Background: High-risk (HR) prostate cancer has a propensity for local and distant progression with ultimate death, mandating aggressive locoregional and systemic treatment approaches to maximize oncologic outcomes. Although brachytherapy (BT) with supplemental therapies has demonstrated favorable biochemical and quality of life outcomes, improvements in overall survival have been hampered by an excessive incidence of non- prostate cancer deaths. In this HR study, we report on biochemical failure (BF), prostate cancer-specific mortality (PCSM), overall mortality (OM) and patterns of death with recommendations for the mitigation of non-prostate cancer deaths. Materials and Methods: From April 1995 to November 2018, 577 consecutive HR patients were treated with LDR BT (97.9% Pd-103). Patients were stratified into three age cohorts: ≤ 59, 60-69 and ≥70 years. The BT prescription dose was prescribed to the prostate gland with generous peri-prostatic margins and the proximal 10mm of the seminal vesicles. 94.6% received supplemental EBRT (45-50.4 Gy) and 63.3% received androgen deprivation therapy (ADT) (median duration 12 months). Post-implant CT-based dosimetry was performed on day 0. BF was defined as a PSA > 0.40 ng/mL after nadir. The cause of death was determined for each patient. Patients with metastatic prostate cancer or non-metastatic castrate resistant prostate cancer who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause. Multiple clinical, pathologic and treatment were evaluated for impact on patient outcomes. Results: Of the patients, 87.5% (median follow-up 8.9 years) presented with a single HR factor. The day 0 D90 was 122.5%. Overall, the 15-year BF, PCSM and OM were 12.4%, 5.6% and 51.7%. When stratified by age, there was no significant difference in BF or PCSM. The median post- treatment PSA in biochemically controlled patients was <0.01 ng/mL. In all three cohorts, OM increased linearly for the first 10 years and then approximately doubled from years 10 to 15. Moreover, 239 patients died: 10.9% due to prostate cancer, 38.1% from cardiovascular (CV) disease and 28.4% from other malignancies (to include one rectal and three bladder cancers). In MVA, BF was most closely related to percent positive biopsies (p < 0.001, SHR 1.018), PCSM to Gleason score (p = 0.004, SHR 2.884) and percent positive biopsies (p = 0.005, SHR 1.021) and OM to age (p < 0.001, HR 1.075) and tobacco (p < 0.001, HR 2.374). Conclusions: Despite high cancer control rates, overall survival was limited by a preponderance of CV and non-prostate cancer deaths, which were 6 times more likely than prostate cancer deaths. The implementation of a comprehensive multidisciplinary survivorship program will be essential to impact longevity in this patient population.

