Battery-Free, Wireless, Ionic Liquid Sensor Arrays to Monitor Pressure and Temperature of Patients in Bed and Wheelchair.

Repositioning is a common guideline for the prevention of pressure injuries of bedridden or wheelchair patients. However, frequent repositioning could deteriorate the quality of patient's life and induce secondary injuries. This paper introduces a method for continuous multi-site monitoring of pressure and temperature distribution from strategically deployed sensor arrays at skin interfaces via battery-free, wireless ionic liquid pressure sensors. The wirelessly delivered power enables stable operation of the ionic liquid pressure sensor, which shows enhanced sensitivity, negligible hysteresis, high linearity and cyclic stability over relevant pressure range. The experimental investigations of the wireless devices, verified by numerical simulation of the key responses, support capabilities for real-time, continuous, long-term monitoring of the pressure and temperature distribution from multiple sensor arrays. Clinical trials on two hemiplegic patients confined on bed or wheelchair integrated with the system demonstrate the feasibility of sensor arrays for a decrease in pressure and temperature distribution under minimal repositioning.

Soft, skin-interfaced microfluidic systems with integrated immunoassays, fluorometric sensors, and impedance measurement capabilities.

Soft microfluidic systems that capture, store, and perform biomarker analysis of microliter volumes of sweat, in situ, as it emerges from the surface of the skin, represent an emerging class of wearable technology with powerful capabilities that complement those of traditional biophysical sensing devices. Recent work establishes applications in the real-time characterization of sweat dynamics and sweat chemistry in the context of sports performance and healthcare diagnostics. This paper presents a collection of advances in biochemical sensors and microfluidic designs that support multimodal operation in the monitoring of physiological signatures directly correlated to physical and mental stresses. These wireless, battery-free, skin-interfaced devices combine lateral flow immunoassays for cortisol, fluorometric assays for glucose and ascorbic acid (vitamin C), and digital tracking of skin galvanic responses. Systematic benchtop evaluations and field studies on human subjects highlight the key features of this platform for the continuous, noninvasive monitoring of biochemical and biophysical correlates of the stress state.

N-Glycan Branching Is Required for Development of Mature B Cells.

Galectins have been implicated in inhibiting BCR signaling in mature B cells but promoting pre-BCR signaling during early development. Galectins bind to branched N-glycans attached to cell surface glycoproteins to control the distribution, clustering, endocytosis, and signaling of surface glycoproteins. During T cell development, N-glycan branching is required for positive selection of thymocytes, inhibiting both death by neglect and negative selection via enhanced surface retention of the CD4/CD8 coreceptors and limiting TCR clustering/signaling, respectively. The role of N-glycan branching in B cell development is unknown. In this study, we report that N-glycan branching is absolutely required for development of mature B cells in mice. Elimination of branched N-glycans in developing B cells via targeted deletion of N-acetylglucosaminyl transferase I (Mgat1) markedly reduced cellularity in the bone marrow and/or spleen and inhibited maturation of pre-, immature, and transitional stage 2 B cells. Branching deficiency markedly reduced surface expression of the pre-BCR/BCR coreceptor CD19 and promoted spontaneous death of pre-B cells and immature B cells in vitro. Death was rescued by low-dose pre-BCR/BCR stimulation but exacerbated by high-dose pre-BCR/BCR stimulation as well as antiapoptotic BclxL overexpression in pre-B cells. Branching deficiency also enhanced Nur77 induction, a marker of negative selection. Together, these data suggest that, as in T cells, N-glycan branching promotes positive selection of B cells by augmenting pre-BCR/BCR signaling via CD19 surface retention, whereas limiting negative selection from excessive BCR engagement.

Active small bowel sparing in intracavitary brachytherapy for cervical cancer.

OBJECTIVE: To propose and evaluate an active method for sparing the small bowel in the treatment field of cervical cancer brachytherapy by prone position procedure. METHODS: The prone position procedure consists of five steps: making bladder empty, prone-positioning a patient on belly board, making the small bowel move to abdomen, filling the bladder with Foley catheter and finally turning the patient into the supine position. The proposed method was applied for the treatment of seven cervical cancer patients. Its effectiveness was evaluated and a correlation between the patient characteristics and the volumetric dose reduction of small bowel was also investigated. Brachytherapy treatment plans were built before and after the proposed method, and their dose-volume histograms were compared for targets and organs-at-risk. In this comparison, all plans were normalized to satisfy the same D90% for high-risk clinical target volume. RESULTS: For the enrolled patients, the average dose of small bowel was significantly reduced from 75.2 ± 4.9 Gy before to 60.2 ± 4.0 Gy after the prone position procedure, while minor dosimetric changes were observed in rectum, sigmoid and bladder. The linear correlation to body mass index, thickness and width of abdominopelvic cavity and bladder volume were 76.2, 69.7, 28.8 and -36.3%, respectively. CONCLUSIONS: The application of prone position procedure could effectively lower the volumetric dose of the small bowel. The dose reduction in the small bowel had a strong correlation with the patient's obesity and abdominal thickness. This means the patients for whom the proposed method would be beneficial can be judiciously selected for safe brachytherapy.

