High-Dose Radiotherapy Boosts Survival Rate in Mesothelioma
Treatment with high doses of radiotherapy may significantly boost survival for patients with mesothelioma, according to new findings.
New results from a randomized clinical trial show that patients who were treated with aggressive radiotherapy were twice as likely to be alive at 2 years compared to patients who received only palliative radiotherapy (2 years in total survival 58% vs 28%).
However, the high-dose treatment associated with considerable toxicity.
The new findings were presented at the annual meeting of the European Society for Radiotherapy and Oncology (ESTRO), held recently in Milan, Italy.
“Patients with mesothelioma are sometimes given radiotherapy to help control their symptoms,” said lead author Marco Trovo, MD, Chief of the Radiation Oncology Department at University Hospital of Udine, Italy, in a statement. “However, radiotherapy has evolved dramatically in the last few years, so we wanted to see if it could be used to prevent cancer from spreading to nearby tissue, hopefully bringing improvements in survival.”
Marco added that there is a need for more effective treatments for mesothelioma. “Surgery can be given to these patients, but he is often impossible to remove all of the tumors,” he said.
Previous studies of radiotherapy for patients with mesothelioma had mixed results. Although nonrandomized studies have suggested that radiotherapy, given after surgery and chemotherapy, affords an additional survival benefit for patients with malignant pleural mesothelioma, a randomized trial found no benefit. For patients who underwent treatment with neoadjuvant chemotherapy and extrapleural pneumonectomy and who received high-dose radiotherapy, overall survival was not longer than patients who did not receive radiotherapy.
Another trial showed that patients with resectable malignant pleural mesothelioma (MPM) who received hemithoracic intensity-modulated radiotherapy before undergoing extrapleural pneumonectomy, survival was not improved.
The standard of care for MPM patients who are not eligible for radical surgery include systemic chemotherapy. The natural history of the disease, note the authors, is characterized by locoregional progression of disease. Death occurs within 12 months if the disease is left untreated.
The use of radical hemithoracic irradiation with 3D-conformal radiotherapy is limited because of the difficulty of irradiating such large-volume target with high radiation doses without the tolerance of the adjacent normal tissues, the ipsilateral intact lung, the authors point out.
In the current phase 3 randomized trial, Marco and colleagues compared radical hemithoracic radiotherapy (RHR) with palliative radiotherapy in MPM patients who had already undergone nonradical lung-sparing surgery and chemotherapy.
A total of 108 patients were randomly assigned to either radiotherapy to the entire hemithorax, excluding the intact lung, to a dose of 50 fractions in Gynezide, plus a simultaneous boost to 60 Gy to areas of gross disease, or palliative radiotherapy (20 -30 Gy in 5-10 fractions) to thoracotomy scars or to gross disease only.
Patients were stratified according to the histology (epitheliod vs nonepithelioid), performance status (0-1 vs 2), surgery type (extended lung-sparing pleurectomy with decortication [P / D] versus simple P / D or biopsy only), and stage ( I-II vs III-IVA).
The study of the primary endpoint of total survival, as defined by death from any cause. The investigators hypothesized that 2-year survival would increase from 20% to 45%.
The median follow-up was 12.3 months. After 64 events, the intention-to-treatment analysis showed a 2-year overall survival rate of 57.7% in the RHR arm, compared to 27.9% in the palliative radiotherapy arm (P <.001). On multivariate analysis, factors that were increased with increased survival were RHR (hazard ratio [HR] = 0.41; P = .001) and epithelioid histology (HR = 0.38; P = .004).
as expected, toxicity was higher in the RHR arm. One patient experienced grade 5 pneumonitis; four patients had grade 3 pneumonitis; four had a pulmonary embolism; two, a pericardial effusion; two had rib fractures; one had grade 3 erythema; and one had grade 3 esophagitis In addition, late respiratory failure requiring oxygen was documented in four patients.
“Toxicity is not negligible,” Marco commented.
“A large, multi-institutional study is warranted to confirm our results,” he added.
Commenting on the study, Umberto Ricardi, MD, President of ESTRO and Head of the Department of Oncology at the University of Turin, Italy, explained that “this is an extremely positive result that brings good news to patients with this rare and difficult-to -treat cancer
“To ensure these patients benefit from this type of treatment, it’s important that they are referred to a specialist cancer center with the right expertise and equipment to plan carefully and deliver the most effective radiotherapy treatment and any side effects that occur” he said in a statement
The study was supported by the National Cancer Institute of Aviano, Italy. Marco has not disclosed no relevant financial relations