Remarkable Success with Precision Radiotherapy in Cancers with Few Metastases

Among all stage 4 cancer patients, the disease course is now known to differ. Some patients with a small number of metastases may achieve long survival with intensive treatment and, rarely, even a complete cure. Having a small number of metastases is called oligometastasis in oncology, and destroying these few metastatic tumors with a local/regional treatment such as radiotherapy is thought to improve survival, although evidence had been insufficient until now. THE LANCET published the SABR-COMET study in April 2019. In a group with 1 to 5 metastatic tumors at any site, comprising approximately 100 patients, a form of external radiotherapy, stereotactic body radiation therapy (SBRT), palliative care was the comparator, and survival improved with SBRT (41 versus 28 months).

How has the concept of “oligometastasis” changed the outlook on stage 4 cancer?

The theory explaining that stage 4 (metastatic) cancers do not all have the same biology, the metastatic spectrum theory, was first described by Dr. Weichselbaum and Hellman . According to this theory, they predicted that some patients would develop only limited metastatic disease called oligometastasis. We now understand this concept much better as oligometastatic disease. Patients with few metastases confined to certain organs have a more favorable disease course than those with widespread metastases, and local treatment with curative intent may be given. Two examples are colon cancer with liver metastases only, and breast cancer with bone metastases only. In breast cancer with only bone metastasis , one nonsurgical cancer treatment or radiotherapy may be applied to the bone metastasis, while the breast tumor receives the standard regional treatment approach.

What are stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS)?

SBRT differs from conventional external radiotherapy in that the total calculated radiation dose is given in a single session or a few sessions (fractions).

Stereotactic radiosurgery (SRS) is used for brain tumors, whereas stereotactic body radiation therapy (SBRT) is used to irradiate organs outside the brain, such as the lungs, bones or liver.

Giving the total calculated dose for SBRT in a few sessions has made it possible both to achieve substantial destruction and to reduce radiation side effects. By providing results close to surgery in early-stage cancers, SBRT has become one of the most popular nonsurgical cancer treatments. It also offers effective results in treating oligometastases, for example spinal cord compression caused by spinal metastasis.

SBRT is thought to act in 3 ways in treating tumors:

• Direct destruction of the tumor by radiation to an extent almost equivalent to surgery,
• Contraction of blood vessels, reducing blood flow to the tumor, and
• Stimulation of the immune system by substances released from damaged cancer cells.

Below, you can see an early-stage tumor in the left lung being treated with SBRT:

Stereotactic techniques require high-resolution imaging. They are particularly preferred for small, well-defined tumors (for example, when lung cancer has metastasized to a single vertebra).

Because a high radiation dose is delivered to a specific point, keeping the patient still (immobilization) is especially important in this method.

The SABR-COMET study

This randomized, open-label phase 2 clinical trial was conducted at 10 hospitals in Canada, the Netherlands, Scotland and Australia. Patients had 1 to 5 metastases, an ECOG performance score of 0-1, and a life expectancy of at least 6 months. After stratification by metastasis count (1–3 versus 4-5), patients were randomized at a 2-to-1 ratio into two arms. The treatment arm received stereotactic ablative radiotherapy (SABR), while the control arm received palliative care (the term SABR was used instead of SBRT in this study). The primary endpoint the study aimed to measure was overall survival.

Findings

• Patients were enrolled between 2012-2016.
• Of 99 patients, 33 (% 33) were assigned to the control group and 66 (% 67) to the SABR group.
• Two (% 3) patients in the SABR group did not receive treatment because they withdrew from the study; two (% 6) control patients also withdrew. 
• In the control group, median follow-up was 25 months, compared with 26 months in the SABR group. 
• Median overall survival was 28 months in the control group and 41 months in the SABR group.
• SABR reduced the risk of death by %43 compared with palliative care alone.
• After SABR, among 66 patients, 3 (% 4-5) experienced treatment-related death, whereas no patient in the control group died as a result of palliative care.

Comment

Stereotactic ablative radiotherapy (SABR) was associated with improved overall survival, meeting this study’s primary endpoint, but in the SABR group of 66 patients, three (% 4-5) had treatment-related deaths. Larger phase 3 trials are needed to demonstrate a definitive overall survival benefit and determine the maximum number of metastatic lesions for which SABR provides a benefit. Recognizing that SABR was compared only with palliative treatment, rather than systemic treatment, it may be an alternative option for carefully selected patients with a limited number of metastases. 

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