Cesium-137 needle brachytherapy boosts after external beam irradiation for locally advanced carcinoma of the tongue and floor of the mouth

PURPOSE: A retrospective study was undertaken to compare local tumor control and complications of external beam radiation therapy with and without interstitial 137Cs needle brachytherapy boost doses. METHODS AND MATERIALS: Two hundred one consecutive patients with locally advanced (T3-T4) cancer of the tongue and floor of the mouth treated with definitive radiotherapy by external beam irradiation with (n = 78) or without (n = 123) low-dose-rate interstitial brachytherapy from 1974 to 1999 were analyzed retrospectively. External beam irradiation was administered with conventional fractionation in 105 patients and administered with accelerated hyperfractionation in 96 patients. RESULTS: The 8-year actuarial local control rates showed a trend toward improved results in the combined-treatment group as a whole and also when it was stratified into patients with base of tongue sites and those with oral tongue and floor of mouth sites. Cox regression analysis for local control showed that the only significant variable was overall treatment time. The use of brachytherapy boost doses was not a significant variable. The 8-year actuarial probability of Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Grades 3-5 late effects was 25% and 35% for patients with and without brachytherapy, respectively (p = not significant), although the crude incidence of mandibular radiation osteonecrosis was 10% and 1.6%, respectively (p =0.001). CONCLUSIONS: This study showed a trend toward improved local control rates for brachytherapy after external beam radiotherapy. The incidence of mandibular osteonecrosis was increased.     

Perioperative high-dose-rate brachytherapy in locally advanced and recurrent gynecological cancer: Final results of a Phase II trial

PurposeTo determine the long-term results of a Phase II trial of perioperative high-dose-rate brachytherapy (PHDRB) in primary advanced or recurrent gynecological cancer.Methods and MaterialsFifty patients with locally advanced and recurrent gynecological cancer suitable for salvage surgery were included. Unirradiated patients (n = 25) received preoperative chemoradiation followed by surgery and PHDRB (16–24 Gy). Previously irradiated patients (n = 25) received surgery and PHDRB alone (32–40 Gy).ResultsMedian followup was 11.5 years. Eight unirradiated patients (32%) developed Grade ≥3 toxic events including two fatal events. Local and locoregional control rates at 16 years were 87.3% and 78.9%, respectively. Sixteen-year disease-free and overall survival rates were 42.9% and 46.4%, respectively. Ten previously irradiated patients (40.0%) developed Grade ≥3 adverse events, including four fatal events. Local and locoregional control rates at 14 years were 59.6% and 42.6%, respectively. Fourteen-year disease-free and overall survival rates were 16.0% and 19.2%, respectively.ConclusionsPHDRB allows effective salvage of a subset of unfavorable gynecological tumors with high-risk surgical margins. Toxicity was unacceptable at the initial dose levels but deescalation resulted in the absence of severe toxicity without a negative impact on locoregional control. A substantial percentage of patients remain alive and controlled at >10 years including a few previously irradiated cases with positive margins.     

Prolonged hormonal therapy and external beam radiation independently increase the risk of Persistent Hypogonadism in men treated with prostate brachytherapy

PurposeTo identify variables that predict persistent hypogonadism and castration in patients with prostate cancer (PCa) treated with brachytherapy (BT).Materials and MethodsA retrospective analysis was performed on 1,053 patients receiving BT ± external beam radiation therapy (EBRT) ± hormone therapy (HT) for NCCN low, intermediate, or high-risk PCa between 1990 and 2011. Patients were categorized as not receiving HT (n = 438, 41.6%), ≤6 months (n = 317, 31.1%) or > 6 months (n = 298, 28.3%) of HT. 572 (54.3%) received BT alone, and 481 had combination therapy. The five- and 10-year freedom from persistent hypogonadism (T < 280 ng/dL) and castration (T < 50 ng/dL) for each group was evaluated with Kaplan-Meier estimates. Multivariable cox proportional hazards models were used to compare the risk of persistent hypogonadism and castration at a median followup of 6.5 years (posttreatment to final T) (IQR: 4.3–9.1 years; range: 1.0–19.2 years).ResultsThe 5-year freedom from hypogonadism rates were 92.4%, 88.9%, and 87.0% for patients with no HT, ≤ 6 months and >6 months of HT, respectively (10-year rates: 66.7%, 55.3%, 40.5%); p < 0.01. The 5-year freedom from castration rates were 99.2%, 98.0%, and 98.4%, respectively (10-year rates: 97.9%, 95.5%, 90.9%); p = 0.078. Number of months of HT (HR = 1.04, p = 0.030) and BT with EBRT vs. BT alone (HR = 1.56, p = 0.010) significantly increased the risk of persistent hypogonadism. Number of months of HT was the only variable which increased the risk of persistent castration (HR = 1.09, p = 0.014).ConclusionsThe addition of EBRT to BT is an independent risk factor for persistent hypogonadism. Prolonged HT additionally increases the risk of persistent hypogonadism and castration.     