N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation.

Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of remyelination promotes permanent neuro-axonal damage. Modification of cell surface receptors with branched N-glycans coordinates cell growth and differentiation by controlling glycoprotein clustering, signaling, and endocytosis. GlcNAc is a rate-limiting metabolite for N-glycan branching. Here we report that GlcNAc and N-glycan branching trigger oligodendrogenesis from precursor cells by inhibiting platelet-derived growth factor receptor-α cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, whereas genetically blocking N-glycan branching markedly inhibits primary myelination. In adult mice with toxin (cuprizone)-induced demyelination, oral GlcNAc prevents neuro-axonal damage by driving myelin repair. In MS patients, endogenous serum GlcNAc levels inversely correlated with imaging measures of demyelination and microstructural damage. Our data identify N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neuroprotective in demyelinating diseases like MS.

Prognostic significance of smoking and alcohol history in young age oral cavity cancer.

OBJECTIVE: To assess prognostic factors of patients with operable oral cavity squamous cell carcinoma (OSCC), focusing on the associations with smoking/alcohol exposure and age. MATERIALS AND METHODS: A total of 247 patients with OSCC who received curative surgery ± adjuvant radiotherapy were analyzed. The patient subgroups were divided according to pretreatment smoking/alcohol exposure. Individuals aged 45 years or less were classified as younger patients. RESULTS: The median follow-up was 52.2 months. The 5-year locoregional progression-free survival (LRFFS), distant metastasis-free survival (DMFS), overall survival (OS), and cancer-specific survival (CSS) rates were 85.2%, 88.3%, 78.1%, and 83.5%, respectively. An advanced stage, differentiation, and lympho-vascular space invasion were significantly associated with lower OS and CSS. In a subgroup analysis of younger patients (n = 49), more smoking/alcohol exposure was significantly associated with better OS (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05-0.95, p = .043). With increasing age, the HR for smoking/alcohol exposure with respect to OS increased up to 11.59 (95% CI: 1.49-89.84, p = .019) in older patients. CONCLUSION: Younger OSCC patients with non- or less smoking/alcohol exposure showed unfavorable outcomes. The prognostic significance of pretreatment smoking/alcohol exposure changed from favorable to detrimental with increasing age in operable OSCC.

Analysis of unexplained carcinoembryonic antigen elevation after curative treatment of locally advanced rectal cancer.

BACKGROUND: To analyze the causes and patterns of unexplained carcinoembryonic antigen (CEA) elevation after curative treatment in locally advanced rectal cancer patients. METHODS: Among the 1309 locally advanced rectal cancer patients treated with curative resection and radiotherapy between January 2001 and June 2011, 325 patients who postoperatively developed abnormal CEA elevation were reviewed. The unexplained CEA elevation was defined as a CEA level higher than 5 ng/mL with no evidence of cancer recurrence at the time of elevation. RESULTS: Of the 325 patients, 143 (44%) had unexplained CEA elevations. The causes were categorized as delayed recurrence (n = 29, 20%), non-colorectal malignancy (n = 10, 7%), and non-malignancy-related conditions (n = 104, 73%). Shorter intervals between treatment and the first CEA elevation, and a higher peak CEA level, were observed in the delayed recurrence group compared with the non-colorectal malignancy or non-malignancy-related group (intervals of 6.8 vs. 44.9 vs. 23.2 months, respectively, p = 0.002; and peak CEA levels of 9.9 vs. 7.1 vs. 6.2 ng/mL, respectively, p = 0.034). In patients who showed delayed recurrence, the interval between the first CEA elevation and diagnosis of recurrence was a median of 13.0 months (range 3.8-60.6 months). Smoking was the most common cause for non-malignancy-related conditions. The patterns of unexplained CEA elevations were defined as sporadic (n = 78, 55%), stationary (n = 37, 26%), and increasing (n = 28, 20%). The patterns were significantly different depending on the cause (p < 0.001). CONCLUSIONS: Analysis of the patterns of unexplained CEA elevations is a reasonable approach to predict the cause of the cancer.

