A novel method for rapid estimation of active bone marrow dose for radiotherapy patients in epidemiological studies.

BACKGROUND: In a dedicated effort to improve the assessment of clonal hematopoiesis (CH) and study leukemia risk following radiotherapy, we are developing a large-scale cohort study among cancer patients who received radiation. To that end, it will be critical to analyze dosimetric parameters of red bone marrow (ABM) exposure in relation to CH and its progression to myeloid neoplasms, requiring reconstruction method for ABM doses of a large-scale patients rapidly and accurately. PURPOSE: To support a large-scale cohort study on the assessment of clonal hematopoiesis and leukemia risk following radiotherapy, we present a new method for the rapid reconstruction of ABM doses of radiotherapy among cancer patients. METHODS: The key idea of the presented method is to segment patient bones rapidly and automatically by matching a whole-body computational human phantom, in which the skeletal system is divided into 34 bone sites, to patient CT images via 3D skeletal registration. The automatic approach was used to segment site-specific bones for 40 radiotherapy patients. Also, we segmented the bones manually. The bones segmented both manually and automatically were then combined with the patient dose matrix calculated by the treatment planning system (TPS) to derive patient ABM dose. We evaluated the performance of the automatic method in geometric and dosimetric accuracy by comparison with the manual approach. RESULTS: The pelvis showed the best geometric performance [volume overlap fraction (VOF): 52% (mean) with 23% (σ) and average distance (AD): 0.8 cm (mean) with 0.5 cm (σ)]. The pelvis also showed the best dosimetry performance [absorbed dose difference (ADD): 0.7 Gy (mean) with 1.0 Gy (σ)]. Some bones showed unsatisfactory performances such as the cervical vertebrae [ADD: 5.2 Gy (mean) with 10.8 Gy (σ)]. This impact on the total ABM dose, however, was not significant. An excellent agreement for the total ABM dose was indeed observed [ADD: 0.4 Gy (mean) with 0.4 Gy (σ)]. The computation time required for dose calculation using our method was robust (about one minute per patient). CONCLUSIONS: We confirmed that our method estimates ABM doses across treatment sites accurately, while providing high computational efficiency. The method will be used to reconstruct patient-specific ABM doses for dose-response assessment in a large cohort study. The method can also be applied to prospective dose calculation within a clinical TPS to support clinical decision making at the point of care.

Full etiologic spectrum of pediatric severe to profound hearing loss of consecutive 119 cases.

Determining the etiology of severe-to-profound sensorineural hearing loss (SP-SNHL) in pediatric subjects is particularly important in aiding the decision for auditory rehabilitation. We aimed to update the etiologic spectrum of pediatric SP-SNHL by combining internal auditory canal (IAC)-MRI with comprehensive and state-of-the-art genetic testings. From May 2013 to September 2020, 119 cochlear implantees under the age of 15 years with SP-SNHL were all prospectively recruited. They were subjected to genetic tests, including exome sequencing, and IAC-MRI for etiologic diagnosis. Strict interpretation of results were made based on ACMG/AMP guidelines and by an experienced neuroradiologist. The etiology was determined in of 65.5% (78/119) of our cohort. If only one of the two tests was done, the etiologic diagnostic rate would be reduced by at least 21.8%. Notably, cochlear nerve deficiency (n = 20) detected by IAC-MRI topped the etiology list of our cohort, followed by DFNB4 (n = 18), DFNB1 (n = 10), DFNB9 (n = 10) and periventricular leukomalacia associated with congenital CMV infection (n = 8). Simultaneous application of state-of-the-art genetic tests and IAC-MRI is essential for etiologic diagnosis, and if lesions of the auditory nerve or central nerve system are carefully examined on an MRI, we can identify the cause of deafness in more than 65% of pediatric SP-SNHL cases.

Natural course of residual hearing preservation with a slim, modiolar cochlear implant electrode array.

PURPOSE: Understanding residual hearing preservation and its natural course following cochlear implantation is important for developing rehabilitation strategies for hearing loss. However, non-uniform evaluation criteria and varying surgical skills pose challenges in fair comparison of the effect of different electrodes on residual hearing preservation. We compared the effect of a slim modiolar electrode (SME) and a slim straight electrode (SSE), implanted by a single surgeon, on progression of residual hearing using different parameters, based on cross-sectional and longitudinal audiological analyses. METHODS: Patients with preoperative low-frequency pure-tone average (LFPTA) ≤85 dB at 250 and 500 Hz and who underwent minimally traumatic surgical techniques were included. The progression of residual hearing using threshold shifts, hearing preservation rate according to the HEARRING classification, and maintenance of functional low-frequency hearing potentially qualifying for a hybrid stimulation was analyzed up to five time points throughout the 1-year follow-up period. RESULTS: Threshold shifts and hearing preservation rates according to the HEARRING classification of the electrodes were comparable from 3 months through 12 months postoperatively. Maintenance of functional low-frequency hearing, required for the usage of a hybrid stimulation, was similar for both electrodes. A substantial proportion of implantees with SME use a hybrid stimulation, resulting in long-term use. However, a difference in the pattern of postoperative residual hearing preservation between the two electrodes is possible, probably due to differences in their physical characteristics and location. Specifically, correlation analysis exhibited that significantly less tight modiolar proximity negatively affect the residual hearing preservation, albeit only at 3 months postoperatively, among patients with the SME. CONCLUSION: Collectively, both SME and SSE implantation showed favorable residual hearing preservation. Our findings further refine the recently proposed hearing preservation with the SME and suggest that the physical characteristics and location of electrodes, in terms of electrode-to-modiolus distance, could affect loss of acoustic hearing in various ways.