Therapy Planning Research Articles

Dosimetric validation of intensity-modulated bolus electron conformal therapy planning and delivery using an anthropomorphic cylindrical head phantom.

This work investigated the dosimetric accuracy of the intensity-modulated bolus electron conformal therapy (IM-BECT) planning and delivery process using the decimal ElectronRT (eRT) treatment planning system. An IM-BECT treatment plan was designed using eRT for a cylindrical, anthropomorphic retromolar trigone phantom. Treatment planning involved specification of beam parameters and design of a variable thickness wax bolus and Passive Radiotherapy Intensity Modulator for Electrons (PRIME) device, which was comprised of 33 tungsten island blocks of discrete diameters from 0.158 to 0.223cm (Intensity Reduction Factors from 0.937 to 0.875, respectively) inside a 10.1×6.7 cm2 copper cutout. For comparison of calculation accuracy, a BECT plan was generated by copying the IM-BECT plan and removing the intensity modulation. For both plans, a 16 MeV electron beam was used with 104.7cm source-to-surface distance to bolus. In-phantom TLD-100 measurements (N=47) were compared with both eRT planned dose distributions, which used the pencil beam redefinition algorithm with modifications for passive electron intensity modulation (IM-PBRA). Dose difference and distance to agreement (DTA) metrics were computed for each measurement point. Comparison of measured dose distributions with planned dose distributions yielded dose differences (calculated minus measured) characterized by a mean and standard deviation of -0.36%±1.64% for the IM-BECT plan, which was similar to -0.36%±1.90% for the BECT plan. All dose measurements were within 5% of the planned dose distribution, with both the BECT and IM-BECT measurement sets having 46/47 (97.8%) points within 3% or within 3mm of the respective treatment plans. It was found that the IM-BECT treatment plan generated using eRT was sufficiently accurate for clinical use when compared to TLD measurements in a cylindrical, anthropomorphic phantom, and was similarly accurate to the BECT treatment plan in the same phantom.

Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma: NRG Oncology/GOG Study 279.

To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Health education for women in postnatal wards at Kenyatta National Hospital, Kenya

Background/Aims Health education for postnatal women after discharge is essential to informing women about nursing infants, self-care, identifying danger signs, therapy, medication and family planning intention. The aim of this study was to examine health education and health promotional messages given to women in the postnatal wards of Kenyatta National Hospital. Methods This descriptive cross-sectional design study was carried out with 105 postnatal women at the Kenyatta National Hospital, Kenya. A semi-structured questionnaire was used to collect data on women's postnatal care knowledge, and the timing and delivery of health education messages. Results The participants were knowledgeable about a number of postnatal care practices but lacking in some areas. Most received information on postnatal care immediately after birth. Healthcare professionals, including nurses, midwives, doctors and nutritionists, were the leading source of information. Health messages were shared in Kiswahili or a mixture of English and Kiswahili. The majority of participants reported they were able to understand the health messages they received. Conclusions Postnatal women were knowledgeable about postnatal care practices, although gaps in their knowledge were evident in some areas. Nurses and midwives working in obstetric wards need to initiate postnatal health education before discharge from the hospital to avoid delays in communicating crucial health messages and ensure that women are adequately informed.

Validation of the Arabic Version of Feeding Handicap Index for Children with Developmental Disabilities (A-FHI-C).

Children with developmental disabilities have different feeding and swallowing problems. The purposes of the present study were to develop an Arabic version of the FHI-C and to evaluate its validity, consistency, and reliability in Arabic children with developmental disabilities for assessing how feeding and swallowing problems impair the physical, functional, and emotional aspects of children's lives. A prospective study including 113 children [62 children with autism spectrum disorder (ASD), 24 with cerebral palsy (CP), 27 with intellectual disability (ID)], in the age range of 2 to 10 years, selected randomly from the swallowing clinic, phoniatrics unit, Otorhinolaryngology department, University hospital between September 2023 and December 2023 complaining of feeding and swallowing problems. Validity was established by comparing patients` scores to typically developed controls (31 children). For test-retest reliability, forty parents filled out the A-FHI-C again two weeks after their initial visit. Cronbach's alpha for A-FHI-C was 0.986, indicating good internal consistency. Intraclass correlation showed 0.850 with a 95% confidence interval from 0.779 to 0.898. All three clinical groups had significantly higher total FHI-C and FHI-C domain scores than the control group, indicating good validation. A-FHI-C was found to have significantly high test-retest reliability. The current study indicates that in children with ASD, CP, ID, feeding problems are more prevalent than children who are typically developed. The scores obtained can be used by phoniatricans to evaluate feeding problems and monitor the progress of the therapy plan in children with developmental disorders.

