Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients treated with a Single Fraction Real-Time High-Dose-Rate (HDR 19Gy)

MRI-TRUS fusion guided Single Frac HDR

Alfonso Gomez-Iturriaga, MD, PhD

Alfonso Gomez-Iturriaga, MD PhD

Francisco Casquero Ocio, MD PhD

High-dose rate brachytherapy (HDR-BT) is an advanced technology theorized to be more advantageous than LDR-BT and External Beam Radiotherapy (EBRT), to the patient himself, and in terms of resource allocation. Studies of HDR-BT monotherapy have encouraging results in terms of biochemical control, patient survival and toxicity, but there are still certain limitations that preclude recommending HDR-BT monotherapy outside the setting of a clinical trial.

The primary endpoint of this study is to evaluate the safety, tolerance and impact on quality of life (QoL) of the BT-HDR 19Gy administered in single fraction in patients with low and intermediate risk prostate cancer. Secondary endpoint is to measure the efficacy, in terms of cancer control and satisfaction of the patients undergoing the experimental treatment.

Forty nine patients will be recruited for the experimental procedure Quality of Life, tolerance, gastrointestinal and genitourinary toxicity will be assessed using standardized procedures and scales. Patient satisfaction with the procedure will be appraised using five-category predetermined Likert scale questions.

Two different types of intermediate analyses will be performed: with 15 and 30 recruited patients.

The experimental treatment tested in this study is very innovative. Since prostate cancer is the most frequent cancer in men in Spain, this trial results are very likely to have a major impact on the standard therapy for prostate cancer in our National Health Service, allowing for a higher number of Hospitals within our country and other countries starting protocols of HDR BT 19Gy in single fraction.

Treatment:

The patient´s treatment will consist of MRI-TRUS fusion single HDR brachytherapy fraction (1 fraction of 1900 cGray).

Brachytherapy performed under general anesthesia as an outpatient procedure

TRUS-MRI fusion:

T2 axial volumetric sequence (VISTA) is imported directly from the picture archiving and communication systems (PACS). Then MR images are reconstructed and segmented. Target volumes (prostate gland, dominant intraprostatic lesions (DILs) Organs at risk (OARs) urethra and rectum are delineated.

A transrectal sagittal volumetric ultrasound image is immediately acquired every 2 degrees, a rapid reconstruction algorithm converts the series of 2D images into a 3D volume, which is then displayed in axial, sagittal and coronal views and transferred to the module of fusion with the MRI.

The MRI images and the real-time sonography examination are displayed on a split-screen with the possibility of overlaying the images live in one image. A graphical user interface is used for rigid manual registration of the ultrasound and MRI volumes. This interface allows for displacements in the three dimensions and rotations, until both images are correctly superimposed.

Then the contoured structures are transferred to the US dataset, and these contours are slightly modified until a perfect matching with the US images is achieved.

Dose prescription:

Ultrasound images with the catheters in place will be exported to Oncentra Prostate. The prostate, Foley catheter and anterior rectal wall will be contoured. Catheters will be reconstructed on the planning system. Anatomy based inverse planning will be used for dwell time optimization.

The homogeneity parameters used for optimization aim are:

-For prostate V100 \> 95%, V150 \<35%, V200 \< 6%, where Vn is the fractional volume of the organ that receives n% of the prescribed dose.

The dose constraints for the organ at risk will be:

* Urethral dmax \< 110% and
* Rectal 1cc \< 60% of prescribed dose.

Endpoints

Feasibility of higher doses administration, toxicity and efficacy will be measured

Single Fraction Real-time High-Dose-Rate Brachytherapy in Patients With Low and Intermediate Risk Prostate Cancer

Prospective Phase II Trial of Single Fraction Real-time High-Dose-Rate (19-HDR) Brachytherapy in Patients With Low and Intermediate Risk Prostate Cancer

Data to be collected are:

i) urinary retention rate and duration ii) maximum International Prostate Symptom Score and time to normalize

Quality of life will be measured through validated instruments including International Prostate Symptom Score and the urinary, bowel and sexual domains of EPIC

Data to be collected: urinary retention rate, International Prostate Symptom Score over time, rectal toxicity and genitourinary toxicity

Patients will be followed with PSA at every follow-up;

Patient Satisfaction will be measured with Likert scale question

Hospital de Cruces

Staff physician department of Radiation Oncology

Behaviors and Mental Disorders

Quality of Life

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

After completion of 46 Gy of external beam radiotherapy subjects will undergo a permanent seed radioactive implant to the prostate using iodine-125 seeds to deliver a dose of 110 Gy

Subjects in this arm will undergo an HDR implant to deliver 15 Gy to the prostate prior to commencing the external beam component of their treatment.

