| Primary location† | .44 | ||||
| Left pleura | 12 | 54.5 | 646 | 41.0 | |
| Right pleura | 10 | 45.5 | 927 | 58.9 | |
| Surgery‡ | .71 | ||||
| Complete macroscopic cytoreduction | 13 | 76.5 | 884 | 80.1 | |
| Incomplete resection | 4 | 23.5 | 219 | 19.9 | |
Abbreviation: PDMM, pleural diffuse malignant mesothelioma.
*Asbestos body count was available in six patients with lymphoma-associated PDMM and 476 patients with asbestos-associated PDMM.
†Twenty-two patients in the asbestos-associated PDMM group did not have primary location information available.
‡Data available in 1,120 patients.
Characteristics of patients with lymphoma-associated PDMM are listed in Table 1 and detailed in Appendix Table A1 (online only). All of these patients received radiation therapy for either Hodgkin lymphoma (n = 20) or non-Hodgkin lymphoma (n = 2), at a median age of 20 years (mean, 25.3 years; range, 7 to 72 years), and developed PDMM after a mean latency period of 21 years (range, 2 to 43 years; Fig 1A). Patients with lymphoma-associated PDMM had similar characteristics as patients with asbestos-associated PDMM (Table 1), except that they were younger (median age, 45 v 64 years, respectively; P < .001). In addition, asbestos bodies in lymphoma-associated PDMM were less numerous than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to the control group without PDMM (median count, 15 v 10 bodies, respectively; P = .6; Fig 1B). Six patients had extrapleural pneumonectomy, seven patients had pleurectomy/decortication, and nine patients had only diagnostic biopsies, with no surgical resection. The hospital morbidities of 13 patients operated on at our institution are listed in Appendix Table A2 (online only) and were similar to our previously published experience.15
Fig 1. (A) Patients received radiation therapy at a median age of 20 years (mean, 25.3 years; 95% CI, 18.1 to 32.4 years) and developed malignant mesothelioma after a mean latency period of 21 years (95% CI, 17 to 25.4 years). The patients with lymphoma-associated pleural diffuse malignant mesothelioma (PDMM) were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001). Crosses represent the mean values, and whiskers represent the 10th and 90th percentiles. (B) Proportion of asbestos body counts in lung tissue from patients with malignant mesothelioma. Asbestos bodies in lymphoma-associated PDMM were less numerous than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to the control group without PDMM (median count, 15 v 10 bodies, respectively; P = .6). Boxes represent the 25th and 75th percentile values, and whiskers represent the 10th and 90th percentiles.
Although epithelioid mesotheliomas more often display a tubular, papillary, or solid pattern, they may also present with other patterns, including deciduoid, clear cell, signet ring cell, and pleomorphic.16–18 Two of the lymphoma-associated PDMMs showed an unusual histology with rhabdoid cells with high-grade cytology and cellular pleomorphism (Fig 2).18,19 The rhabdoid component was characterized by the presence of discohesive cells, with abundant cytoplasm and eccentric nuclei with prominent nucleoli.
Fig 2. Representative cases of malignant mesothelioma in patients with a history of radiation treatment for Hodgkin lymphoma. (A) Epithelioid morphology was seen in all patients (seven had epithelioid subtype, and one had biphasic subtype). (B) Nuclear pleomorphism was marked in two patients. (C) Signet ring–like cells were focally present in three patients. (D) Myxoid morphology characterized one malignant mesothelioma. (E) Clear cells were seen in one patient. (F) Necrosis was present in two patients.
A second unusual morphology encountered in this series of lymphoma-associated PDMM is a rare subtype called myxoid mesothelioma.20 This is an epithelial mesothelioma where the tumor cells are embedded in large pools of mucin. Features such as those described in this series of radiation therapy–associated mesotheliomas after treatment for lymphoma are unique, and few individual case reports have been previously described in the literature.21
The median follow-up time of the overall group was 11.4 months (mean, 17.6 months; 95% CI, 16.6 to 18.5 months). The median potential follow-up time using censored data for the same group of patients was 15.6 months (mean, 25.6 months; 95% CI, 21.3 to 29.8 months). Univariate Cox regression analysis showed that female sex, age ≤ 65 years, complete macroscopic cytoreductive surgery, and epithelioid histology were favorable prognostic indicators for overall survival (all with P < .001; Table 2). We found no significant differences in overall survival between patients with left-sided and right-sided malignant mesothelioma (P = .78).
