logo white

2.3 Diagnosis of Mesothelioma

eToolkit Menu

Respiratory Medicine: Malignant Pleural Mesothelioma

Takashi Kijima, Takashi Nakano, Kozo Kuribayashi, Toshiyuki Minami, Ryo Takahashi, Koji Mikami, Takashi Yokoi

Clinical Symptoms

Kozo Kuribayashi, M.D., Ph.D.

The main symptoms of malignant pleural mesothelioma (MPM) are chest pain, dyspnea, and non-productive cough. Patients may also have unexplained fever and weight loss, but in the early stage of MPM, there are no symptoms; the chest oppression sensation and exertional dyspnea are realized with the increase in pleural effusion. Although the cough is not strong, the cough comes out in the initial stage of the disease by the stimulation of pleural effusion transfer by body movement. Chest pain is absent early in the disease but develops gradually as chest wall invasion begins. However, these symptoms are not characteristic of mesothelioma and are often delayed in early detection.(1) As the disease progresses, the tumor grows markedly, the chest wall and vertebral bodies become highly infiltrated, and pain becomes the main symptom. In general, patients with MPM have more severe subjective symptoms than patients with other cancers.(2)

Diagnostic Approach

Kozo Kuribayashi, M.D., Ph.D.

MPM arises from the parietal pleura for poorly understood reasons. The earliest identifiable clinical feature is pleural effusion, and asymptomatic pleural effusion is often detected by screening.(3) Pleural thickening is also a frequent finding in MPM.(4) In early mesothelioma, pleural effusion alone or pleural thickening is slight, and it is necessary to pay attention to pleural irregularity in the mediastinum and between lobes.(5)

Typically, patients present with the following four findings:

  1. circumferential pleural thickening surrounding the lung (pleural rind),
  2. nodular pleural thickening,
  3. pleural thickening of more than 1 cm in thickness, and
  4. mediastinal pleural thickening.

These findings are important in differentiating between benign and malignant pleural lesions; the sensitivities are 41%, 51%, 36%, and 56%, respectively, and the specificities are reported to be 100%, 94%, 94%, and 88%, respectively.(6) If one or more of these findings are present, the possibility of malignancy is extremely high.(7,8)

Therefore, if a patient with a history of asbestos exposure has pleural effusion or pleural thickening, MPM should be listed as one of the differential diagnoses, and a definitive diagnosis should be obtained actively.

The definitive diagnosis of pleural mesothelioma requires definitive tissue diagnosis by pleural biopsy, which may include percutaneous needle biopsy (blind biopsy, image-guided biopsy with computed tomography or ultrasound), medical (under local anesthesia) thoracoscopic biopsy, or surgical (thoracoscopic thoracotomy) biopsy. The gold standard for biopsy is thoracoscopy, and the diagnosis rate is reported to be over 95%.(9,10)

The process leading to a definitive diagnosis of MPM is shown in Figure 1

Development, progression, and tumor, node and metastasis (TNM) classification

Toshiyuki Minami, M.D., Ph.D.

Development and progression

MPM arises from neoplastic transformation of mesothelial cells of the pleura. Epidemiological studies have proven that occupational and environmental exposure to asbestos is the main cause of the development of MPM.(11) Once asbestos is inhaled, it penetrates the alveolar barrier and reaches the lung interstitium. Asbestos is then pulled out from the lung interstitium by pulmonary lymph flow and subsequently translocated across the visceral pleura due to the increase of pulmonary interstitial pressure mediated by asbestos-induced inflammation. Subsequently, asbestos appears in the pleural space where the pleural fluid is continuously being discharged through stomata in the parietal pleura. Asbestos is carried away by convective pleural fluid flow and finally accumulates in the parietal pleural stomata.(12,13) Thus, asbestos mainly affects the parietal mesothelium rather than the visceral mesothelium.

