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

Skull base or cervical vertebral osteomyelitis following chemoradiotherapy for pharyngeal carcinoma: A serious but treatable complication

Osteomyelitis, infection of the bone and marrow, following high dose (chemo-)radiotherapy for head and neck cancer is uncommon and rarely seen in the cervical spine or temporal bone. Due to its proximity to critical structures, osteomyelitis in the latter regions could carry potentially important consequences. Furthermore, involvement near the skull base (e.g. temporal bone and high cervical vertebrae) presents unique challenges in diagnosis (especially in the differentiation from disease recurrence) and treatment, making early detection and timely intervention critical. In this report, we describe two cases of osteomyelitis, one involving the temporal bone and the other affecting the 2nd and 3rd cervical vertebrae, diagnosed and treated with good outcome in the setting of definitive chemoradiotherapy for locally advanced pharyngeal carcinomas. We suggest that for new or evolving post-radiotherapy osseous changes in regions that have received a high dose of radiotherapy, associated with unexpected and deteriorating spinal symptoms such as pain and spasm, radiation-related osteomyelitis should be considered in the differential diagnosis from tumor progression. Timely referral to a surgical oncologist and infectious diseases specialist is paramount in achieving satisfactory clinical outcomes

Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy

Purpose: To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases. Methods: A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1–10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every 3 months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline. Results: Forty-six patients survived ≥ 3 months after treatment. Age (OR 1.12 (1.04–1.21), p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06–1.52, p = 0.02) and baseline Fazekas score ≥ 3/6 (OR 6.4, 95% CI 1.7–24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pre-treatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized. Conclusion: A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small and hypothesis-generating, we propose that radiation oncologists should exercise caution in prescribing WBRT if leukoencephalopathy is present on pre-treatment imaging. Trial Registration: clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010. https://clinicaltrials.gov/ct2/show/NCT01046123Medicine, Faculty ofNon UBCSurgery, Department ofReviewedFacult

Qualitative Assessment of Academic Radiation Oncology Department Chairs\u27 Insights on Diversity, Equity, and Inclusion: Progress, Challenges, and Future Aspirations

PURPOSE: A lack of diversity has been observed in radiation oncology (RO), with women and certain racial/ethnic groups underrepresented as trainees, faculty, and practicing physicians. We sought to gain a nuanced understanding of how to best promote diversity, equity, and inclusion (DEI) based on the insights of RO department chairs, with particular attention given to the experiences of the few women and underrepresented minorities (URMs) in these influential positions. METHODS AND MATERIALS: From March to June 2016, we conducted telephone interviews with 24 RO department chairs (of 27 invited). Purposive sampling was used to invite all chairs who were women (n = 13) or URMs (n = 3) and 11 male chairs who were not URMs. Multiple analysts coded the verbatim transcripts. RESULTS: Five themes were identified: (1) commitment to DEI promotes quality health care and innovation; (2) gaps remain despite some progress with promoting diversity in RO; (3) women and URM faculty continue to experience challenges in various career domains; (4) solutions to DEI issues would be facilitated by acknowledging realities of gender and race; and (5) expansion of the career pipeline is needed. CONCLUSIONS: The chairs\u27 insights had policy-relevant implications. Bias training should broach tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage students before their application to medical school