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

Pd-103

Gregory S. Merrick, MD

Kent E. Wallner, MD

The purpose of this study is to determine the most appropriate radiation implant dose for palladium-103 monotherapy. Radiation dose is related to potential cure. From previously published studies, it appears that the prescribed radiation dose can be reduced by 14-20% without any difference in potential cure (in this study, the dose is being decreased 10%). Although most patients tolerate brachytherapy well, complications to appear to be related to radiation exposure to normal structures (i.e. urethra, rectum and proximal penis). By reducing the prescribed dose, it is conceivable that fewer patients will experience side effects and complications.

In calendar year 2003, approximately 220, 000 men will be diagnosed with prostate cancer and approximately 30,000 will die. The vast majority of men will be diagnosed with clinically organ-confined disease with potentially curative treatments including radical prostatectomy, external beam radiation therapy and brachytherapy. Within the uro-oncology community, the selection of one modality over another remains controversial.

Over the past decade, transperineal ultrasound-guided permanent prostate brachytherapy using either Pd-130 or I-125 has been increasingly utilized as definitive management for early stage carcinoma of the prostate gland. This resurgence of interest in prostate brachytherapy was the result of several technologic advances including the evolution of transrectal ultrasonography, the development of a closed transperineal approach and the availability of sophisticated treatment planning computers. These imaging and planning advances significantly improved the accuracy of seed placement. In addition, the advent of CT-based postoperative dosimetry in the early 1990's provided a unique opportunity to evaluate quality and proactively predict outcome and complications.

Prostate brachytherapy represents the ultimate 3-dimensional conformal therapy and permits dose escalation far exceeding other modalities. Following permanent prostate brachytherapy with or without supplemental external beam radiation therapy, favorable long term biochemical outcomes have been reported for patients with low, intermediate and high risk features with a morbidity profile that compares favorably with competing local modalities (1,2)2).

Although there is no definitive evidence suggesting that either Pd-103 or I-125 is more efficacious than the other in terms of cure or side effects/complications, preliminary results of a prospective randomized trial suggests that Pd-103 may be more "dose forgiving" than I-125 (3). Long-term results demonstrate cancer eradication is highly correlated with delivered radiation dose. To date, postoperative dosimetry has primarily been described in terms of V 100/150/200 (volume of the gland receiving 100%, 150% and 200% of the prescription dose) and the D90 (the dose delivered to 90% of the prostate gland). Following I-125 monotherapy, A D90 greater than or equal to 140 Gy (day 30 dosimetry) is required for optimal long-term biochemical control (4,5)4)5). A dose of 140 Gy represents 96% of the standard I-125 prescription dose (145 Gy). In contrast, following Pd-103 monotherapy, A D90 greater than or equal to 100 Gy (day 30 dosimetry) and a D90 greater than or equal to 108 Gy (median day 22 dosimetry) have been reported to predict optimal biochemical outcomes (6,7)6)7). These Pd-103 doses represent 80% and 86% of the standard monotherapy prescription dose (125 Gy). In addition, a prospective randomized trial demonstrated that coverage of 90% or more of the prostate by 124 Gy of Pd-103 yields 98% change of being cancer-free three years following treatment (3).

Because of some seed placement uncertainty, however, the pre-plans are designed to deliver a higher radiation dose than necessary to most of the prostate gland (8). Additionally, there is a variable amount of edema that occurs from the implant procedure, moving seeds farther away from each other, again requiring a higher planned dose than actually needed.

Delivered radiation dose is paramount to securing long-term freedom from biochemical progression. Previously Merrick and colleagues reported that postoperative dosimetric quality for Pd-103 and I-125 in terms of V 100/150/200 and D90 were independent of prostate size, isotope selection, radiation implant dose prescription, the use of supplemental external beam radiation therapy, neoadjuvant androgen deprivation therapy and patient age (8-12)8)9)10)11)12). These results demonstrate the dosimetric reproducibility of Pd-103 across all implant scenarios. A review of the last 200 consecutive Pd-103 implants at the Schiffler Cancer Center illustrates similar dosimetric outcomes for patients implanted with 125 Gy versus 115 Gy.

Although the morbidity profile of permanent prostate brachytherapy compares favorably with competing local modalities, side effects and complications do occur. Delivered radiation dose to the urethra, rectum and proximal penis strongly correlate with brachytherapy-related morbidity (2, 13-18)13)14)15)16)17)18).

