Juanita Crook

Prognostic factors for newly diagnosed prostate cancer and their role in treatment selection.

Adenocarcinoma of the prostate is extremely heterogeneous, ranging from an indolent chronic illness to an aggressive rapidly fatal systemic malignancy. The classic prognostic factors of tumor stage, prostate specific antigen level, and Gleason score have been used for over a decade to categorize patients at the time of diagnosis into broad risk groups that help to determine appropriate management. Although the grouping of patients into favorable, intermediate, and high-risk categories has become standard, and the categories continue to define distinct prognostic subgroups, considerable heterogeneity exists within each risk group. As a range of management options are available, additional prognostic factors can be considered when determining the treatment approach for an individual patient. We review these additional prognostic variables under the headings of patient-related, tumor-related, and treatment-related. The influence of each of these factors may vary depending on treatment factors such as dose, the radiation modality, or the use of concomitant androgen ablation.

Report on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers.

PURPOSE Permanent breast seed implant is an accelerated partial breast irradiation technique realizing the insertion of (103)Pd seeds in the seroma after lumpectomy. We report the 5-year efficacy and tolerance for a cohort, pooling patients from 3 clinical trials. METHODS AND MATERIALS The trials accrued postmenopausal patients with infiltrating ductal carcinoma or ductal carcinoma in situ ≤3 cm and clear surgical margins, who were node negative, and had a planning target volume <120 cm(3). The outcomes included overall and disease-free survival and local and contralateral recurrence at 5 years. The true local recurrence rate was compared using 2-tailed paired t tests for estimates calculated using the Tufts University ipsilateral breast tumor recurrence and Memorial Sloan Kettering ductal carcinoma in situ nomograms. RESULTS The cohort included 134 patients, and the observed local recurrence rate at a median follow-up period of 63 months was 1.2% ± 1.2%, similar to the estimate for whole breast irradiation (P=.23), significantly better than for surgery alone (relative risk 0.27; P<.001), and significantly lower than contralateral recurrence (relative risk 0.33; P<.001). The 5-year overall survival rate was 97.4% ± 1.9%, and the disease-free survival rate was 96.4% ± 2.1%. At 2 months, 42% of the patients had erythema, 20% induration, and 16% moist desquamation. The rate of mainly grade 1 telangiectasia was 22.4% at 2 years and 24% at 5 years. The rate of asymptomatic induration was 23% at 2 years and 40% at 5 years. CONCLUSIONS The 5-year data suggest that permanent breast seed implantation is a safe accelerated partial breast irradiation option after lumpectomy for early-stage breast cancer with a tolerance profile similar to that of whole breast irradiation.

Skin dose in breast brachytherapy: Defining a robust metric

PURPOSE To define a simple, robust, and relevant metric for measuring skin dose in breast brachytherapy. METHODS AND MATERIALS Postoperative treatment plans (Day 0) for 15 permanent breast seed implant (PBSI) and 10 multicatheter high-dose-rate (MC-HDR) brachytherapy patients were included. Retrospectively, three skin structures were contoured: 2 mm external from the body; and subsurface layers 2 mm and 4 mm thick. Maximum point dose (Dmax), doses to small volumes (e.g., D0.2cc), and the volumes receiving a percentage of the prescription dose (V%, e.g., V66) were calculated. D0.2cc was investigated as a surrogate to the dose given to 1 cm(2) of skin (D1cm(2)). Pearson product-moment correlation (R(2)) was computed between metrics. RESULTS Observed trends were consistent across brachytherapy technique. V% did not correlate well with any other metrics: median (range) R(2), 0.63 (0.43, 0.77) and 0.69 (0.3, 0.89) for PBSI and MC-HDR, respectively. Dmax was inconsistently correlated across contours and not well correlated with doses to small volumes: median (range) R(2), 0.85 (0.76, 0.93) and 0.88 (0.83, 0.93) for PBSI and MC-HDR, respectively. In contrast, doses to small volumes were consistently well correlated, even across skin layers: D0.1cc vs. D0.2cc median (range) R(2), 0.98 (0.97, 0.99) and 0.97 (0.94, 0.99) for PBSI and MC-HDR, respectively. CONCLUSIONS Doses to small volumes are robust measures of breast skin dose and given skins strong area effect, D0.2cc for a 2 mm thick skin layer, a simple surrogate of D1cm(2), is recommended for recording skin dose in any breast brachytherapy. Dmax is not robust and should be avoided.

A Phase II trial of 8 weeks of degarelix for prostate volume reduction: Efficacy and hormonal recovery

PURPOSE The purpose of this study was to determine the efficacy of 8 weeks of degarelix for prostate downsizing before interstitial brachytherapy. We also report associated toxicity and the time course of endocrine recovery over the following 12 months. METHODS AND MATERIALS Fifty patients were accrued to an open-label Phase II clinical trial (www.clinicaltrials.gov ID NCT01446991). Baseline prostate transrectal ultrasound (TRUS) was performed on all patients followed by degarelix administration and a repeat TRUS at Week 8. Brachytherapy was performed within 4 weeks of the 8-week TRUS for all patients who achieved suitable downsizing. RESULTS The median prostate volume was reduced from 65.0 cc (interquartile range [IQR]: 55.2-80.0 cc) to 48.2 cc at 8 weeks (IQR: 41.2-59.3 cc), representing a median decrease of 26.2% (IQR: 21-31%). Functional recovery of testosterone within an age-adjusted normal range occurred at a median of 34.1 weeks (IQR: 28.2-44.5 weeks) from the date of the final injection. Despite this recovery, follicle-stimulating hormone and luteinizing hormone levels remained abnormally elevated throughout 12 months. Quality-of-life implications are discussed. CONCLUSIONS Degarelix is effective for prostate downsizing before prostate brachytherapy with a median volume decrease of 26.2% by 8 weeks. Despite the short course of treatment and eventual testosterone recovery, follicle-stimulating hormone and luteinizing hormone remain elevated beyond 12 months. Further investigation with randomized comparisons to other hormonal agents is warranted.