William Foster

Randomized non-inferiority trial of Bicalutamide and Dutasteride versus LHRH agonists for prostate volume reduction prior to I-125 permanent implant brachytherapy for prostate cancer

OBJECTIVEnTo determine the efficacy and toxicity of a 3-month regimen of Dutasteride and Bicalutamide compared to LHRH agonists for prostate volume (PV) reduction prior to permanent implant prostate brachytherapy (PIPB).nnnMATERIAL AND METHODSnPatients with low-risk or low-tier intermediate risk prostate cancer eligible for PIPB with a prostate volume greater than 50 cc were randomized to either Dutasteride 0.5 mg Bicalutamide 50 mg daily and Tamoxifen 10 mg daily for 3 months (D+B group) or to a 3 month dose of an LHRH agonist and Bicalutamide daily for 1 month (LHRH group). Their PV was measured at baseline and at pre-implant. Non-inferiority analysis was completed for the relative (%) PV reduction. IPSS and EPIC questionnaires were completed at baseline, pre-implant and at 1, 3, 6, 12, 18 and 24 months post-treatment. IPSS and EPIC comparisons were based on superiority analysisnnnRESULTSn60 patients were randomized (31 to LHRH group and 29 to D+B group). Mean relative PV reduction (SD) was 35.5% (8.9) in the LHRH group and 31.7% (9.6) in the D+B group. The upper bound of the 95% confidence for the interval for the difference between groups favouring LHRH agonists for PV reduction was 8.6 which did not cross the 10% non-inferiority margin meaning D+B is non-inferior to LHRH agonist for PV reduction, although 5/29 (17%) of those in the D+B group required longer duration of D+B to achieve adequate volume reduction. There were no statistically significant differences in IPSS scores over the entire follow-up period. EPIC sexual summary score was significantly better in the D+B group at pre-implant, 1 month, 3 months post-implant.nnnCONCLUSIONnDutasteride and Bicalutamide is a regimen of non-inferior efficacy to LHRH agonist based regimens for prostate volume reduction prior to permanent implant prostate brachytherapy. D+B has less sexual toxicity compared to LHRH agonists prior to implant and for the first 6 months after implant. D+B is therefore an option to be considered for prostate volume reduction prior to PIPB.

High-dose-rate brachytherapy boost for prostate cancer treatment: Different combinations of hypofractionated regimens and clinical outcomes

PURPOSEnTo report the outcomes of our high-dose-rate brachytherapy (HDR-BT) boost experience in localized prostate cancer treated with different combinations of radiation doses and fractionation.nnnMATERIAL AND METHODSnBetween 1999 and 2011, 832 patients were treated with different regimens of external beam radiotherapy (EBRT) and HDR-BT. These regimens were converted into three biologically effective dose (BED) groups. The biochemical failure-free survival (BFFS), reported with the phoenix definition and prostate-specific antigen (PSA) >0.2ng/ml at 5-year, genitourinary (GU) and gastrointestinal (GI) toxicities were compared between the groups.nnnRESULTSnThe 5-, 10-year BFFS for the entire cohort were 94.6% and 92.5%, for overall survival (OS) 96.1% and 80.3% and for prostate cancer-specific survival (PCSS) 99.5% and 97.8%. The percentage of patients with a 5-year PSA level <0.2ng/ml was 68.6%, 78.7% and 86.7% in the BED group of <250, 250-260 and >260Gy (p=0.005) while the 5-year BFFS rates according to phoenix definition were 97.3%, 94.3% and 94.9% for BED group <250, 250-260 and >260Gy (p=0.453). On multivariate logistic regression, patients in the BED>260Gy group were significantly more likely to remain free from 5-year PSA values ≥0.2ng/mL compared with those in the BED<250Gy group (OR: 0.350, p=0.011). Grade≥3 acute GU toxicity was reported in 2 patients (4.7%) for BED>260Gy while grade≥3 late GU toxicity was reported in 6 (1.7%) and 9 (4.9%) patients for 250-260Gy and >260Gy BED groups.nnnCONCLUSIONSnThe increase in BED with the hypofractionated regimens correlates with an improvement in biochemical control with of urinary toxicity. This increase in urinary toxicity is small and clinically acceptable.

Use of 3D transabdominal ultrasound imaging for treatment planning in cervical cancer brachytherapy: Comparison to magnetic resonance and computed tomography