Comparison between Volumetric Modulated arc Therapy based Coplanar and Noncoplanar Planning for Stereotactic Body Radiation Therapy of Liver

The study aims to investigate potential dosimetric benefits between non-coplanar and coplanar beam arrangements of Volumetric-Modulated Arc Therapy (VMAT) plans for liver stereotactic body radiotherapy (SBRT). Thirteen patients who had undergone liver SBRT treatment in our department were chosen retrospectively for the study. Two sets of SBRT-VMAT plans namely, non-coplanar (NC-VMAT) and Coplanar (C-VMAT) were generated in Monaco(v5.11) planning system for Elekta Versa HD Linac using unflatten 6MV photon. The NC-VMAT plans were created by two/three non-coplanar partial arcs with couch rotation of ±150 and had an arc span of 1300 to 1600 whereas the C-VMAT plans consisted of a full arc. Both plans were compared by statistically analyzing various dosimetric and technical parameters. There is no statistically significant difference observed between the C-VMAT and NC-VMAT plans for planning target volume (PTV) coverage. However, the spine dose (D1cc) was much less in the NC-VMAT plan compared to the C-VMAT plan, with mean values of 6.127 ± 3.08Gy and 9.058 ± 4.76Gy, respectively (p-value=0.002). The low dose spillage to the healthy tissue was compared by the volume receiving 5Gy (V5Gy) and 10Gy (V10Gy). V5Gy of the NC-VMAT plan was 2399.23±1870.76cc while that of C-VMAT plans was 2835.36±1930.20cc with the p-value <0.001. Moreover, the monitor units(MU) were less with NC-VMAT than with C-VMAT SBRT plans (p=0.015). The plan quality of NC-VMAT plans was favorable compared to C-VMAT plans for liver SBRT especially in reducing spine dose, low dose spillage to healthy tissue, and MU.

Artificial Intelligence-Based Radiotherapy Contouring and Planning to Improve Global Access to Cancer Care.

Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world. The RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale. For cervical cancer, RPA plans using bony landmarks were scored as usable as-is in 81% (with minor edits 93%); using soft tissue contours, plans were scored as usable as-is in 79% (with minor edits 96%). For postmastectomy breast cancer, RPA plans were scored as usable as-is in 44% (with minor edits 91%). For whole-brain treatment, RPA plans were scored as usable as-is in 67% (with minor edits 99%). For head/neck cancer, the normal tissue autocontours were acceptable as-is in 89% (with minor edits 97%). The clinical target volumes (CTVs) were acceptable as-is in 40% (with minor edits 93%). The volumetric-modulated arc therapy (VMAT) plans were acceptable as-is in 87% (with minor edits 96%). For cervical cancer, the normal tissue autocontours were acceptable as-is in 92% (with minor edits 99%). The CTVs for cervical cancer were scored as acceptable as-is in 83% (with minor edits 92%). The VMAT plans for cervical cancer were acceptable as-is in 99% (with minor edits 100%). The RPA, a web-based tool designed to improve access to high-quality RT in low-resource settings, has high rates of clinical acceptability by practicing clinicians around the world. It has significant potential for successful implementation in low-resource clinics.

Teleassistance Telerehabilitation Services for urgent mental health needs of people with Intellectual and Developmental disabilities

