Prostate Virtual High-dose-rate Brachytherapy Boost: 5-Year Results from the PROMETHEUS Prospective Multicentre Trial.

BACKGROUND AND OBJECTIVE: Despite the high efficacy of high-dose-rate brachytherapy boost (HDRB) in the management of prostate cancer (PC), use of this approach is declining. Similar dosimetry can be achieved using stereotactic body radiotherapy or "virtual HDRB" (vHDRB). The aim of the multicentre, single-arm, phase 2 PROMETHEUS trial (ACTRN12615000223538) was to evaluate the safety and efficacy of vHDRB in patients with PC. METHODS: Patients with intermediate-risk PC or selected patients with high-risk PC were eligible for inclusion. vHDRB was given as 19-20 Gy in two fractions, delivered 1 wk apart, followed by conventionally fractionated external beam radiotherapy (EBRT) at 46 Gy in 23 fractions or 36 Gy in 12 fractions. The primary endpoint was the biochemical/clinical relapse-free rate (bcRFR). Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and quality of life (QoL) data were collected used the Expanded Prostate Cancer Index Composite-26 questionnaire. KEY FINDINGS AND LIMITATIONS: From March 2014 to December 2018, 151 patients (74% intermediate risk, 26% high risk) with a median age of 69 yr were treated across five centres. Median follow-up was 60 mo. The 5-yr bcRFR was 94.1% (95% confidence interval [CI] 90-98%) and the local control rate was 98.7%. Acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity occurred in 6.6% and 23.2% of patients, respectively, with no acute grade 3 toxicity. At 60 mo after treatment, the prevalence of late grade ≥2 GI toxicity was 1.7% (95% CI 0.3-6.5%) and the prevalence of late grade ≥2 GU toxicity was 3.3% (95% CI 1.1-8.8%). Between baseline and 60 mo, QoL improved for urinary obstructive and hormonal domains, was stable for the bowel domain, and deteriorated slightly for the sexual and urinary incontinence domains. CONCLUSIONS: Delivery of gantry-based vHDRB followed by conventionally fractionated EBRT is feasible in a multicentre setting, with high 5-yr bcRFR and low toxicity. This approach is being compared with prostate ultrahypofractionated radiotherapy in the TROG 18.01 NINJA randomised trial (ACTRN12618001806257). PATIENT SUMMARY: The PROMETHEUS trial investigated noninvasive high-dose precision radiotherapy combined with conventional radiotherapy in patients with prostate cancer. We found that this new technique was well tolerated and resulted in better cancer control outcomes than historically reported.

Leptomeningeal neuraxis relapse in glioblastoma is an uncommon but not rare event associated with poor outcome.

BACKGROUND: Spinal neuraxis leptomeningeal metastasis (LM) relapse in glioblastoma is an uncommon event that is challenging to manage. This study aims to determine the incidence, associated factors, and outcome of LM relapse in patients with glioblastoma managed with radical intent. METHODS: Patients managed for glioblastoma using the EORTC-NCIC (Stupp) Protocol from 2007 to 2019 were entered into a prospective ethics-approved database. Follow-up included routine cranial MRI surveillance with further imaging as clinically indicated. LM relapse was determined by MRI findings and/or cerebrospinal fluid analysis. The chi-square test of independence was used to evaluate clinico-pathologic factors associated with increased risk of subsequent LM relapse. Median survival post-LM relapse was calculated using Kaplan-Meier technique. RESULTS: Four-hundred-and-seven patients were eligible, with median follow-up of 60 months for surviving patients. Eleven (2.7%) had LM at first relapse and in total 21 (5.1%) experienced LM in the entire follow-up period. Sites of LM relapse were 8 (38%) focal spinal, 2 (10%) focal brainstem medulla and 11 (52%) diffuse spinal. Median overall survival from initial diagnosis for the entire cohort was 17.6 months (95% CI 16.7-19.0). Median survival from LM relapse to death was 39 days (95% CI: 19-107). Factors associated with LM relapse were age less than 50 years (p < 0.01), initial disease located in the temporal lobe (p < 0.01) and tumours lacking MGMT promoter methylation (p < 0.01). CONCLUSIONS: LM relapse is an uncommon but not rare event in patients managed radically for glioblastoma. It is associated with poor outcome with the majority of patients deceased within two months of recognition.

Virtual HDR Boost for Prostate Cancer: Rebooting a Classic Treatment Using Modern Tech.

Prostate cancer (PC) is the most common malignancy in men. Internal radiotherapy (brachytherapy) has been used to treat PC successfully for over a century. In particular, there is level-one evidence of the benefits of using brachytherapy to escalate the dose of radiotherapy compared with standard external beam radiotherapy approaches. However, the use of PC brachytherapy is declining, despite strong evidence for its improved cancer outcomes. A method using external beam radiotherapy known as virtual high-dose-rate brachytherapy boost (vHDRB) aims to noninvasively mimic a brachytherapy boost radiation dose plan. In this review, we consider the evidence supporting brachytherapy boosts for PC and the continuing evolution of vHDRB approaches, culminating in the current generation of clinical trials, which will help define the role of this emerging modality.

Family history of venous thromboembolism in the paediatric population: The need for a standardized definition.

Positive family history is known to be an independent risk factor for venous thromboembolic (VTE) that may or may not reflect an underlying hereditary disorder. However, there is no clear standardized definition of what constitutes a positive family history for VTE in children. We aimed to assess the current published definitions of positive family history as a risk factor for VTE in children and ascertain if any consensus exists. METHODS: We conducted a literature review through two major databases PUBMED and EMBASE (1969-June 2018). Three different search statements were used for each database to maximize the number of relevant results, giving rise to 1050 non-duplicated papers. RESULTS: Of the 1050 papers, 32 articles demonstrated 18 separate definitions on what constitutes a positive family history in paediatric studies. Variations in definitions were related to the closeness of kinship (first or second-degree relatives), whether thrombosis was provoked or unprovoked, the age of presentation of thrombosis in the kinship, and clinical vs. laboratory definition of positive family history. Of the definitions, 1st degree relative/s developing VTE at any age whether provoked or unprovoked was most commonly described. CONCLUSION: According to this literature review, the definition of a positive family history in paediatric populations is non-standardized amongst current published papers. To enable accurate comparisons across studies and improve clinical risk assessment, we therefore propose the need for a standardized definition of what constitutes a positive family history.

Identification of common nail and skin disorders.

UNLABELLED: NARRATIVE REVIEW: The following review discusses the more common disorders of the perionychium and skin likely to be observed by the hand therapist. To assist the therapist in recognition of abnormalities, the anatomy, physiology, and basic function of the normal nail unit are described. Indications of when disorders of the nail, resulting from trauma, infections, and neoplasms, require referral to another practitioner are discussed. Characteristics of abnormal skin conditions are described with an emphasis on differentiating benign from malignant lesions. By knowing the suspicious characteristics of nail and skin disorders, the upper extremity therapist can positively impact the well-being of his or her patients through quick referral, leading to early diagnosis and treatment of potentially serious disease. LEVEL OF EVIDENCE: 5.