Both parietal and visceral mesothelium are composed of a single layer of mesothelial cells. When asbestos reaches the parietal pleura, it induces necrosis in mesothelial cells along with the extracellular release of damage-associated molecular patterns, such as high-mobility group protein B1 (HMGB1), while also triggering the activation of the Nod-like receptor protein 3 (NLRP3) inflammasome. While HMGB1 activates nuclear factor κB (NFκB) and induces tumor necrosis factor α (TNFα) secretion and pro-interleukin 1β (pro-IL1β) production through the interaction with Toll-like receptor 4, the activated NLRP3 inflammasome promotes maturation and secretion of IL1β.(14) Asbestos cannot be completely eliminated and remains in place for a long time despite undergoing phagocytosis by macrophages.(13,15) Macrophages attempting to phagocytose asbestos also release abundant inflammatory cytokines such as TNFα and IL1β by a similar mechanism. Several studies have indicated that TNFα and IL1β play key roles in asbestos-related mesothelial carcinogenesis.(16,17) Thus, persistent inflammation in parietal mesothelium contributes to the development of MPM.

Even after the transformation of mesothelial cells into malignant mesothelioma, inflammatory cytokines derived from tumor-associated macrophages (TAMs), a major component of the MPM microenvironment, continue to play a huge role in the progression of MPM. A recent study demonstrated that MPM cells abundantly express the IL1 receptor, and tumor-associated macrophage-derived IL1β enhances the malignant potential of MPM cells.(18) Thus, persistent inflammation in the mesothelium contributes not only to the development but also to the progression of MPM.

Tumor, node and metastasis (TNM) classification

Once MPM develops, it spreads along the pleural surface. Unlike other types of cancer, a concentrically enlarging mass recognized as the primary tumor is rarely detected. Multiple nodules are diffusely observed in the pleural cavity accompanied by pleural effusion.(19) Due to the unique extension and the low incidence of MPM, a universally accepted TNM classification for MPM has remained unestablished. The International Association for the Study of Lung Cancer (IASLC) performed a large-scale retrospective analysis of the prognosis of patients with MPM to establish a novel staging system in MPM. According to the IASLC’s information, the eighth edition of TNM classification for MPM was published and is currently available (Tables 1, 2).(20)

Table 1. TNM classification for malignant pleural mesothelioma

T descriptors

The T component of the TNM classification refers to the primary tumor. In most malignancies, it is determined by measuring the size of the primary tumor. However, it is quite difficult to measure the size of the tumor in MPM because MPM spreads diffusely along the surface of the pleura. Therefore, T descriptors in MPM are determined by which parts of the pleural surfaces are involved, as shown in Table 1.(19) It is clinically valuable to determine a T descriptor reported to be associated with overall survival (OS) in MPM patients receiving surgical management.(21)

N descriptors

The N component of the TNM classification defines lymph node metastasis. As shown in Table 1, N descriptors for MPM are divided into three categories: N0, N1, and N2. Several studies demonstrated that the survival of patients with nodal metastasis (N1 and N2) was significantly worse than that of patients without nodal metastasis (N0).(20,22) In particular, pathologically proven nodal metastasis exhibits a strong correlation with poor prognosis.(22) Thus, N descriptors are very important to predict the outcome, especially in patients who have received cytoreductive surgery.

M descriptors

Similar to other types of malignant tumors, the M component of the TNM classification describes the presence of distant metastasis (Table 1). The IASLC reported that the OS of patients with distant metastasis (M1) was shorter than that of patients with maximally locally advanced tumors.(23) Therefore, only M1 cases are categorized as stage IV.

Staging system

Based on statistical analysis of survival data of patients with MPM, the IASLC proposed a novel staging system (Table 2).(20,23) Although this is the first evidence-based staging system in MPM, accumulation of further clinical data will be necessary to confirm its reliability.

Table 2. Staging system for malignant pleural mesothelioma

Surgical Treatment

Ryo Takahashi, M.D., Ph.D.

Surgery for MPM plays an important role, whether with curative or palliative intent. In this section, we review cytoreductive surgery with curative intent. Cytoreductive surgery is recommended for certain patients with early-stage (I to III) MPM who are medically operable.(24,27) It is essential that patients are considered carefully before surgery is performed.

