Mira Keyes

Testosterone recovery following prolonged adjuvant androgen ablation for prostate carcinoma

This study was conducted to describe the rate and completeness of the recovery of testosterone production following prolonged temporary androgen ablative therapy in men with prostate carcinoma undergoing curative radiation therapy.

Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A Single-Institution Matched-Pair Analysis

PURPOSEnIn the absence of randomized study data, institutional case series have shown brachytherapy (BT) to produce excellent biochemical control (bNED) in patients with localized prostate cancer compared with alternative curative treatments. This study was designed to overcome some of the limitations of case series studies by using a matched-pair design in patients treated contemporaneously with BT and external beam radiation therapy (EBRT) at a single institution.nnnMETHODS AND MATERIALSnSix hundred one eligible patients treated between 1998 and 2001 were prospectively followed up in our institutional databases and matched on a 1:1 basis for the following known prognostic variables: prostate-specific antigen (PSA) level, Gleason score, T stage, the use and duration of neoadjuvant androgen deprivation therapy, and the percentage of positive tissue core samples. Two hundred seventy-eight perfect matches of patients (139 in each group) with low- and intermediate-risk cancer were further analyzed. bNED (Phoenix definition) was the primary endpoint. Other endpoints were toxicity, PSA kinetics, and the secondary use of androgen deprivation therapy.nnnRESULTSnThe 5-year bNED rates were 95% (BT) and 85% (EBRT) (p < 0.001). After 7 years, the BT bNED result was unchanged, but the rate in EBRT patients had fallen to 75%. The median posttreatment PSA nadirs were 0.04 ng/mL (BT) and 0.62 ng/mL (EBRT, p < 0.001), which predicted a higher ongoing treatment failure rate in association with EBRT use than with BT use. Late urinary toxicity and rectal/bowel toxicity were worse in patients treated with BT and EBRT, respectively.nnnCONCLUSIONSnBT for both low-risk and selected intermediate-risk cancers achieves exceptional cure rates. Even with dose escalation, it will be difficult for EBRT to match the proven track record of BT seen over the past decade.

Prostate brachytherapy postimplant dosimetry: a comparison of prostate quadrants

PURPOSEnTo investigate postimplant dosimetry for different regions of the prostate gland in patients treated with transperineal 125Iodine brachytherapy implants for low- and intermediate-risk prostate cancer.nnnMETHODS AND MATERIALSnTwo hundred eighty-four patients treated with permanent interstitial prostate brachytherapy comprised the study population. A nonuniform, urethral-sparing algorithm was used to plan all patients. Prostate contours were outlined on postimplant CT images. Prostate volumes were then divided into four quadrants: anterior-superior quadrant (ASQ), posterior-superior quadrant (PSQ), anterior-inferior quadrant (AIQ), and posterior-inferior quadrant (PIQ). Dose-volume histograms (DVHs) were calculated for the whole prostate and each quadrant.nnnRESULTSnThe mean postimplant V(100) +/- 95% confidence (the percent prostate volume encompassed within the isodose surface comprising the prescription dose = 144 Gy) for the ASQ was 78.5 +/- 1.9, which was significantly lower than that of the PSQ, AIQ, and PIQ in which the V(100) plus minus 95% confidence values were 94.9 +/- 0.8, 92.6 +/- 1.2, and 98.7 +/- 0.3, respectively. The mean V(100) +/- 95% confidence for the whole prostate was 90.4 +/- 0.8. Mean values for V(150) and D(90) (the minimum dose in Gy received by 90% of the target volume) for the four quadrants and the whole prostate showed similar results.nnnCONCLUSIONSnUnderdosed areas of the planning target volume (PTV), if present, were largely confined to the ASQ, which received a significantly lower dose, on average, compared to the other three quadrants of the prostate.

