Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Patch Test Results Among Older Adults: A Retrospective Analysis of the North American Contact Dermatitis Group Data (2009-2020)

Allergic contact dermatitis (ACD) in older adults (OA) represents a significant health burden, but few studies examine the prevalence and characteristics of contact allergy and ACD in this population. To compare positive and clinically relevant patch test results in OA versus younger adults (YA) and children. Retrospective analysis of patch test results obtained in OA (≥65 years), YA (19-64 years), and children (≤18 years) by the North American Contact Dermatitis Group, 2009 to 2020. Of 28,177 patients patch tested, 5366 (19.0%) were OA. OA were more likely to have a final primary diagnosis of ACD as compared with YA (50.8% vs 49.2%,  = 0.035) and children (44.6%,  \u3c 0.0001). The primary site of dermatitis also differed by age group, with OA having a higher proportion of dermatitis affecting the trunk, scalp, anogenital region, and under clothing, and a lower proportion of dermatitis affecting the face, lips, and feet. Retrospective design, lack of follow-up, and referral population. OA were as likely and were statistically even more likely to have a final primary diagnosis of ACD compared with YA and children. Anatomic site of dermatitis also differed by age group. This underscores the need for patch testing in OA when ACD is suspected

Patch testing with cobalt in children and adolescents: North American contact dermatitis group experience, 2001-2018

BACKGROUND: Allergic contact dermatitis (ACD) to cobalt is more common in children and adolescents than adults. However, detailed information on sites and sources of cobalt ACD is limited. OBJECTIVES: To assess trends in positive and clinically relevant patch test reactions to cobalt in children and associated patient characteristics, common sources and body sites affected. METHODS: A retrospective analysis of children (\u3c18 years) patch tested to cobalt by the North American Contact Dermatitis Group between 2001 and 2018. RESULTS: Of 1919 children patch tested, 228 (11.9%) and 127 (6.6%) had a positive/allergic or currently relevant patch test reaction to cobalt, respectively. The most common primary body sites affected were scattered generalized (30.0%), face, not otherwise specified (10.6%) and trunk (10.1%). Patients with allergic and currently relevant allergic patch test reactions were more likely to have a primary site of trunk (p = 0.0160 and p = 0.0008) and ears (p = 0.0005 and p \u3c 0.0001). Affected body site(s) varied by cobalt source among patients with currently relevant reactions, especially for less common sources. The most commonly identified sources of cobalt included jewellery, belts and clothing. CONCLUSIONS: Positive patch test reactions to cobalt were common in children. The most common body site was scattered generalized and the sources of cobalt varied by body site

Patch Testing to Paraphenylenediamine: The North American Contact Dermatitis Group Experience (1994-2018)

Paraphenylenediamine (PPD) is an aromatic amine dye that may cause allergic contact dermatitis. This study examines the epidemiology of allergic patch test reactions to PPD. This retrospective analysis characterizes individuals tested to PPD (1% petrolatum) by the North American Contact Dermatitis Group (1994-2018). Demographics and dermatitis site(s) were compared between PPD-allergic and PPD-negative patients. PPD reactions were analyzed by reaction strength, clinical relevance, occupational relatedness, and source as well as coreactivity with structurally related compounds. Of 54,917 patients tested to PPD, 3095 (5.6%) had an allergic patch test reaction. Compared with PPD-negative patients, PPD-allergic patients had significantly greater odds of age \u3e40 years (odds ratio [OR] 1.55 [95% confidence interval; CI 1.43-1.69]) and female gender (OR 1.52 [95% CI 1.41-1.66]), but lower odds of being White (OR 0.66 [95% CI 0.60-0.71]). The most common primary anatomic sites of dermatitis were face (25.5%), hands (21.9%), and scattered/generalized pattern (15.5%). Over half (55.3%) of PPD reactions were ++ or +++ at the final reading and 60.9% were currently relevant. Common exposure sources included hair dye (73.5%) and clothing/shoes/apparel (3.9%). Occupationally related reactions occurred in 8.3%, most commonly in hairdressers/cosmetologists (72.8%). The most common coreactions were benzocaine (11.3%), -isopropyl-\u27-phenyl--phenylenediamine (6.7%), disperse dye mix (6.5%), and black rubber mix (5.1%). The 24-year percentage of allergic reactions to PPD was 5.6%. PPD allergy was associated with female gender and age \u3e40 years. PPD allergic patients were less likely to be White. Allergic reactions were usually clinically relevant and hair dye was the most frequently identified source

Patch Testing to Chlorhexidine Digluconate, 1% Aqueous: North American Contact Dermatitis Group Experience, 2015-2020

