Radiation hematologic toxicity prediction for locally advanced rectal cancer using dosimetric and radiomics features.

BACKGROUND: Hematologic toxicity (HT) is a common adverse tissue reaction during radiotherapy for rectal cancer patients, which may lead to various negative effects such as reduced therapeutic effect, prolonged treatment period and increased treatment cost. Therefore, predicting the occurrence of HT before radiotherapy is necessary but still challenging. PURPOSE: This study proposes a hybrid machine learning model to predict the symptomatic radiation HT in rectal cancer patients using the combined demographic, clinical, dosimetric, and Radiomics features, and ascertains the most effective regions of interest (ROI) in CT images and predictive feature sets. METHODS: A discovery dataset of 240 rectal cancer patients, including 145 patients with HT symptoms and a validation dataset of 96 patients (63 patients with HT) with different dose prescription were retrospectively enrolled. Eight ROIs were contoured on patient CT images to derive Radiomics features, which were then, respectively, combined with the demographic, clinical, and dosimetric features to classify patients with HT symptoms. Moreover, the survival analysis was performed on risky patients with HT in order to understand the HT progression. RESULTS: The classification models in ROIs of bone marrow and femoral head exhibited relatively high accuracies (accuracy = 0.765 and 0.725) in the discovery dataset as well as comparable performances in the validation dataset (accuracy = 0.758 and 0.714). When combining the two ROIs together, the model performance was the best in both discovery and validation datasets (accuracy = 0.843 and 0.802). In the survival analysis test, only the bone marrow ROI achieved statistically significant performance in accessing risky HT (C-index = 0.658, P = 0.03). Most of the discriminative features were Radiomics features, and only gender and the mean dose in Irradvolume was involved in HT. CONCLUSION: The results reflect that the Radiomics features of bone marrow are significantly correlated with HT occurrence and progression in rectal cancer. The proposed Radiomics-based model may help the early detection of radiotherapy induced HT in rectal cancer patients and thus improve the clinical outcome in future.

Passage of exogeneous fine particles from the lung into the brain in humans and animals.

There are still significant knowledge gaps in understanding the intrusion and retention of exogeneous particles into the central nervous system (CNS). Here, we uncovered various exogeneous fine particles in human cerebrospinal fluids (CSFs) and identified the ambient environmental or occupational exposure sources of these particles, including commonly found particles (e.g., Fe- and Ca-containing ones) and other compositions that have not been reported previously (such as malayaite and anatase TiO2), by mapping their chemical and structural fingerprints. Furthermore, using mouse and in vitro models, we unveiled a possible translocation pathway of various inhaled fine particles from the lung to the brain through blood circulation (via dedicated biodistribution and mechanistic studies). Importantly, with the aid of isotope labeling, we obtained the retention kinetics of inhaled fine particles in mice, indicating a much slower clearance rate of localized exogenous particles from the brain than from other main metabolic organs. Collectively, our results provide a piece of evidence on the intrusion of exogeneous particles into the CNS and support the association between the inhalation of exogenous particles and their transport into the brain tissues. This work thus provides additional insights for the continued investigation of the adverse effects of air pollution on the brain.

Impact of radiation source activity on short- and long-term outcomes of cervical carcinoma patients treated with high-dose-rate brachytherapy: A retrospective cohort study.

OBJECTIVE: High-dose-rate (HDR) afterloading brachytherapy using Iridium-192 source involves large radiation activity varieties due to fast decay. It was unknown but clinically desirable to evaluate its impacts on patient outcomes to support more informed decisions. METHODS: Data of 510 cervical carcinoma (CC) patients were retrospectively included. High-radioactive (HR) and low-radioactive (LR) groups were statistically defined per patient-specific average mean-dose-rate (MDR) of all fractions. The cutoffs were calculated using R-3.6.1 packages based on significance of correlation with binary outcome or survival time. Categorized 1-month and 3-month follow-up results were analyzed as short-term outcomes. Long-term outcomes were evaluated using local recurrence-free survival (LRFS) and metastatic recurrence-free survival (MRFS). Propensity-score-matched (PSM) pairs were generated to reduce bias. RESULTS: The median follow-up time was 47.1 months (interquartile range: 33.9 months-66.4 months), involving MDR varieties of up to 9 folds ranging from 6059.99 cGy/h to 54013.66 cGy/h due to 17 source replacements at intervals ranging from 93 days-199 days. Both short-term (1-month: p = 0.22; 3-month: p = 0.79) and long-term (LRFS: p = 0.10; MRFS: p = 0.46) outcomes showed no significant difference between HR and LR. Subgroup analysis displayed significantly better results in LR for stage I-II (3-month, p = 0.02) and stage II (LRFS, p = 0.04) patients. Both LRFS and MRFS of LR were significantly non-inferior to HR (p ≤ 0.02). CONCLUSIONS: LR is clinically non-inferior or partially superior to HR for CC treatment using HDR, which dispels concerns of potentially undermined patient outcomes when source replacement is delayed.

