Prostate Cancer
Conditions
Keywords
prostate neoplasms, interstitial radiation, High dose rate prostate brachytherapy, dose escalation
Brief summary
This study will investigate the feasibility of using technology of ultrasound guided HDR brachytherapy to focally increase dose to regions within the prostate that are heavily infiltrated with cancer. Such regions, referred to as dominant intraprostatic lesions (DIL) can be visualized using diffusion contrast enhanced MRI employing an endo-rectal coil. The magnetic resonance (MR) images can be fused with the planning transrectal ultrasound (TRUS) prior to the brachytherapy procedure to design a dose distribution that will encompass the malignant volume with higher than the prescription dose. By its nature, brachytherapy has subvolumes that receive (for example)125% of the prescription dose or 150% of the prescription dose. With TRUS-guided and TRUS-planned HDR these areas can be manipulated to coincide with the DIL. The limit of dose escalation has been reached at whole prostate external beam doses of 81-86 Gy and still failure rates for intermediate and high risk disease are unacceptable. There is much interest in focal dose escalation and TRUS-guided HDR brachytherapy is perfectly suited to achieving this.
Detailed description
Methods: If a dominant nodule is visualized on dynamic contrast enhanced (DCE) MRI, it will be contoured in 3D and the images fused to the planning TRUS study that is done in preparation for brachytherapy (of any type: seeds or HDR). The patient's treatment will consist of the standard combined external beam (4600 centiGray (cGy) in 23 fractions) and HDR brachytherapy boost (2 fractions of 1000 cGy given on days 5 and 15 of the external beam course). During each HDR treatment the plan will be manipulated such that the normally occurring high dose regions (125%, 150%) are positioned at the site of the identified disease. Normally approximately 60% of the prostate volume receives 125% of the dose and 30% receives 150%. By ensuring that the inherent dosimetry favors treatment of the known cancer, no region of the prostate would be underdosed. HDR treatments are performed under general anesthesia as an out patient procedure. Statistical Analysis: This is a feasibility study and the data reported will be descriptive including the frequency with which the DIL can be visualized in this population, the DIL volume compared to total prostate volume, and the isodose that can encompass the DIL without violating dose constraints to adjacent organs (urethra and bladder). Toxicity will be monitored and efficacy will be assessed by repeat DCE MRI at 12 months and biopsy at 30 months.
Interventions
RADIATIONHDR interstitial brachytherapy
2 treatments of 1000 cGy will be delivered to the entire prostate volume while escalating the dose to the visible disease to 1250 cGy
Sponsors
British Columbia Cancer Agency
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* histologically proven adenocarcinoma of the prostate * intermediate or high risk prostate cancer * Intermediate risk prostate cancer patients must have: * Clinical stage ≤ T2c, * Gleason score = 7 and initial prostate specific antigen (iPSA) ≤ 20, or * Gleason score ≤ 6 and iPSA \> 10 and ≤ 20. * High risk patients may have * Clinical stage T3 * Gleason score 8-10 * PSA \> 20 ng/ml * fit for general anesthetic. * unilateral disease with either a palpable nodule or a cluster of positive biopsies from a single region suggesting the presence of dominant nodule. * estimated life expectancy of at least 10 years. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2. * no contraindications to interstitial prostate brachytherapy. * if on coumadin therapy must be able to stop safely for 7 days. * must not have any contraindications to MRI
Exclusion criteria
* Does not meet staging criteria for intermediate or high risk prostate cancer * Does not have a localized high volume of intraprostatic disease * unfit for general anesthetic * MRI contraindicated * unable to stop blood thinners * Life expectancy \< 10 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Mean Dose to 90% of DIL Volume | 12 months | Feasibility of dose escalation to a minimum dose of 125% of prescription to 90% of the dominant intra-porstatic lesion (DIL) volume as defined on multiparametric endo-rectal magnetic resonance imaging (mpMRI) without exceeding critical organ dose constraints (Urethral volume receiving 115%= 0, Dose to 1cc of rectal wall \< 7 Gy). 2 Fractions were performed and the mean dose to 90% of DIL volume was averaged. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Toxicity | 24 months | Time to normalize International Prostate Symptom Score (months). Score range 0-35 with 35 being worst outcome. Normalization refers to a return to baseline urinary function prior to treatment. |
| Prostate Specific Antigen(PSA) Response at 5-years | 5 years | Efficacy assessed by biochemical PSA response reported at median 5 year follow up. |
Countries
Canada
Participant flow
Recruitment details
Aim of protocol was to have 25 patients for whom dominant lesion identified on MRI and dose escalation feasible with HDR brachytherapy
Pre-assignment details
One patient consented but ineligible because did not have a visible lesion on the MRI of his prostate.
Participants by arm
| Arm | Count |
|---|---|
| HDR Interstitial Brachytherapy HDR prostate brachytherapy with dose escalation to 1250 cGy to the MRI-defined dominant intraprostatic lesion
HDR interstitial brachytherapy: 2 treatments of 1000 cGy will be delivered to the entire prostate volume while escalating the dose to the visible disease to 1250 cGy | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | HDR Interstitial Brachytherapy |
|---|---|
| Age, Continuous | 63 years |
| Baseline PSA ng/mL | 10.4 ng/mL |
| clinical stage Stage T1c | 3 participants |
| clinical stage Stage T2a | 7 participants |
| clinical stage Stage T2b | 15 participants |
| Gleason score Gleason 7 | 23 participants |
| Gleason score Gleason 8 or 9 | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 5 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Average Mean Dose to 90% of DIL Volume
Feasibility of dose escalation to a minimum dose of 125% of prescription to 90% of the dominant intra-porstatic lesion (DIL) volume as defined on multiparametric endo-rectal magnetic resonance imaging (mpMRI) without exceeding critical organ dose constraints (Urethral volume receiving 115%= 0, Dose to 1cc of rectal wall \< 7 Gy). 2 Fractions were performed and the mean dose to 90% of DIL volume was averaged.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Rate (HDR) Interstitial Brachytherapy | Average Mean Dose to 90% of DIL Volume | 13.25 Grays | Standard Deviation 1.1 |
Secondary
Acute Toxicity
Time to normalize International Prostate Symptom Score (months). Score range 0-35 with 35 being worst outcome. Normalization refers to a return to baseline urinary function prior to treatment.
Time frame: 24 months
Population: Months to normalization of International Prostate Symptom Score following treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High Dose Rate (HDR) Interstitial Brachytherapy | Acute Toxicity | 1.5 months |
Secondary
Prostate Specific Antigen(PSA) Response at 5-years
Efficacy assessed by biochemical PSA response reported at median 5 year follow up.
Time frame: 5 years
Population: All 25 underwent dose escalation to dominant lesion in prostate to median 132% of prescription dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High Dose Rate (HDR) Interstitial Brachytherapy | Prostate Specific Antigen(PSA) Response at 5-years | 0.06 ng/ml |