Image-guided Radiotherapy for Prostate Cancer

(MIDAS-Prostate Trial)

Overseen By Srinivas Raman

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Para-aortic nodes, Distant metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new form of radiation therapy, Image-guided Radiotherapy (IGRT), for men with recurrent prostate cancer after surgery. The focus is on using imaging to target and intensify radiation at cancer sites while minimizing exposure to healthy areas. This approach aims to improve outcomes and reduce side effects. Men who have undergone prostate cancer surgery and show signs of recurrence based on imaging tests might be eligible. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future treatment options.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this image-guided radiotherapy is safe for prostate cancer patients?

Research shows that image-guided radiotherapy (IGRT) for prostate cancer is generally safe and well-tolerated. Studies have found that survival rates for patients undergoing IGRT are similar to those who do not, indicating no harm to survival chances. One study found that patients receiving frequent daily IGRT had better outcomes in preventing cancer recurrence, as stable cancer markers after treatment demonstrated.

While side effects can occur, they usually affect the pelvic area, such as bowel or bladder issues, and are often manageable. Importantly, studies have not identified any unexpected or severe safety concerns with IGRT. This makes IGRT a promising option for treating prostate cancer, especially when carefully planned and monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about image-guided radiotherapy for prostate cancer because it allows for more precise targeting of cancerous cells. Unlike traditional radiotherapy options, this method uses molecular imaging to adjust radiation doses—escalating them for areas with recurrent disease and reducing them for healthy tissues. This tailored approach aims to maximize treatment effectiveness while minimizing side effects, potentially offering a more personalized and less harmful treatment option for patients.

What evidence suggests that image-guided radiotherapy is effective for prostate cancer?

Research has shown that image-guided radiotherapy (IGRT), the treatment under study in this trial, can benefit prostate cancer patients. Studies have found that IGRT lowers levels of certain markers indicating cancer activity, aiding in tumor control. It also reduces the risk of side effects related to the stomach and urinary systems, which are common with radiation treatments. However, while IGRT can better control cancer and lessen some side effects, it has not been proven to significantly increase overall survival rates over five years. Overall, IGRT is a promising method for precisely targeting recurring prostate cancer. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for men over 18 with a history of prostate cancer, who've had surgery but are now experiencing a relapse confirmed by PSMA PET scans. They should be relatively healthy and active (ECOG 0-1) and have no more than five positive nodes on their scan. Men with contraindications to radiation, distant metastasis, chronic pelvic inflammation, or previous pelvic radiation can't join.

Inclusion Criteria

I am a man over 18 years old.

My cancer has returned and is shown on a PSMA PET scan.

I have had surgery to remove my prostate.

Exclusion Criteria

My cancer has spread to the lymph nodes near my aorta or to distant parts of my body.

I have had radiation treatment in my pelvic area.

I cannot undergo radiation therapy due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive molecular imaging informed radiation dose escalation to sites of recurrent disease and de-escalation to uninvolved areas

12 weeks

Weekly visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Visits at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Image-guided Radiotherapy

Trial Overview The study tests if adjusting the radiation dose based on molecular imaging can help in treating prostate cancer that has come back after surgery. Participants will get higher doses at the recurrence site and lower doses elsewhere. The effects will be monitored for up to five years.

How Is the Trial Designed?

Group I: Molecular Imaging Informed Radiation Dose Escalation and De-escalation Experimental Treatment 1 Intervention

Molecular imaging informed radiation dose escalation to sites of recurrent disease and de-escalation to uninvolved areas.

Image-guided Radiotherapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Image-guided Radiation Therapy for:

• Prostate cancer
• Various cancers requiring radiation therapy

Approved in European Union as Image-guided Radiation Therapy for:

• Prostate cancer
• Various cancers requiring radiation therapy

Approved in Canada as Image-guided Radiation Therapy for:

• Prostate cancer
• Various cancers requiring radiation therapy

Approved in Japan as Image-guided Radiation Therapy for:

• Prostate cancer
• Various cancers requiring radiation therapy

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study involving 40 prostate cancer patients undergoing curative radiotherapy, both surface imaging and trans-abdominal ultrasound (US) were used to assess patient setup and internal organ variations, revealing significant differences in systematic errors only in the lateral direction.

The findings suggest that surface imaging can effectively predict setup errors detected by US, indicating that these two imaging modalities could work together as complementary, non-invasive tools for improving the precision of radiotherapy in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-dimensional surface and ultrasound imaging for daily IGRT of prostate cancer. Krengli, M., Loi, G., Pisani, C., et al.[2018]

Patients treated with high-dose image-guided radiotherapy (IGRT) for prostate cancer experienced significantly lower rates of late urinary toxicity (10.4%) compared to those treated with high-dose intensity-modulated radiotherapy (IMRT) (20.0%), indicating a safer profile for IGRT.

