Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial

Our plain-English summary of Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial, by O. Riesterer, I.F. Ciernik, R.A. Stahel, et al (Radiotherapy and Oncology, 2019).

The study

• Authors: O. Riesterer, I.F. Ciernik, R.A. Stahel, A. Xyrafas, D.M. Aebersold, L. Plasswilm, E. Mahmut Ozsahin, D.R. Zwahlen, K. Nackaerts, F. Zimmermann, L. Sabrina Stark, W. Weder, J. Krayenbuehl, Swiss Group for Clinical Cancer Research (SAKK)
• Journal: Radiotherapy and Oncology
• Published: 2019;138:121-125
• Type of article: Randomized trial
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Postoperative radiotherapy after extrapleural pneumonectomy of malignant pleural mesothelioma was investigated in the randomized phase II trial SAKK17/04. The relapse rate within the high and/or low-dose PTV without previous distant failure was 24%, the isolated in-field-relapse rate within the PTVs was 5% and the distant relapse rate outside of the PTVs was 81%. Clinical outcome was mainly determined by distant disease progression outside of the radiation field.

Copyright © 2019 Elsevier B.V. All rights reserved.

In plain English

This short communication reported an analysis from SAKK 17/04, a randomized phase II trial in patients with malignant pleural mesothelioma treated with chemotherapy and extrapleural pneumonectomy (surgery removing the lung and pleura). Of 54 randomized patients, 27 were assigned to high-dose radiotherapy to the operated side of the chest. The authors compared follow-up scans with the radiation target areas in 21 of them. Six were excluded, including 4 who died within three months after radiotherapy. Over a median follow-up of 17 months, 18 of the 21 (86%) had a recurrence. First recurrence involved the radiation target areas in 5 patients (24%). In only 1 patient (5% of the 21) was the first recurrence confined to those areas. Seventeen (81%) had recurrences outside the target areas. The same side of the chest was a site of first relapse less often with radiotherapy than without (33% vs. 69%, p = 0.02). The authors concluded that radiotherapy gave reasonably high local control but remained futile for most patients because of progression outside the target areas. They urged caution because of small numbers, varied techniques, no central plan review and early deaths.

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: Short communication: an analysis of where tumors first recurred in the radiotherapy arm of a multicenter randomized phase II trial (SAKK 17/04), compared with the radiation target volumes
• Who was studied: Patients with malignant pleural mesothelioma in the SAKK 17/04 trial (centers in Switzerland and Belgium). 153 were enrolled and 54 were randomized after complete resection, 27 per arm. Follow-up images of 21 radiotherapy-arm patients could be evaluated.
• Exposure: High-dose radiotherapy to the hemithorax (the operated side of the chest) after induction chemotherapy and extrapleural pneumonectomy. Several techniques were used (3D-CRT, IMRT/VMAT, helical tomotherapy). A low-dose target volume was treated to about 45 to 46 Gy and a boost (high-risk) volume to 55.9 to 57.6 Gy.
• Main results:
  • Among the 21 evaluable irradiated patients, 18 (86%) had radiologically documented recurrences (median follow-up 17 months, range 3.4 to 61.5).
  • Site of first relapse among the 21 evaluable patients: only within the target volumes in 1 patient (5%), both within and outside in 4 (19%), and only outside in 13 (62%).
  • All 5 local recurrences (24%) were in the low-dose target volume. In 2 of the 5 (10%), recurrences were also seen in the high-dose (boost) volume.
  • Median time to local tumor recurrence was 9.4 months (range 6.2 to 12.1 months).
  • 17 of the 21 patients (81%) had recurrences outside the target volumes.
  • Recurrences outside the target volumes were in the opposite (contralateral) hemithorax in 8 patients (38%), the mediastinum in 4 (19%) and the abdomen in 7 (33%).
  • 2 recurrences were at the lower border of the target volumes. One was judged a geographic miss just outside the target volume. The other overlapped it and was counted as local.
  • Comparing the two trial arms, the same-side (ipsilateral) hemithorax was less often a site of first relapse in the irradiated arm than in the arm without radiotherapy: 33% vs. 69%, p = 0.02.
• The authors' conclusion: The authors concluded that radiotherapy as given in the trial produced a reasonably high local tumor control rate but remained futile for most patients because of progression outside the target volumes. They wrote that it cannot be recommended for routine use in all patients with malignant pleural mesothelioma but may still be offered to carefully selected patients.
• Limitations the authors state:
  • The low number of randomized patients, varied radiotherapy techniques, no central review of treatment plans, and a high proportion of irradiated patients dying early.
  • A relatively high exclusion rate and early deaths without imaging of relapse (probably due to treatment complications) were described as major caveats.
  • It could not be determined whether the reduction in same-side chest relapse was durable, because most patients with relapse no longer had regular imaging.

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: Extrapleural Pneumonectomy (EPP), Pleural Mesothelioma, Disease Progression.

Related studies

• Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series — S. Tonoli, P. Vitali, et al. (2011)
• 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)
• High-dose-rate surface brachytherapy to boost elongated, curvilinear incisional scars after extrapleural pneumonectomy for malignant pleural mesothelioma treated with adjuvant intensity-modulated radiation therapy — L.A. Doyle, T.N. Showalter, et al. (2010)
• Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals — A. Bille, E. Belcher, et al. (2012)
• Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma — Y. Matsuo, K. Shibuya, et al. (2017)
• Second surgery for recurrence of malignant pleural mesothelioma after extrapleural pneumonectomy — L. Politi, G. Borzellino (2010)

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