Temporal effect of neoadjuvant androgen deprivation therapy on PSA kinetics following permanent prostate brachytherapy with or without supplemental external beam radiation

PURPOSE: To evaluate the effect of neoadjuvant androgen deprivation therapy on PSA kinetics following brachytherapy with or without supplemental external beam radiation therapy (XRT), to evaluate the magnitude and duration of the peak PSA, and to compare potential differences in PSA response curves between biochemically disease-free and failed patients. MATERIALS AND METHODS: From November 1995 through August 2000, 179 consecutive patients with clinical T1b-T3a NxM0 (2002 AJCC) prostate cancer received neoadjuvant androgen deprivation therapy (median, 4 months) prior to brachytherapy using (103)Pd or (125)I with or without supplemental XRT. The median follow-up was 56 months. Following brachytherapy, PSA determinations were obtained at 3 months and then every 6 months thereafter. A median and mean of 9 and 9.5 PSA determinations, respectively, were obtained per patient. Biochemical disease-free survival was defined by the ASTRO and Houston definitions with both definitions used to determine the rate of overestimation of early biochemical failure secondary to testosterone recovery. RESULTS: Although a trend for higher baseline and peak PSA was noted in (125)I monotherapy patients, the difference between the 4 groups was not statistically significant (p = 0.088). Changes in PSA over time, however, were statistically significant (p = 0.042). For all 4 groups, the peak PSA occurred approximately 15-21 months following brachytherapy. For biochemically disease-free patients, the median PSA increase above nadir was 0.1 ng/mL, and the median number of consecutive rises in PSA was 1. Using the ASTRO and Houston definitions, only 2.3% and 0.6% of patients would have been inadvertently scored as failures. CONCLUSIONS: In brachytherapy patients receiving 3-6 months of neoadjuvant androgen deprivation therapy, the median PSA increase above nadir was 0.1 ng/mL. The ASTRO and Houston definitions of biochemical failure inadvertently scored only 2.3% and 0.6% of patients as failures.     

Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate

PurposeA Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant.Methods and MaterialsFrom 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6 Gy to the entire prostate and 9 Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70 Gy. Patients received 50.4 Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128 Gy (α/β = 3). Patients whose pretreatment PSA was ≥10 ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation.ResultsMedian followup was 53 months (9–68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32 ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities.ConclusionsSingle-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer.     

Comparison study of the partial-breast irradiation techniques: Dosimetric analysis of three-dimensional conformal radiation therapy,electron beam therapy,and helical tomotherapy depending on various tumor locations

The partial-breast irradiation (PBI) technique, an alternative to whole-breast irradiation, is a beam delivery method that uses a limited range of treatment volume. The present study was designed to determine the optimal PBI treatment modalities for 8 different tumor locations. Treatment planning was performed on computed tomography (CT) data sets of 6 patients who had received lumpectomy treatments. Tumor locations were classified into 8 subsections according to breast quadrant and depth. Three-dimensional conformal radiation therapy (3D-CRT), electron beam therapy (ET), and helical tomotherapy (H-TOMO) were utilized to evaluate the dosimetric effect for each tumor location. Conformation number (CN), radical dose homogeneity index (rDHI), and dose delivered to healthy tissue were estimated. The Kruskal-Wallis, Mann-Whitney U, and Bonferroni tests were used for statistical analysis. The ET approach showed good sparing effects and acceptable target coverage for the lower inner quadrant—superficial (LIQ-S) and lower inner quadrant—deep (LIQ-D) locations. The H-TOMO method was the least effective technique as no evaluation index achieved superiority for all tumor locations except CN. The ET method is advisable for treating LIQ-S and LIQ-D tumors, as opposed to 3D-CRT or H-TOMO, because of acceptable target coverage and much lower dose applied to surrounding tissue.     

Accelerated partial breast irradiation for suitable elderly women using a single fraction of multicatheter interstitial high-dose-rate brachytherapy: Early results of the Single-Fraction Elderly Breast Irradiation (SiFEBI) Phase I/II trial

Purpose/ObjectiveTo evaluate feasibility and early clinical outcomes of a single fraction of multi-catheter interstitial high-dose rate brachytherapy for accelerated partial breast irradiation (APBI) in the elderly.Material/MethodsFrom November 2012 to September 2014, 26 patients (≥70) with early breast cancer were enrolled in a prospective phase II trial (NCT01727011). After lumpectomy, intra-operative catheter implant was performed for post-operative APBI (single fraction 16 Gy). Surveillance was achieved at 1, 3 and 6 months after APBI, then twice a year. Acute toxicity was investigated. Early cosmetic outcome was analyzed (patient, radiation oncologist, 2 observers). Local and regional relapse-free survival, cancer specific survival and overall survival were analyzed.ResultsMedian age was 77 years [69–89]. Median CTV was 41 cc [22-95]. Acute toxicity was observed in 18 pts (70%) with a total of 44 events: G1: 75.7%; G2: 22.8%; G3: 4.5%. Breast fibrosis (31.8%), puncture site inflammation (13.6%) and skin hyperpigmentation (11.4%) were the most frequent side effects. Cosmetic evaluation at 6 months was excellent/good in 88%, 92%, 85% and 88% for patient, radiation oncologist, observer #1 and #2 respectively. With a median follow-up of 37.2 months [35.6-42.3], side effects were G1: 4 pts (15%) and G2: 1 pt (4%). Three-year Local and regional relapse-free survival, cancer specific survival and overall survival rates were 100%, 100%, 100% and 95.2% respectively.ConclusionsFor elderly early breast cancer, a post-operative multi-catheter interstitial high-dose rate brachytherapy single dose (16 Gy) appears feasible. Acute toxicity is acceptable as well as early cosmetic outcome. Oncologic outcome seems encouraging and allows going forward with new clinical trials focusing on single fraction APBI.