Ablative dose proton beam therapy for stage I and recurrent non-small cell lung carcinomas : Ablative dose PBT for NSCLC.

PURPOSE: To evaluate the efficacy and safety of ablative dose hypofractionated proton beam therapy (PBT) for patients with stage I and recurrent non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: A total of 55 patients with stage I (n = 42) and recurrent (n = 13) NSCLC underwent hypofractionated PBT and were retrospectively reviewed. A total dose of 50-72 CGE (cobalt gray equivalent) in 5-12 fractions was delivered. RESULTS: The median follow-up duration was 29 months (range 4-95 months). There were 24 deaths (43.6%) during the follow-up period: 11 died of disease progression and 13 from other causes. Kaplan-Meier overall survival rate (OS) at 3 years was 54.9% and the median OS was 48.6 months (range 4-95 months). Local progression was observed in 7 patients and the median time to local progression was 9.3 months (range 5-14 months). Cumulative actuarial local control rate (LCR), lymph node metastasis-free survival, and distant metastasis-free survival rates at 3 years were 85.4, 78.4, and 76.5%, respectively. Larger tumor diameter was significantly associated with poorer LCR (3-year: 94% for ≤3 cm vs. 65% for >3 cm, p = 0.006) on univariate analysis and also an independent prognostic factor for LCR (HR 6.9, 95% CI = 1.3-37.8, p = 0.026) on multivariate analysis. No grade 3 or 4 treatment-related toxicities developed. One grade 5 treatment-related adverse event occurred in a patient with symptomatic idiopathic pulmonary fibrosis. CONCLUSIONS: Ablative dose hypofractionated PBT was safe and promising for stage I and recurrent NSCLC.

POK/ZBTB proteins: an emerging family of proteins that regulate lymphoid development and function.

The germinal center (GC) is a unique histological structure found in peripheral lymphoid organs. GCs provide an important source of humoral immunity by generating high affinity antibodies against a pathogen. The GC response is tightly regulated during clonal expansion, immunoglobulin modification, and affinity maturation, whereas its deregulation has a detrimental effect on immune function, leading to development of diseases, such as lymphoma and autoimmunity. LRF (lymphoma/leukemia-related factor), encoded by the ZBTB7A gene, is a transcriptional repressor belonging to the POK (POZ and Krüppel)/ZBTB (zing finger and BTB) protein family. LRF was originally identified as a PLZF (promyelocytic leukemia zinc finger) homolog that physically interacts with BCL6 (B-cell lymphoma 6), whose expression is required for GC formation and associated with non-Hodgkin's lymphoma. Recently, our group demonstrated that LRF plays critical roles in regulating lymphoid lineage commitment, mature B-cell development, and the GC response via distinct mechanisms. Herein, we review POK/ZBTB protein function in lymphoid development, with particular emphasis on the role of LRF in GC B cells.

LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance.

Hematopoietic stem cells (HSCs) are the most primitive cells in the hematopoietic system and are under tight regulation for self-renewal and differentiation. Notch signals are essential for the emergence of definitive hematopoiesis in mouse embryos and are critical regulators of lymphoid lineage fate determination. However, it remains unclear how Notch regulates the balance between HSC self-renewal and differentiation in the adult bone marrow (BM). Here we report a novel mechanism that prevents HSCs from undergoing premature lymphoid differentiation in BM. Using a series of in vivo mouse models and functional HSC assays, we show that leukemia/lymphoma related factor (LRF) is necessary for HSC maintenance by functioning as an erythroid-specific repressor of Delta-like 4 (Dll4) expression. Lrf deletion in erythroblasts promoted up-regulation of Dll4 in erythroblasts, sensitizing HSCs to T-cell instructive signals in the BM. Our study reveals novel cross-talk between HSCs and erythroblasts, and sheds a new light on the regulatory mechanisms regulating the balance between HSC self-renewal and differentiation.

Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology.

