High-Dose Radiotherapy Boosts Survival Rate in Mesothelioma

Roxanne Nelson, RN, BSN

May 07, 2019

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 only received palliative radiotherapy (overall survival at 2 years was 58% vs 28%).

However, the high-dose treatment was 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 now be used to prevent the cancer from spreading to nearby tissue, hopefully bringing improvements in survival."

Marco added that there is an urgent need for more effective treatments for mesothelioma. "Surgery can be given to these patients, but it is often impossible to remove all of the tumor," 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 extra 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 that of patients who did not receive radiotherapy.

Another trial showed that for 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 candidates for radical surgery includes 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 a large-volume target with high radiation doses without exceeding the tolerance of the adjacent normal tissues, especially 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 receive either radiotherapy to the entire hemithorax, excluding the intact lung, to a dose of 50 Gy in 25 fractions, 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 the gross disease only.

Patients were stratified according to histology (epitheliod vs nonepithelioid), performance status (0–1 vs 2), surgery type (extended lung-sparing pleurectomy with decortication [P/D] vs simple P/D or biopsy only), and stage (I–II vs III–IVA).

The study's primary endpoint was overall survival, defined as the amount of time from enrollment until 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-treat 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 associated 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 larger, 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 carefully plan and deliver the most effective radiotherapy treatment and manage any side effects that occur," he said in a statement.

The study was supported by the National Cancer Institute of Aviano, Italy. Marco has disclosed no relevant financial relationships.

ESTRO 38: Abstract OC-0500. Presented April 29, 2019.

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