Chlorhexidine is an antiseptic that may cause allergic contact dermatitis. To describe the epidemiology of chlorhexidine allergy and characterize positive patch test reactions. This retrospective study analyzed patients patch tested to chlorhexidine digluconate 1% aqueous by the North American Contact Dermatitis Group, 2015-2020. Of 14,731 patients tested to chlorhexidine digluconate, 107 (0.7%) had an allergic reaction; of these, 56 (52.3%) reactions were currently clinically relevant. Most (59%) reactions were mild (+), followed by strong (++, 18.7%) and very strong (+++, 6.5%). Common primary dermatitis anatomic sites in chlorhexidine-positive patients were hands (26.4%), face (24.5%), and scattered/generalized distribution (17.9%). Compared with negative patients, chlorhexidine-positive patients were significantly more likely to have dermatitis involving the trunk (11.3% vs 5.1%;  = 0.0036). The most commonly identified source category was skin/health care products (n = 41, 38.3%). Only 11 (10.3%) chlorhexidine reactions were occupationally related; of these, 81.8% were in health care workers. Chlorhexidine digluconate allergy is uncommon, but often clinically relevant. Involvement of the hands, face, and scattered generalized patterns was frequent. Occupationally related reactions were found predominantly in health care workers

Occupational Contact Dermatitis in Dental Personnel: A Retrospective Analysis of the North American Contact Dermatitis Group Data, 2001 to 2018

BACKGROUND: Dental personnel are at risk of developing occupational contact dermatitis. OBJECTIVES: The aims of the study were to determine prevalence of occupational contact dermatitis in dental personnel referred for patch testing and to characterize relevant allergens and sources. METHODS: The study used a retrospective, cross-sectional analysis of the North American Contact Dermatitis Group (NACDG) data, 2001-2018. RESULTS: Of 41,109 patients, 585 (1.4%) were dental personnel. Dental personnel were significantly more likely than nondental personnel to be female (75.7% vs 67.4%, P \u3c 0.0001), have occupationally related dermatitis (35.7% vs 11.5%, P \u3c 0.0001), and/or have primary hand involvement (48.6% vs 22.5%, P \u3c 0.0001). More than one quarter of dental personnel (62/585, 27.7%) had 1 or more occupationally related allergic patch test reaction(s). There were 249 occupationally related reactions to NACDG screening allergens, most commonly glutaraldehyde (18.1%), thiuram mix (16.1%), and carba mix (14.1%). The most common sources of NACDG screening allergens were gloves (30.7%), dental materials (26.6%), and sterilizing solutions (13.1%). Seventy-three dental personnel (12.5%) had 1 or more positive patch test reactions to occupationally related allergen(s)/substances not on the screening series. Occupationally related irritant contact dermatitis was identified in 22.2% (n = 130) of dental personnel, most commonly to nonskin soaps/detergents/disinfectants (32.0%). CONCLUSIONS: Occupational contact dermatitis is common in dental personnel referred for patch testing. Comprehensive testing beyond screening series is important in these patients

Patch Test Reactions Associated With Topical Medications: A Retrospective Analysis of the North American Contact Dermatitis Group Data (2001-2018)

BACKGROUND/OBJECTIVES: Topical medications may lead to allergic contact dermatitis. This study characterized positive patch test reactions associated with medications in patients evaluated by the North American Contact Dermatitis Group (NACDG). METHODS: This study is a retrospective analysis of the NACDG data (2001-2018). Patients with at least 1 positive patch test reaction associated with a medication source were included. Allergens, reaction characteristics, clinical relevance, and source details were tabulated. RESULTS: Of 43,722 patients, 6374 (14.6%) had positive allergic patch test reactions associated with 1 or more topical medication sources. Patients with versus without allergic reactions to medications were more likely to be older than 40 years (P \u3c 0.0001) and/or have primary sites of dermatitis on the legs, anal/genital region, or trunk (P \u3c 0.0001). There were 8787 reactions to NACDG allergens; the most common were neomycin (29.4%), bacitracin (29.1%), propylene glycol 100% (10.6%), tixocortol-17-pivalate (10.0%), lidocaine (7.9%), budesonide (4.9%), and dibucaine (4.4%). Propylene glycol 100% was the most common inactive ingredient (10.6%). Current relevance was present in 61.0%. A total of 6.5% of the individuals with medication allergy would have had 1 or more positive patch test reactions missed if only tested to the NACDG screening series. CONCLUSIONS: Positive patch test reactions associated with topical medications were common (14.6%), and most were clinically relevant. Patients with topical medication allergy were twice as likely to have anal/genital involvement. Active ingredients, especially neomycin, bacitracin, and tixocortol-17-pivalate, were frequent culprits