Efficacy, toxicity, and quality-of-life outcomes of ultrahypofractionated radiotherapy in patients with localized prostate cancer: A single-arm phase 2 trial from Asia.

AIMS: Ultra-hypofractionated radiotherapy (UHF-RT) is widely utilized in men with localized prostate cancer (PCa). There are limited data in Asian cohorts. We report the outcomes of a single-arm, phase II trial of UHF-RT from an Asian center. METHODS: We recruited men with histologically confirmed, nonmetastatic localized PCa. UHF-RT regimens were 36.25 Gy (Cohort A) and 37.5 Gy (Cohort B) delivered in five fractions every other day over 1.5-2.5 weeks. Primary endpoint was physician-scored late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs). Quality-of-life (QoL) was assessed by Expanded Prostate Cancer Index Composite (EPIC) at baseline, 1- and 2-year post-UHF-RT. RESULTS: Between March 2014 and August 2019, 105 men were recruited; four were subsequently excluded from analysis. Median age was 68.0 (Interquartile range (IQR): 63.8-73.0) years. 26 (24.8%) and 68 (64.8%) men had NCCN-defined low-and intermediate-risk PCa, respectively. No late ≥G3 GU or GI toxicities were reported in both cohorts. Peak incidence of acute ≥G2 GU AEs at 14 days post-UHF-RT was 23.6% (17/72) and 24.0% (6/25) in Cohorts A and B, respectively; ≥G2 GI AEs were observed in 9.7% (7/72) and 36.0% (9/25), respectively. Late ≥G2 GU and GI AEs occurred in 4.7% and 3.1% of Cohort A patients, and 5.0% in Cohort B at 12 months, with no AEs at 24 months. EPIC scores changed minimally across all domains. At a median follow-up of 44.9 months, we recorded one (1.3%) biochemical relapse by the Phoenix criteria (Cohort A). CONCLUSION: UHF-RT is well tolerated in Asian men and can be a recommended fractionation schema for localized PCa.

Moral case deliberation.

Ethical dilemmas in general are characterised by a choice between two mutually excluding options neither of which is satisfactory, because there always will be a form of moral damage. Within the context of medicine several ethics support services have been developed to support healthcare professionals in dealing with ethical dilemmas, including moral case deliberation. In this article, we describe how moral case deliberation works in daily practice, illustrated with a case example from the neurology ward. The article is meant as an introduction to moral case deliberation according to the dilemma method. We show its relevance to the clinic and the context needed to put it into practice.

Preserved muscle oxidative metabolic phenotype in newly diagnosed non-small cell lung cancer cachexia.

BACKGROUND: Cachexia augments cancer-related mortality and has devastating effects on quality of life. Pre-clinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype (OXPHEN) stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate the presence of muscle OXPHEN loss in newly diagnosed patients with lung cancer, especially in those with cachexia. METHODS: Quadriceps muscle biopsies of comprehensively phenotyped pre-cachectic (n = 10) and cachectic (n = 16) patients with non-small cell lung cancer prior to treatment were compared with healthy age-matched controls (n = 22). OXPHEN was determined by assessing muscle fibre type distribution (immunohistochemistry), enzyme activity (spectrophotometry), and protein expression levels of mitochondrial complexes (western blot) as well as transcript levels of (regulatory) oxidative genes (quantitative real-time PCR). Additionally, muscle fibre cross-sectional area (immunohistochemistry) and systemic inflammation (multiplex analysis) were assessed. RESULTS: Muscle fibre cross-sectional area was smaller, and plasma levels of interleukin 6 were significantly higher in cachectic patients compared with non-cachectic patients and healthy controls. No differences in muscle fibre type distribution or oxidative and glycolytic enzyme activities were observed between the groups. Mitochondrial protein expression and gene expression levels of their regulators were also not different. CONCLUSION: Muscle OXPHEN is preserved in newly diagnosed non-small cell lung cancer and therefore not a primary trigger of cachexia in these patients.

Primary intracranial germ cell tumours: experience of a single South-East Asian institution.

Primary intracranial germ cell tumours (ICGCT) are a rare group of brain tumours arising predominantly in the paediatric and pre-adult population, accounting for up to 9.5% of paediatric brain tumours in East Asia. The National Cancer Centre Singapore (NCCS) is a tertiary referral centre for patients from all over South-East Asia. Our study aims to describe the characteristics of ICGCT patients in South-East Asia. Data on all patients with ICGCT who were seen at the Therapeutic Radiology Department of NCCS from 2000 to 2013 were collected retrospectively. Patient demographics, disease characteristics and treatment outcomes were analysed. Characteristics and survival of our patients were similar to other centres. Pure germinomas demonstrated 5 year overall survival (OS) and disease-free survival (DFS) rates of 89.2% (95% confidence interval [CI] 60.2-97.5) and 85.2% (95%CI 60.8-95.0) respectively. Secreting germinomas, non-germinomatous germ cell tumours and mixed germ cell tumours were evaluated together and demonstrated 5 year OS of 70.6% (95%CI 41.0-87.3) and DFS of 61.4% (95%CI 31.9-81.3). Patients ⩽ 12 years had marginally better 5 year OS than their older counterparts (81.0% [95%CI 49.5-93.9] versus 77.9% [95%CI 47.3-92.0], respectively). Patients who underwent extended field radiotherapy had longer OS and DFS than those who received local field irradiation. Treatment outcomes of our ICGCT patients are comparable with those in other Asian and Western centres. Extended field radiotherapy is a pivotal component of ICGCT treatment. Adding chemotherapy confers no extra survival benefit in treating germinomas. Treatment of mixed germ cell tumours and non-germinomatous germ cell tumours involves a multidisciplinary approach that varies for each histological subtype.

Frameless linac-based stereotactic radiosurgery treatment for SUNCT syndrome targeting the trigeminal nerve and sphenopalatine ganglion.

BACKGROUND: The short-lasting unilateral neuralgiform headache associated with conjunctival injection and tearing or SUNCT syndrome was first described in the 1970s. This paper is the first in the literature that describes the successful use of stereotactic radiosurgery (SRS) using a non-invasive frameless technique, targeting both the trigeminal nerve and the sphenopalatine ganglion in the management of intractable SUNCT. We also discuss the role of selecting peripheral targets in the management of this rare headache syndrome. METHODS: Among patients treated for functional pain disorders in our radiosurgery unit using the frameless technique since August 2011, one patient with symptoms matching the International Classification of Headache Disorders-2 (ICHD-II) criteria of SUNCT syndrome was identified. The multi-disciplinary case records of this patient were retrospectively reviewed and reported. RESULTS: Our patient had symptoms resembling the ICHD-II diagnostic criteria of SUNCT, which was refractory to medical treatment. Ninety Gy was delivered to the trigeminal root entry zone and 80 Gy was delivered to the sphenopalatine ganglion. At 16 months' follow-up, she was pain free with minimal side effects. CONCLUSIONS: Frameless linear accelerator (linac)-based SRS targeting the trigeminal nerve and sphenopalatine ganglion remained successful in our patient at 16 months. Longer follow-up and further experience will determine the efficacy and safety of this approach. We suggest that frameless SRS is a convenient and attractive non-invasive option for patients with medically refractory SUNCT.