Purpose: The 44/20 and 20/0 randomized trials evaluated whether different external beam radiation therapy (EBRT) dosing regimens prior to brachytherapy affected biochemical failure (BF). We report long-term outcomes of both trials and evaluate whether biological equivalent dose (BED) was associated with reduced BF in the combined trial cohort. Methods and Materials: Both trials enrolled patients with clinical T1c to T2b, Gleason scores 7 to 9, and/or a pretreatment prostate-specific antigen (PSA) 10 to 20 ng/mL disease. The 44/20 trial randomized patients to 44 Gy EBRT with 90 Gy palladium (Pd)-103 versus 20 Gy EBRT with 115 Gy Pd-103. The subsequent 20/0 trial randomized patients to the 20 Gy arm versus monotherapeutic 125 Gy Pd-103. For each trial, univariate Fine-Gray analysis evaluated whether the treatment arm was associated with BF for the entire cohort and the unfavorable intermediate-risk (UIR) subgroup. For the combined trial cohort, multivariate Fine-Gray analysis evaluated whether BED was associated with BF while adjusting for clinical factors. Results: There were 247 analyzable patients in the 44/20 trial. At a median follow-up of 13.7 years, there were no differences in BF for the entire cohort (subdistribution hazard ratio [sHR] 0.99; 95% CI, 0.43, 2.276; P = .97) or the UIR subgroup (sHR 0.72; 95% CI, 0.25, 2.08; P = .55). There were 383 analyzable patients in the 20/0 trial. At a median follow-up of 10.4 years, there were no differences in BF for the entire cohort (sHR 0.42; 95% CI, 0.13-1.80; P = .15) or the UIR subgroup (sHR 0.81; 95% CI, 0.16-4.03; P = .80). For the combined cohort (630 patients), BED was not associated with BF (1.00; 95% CI, 0.98-1.02; P = .88) on multivariate analyses while adjusting for androgen deprivation therapy utilization, 4-tiered National Comprehensive Cancer Network category, and year of treatment. Conclusions: Brachytherapy monotherapy should be a standard-of-care treatment for clinically localized, intermediate-risk prostate cancer, including UIR disease. (c) 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Purpose/Objective(s) To evaluate the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in predicting biochemical failure (BF) and prostate cancer specific mortality (PCSM) in higher-risk prostate cancer patients implanted with Pd-103. Materials/Methods Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pre-treatment prostate-specific antigen (PSA) of 10-20 ng/mL. Trial 44/20 randomized 247 patients to 44 Gy + 90 Gy Pd-103 vs. 20 Gy with 115 Gy Pd-103. The subsequent 20/0 trial randomized 383 patients to the 20 Gy arm vs. monotherapeutic 125 Gy Pd-103. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins using extracapsular seeds and implantation of the proximal 10-12 mm of the seminal vesicles. Post-implant computerized tomography (CT) based dosimetry was performed on day 0. Biochemical failure (BF) was defined as a PSA > 0.40 ng/mL after nadir. Multiple clinical, pathologic and treatment parameters were evaluated for impact on BF, PCSM, and overall mortality (OM). Results For all 630 patients, the median follow up was 11.8 years with a day 0 D90 of 121.9% of prescription and a V100 of 98.3%. The 13-year BF, PCSM and OM were 5.8%, 1.0%, 30.4%, respectively. For the 44/20 patients (median follow up 13.7 years) BF, PCSM & OM were 8.9%, 2.4% and 39.7% while BF, PCSM & OM for 20/0 (median follow-up 10.4 years) were 3.6%, 0.0% in 21.5%. In part, the difference in outcome between the two groups was due to a significant difference in the number of accrued Gleason score (GS) 8-9 patients (15.8% versus 1.6%). BF and PCSM for FIR, UIR and HR were 3.5% and 0.0%, 7.5% and 1.9%, and 15.2%, and 4.3%, respectively. The median time to BF was 5.1 (range = 0.7-10.7), 4.6 (range = 0.7-12.3), and 2.9 (range = 0.2-7.8) years for FIR, UIR and HR. Neither the addition of EBRT or dose impacted BF (Table) or PCSM. In multivariate analysis, BF was most closely related to pre-implant PSA (P = 0.019, HR = 1.154), GS (P = 0.008, HR = 1.748), and percent positive biopsies (P = 0.015, HR = 1.020). PCSM was most closely related to pre-implant PSA (P = 0.02, HR = 1.218) and GS (P < 0.001, HR = 4.178). For all biochemically controlled patients, the median PSA was< 0.02 ng/mL. Conclusion In this study, consistent, high-quality Pd-103 dose distributions with aggressive extra-capsular and proximal seminal vesicle coverage resulted in durable biochemical control rates in patients with higher-risk features. The addition of supplemental EBRT did not impact BF or PCSM.

SF-PORT is associated with a very low LRR which has proven durable with long-term follow-up. The LRR for SF-PORT appears lower than historical controls treated with surgery alone for patients with resected, stage I/II MCC with high-risk features.