|
| Characteristic | Univariate Analysis | Multivariate Analysis | ||||
|---|---|---|---|---|---|---|
| HR | 95% CI | P | HR | 95% CI | P | |
| Sex: female v male | 1.49 | 1.3 to 1.70 | < .001 | 1.32 | 1.12 to 1.56 | .001 |
| Age: ≤ v > 65 years | 1.40 | 1.26 to 1.55 | < .001 | 1.20 | 1.06 to 1.37 | .005 |
| Primary location*: left pleura v right pleura | 1.02 | 0.91 to 1.13 | .78 | 0.89 | 0.79 to 1.02 | .087 |
| Surgery: complete macroscopic cytoreduction v incomplete resection | 1.70 | 1.46 to 1.99 | < .001 | 1.68 | 1.43 to 1.96 | < .001 |
| Histology: epithelioid v nonepithelioid | 2.20 | 1.97 to 2.45 | < .001 | 2.06 | 1.80 to 2.36 | < .001 |
| History of lymphoma: yes v no | 1.71 | 1.09 to 2.70 | .018 | 1.83 | 1.09 to 3.06 | .022 |
Abbreviation: HR, hazard ratio.
*Twenty-two patients were excluded from the analysis because of indeterminate tumor location.
As in previous published studies,22 the median overall survival time was significantly better among patients with epithelioid histology (17 months) than among patients with biphasic histology (9.5 months) and sarcomatoid histology (6.4 months; P < .001). Furthermore, patients with lymphoma-associated PDMM had a significantly longer overall survival than patients with asbestos-associated PDMM (median survival, 32.5 v 12.7 months, respectively; P = .018; Fig 3).
Fig 3. Kaplan-Meier estimates of overall survival among patients with lymphoma-associated and asbestos-associated pleural diffuse malignant mesothelioma (PDMM). The median overall survival time was significantly better among patients with lymphoma-associated PDMM than it was among patients with asbestos-associated PDMM (median, 32.5 v 12.7 months, respectively; P = .018).
After adjusting for significant variables by multivariate analysis, we found that female sex (P = .001), age ≤ 65 years (P = .005), complete macroscopic cytoreductive surgery (P < .001), and epithelioid histology (P < .001) were independent favorable predictors for overall survival. Furthermore, history of previous radiation for lymphoma was also an independent favorable predictor for overall survival (P = .022; Table 2).
Although it is well established that the majority of PDMMs are caused by exposure to asbestos fibers, a minority of patients have no known history of asbestos exposure that could be documented, and the etiology is less clear. One of the recently postulated important causes of PDMM is prior radiation therapy for a variety of malignancies.8,23,24 Furthermore, recent published studies reported a significant increased risk of malignant mesothelioma after radiation treatment for Hodgkin lymphoma.12 However, the clinicopathologic characteristics of malignant mesotheliomas arising in patients with a previous history of chest irradiation for lymphomas have not been established in detail. In the present study, we investigated a large series of consecutive patients diagnosed with malignant mesothelioma at a single institution to identify the patients who had a history of prior chest irradiation for lymphoma. We found that patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and have a longer overall survival compared with patients with asbestos-associated PDMM.
Generally, most postradiation mesotheliomas occur after treatment for a previous malignancy, the most frequently described of which has been Hodgkin lymphoma. Other documented tumors that have been associated with the development of PDMM after radiotherapy include Wilms tumor, breast carcinomas, and seminomas.25 Conversely, patients with a history of Hodgkin lymphoma who have received radiation therapy with or without chemotherapy have an increased relative risk of developing multiple malignancies.12 A large study that pooled 13 population-based registries from North America and Europe reported the relative risk (RR) for the development of subsequent malignancies after radiation treatment for Hodgkin lymphoma. The highest RR was for mesothelioma. The reported RRs and malignancies were as follows: malignant mesothelioma (RR, 19.5), sarcomas of soft tissue and bone (RR, 11.7), carcinoma of the stomach (RR, 9.5), carcinoma of the breast in women (RR, 6.1), and thyroid carcinoma (RR, 3.1).12
We studied 1,618 consecutive patients who were diagnosed with PDMM in a 15-year period and identified 22 patients who received treatment with radiotherapy (plus or minus chemotherapy) to the chest for the treatment of Hodgkin and non-Hodgkin lymphoma. For these patients with lymphoma-associated PDMM, the lymphoma was diagnosed at a median age of 20 years (mean, 25.3 years; 95% CI, 18.1 to 32.4 years). This relatively young age for lymphoma diagnosis is consistent with other reports that found that the risk of mesothelioma after RT (and chemotherapy) treatment for lymphoma is higher for younger patients.12,13 As in previous studies, these patients developed malignant mesothelioma after an average latency period of 21 years, characteristic of radiation-related solid tumors.13,25 In contrast to other studies,25 we found that patients with lymphoma-associated PDMM have similar female-to-male sex ratios (1:3.4 v 1:3.8, respectively; P = .82) and hemithoracic distribution as asbestos-associated PDMM (P = .44). However, shorter latency periods in patients with Hodgkin lymphoma have been reported, possibly induced by complex interactions between multiple factors such as radiation, immunosuppressive effects related to lymphoma, and the synergistic effect of chemotherapy.13 We are not able to comment on the risk of lymphoma-associated PDMM as a function of RT dose. In our series, the available RT doses ranged from 30 to 46 Gy, which is a typical range for lymphoma treatment.