Abstract Persons with intellectual disability (PwID) and/or and autism spectrum disorder with high support needs (ASD-HSN) have resulted to be among the most vulnerable populations to COVID-19 and distress factors associated to the measures for containing its spread. Many health, rehabilitation, and assistance needs were managed through the use of telemedicine, specifically teleassistance (TA) and telerehabilitation (TR), with regard to the prevention and treatment of the epidemic illness as well as the continuity of care required for the condition of developmental disability and co-occurring physical or mental disorders. TA and TR can function either directly or indirectly with the PwID/ASD; in the latter case, a family member, a regular caregiver, or a technician provides local mediation. This paper examines the most common TA and TR activities, along with their requirements, applications, and goals. All of these activities should be in line with the overarching goal of each customized therapy and rehabilitation plan, which is to enhance and support the quality of life for people with intellectual and developmental disabilities. Studies on TA and TR efficacy for PwID/ASD are limited, especially concerning adulthood. The scant research that is currently available demonstrates efficacy in maintaining or marginally enhancing cognitive, adaptive, and vocational skills. In addition to managing both routine and unusual activities as well as critical episodes, family members and other caregivers reported feeling more empowered about their educational and interpersonal abilities with the PwID/ASD. The primary benefits over traditional in-person services have been found to be greater accessibility and availability as well as a reduction in both physical and psychological distance. The primary limits include the absence of all elements of the therapeutic alliance pertaining to face-to-face communication, possible poor ability to use technology, accessibility of the technology itself, concerns regarding privacy, and variables that divert attention connected to the household setting. Even while telemedicine has proven to be feasible and beneficial thus far, it is doubtful that traditional techniques will be able to be replaced, at least not anytime soon. Telemedicine could, nonetheless, serve as a useful addition, integration, or short-term substitute. Future studies should provide light on the indications, contextual deployment, efficacy evaluation, and operational stability over time of certain TA and TR activities in addition to the use of artificial intelligence, machine learning, and interactive avatars.Disclosure of InterestNone Declared

Role of impulse oscillometry together with diffusing capacity of the lungs for carbon monoxide and high-resolution computed tomography for the chest in early diagnosis of interstitial lung disease in patients with connective tissue diseases

Abstract Background Connective tissue diseases (CTDs) are systemic autoimmune disorders characterized by repeated lung involvement. Interstitial lung disease (ILD) can arise from nearly any CTD, imposing a significant burden on patients and strongly affecting their prognosis. Addressing the gaps in early diagnosis, monitoring, and treatment of these patients requires a comprehensive and multidisciplinary approach for optimal management. Aim To find the best modality for early diagnosis of ILD in patients with connective tissue disorders through the use of diffusing capacity of the lungs for carbon monoxide (DLCO), impulse oscillometry (IOS) and high-resolution computed tomography (HRCT) chest. Patients and methods This study was cross-sectional, analytical, and observational was conducted on 60 patients who were diagnosed with CTD, during the period from March 2022 to March 2023, who were admitted to Chest and Rheumatology Department or outpatient clinics visitors, to Ain Shams University Hospitals. Results The sensitivity of DLCO, HRCT, and IOS in detecting interstitial affection in CTD patients was 90, 81.5, and 72.2%, respectively. There is high statistical significance between DLCO and both CT chest and IOS in detecting ILD in CTD patients. There is a highly significant correlation between DLCO with Spirometric parameters (forced vital capacity, forced expiratory volume 1 s) and between DLCO with IOS parameters (actual ×5). Conclusion ILD should always be considered in patients with CTD. Diagnosis of CTD-ILD is challenging so early diagnosis of ILD using DLCO, HRCT chest or by using IOS is important as it could affect therapy plans.

Robustness analysis of dynamic trajectory radiotherapy and volumetric modulated arc therapy plans for head and neck cancer

Background and purposeDynamic trajectory radiotherapy (DTRT) has been shown to improve healthy tissue sparing compared to volumetric arc therapy (VMAT). This study aimed to assess and compare the robustness of DTRT and VMAT treatment-plans for head and neck (H&N) cancer to patient-setup (PS) and machine-positioning uncertainties. Materials and methodsThe robustness of DTRT and VMAT plans previously created for 46 H&N cases, prescribed 50–70 Gy to 95 % of the planning-target-volume, was assessed. For this purpose, dose distributions were recalculated using Monte Carlo, including uncertainties in PS (translation and rotation) and machine-positioning (gantry-, table-, collimator-rotation and multi-leaf collimator (MLC)). Plan robustness was evaluated by the uncertainties’ impact on normal tissue complication probabilities (NTCP) for xerostomia and dysphagia and on dose-volume endpoints. Differences between DTRT and VMAT plan robustness were compared using Wilcoxon matched-pair signed-rank test (α = 5 %). ResultsAverage NTCP for moderate-to-severe xerostomia and grade ≥ II dysphagia was lower for DTRT than VMAT in the nominal scenario (0.5 %, p = 0.01; 2.1 %, p < 0.01) and for all investigated uncertainties, except MLC positioning, where the difference was not significant. Average differences compared to the nominal scenario were ≤ 3.5 Gy for rotational PS (≤ 3°) and machine-positioning (≤ 2°) uncertainties, <7 Gy for translational PS uncertainties (≤ 5 mm) and < 20 Gy for MLC-positioning uncertainties (≤ 5 mm). ConclusionsDTRT and VMAT plan robustness to the investigated uncertainties depended on uncertainty direction and location of the structure-of-interest to the target. NTCP remained on average lower for DTRT than VMAT even when considering uncertainties.

