Frameless versus frame-based stereotactic radiosurgery for intracranial arteriovenous malformations: A propensity-matched analysis.

Objective: The frameless linear accelerator (LINAC) based stereotactic radiosurgery (SRS) has been evolving with a reduction in patient discomfort. However, there was limited evidence comparing frame-based and frameless SRS for intracranial arteriovenous malformations (AVM). We aimed to compare the treatment outcomes between frame-based and frameless LINAC SRS. Materials and Methods: This retrospective cohort compared the outcomes of frame-based LINAC SRS (1998-2009) with frameless LINAC SRS (2010-2020). The primary outcome was the obliteration rate. The other outcomes included the neurological, radiological, and functional outcomes after SRS. A matched cohort was identified by propensity scores for further comparisons. Results: A total of 65 patients were included with a mean follow-up time of 13.2 years (158.5 months). There were 40 patients in the frame-based group and 25 patients in the frameless group. The overall obliteration rate was comparable (Frame-based 82.5% vs Frameless 80.0%, p = 0.310) and not significantly different over time (log-rank p = 0.536). The crude post-SRS hemorrhage rate was 1.5% and the incidence was 0.3 per 100 person-years. There were 67.7% of patients with AVM obliteration without new persistent neurological deficits at the last visit and 56.9% of patients with AVM obliteration without any deficits (transient or persistent) during the entire follow-up period. Four patients (8.0%) developed late onset persistent adverse radiation effects (more than 96 months after SRS) among 50 patients with more than 8-year surveillance. In the propensity-matched cohort of 42 patients, there was no significant difference in AVM obliteration (Frame-based vs Frameless, log-rank p = 0.984). Conclusion: Frameless and frame-based LINAC SRS have comparable efficacy in intracranial AVM obliteration. A longer follow-up duration may further characterize the rate of late adverse radiation effects in frameless SRS.

Challenges of Data Availability and Use in Conducting Health-EDRM Research in a Post-COVID-19 World.

Disasters disrupt communication channels, infrastructure, and overburden health systems. This creates unique challenges to the functionality of surveillance tools, data collection systems, and information sharing platforms. The WHO Health Emergency and Disaster Risk Management (Health-EDRM) framework highlights the need for appropriate data collection, data interpretation, and data use from individual, community, and global levels. The COVID-19 crisis has evolved the way hazards and risks are viewed. No longer as a linear event but as a protracted hazard, with cascading and compound risks that affect communities facing complex risks such as climate-related disasters or urban growth. The large-scale disruptions of COVID-19 show that disaster data must evolve beyond mortality and frequency of events, in order to encompass the impact on the livelihood of communities, differentiated between population groups. This includes relative economic losses and psychosocial damage. COVID-19 has created a global opportunity to review how the scientific community classifies data, and how comparable indicators are selected to inform evidence-based resilience building and emergency preparedness. A shift into microlevel data, and regional-level information sharing is necessary to tailor community-level interventions for risk mitigation and disaster preparedness. Real-time data sharing, open governance, cross-organisational, and inter-platform collaboration are necessary not just in Health-EDRM and control of biological hazards, but for all natural hazards and man-made disasters.

Open-label, phase IIa study of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma.

PURPOSE: This study (NCT02083354) assessed the efficacy and safety of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma. METHOD: Overall, 77 patients of East Asian origin (including 61 from Mainland China) with unresectable or metastatic BRAF V600-mutant cutaneous melanoma were enrolled. Prior treatment was allowed except with BRAF/MEK inhibitors. Patients received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary end-point was objective response rate (ORR) using Response Evaluation Criteria in Solid Tumours 1.1. Secondary end-points were duration of response (DOR), progression-free survival (PFS), overall survival (OS), pharmacokinetics and safety. RESULTS: At data cutoff (February 23, 2018; median follow-up, 8.3 months), treatment was ongoing in 36 patients (47%). The median age was 52 years; 32% of patients had elevated lactate dehydrogenase, and 84% had received prior systemic therapy. ORR was 61% (95% confidence interval: 49.2-72.0), with four patients (5%) achieving complete response. Median DOR and PFS were 11.3 and 7.9 months, respectively. Median OS was not reached. The most common adverse event (AE) of any grade was pyrexia (56%). Grade ≥III AEs occurred in 29 patients (38%). The most common grade ≥III AEs were pyrexia (8%) and anaemia (6%). AEs led to permanent discontinuation in five patients (6.5%). Mean Cmax for dabrafenib and trametinib was 3560 and 11.5 ng/mL (day 1) and 2680 and 27.1 ng/mL (day 15), respectively. CONCLUSION: These results support the efficacy and tolerability of dabrafenib in combination with trametinib in East Asian patients with unresectable or metastatic BRAF V600-mutant cutaneous melanoma.

Outcomes of neoadjuvant chemotherapy using gemcitabine and cisplatin in muscle invasive bladder cancer: A retrospective analysis of the patient and treatment factors in a single institute.

BACKGROUND: Meta-analysis had shown a significant 5% absolute survival benefit in favour of neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy before radical cystectomy (RC) and pelvic lymphadenectomy (PLND) for patients with muscle invasive bladder cancer (MIBC). Those who had pathological complete response (pCR) to NAC could have long-term progression-free survival (PFS) and overall survival (OS). AIM: To identify the treatment and patient factors which could predict a pCR to NAC and the associated PFS and OS in a single institute. METHODS AND RESULTS: We retrospectively reviewed the records of patients who had received NAC with gemcitabine and cisplatin (GC) in our centre from January 2004 to December 2017. The patients' age, tumour stage, baseline estimated glomerular filtration rate (eGFR), chemotherapy chart, and pathological information were recorded. There were 25 men and five women who had received NAC followed by RC. pCR was noted in the surgical specimen of 11 (37%) patients. The mean dose of gemcitabine was significantly higher in the pCR group than the non-pCR group (9850 vs 7852 mg, P = 0.039) as was the dose-intensity of cisplatin (87.4% vs 71.3%, P = 0.044). After a median follow-up of 38 months (range 4.3-154), seven patients had disease progression. The estimated 3-year PFS is 74.9% (95% confidence interval [CI], 66.7%-83.3%). None of the patients who achieved pCR relapsed, while six out of seven patients who had pN1 disease developed distant metastasis (DM). Only two patients died of DM while two other patients died of unrelated causes. The estimated 3-year OS is 88.9% (95% CI 82.8%-95%). CONCLUSIONS: We have demonstrated that the dose intensity of GC is a major determinant of pCR, which predicts longer RFS and OS. Further research in gene expression profiling of MIBC to help selecting patient for NAC is needed.

Primary yolk sac tumour of the urinary bladder: A case report and review of the literature.

We present a case of rare primary yolk sac tumour of the urinary bladder in adulthood. A 31-year-old female patient presented with a history of chronic ketamine abuse, which has not previously been shown to be associated with malignancy development. The final diagnosis was established only after radical cystectomy. A computed tomography (CT) scan showed paraaortic lymph node metastasis. The patient was treated with systemic chemotherapy. A review of the literature revealed that surgical excision and cisplatin-based chemotherapy remain to be the standard of care for extragonadal yolk sac tumours.