Although some patients in our study have a reported exposure to asbestos, the asbestos body count in lymphoma-associated PDMM was much lower than that seen for asbestos-associated PDMM (median count, 15 v 325 asbestos bodies, respectively; P = .0007) and similar to the non-PDMM control group used in our laboratory (Fig 1B).
We performed a thorough histopathologic review of all malignant mesotheliomas induced by prior radiation secondary to Hodgkin and non-Hodgkin lymphoma and showed that the distribution of histologic types among these patients is similar to the distribution seen in asbestos-associated PDMM (P = .21). Surprisingly, we found that 32% of lymphoma-associated PDMMs have unusual histologic patterns, with high-grade cytology with pleomorphic rhabdoid cells and myxoid features. Unusual histologies in malignant mesothelioma are extremely uncommon and rarely reported. Interestingly, few case reports or small series have described patients with uncommon histologic features and previous radiation in their medical histories.17,21
As in previously published reports,22,26 the most important predictor of survival for the patients in our study was the histologic type. Patients with epithelioid mesothelioma have a better overall survival than patients with biphasic or sarcomatoid mesothelioma. Although previous studies reported that radiation-associated mesothelioma has a dismal prognosis compared with asbestos-associated mesothelioma,25 we found that patients with lymphoma-associated malignant mesothelioma have a significantly improved overall survival (median, 32.5 v 12.7 months, respectively; P = .018; Fig 3), despite similar surgical approaches. In our series, patients with lymphoma-associated malignant mesothelioma had a 41% reduction in the risk of death in univariate analysis (reciprocal hazard ratio, 0.59; 95% CI, 0.46 to 0.93; P = .018), and as depicted in Table 2, this risk reduction was maintained after we adjusted for all the significant prognostic characteristics in multivariate analysis (reciprocal hazard ratio, 0.55; 95% CI, 0.33 to 0.92; P = .022).
In conclusion, patients with lymphoma-associated PDMM have particular features when compared with those with asbestos-associated PDMM. Some of the features are similar to those for asbestos-associated PDMM (sex distribution, tumor location, and histologic type). Other characteristics, however, are different and include unusual cytologic and histopathologic features, younger age at diagnosis, and longer overall survival. These findings most likely reflect the complexity of this extremely unusual type of malignant neoplasm. Mechanistic explanations for these associations are needed to improve our understanding of tumor morphogenesis and to help with the diagnostic recognition of tumors that have developed along various molecular pathways. Such diagnostic advances would likely have subsequent implications for patient management.
Supported by the International Mesothelioma Program.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Although all authors completed the disclosure declaration, the following author(s) and/or an author's immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory Role: Lucian Chirieac, Medical Science Affiliates (C), Willcox & Savage (C), DeHay & Elliston (C) Stock Ownership: None Honoraria: None Research Funding: Raphael Bueno, Genentech, Castle Biosciences Expert Testimony: None Patents: None Other Remuneration: None
Conception and design: Lucian R. Chirieac, David J. Sugarbaker
Administrative support: David J. Sugarbaker
Provision of study materials or patients: David J. Sugarbaker
Collection and assembly of data: Lucian R. Chirieac, Beow Y. Yeap, William G. Richards, Tamara Tilleman, Elizabeth H. Baldini, John Godleski, David J. Sugarbaker
Data analysis and interpretation: Lucian R. Chirieac, Justine A. Barletta, Beow Y. Yeap, William G. Richards, Tamara Tilleman, Raphael Bueno, David J. Sugarbaker
Manuscript writing: All authors
Final approval of manuscript: All authors
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Acknowledgment
We thank Deborah O'Leary for her editorial assistance in preparing the manuscript and Leonard Friedman for the registry database queries.