MCC is a rare aggressive skin cancer with a high(∼20%) risk of local recurrence. Postoperative radiotherapy(PORT) significantly improves local control in early-stage MCC and is typically indicated if baseline risk factor(s) are present (positive/narrow surgical margins, primary tumor >1cm, head/neck (HN) location, immunosuppression (IMS), and lymphovascular invasion(LVI)). However, conventionally fractionated PORT (C-PORT; ∼50 Gy in 25 fractions) may result in morbidity and financial/travel burden. Our previously reported, early experiences with 8 Gy single fraction (SF-PORT) demonstrate high rates of in-field control and low toxicity in the metastatic and adjuvant settings. Here we present updated 2-year outcomes of SF-PORT as an alternative to C-PORT for resected Stage I-II MCC. Forty-six patients (Stage I, 80%; Stage II, 20%) received SF-PORT to the primary tumor site at a median 44 days after: wide local excision (85%), shave/excisional biopsy only (13%), or Mohs (2%). Of 9 patients who received elective nodal SF-PORT, 8 did not have a sentinel lymph node biopsy. HN (74%) was the most common primary site, followed by extremity (22%) and trunk (4%). At median follow-up of 2.3 years (range 0.2-5.0), 44/46 patients (96%) had no in-field locoregional recurrence. Both of the in-field recurrences arose in draining nodal basins of HN primary lesions (1 with LVI). There were also 2 out-of-field regional nodal recurrences (1 patient with IMS; 0/2 received nodal RT). No MCC-specific deaths were observed. The most common side effect was in-field Grade 1 erythema (13%); no side effects > Grade 1 (CTCAE v5) were noted. While C-PORT is commonly recommended for MCC with multiple risk factors, management varies across institutions and some elect observation. For patients with a low-moderate baseline risk profile, these data suggest SF-PORT can be considered as it affords a high rate of in-field control and minimal toxicity in early-stage MCC.

This work has shown that margins of lung blocks could affect the dose to lungs and heart substantially, despite the indifference that the commonly used point dose parameter, point dose behind the blocks, indicates. A 3D TBI model could provide more dosimetry data to help future studies to correlate TBI-associated toxicity to the heart and lungs.

No data exist on radiation therapy utilization and outcomes for patients with cancer who are also experiencing homelessness. We hypothesize that homeless patients with cancer have unique barriers to care that adversely affect receipt of optimal radiation therapy (XRT) and negatively impact cancer outcomes. We present the first descriptive demographics for this underserved population and explore radiation-specific factors that may affect outcomes. The records of patients referred for XRT at three academic and community hospitals in King County, WA were retrospectively reviewed. Patients were considered to be homeless at the time of referral per the Department of Housing and Urban Development definition. A 2015-2019 survey of persons experiencing homelessness in King County was used as a demographic comparison. Descriptive analyses employed the Chi-Square test and Welch's t-test, for categorical and continuous variables, respectively. Survival was estimated using the Kaplan-Meier method and log-rank test. 26 patients referred for XRT between 2009 and 2019 were identified, with 35 XRT courses recommended. Mean age and ECOG performance status was 55 years and 1.4, respectively. While 53% of homeless persons in King County were African American, Hispanic, or Native American, only 20% of patients referred for XRT identified as such (p<0.001). A plurality of patients had anorectal (12%), gynecologic (24%), or head and neck (20%) primaries. At time of referral, 73% of patients had advanced disease. The median time from date of referral to XRT start was 31.5 and 42.5 days for insured (52%) and uninsured (48%) patients, respectively (p = 0.001). 84% of patients received counseling from social work; 56% received pecuniary assistance. The median number of treatments per course was 12 (range 1-35); there were 2 single-fraction XRT courses. 91% of patients completed the recommended course of XRT. 88% of patients received systemic therapy, if recommended. Among 17 patients treated with curative intent, 65% of XRT courses had treatment interruptions, with an average delay of 8 days. With a median follow up of 13 months (range 0.4-105), median overall- and recurrence free survival was 18 and 14 months, respectively. The median OS for curative and palliative-intent patients were 20 vs. 10 months (p = 0.078). It is not known how many homeless patients with cancer who may benefit from XRT but are not referred for treatment. These data support the routine referral of this vulnerable patient population, when indicated, despite any perceived logistical barriers. However, there may be racial disparities to referral patterns for XRT. We report that homeless patients referred for XRT are given considerable support, with an excellent rate of treatment completion. Challenges remain in terms of treatment delay, particularly for uninsured patients and those treated with curative intent, where there is high level evidence to show that delays are deleterious to outcomes.

