Mesothelioma

Epidemiology

  • 3000 patients diagnosed yearly.
  • 70-80% related to asbestos exposure.
  • M>F
  • Peak incidence in 5th to 7th decade.
  • 96% occurs after 20+ years latency period after asbestos exposure

Pathology

  • Sarcomatous
  • Epithelial (best prognosis of 3 subtypes)
  • Mixed

Staging

T-stage:

  • T1a - involves ipsilateral parietal pleura, no involvement of visceral pleura.
  • T1b - involves ipsilateral parietal pleura, focal involvement of visceral pleura.
  • T2 - involves ipsilateral pleural surfaces with at least one of the following: 1) confluent visceral pleural tumor, 2) invasion of diaphragmatic muscle, or 3) invasion of lung parenchyma
  • T3 - involves any of ipsilateral pleural sufaces with at least one of the following: 1) invasion of the endothoracic fascia, 2) invasion into mediastinal fat, 3) solitary focus of tumor invading the soft tissues of the chest wall, 4) non-transmural involvement of the pericardium
  • T4 - involves any of ipsilateral pleural surfaces with at least one of the following: 1) diffuse or multifocal invasion of soft tissues of the chest wall, 2) any rib involvement, 3) invasion through diaphragm to the peritoneum, 4) invasion or any mediastinal organs, 5) direct extension to the contralateral pleura, 5) invasion into the spine, 6) extension to the internal surface of the pericardium, 7) pericardial effusion with positive cytology, 8) invasion of the myocardium, 9) invasion of the brachial plexus

N-stage:

  • N0 - none
  • N1 - ipsilateral bronchopulmonary and/or hilar lymph nodes
  • N2 - subcarinal, and/or ipsilateral internal mammary or mediastinal lymph nodes
  • N3 - contralateral mediastinal, internal mammary, or hilar lymph nodes, and/or ipsilateral or contralateral supraclavicular or scalene lymph nodes

M-stage:

  • M0 - no
  • M1 - yes

Overall stage:

  • IA - T1a N0
  • IB - T1b N0
  • II - T2 N0
  • III - T1-2 N1-2, T3 N0-2
  • IV - T4, N3, M1

Prognostic Factors

CALGB Prognostic Index - Based on a trial of 337 patients treated for malignant mesothelioma in 7 phase II CALGB trials.

  • Pleural Involvement
  • LDH>500 IU/L
  • Poor KPS
  • Non-epithelial histology
  • Age>75

Treatment

General

  • Trimodality therapy is treatment of choice for non-metastatic mesothelioma.
  • Extrapleural pneumonectomy is surgical procedure of choice.
  • Adjuvant radiotherapy includes hemithorax irradiation.
  • 10% patients fail at biopsy tract.

Surgery

EPP
Extrpleural pneumonectomy is an en bloc resection of the entire pleura, lung, and diaphragm with or without resection of the pericardium.
PleurectomY
excision of part of the pleura.
  • Irradiaiton after pleural decortication results in a higher rate of local failure rate compared to EPP and post-operative radiation

Chemotherapy

  • Most effective at this point seems to be Cisplatin and antifolate permetrexed has 12.1 month median surival. [1]

Radiation

General

  • RT reduces local failure after surgical resection
  • RT provide effective palliation for metastatic patients

Target Volume

  • Ipsilateral mediastinum
  • Biopsy tract (commonly spreads along the biopsy tract)
  • Superior: thoracic inlet
  • medial: ipsilateral nodal regions, trachea and subcarinal regions, or the vertebral body
  • posterior mediastinal structures need not be included
  • anteriomedial: use clip and treat
  • inferior: insertion of the diaphragm

Dose

  • post-operative RT is well tolerated
  • 54 Gy to Target Volume (MSK) [((bibcite yajnik ))]
  • IMRT may be used as long as contralateral lung tolerance is respected. V20 < 20% and mean < 9.5 Gy.

Studies

Conventional (3D)

  • MSKCC Experience PMID 7144218. McCormack, P. et al. "Surgical treatment of pleural mesothelioma." Journal of Thoracic Cardiovascular Surgery. 1982 Dec;84(6):834-42
    • 170 pts at MSKCC tx'd from 1939 to 1981 for pleural mesothelioma. Variation in tx regimens, but after 1972, pts tx'd w/ pleurectomy (w/o lung resection) w/ adjuvant ext beam xrt or brachy. Median survival for surg + xrt cohort was 21 months w/ better local control than surg alone.
    • Conclusion: multi-modality approach including surgery, xrt and chemo led to better overall survival.
  • Brigham & Women's Series PMID 9869758. Sugarbaker, D. et al. "Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma," Journal of Thoracic Cardiovascular Sugery. 1999 Jan;117(1):54-63
    • 183 patients, resectable mesothelioma with KPS>70. Patients treated with extrapleural pneumonectomy, adjuvant chemoxrt (30 Gy in 1.5 Gy fx to hemithorax w/ boost to 50.4 Gy, concurrent taxol), adjuvant taxol.
    • Peri-operative mortality 3.8%, subgroup w/ extended survival were epithelial type, negative extrapleural nodes, negative margins. 5 yr OS 46% w/ all 3 positive prognostic factors.
  • MSKCC Modern Series PMID 11581615. Rusch, V. et al. "A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma," Journal of Thoracic Cardiovascular Sugery. 2001 Oct;122(4):788-95
    • 88 patients tx'd from 1995-1998 with 54 Gy hemithoracic xrt after complete resection. 70% extrapleural pneumonectomies.
    • Xrt reduced local recurrence; pts treated w/ extrapleural pneumonectomy w/ adjuvant chemoxrt failed at distant sites.

Intensity Modulated Radiation Therapy

Early studies showed improved local control over historical controls. Recent publication from BWH shows a significant mortality from radiation induced pneumonitis.

  • Brigham & Women's Series PMID 16751058. Allen, AM. 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.
    • Pts treated to 54 Gy in 1.8 Gy fractions. Contralateral lung limited to V20 of 20%. 6 of 13 patients developed fatal radiation pneumonitis.
    • Conclusion: metrics such as V5 and MLD should be used in addition to V20 to determine patient tolerance to xrt.
Bibliography
1. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. 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. PMID: 12860938
2. Yajnik S, Rosenzweig KE, Mychalczak B, Krug L, Flores R, Hong L, Rusch VW. Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1319-26. PMID: 12873676
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