Clathrin-dependent endocytosis is an essential cellular process shared by all cell types. Despite this, precisely how endocytosis is regulated in a cell-type-specific manner and how this key pathway functions physiologically or pathophysiologically remain largely unknown. PICALM, which encodes the clathrin adaptor protein PICALM, was originally identified as a component of the CALM/AF10 leukemia oncogene. Here we show, by employing a series of conditional Picalm knockout mice, that PICALM critically regulates transferrin uptake in erythroid cells by functioning as a cell-type-specific regulator of transferrin receptor endocytosis. While transferrin receptor is essential for the development of all hematopoietic lineages, Picalm was dispensable for myeloid and B-lymphoid development. Furthermore, global Picalm inactivation in adult mice did not cause gross defects in mouse fitness, except for anemia and a coat color change. Freeze-etch electron microscopy of primary erythroblasts and live-cell imaging of murine embryonic fibroblasts revealed that Picalm function is required for efficient clathrin coat maturation. We showed that the PICALM PIP2 binding domain is necessary for transferrin receptor endocytosis in erythroblasts and absolutely essential for erythroid development from mouse hematopoietic stem/progenitor cells in an erythroid culture system. We further showed that Picalm deletion entirely abrogated the disease phenotype in a Jak2(V617F) knock-in murine model of polycythemia vera. Our findings provide new insights into the regulation of cell-type-specific transferrin receptor endocytosis in vivo. They also suggest a new strategy to block cellular uptake of transferrin-bound iron, with therapeutic potential for disorders characterized by inappropriate red blood cell production, such as polycythemia vera.

Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis.

PURPOSE: To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). PATIENTS AND METHODS: Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. RESULTS: Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0%) patients, partial response in 15 (55.6%), stable disease in 10 (37%), and progressive disease in 2 (7.4%) patients, with an objective response rate of 55.6%. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6% vs. 51.3%), relapse-free survival (RFS; 20% vs. 0%) and OS (80% vs. 25%) rates than nonresponders (p<0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS. CONCLUSION: Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients.

Effect of Lactobacillus Rhamnosus GG for Regulation of Inflammatory Response in Radiation-Induced Enteritis.

The purpose of this study was to investigate the role of Lactobacillus rhamnosus GG (LGG) probiotics in radiation enteritis using in vivo mice. A total of 40 mice were randomly assigned to four groups: control, probiotics, radiotherapy (RT), and RT + probiotics. For the group of probiotics, 0.2 mL of solution that contained 1.0 × 108 colony-forming units (CFU) of LGG was used and orally administered daily until sacrifice. For RT, a single dose of 14 Gy was administered using a 6 mega-voltage photon beam to the abdominopelvic area. Mice were sacrifice at day 4 (S1) and day 7 (S2) after RT. Their jejunum, colon, and stool were collected. A multiplex cytokine assay and 16 s ribosomal RNA amplicon sequencing were then performed. Regarding cytokine concentrations in tissues, pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein-1, showed significantly decreased protein levels in colon tissues of the RT + probiotics group than in the RT alone group (all p < 0.05). As for comparing microbial abundance through alpha-diversity and beta-diversity, no significant differences were observed between the RT + probiotics and RT alone groups, except for an increase in alpha-diversity in the stool of the RT + probiotics group. Upon analysis of differential microbes based on treatment, the dominance of anti-inflammatory-related microbes, such as Porphyromonadaceae, Bacteroides acidifaciens, and Ruminococcus, was observed in the jejunum, colon, and stool of the RT + probiotics group. With regard to predicted metabolic pathway abundances, the pathways associated with anti-inflammatory processes, such as biosynthesis of pyrimidine nucleotides, peptidoglycans, tryptophan, adenosylcobalamin, and propionate, were differentially identified in the RT + probiotics group compared to the RT alone group. Protective effects of probiotics on radiation enteritis were potentially derived from dominant anti-inflammation-related microbes and metabolites.

Current evidence and the potential role of proton beam therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and external beam radiation therapy has emerged as a promising approach for managing HCC. Proton beam therapy (PBT) offers dosimetric advantages over X-ray therapy, with superior physical properties known as the Bragg peak. PBT holds promise for reducing hepatotoxicity and allowing safe dose-escalation to the tumor. It has been tried in various clinical conditions and has shown promising local tumor control and survival outcomes. A recent phase III trial demonstrated the non-inferiority of PBT in local tumor control compared to current standard radiofrequency ablation in early-stage HCC. PBT also tended to show more favorable outcomes compared to transarterial chemoembolization in the intermediate stage, and has proven effective in-field disease control and safe toxicity profiles in advanced HCC. In this review, we discuss the rationale, clinical studies, optimal indication, and future directions of PBT in HCC treatment.