Juanita M Crook, MD

Optimal non surgical treatment of prostate cancer requires dose escalation which is frequently provided by adding a brachytherapy "boost" to a short course of external beam radiotherapy. The hypothesis in this randomized study is that a High Dose Rate (HDR) brachytherapy boost leads to equivalent or better Prostate Specific Antigen (PSA) recurrence-free survival when compared to a Low Dose Rate (LDR) brachytherapy boost and that it is associated with a more favorable toxicity profile and improved quality of life.

Men with intermediate or high risk prostate cancer who are technically suitable for prostate brachytherapy based on prostate size and voiding function and who are interested in this modality of treatment will be approached for randomization between either high dose rate (single 15 Gray) or low dose rate permanent seed implant (110 Gray) brachytherapy. Baseline International Prostate Symptom score, Quality of Life Assessment and International Index of Erectile Function will be recorded and then every 3 months for the first year and every 6 months to 3 years. Androgen deprivation treatment is allowed for 6 or 12 months.

Improving Quality of Life After Prostate Brachytherapy: a Comparison of HDR and LDR Brachytherapy

IMPROVING QUALITY OF LIFE AFTER OPTIMAL RADIOTHERAPY FOR INTERMEDIATE AND HIGH RISK PROSTATE CANCER: A Randomized Comparison of HDR Versus LDR BRACHYTHERAPY BOOST

regular PSA monitoring every 6 months to 3 years and then annually to determine PSA recurrence free survival

Quality of life will be measured through validated instruments including International Prostate Symptom Score (IPSS), the International Index of Erectile Function ((IEF), and the urinary, bowel and sexual domains of the Expanded Prostate Cancer Index Composite (EPIC). IPSS has 7 questions related to voiding symptoms, each scored 0-5, with a higher score indicating worse symptoms. IIEF has 5 questions, each scored 0-5 with a higher score indicating better function. EPIC has several questions for each domain with an overall higher score associated with better QoL in that domain.

Quality of Life will be assessed to 5 years using the validated instruments International Prostate Symptom Score, International Index Erectile Function and EPIC

BC Cancer Foundation

British Columbia Cancer Agency

Carcinoma

Central Nervous System Depressants

Anesthetics

Radiation. High dose rate prostate brachytherapy is delivered under anesthesia in 2 procedures, 1-2 weeks apart.

HDR brachytherapy is also accomplished as an out-patient.

Temporary implantation of radioactive material into the prostate in the form of a stepping source of Iridium 192 that travels through 16-18 needles or catheters strategically placed through the prostate.

High dose rate prostate brachytherapy

Juanita Crook, MD

Hamid Raziee, MD

Bibi Naghibi Torbati, MD

This is an observational single-center trial for patients with localized prostate cancer suitable for High Dose Rate (HDR) brachytherapy as monotherapy. This study takes a multi-omics approach to study the mechanism of action of HDR brachytherapy through metabolomics, immunological, transcriptomics, and spectroscopic profiling. The results of this study will clarify the optimal dose for HDR prostate brachytherapy by documenting the dose-response relationship seen in the changing tumor metabolites after HDR brachytherapy and investigate the immunogenicity of HDR brachytherapy.

High Dose Rate (HDR) prostate brachytherapy is an effective and highly conformal means of delivering curative radiation to the prostate. Because of the high dose rate, initial studies applied this treatment cautiously in multiple sessions or fractions but this has gradually been reduced from 54 Gy in 9 fractions to 42 Gy in 6, then 36 Gy in 3, then 27 Gy in 2 and finally to one single fraction of 19 Gy. Each change in fractionation was calculated to be equivalent to the previous, and remarkably, efficacy was maintained until the final stage when treatment was reduced to a single fraction. This resulted in a significant drop in cure rates from over 90% to approximately 65%. The investigators assume that the prior fractions served to sensitize the tumor to subsequent radiation; however, this remains an open question.

This observational single-center trial for localized prostate cancer suitable for brachytherapy as monotherapy takes a novel multi-omics approach to study the mechanism of action of High Dose Rate (HDR) brachytherapy through metabolomics, immunological, transcriptomics, and spectroscopic profiling. This is achieved through (1) measurement of changes in metabolites as determined by Raman spectroscopy, (2) analysis of circulating tumor DNA in peripheral blood plasma, (3) evaluation of the changes in immune response by single cell RNA (scRNA)-sequencing, and (4) evaluation of gut microbiome composition before and after treatment. Secondary endpoints of the study include PSA nadir, time to nadir, PSA at 4 years and patterns of failure.