Background: Worldwide, nearly 570,000 women are diagnosed with cervical cancer each year, with 85% of new cases in low- and middle-income countries. The African continent is home to 35 of 40 countries with the highest cervical cancer mortality rates. In 2014, a partnership involving a rural region of Senegal, West Africa, was facing cervical cancer screening service sustainability barriers and began adapting regional-level policy to address implementation challenges. Objective: This manuscript reports the findings of a systematic literature review describing the implementation of decentralized cervical cancer prevention services in Africa, relevant in context to the Senegal partnership. We report barriers and policy-relevant recommendations through Levesque's Patient-Centered Access to Healthcare Framework and discuss the impact of this information on the partnership's approach to shaping Senegal's regional cervical cancer screening policy. Methods: The systematic review search strategy comprised two complementary sub-searches. We conducted an initial search identifying 4272 articles, then applied inclusion criteria, and ultimately 19 studies were included. Data abstraction focused on implementation barriers categorized with the Levesque framework and by policy relevance. Results: Our findings identified specific demand-side (clients and community) and supply-side (health service-level) barriers to implementation of cervical cancer screening services. We identify the most commonly reported demand- and supply-side barriers and summarize salient policy recommendations discussed within the reviewed literature. Conclusions: Overall, there is a paucity of published literature regarding barriers to and best practices in implementation of cervical cancer screening services in rural Africa. Many articles in this literature review did describe findings with notable policy implications. The Senegal partnership has consulted this literature when faced with various similar barriers and has developed two principal initiatives to address contextual challenges. Other initiatives implementing cervical cancer visual screening services in decentralized areas may find this contextual reporting of a literature review helpful as a construct for identifying evidence for the purpose of guiding ongoing health service policy adaptation.

Purpose To evaluate the impact of supplemental external beam radiation therapy (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and erectile function. Material and methods Patient administered urinary, bowel, and erectile quality of life (QoL) instrument were obtained prior to treatment and following brachytherapy. The study population was comprised of the 457 patients who were alive as of June 2016, had been randomized to two markedly different supplemental EBRT dose regimens and a third arm without supplemental EBRT, and had completed the June 2016 QoL survey. The need for urinary or bowel surgical intervention was prospectively recorded during routine follow-up. Multiple parameters were evaluated for effect on outcomes. Results The urinary catheter was removed on day 0 in 92.1% of patients and 0.4% required a post-implant transurethral prostatic resection (TURP). On average, the International Prostate Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral strictures was 5.3%. No significant differences were discerned between baseline and post-implant rectal function assessment score (RFAS), and no patient developed a rectal ulcer or fistula. The 10-year potency preservation rate was 50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function. Urethral strictures were most closely related to bulbomembranous urethral brachytherapy doses, post-implant rectal function to pre-implant hemorroidal bleeding, and RFAS and erectile function to pre-brachytherapy international index of erectile function and age. Conclusions Supplemental EBRT did not significantly effect catheter dependency, IPSS resolution, urethral stricture rate, the need for post-implant TURP, bowel, or erectile function. Careful attention to brachytherapy dose distributions appears to be most important in minimizing post-brachytherapy morbidity.