Pattern of practice for postoperative management of endometrial cancer in Korea: a survey by the Korean Gynecologic Oncology Group and the Korean Radiation Oncology Group (KGOG 2028-KROG 2104).

OBJECTIVE: This study aimed to investigate the current status of postoperative management of uterine endometrial cancer (EC) in Korea. METHODS: A mail survey was administered to members of the Korean Gynecologic Oncology Group and Korean Radiation Oncology Group. A total of 38 gynecologic cancer surgeons (GYNs) and 31 radiation oncologists (RO) in 43 institutions was responded. The questionnaire consisted of general questions for clinical decision and clinical case questions. The GYN and RO responses were compared using chi-square statistics. RESULTS: The 2 expert groups had similar responses for clinical decision based on the results of the Gynecologic Oncology Group (GOG)-249 and Postoperative Radiation Therapy for Endometrial Carcinoma-III trials in the early-stage EC. In contrast, the responses based on GOG-258 results differed, as GYNs most frequently opted for sequential chemotherapy (CTx) and radiotherapy (RT), while ROs preferred concurrent chemoradiotherapy in locally advanced stage (p<0.05). Based on the GOG-258, GYNs preferred CTx alone for adjuvant treatment of serous or clear cell adenocarcinoma histology, whereas ROs advocated for combined CTx and RT (sequential or concurrent). Among the clinical case questions, GYNs were more likely than ROs to choose CTx alone rather than the combination of CTx and RT (sequential or concurrent) as the answers to case questions representing patients with locally advanced stage or unfavorable histology (all p<0.05). CONCLUSION: The present study showed several different opinions of GYNs and ROs regarding adjuvant treatment for EC, particularly for adjuvant RT in advanced stage or unfavorable histology.

Feature Importance Analysis of a Deep Learning Model for Predicting Late Bladder Toxicity Occurrence in Uterine Cervical Cancer Patients.

(1) In this study, we developed a deep learning (DL) model that can be used to predict late bladder toxicity. (2) We collected data obtained from 281 uterine cervical cancer patients who underwent definitive radiation therapy. The DL model was trained using 16 features, including patient, tumor, treatment, and dose parameters, and its performance was compared with that of a multivariable logistic regression model using the following metrics: accuracy, prediction, recall, F1-score, and area under the receiver operating characteristic curve (AUROC). In addition, permutation feature importance was calculated to interpret the DL model for each feature, and the lightweight DL model was designed to focus on the top five important features. (3) The DL model outperformed the multivariable logistic regression model on our dataset. It achieved an F1-score of 0.76 and an AUROC of 0.81, while the corresponding values for the multivariable logistic regression were 0.14 and 0.43, respectively. The DL model identified the doses for the most exposed 2 cc volume of the bladder (BD2cc) as the most important feature, followed by BD5cc and the ICRU bladder point. In the case of the lightweight DL model, the F-score and AUROC were 0.90 and 0.91, respectively. (4) The DL models exhibited superior performance in predicting late bladder toxicity compared with the statistical method. Through the interpretation of the model, it further emphasized its potential for improving patient outcomes and minimizing treatment-related complications with a high level of reliability.

Spastic cerebral palsy in children: dynamic sonoelastographic findings of medial gastrocnemius.

PURPOSE: To study the elastic properties of the medial gastrocnemius (GCM) in children with spastic cerebral palsy. MATERIALS AND METHODS: The study protocol was approved by the Research Ethics Committee of the hospital, and informed consent was obtained from each child's parent. Fifteen children with spastic cerebral palsy (group 1) and 13 children without neurologic and musculoskeletal disabilities (group 2) were included. Because group 1 included three children with hemiplegia, the total number of legs examined was 27. Children in group 2 had both legs examined, for a total of 26 legs studied. The modified Ashworth scale score of the ankle in group 1 was assessed by a physical therapist. A physiatrist performed ultrasonography and dynamic sonoelastography (DS) together, measured the thickness of the GCM, and calculated the GCM ratio in both groups. On color-scaled DS images, the DS score of the GCM was graded from DS 1 (purple to green: soft) to DS 4 (red: stiff), and the color histogram of the GCM was subsequently analyzed. Strain ratio and local shear wave velocity were calculated in the GCM and the soleus muscle by using acoustic radiation force impulse imaging. RESULTS: The GCM ratio in group 1 was significantly smaller than that in group 2. The DS score of GCM in group 1 was significantly higher than that in group 2. The median red pixel values were significantly higher, and the blue pixel values were significantly lower on color histogram in group 1 than those in group 2. The strain ratio in group 1 was significantly lower than that in group 2, and the local shear wave velocity of GCM in group 1 was higher than that in group 2. There were significant correlations between the modified Ashworth scale scores and DS parameters. CONCLUSION: DS demonstrated a difference in muscle stiffness in the GCM between children with spastic cerebral palsy and those without neurologic and musculoskeletal disabilities.