PURPOSEnTo evaluate if the addition of 3D transabdominal ultrasound (3DTAUS) imaging to computed tomography (CT) can improve treatment planning in 3D adaptive brachytherapy when compared with CT-based planning alone, resulting in treatment plans closer to the ones obtained using magnetic resonance imaging (MRI)-based planning.nnnMETHODS AND MATERIALSnFive patients with cervical cancer undergoing brachytherapy underwent three imaging modalities: MRI, CT, and CT-3DTAUS. Volumes were delineated by a radiation oncologist and treatment plans were optimized on each imaging modality. To compare treatment plans, the dwell times optimized on MRI were transferred on CT and CT-3DTAUS images and dose parameters were reported on volumes of the receiving imaging modality. The plans optimized on CT and CT-3DTAUS were also copied and evaluated on MRI images.nnnRESULTSnTreatment plans optimized and evaluated on the same imaging modalities were clinically acceptable but statistically different (p < 0.05) from one another. MR-based plans had the highest target coverage (98%) and CT-based plans the lowest (93%). For all treatment plans evaluated on MRI, the target coverage was equivalent. However, a decrease in target coverage (V100) was observed when MR-based plans were applied on CT-3DTAUS (6%) and CT (13%) with p < 0.05. An increase in the rectum/sigmoid dose (D2cc) was observed with both CT-3DTAUS-based (0.6xa0Gy) and CT-based planning (1xa0Gy) when compared with MR-based plans, whereas bladder dose stayed similar.nnnCONCLUSIONSnWhen compared with CT-based planning, the addition of 3DTAUS to CT results in treatment plans closer to MR-based planning. Its use reduces the high-risk clinical target volume overestimation typically observed on CT, improving coverage of the target volume while reducing dose to the organs at risk.

Dosimetric evaluation of three adaptive strategies for prostate cancer treatment including pelvic lymph nodes irradiation

PURPOSEnThe movements of the prostate relative to the pelvic lymph nodes during intensity-modulated radiation therapy treatment can limit margin reduction and affect the protection of the organs at risk (OAR). In this study, the authors performed an analysis of three adaptive treatment strategies that combine information from both bony and gold marker registrations. The robustness of those treatments against the interfraction prostate movements was evaluated.nnnMETHODSnA retrospective study was conducted on five prostate cancer patients with 7-13 daily cone-beam CTs (CBCTs). The clinical target volumes (CTVs) consisting of pelvic lymph nodes, prostate, and seminal vesicles as well as the OARs were delineated on each CBCT and the initial CT. Three adaptive strategies were analyzed. Two of these methods relied on a two-step patient positioning at each fraction. First step: a bony registration was used to deliver the nodal CTV prescription. Second step: a gold marker registration was then used either to (1) complete the dose delivered to the prostate (complement); (2) or give almost the entire prescription to the prostate with a weak dose gradient between the targets to compensate for possible motions (gradient). The third method (COR) used a pool of precalculated plans based on images acquired at previous treatment fractions. At each new fraction, a plan is selected from that pool based on the daily position of prostate center-of-mass. The dosimetric comparison was conducted and results are presented with and without the systematic shift in the prostate position on the CT planning. The adaptive strategies were compared to the current clinical standard where all fractions are treated with the initial nonadaptive plan.nnnRESULTSnThe minimum daily prostate D95% is improved by 2%, 9%, and 6% for the complement, the gradient, and the COR approaches, respectively, compared to the nonadaptive method. The average nodal CTV D95% remains constant across the strategies, except for the gradient approach where a reduction of 7% is observed. However, a correction of the systematic shift reduced the problem, and the adaptive strategies remain robust against the prostate movement across the fraction. The bladder V55Gy is reduced by 35% on average for the adaptive strategies.nnnCONCLUSIONSnBecause they offer increased CTV coverage and OAR sparing, adaptive methods may be suitable candidates for simple and efficient adaptive treatment strategies for prostate cancer. Margin reduction and systematic error correction in the prostate position improve the protection of the OAR and the dose coverage. A cumulative dose to simulate a complete treatment would show real effects and allow a better comparison between each method.

Validation of the French-Canadian version of the Expanded Prostate Cancer Index Composite (EPIC) in a French-Canadian population

INTRODUCTIONnThis study aims to empirically validate the French-Canadian version of the Expanded Prostate Cancer Index Composite (EPIC), a measure of health-related quality of life for prostate cancer patients.nnnMETHODSnTwo hundred fifty-one participants completed a battery of self-report scales, including the French-Canadian version of the EPIC, after having received radiation therapy or radical prostatectomy for prostate cancer.nnnRESULTSnThe internal consistency for the urinary incontinence, bowel, and sexual domains of the EPIC-26 was high (Cronbachs alpha coefficients from 0.80-0.92), while coefficients for the urinary irritation/obstruction (0.59) and hormonal (0.67) domains were lower. Item-total correlations (rs=0.15-0.85), and temporal stability (rs=0.72-0.93) generally supported the reliability of the instrument. The five-factor structure of the EPIC-26 was confirmed for the most part. The construct validity of the instrument was also supported by high correlations obtained between each domain and measures assessing similar constructs (rs=-0.56-0.83). The EPIC also showed an excellent sensitivity to change with significant differences obtained on EPIC scores (all p<0.05) between pre- and post-prostate cancer treatment.nnnCONCLUSIONSnThe psychometric qualities of the French-Canadian version of the EPIC are well-supported, thus providing a valid tool to assess health-related quality of life in prostate cancer patients.