The study will enroll 100 men with localized prostate cancer suitable for brachytherapy as monotherapy. HDR brachytherapy is given in 2 fractions, each one under anesthesia, making it possible to obtain biopsies painlessly at both baseline prior to any treatment, and 1-2 weeks later prior to the second half of treatment. The results of this study will clarify the dose-response relationship for HDR brachytherapy, help to define the optimal dose, clarify the metabolic response to HDR brachytherapy, and investigate the potential immunogenicity of HDR brachytherapy.

Multi-omic Approach to Study HDR Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer

Multi-omic Approach to Study High Dose Rate (HDR) Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer

We will report the most important biomolecules altered by radiation (importance determined by the relative change of the score as a component of the Raman spectrum before and after radiation) and whether that observed change corelates with PSA outcome for each individual patient

Number of patients with a (transient) increase in circulating tumor DNA after a single fraction of high-dose rate prostate brachytherapy will be reported

single cell-RNA sequencing of immune cell populations before and after 13.5 Gray of radiation will be used for each individual patient and the number of patients with a change in gene expression (through activation or inactivation) will be reported

To determine microbial composition before brachytherapy and report for the individual patient whether diversity in composition is changed or skewed after treatment with high dose rate prostate brachytherapy. Second assessment is after completion of both fractions of radiation. Number of patients with alteration in microbial composition will be reported.

PSA recorded every 6 months to 5 years and then annually to 10 years

4-year PSA \< 0.2 ng/ml (indicative of cure)

Acute and long-term toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE V5) at each follow up time point

University of British Columbia

Vancouver Prostate Centre

Professor of Radiation Oncology

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Participants will receive the same radiotherapy technique, methods, and delivery will as standard of care 3 hours apart instead of receiving the radiotherapy on separate days.

High dose rate brachytherapy delivered in 13.5 Gy x 2 fractions over a single implant procedure 3 hours apart

High Dose Rate Monotherapy

Jamese Johnson

I-Chow Hsu, MD

This is a single center single arm prospective pilot study investigating the safety of high dose rate (HDR) brachytherapy as monotherapy delivered in 2 fractions 3 hours apart. HDR monotherapy has been established as safe and effective in this context, however previous studies have delivered 2 fractions on separate days, or at least 6 hours apart. Clinically, this regimen, if shown to be safe and effective in future studies, has the potential to reduce operative resources and logistical stresses on brachytherapy departments.

PRIMARY OBJECTIVES:

I. To determine the safety of HDR monotherapy 13.5 Gy x 2 fractions delivered 3 hours apart in patients with low and intermediate risk prostate cancer.

SECONDARY OBJECTIVES:

I. To describe the prostate specific antigen (PSA) kinetics associated with HDR brachytherapy monotherapy 13.5 Gy x 2 fractions delivered 3 hours apart for low and intermediate risk prostate cancer.

OUTLINE:

Treatment will be administered on an outpatient basis. All treatment will be delivered over a single day. Participants will be followed for 6 months after last treatment or removal from study, or until death, whichever occurs first. Additional Follow up will be as per usual guidelines for prostate cancer, every 3 months following treatment with PSA for the first year, then every 4 months after year 2, and every 6 months after year 3 until 5 years of follow up are completed.

Two-fraction HDR Monotherapy for Localized Prostate Cancer

Two-fraction High Dose Rate Brachytherapy as Monotherapy Delivered Three Hours Apart in Localized Prostate Cancer: A Pilot Study

The proportion of participants with reported grade 3 or higher genitourinary (GU) or gastrointestinal (GI) toxicities, as graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported.

The mean (average) PSA nadir after treatment will be reported along with standard deviations.

The mean (average) time to PSA nadir after treatment will be reported along with standard deviations.

The mean change over time on scores for the International Prostate Symptom Score (IPSS) will be reported along with standard deviations. The IPSS measures the severity of lower urinary tract symptoms and erectile function with lower numbers indicating less change in symptoms. Seven questions with scores ranging from 1-5 are summed to create a total score. Scores of 1-7 indicate mild symptoms, scores of 8-19 indicate moderate symptoms, and scores of 20-35 indicate severe symptoms.

University of California, San Francisco

Patients treated with dose escalation to Dominant Intraprostatic Lesions

MRI-TRUS fusion guided real time HDR

Alfonso Gomez-Iturriaga, MD

The Magnetic Resonance (MR) provides high resolution of soft tissue images allowing an appropriate assessment of the local extent of the disease. Recent studies have shown an increase in sensitivity and specificity for the detection of Dominant intraprostatic lesions when using multiparametric MRI as a diagnostic tool in the staging of the disease.

Among the various irradiation techniques currently available for prostate cancer, Brachytherapy is the superior in terms of dose conformation; this conformation allows greater dose escalation, adjusting the isodoses to the prostate with exquisite accuracy, keeping healthy adjacent organs, such as the urethra and rectum, in a tolerable dose range

Brachytherapy companies have recently developed software allowing for TRUS-MR image fusion.