A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute.

BACKGROUND: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using both modalities. METHODS: We retrospectively reviewed the records of patients who underwent nCRT for ESCC between 2001 and 2020. A median of 41.4 Gy or cobalt gray equivalents of radiation was delivered using either photons or protons, with concurrent chemotherapy. Dosimetric and clinical parameters were compared between the two groups. RESULTS: Of the 31 patients, the lungs and heart of the proton group (n = 15) were exposed to significantly less radiation compared to the photon group (n = 16). No significant differences in short-term postoperative outcomes or lymphocyte count were observed between the groups, and there were no significant differences between the photon and proton groups in 2-year overall survival (67.8% vs. 68.6%, p = 0.867) or 2-year disease-free survival (33.3% vs. 34.5%, p = 0.749), with a median follow-up of 17 months. CONCLUSIONS: PBT provided a significant dosimetric benefit over photon-based RT during nCRT for ESCC; however, it did not improve clinical outcomes.

Interobserver Variability Prediction of Primary Gross Tumor in a Patient with Non-Small Cell Lung Cancer.

This research addresses the problem of interobserver variability (IOV), in which different oncologists manually delineate varying primary gross tumor volume (pGTV) contours, adding risk to targeted radiation treatments. Thus, a method of IOV reduction is urgently needed. Hypothesizing that the radiation oncologist's IOV may shrink with the aid of IOV maps, we propose IOV prediction network (IOV-Net), a deep-learning model that uses the fuzzy membership function to produce high-quality maps based on computed tomography (CT) images. To test the prediction accuracy, a ground-truth pGTV IOV map was created using the manual contour delineations of radiation therapy structures provided by five expert oncologists. Then, we tasked IOV-Net with producing a map of its own. The mean squared error (prediction vs. ground truth) and its standard deviation were 0.0038 and 0.0005, respectively. To test the clinical feasibility of our method, CT images were divided into two groups, and oncologists from our institution created manual contours with and without IOV map guidance. The Dice similarity coefficient and Jaccard index increased by ~6 and 7%, respectively, and the Hausdorff distance decreased by 2.5 mm, indicating a statistically significant IOV reduction (p < 0.05). Hence, IOV-net and its resultant IOV maps have the potential to improve radiation therapy efficacy worldwide.

Optimal Definition of Biochemical Recurrence in Patients Who Receive Salvage Radiotherapy Following Radical Prostatectomy for Prostate Cancer.

PURPOSE: This study proposed the optimal definition of biochemical recurrence (BCR) after salvage radiotherapy (SRT) following radical prostatectomy for prostate cancer. MATERIALS AND METHODS: Among 1,117 patients who had received SRT, data from 205 hormone-naïve patients who experienced post-SRT prostate-specific antigen (PSA) elevation were included in a multi-institutional database. The primary endpoint was to determine the PSA parameters predictive of distant metastasis (DM). Absolute serum PSA levels and the prostate-specific antigen doubling time (PSA-DT) were adopted as PSA parameters. RESULTS: When BCR was defined based on serum PSA levels ranging from 0.4 ng/mL to nadir+2.0 ng/mL, the 5-year probability of DM was 27.6%-33.7%. The difference in the 5-year probability of DM became significant when BCR was defined as a serum PSA level of 0.8 ng/ml or higher (1.0-2.0 ng/mL). Application of a serum PSA level of ≥ 0.8 ng/mL yielded a c-index value of 0.589. When BCR was defined based on the PSA-DT, the 5-year probability was 22.7%-39.4%. The difference was significant when BCR was defined as a PSA-DT ≤ 3 months and ≤ 6 months. Application of a PSA-DT ≤ 6 months yielded the highest c-index (0.660). These two parameters complemented each other; for patients meeting both PSA parameters, the probability of DM was 39.5%-44.5%; for those not meeting either parameter, the probability was 0.0%-3.1%. CONCLUSION: A serum PSA level > 0.8 ng/mL was a reasonable threshold for the definition of BCR after SRT. In addition, a PSA-DT ≤ 6 months was significantly predictive of subsequent DM, and combined application of both parameters enhanced predictability.