Does prostate volume has an impact on biochemical failure in patients with localized prostate cancer treated with HDR boost

PURPOSEnTo compare biochemical failure free survival (BFFS) of patients with small and large prostate glands treated with external beam radiation therapy (EBRT) and HDR (high dose rate) brachytherapy boost.nnnMATERIALS AND METHODSnBetween 2002 and 2012, 548 patients were treated with EBRT followed by HDR boost. The effect of covariates and prostate volume on biochemical failure was analyzed by survival analysis and Cox regression model.nnnRESULTSnThe median follow-up and age were not different between the two groups. The mean prostate gland volume at the time of CT planning was 48.1 and 76.0cc in small (<60cc) and large (⩾ 60cc) prostate volume, respectively (p<0.001). When PSA bounces were excluded, there was no significant difference between the two groups with a 5-years BFFS of 95.8% vs 92.3%, p=0.094. There were no significant differences between the two groups for urinary symptoms (IPSS) as well as acute and late GI toxicities.nnnCONCLUSIONSnThis study showed that a HDR brachytherapy boost in large prostate gland cases is feasible at the price of increased PSA bounces. When the benign bounces are excluded, there is no significant difference between the two groups for tumor control and toxicity. Therefore, in our experience, there is no rational precluding the use of HDR boost in patients with a prostate size of 60 cc or more so long as an adequate dosimetry is achievable.

Does Seed Migration Increase the Risk of Second Malignancies in Prostate Cancer Patients Treated With Iodine-125 Loose Seeds Brachytherapy?

PURPOSEnTo evaluate the risk of second malignancies after migration of seeds (MS) in prostate cancer patients treated with 125I loose seeds brachytherapy.nnnMETHODS AND MATERIALSnData from 2802 prostate cancer patients treated with 125I loose seeds brachytherapy in 3 Canadian centers were reviewed. After seeds implant, all patients underwent postimplant pelvic radiography and computed tomography scan for postimplant dosimetry. These images were used to assess whether seed migration occurred. The incidence of second malignancies was determined through the review of patient charts. The 7- and 10-year cumulative incidences of second malignancies and their 95% confidence intervals (CIs) were calculated. Fine and Gray competing risk regression analysis was used to assess the factors associated with the development of second malignancies.nnnRESULTSnMean age and median follow-up were 63.5xa0years and 74 (range, 12-246) months, respectively. Migration of seeds occurred in 263 of 2802 patients (9.4%). Second malignancy occurred in 87 patients (3.1%) for the entire cohort and was not different between patients who experienced MS (9, 3.4%) and those who did not (78, 3.1%) (P = .755). The 7-year cumulative incidence rates of second malignancies were 2.95% (95% CI 1.20%-6.00%) (with MS) versus 2.82% (2.10%-3.70%) (without MS) (P = .756). The corresponding values at 10xa0years were 6.16% (2.20%-12.3%) versus 4.51% (3.20%-5.50%) (P = .570). Migration of seeds did not seem to be a significant predictive factor for second malignancies development (adjusted hazard ratio 1.27 [95% CI 0.63-2.55]; P = .510). In both models, only advanced age was significantly associated with second malignancies development.nnnCONCLUSIONSnThese results did not show an increased risk of second malignancies associated with MS after 125I loose seeds brachytherapy for prostate cancer patients. Longer follow-up and more events are required to better correlate MS and second malignancies.

SU-E-T-593: Comparison of Three IMRT Adaptive Methods: The Case of Prostate Cancer

PURPOSEnIndependant movements of prostate and pelvic lymph nodes during IMRT can limit margin reduction and affect the protection of organs-at-risk (OAR). In this study we perform an analysis of three adaptive treatments that combine information from both bony and gold marker registrations. The efficiency of those treatments against interfraction prostate movements was evaluated.nnnMETHODSnA retrospective study was conducted on four prostate cancer patients with 5 to 10 daily CBCTs. Clinical target volumes (CTVs) consisting of pelvic lymph nodes, prostate and seminal vesicles (SV) and OAR were delineated on each CBCT and on the initial CT. Three adaptive methods were analyzed. Two methods relied on a double patient positioning at each fraction. For these, nodal CTVs prescription was delivered on bony registration. Gold markers match was then used either to: (1) complete the dose delivered to prostate and SV (Complement); (2) give almost the entire prescription to prostate and SV with slow gradient between targets to compensate for motions (Controlled Gradient). The third method (COR) used a pool of pre-calculated plans from anterior fractions where the plan with the prostate center of mass closest to the daily anatomy was chosen. Adaptive techniques were compared to the standard non-corrected CT plan.nnnRESULTSnWith adaptive techniques, prostate and SV V(100%) is improved by 4% compared to non-corrective method. This improvement does not Result in dose increase to OAR. EUD to bladder is reduced with an average reduction of 15% for COR.nnnCONCLUSIONnBecause of their increase in CTV coverage and OAR sparing, COR and Complement methods may be good candidates for simple and effective adaptive treatment strategies for prostate cancer. Further improvements may be obtained by tuning CTV margins. A cumulative dose to simulate a complete treatment will show real effects and allow better comparison between each method. Ministere de la Sante et des Services Sociaux.