The purpose of this study is to demonstrate the feasibility of the delivery of a higher than prescription dose to the dominant intra-prostatic nodule as defined on multiparametric MRI.

Dose to prostate, and adjacent structure will remain the same as the current treatment practice. Timing and the delivery of brachytherapy will not change from our current practice

Treatment:

The patient's treatment will consist of combined Hypofractionated external beam (3750 cGray in 15 fractions) and MRI-TRUS fusion HDR brachytherapy boost (1 fraction of 1500 cGray.

Brachytherapy performed under general anesthesia as an outpatient procedure

TRUS-MRI fusion:

T2 axial volumetric sequence (VISTA) is imported directly from the picture archiving and communication systems (PACS). Then MR images are reconstructed and segmented. Target volumes (prostate gland, dominant intraprostatic lesions (DILs)and Organs at risk (OARs) urethra and rectum are delineated.

A transrectal sagittal volumetric ultrasound image is immediately adquired every 2 degrees, a rapid reconstruction algorithm converts the series of 2D images into a 3D volume, which is then displayed in axial, sagittal and coronal views and transferred to the module of fusion with the MRI.

The MRI images and the real-time sonography examination are displayed on a split-screen with the possibility of overlaying the images live in one image. A graphical user interface is used for rigid manual registration of the ultrasound and MRI volumes. This interface allows for displacements in the three dimensions and rotations, until both images are correctly superimposed.

Then the contoured structures are transferred to the US dataset, and these contours are slightly modified until a perfect matching with the US images is achieved.

Dose prescription:

The homogeneity parameters used for optimization aim for prostate V100 \> 98%, V150 of 25-33%, V200 \< 8%, where Vn is the fractional volume of the organ that receives n% of the prescribed dose, urethral dmax \< 115% and rectal 1cc \< 70% of prescribed dose.

The treatment plan will be manipulated such that the normally occurring high dose regions (125%, 150%) are positioned at the site of the identified disease

Endpoints Feasibility of higher doses administration, toxicity and efficacy will be measured

Dose Escalation to Dominant Intraprostatic Lesions (DIL) With MRI-TRUS Fusion High Dose Rate (HDR) Prostate Brachytherapy

Phase II Study of Dose Escalation to Dominant Intraprostatic Lesions (DIL) With MRI-TRUS Fusion Real Time High Dose Rate (HDR) Brachytherapy in Patients With Intermediate and High Risk Prostate Cancer

Use the multiparametric MRI to identify dominant intraprostatic lesions (DIL) and deliver higher doses to these lesions with real time HDR brachytherapy. The procedure will be considered feasible if DIL is covered by the 125% of prescription dose while respecting tolerance doses of adjacent normal organs

Patients will be followed with PSA at every follow-up; Multiparametric MRI: at 12 months and 30 months; and TRUS guided biopsy: at 30 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Single Fraction Real-time High-Dose-Rate Brachytherapy in Patients With Low and Intermediate Risk Prostate Cancer	NCT02342054	Prostate Cancer	MRI-TRUS fusion...	18 Years -	Hospital de Cruces
Improving Quality of Life After Prostate Brachytherapy: a Comparison of HDR and LDR Brachytherapy	NCT01936883	Prostate Cancer	HDR LDR	45 Years - 80 Years	British Columbia Cancer Agency
Multi-omic Approach to Study HDR Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer	NCT06200974	Localized Prost...	High dose rate ...	18 Years -	British Columbia Cancer Agency
Two-fraction HDR Monotherapy for Localized Prostate Cancer	NCT05665738	Prostate Adenoc... Localized Prost...	High Dose Rate ...	18 Years -	University of California, San Francisco
Multi-omic Approach to Study HDR Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer	NCT06200974	Localized Prost...	High dose rate ...	18 Years -	British Columbia Cancer Agency
Two-fraction HDR Monotherapy for Localized Prostate Cancer	NCT05665738	Prostate Adenoc... Localized Prost...	High Dose Rate ...	18 Years -	University of California, San Francisco
Single Fraction Real-time High-Dose-Rate Brachytherapy in Patients With Low and Intermediate Risk Prostate Cancer	NCT02342054	Prostate Cancer	MRI-TRUS fusion...	18 Years -	Hospital de Cruces
Dose Escalation to Dominant Intraprostatic Lesions (DIL) With MRI-TRUS Fusion High Dose Rate (HDR) Prostate Brachytherapy	NCT01909388	Prostate Cancer	MRI-TRUS fusion...	18 Years -	Hospital de Cruces

Spots Global Cancer Trial Database for high dose rate