A Simulated Dosimetric Study of Contribution to Radiotherapy Accuracy by Fractional Image Guidance Protocol of Halcyon System.

PURPOSE: Frequency of conventional kV-image guidance is sometimes sacrificed to reduce concomitant risk, leaving deviations of unguided fractions unknown. MV-imaging and treatment dose can be collectively optimized on Halcyon, where fractional MVCBCT provides complete anatomic records for course-wide dose reconstruction. By retrospective dose accumulation, this work simulated the impact of imaging frequency on patient treatment dose on the platform of Halcyon. METHODS: Four hundred and sixteen MVCBCT image sets from 16 patients of various tumor sites treated with radiotherapy on Halcyon were retrospectively selected. After applying the image-guided couch shifts of the clinical records, deformable image registration was performed using Velocity software, to deform the planning CTs to the corresponding MVCBCTs, generating pseudo CTs representing the actual anatomies on the treatment day. Fractional treatment dose was reconstructed on pseudo CTs for accumulation, representing the actual patient dose (Ddaily). To simulate weekly image guidance, fractional dose was reconstructed and accumulated by incorporating 1 CBCT-guided corrections and 4 laser-guided setups of each week (Dweekly). Limited by partially imaged volumes and different organs-at-risk of various sites, only target dose-volume parameters were evaluated across all patients. RESULTS: GTV_D98%, CTV_D98%, PTV_D90%, PTV_D95%, PGTV_D90%, and PGTV_D95% were evaluated, where Dx% means the minimal dose received by x% volume. Pairwise comparisons were made between plan dose and Ddaily, Ddaily and Dweekly respectively. PGTV_D95% of accumulated Dweekly were significantly lower than those of accumulated Ddaily by up to 32.90% of prescription dose, suggesting that weekly-guidance may result in unacceptable under dose to the target. The broad distribution of fractional differences between Ddaily and Dweekly suggested unreliable patient positioning based on aligning surface markers to laser beams, as a popular approach broadly used on conventional Linac systems. Slight target under-dose was observed on daily reconstructed results compared with planned dose, which provided quantitative data to guide clinical decisions such as the necessity of adaptive radiotherapy. CONCLUSION: Fractional image guided radiotherapy on Halcyon provides more reliable treatment accuracy than using sacrificed imaging frequency, which also provides complete anatomic records for deformable dose reconstruction supporting more informed clinical decisions.

Brain-derived neurotrophic factor stimulation of T-type Ca2+ channels in sensory neurons contributes to increased peripheral pain sensitivity.

Although brain-derived neurotrophic factor (BDNF) is implicated in the nociceptive signaling of peripheral sensory neurons, the underlying mechanisms remain largely unknown. Here, we elucidated the effects of BDNF on the neuronal excitability of trigeminal ganglion (TG) neurons and the pain sensitivity of rats mediated by T-type Ca2+ channels. BDNF reversibly and dose-dependently enhanced T-type channel currents through the activation of tropomyosin receptor kinase B (TrkB). Antagonism of phosphatidylinositol 3-kinase (PI3K) but not of its downstream target, the kinase AKT, abolished the BDNF-induced T-type channel response. BDNF application activated p38 mitogen-activated protein kinase (MAPK), and this effect was prevented by inhibition of PI3K but not of protein kinase A (PKA). Antagonism of either PI3K or p38 MAPK prevented the BDNF-induced stimulation of PKA activity, whereas PKA inhibition blocked the BDNF-mediated increase in T-type currents. BDNF increased the rate of action potential firing in TG neurons and enhanced the pain sensitivity of rats to mechanical stimuli. Moreover, inhibition of TrkB signaling abolished the increased mechanical sensitivity in a rat model of chronic inflammatory pain, and this effect was attenuated by either T-type channel blockade or knockdown of the channel Cav3.2. Together, our findings indicate that BDNF enhances T-type currents through the stimulation of TrkB coupled to PI3K-p38-PKA signaling, thereby inducing neuronal hyperexcitability of TG neurons and pain hypersensitivity in rats.

The operating performance of a biotrickling filter with Lysinibacillus fusiformis for the removal of high-loading gaseous chlorobenzene.

Removal of gaseous chlorobenzene (CB) by a biotrickling filter (BTF) filled with modified ceramics and multi-surface hollow balls during gas-liquid mass transfer at the steady state was by microbial degradation rather than dissolution in the spray liquid or emission into the atmosphere. The BTF was flexible and resistant to the acid environment of the spray liquid, with the caveat that the spray liquid should be replaced once every 6-7 days. The BTF, loaded with Lysinibacillus fusiformis, performed well for purification of high-loading CB gas. The maximum CB gas inlet loading rate, 103 g m(-3) h(-1), CB elimination capacity, 97 g m(-3) h(-1), and CB removal efficiency, 97.7 %, were reached at a spray liquid flow rate of 27.6 ml min(-1), an initial CB concentration of up to 1,300 mg m(-3), and an empty bed retention time of more than 45 s.