Stereotactic Body Radiotherapy for Extracranial Oligometastatic Disease from Head and Neck Primary Cancers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. METHODS: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. RESULTS: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. CONCLUSIONS: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

Preliminary Observations of Resting-State Magnetoencephalography in Nonmedicated Children with Obsessive-Compulsive Disorder.

Background: Cortico-striato-thalamo-cortical (CSTC) network alterations are hypothesized to contribute to symptoms of obsessive-compulsive disorder (OCD). To date, very few studies have examined whether CSTC network alterations are present in children with OCD, who are medication naive. Medication-naive pediatric imaging samples may be optimal to study neural correlates of illness and identify brain-based markers, given the proximity to illness onset. Methods: Magnetoencephalography (MEG) data were analyzed at rest, in 18 medication-naive children with OCD (M = 12.1 years ±2.0 standard deviation [SD]; 10 M/8 F) and 13 typically developing children (M = 12.3 years ±2.2 SD; 6 M/7 F). Whole-brain MEG-derived resting-state functional connectivity (rs-fc), for alpha- and gamma-band frequencies were compared between OCD and typically developing (control) groups. Results: Increased MEG-derived rs-fc across alpha- and gamma-band frequencies was found in the OCD group compared to the control group. Increased MEG-derived rs-fc at alpha-band frequencies was evident across a number of regions within the CSTC circuitry and beyond, including the cerebellum and limbic regions. Increased MEG-derived rs-fc at gamma-band frequencies was restricted to the frontal and temporal cortices. Conclusions: This MEG study provides preliminary evidence of altered alpha and gamma networks, at rest, in medication-naive children with OCD. These results support prior findings pointing to the relevance of CSTC circuitry in pediatric OCD and further support accumulating evidence of altered connectivity between regions that extend beyond this network, including the cerebellum and limbic regions. Given the substantial portion of children and youth whose OCD symptoms do not respond to conventional treatments, our findings have implications for future treatment innovation research aiming to target and track whether brain patterns associated with having OCD may change with treatment and/or predict treatment response.

Sodium-Glucose Cotransporter 2 Inhibitors, All-Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta-Analysis and Meta-Regression.

Background This study aimed to assess the effectiveness of sodium-glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes. Methods and Results We conducted a Bayesian meta-analysis of randomized controlled trials comparing sodium-glucose cotransporter 2 inhibitors with placebo. We used meta-regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty-three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes. There was little evidence for ertugliflozin and sotagliflozin versus placebo for reducing all-cause and cardiovascular mortality. There was no association between treatment effects for all-cause and cardiovascular mortality and the control group event rates. There was evidence for a reduction in the incidence of heart failure for empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin versus placebo (probability RR <1.00 of ≥99.3%) and weaker, albeit positive, evidence for acute myocardial infarction for the first 3 agents (probability RR <1.00 of 89.0%-95.2%). There was little evidence of any agent except canagliflozin for reducing the incidence of stroke. Conclusions Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause and cardiovascular mortality versus placebo. Treatment effects of sodium-glucose cotransporter 2 inhibitors versus placebo do not vary by baseline risk.

Radiotherapy as a Single Modality in Primary Seminoma of the Prostate.

Extragonadal germ cell tumors (EGCTs) are uncommon, and those involving the prostate are rare. We report on a primary seminoma of the prostate in a 56-year-old male presenting with scrotal pain, urinary frequency and urgency, and erectile dysfunction. Digital rectal examination revealed a hard, markedly enlarged prostate projecting posteriorly into the rectum. All 12 cores from ultrasound-guided prostate biopsy revealed malignant cells that stained positive for OCT4, PLAP, and CD117. Imaging revealed a 10.2 cm x 7.8 cm x 8.4 cm prostate mass with irregular nodular margins extending superiorly to the base of the bladder and posteriorly abutting the anterior rectal wall. There was no evidence of distant metastatic disease on both nuclear medicine and CT scans of the chest, abdomen, and pelvis. An 11 mm right internal iliac lymph node and several tiny sub-centimeter external iliac nodes were noted bilaterally. The patient was treated with radiotherapy to the prostate and pelvic lymph nodes. The pelvic lymph nodes were treated with 20 Gy in eight fractions, followed by a boost to the prostate for a further 20 Gy in eight fractions. There was a significant response during treatment that allowed an adaptive boost for a further 10 Gy in four fractions to bring the total dose to the prostate to 50 Gy in 20 fractions. Treatment was well tolerated. Adjuvant chemotherapy was not recommended. He remains disease-free 24 months post-treatment. This case report indicates that like most seminomas, extragonadal seminomas are exquisitely sensitive to radiotherapy and may be considered for the primary treatment of non-metastatic disease. To our knowledge, this is the first reported case of the sole use of radiotherapy to treat a primary seminoma of the prostate.