The principle of surgical oncology is to resect all gross tumors with an adequate margin. However, microscopically free resection with a secure margin cannot be obtained in MPM surgery due to its anatomical location. Therefore, curative resection (R0 resection) cannot be achieved in MPM surgery and the surgical goal for MPM is to achieve macroscopic complete resection (R1 resection) by resecting all visible and palpable lesions.(21) The presence of residual tumor cells must be tolerated pathologically in R1 resection, which can lead to a decrease of curability.

Since surgical cytoreduction as a single modality is generally insufficient as noted above, it is strongly recommended that multimodal therapy with chemotherapy and/or radiation therapy be administered. Effective pre- or postoperative chemotherapy and/or adjuvant radiation therapy should be given for patients for whom cytoreductive surgery is performed.(24,27) Regarding histology, surgery for epithelioid and mixed-type MPM is recommended. Patients with confirmed sarcomatoid-type MPM are not candidates for surgery because chemotherapy is generally not effective with a poor prognosis.(28,29)

Surgical resection for patients with MPM mainly consists of extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). In EPP, the involved pleura, ipsilateral lung, diaphragm, and pericardium is resected en bloc. P/D refers to the resection of all gross tumors with parietal and visceral pleura, sparing the ipsilateral lung. Extended P/D refers to the removal of the diaphragm and pericardium in addition to standard P/D. The choice of surgical form is controversial because there are no randomized control studies comparing EPP and P/D surgery. In the past, EPP was the most commonly used approach because it was hypothesized that EPP was less likely than P/D to leave residual malignant cells. Nevertheless, recent studies have reported that neither EPP nor P/D results in complete R0 resections and a systematic review comparing EPP and P/D shows similar OS (MST: 12-22 months vs. 13-29 months).(30-32) There has been a shift in choice of surgical form toward extended P/D in place of EPP because EPP is associated with a higher morbidity and mortality than is P/D.

As another limitation, we have no established indication for MPM surgery because there is no scientific evidence that surgical treatment improves the prognosis, and selection bias is often present in retrospective studies. Patients chosen for surgery must be carefully selected and considered by multidisciplinary experts.

Role of Radiation Therapy

Koji Mikami, M.D., Ph.D.

Role of radiation therapy of malignant pleural mesothelioma

​Radiation therapy (RT) for MPM is currently used as part of multimodal therapy. However, RT alone is not recommended for treatment. RT after surgical intervention was associated with improved survival in the largest retrospective study of adjuvant radiotherapy.(33) RT is widely used for other purposes, such as palliative treatment for cancerous pain and as port-site prophylaxis without chemotherapy

Adjuvant hemithoracic radiation therapy after extrapleural pneumonectomy

​Postoperative adjuvant chemotherapy after EPP may reduce the local recurrence rate.(34-37) The recommended radiation dose for adjuvant therapy following EPP is 45-60 Gy in 1.8-2.0 Gy. A dose of 54 Gy given to the entire hemithorax, the thoracotomy incision, and sites of chest drains was well-tolerated.(28,38)

Adjuvant hemithoracic radiation therapy after pleurectomy/decortication

​P/D is considered to be a less invasive surgery than EPP. However, in the presence of normal lungs, high-dose conventional RT to the entire hemithorax does not show prolonged survival and instead significantly enhanced toxicity.(39-40)

With advances in RT technology, hemithoracic irradiation by intensity-modulated radiation (IMRT) after P/D has been performed. IMRT is an advanced radiation technology that can more effectively avoid irradiation of normal tissues by concentrating radiation on the tumor with a high dose. IMRT can avoid irradiating the ipsilateral lung, heart, and intra-abdominal organs and may be more effective and less toxic in treatment. Therefore, IMRT has been applied as a standard method in recent clinical trials. However, contralateral low-dose radiation may increase the risk of fatal radiation pneumonia.(41)

In a Phase II study evaluating the use of hemithoracic pleural IMRT (50.4 Gy/28 Fr) following chemotherapy and P/D, radiation pneumonitis was reported in 30% (8/27) of evaluable cases (grade 2 in 6 patients, grade 3 in 2 patients) that was reversible with corticosteroids.(42) This study showed the safety of this new trimodal therapy. Hemithoracic IMRT may be the new standard treatment after P/D, and a direct comparison study with adjuvant chemotherapy should be considered to validate the efficacy of postoperative hemithoracic IMRT.

