Precision RT May Prove Curative in Oligometastatic Cancer

Pam Harrison

October 19, 2018

SAN ANTONIO — The use of stereotactic ablative radiotherapy (SABR) significantly prolongs overall survival (OS) and doubles progression-free survival (PFS) in patients with limited metastatic spread from a variety of primary tumors compared with standard of care, a randomized phase 2 study known as SABR-COMET suggests.

"The oliogometastatic paradigm suggests that patients with a limited number of metastases may be curable if all sites of disease are eradicated with ablative therapies such as surgery or radiation," David Palma, MD, PhD, London Health Sciences Center, Ontario, Canada, explained to Medscape Medical News.

"But until now, we have not had good, randomized evidence [to support this paradigm], so it's been debated over many years as to whether patients with a few — 'oligo' — metastases should be treated aggressively," he added.

"As far as we are aware, this is the strongest evidence yet that supports this paradigm, so while we don't know yet if these patients are cured, this does look promising," Palma observed.

Asked by Medscape Medical News to comment on the findings, Brian Kavanagh, MD, MPH, chair of the American Society for Radiation Oncology (ASTRO) and of the Department of Radiation Oncology at the University of Colorado School of Medicine, Aurora, felt that the SABR-COMET study was "groundbreaking" and that it will resonate for many years to come.

"David Palma and his team flipped the script on metastatic disease," he said in an email.

For decades, the assumption has been that using radiotherapy to eliminate small deposits of cancer scattered throughout the body would be an exercise in futility, Kavanagh noted.

"But Dr Palma's team has now shown that at least for some patients, there is an opportunity to improve patient outcomes with modern, precise radiation techniques targeting isolated metastases," he wrote.

"Taken together with a similar trial being reported at this year's ASTRO meeting, we even have independent validation of this concept across multiple tumor types," Kavanagh said.

Median OS: 41 vs 28 months

SABR-COMET is an open-label, randomized study that involves 99 patients, all of whom had undergone previous treatment but whose cancer had recurred in as many as five different sites. The great majority of cancers recurred in one to three sites.

Patients had had a range of cancers, most commonly of the breast, lung, colon, and rectum, but also of the prostate.

Patients were randomly assigned to receive either stereotactic radiotherapy or palliative standard of care (either chemotherapy or immunotherapy or palliative radiotherapy.)

At a median follow-up of 27 months, median OS in the stereotactic radiotherapy arm was 41 months, compared with 28 months for the standard-of-care arm (P = .09), for an overall survival gain of 13 months for patients treated with stereotactic radiotherapy.

Median PFS was 12 months in the stereotactic radiotherapy arm, compared with 6 months in the standard-of-care arm (P = .022).

Unlike conventional radiotherapy, SABR — also known as stereotactic body radiation therapy — allows oncologists to give patients very large doses of radiation in only three to five treatments.

It also allows interventionalists, using image-guided techniques, to target tumors much more precisely than they could 10 or 15 years ago.

Stereotactic radiotherapy is performed as an outpatient procedure, so patients do not have to come into hospital, Palma noted. It is highly effective precisely because the doses used are much larger than oncologists were able to give in the past.

The rate of side effects of grade ≥2 was higher, at 30% in the stereotactic radiotherapy arm, compared with only 9% in the standard-of-care arm.

The most common of these side effects were fatigue, dyspnea, and muscle, joint, and bone pain.

Three treatment-related deaths occurred in the stereotactic radiotherapy arm.

Palma noted that a 30% side effect rate is in keeping with other treatments for cancer, such as surgery to treat lung cancer.

Importantly, there were no differences in quality of life at either 6 months or later in the trial, nor were there any differences in scores on the physical, social, functional, or emotional quality-of-life subscales between the two treatment groups.

Investigators are proceeding with a second, similarly designed study in which they are planning to treat patients who have up to 10 sites of recurrence.

In this trial, "we are going to be giving a bit lower dose of the stereotactic radiation in order to keep the side effects as low as possible," Palma noted.

In the meantime, the investigators have modified the current study so as to be able to follow patients up for 10 years instead of the original 5 years as planned.

"Often in cancer, we define cure as getting patients out to 5 years, and for some cancers, out to 10 years, without the cancer coming back," Palma observed.

"And in this study, a proportion of patients were getting out to 5 years without having the cancer come back, or else we've treated additional spots of cancer that have come back with the radiation therapy again," he added.

"Since these results were so good, we've extended the study out to 10 years so we can get a better idea if these patients are actually being cured or not," Palma noted.

Funding for the study was provided by the Ontario Institute for Cancer Research and a catalyst grant from the London Regional Cancer Program. Dr Palma and Kavanagh have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 2018. Abstract 5, to be presented October 22, 2018.

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