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

Trial Summary

What is the purpose of this trial?

This is a Phase II prospective sing-arm trial that is recruiting 60 participants from patients that have biochemical failure after radical prostatectomy with local or regional recurrence proven by PSMA PET. Participants of this study will receive molecular imaging informed radiation dose escalation to site of recurrent disease and de-escalation to uninvolved areas. Participants will be follow-up as per standard of care up to 5 years post-treatment.

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 data supports the effectiveness of the treatment Image-guided Radiotherapy for Prostate Cancer?

Research shows that Image-guided Radiotherapy (IGRT) improves the accuracy of radiation delivery, which can reduce side effects and improve outcomes for prostate cancer patients. Studies have found that IGRT, especially when combined with intensity-modulated radiation therapy (IMRT), results in lower toxicity and better control of cancer compared to older methods without daily image guidance. ^{1 2 3 4 5}

Is image-guided radiotherapy (IGRT) safe for humans?

Research shows that image-guided radiotherapy (IGRT) for prostate cancer generally results in fewer acute toxicities (short-term side effects) compared to treatments without image guidance, suggesting it is safe for use in humans. ^{1 4 5 6 7}

How is Image-guided Radiotherapy (IGRT) different from other treatments for prostate cancer?

Image-guided Radiotherapy (IGRT) is unique because it uses imaging techniques like ultrasound and cone beam CT to precisely target the prostate, allowing for more accurate radiation delivery and reducing damage to surrounding healthy tissue. This precision helps in adapting to daily changes in prostate position, which can improve treatment outcomes and reduce side effects compared to traditional radiotherapy methods. ^{1 2 3 4 8}

Eligibility Criteria

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

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

I am a man over 18 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Comparison of ultrasound and implanted seed marker prostate localization methods: Implications for image-guided radiotherapy. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Three-dimensional surface and ultrasound imaging for daily IGRT of prostate cancer. [2018]

5. England 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. [2021]

6. United States 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. [2022]

7. Japan 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. [2018]

8. Ireland 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. [2022]