Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy

Our plain-English summary of Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy, by M. Trovo, D. Franceschini, C. Furlan, et al (La Radiologia Medica, 2019).

The study

• Authors: M. Trovo, D. Franceschini, C. Furlan, F. Pietrobon, S. Vagge, E. Farina, A. Revelant, L. Visani, V. Maragna, G. Parisi, V. Scotti
• Journal: La Radiologia Medica
• Published: 2019;124(9):854-859
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To assess the outcome of malignant pleural mesothelioma patients treated with extra-pleural pneumonectomy (EPP) and adjuvant radiotherapy (RT), using the most advanced radiotherapeutic techniques, namely image-guided intensity-modulated RT (IG-IMRT).

Methods And Materials: Fifty-four patients were analyzed. Minimum radiation dose was 50 Gy (2 Gy/fr). Planning target volume encompassed the entire hemithorax, including the ipsilateral mediastinum if interested by disease, the pericardium and diaphragm, and any drain sites. The study endpoints included loco-regional control (LRC), distant metastases free survival (DMFS), and overall survival (OS), as well as radiation-related toxicity.

Results: Major patients and treatment characteristics were the following: median age 62 years, epithelioid histology in 51 (94%) cases, locally advanced disease in 41 (90%) cases, and metastatic mediastinal lymph nodes in 27 patients (50%). Only 7 patients (13%) had gross residual disease after surgery. Chemotherapy was administered in 38 patients (70%). Median follow-up was 16 months (range 0-73 months). Median and 2-year OS were 21 months and was 43.8%, respectively. The predominant pattern of failure was distant: 34 patients (62.9%) developed some component of distant failure, and only 5 patients (9.2%) developed an isolated loco-regional recurrence. The estimates of LRC and DMFS at 2 years were 63.4% and 43.4%, respectively. Three fatal pneumonitis were documented. Other major toxicities included: Grade 2 and 3 pneumonitis in 1 and 2 cases, respectively, 1 case of bronchial fistula, pleural empyema, and Grade 3 esophagitis, respectively.

Conclusions: Although executed in the era of high-technology radiotherapy (IG-IMRT), EPP should not be routinely performed.

In plain English

This retrospective study used prospective databases from four academic centers in Italy. It looked at 54 patients with malignant pleural mesothelioma treated from 2003 to 2014 by extra-pleural pneumonectomy, an operation, followed by image-guided intensity-modulated radiotherapy planned at 50 to 60 Gy. Two patients stopped radiotherapy early because their disease spread. The radiotherapy targeted the entire affected side of the chest. Most patients (51) had epithelioid tumors, and 38 also received chemotherapy. The study did not examine asbestos exposure. Over a median of 16 months of follow-up, 38 patients (70%) died of disease. Counting from the end of radiotherapy, median overall survival was 21 months and 2-year overall survival was 43.8%. Cancer spread to distant sites in 34 patients (62.9%), most often the peritoneum. Only 5 (9.2%) had a recurrence limited to the chest region and nearby lymph nodes. Three patients died of pneumonitis (lung inflammation) within 6 months of finishing radiotherapy. The authors concluded that extra-pleural pneumonectomy, even with modern radiotherapy, should not be routinely performed. They noted that only patients who successfully completed surgery were included, and that surgical deaths and complications were not counted.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of patient data from prospective databases at four academic centers (case series of treated patients)
• Who was studied: 54 patients with malignant pleural mesothelioma treated with extra-pleural pneumonectomy and postoperative image-guided IMRT at four academic centers in Italy between 2003 and 2014. Median age was 62 (range 43 to 77). 39 were male and 15 female. 51 (94%) had epithelioid histology, 49 (90%) had stage III to IVA disease, and 27 (50%) had metastatic mediastinal lymph nodes. Of the 66 patients treated in this period, those lost to follow-up or given palliative radiation doses were excluded.
• Exposure: This was a treatment study, not a study of asbestos exposure. All patients had extra-pleural pneumonectomy followed by image-guided intensity-modulated radiotherapy to the whole hemithorax. Total doses ranged from 50 to 60 Gy in 25 to 30 fractions. Radiotherapy was interrupted in two patients because of systemic disease progression. 38 patients (70%) also received chemotherapy (cisplatin/carboplatin and pemetrexed).
• Main results:
  • Radiotherapy was interrupted in two patients because of systemic progression of disease. These patients were included in the survival analysis. All other patients completed radiotherapy.
  • Survival and control estimates were calculated from the date radiotherapy was completed, not from diagnosis or surgery.
  • Among the 54 patients, median overall survival was 21 months and 2-year overall survival was 43.8%. 38 patients (70%) died of disease during a median follow-up of 16 months (range 0 to 73 months).
  • The main pattern of failure was distant: 34 patients (62.9%) developed some distant failure. Only 5 patients (9.2%) had an isolated loco-regional recurrence.
  • Initial sites of distant failure were peritoneum (14), lung (10), contralateral pleura (6), liver (3) and bone (1).
  • Estimated loco-regional control at 2 years was 63.4%, and distant metastasis-free survival at 2 years was 43.4%.
  • None of the factors tested (age, sex, performance status, histologic subtype, stage, gross residual disease, chemotherapy) correlated with overall survival in univariate analysis.
  • Three patients had fatal (Grade 5) pneumonitis within 6 months after radiotherapy.
  • Other major toxicities were Grade 2 pneumonitis in 1 case and Grade 3 pneumonitis in 2 cases. There was 1 case each of bronchial fistula, pleural empyema and Grade 3 esophagitis. Nine patients reported severe fatigue.
• The authors' conclusion: The authors concluded that extra-pleural pneumonectomy, even when combined with high-technology radiotherapy (IG-IMRT), should not be routinely performed. They suggested that lung-sparing surgery probably represents a valid option for these patients.
• Limitations the authors state:
  • Possible patient selection bias: only patients who successfully underwent extra-pleural pneumonectomy were included.
  • Surgery-related toxicities and deaths were not considered in the analysis.
  • Patients who progressed immediately after surgery or chemotherapy were not included.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pneumonectomy, Intensity-Modulated Radiation Therapy (IMRT), Pleural Mesothelioma, Hemithorax, Mediastinum, Pericardium, Diaphragm, Overall Survival.

Related studies

• Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma — Y. Matsuo, K. Shibuya, et al. (2017)
• Intensity modulated radiation therapy after extra-pleural pneumonectomy for malignant pleural mesothelioma is feasible without fatal pulmonary toxicity and provides good survival — S. Jhavar, J. Pruszynski, et al. (2018)
• Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma — A. Chi, Z. Liao, et al. (2011)
• Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series — H.Y. Pan, S. Jiang, et al. (2015)
• Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma — D.R. Gomez, D.S. Hong, et al. (2013)
• Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma — T. Ebara, H. Kawamura, et al. (2012)

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