Enhancing Brain Tumor Diagnosis: A Synergistic Approach with Support Vector Machines and Decision Trees for Improved Detection and Segmentation

Abstract: Brain tumor identification and segmentation are critical components of modern medical imaging, facilitating timely diagnoses and effective therapy planning. This paper introduces an innovative methodology that harmoniously integrates Support Vector Machines (SVM) and Decision Tree methods. SVM adeptly classifies brain images into tumor and nonneoplastic regions, harnessing its proficiency with complex datasets. Decision Tree methods complement this process, providing transparent segmentation that accurately delineates intricate tumor boundaries. The synergy between SVM and Decision Tree methods establishes a robust framework for brain tumor identification. This novel approach holds promise for enhanced diagnosis speed, particularly valuable in time-sensitive medical scenarios. Emphasizing potential advancements in patient care outcomes, the methodology enables tailored treatment plans with greater precision. Positioned at the core of brain image analysis, this novel methodology signifies a substantial step forward in healthcare practices, fostering personalized approaches to brain tumor diagnosis and treatment.

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival

We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.

Enhancing Neurorehabilitation through Closed-Loop Control of Robotic Exoskeletons and Brain-Computer Interfaces

Neurorehabilitation is an important part of getting better for people who have nerve illnesses or accidents. Brain-computer interfaces (BCIs) and robotic exoskeletons have shown promise in better recovery results by allowing focused therapy and making neurons more flexible. This paper gives an outline of the current study on closed-loop control systems that combine robotic exoskeletons and brain-computer interfaces (BCIs) for neurorehabilitation. It also talks about the pros and cons of these systems. Closed-loop control systems try to make two-way communication possible between the user's brain activity (measured by BCIs) and the robotic suit. This way, treatments can be changed in real time based on the user's neurological signs. This method makes it possible for more personalized and flexible therapy plans, which can help people recover their movement skills and become more useful. When BCIs are combined with artificial exoskeletons, they offer many benefits, such as exact control over movement parameters, increased involvement and motivation through immersive feedback, and the chance to induce learning by coordinating brain activity and physical output. To make these systems work better, though, problems like signal processing delay, calibration issues, and the need for user training must be fixed. Recent research has shown that closed-loop control systems can be used and might be helpful in a number of neurorehabilitation situations, such as helping people who have had a stroke or spinal cord injury get their movement skills back and helping people with neurological conditions regain their independence. In the future, researchers should work on improving these systems' algorithms and hardware, running large-scale clinical studies to show that they work, and finding new ways to improve neurorehabilitation results by combining modern technology.

Assessing the adequacy of a 5-mm planning target volume margin for 4D-CT scan-based image-guided radiotherapy for locally advanced carcinoma of the lung

In developed nations, 4D-computed tomography (4D-CT)-based image-guided radiotherapy (IGRT) has become the standard for treating lung carcinoma patients, with the primary goal of achieving disease cure. However, its usage in India remains limited. Here, we compared target volume delineation for radical radiation planning in patients with locally advanced lung carcinoma using helical free-breathing CT (FBCT) and 4D-CT. In addition, we assessed the adequacy of a 5-mm planning target volume (PTV) margin with 4D-CT planning. Fifty patients with locally advanced lung cancer were enrolled in the study. Each patient underwent contouring based on 4D-CT to generate an internal target volume, and a 5-mm PTV margin (PTV_4D) was added for radical radiation. Subsequently, each patient underwent two intensity-modulated radiation therapy (IMRT) plans with comparable planning and optimization parameters. One plan was based on the FBCT-based volume (PTV_3D), while the other was based on the 4D-CT-based volume (PTV_4D). PTV, organ at risk (OAR) dose, and PTV coverage by 95% of the prescribed dose (PTVD 95_3D vs. PTVD 95_4D) were compared between the two schemes. Results revealed that 4D-CT-based planning reduced PTV (mean PTV volume: 539 cc vs. 782 cc) and lowered OAR doses (mean lung dose: 13 Gy vs. 15 Gy; mean esophagus dose: 18.5 Gy vs. 21.15 Gy; mean spinal cord max dose: 35.59 Gy vs. 37.39 Gy). At 3 months after treatment imaging, 40% of the patients showed a complete response, 48% showed a partial response, 4% showed stable disease, and 8% showed progressive disease. In conclusion, 4D-CT-based radiation planning for locally advanced lung carcinoma with a reduced PTV margin of 5 mm can dramatically decrease the PTV and OAR doses without sacrificing PTV coverage compared to FBCT-based planning. However, daily online image guidance or at least a well-defined offline image guidance protocol is recommended when employing such a small PTV margin.