Electromagnetic (EM) catheter path tracking in ultrasound-guided brachytherapy of the breast.

PURPOSE: To evaluate a novel navigation system for breast brachytherapy, based on ultrasound (US)-guided catheter needle implantations followed by electromagnetic (EM) tracking of catheter paths. METHODS: Breast phantoms were produced, containing US-visible tumors. Ultrasound was used to localize the tumor pose and volume within the phantom, followed by planning an optimal catheter pattern through the tumor using navigation software. An electromagnetic (EM)-tracked catheter needle was used to insert the catheters in the desired pattern. The inserted catheters were visualized on a post-implant CT, serving as ground truth. Electromagnetic (EM) tracking and reconstruction of the inserted catheter paths were performed by pulling a flexible EM guidewire through each catheter, performed in two clinical brachytherapy suites. The accuracy of EM catheter tracking was evaluated by calculating the Hausdorff distance between the EM-tracked and CT-based catheter paths. The accuracy and clinical feasibility of EM catheter tracking were also evaluated in three breast cancer patients, performed in a separate experiment room. RESULTS: A total of 71 catheter needles were implanted into 12 phantoms using US guidance and EM navigation, in an average ± SD time of 8.1 ± 2.9 min. The accuracy of EM catheter tracking was dependent on the brachytherapy suite: 2.0 ± 1.2 mm in suite 1 and 0.6 ± 0.2 mm in suite 2. EM catheter tracking was successfully performed in three breast brachytherapy patients. Catheter tracking typically took less than 5 min and had an average accuracy of 1.7 ± 0.3 mm. CONCLUSION: Our preliminary results show a potential role for US guidance and EM needle navigation for implantation of catheters for breast brachytherapy. EM catheter tracking can accurately assess the implant geometry in breast brachytherapy patients. This methodology has the potential to evaluate catheter positions directly after the implantation and during the several fractions of the treatment.

Income Disparities in Absolute Cardiovascular Risk and Cardiovascular Risk Factors in the United States, 1999-2014.

Importance: Large improvements in the control of risk factors for cardiovascular disease have been achieved in the United States, but it remains unclear whether adults in all socioeconomic strata have benefited equally. Objective: To assess temporal trends in 10-year predicted absolute cardiovascular risk and cardiovascular risk factors among US adults in different socioeconomic strata. Design, Setting, and Participants: A cross-sectional analysis was conducted using data on adults 40 to 79 years of age without established cardiovascular disease from the 1999 to 2014 National Health and Nutrition Examination Survey. Exposures: Socioeconomic status was based on the family income to poverty ratio and participants were divided into the following 3 groups: high income (family income to poverty ratio, ≥4), middle income (>1 and <4), or at or below the federal poverty level (≤1). Main Outcomes and Measures: We assessed predicted absolute cardiovascular risk using the pooled cohort equation. We assessed the following 4 risk factors: systolic blood pressure, smoking status, diabetes, and total cholesterol. Results: Of the 17 199 adults whose data were included in the study (8828 women and 8371 men; mean age, 54.4 years), from 1999-2014, trends in the percentage of adults with predicted absolute cardiovascular risk of 20% or more, mean systolic blood pressure, and the percentage of current smokers varied by income strata (P ≤ .02 for interaction). For adults with incomes at or below the federal poverty level, there was little evidence of a change in any of these outcomes across survey years (cardiovascular risk ≥20%, 14.9% [95% CI, 12.9%-16.8%] in 1999-2004; 16.5% [95% CI, 13.7%-19.2%] in 2011-2014; P = .41; mean systolic blood pressure, 127.6 [95% CI, 126.1-129.0] mm Hg in 1999-2004; 126.8 [95% CI, 125.2-128.5] mm Hg in 2011-2014; P = .44; and smoking, 36.5% [95% CI, 32.1%-41.0%] in 1999-2004; 36.0% [95% CI, 31.1%-40.8%] in 2011-2014; P = .87). For adults in the high-income stratum, these variables decreased across survey years (cardiovascular risk ≥20%, 12.0% [95% CI, 10.7%-13.3%] in 1999-2004; 9.5% [95% CI, 8.2%-10.7%] in 2011-2014; P = .003; systolic blood pressure, 126.0 [95% CI, 125.0-126.9] mm Hg in 1999-2004; 122.3 [95% CI, 121.3-123.3] mm Hg in 2011-2014; P < .001; and smoking, 14.1% [95% CI, 12.0%-16.2%] in 1999-2004; 8.8% [95% CI, 6.6%-11.0%] in 2011-2014; P = .001). Trends in the percentage of adults with diabetes and the mean total cholesterol level did not vary by income. Conclusions and Relevance: Adults in each socioeconomic stratum have not benefited equally from efforts to control cardiovascular risk factors.