Palliative radiation therapy for local symptoms by disease

​The optimal dose of palliative RT is still unclear.(43-44) A dose of 20-40 Gy was effective for alleviating chest pain in patients with MPM chest pain.(45-47) In a retrospective study, more than 40 Gy in 4 weeks was effective for dyspnea, dysphagia, superior vena cava obstruction, and symptoms of brain metastases.(48)

General Treatment

Takashi Yokoi, M.D., Ph.D.

Treatment of malignant mesothelioma is determined by comprehensively evaluating staging by the International Mesothelioma Interest Group (IMIG) classification and histological classification by the World Health Organization (WHO) classification. Generally, surgery is the main treatment for resectable cases, and chemotherapy is the main treatment for unresectable or postoperative recurrence cases. On the other hand, RT is often given as part of multidisciplinary treatment combined with surgery and may be given as palliative therapy for the purpose of pain control.

It is often difficult to determine the indication for surgery and RT for MPM, and it is necessary to make a multidisciplinary decision involving a respiratory physician, respiratory surgeon, and oncologist.

First-line treatment

​The gold standard in chemotherapy as first-line treatment is pemetrexed in combination with cisplatin (CDDP). Treatment with pemetrexed plus CDDP showed significantly better OS, progression-free survival (PFS), and overall response rate (ORR) compared with CDDP alone in a Phase III trial (median survival time (MST) 12.1 months vs. 9.3 months, median PFS 5.7 months vs. 3.9 months, ORR 41.3% vs. 16.7%).(49) In this study, the median number of treatment courses in those taking pemetrexed plus CDDP was 6 courses. In principle, continued treatment with pemetrexed plus CDDP is recommended until progressive disease (PD) or intolerable toxicity develops, although 4-6 courses of administration may be sufficient.
It is expected that pemetrexed plus carboplatin (CBDCA) may be selected when CDDP administration is difficult due to renal dysfunction or poor performance status (PS). There have been two Phase II trials of pemetrexed plus CBDCA combination therapy, although the response rate is slightly inferior to the previously reported pemetrexed plus CDDP combination therapy.(50,51) However, time to progression (TTP) and OS were almost the same, and toxicity was mild except for neutropenia and anemia. Therefore, it may be considered in cases where CDDP administration is difficult. The efficacy of maintenance treatment with pemetrexed, such as in lung cancer, has not been shown.(52)

Second-line treatment

​There is little evidence of second-line treatments for MPM. In a retrospective study, re-treatment with pemetrexed plus platinum combination therapy for pemetrexed pre-treated patients significantly reduced the risk of death than pemetrexed alone (HR: 0.11; p<0.001).(53) Therefore, re-administration of pemetrexed plus platinum may be considered in cases in which the effect of pemetrexed plus platinum is observed in first-line treatment.

Nivolumab, the programmed death-1 antibody, showed an ORR of 29%, median PFS of 6.1 months, and a 6-month survival rate of 85%, regardless of histological type, in a Phase II study of previously treated Japanese patients.(54) In addition, in a NivoMes Phase II study of Dutch treated MPM patients, nivolumab showed an ORR of 24%, a median PFS of 2.6 months, and a 6-month survival rate of 74%.(34) Although both studies were single-arm Phase II studies, the efficacy of nivolumab has been reproducibly demonstrated. However, nivolumab is approved only in Japan.

Monotherapy with vinorelbine (VNR) or gemcitabine (GEM) in second-line treatment have had limited effects in Phase II trials, but their ORR was 7% to 24% and OS was 8.0 to 10.6 months.(37,55,56) Therefore, VNR or GEM administration may be considered in second-line therapy.

Prognosis

Takashi Yokoi, M.D., Ph.D.

The prognosis of MPM is poor regardless of histological type, but it is particularly poor for the sarcomatoid type. In a large retrospective study, epithelioid disease experienced the highest median OS (14.4 months), followed by biphasic (9.5 months) and sarcomatoid (5.3 months) disease.(57) After propensity matching in this study, surgery improved OS for the epithelioid (20.9 vs. 14.7 months, P < .001) and biphasic types (14.5 vs. 8.8 months, P=.013), but not the sarcomatoid type (11.2 vs. 6.5 months, P=.140). Furthermore, on multivariable analysis, chemotherapy was independently associated with improved OS (HR; 0.72, 95% CI; 0.59-0.86, p <.001). Based on the above, multimodal therapy for MPM is likely to improve the prognosis and should be actively investigated.