Age Encoded Adversarial Learning for Pediatric CT Segmentation.

Organ segmentation from CT images is critical in the early diagnosis of diseases, progress monitoring, pre-operative planning, radiation therapy planning, and CT dose estimation. However, data limitation remains one of the main challenges in medical image segmentation tasks. This challenge is particularly huge in pediatric CT segmentation due to children's heightened sensitivity to radiation. In order to address this issue, we propose a novel segmentation framework with a built-in auxiliary classifier generative adversarial network (ACGAN) that conditions age, simultaneously generating additional features during training. The proposed conditional feature generation segmentation network (CFG-SegNet) was trained on a single loss function and used 2.5D segmentation batches. Our experiment was performed on a dataset with 359 subjects (180 male and 179 female) aged from 5 days to 16 years and a mean age of 7 years. CFG-SegNet achieved an average segmentation accuracy of 0.681 dice similarity coefficient (DSC) on the prostate, 0.619 DSC on the uterus, 0.912 DSC on the liver, and 0.832 DSC on the heart with four-fold cross-validation. We compared the segmentation accuracy of our proposed method with previously published U-Net results, and our network improved the segmentation accuracy by 2.7%, 2.6%, 2.8%, and 3.4% for the prostate, uterus, liver, and heart, respectively. The results indicate that our high-performing segmentation framework can more precisely segment organs when limited training images are available.

Chronometric TMS-fMRI of personalized left dorsolateral prefrontal target reveals state-dependency of subgenual anterior cingulate cortex effects

Transcranial magnetic stimulation (TMS) applied to a left dorsolateral prefrontal cortex (DLPFC) area with a specific connectivity profile to the subgenual anterior cingulate cortex (sgACC) has emerged as a highly effective non-invasive treatment option for depression. However, antidepressant outcomes demonstrate significant variability among therapy plans and individuals. One overlooked contributing factor is the individual brain state at the time of treatment. In this study we used interleaved TMS-fMRI to investigate the influence of brain state on acute TMS effects, both locally and remotely. TMS was performed during rest and during different phases of cognitive task processing. Twenty healthy participants were included in this study. In the first session, imaging data for TMS targeting were acquired, allowing for identification of individualized targets in the left DLPFC based on highest anti-correlation with the sgACC. The second session involved chronometric interleaved TMS-fMRI measurements, with 10 Hz triplets of TMS administered during rest and at distinct timings during an N-back task. Consistent with prior findings, interleaved TMS-fMRI revealed significant BOLD activation changes in the targeted network. The precise timing of TMS relative to the cognitive states during the task demonstrated distinct BOLD response in clinically relevant brain regions, including the sgACC. Employing a standardized timing approach for TMS using a task revealed more consistent modulation of the sgACC at the group level compared to stimulation during rest. In conclusion, our findings strongly suggest that acute local and remote effects of TMS are influenced by brain state during stimulation. This study establishes a basis for considering brain state as a significant factor in designing treatment protocols, possibly improving TMS treatment outcomes.

Anxiety and Depressive Disorders in Adolescents. Contemporary Psycho-spiritual and Therapeutic Values

This work is a continuation of a study on `Depressive and anxiety disorders in adolescents. A psycho-spiritual approach and statistical contextualization` and highlights from a theoretical perspective the interdependent relationship between the spiritual and mental health, which should be seriously contemplated when creating a therapy plan for adolescents with depressive and anxiety disorders. It also deals with the connection between health and the temptations of the current world, which theology and spirituality distinguish in the multitude of emotional and psychological disorders. Additionally, this study showcases the psychotherapies in a synthetic manner: cognitive-behavioral, existential, logotherapy and interpersonal psychotherapy and highlights the inherent value of their interconnection with religious acts such as fasting, prayer, confession, which support the medical-psychological therapeutics, providing adolescents with discipline in the process of healing these contemporary pathologies.