In summary, the available literature suggests that the Pd-103 doses necessary for cure care substantially less than currently prescribed, postoperative dosimetry has consistently demonstrated high intraprostatic doses and brachytherapy-related morbidity is related to radiation doses to normal surrounding structures. As such, we proposed to conduct a prospective randomized trial evaluating the effect of a 12% reduction in prescription dose (125 Gy vs. 110 Gy) on the ultimate cure and complication rates for low risk prostate cancer (PSA greater than or equal to 10 ng/mL, Gleason score greater than or equal to 6 and clinical stage T1b-T2b). To assure that the dose is adequate, intraoperative and postoperative dosimetry will be performed. Intraoperative dose evaluation will allow additional seeds to be implanted if needed to achieve minimum required dose.

Pd-103 Dose De-Escalation for Early Stage Prostate Cancer: A Prospective Randomized Trial

PSA determinations will be obtained 3 months following implantation and then every 6 months.

Androgen deprivation therapy will not be initiated unless the PSA exceeds 10 ng/mL or distant metastases are detected.

Following brachytherapy, I-PSS will be obtained on months 1, 3, 6, 12, 18, 24, 36, 48, 60.

Following brachytherapy, R-FAS will be obtained on months 12, 36 and 60.

Following brachytherapy, IIEF will be obtained on months 12, 36 and 60.

Post implant quality of life evaluations will be forwarded to Dr. G. Merrick as appropriate.

Schiffler Cancer Center

Medical Director

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Stranded palladium seed interstitial radioactive seed implant to seroma with margin with 3 dimensional ultrasound and CT guidance

Interstitial implantation of stranded palladium 103 seeds in seroma with a margin

Stranded palladium seed interstitial implant

guidance of placement of interstitial needles in breast

3 dimensional breast ultrasound

Breast CT for planning and assessing interstitial implantation of radioactive seeds

Computerized tomography (CT)

Juanita Crook, MD

Permanent Breast Seed Implant (PBSI) has been demonstrated to be a well accepted and well tolerated form of partial breast radiotherapy. This protocol aims to build on the initial experience and to further refine the technique and collect toxicity and cost data, especially in comparison to alternate forms of breast radiotherapy.

25 women with low stage (pT1pN0) breast cancer, grade 1 or 2, will be accrued for adjuvant partial breast radiotherapy using PBSI and prospectively followed for 5 years. The primary aims is to evaluate implant quality according to recognized dosimetric parameters. Secondary aims include elaboration of approaches to different technical scenarios imposed by variation in seroma size, shape and location within the breast (expanding the technical manual to include recommended approaches to implants in different sectors of the breast and in different size breasts), incorporation of the use of live 3D ultrasound in the procedure (as opposed to current use of 2D US), assessment of patient acceptance and quality of life, physician assessment of cosmesis, assessment of toxicity, and recording of cost to the patient and health care system compared to alternate forms of breast radiotherapy.

Partial Breast Irradiation Using Interstitial Permanent Palladium-103 Seed Implant

Post implant CT evaluation to report dosimetric parameters including the minimum dose in Gray to 90% of the target volume (D90) and the percentage of the target volume (seroma, seroma with 5 mm margin, seroma with 10 mm margin) receiving 100% of the prescribed dose (V100).

US and CT evaluation to record the range of seroma volumes and quadrant location in the breast acceptable for implantation

Post implant CT evaluation describing dosimetric parameters (D90 and V100 as above in Outcome 1) with the use of 3D ultrasound and with 2D ultrasound

Physician assessed using the questionnaire from the Radiation Therapy Oncology Group (RTOG) and National Surgical Adjuvant Breast Project (NSABP)

Physician assessed using the Common Terminology Criteria for Adverse Events (CTCAE V4) form

Patient assessed using the RTOG/NSABP Breast Cancer Quality of Life Assessment form

Post implant CT assessment describing calculated doses to lung, ribs and heart described as the highest dose to 1 cc of the specific organ tissue and skin dose recorded as an area 1 cm by 1 cm by 2 mm thick (1cmx1cmx0.2cm)

Cost to health care system (Canadian dollars) and patient (expenses and lost wages in Canadian dollars)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pd-103 Dose De-Escalation for Early Stage Prostate Cancer: A Prospective Randomized Trial	NCT00247312	Prostatic Neopl...	Pd-103	-	Schiffler Cancer Center
Partial Breast Irradiation Using Interstitial Permanent Palladium-103 Seed Implant	NCT02297672	Early Stage Bre...	Stranded pallad... 3 dimensional b... Computerized to...	55 Years - 80 Years	British Columbia Cancer Agency
Partial Breast Irradiation Using Interstitial Permanent Palladium-103 Seed Implant	NCT02297672	Early Stage Bre...	Stranded pallad... 3 dimensional b... Computerized to...	55 Years - 80 Years	British Columbia Cancer Agency

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