Clinical outcome of postoperative highly conformal versus 3D conformal radiotherapy in patients with malignant pleural mesothelioma

Our plain-English summary of Clinical outcome of postoperative highly conformal versus 3D conformal radiotherapy in patients with malignant pleural mesothelioma, by J. Krayenbuehl, P. Dimmerling, I.F. Ciernik, et al (Radiation Oncology, 2014).

The study

• Authors: J. Krayenbuehl, P. Dimmerling, I.F. Ciernik, O. Riesterer
• Journal: Radiation Oncology
• Published: 2014;9:32
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Radiotherapy (RT) is currently under investigation as part of a trimodality treatment of malignant pleural mesothelioma (MPM). The introduction of highly conformal radiotherapy (HCRT) technique improved dose delivery and target coverage in comparison to 3-dimensional conformal radiotherapy (3DCRT). The following study was undertaken to investigate the clinical outcome of both radiation techniques.

Methods: Thirty-nine MPM patients were treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant RT. Twenty-five patients were treated with 3DCRT, and 14 with HCRT (Intensity modulated radiotherapy or volumetric modulated arc therapy). Overall survival, disease free survival, locoregional recurrence and pattern of recurrence were assessed. A matched pair analysis was performed including 11 patients of each group.

Results: After matching for gender, age, histology, tumor stage and resection status, HCRT seemed superior to 3DCRT with a local relapse rate of 27.3% compared to 72.7% after 3DCRT (p = 0.06). The median time to local relapse was increased by 49% with HCRT in comparison to 3DCRT from 10.9 ± 5.4 months to 16.2 ± 3.1 months (p = 0.06). The median overall survival was 22.3 ± 15.3 months for HCRT and 21.2 ± 9.2 months for 3DCRT (p = 0.57). Recurrence analysis showed that in-field local relapses occurred in previously underdosed regions of the tumor bed in 16% of patients treated with 3DCRT and in 0% of HCRT patients.

Conclusions: The use of HCRT increases the probability of local control as compared to 3DCRT by improving target volume coverage. HCRT did not improve overall survival in this patient series due to the high rate of distant recurrences.

In plain English

This retrospective study reviewed 39 consecutive patients with malignant pleural mesothelioma treated at Zurich University Hospital between 1999 and 2011. All had chemotherapy, then extrapleural pneumonectomy, then radiotherapy. Twenty-five received older 3D conformal radiotherapy (3DCRT) and 14 newer highly conformal radiotherapy (HCRT). The study compared 22 patients matched in pairs. Three of 11 HCRT patients (27.3%) and 8 of 11 3DCRT patients (72.7%) had a local relapse. Median time to local relapse, counted from the start of chemotherapy, was 16.2 months in the HCRT group and 10.9 months in the 3DCRT group (p = 0.06), which the authors called a tendency. Median overall survival in the pairs was 22.3 months (HCRT) and 21.2 months (3DCRT) (p = 0.57). Nine of 11 patients in each matched group developed metastases. In 4 of 25 3DCRT patients (16%), relapses inside the treated area occurred where the dose was below that prescribed. No HCRT relapse occurred in a clearly underdosed region. The authors concluded that HCRT is likely to improve local control but did not improve survival, owing to frequent distant relapse.

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 single-institution review of treatment outcomes comparing two radiotherapy techniques, with a matched-pair analysis of a subset
• Who was studied: 39 consecutive patients with malignant pleural mesothelioma (clinical stage T1-T3, N0-2, M0) treated at Zurich University Hospital, Switzerland, between 1999 and 2011. They had neoadjuvant chemotherapy (pemetrexed and cisplatin), extrapleural pneumonectomy and radiotherapy: 25 with 3DCRT and 14 with HCRT (11 IMRT, 3 VMAT). A matched-pair analysis included 11 patients from each group.
• Exposure: The study did not examine asbestos exposure. It compared two postoperative radiotherapy techniques. The 3DCRT group (treated 1999 to 2005) received 25 x 1.8 Gy = 45 Gy to the hemithorax plus a boost of 7 x 1.8 Gy = 12.6 Gy to the incompletely resected area (total 57.6 Gy). The HCRT group (IMRT or VMAT, used from 2005) received 26 x 1.75 Gy = 45.5 Gy to the hemithorax, with a simultaneous boost of 26 x 2.15 Gy = 55.9 Gy to the R1/R2 region.
• Main results:
  • Matched pairs (11 per group): local relapse occurred in 3 HCRT patients (27.3%) and 8 3DCRT patients (72.7%). The abstract gives p = 0.06 for this comparison.
  • Matched pairs: median time to local relapse, measured from the start of neoadjuvant chemotherapy, was 10.9 plus or minus 5.4 months in the 3DCRT group and 16.2 plus or minus 3.1 months in the HCRT group (p = 0.06).
  • Matched pairs: 9 HCRT patients (81.8%) and 9 3DCRT patients (81.8%) developed metastases. The difference in disease-free survival was not significant (p = 0.72). Median overall survival was 22.3 plus or minus 15.3 months for HCRT and 21.2 plus or minus 9.2 months for 3DCRT (p = 0.57).
  • Entire cohort: median overall survival was 20.8 plus or minus 14.4 months in the HCRT group (n = 14) and 26.9 plus or minus 11.8 months in the 3DCRT group (n = 25) (p = 0.48).
  • Entire cohort: locoregional relapse occurred in 4 HCRT patients (28.6%) and 15 3DCRT patients (60%). For local control the article reports p = 0.30.
  • Recurrence analysis: in 4 of 25 3DCRT patients (16%), in-field recurrences occurred in regions that received only 30 to 43 Gy instead of the prescribed 45 Gy or more. Among HCRT patients, the 3 in-field relapses were in areas treated with 43 Gy to 59 Gy, none in a clearly underdosed region.
  • Entire cohort: distant recurrences occurred in 10 HCRT patients (71.4%) and 20 3DCRT patients (80%).
  • Entire cohort: death from intercurrent disease (most often cardiac events) occurred in 4 HCRT patients (29%) and 1 3DCRT patient (4%).
• The authors' conclusion: The authors concluded that HCRT after extrapleural pneumonectomy is likely to improve local control rates. In this series the improvement did not improve overall survival, because of high rates of distant relapse. Further improvement of trimodal or systemic therapy is required.
• Limitations the authors state:
  • The authors stated that patient selection is the most likely explanation for the higher rate of deaths from intercurrent (mostly cardiac) disease after HCRT.
  • When comparing their local control rates with another IMRT series, the authors noted patient selection and the retrospective study design as possible explanations.
  • The authors stated that no data were available comparing the two techniques for toxicity to the esophagus, heart, liver and kidney.

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: Pleural Mesothelioma, Neoadjuvant Therapy, Extrapleural Pneumonectomy (EPP), Overall Survival, Histology, Median Overall Survival.

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• Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy — M. Trovo, D. Franceschini, et al. (2019)
• Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma — T. Ebara, H. Kawamura, et al. (2012)
• Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study — T. Treasure, L. Lang-Lazdunski, et al. (2011)
• Resection and IORT followed by three-dimensional conformal radiotherapy with or without adjuvant chemotherapy for malignant mesothelioma — D.M. Jablons, M. Roach, et al. (1997)
• Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk? — P. Mordant, K. McRae, et al. (2016)

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