E. Vigneault

Brachytherapy improves biochemical failure-free survival in low- and intermediate-risk prostate cancer compared with conventionally fractionated external beam radiation therapy: a propensity score matched analysis.

PURPOSEnTo compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone.nnnMETHODS AND MATERIALSnPatient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups.nnnRESULTSnPropensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500).nnnCONCLUSIONSnPropensity score matched analysis showed that BT options led to statistically significant improvements in bFFS in low- and intermediate-risk prostate cancer patient populations.

The prostate cancer risk stratification (ProCaRS) project: recursive partitioning risk stratification analysis.

BACKGROUNDnThe Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema.nnnMETHODSnThe RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively.nnnRESULTSnThe recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30).nnnCONCLUSIONSnProposed RS subcategories have been identified by a RPA of the ProCaRS database.

Canadian Prostate Brachytherapy in 2012

Prostate brachytherapy can be used as a monotherapy for low- and intermediate-risk patients or in combination with external beam radiation therapy (EBRT) as a form of dose escalation for selected intermediate- and high-risk patients. Prostate brachytherapy with either permanent implants (low dose rate [LDR]) or temporary implants (high dose rate [HDR]) is emerging as the most effective radiation treatment for prostate cancer. Several large Canadian brachytherapy programs were established in the mid- to late-1990s. Prostate brachytherapy is offered in British Columbia, Alberta, Manitoba, Ontario, Quebec and New Brunswick. We anticipate the need for brachytherapy services in Canada will significantly increase in the near future. In this review, we summarize brachytherapy programs across Canada, contemporary eligibility criteria for the procedure, toxicity and prostate-specific antigen recurrence free survival (PRFS), as published from Canadian institutions for both LDR and HDR brachytherapy.

Calcifications in low-dose rate prostate seed brachytherapy treatment: Post-planning dosimetry and predictive factors

BACKGROUND AND PURPOSEnThe brachytherapy dose algorithm of the American Association of Physicists in Medicine Task Group (TG) Report 43 overrides all tissue materials with water. In reality, dose discrepancies will occur around tissue calcifications. This study investigates these perturbations in low dose rate prostate brachytherapy dosimetry.nnnMATERIALS AND METHODSn43 cancer patients with prostatic calcifications are identified. Geant4 Monte Carlo (MC) simulations are made with materials assigned based on TG186 recommendations. Five dose calculation scenarios are presented: MC in water (MCW), MCW with calcifications, (MCCA), MCCA with seeds (MCCASEED) and full tissue definition and seeds with dose to medium in medium (FMC) and dose to water in medium (FMC-Dw,m).nnnRESULTSnThe mean FMC prostate D90 (V100) difference relative to TG43 is -6.4% (range [-1.8, -14.1]) (-2.6% [-0.3, -6.7]). For MCCA we obtained -3.9% [-1.0, -8.7] (-1.5% [-0.2, -4.1]). The mean urethra D10 difference is -4.5% [-1.3, -9.9] for FMC, -2.4% [-0.7, -5.1] with MCCA. FMC-Dw,m D90 has a -0.45% smaller dose difference than FMC on average. The calcification/prostate volume ratio is a good predictor of dose perturbation (R(2)=0.75).nnnCONCLUSIONnBased on these results, calcifications alter the dose coverage and may have severe dose perturbation that requires recalculation.

Quantifying the effect of seed orientation in postplanning dosimetry of low-dose-rate prostate brachytherapy

PURPOSEnRadioactive seed orientations are usually ignored in clinical brachytherapy dosimetry for prostate implants. Associated with the anisotropic dose distribution of seeds, these orientations could cause dose differences between the planning configurations and the clinical postplanning dosimetry. This study will quantify the impact of seed orientation on the dosimetry.nnnMETHODSn3D seed positions and θ and φ polar angles were obtained using five independent fluoroscopic images for 287 patients. Five dose calculation methods are compared: TG43-1D (1), TG43-2D parallel to implant axis (2) and with orientations (3), Monte Carlo (MC) simulations parallel (4), and MC simulations with orientations (5). GEANT4 v4.9.6 MC simulations were made in 1 mm(3) voxelized geometries based on the DICOM-RT information. Materials were assigned using thresholds based on the HU number, as recommended in TG186 reports. Seed voxels are overridden with prostatic materials and the layered mass geometry [Enger et al., Phys. Med. Biol. 57(19), 6269-6277 (2012)] allows subsequent placement of the source geometry. 500 million histories were used per patient. 3D dose and DVHs for each structure were calculated.nnnRESULTSnThe various seed orientations do not result in statistically significant differences on the dose metrics for the clinical target volume (CTV) or the urethra, based on the Student t-test p-value. Difference as low as -0.238% and 0.059% has been seen on the CTV D90, respectively, for the MC and the TG43. The difference between parallel and oriented calculations for the organs at risk (OARs) can differ by 2% on average.nnnCONCLUSIONSnBased on the results from this study, seed orientations have no significant impact of CTV and urethra dose metrics but can affect OARs that are external to the CTV.

Management of Bartholin’s gland carcinoma using high-dose-rate interstitial brachytherapy boost

PURPOSEnTo describe the patterns of use, clinical outcomes, and dose-volume histogram parameters of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the management of Bartholins gland cancer.nnnMETHODS AND MATERIALSnFive patients with Stage II-III Bartholins gland carcinoma treated with CT-based HDR-ISBT boost were reviewed. Plans were generated using an inverse planning simulated annealing algorithm. Dose-volume histogram parameters were assessed. The total doses of HDR-ISBT and EBRT were converted to total equivalent dose in 2Gy (EQD2).nnnRESULTSnAll 5 patients received HDR-ISBT as a boost (median dose, 30Gy) after EBRT (median dose, 45Gy). Three patients received postoperative irradiation for gross residual tumor or positive surgical margins and 2 patients were treated by primary chemoradiotherapy. The median V100, D90, and D100 for the CTV were 98.3%, 89Gy10, and 64Gy10 (EQD2), respectively. A complete response was observed in all patients. No local recurrence occurred. All patients remain alive and free of disease (median followup, 78 months; range, 8-93). Severe vaginal toxicities were observed, including vaginal necrosis that resolved with hyperbaric oxygen therapy.nnnCONCLUSIONSnHDR-ISBT boost after EBRT offers excellent long-term local control in patients with Bartholins gland carcinoma. HDR-ISBT should be considered for positive surgical margins or residual tumor after surgery and for locally advanced malignancies treated by primary chemoradiotherapy.