Acknowledgments:

The Authors of this section would like to thank Editage for English editing (current page of e-Toolkit only).

 

References

  1. Baas P, Fennell D, Kerr KM, Van Schil PE, Haas RL, Peters S, et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v31-39. doi: https://doi.org/10.1093/annonc/mdv199 PMID: 26223247
  2. Dyer DS, Mohammed T-LH, Kirsch J, Amorosa JK, Brown K, Chung JH, et al. ACR appropriateness Criteria® chronic dyspnea: suspected pulmonary origin. J Thorac Imaging. 2013 Sep;28(5):W64-66. doi: https://doi.org/10.1097/rti.0b013e31829a2dc3 PMID: 23846109
  3. Kawashima A, Libshitz HI. Malignant pleural mesothelioma: CT manifestations in 50 cases. AJR Am J Roentgenol. 1990 Nov;155(5):965–9. doi: https://doi.org/10.2214/ajr.155.5.2120965 PMID: 2120965
  4. Okten F, Köksal D, Onal M, Ozcan A, Simşek C, Ertürk H. Computed tomography findings in 66 patients with malignant pleural mesothelioma due to environmental exposure to asbestos. Clin Imaging. 2006 Jun;30(3):177–80. doi: https://doi.org/10.1016/j.clinimag.2005.12.027 PMID: 16632152
  5. Kato K, Gemba K, Fujimoto N, Aoe K, Takeshima Y, Inai K, et al. Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion. Eur J Radiol. 2016 Sep;85(9):1594–600. doi: https://doi.org/10.1016/j.ejrad.2016.06.013 PMID: 27501894
  6. Leung AN, Müller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. AJR Am J Roentgenol. 1990 Mar;154(3):487–92. doi: https://doi.org/10.2214/ajr.154.3.2106209 PMID: 2106209
  7. Yilmaz U, Polat G, Sahin N, Soy O, Gülay U. CT in differential diagnosis of benign and malignant pleural disease. Monaldi Arch Chest Dis. 2005 Mar;63(1):17–22. doi: https://doi.org/10.4081/monaldi.2005.653 PMID: 16035560
  8. Metintas M, Ucgun I, Elbek O, Erginel S, Metintas S, Kolsuz M, et al. Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases. Eur J Radiol. 2002 Jan;41(1):1–9. doi: https://doi.org/10.1016/s0720-048x(01)00426-0 PMID: 11750145
  9. Grossebner MW, Arifi AA, Goddard M, Ritchie AJ. Mesothelioma–VATS biopsy and lung mobilization improves diagnosis and palliation. Eur J Cardiothorac Surg. 1999 Dec;16(6):619–23. doi: https://doi.org/10.1016/s1010-7940(99)00323-1 PMID: 10647830
  10. Boutin C, Rey F. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: Diagnosis. Cancer. 1993 Jul 15;72(2):389–93. doi: https://doi.org/10.1002/1097-0142(19930715)72:2%3C389::aid-cncr2820720213%3E3.0.co;2-v PMID: 8319170
  11. Robinson BM. Malignant pleural mesothelioma: an epidemiological perspective. Ann Cardiothorac Surg. 2012;1(4):491-6. doi: https://dx.doi.org/10.3978%2Fj.issn.2225-319X.2012.11.04 PMID: 23977542
  12. Miserocchi G, Sancini G, Mantegazza F, Chiappino G. Translocation pathways for inhaled asbestos fibers. Environ Health. 2008;7:4. doi: https://doi.org/10.1186/1476-069x-7-4 PMID: 18218073
  13. Donaldson K, Murphy FA, Duffin R, Poland CA. Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol. 2010;7:5. doi: https://doi.org/10.1186/1743-8977-7-5 PMID: 20307263
  14. Howrylak JA, Nakahira K. Inflammasomes: Key Mediators of Lung Immunity. Ann Rev Physiol. 2017 Feb 10;79:471–94. doi: https://doi.org/10.1146/annurev-physiol-021115-105229 PMID: 28192059
  15. Carbone M, Adusumilli PS, Alexander HR, Baas P, Bardelli F, Bononi A, et al. Mesothelioma: Scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019 Sep;69(5):402–29. doi: https://doi.org/10.3322/caac.21572 PMID: 31283845