Outcomes following iodine-125 brachytherapy in patients with Gleason 7, intermediate risk prostate cancer: A population-based cohort study

BACKGROUND AND PURPOSEnTo evaluate outcome in patients with Gleason 7 prostate cancer treated with iodine-125 brachytherapy at the British Columbia Cancer Agency.nnnMATERIALS AND METHODSnBetween 20th July 1998 and 7th February 2006, 1500 patients underwent I-125 prostate brachytherapy without supplemental external beam radiation therapy. Of these, 439 had Gleason 7 disease; 362 had Gleason 3+4 and 77 had 4+3 disease. Generally, patients received 6 months of androgen suppression. We compared biochemical no evidence of disease (bNED) between patients with Gleason ≤ 6 and Gleason 7 and between Gleason 3+4 and 4+3 using the Phoenix definition of biochemical recurrence.nnnRESULTSnMedian follow-up was 60 months. Estimated 5 year bNED was 97% for patients with Gleason score ≤ 6 and 94% for patients with Gleason 7 disease (p=0.037). Estimated bNED was 95% and 94% for 3+4 and 4+3, respectively (p=0.791). There was no difference in bNED between implants achieving D90 ≥ versus<the median value (150.5 Gy) or ≥ versus<140 Gy.nnnCONCLUSIONSnI-125 brachytherapy with 6 months of ADT demonstrates excellent bNED rates in Gleason 7 disease. We found no evidence of a difference between patients with Gleason 3+4 versus 4+3 disease.

Urethral and periurethral dosimetry in prostate brachytherapy: is there a convenient surrogate?

PURPOSEnTo assess and compare two models for a surrogate urethra to be used for postimplant dosimetry in prostate brachytherapy.nnnMETHODS AND MATERIALSnTwenty men with a urinary catheter present at the time of postimplant computed tomographic imaging were studied. Urethral and periurethral volumes were defined as 5-mm and 10-mm diameter volumes, respectively. Three contours of each were used: one contour of the true urethra (and periurethra), and two surrogate models. The true volumes were centered on the catheter center. One surrogate model used volumes centered on the geometrical center of each prostate contour (centered surrogate). The other surrogate model was based on the average deviation of the true urethra from a reference line through the geometrical center of the axial midplane of the prostate (deviated surrogate). Maximum point doses and the D(10), D(25), D(50), D(90), V(100), V(120), and V(150) of the true and surrogate volumes were measured and compared (D(n) is the minimum dose [Gy] received by n% of the structure, and V(m) is the volume [%] of the structure that received m% of the prescribed dose) as well as the distances between the surrogate urethras and the true urethra.nnnRESULTSnDoses determined from both surrogate urethral and periurethral volumes were in good agreement with the true urethral and periurethral doses except in the superior third of the gland. The deviated surrogate provided a physically superior likeness to the true urethra. Certain dose-volume histogram (DVH)-based parameters could also be predicted reasonably well on the basis of the surrogates. Correlation coefficients > or =0.85 were seen for D(25), D(50), V(100), V(120), and V(150) for both models. All the other parameters had correlation coefficients in the range of 0.73 - 0.85.nnnCONCLUSIONSnBoth surrogate models predicted true urethral dosimetry reasonably well. It is recommended that the simpler deviated surrogate would be a more suitable surrogate for routine clinical practice.

Should women younger than 40 years of age with invasive breast cancer have a mastectomy? 15-year outcomes in a population-based cohort.

PURPOSEnOptimal local management for young women with early-stage breast cancer remains controversial. This study examined 15-year outcomes among women younger than 40 years treated with breast-conserving surgery plus whole-breast radiation therapy (BCT) compared with those treated with modified radical mastectomy (MRM).nnnMETHODS AND MATERIALSnWomen aged 20 to 39 years with early-stage breast cancer diagnosed between 1989 and 2003 were identified in a population-based database. Primary outcomes of breast cancer-specific survival (BCSS), overall survival (OS) and secondary outcomes of local relapse-free survival (LRFS), locoregional relapse-free survival (LRRFS), and distant relapse-free survival (DRFS) were calculated using Kaplan-Meier methods and compared between BCT and MRM cohorts using log-rank tests. A planned subgroup analysis was performed on patients considered ideal for BCT (ie, T1N0, negative margins and no extensive ductal carcinoma in situ) and in whom local therapy may have the largest impact on survival because of low systemic risk.nnnRESULTSn965 patients were identified; 616 had BCT and 349 had MRM. The median follow-up time was 14.4 years (range, 8.4-23.3 years). Overall, 15-year rates of BCSS (76.0% vs 74.1%, P=.62), OS (74.2% vs 73.0%, P=.75), LRFS (85.4% vs 86.5%, P=.95), LRRFS (82.2% vs 81.6%, P=.61), and DRFS (74.4% vs 71.6%, P=.40) were similar between the BCT and MRM cohorts. In the ideal for BCT subgroup, there were 219 BCT and 67 MRM patients with a median follow-up time of 15.5 years. The 15-year BCSS (86.1% vs 82.9%, P=.57), OS (82.6% vs 82.9%, P=.89), LRFS (86.2% vs 84.2%, P=.50), LRRFS (83.1% vs 78.3%, P=.24), and DRFS (84.8% vs 79.1%, P=.17) were similar in the BCT and MRM cohorts.nnnCONCLUSIONSnThis population-based analysis with long-term follow-up confirmed that women younger than 40 years treated with BCT had similar 15-year outcomes compared with MRM. Young age alone is not a contraindication to BCT.

