Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

COVID-19 Infection May Not Produce Lasting Immunity in Non-vaccinated Young Adults: A Retrospective Review of COVID-19 Antibody Data.

Background Despite progress in achieving herd immunity through recovery from previous infection and vaccination efforts, the COVID-19 pandemic continues to be an imminent health concern. Exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral antigen through infection or vaccination facilitates immune system efficacy against future infection, but it is currently unclear how long this immunity lasts. Therefore, understanding the necessary exposures to produce adequate antibody levels and the duration of this humoral response to prevent infection is imperative in updating guidelines for vaccination and ultimately ending this public health crisis.  Aims This study aimed to compare the presence of serum antibodies in younger and older age groups to determine how vaccination and previous infection compare as indicators of immunity against COVID-19. We also evaluated age to determine its role in antibody presence. We hope that this information will be helpful to the public to develop the best recommendations for vaccination guidelines concerning distinct demographics. â€‹ Materials and methods In this retrospective data analysis, we evaluated saliva SARS-CoV-2 test results taken from 309 subjects (192F/117M; median age=53.4) during a community fair in Crawford County, PA. We sorted the subjects into groups based on age, reported infection with the COVID-19 virus, and vaccination status. We then performed a Chi-square analysis to compare the frequency of positive SARS-CoV-2 antibody tests within these groups. Results The vaccinated but not previously-infected cohort (n=146, 81.5%) was significantly more likely to have antibodies than the unvaccinated infected cohort (n=55, 65.5%; p<0.0001). In the previously-infected, unvaccinated cohort, individuals who were 55 and older were more likely to have antibodies than younger individuals (p<0.0157), but no age-dependent difference was observed among vaccinated individuals. Conclusions The results suggest that vaccination provides a more durable immune response than recovery from infection, and there is an age-dependent humoral response following previous infection but not vaccination. Practically speaking, this information implies that despite popular misconception, individuals under the age of 55 must receive a COVID-19 vaccine despite the previous infection as they are significantly less likely to have antibodies following infection than their counterparts who are over the age of 55.

Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy.

Treating breast cancer brain metastases (BCBMs) is challenging. Na+/I- symporter (NIS) expression in BCBMs would permit their selective targeting with radioiodide (131I-). We show impressive enhancement of tumor response by combining131I- with gemcitabine (GEM), a cytotoxic radiosensitizer. Nude mice mammary fat-pad (MFP) tumors and BCBMs were generated with braintropic MDA-MB-231Br cells transduced with bicistronically-linked NIS and firefly luciferase cDNAs. Response was monitored in vivo via bioluminescent imaging and NIS tumor expression.131I-/GEM therapy inhibited MFP tumor growth more effectively than either agent alone. BCBMs were treated with: high or low-dose GEM (58 or 14.5 mg/Kg×4); 131I- (1mCi or 2×0.5 mCi 7 days apart); and 131I-/GEM therapy. By post-injection day (PID) 25, 82-86% of controls and 78-83% of 131I--treated BCBM grew, whereas 17% low-dose and 36% high-dose GEM regressed. The latter tumors were smaller than the controls with comparable NIS expression (~20% of cells). High and low-dose 131I-/ GEM combinations caused 89% and 57% tumor regression, respectively. High-dose GEM/131I- delayed tumor growth: tumors increased 5-fold in size by PID45 (controls by PID18). Although fewer than 25% of cells expressed NIS, GEM/131I- caused dramatic tumor regression in NIS-transduced BCBMs. This effect was synergistic, and supports the hypothesis that GEM radiosensitizes cells to 131I-.

Clipping of previously coiled cerebral aneurysms: efficacy, safety, and predictors in a cohort of 111 patients.

OBJECTIVE With the increasing number of aneurysms treated with endovascular coiling, more recurrences are being encountered. The aim of this study was to evaluate the efficacy and safety of microsurgical clipping in the treatment of recurrent, previously coiled cerebral aneurysms and to identify risk factors that can affect the outcomes of this procedure. METHODS One hundred eleven patients with recurrent aneurysms whose lesions were managed by surgical clipping between January 2002 and October 2014 were identified. The rates of aneurysm occlusion, retreatment, complications, and good clinical outcome were retrospectively determined. Univariate and multivariate logistic regressions were performed to identify factors associated with these outcomes. RESULTS The mean patient age was 50.5 years, the mean aneurysm size was 7 mm, and 97.3% of aneurysms were located in the anterior circulation. The mean follow-up was 22 months. Complete aneurysm occlusion, as assessed by intraoperative angiography, was achieved in 97.3% of aneurysms (108 of 111 patients). Among patients, 1.8% (2 of 111 patients) had a recurrence after clipping. Retreatment was required in 4.5% of patients (5 of 111) after clipping. Major complications were observed in 8% of patients and mortality in 2.7%. Ninety percent of patients had a good clinical outcome. Aneurysm size (OR 1.4, 95% CI 1.08-1.7; p = 0.009) and location in the posterior circulation were significantly associated with higher complications. All 3 patients who had coil extraction experienced a postoperative stroke. Aneurysm size (OR 1.2, 95% CI 1.02-1.45; p = 0.025) and higher number of interventions prior to clipping (OR 5.3, 95% CI 1.3-21.4; p = 0.019) were significant predictors of poor outcome. An aneurysm size > 7 mm was a significant predictor of incomplete obliteration and retreatment (p = 0.018). CONCLUSIONS Surgical clipping is safe and effective in treating recurrent, previously coiled cerebral aneurysms. Aneurysm size, location, and number of previous coiling procedures are important factors to consider in the management of these aneurysms.

Ex vivo Evans blue assessment of the blood brain barrier in three breast cancer brain metastasis models.

The limited entry of anticancer drugs into the central nervous system represents a special therapeutic challenge for patients with brain metastases and is primarily due to the blood brain barrier (BBB). Albumin-bound Evans blue (EB) dye is too large to cross the BBB but can grossly stain tissue blue when the BBB is disrupted. The course of tumor development and the integrity of the BBB were studied in three preclinical breast cancer brain metastasis (BCBM) models. A luciferase-transduced braintropic clone of MDA-231 cell line was used. Nude mice were subjected to stereotactic intracerebral inoculation, mammary fat pad-derived tumor fragment implantation, or carotid artery injections. EB was injected 30 min prior to euthanasia at various timepoints for each of the BCBM model animals. Serial bioluminescent imaging demonstrated exponential tumor growth in all models. Carotid BCBM appeared as diffuse multifocal cell clusters. EB aided the localization of metastases ex vivo. Tumor implants stained blue at 7 days whereas gross staining was not evident until day 14 in the stereotactic model and day 28 for the carotid model. EB assessment of the integrity of the BBB provides useful information relevant to drug testing in preclinical BCBM models.