The first report from a phase II, multi-centre clinical
trial indicates that stereotactic radiation can extend long-term survival for
some patients with stage-IV cancers while maintaining their quality of life.
The study is published in the January issue of International Journal of
Radiation Oncology * Biology * Physics (Red Journal), the flagship
scientific journal of the American Society for Radiation Oncology (ASTRO).

“Despite many advances in cancer care over the last 20
to 30 years, some patients still go on to develop metastatic or stage-IV
disease. Generally speaking, radiation therapy in that setting has been used
only to make the patient comfortable,” said Dwight E. Heron, MD, MBA, FACRO,
FACR, senior author of the study and director of radiation services at UPMC
Hillman Cancer Center in Pittsburgh.

“It also has been the case, however, that a small
number of patients with stage-IV disease could have surgery to remove their
metastases and live a long time. And so our question was, could we use highly
focused radiation to destroy those tumours and have the same effect as surgery?
The initial answer from this large prospective trial is yes.”

Patients in the trial were treated with stereotactic radiation,
a form of high-precision cancer therapy that delivers substantially higher
doses of radiation to the tumour site in one to five treatment sessions.
Increasing evidence points to stereotactic radiation as a viable alternative
when patients cannot undergo surgery to remove metastatic tumours.

“With stereotactic radiation, we use a different type
of highly precise local therapy to target tumours in the lungs, liver, bones or
kidneys with precision that is analogous to surgery, and with very few side
effects or harm to the patient’s quality of life,” said Dr Heron, who is
also a professor of radiation oncology, otolaryngology and head and neck
surgery at the University of Pittsburgh School of Medicine.

In this phase II trial, Dr. Heron and his colleagues
enrolled 147 patients across three large cancer centres to evaluate the safety
and feasibility of stereotactic radiation for a variety of oligometastatic
cancers. Each patient had up to five metastases – most had either one (71%) or
two (19%) – in one to three new sites. The metastases were located most
commonly in the lung (52%), followed by lymph nodes (16.5%), bone (15%) or
liver (7%).

All patients received stereotactic radiation to all
metastatic sites. Radiation dosing and fractionation were dependent on the size
and location of each metastasis. All patients had good performance status (ECOG
0-1) and a life expectancy of more than 6 months. Median follow-up time for
this report was 41 months (range=14.6-59.0).

Following treatment with stereotactic radiation, more than
eight in ten patients (84%) survived at least 1 year, and four in ten (43%)
survived 5 years or longer. The median overall survival (OS) time was 42.3
months.

Local recurrences were uncommon; half of the patients
experienced complete (26%) or partial (26%) remission following treatment. An
additional third (32%) had stable disease, meaning their cancer did not progress
or recede. The remaining patients either had local progression following
treatment (14%) or their response could not be determined (12%). Distant
recurrences were more common, with a median time of 8.7 months until distant
progression. The one-year and five-year rates of distant progression free
survival (DPFS) were 44% and 17%, respectively.

The type of primary tumour was associated with both OS
(p=0.002) and DPFS (p=0.008). Patients with primary breast (9% of patients),
prostate (7.5%) and colorectal (21%) tumours had longer survival than those
with primary lung (22%) or head and neck (11%) tumours.

Severe side effects were limited. Just under 10% of patients
experienced short-term toxicity of grade-2 or higher, including one grade-3 case
each of labored breathing, skin inflammation and anemia. Even fewer patients
had severe long-term toxicity, with one grade-3 ureter obstruction and one
grade-4 obstruction of the small bowel.

A unique aspect of the trial design was the decision to use
patient-reported rather than physician-assessed quality of life (QoL). Patients
reported no significant changes in their quality of life immediately after
completing stereotactic radiation, nor at 6 weeks, 3 months and 9 months
follow-up. At the 6- and 12-month marks, QoL was significantly better than
before treatment.

Dr Heron said his team plans to continue enrolling patients
into the trial, with a goal of expanding the current 147 patients to roughly
200 total patients. Moving forward with additional trials, they also will look
at treating patients with larger numbers of metastatic lesions and combining
stereotactic radiation with emerging treatments such as immunotherapy.

“In combination with immunotherapy, stereotactic
radiation therapy may set a new bar for achieving better outcomes, lowering side
effects and improving our patients’ quality of life,” said Dr Heron.

This trial adds to the growing body of evidence supporting
the use of stereotactic radiation for oligometastatic cancers. Two randomised,
phase II trials presented at the most recent ASTRO Annual Meeting, for example,
also found the treatment may lengthen survival, sometimes dramatically, for
patients with stage-IV disease. If validated through larger randomised trials,
radiation therapy could be utilised as a safe and effective approach to improve
outcomes for patients with cancers that have begun to spread throughout the
body.

Source: American Society for Radiation
Oncology

Reference: Sutera
P, et al. Initial Results of a Multicenter Phase 2 Trial of Stereotactic
Ablative Radiation Therapy for Oligometastatic Cancer. International Journal of
Radiation Oncology*Biology*Physics, January 2019; 103 (1). https://www.redjournal.org/article/S0360-3016(18)33573-9/fulltext