|
| Patient No. | Sex | Age at Lymphoma Treatment (years) | Treatment for Lymphoma | RT Dose (Gy) | Latency Period From Radiation to PDMM (years) | Primary Location of PDMM | Age at PDMM (years) | Histology of PDMM | Asbestos Exposure (count) | Survival (months) | Survival Status |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M | 10 | Chemo/RT | Unk | 26 | Right | 37 | Epithelioid | Yes (NR) | 32 | Dead |
| 2 | M | 22 | Chemo/MOPP/RT | Unk | 16 | Right | 38 | Epithelioid | Yes (NR) | 18 | Dead |
| 3 | M | 20 | RT | Unk | 22 | Right | 42 | Epithelioid | NR (NR) | 44 | Dead |
| 4 | M | 7 | RT/MOPP | 35 | 24 | Left | 32 | Epithelioid | No (56) | 56 | Dead |
| 5 | M | 12 | RT | 40 | 23 | Left | 35 | Epithelioid | No (12) | 11 | Dead |
| 6 | M | 14 | RT (mantle/para-aortic) | 46 | 13 | Left | 27 | Epithelioid | No (NR) | 61 | Dead |
| 7 | M | 24 | RT (mantle) | Unk | 25 | Right | 49 | Epithelioid | No (15) | 17 | Dead |
| 8 | M | 26 | RT/Chemo | Unk | 8 | Left | 34 | Epithelioid | No (0) | 44 | Dead |
| 9 | M | 31 | RT (mantle) | Unk | 25 | Left | 56 | Epithelioid | No (21) | 4 | Dead |
| 10 | M | 21 | RT | Unk | 38 | Left | 58 | Epithelioid | Yes (NR) | 43 | Dead |
| 11 | F | 41 | Chemo/MOPP/RT | Unk | 18 | Right | 59 | Biphasic | NR (NR) | 5 | Dead |
| 12 | F | 18 | RT (mantle) | Unk | 43 | Right | 61 | Epithelioid | Yes (NR) | 15 | Dead |
| 13 | F | 14 | RT (mantle) | Unk | 15 | Left | 29 | Epithelioid | No (NR) | 79 | Alive |
| 14 | M | 20 | RT (mantle) | Unk | 20 | Right | 40 | Epithelioid | No (NR) | 33 | Dead |
| 15 | M | 19 | RT | 30 | 37 | Left | 55 | Biphasic | No (NR) | 52 | Alive |
| 16 | F | 19 | RT (mantle) | Unk | 23 | Right | 42 | Epithelioid | No (NR) | 4 | Dead |
| 17 | M | 26 | RT (mantle) | Unk | 25 | Right | 51 | Epithelioid | NR (NR) | 59 | Dead |
| 18 | M | 20 | RT/Chemo (MOPP) | Unk | 27 | Left | 47 | Epithelioid | NR (NR) | 0 | Alive |
| 19 | M | 39 | RT | Unk | 21 | Right | 60 | Biphasic | NR (NR) | 4 | Dead |
| 20 | M | 17 | RT/Chemo | Unk | 13 | Left | 30 | Epithelioid | Yes (NR) | 68 | Dead |
| 21 | F | 72 | RT/Chemo | Unk | 7 | Left | 79 | Epithelioid | NR (NR) | 12 | Dead |
| 22 | M | 65 | RT/Chemo | Unk | 2 | Left | 66 | Epithelioid | NR (NR) | 8 | Dead |
Abbreviations: Chemo, chemotherapy; MOPP, mechlorethamine, vincristine, procarbazine, and prednisone; NR, not reported; PDMM, pleural diffuse malignant mesothelioma; RT, radiotherapy; Unk, unknown.
|
| Patient Order No. | Surgical Procedure | Postoperative Complications |
|---|---|---|
| 1 | No resection as a result of tumor extent | |
| 2 | No resection as a result of tumor extent | |
| 3 | No resection as a result of tumor extent | |
| 4 | EPP | Vocal chord paralysis, aspiration pneumonia, ARDS → trach/PEG; recovered, long-term survivor 54 months |
| 5 | EPP | No complications |
| 6 | EPP/cisplatin HIOC | No complications; long-term survivor 59 months |
| 7 | EPP/cisplatin HIOC | Pulmonary embolus, atrial fibrillations |
| 8 | EPP | Vocal chord paralysis, herniation through diaphragm patch |
| 9 | EPP/cisplatin HIOC | Wound infection, pulmonary embolus, atrial fibrillation, multiorgan failure, death |
| 10 | P/D | No complications; long-term survivor 40 months |
| 11 | P/D/cisplatin HIOC | Pneumonia, respiratory failure, death |
| 12 | P/D | Reintubation, prolonged length of stay in hospital |
| 13 | P/D | No complications; long-term survivor 13 years |
| 14 | P/D with HIOC, brachytherapy | No complications |
| 15 | P/D with HIOC | No complications |
| 16 | No resection as a result of tumor extent | |
| 17 | No resection; outside slide evaluation only | |
| 18 | No resection; outside slide evaluation only | |
| 19 | No resection; outside slide evaluation only | |
| 20 | No resection; biopsy only | |
| 21 | P/D with chemical wash | No complications |
| 22 | No resection; biopsy only |
Abbreviations: ARDS, acute respiratory distress syndrome; EPP, extrapleural pneumonectomy; HIOC, hyperthermic intraoperative intracavitary cisplatin perfusion; P/D, pleurectomy/decortication; PDMM, pleural diffuse malignant mesothelioma; trach/PEG, tracheostomy and percutaneous endoscopic gastrostomy.