For high-risk prostate cancer patients, IGRT not only reduced urinary toxicity but also improved biochemical tumor control compared to IMRT, suggesting that daily tracking of target positioning enhances treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Zelefsky, MJ., Kollmeier, M., Cox, B., et al.[2022]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

Prostate cancer patients receiving image-guided radiotherapy (IGRT) experienced significantly less severe acute toxicity, such as urinary frequency, diarrhoea, and fatigue, compared to those who did not receive IGRT, with 23% vs 7% for urinary frequency ≥G3 and 15% vs 3% for diarrhoea ≥G2.

The onset of these toxicities was earlier in the non-IGRT group, indicating that IGRT not only reduces the severity of symptoms but also delays their onset, leading to a more tolerable treatment experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Gill, S., Thomas, J., Fox, C., et al.[2021]

In a study of 26 patients undergoing post-prostatectomy radiation therapy, daily image-guided radiation therapy (IGRT) effectively localized the prostate bed, with average movements recorded in three dimensions, indicating the need for precise targeting during treatment.

The treatment was generally well-tolerated, with most patients experiencing only mild (grade 1) symptoms, and no severe (grade 3 or higher) acute toxicity, suggesting that IGRT is a safe option for improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate bed localization with image-guided approach using on-board imaging: reporting acute toxicity and implications for radiation therapy planning following prostatectomy. Sandhu, A., Sethi, R., Rice, R., et al.[2022]

Image-guided radiotherapy (IGRT) using kilovoltage cone beam computed tomography (kV-CBCT) and ultrasound (US) is effective for accurately targeting tumors, particularly in cases of prostate displacement before treatment.

Both kV-CBCT and US-IGRT require specialized knowledge for proper application, and further research is needed to understand their impact on the organization and efficiency of radiotherapy departments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Considerations in Cone Beam and Ultrasound IGRT Systems in Prostate Localization: A Review of the Literature. Tran, WT.[2019]

In a study involving 40 prostate cancer patients, ultrasound (US) localization showed a significant mean discrepancy of 8.8 mm compared to fiducial seed marker (SM) localization, indicating that US may introduce greater variability in treatment positioning.

The findings suggest that larger planning target volume (PTV) margins are needed when using US for image-guided radiotherapy (approximately 9 mm) compared to SM (approximately 3 mm), highlighting the importance of choosing the right localization method for accurate treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of ultrasound and implanted seed marker prostate localization methods: Implications for image-guided radiotherapy. Scarbrough, TJ., Golden, NM., Ting, JY., et al.[2016]

Patients with high-risk prostate cancer treated with image-guided intensity-modulated radiotherapy (IG-IMRT) experienced significantly lower rates of gastrointestinal (GI) toxicity (5.8%) compared to those treated with 3D conformal radiotherapy (3DCRT) (57.3%), indicating that IG-IMRT is a safer option.

Both IG-IMRT and 3DCRT showed similar rates of biochemical progression-free survival at 3 years (90.3% for IG-IMRT vs. 86.0% for 3DCRT), suggesting that while IG-IMRT reduces toxicity, it does not compromise treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. Sveistrup, J., af Rosenschöld, PM., Deasy, JO., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9668680/

The role of image-guided radiotherapy in prostate cancer IGRT was associated with an improvement in biochemical tumor control and a reduction in GI and acute GU toxicity, but did not significantly improve 5-year OS ...

2. redjournal.org redjournal.org/article/S0360-3016(22)02962-5/fulltext

The Impact of Image Guided Radiation Therapy (IGRT) on ... This is the first meta-analysis to demonstrate that IGTR control in prostate cancer significantly reduces G2+ acute GI and GU toxicity and improves PSA relapse ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0167814024002317/pdf

Image guided radiotherapy in curative treatment for ... Daily 3-D IGRT did not improve side effects, health related quality of life or progression free survival as compared to weekly 2-D IGRT in treatment of prostate ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2012.30.5_suppl.12

Clinical outcomes with high-dose image guided ... Methods: 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based upon ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214122

Fifteen-Year Outcomes after Monitoring, Surgery, or ... After 15 years of follow-up, prostate cancer–specific mortality was low regardless of the treatment assigned.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8506193/

Safety of image-guided radiotherapy in definitive ... We demonstrated that the overall survival for prostate cancer patients with IGRT was not worse than those who did not undergo IGRT.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405630822001008

The role of image-guided radiotherapy in prostate cancer Compared with weekly IGRT, high-frequency daily IGRT could lead to greater 3-year biochemical failure-free survival (BFFS) benefit in prostate cancer patients.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04035642

Phase II Study of Single-Dose Image-Guided Radiotherapy ... The present study evaluates clinical outcomes and treatment-related toxicity following definitive ultra-high single dose external beam radiotherapy.

9. thegreenjournal.com thegreenjournal.com/article/S0167-8140(19)33453-X/fulltext

A randomised assessment of image guided ... We present a pre-planned analysis of the impact of IGRT on dosimetry and acute/late pelvic side effects using gastrointestinal and genitourinary clinician and ...

10. practicalradonc.org practicalradonc.org/article/S1879-8500(22)00320-4/abstract

Quality and Safety Considerations in Image Guided ... This updated report on image guided radiation therapy (IGRT) is part of a series of consensus-based white papers previously published by the ...