Comparison of methods for calculating rectal dose after 125I prostate brachytherapy implants

PURPOSEnTo compare several different methods of calculating the rectal dose and examine how accurately they represent rectal dose surface area measurements and, also, their practicality for routine use.nnnMETHODS AND MATERIALSnThis study comprised 55 patients, randomly selected from 295 prostate brachytherapy patients implanted at the Vancouver Cancer Center between 1998 and 2000. All implants used a nonuniform loading of 0.33 mCi (NIST-99) 125I seeds and a prescribed dose of 144 Gy. Pelvic CT scans were obtained for each patient approximately 30 days after implantation. For the purposes of calculating the rectal dose, several structures were contoured on the CT images: (1) a 1-mm-thick anterior rectal wall, (2) the anterior half rectum, and (3) the whole rectum. Point doses were also obtained along the anterior rectal surface. The thin wall contour provided a surrogate for a dose-surface histogram (DSH) and was our reference standard rectal dose measurement. Alternate rectal dose measurements (volume, surface area, and length of rectum receiving a dose of interest [DOI] of > or =144 Gy and 216 Gy, as well as point dose measures) were calculated using several methods (VariSeed software) and compared with the surrogate DSH measure (SA(DOI)).nnnRESULTSnThe best correlation with SA(144 Gy) was the dose volumes (whole or anterior half rectum) (R = 0.949). The length of rectum receiving > or =144 Gy also correlated well with SA(144 Gy) (R > or =0.898). Point dose measures, such as the average and maximal anterior dose, correlated poorly with SA(144 Gy) (R < or =0.649). The 216-Gy measurements supported these results. In addition, dose-volume measurements were the most practical (approximately 6 min/patient), with our surrogate DSH the least practical (approximately 20 min/patient).nnnCONCLUSIONnDose-volume measurements for the whole or anterior half rectum, because they were the most practical measures and best represented the DSH measurements, should be considered a standard method of reporting the rectal dose when calculating the DSH is not practical. Average or maximal anterior rectal doses are not reliable indicators of surface area dosimetry.

Population-based validation of a policy change to use long-term androgen deprivation therapy for cT3–4 prostate cancer: Impact of the EORTC22863 and RTOG 85-31 and 92-02 trials

PURPOSEnAfter publication of EORTC-22863 trial, prolonged androgen deprivation therapy (ADT) combined with radiation therapy (RT) became standard policy for high-risk prostate cancer patients in British Columbia (BC) in 1997. We evaluated whether population-based survival improved after this policy change.nnnPATIENTS AND METHODSnTwo cohorts comprising all patients with T3-T4 prostate cancer treated with curative-intent RT in BC were reviewed. The Early cohort (n=730) was all patients treated between 1993 and 1995, and the Late cohort (n=584) was all patients treated between 1999 and 2001. The BC Cancer Registry, which collects data on survival, was linked to RT and pharmacy databases. Duration of ADT, age, stage, grade, presenting PSA, and Charlson comorbidity index (CCI; none=0, minor=1, major=2+), were abstracted from charts.nnnRESULTSnUsage of ≥6 months and ≥18 months of neoadjuvant and adjuvant ADT increased from 14% and 1% to 97% and 59% (p<0.0001). Baseline characteristics were similar, except for lower Gleason score (G2-6: 45% vs. 20%, G7: 35% vs. 48%, G8-10: 19% vs. 32%; p<0.0001), higher T-stage (T4: 9% vs. 5%, p=0.004) and higher comorbidity (CCI 0: 62% vs. 71%, CCI 1: 26% vs. 20%, CCI 2+: 11% vs. 9%, p=0.002) in the Early cohort. Disease-specific survival adjusted for competing risks from other causes mortality was improved (90% vs. 86%, p=0.042). On multivariate analysis, the Late cohort was independently associated with improved 8-year overall survival (76% vs. 64%, p=0.0002).nnnCONCLUSIONSnThis population-based study demonstrated improved overall survival following a policy change to use of prolonged ADT with curative RT for patients with T3-T4 prostate cancer.

