Researchers in the U.K. are measuring the post-surgery effectiveness of prophylactic radiotherapy in reducing the chances of a patient developing new tumors along the incision path.
Although the procedure became standard practice more than a decade ago, continued debate over its effectiveness has led to the latest, multicenter clinical trial that began recently with more than 200 new mesothelioma patients.
“This [trial] will answer the question, ‘Is prophylactic radiotherapy of benefit to patients with large biopsy or chest wall incision sites in mesothelioma?'” lead researcher Dr. Nick Maskell, of the University of Bristol School of Sciences, told Asbestos.com. “This is the first, properly powered study to answer that question.”
The intent of radiotherapy is to prevent or reduce Procedural Tract Metastases (PTM), an often painful condition that can accelerate progression of mesothelioma.
Debate Over Usefulness of Radiotherapy Post-Surgery
Acceptance of the procedure stemmed from a much smaller sampling at one center in 1995 that produced a significant difference between patients who had radiotherapy immediately after surgery and those who did not. Although two ensuing studies in the U.K. produced less definitive results, the acceptance of the procedure continued.
Radiotherapy kills mesothelioma cells in the laboratory, but high doses of radiation are limited because of unacceptable toxicity. The lower dose radiation has minimal side effects, but its effectiveness remains questionable in preventing mesothelioma metastasis. In those earlier follow-up studies, the occurrence of PTM was identified in those who received radiation and those who did not.
“We genuinely don’t know what to expect now,” Maskell said. “As a properly run randomized clinical trial, we have no idea until the results are unblinded.”
Maskell expects to finish the study after the last patient crosses the 12-month mark in late August.
Immediate or Deferred Radiotherapy Groups
Patients in the on-going study will be randomized to receive either immediate radiotherapy after surgical intervention or deferred radiotherapy if PTM develops.
The primary outcome measure is the rate of PTM until death or 12 months (whichever occurs first). Secondary outcome measures include quality of life, radiotherapy toxicity and chest pain.
In a recent survey of U.K. cancer centers, 75 percent routinely offered prophylactic radiotherapy, although patient selection and treatment protocols were varied. The increasing use of indwelling pleural catheters has added to the uncertainty surrounding PTMs and radiotherapy.
The study will be conducted at six different cancer centers within the U.K. According to researchers, “the primary research question is to evaluate whether prophylactic radiotherapy prevents PTM following large bore pleural procedures in MPM.”
According to the trial details in the British Medical Journal (BMJ), the secondary research questions include:
- Does radiotherapy lead to differences in patient symptoms and quality of life, as compared to radiotherapy given in the event PTM develops?
- Does radiotherapy cause toxicity and impact the quality of life?
- What is the patient experience of immediate and deferred radiotherapy?
- What proportions of PTM are symptomatic, and to what extend is that modulated by giving radiotherapy?
- Is there a subgroup of mesothelioma in which radiotherapy is effective in reducing PTM?
- Is deferred radiotherapy (given when a nodule appears) as effective as radiotherapy in controlling symptoms?
- What are the economic health implications of giving radiotherapy when compared to deferred radiotherapy?
Quality of Life Is also Measured
Those patients in the Immediate Radiotherapy Group will be treated within 35 days of the pleural procedure. The treatment will include three doses, or fractions, over three days.
If patients in the immediate group develop a PTM, further radiotherapy treatment is at the discretion of the treating oncologist.
If patients in the deferred group are diagnosed with PTM, they will receive treatment within 35 days of the diagnosis. They will receive the same energy beam arrangement, technique and dose as those in the immediate radiotherapy group.
Follow-up exams will be done at intervals of one, three, six, nine and 12 months after the randomization process to determine quality of life regarding radiotherapy and the development or lack of development of PTM.
“In the U.K., we’re running more high-quality trials for mesothelioma than ever before,” Maskell said. “I hope it translates into progress toward better treatment options.”