PURPOSE: To evaluate whether supplemental external beam radiotherapy (EBRT) is essential to maximize Pd-103 brachytherapy outcomes in patients with unfavorable intermediate-risk (IR) disease.METHODS AND MATERIALS: A total of 630 patients were assessed from two prospective randomized brachytherapy trials evaluating the role of supplemental EBRT in patients with higher risk features. Patients were stratified into unfavorable IR (primary Gleason pattern 4, >= 50% positive biopsies, or IR features), favorable IR, and high-risk (HR) cohorts. Median follow-up was 7.5 years. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a prostate-specific antigen >0.40 ng/mL after nadir. Patients with metastatic prostate cancer or nonmetastatic castrate-resistant disease who died of any cause were classified as dead of prostate cancer. Multiple parameters were evaluated for effect on outcomes.RESULTS: The 10-year BF for favorable IR, unfavorable IR, and HR was 1.7%, 6.6%, and 15.5% (p < 0.001). At 10 years, prostate cancer-specific mortality (PCSM) and overall mortality (OM) were 0% and 20.4%, 2.1% and 23.2%, and 4.3% and 42.4% for favorable IR, unfavorable IR, and HR. Although unfavorable IR patients had a greater incidence of BF, PCSM, and OM when compared with favorable IR, neither the addition nor dose of supplemental EBRT influenced outcome.CONCLUSIONS: Outcomes for favorable IR were superior to those with unfavorable IR. Within the confines of this study, neither the addition nor dose of supplemental EBRT influenced BF, PCSM, or OM in patients with IR disease. (C) 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

PURPOSE: To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 (Pd-103) brachytherapy for high-risk prostate cancer patients.METHODS AND MATERIALS: Trial 44/20 randomized patients to 44 Gy plus 90 Gy Pd-103 vs. 20 Gy with 115 Gy Pd-103, and the subsequent trial randomized patients to the 20 Gy arm vs. 125 Gy Pd-103 without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pretreatment prostate-specific antigen (PSA) 10-20 ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40 ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D-90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes.RESULTS: In 44/20 trial, 13-year BF, prostate cancer specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20 Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0 Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of <0.02 ng/mL.CONCLUSIONS: With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8-9 was too small to determine the role of supplemental EBRT in that cohort. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

An optimal treatment regimen for localized prostate cancer (PCa) is yet to be determined. Increasing evidence reveals a lower α/β ratio for PCa with hypofractionated radiation therapy (HFRT) regimens introduced to exploit this change in therapeutic ratio. HFRT also results in shortened overall treatment times of 4 to 5 weeks, thus reducing staffing and machine burden, and, more importantly, patient stress. This review evaluates pretreatment characteristics, outcomes, and toxicity for 15 HFRT studies on localized PCa. HFRT results in comparable or better biochemical relapse-free survival and toxicity and is a viable option for localized PCa.

PURPOSE: Recent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT.METHODS AND MATERIALS: Between April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters.RESULTS: At 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p = 0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p = 0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p = 0.14).CONCLUSIONS: Men with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern 5. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

PURPOSE:To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment.METHODS AND MATERIALS:Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike.RESULTS:There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase ≥ 25%, 23% of men experienced a decrease ≥ 25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21).CONCLUSION:Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response does not seem related to temporal testosterone changes.

PURPOSE: To evaluate outcome in the most unfavorable subset of high-risk prostate cancer patients treated with a combination of supplemental external beam radiation therapy (EBRT) and brachytherapy.METHODS AND MATERIALS: Very high-risk prostate cancer was defined as follows: any Gleason score 10, Gleason score 8-9 with >50% of the biopsy cores positive for malignancy, Gleason score 8-9 with a prostate-specific antigen (PSA) >20 ng/mL, any clinical stage T3, or any PSA >40 ng/mL. One hundred thirty-one patients were identified who met the aforementioned criteria. The median followup was 6.6 years. One hundred twenty (91.6%) patients received supplemental EBRT and 100 (76.4%) received androgen deprivation therapy (median duration, 19.5 months; range, 4-36 months). The median postimplant day 0 D-90 (i.e., the minimum percentage of the prescription dose that covers the planning target volume) was 121.9% of prescription dose. Multiple clinical treatment and dosimetric parameters were evaluated for impact on the evaluated survival parameters.RESULTS: The median pretreatment PSA and Gleason score were 11.0 ng/mL and 8. One hundred ten (84%) patients had a Gleason score >= 8. At 9 and 12 years, the cause-specific survival, biochemical progression-free survival, and overall survival were 91.0% and 86.5%, 87.3% and 87.3%, and 70.5% and 60.5%, respectively. The most common cause of death was heart disease (22.2%) with deaths from nonprostate cancer (12.7%) and prostate cancer (8.3%) being less likely.CONCLUSIONS: Permanent interstitial brachytherapy usually with supplemental EBRT and androgen deprivation therapy results in excellent biochemical control and cause-specific survival in the most unfavorable subset of high-risk prostate cancer patients. Death from diseases of the heart was more than twice as likely as death from prostate cancer. (C) 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

