MRI- and PET-Guided Interstitial Brachytherapy for Postsurgical Vaginal Recurrences of Cervical Cancer: Results of Phase II Study.

PURPOSE: This phase II study evaluated the utility of magnetic resonance imaging (MRI) and positron emission tomography for planning radiation and brachytherapy in patients with postsurgical recurrence of cervical cancer. METHODS AND MATERIALS: The study (NCT01391065) recruited patients with residual or recurrent disease after hysterectomy. Patients underwent baseline T2 weighted (T2W) MRI, 18F-flouro-deoxyglucose (18F-FDG), 18F-flouro thymidine (18F-FLT) and 18F-flouromisonidazole (18F-F Miso) positron emission tomography (PET) and received external radiation (50 Gy/25 fractions for 5 weeks) and weekly cisplatin (40 mg/m2). MRI was performed at brachytherapy and used for delineation of clinical target volume (CTV). Patients with parametrial disease at baseline received interstitial brachytherapy (16-20 Gy/4-5 fractions) and those with vaginal disease received intracavitary brachytherapy (12-14 Gy/2-4 fractions). Kaplan-Meier analysis was performed to evaluate locoregional relapse, disease free survival, and overall survival. Common Toxicity Criteria for adverse event reporting (CTCAE) v4.1 was used for toxicity scoring and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questtionaire Core 30 (QLQC-30) and Cx 24 for quality-of-life reporting. RESULTS: Between January 2011 and February 2016, 60 patients were included, of which 50 received study treatment. The mean gross tumor volume on T2 W MR was 20 (IQR 3.6-90) cc. The metabolic tumor volume was 15 (interquartile range [IQR] 2.1-56.1) cc. The median FLT volume was 10 (IQR 0-48) cc. A total of 8 patients had 18-F F Miso uptake. The median CTV at brachytherapy was 38 (12-85) cc. The median CTVD90 and D 98 was 71 (53-74) and 74 (53-74) Gy. At a median follow-up of 60 (5-93) months, the 5-year local control, disease free survival, and overall survival were 84%, 73%, and 74.5%, respectively. Grade III and IV proctitis and cystitis were observed in 4% and 2% of patients. On multivariate analysis baseline tumor volume, on T2 W MR impacted disease free (91% vs 65%, P = .03) and overall survival (96% vs 77%, P = .06). CONCLUSIONS: Image-guided assisted radiation and brachytherapy are associated with good to excellent local control and survival in patients with vaginal recurrences of cervical cancer.

Epidemiology and Clinical Features of Human Coronaviruses in the Pediatric Population.

BACKGROUND: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized. METHODS: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children's hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression. RESULTS: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9-13.1) and cardiovascular (OR = 3.9; 95% CI, 1.6-9.5), genetic/congenital (OR = 2.8; 95% CI, 1.1-7.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7-12.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1-7.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types. CONCLUSIONS: Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.

Multilocus sequence analysis of Thermoanaerobacter isolates reveals recombining, but differentiated, populations from geothermal springs of the Uzon Caldera, Kamchatka, Russia.

Thermal environments have island-like characteristics and provide a unique opportunity to study population structure and diversity patterns of microbial taxa inhabiting these sites. Strains having ≥98% 16S rRNA gene sequence similarity to the obligately anaerobic Firmicutes Thermoanaerobacter uzonensis were isolated from seven geothermal springs, separated by up to 1600 m, within the Uzon Caldera (Kamchatka, Russian Far East). The intraspecies variation and spatial patterns of diversity for this taxon were assessed by multilocus sequence analysis (MLSA) of 106 strains. Analysis of eight protein-coding loci (gyrB, lepA, leuS, pyrG, recA, recG, rplB, and rpoB) revealed that all loci were polymorphic and that nucleotide substitutions were mostly synonymous. There were 148 variable nucleotide sites across 8003 bp concatenates of the protein-coding loci. While pairwise F ST values indicated a small but significant level of genetic differentiation between most subpopulations, there was a negligible relationship between genetic divergence and spatial separation. Strains with the same allelic profile were only isolated from the same hot spring, occasionally from consecutive years, and single locus variant (SLV) sequence types were usually derived from the same spring. While recombination occurred, there was an "epidemic" population structure in which a particular T. uzonensis sequence type rose in frequency relative to the rest of the population. These results demonstrate spatial diversity patterns for an anaerobic bacterial species in a relative small geographic location and reinforce the view that terrestrial geothermal springs are excellent places to look for biogeographic diversity patterns regardless of the involved distances.