The effect of loose versus stranded seeds on biochemical no evidence of disease in patients with carcinoma of the prostate treated with iodine-125 brachytherapy

PURPOSEnThe British Columbia Cancer Agency has been performing iodine-125 prostate brachytherapy since 1998, initially using loose seeds and phasing into the exclusive use of RAPIDStrand (RS) (Oncura Inc., Plymouth Meeting, PA) by November 2000. The aim of this study was to investigate rates of biochemical no evidence of disease (bNED) in patients treated with loose seeds compared with RS from this population-based cohort.nnnMETHODS AND MATERIALSnBetween July 1998 and February 2006, 1500 implants were performed (327 loose and 1173 RS). Biochemical failure is reported using the Phoenix definition and prostate-specific antigen (PSA) >0.4ng/mL at ≥48 months postimplant. Actuarial estimates were calculated by the Kaplan-Meier method. Analysis was repeated with the first 100 loose and stranded implants excluded to assess the learning curve effect. Log-rank test was used to evaluate differences in bNED. Variables showing association with bNED were included in a multivariate model.nnnRESULTSnThere was no difference between loose and stranded seeds. Estimated rate of bNED was 93.5% (95% confidence interval [CI], 90.6-96.4) at 7 years for patients treated with loose seeds and 94.0% (95% CI, 91.8-96.2) for patients treated with RS according to Phoenix definition (p=0.846). Using the PSA >0.4ng/mL definition, estimated rates were 91.3% (95% CI, 88.0-94.6) and 91.9% (95% CI, 89.7-94.1) for loose and stranded seeds, respectively (p=0.871). Exclusion of the first 100 loose and stranded implants also revealed no difference in bNED.nnnCONCLUSIONnThis study of 1500 patients treated with iodine-125 brachytherapy demonstrates no difference in bNED between loose and stranded seeds, using either Phoenix or PSA >0.4ng/mL definitions of biochemical failure.

Current state of brachytherapy teaching in Canada: A national survey of radiation oncologists, residents, and fellows

PURPOSEnThe objective of the present study was to determine perceptions and barriers concerning brachytherapy (BT) teaching in Canada to guide the development of a BT credentialing process.nnnMETHODS AND MATERIALSnIn May 2013, an electronic survey was sent to all radiation oncologists, program directors, residents, and fellows in Canada. Questions were asked regarding demographics, practice patterns, teaching methods and assessment, curriculum content, perceptions on resident education, and barriers to resident teaching.nnnRESULTSnOne hundred twenty-one staff radiation oncologists and 32 residents responded to the survey. Only 54% of respondents stated that their center had defined specific written objectives with respect to knowledge, skills, and attitudes required for a resident to be competent in BT. The main barriers to BT teaching were stated as being the lack of Royal College guidance (55%), heavy clinical workload (49%), lack of time (37%), and the fact that too much emphasis is placed on passing examinations (32%). Ninety-seven percent of respondents felt that it was important or very important that some elements of BT be included in the mainstream radiation oncology curriculum. Eighty percent of respondents were in agreement with the development of a formal credentialing process by the Royal College of Physicians and Surgeons of Canada, which would lead to separate certification in BT.nnnCONCLUSIONSnThe results of this study show the importance of developing specific BT curriculum and emphasize the need for a credentialing process.