PURPOSE: Several prominent publications have identified an overall association between tobacco use and an increased risk of disease recurrence and disease-specific mortality in prostate cancer patients. The authors explored whether tobacco use adversely impacts treatment outcomes in men treated with permanent interstitial brachytherapy.METHODS AND MATERIALS: From April 1995 to August 2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.5 years. The role of tobacco use as a prognostic factor for biochemical progression-free survival, cause-specific survival, and overall survival was investigated. Differences in survival between smokers and nonsmokers were compared using Kaplan-Meier curves and log-rank tests.RESULTS: Current smokers presented with a lower body mass index (p<0.001), smaller prostate size (p = 0.003), younger age (p<0.001), higher prostate-specific antigen level ( p = 0.002), a trend toward higher percentage biopsy core involvement (p = 0.08), higher incidence of perineural invasion (p = 0.015), and higher risk disease (p<0.001) than former or nonsmokers. There was no difference in biochemical progression-free survival (p = 0.30) or cause-specific survival (p = 0.72) at 10 years for smokers compared with nonsmokers. On univariate and multivariate analysis, tobacco use was an adverse risk factor for overall survival (p<0.001). There was no association between smoking and any prostate cancer-specific outcome.CONCLUSIONS: Smokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers. (C) 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Cystic fibrosis (CF), the most common inherited disease in the Caucasian population, is caused by mutations of the CFTR gene, coding for an anion channel responsible for chloride movement, determining transepithelial salt transport, fluid flow and ion concentrations. Cystic fibrosis is determined by chronic lung disease, marked by airway surface dehydration, reduced mucus clearance and increased mucus obstruction, impaired bacterial killing and inflammation and continuous destruction of the lung tissue. The lack of suitable CF mouse models has so far impeded the understanding of disease mechanisms and the development of novel therapies. Recently, a pig model reflecting the main hallmarks of the human disease in the respiratory, gastrointestinal and genital tracts has been reported (Rogers et al. 2008 Science 321, 1837–1841). In the present study, we generated a new CF pig model by disrupting the CFTR gene using an approach that differs in 3 major aspects from the previously published model: (1) gene targeting was achieved using a modified bacterial artificial chromosome (BAC) vector; (2) transcription of the CFTR gene was completely prevented; and (3) homozygous CFTR mutant pigs were derived by nuclear transfer from cells in which both alleles were inactivated by sequential BAC targeting. We characterised 2 cloned litters with a total of 13 piglets (including 4 stillborns). All piglets showed a characteristic CF multi-organ disease with severe meconium ileus, microcolon, microgallbladder, hypoplasia of the exocrine pancreas, congenital aplasia of the vas deferens and malformations of the trachea. In contrast to the recently published CF pig, where the majority of the intestinal obstructions occurred proximal to the ileocecal junction, we found obstructions exclusively distal to this site. We thus present a novel pig model for CF that reflects the main hallmarks of the human disease. It confirms the suitability of the CFTR mutant pig for cystic fibrosis research and increases the availability of CF models for molecular and translational CF research. The help by Prof. K. Heinritzi and his team from the Pig Clinic, LMU Munich, is gratefully acknowledged. This study was supported by Mukoviszidose e.V.