Strategies to Reduce Radiotherapy Side Effects and Treatment

Strategies to Reduce Radiotherapy Side Effects and Treatment Time: Abe Alexander BSc MD FRCPC Radiation Oncologist & Clinical Associate Professor BC Cancer-Victoria

Outline Space OAR Hydrogel to reduce radiotherapy-related side effects. Prostate Stereotactic Ablative Radiotherapy (SABR) Reduced treatment time. Potential for more favorable outcomes. Potential to combine these technologies to further improve outcomes

Prostate cancer is common Prostate cancer is the most commonly diagnosed cancer in men, and the 3 rd most common cause of cancer death in men. >20, 000 men diagnosed/year in Canada. >4000 deaths/year Canadian Cancer Society

Management options for localized prostate cancer Active Surveillance Surgery (Radical prostatectomy) External Beam Radiotherapy. Prostate Brachytherapy Each has its advantages and disadvantages. Choice depends on age, health status, disease risk, stage, grade, other health conditions, preferences

External Beam Radiotherapy Treatment of choice for many men. Non-invasive. Requires 20 -40 fractions over 4 -8 weeks. Favorable side effect profile. Short and long-term bowel toxicity can be a problem for some men.

Why does prostate radiotherapy cause bowel side effects? The rectum sits against the prostate. Part of it is within the high dose radiation field.

Improvements in technology have reduced the size of the high dose region. It is impossible for these measures alone to eliminate high dose to the rectum 10 -22% have significant long-term bowel side effects that affect quality of life RTOG 0415, CHHi. PS, PROFIT

Space OAR Hydrogel A novel product to move the rectum away from the prostate, out of the high dose region

Polyethylene Glycol polymer injected between the prostate and rectum forming a gel that pushes the rectum away from prostate by about 1. 5 -2 cm.

Outpatient procedure done under local anaesthetic. Trans-rectal ultrasound guides placement. Done about 3 weeks prior to starting radiotherapy. Gel is stable for 3 -4 months, then slowly dissolves.

Rectum Prostate Space OAR Hydrogel

Space OAR Application has moved the rectum out of the high dose radiation region. Before Rectum (brown) After High dose region (blue/green/yellow) Space OAR Hydrogel

Space OAR Hydrogel Clinical Trial 222 men with prostate cancer having radiotherapy. 1/3 randomly assigned Space OAR Hydrogel. All received standard EBRT

Clinical Trial results: Reduced rate of long-term bowel toxicity: 10% vs 2% Moderate to severe effects: 6% vs 0% Improved bowel-related quality of life Reduced rate of urinary incontinence. 15% vs 4% May reduce the rate of sexual dysfunction. No detrimental effects on disease control

Victoria Space OAR Hydrogel Program Approximately 80 patients have received Space OAR Hydrogel >90% report ‘no change’ or ‘improved’ bowel function score after radiation.

Future plans Expand the use of Space OAR Hydrogel to other BC Cancer Sites. Expand the use to a wider variety of radiation techniques Prostate Brachytherapy Prostate Stereotactic Ablative Radiotherapy

Prostate Stereotactic Ablative Radiotherapy (SABR) A relatively novel form of high precision prostate external beam radiotherapy that delivers treatment in a small number of large dose sessions or fractions (<5).

Advantages of Prostate SABR Convenience May have superior disease control May have more favorable side effect profile

Because each treatment (or fraction) delivers a much larger sized dose than conventional EBRT, SABR must be delivered in a very precise and accurate fashion, with the radiation tightly focussed on the prostate, in order to avoid damage to normal tissues.

What is involved with SABR delivery? 1. Accurate patient setup and targeting of the prostate on each day of treatment. (Aim correctly) 2. Highly conformal radiation delivery. (Radiation highly focussed on target) 3. Minimize patient/prostate motion during radiation delivery. (Make sure we hit the target)

1. Accurate Targeting of the prostate Gold seeds inserted into prostate as ‘fiducial markers’

Robotic couch moves patient so that the markers (and prostate) are in the correct position

CT scan confirms correct positioning before radiation is delivered.

What is involved with SABR delivery? 1. Accurate patient setup and targeting of the prostate on each day of treatment. (Aim correctly) 2. Highly conformal radiation delivery. (Radiation highly focussed on target) 3. Minimize patient/prostate motion during radiation delivery. (Make sure we hit the target)

Volumetric modulated arc therapy: A complex planning & delivery technique to conform the high dose radiation region tightly to the prostate

What is involved with SABR delivery? 1. Accurate patient setup and targeting of the prostate on each day of treatment. (Aim correctly) 2. Highly conformal radiation delivery. (Radiation highly focussed on target) 3. Minimize patient/prostate motion during radiation delivery. (Make sure we hit the target)

Minimizing patient motion while beam is on: Ultra-fast treatment delivery, called 10 x Flattening Filter free mode, <1 -2 minutes. Radiation machine can take periodic images during treatment and move patient if prostate has moved. Many other methods available.

The end result is a highly focussed, accurate, precise radiation treatment that can be delivered in 5 sessions, each lasting only a few minutes.

Is SABR as good as other treatment options? Comparisons with other treatments ongoing. A large Swedish trial with 5 years of follow-up demonstrated that 7 fraction SABR is at least as effective as conventional EBRT. Ongoing UK trial of 5 fraction SABR demonstrated favorable acute side effects, similar to EBRT. Retrospective data suggests SABR may have similar outcomes as brachytherapy, better than EBRT Widmark 2019 (Hypo. RT PC), Brand 2019 (PACE-B), Loblaw 2016

BC Cancer ASSERT study Recently completed randomized phase 2 trial comparing prostate SABR with conventional EBRT. Results pending

Prostate SABR in BC Coronovirus pandemic provides further rationale for SABR, as a COVID mitigation strategy to minimize patient footprint at Cancer Centers. Plans to begin offering prostate SABR on registry study in the near future.

Future Directions? Combining Space OAR Hydrogel and Prostate SABR?

Rationale for SABR + Space OAR Hydrogel Data suggests that ‘dose escalated SABR’ may result in higher rates of disease control Dose ‘escalated SABR’ is associated with unacceptable rates of moderate to severe rectal side effects. Combining SABR and Space OAR Hydrogel may allow for the safe delivery of escalated doses of SABR, potentially improving disease control. Hannan 2016. European J of Cancer. 59: 142 -51

Thank you! Questions?