  16. Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z, et al. TNF-alpha inhibits asbestos-induced cytotoxicity via a NF-kappaB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10397–402. doi: https://doi.org/10.1073/pnas.0604008103 PMID: 16798876
  17. Wang Y, Faux SP, Hallden G, Kirn DH, Houghton CE, Lemoine NR, et al. Interleukin-1beta and tumour necrosis factor-alpha promote the transformation of human immortalised mesothelial cells by erionite. Int J Oncol. 2004 Jul;25(1):173–8. https://pubmed.ncbi.nlm.nih.gov/15202003/ PMID: 15202003
  18. Horio D, Minami T, Kitai H, Ishigaki H, Higashiguchi Y, Kondo N, et al. Tumor‐associated macrophage‐derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma. Cancer Sci. 2020 Aug;111(8):2895–906. doi: https://dx.doi.org/10.1111%2Fcas.14523 PMID: 32530527
  19. Nowak AK, Chansky K, Rice DC, Pass HI, Kindler HL, Shemanski L, et al. The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma. J Thorac Oncol. 2016 Dec;11(12):2089–99. doi: https://doi.org/10.1016/j.jtho.2016.08.147 PMID: 27687963
  20. Berzenji L, Van Schil PE, Carp L. The eighth TNM classification for malignant pleural mesothelioma. Transl Lung Cancer Res. 2018 Oct;7(5):543–9. doi: https://dx.doi.org/10.21037%2Ftlcr.2018.07.05 PMID: 30450292
  21. Rusch VW, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. Initial analysis of the international association for the study of lung cancer mesothelioma database. J Thorac Oncol. 2012 Nov;7(11):1631–9. doi: https://doi.org/10.1097/jto.0b013e31826915f1 PMID: 23070243
  22. Rice D, Chansky K, Nowak A, Pass H, Kindler H, Shemanski L, et al. The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma. J Thorac Oncol. 2016 Dec;11(12):2100–11. doi: https://doi.org/10.1016/j.jtho.2016.09.121 PMID: 27687964
  23. Rusch VW, Chansky K, Kindler HL, Nowak AK, Pass HI, Rice DC, et al. The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma. J Thorac Oncol. 2016 Dec;11(12):2112–9. doi: https://doi.org/10.1016/j.jtho.2016.09.124 PMID: 27687962
  24. Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, et al. NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016. J Natl Compr Canc Netw. 2016 Jul;14(7):825–36. doi: https://doi.org/10.6004/jnccn.2016.0087 PMID: 27407123
  25. Kindler HL, Ismaila N, Armato SG, Bueno R, Hesdorffer M, Jahan T, et al. Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 May 1;36(13):1343–73. doi: https://doi.org/10.1200/jco.2017.76.6394 PMID: 29346042
  26. Tsao AS, Lindwasser OW, Adjei AA, Adusumilli PS, Beyers ML, Blumenthal GM, et al. Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation. J Thorac Oncol. 2018 Nov;13(11):1655–67. doi: https://doi.org/10.1016/j.jtho.2018.08.2036 PMID: 30266660
  27. Scherpereel A, Opitz I, Berghmans T, Psallidas I, Glatzer M, Rigau D, et al. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. Eur Respir J. 2020 Jun;55(6). doi: https://doi.org/10.1183/13993003.00953-2019 PMID: 32451346
  28. Meyerhoff RR, Yang C-FJ, Speicher PJ, Gulack BC, Hartwig MG, D’Amico TA, et al. Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database. J Surg Res. 2015 Jun 1;196(1):23–32. doi: https://doi.org/10.1016/j.jss.2015.01.043 PMID: 25791825
  29. Vigneswaran WT, Kircheva DY, Ananthanarayanan V, Watson S, Arif Q, Celauro AD, et al. Amount of Epithelioid Differentiation Is a Predictor of Survival in Malignant Pleural Mesothelioma. Ann Thorac Surg. 2017 Mar;103(3):962–6. doi: https://doi.org/10.1016/j.athoracsur.2016.08.063 PMID: 27765170