Abstract 6974: Spatial exosome analysis reveals the location heterogeneity of exosomal miRNAs in ovarian cancer patients

Abstract Extracellular vesicles (EVs), including exosomes, are recognized as promising functional tools involved in cancer progression. Although evidence of the functions of EV in cancer biology has been accumulating, optimizing EV isolation is still a major challenge. In ovarian cancer, peritoneal dissemination is a crucial prognostic factor due to the lack of effective treatment, and EVs in malignant ascites play a key role for progression. In this study, we invented cellulose nanofiber (CNF) sheets which enable to capture EVs from approximately 10 μL of biofluids and enabled the analysis of the bioactive molecules included in the EVs (Nature Communications 2023). By attaching CNF sheets to moistened organs, the EVs in trace amounts of ascites were collected, which was sufficient to perform small RNA sequence analyses. In the ovarian cancer mouse model, CNF sheets enabled the detection of cancer-associated miRNAs from the very early phase when the mice did not have apparent ascites, and the EVs from different locations, such as pelvic walls or liver surfaces, had unique miRNA profiles. To confirm the utility of the CNF sheets in cancer patients, we directly collected the EVs on the organ surfaces by the EV attachment method during surgery under appropriate ethical institutional approval with individual consent. EVs were collected from the pelvic peritoneum, omentum, liver surface, or tumor surface, and the miRNA profiling demonstrated each location formed unique clusters. Notably, several tumor-suppressive miRNAs have been identified in liver surface EVs, such as miR-122-3p, and this is consistent with actual ovarian cancer cell progression, which tends to metastasize to the diaphragm rather than to the liver surface. In addition, the trajectory analysis revealed that the pattern of connection in each site was different between patients with localized and advanced disease. We identified ten miRNAs were high in tumors and in EVs from tumor rupture sites, and the level of each miRNA decreased with distance from the primary tumors. Among ten miRNAs, hsa-miR-200b-3p and hsa-miR-429 were confirmed as highly expressed in tumor tissues compared to adjacent normal tissues or benign tumors, and three miRNAs in serum, urine and saliva decreased post-surgery. In summary, spatial CNF sheet analyses in patient bodies identified location-based heterogeneity in EV-miRNA profiles, and the profiles reflected disease conditions. This new method could provide unveiled biological aspects of EVs, and suggest a clinical strategy contributing to cancer diagnosis, staging evaluation, and therapy planning. Citation Format: Akira Yokoi, Kosuke Yoshida, Yusuke Yamamoto, Takao Yasui, Hiroaki Kajiyama. Spatial exosome analysis reveals the location heterogeneity of exosomal miRNAs in ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6974.

Clinical physiology: the crucial role of MRI in evaluation of peripheral artery disease.

Peripheral artery disease (PAD) is a common vascular disease that primarily affects the lower limbs and is defined by the constriction or blockage of peripheral arteries and may involve microvascular dysfunction and tissue injury. Patients with diabetes have more prominent disease of microcirculation and develop peripheral neuropathy, autonomic dysfunction, and medial vascular calcification. Early and accurate diagnosis of PAD and disease characterization are essential for personalized management and therapy planning. Magnetic resonance imaging (MRI) provides excellent soft tissue contrast and multiplanar imaging capabilities and is useful as a noninvasive imaging tool in the comprehensive physiological assessment of PAD. This review provides an overview of the current state of the art of MRI in the evaluation and characterization of PAD, including an analysis of the many applicable MR imaging techniques, describing the advantages and disadvantages of each approach. We also present recent developments, future clinical applications, and future MRI directions in assessing PAD. The development of new MR imaging technologies and applications in preclinical models with translation to clinical research holds considerable potential for improving the understanding of the pathophysiology of PAD and clinical applications for improving diagnostic precision, risk stratification, and treatment outcomes in patients with PAD.

