Post-Surgery Hemithoracic Radiotherapy Not Supported in Mesothelioma

No obvious benefit of hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma

medwireNews: Phase II trial results suggest that patients with malignant pleural mesothelioma do not benefit from hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy.

The SAKK 17/04 investigators say in The Lancet Oncology that high-dose hemithoracic radiotherapy following macroscopically complete resection results in “an additional treatment burden without benefiting patients”.

Of 151 treatment-naive patients with stage I to III disease who received neoadjuvant cisplatin plus pemetrexed, 96 (64%) underwent extrapleural pneumonectomy, resulting in a complete macroscopic resection. And 54 of these patients continued to the second part of the trial, in which they were randomly assigned to either receive high-dose hemithoracic radiotherapy – where the median total dose was 55.9 Gy – or undergo observation.

The team led by Rolf Stahel, from University Hospital of Zurich in Switzerland, notes that 20 eligible patients did not consent to enrolment in the second part, which they assume was due to “both the heavy burden of neoadjuvant chemotherapy and extrapleural pneumonectomy and the unknown benefit of hemithoracic radiotherotherapy”.

And indeed, there was only a “slight improvement” in the primary endpoint of locoregional relapse-free survival in the radiotherapy (n=27) compared with the observation (n=27) arm, with a median from surgery of 9.4 versus 7.6 months. The corresponding times from registration were 12.2 and 11.0 months.

The researchers note that they were unable to enrol the intended number of participants in the radiotherapy arm, but add that their goal of improving locoregional relapse-free survival by 1 year is “out of reach with our broad patient selection”.

Calculated from registration, overall survival (OS) was a median of 19.3 months for patients who received radiotherapy and 20.8 months for those who did not. This was longer than the median OS of 15.0 months for all 151 enrolled patients, but the authors of a linked comment say that this cannot be attributed to treatment as “a prerequisite to being randomly assigned was continued survival with WHO performance status 0–2.”

Nausea or vomiting was the most frequent grade 3 or worse adverse event induced by radiotherapy, observed in 11% of participants, followed by oesophagitis (7%) and pneumonitis (7%). And one death was attributed to radiotherapy-related pneumonitis.

“Taken together with recent developments in lung-sparing surgery with extended pleurectomy and decortication, these are sobering results suggesting that our concepts for the treatment of malignant pleural mesothelioma developed over the past two decades need to be revised and alternative treatment options need to be considered”, the team concludes.

Commentator Robert Rintoul, from Papworth Hospital in Cambridge, UK, and co-authors agree with the conclusion, adding that “[t]he heterogeneity of mesothelioma and the multiplicity of treatments make it impossible to separate the signal from the noise without control groups.

“More randomised trials are needed so that even if the lives of patients with mesothelioma cannot be extended, at least they will not be given treatments that make their lives worse.”

References

Stahel RA, Riesterer O, Xyrafas A, et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.Lancet Oncol 2015; Advance online publication 01 November. doi: dx.doi.org/10.1016/S1470-2045(15)00208-9

Rintoul RC, Treasure T, Macbeth F. Multimodal treatment for malignant pleural mesothelioma.Lancet Oncol 2015; Advance online publication 01 November. doi: dx.doi.org/10.1016/S1470-2045(15)00253-3

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