  30. Cao CQ, Yan TD, Bannon PG, McCaughan BC. A systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Oncol. 2010 Oct;5(10):1692–703. doi: https://doi.org/10.1097/jto.0b013e3181ed0489 PMID: 20802345
  31. Cao C, Tian DH, Pataky KA, Yan TD. Systematic review of pleurectomy in the treatment of malignant pleural mesothelioma. Lung Cancer. 2013 Sep;81(3):319–27. doi: https://doi.org/10.1016/j.lungcan.2013.04.024 PMID: 23769317
  32. Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD. A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer. 2014 Feb;83(2):240–5. doi: https://doi.org/10.1016/j.lungcan.2013.11.026 PMID: 24360321
  33. Lewis GD, Dalwadi SM, Farach A, Brian Butler E, Teh BS. The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma. Ann Surg Oncol. 2019 Jun;26(6):1879–85. doi: https://doi.org/10.1245/s10434-019-07235-9 PMID: 30798447
  34. Quispel-Janssen J, van der Noort V, de Vries JF, Zimmerman M, Lalezari F, Thunnissen E, et al. Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma. J Thorac Oncol. 2018 Oct;13(10):1569–76. doi: https://doi.org/10.1016/j.jtho.2018.05.038 PMID: 29908324
  35. Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and Gemcitabine as Second- or Third-Line Therapy for Malignant Pleural Mesothelioma. Lung Cancer. 2014 Jun;84(3):271–4. doi: https://dx.doi.org/10.1016%2Fj.lungcan.2014.03.006 PMID: 24690410
  36. Jänne PA, Wozniak AJ, Belani CP, Keohan M-L, Ross HJ, Polikoff JA, et al. Pemetrexed alone or in combination with cisplatin in previously treated malignant pleural mesothelioma: outcomes from a phase IIIB expanded access program. J Thorac Oncol. 2006 Jul;1(6):506–12.https://pubmed.ncbi.nlm.nih.gov/17409909/ PMID: 17409909
  37. van Meerbeeck JP, Baas P, Debruyne C, Groen HJ, Manegold C, Ardizzoni A, et al. A Phase II study of gemcitabine in patients with malignant pleural mesothelioma. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. Cancer. 1999 Jun 15;85(12):2577–82. doi: https://doi.org/10.1002/(sici)1097-0142(19990615)85:12%3C2577::aid-cncr13%3E3.3.co;2-j PMID: 10375105
  38. Mirarabshahii P, Pillai K, Chua TC, Pourgholami MH, Morris DL. Diffuse malignant peritoneal mesothelioma–an update on treatment. Cancer Treat Rev. 2012 Oct;38(6):605–12. doi: https://doi.org/10.1016/j.ctrv.2011.10.006 PMID: 22104079
  39. Baldini EH. Radiation therapy options for malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg. 2009;21(2):159–63. doi: https://doi.org/10.1053/j.semtcvs.2009.06.009 PMID: 19822288
  40. Gupta V, Mychalczak B, Krug L, Flores R, Bains M, Rusch VW, et al. Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):1045–52. doi: https://doi.org/10.1016/j.ijrobp.2005.03.041 PMID: 16054774
  41. Allen AM, Czerminska M, Jänne PA, Sugarbaker DJ, Bueno R, Harris JR, et al. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):640–5. doi: https://doi.org/10.1016/j.ijrobp.2006.03.012 PMID: 16751058
  42. Rimner A, Zauderer MG, Gomez DR, Adusumilli PS, Parhar PK, Wu AJ, et al. Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma. J Clin Oncol. 2016 Aug 10;34(23):2761–8. doi: https://doi.org/10.1200/jco.2016.67.2675 PMID: 27325859
  43. van Thiel ERE, Surmont VF, van Meerbeeck JP. Malignant pleural mesothelioma: when is radiation therapy indicated? Expert Rev Anticancer Ther. 2011 Apr;11(4):551–60. doi: https://doi.org/10.1586/era.10.169 PMID: 21504322
  44. Waite K, Gilligan D. The role of radiotherapy in the treatment of malignant pleural mesothelioma. Clin Oncol (R Coll Radiol). 2007 Apr;19(3):182–7. doi: https://doi.org/10.1016/j.clon.2006.12.006 PMID: 17359904
  45. van Zandwijk N, Clarke C, Henderson D, Musk AW, Fong K, Nowak A, et al. Guidelines for the diagnosis and treatment of malignant pleural mesothelioma. J Thorac Dis. 2013 Dec;5(6):E254–307. doi: https://dx.doi.org/10.3978%2Fj.issn.2072-1439.2013.11.28 PMID: 24416529
  46. Boutin C, Rey F, Viallat JR. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma. A randomized trial of local radiotherapy. Chest. 1995 Sep;108(3):754–8. doi: https://doi.org/10.1378/chest.108.3.754 PMID: 7656629
  47. de Graaf-Strukowska L, van der Zee J, van Putten W, Senan S. Factors influencing the outcome of radiotherapy in malignant mesothelioma of the pleura–a single-institution experience with 189 patients. Int J Radiat Oncol Biol Phys. 1999 Feb 1;43(3):511–6. doi: https://doi.org/10.1016/s0360-3016(98)00409-x PMID: 10078630
  48. Gordon W, Antman KH, Greenberger JS, Weichselbaum RR, Chaffey JT. Radiation therapy in the management of patients with mesothelioma. Int J Radiat Oncol Biol Phys. 1982 Jan;8(1):19–25. doi: https://doi.org/10.1016/0360-3016(82)90379-0 PMID: 6174494
  49. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636–44. doi: https://doi.org/10.1200/jco.2003.11.136 PMID: 12860938
  50. Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006 Mar 20;24(9):1443–8. doi: https://doi.org/10.1200/jco.2005.04.3190 PMID: 16549838
  51. Castagneto B, Botta M, Aitini E, Spigno F, Degiovanni D, Alabiso O, et al. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol. 2008 Feb;19(2):370–3. doi: https://doi.org/10.1093/annonc/mdm501 PMID: 18156144
  52. Dudek AZ, Wang X, Gu L, Duong S, Stinchcombe TE, Kratzke R, et al. Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901. Clin Lung Cancer. 2020 Nov;21(6):553-561.e1. doi: https://doi.org/10.1016/j.cllc.2020.06.025 PMID: 32727707
  53. Zucali PA, Simonelli M, Michetti G, Tiseo M, Ceresoli GL, Collovà E, et al. Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer. 2012 Mar;75(3):360–7. doi: https://doi.org/10.1016/j.lungcan.2011.08.011 PMID: 21937142
  54. Okada M, Kijima T, Aoe K, Kato T, Fujimoto N, Nakagawa K, et al. Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT). Clin Cancer Res. 2019 Sep 15;25(18):5485–92. doi: https://doi.org/10.1158/1078-0432.ccr-19-0103 PMID: 31164373
  55. Steele JP, Shamash J, Evans MT, Gower NH, Tischkowitz MD, Rudd RM. Phase II study of vinorelbine in patients with malignant pleural mesothelioma. J Clin Oncol. 2000 Dec 1;18(23):3912–7. doi: https://doi.org/10.1200/jco.2000.18.23.3912 PMID: 11099320
  56. Stebbing J, Powles T, McPherson K, Shamash J, Wells P, Sheaff MT, et al. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer. 2009 Jan;63(1):94–7. doi: https://doi.org/10.1016/j.lungcan.2008.04.001 PMID: 18486273
  57. Verma V, Ahern CA, Berlind CG, Lindsay WD, Shabason J, Sharma S, et al. Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact of Surgical Resection on Overall Survival. Clin Lung Cancer. 2018 Nov;19(6):e901–12. doi: https://doi.org/10.1016/j.cllc.2018.08.007 PMID: 30224273

Sign up to our newsletter

Sign up
Skip to content