Abstract 510: Flow cytometry evaluation of cell cycle arrest in A549 human non-small cell lung cancer cells and tumors following treatment with cell cycle inhibitors: A multifaceted approach to targeting cancer

Abstract The contemporary landscape of cancer treatment has witnessed significant progress with FDA-approved targeted drugs. The FDA's Project Optimus has underscored the growing need for innovative pharmacodynamic endpoints to determine the optimal biological dose in clinical development. Flow cytometry, a potent analytical tool in clinical and preclinical labs, now plays a leading role in cancer research, enabling the evaluation of new drug effects on cell cycle regulation and consideration of rational drug combinations with approved drugs. At TD2, we strive to enhance the translatability of in vitro induced cell cycle arrest studies to in vivo biomarker proof of concept and efficacy. We employ a comprehensive approach, utilizing flow cytometry to assess cell cycle dynamics in cultured cells and in vivo tumor models after treatment with approved and novel drugs. This abstract focuses on the translational relevance of combined in vitro and in vivo testing of well-known drugs that disrupt the cell cycle, laying the foundation for optimized treatment strategies and potentially personalized cancer therapies. Human A549 non-small cell lung carcinoma cells were treated with either thymidine (2.0mM) or the microtubule-depolymerizing drug nocodazole (100ng/ml) for 18 hours, then examined by flow cytometry. Thymidine induced a greater than 85% S-phase arrest, while nocodazole induced a greater than 88% G2/M-phase arrest. A549 cells (5 × 106 cells/mouse) were subcutaneously implanted in SCID mice, followed by treatment with an FDA-approved cell cycle inhibitor, Palbociclib, or cisplatin chemotherapy. Palbociclib, a CDK4/6 inhibitor, and low-dose cisplatin treatment resulted in an increased accumulation of cells in the G0/G1 phase, greater than 80% for each. Both treatments exhibited promising anti-cancer activity, with tumor growth inhibition (TGI) of 69% and 87%, respectively. Our findings highlight flow cytometry's multifaceted utility in assessing cell cycle arrest, providing a comprehensive view of agent effects on cancer cells in culture and within the complex in vivo tumor microenvironment. Determining the impact of any new drug on specific cell cycle checkpoints could allow for a more strategic plan for combination therapy. Integrating flow cytometry could enable early biomarker monitoring of tumor cell cycle changes, offering insights into the therapeutic potential of new agents alone or in combination. This multidimensional evaluation contributes to understanding cancer biology and has the potential to guide the development of novel therapeutic strategies, optimize treatment regimens to identify optimal biological doses, and improve patient outcomes in the era of precision medicine. Citation Format: Erin E. Trachet, Emily Cluff, Ana Lemos de Matos, Damaris Diaz, Chelsea Holmquist, Paul Gonzales. Flow cytometry evaluation of cell cycle arrest in A549 human non-small cell lung cancer cells and tumors following treatment with cell cycle inhibitors: A multifaceted approach to targeting cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 510.

Minimum imaging dose for deep learning-based pelvic synthetic computed tomography generation from cone beam images

Background and purposeDaily cone-beam computed tomography (CBCT) in image-guided radiotherapy administers radiation exposure and subjects patients to secondary cancer risk. Reducing imaging dose remains challenging as image quality deteriorates. We investigated three imaging dose levels by reducing projections and correcting images using two deep learning algorithms, aiming at identifying the lowest achievable imaging dose. Materials and methodsCBCTs were reconstructed with 100%, 25%, 15% and 10% projections. Models were trained (30), validated (3) and tested (8) with prostate cancer patient datasets. We optimized and compared the performance of 1) a cycle generative adversarial network (cycleGAN) with residual connection and 2) a contrastive unpaired translation network (CUT) to generate synthetic computed tomography (sCT) from reduced imaging dose CBCTs. Volumetric modulated arc therapy plans were optimized on a reference intensity-corrected full dose CBCTcor and recalculated on sCTs. Hounsfield unit (HU) and positioning accuracy were evaluated. Bladder and rectum were manually delineated to determine anatomical fidelity. ResultsAll sCTs achieved average mean absolute mean absolute error/structural similarity index measure/peak signal-to-noise ratio of ⩽59HU/⩾0.94/⩾33 dB. All dose-volume histogram parameter differences were within 2 Gy or 2%. Positioning differences were ⩽0.30 mm or 0.30°. cycleGAN with Dice similarity coefficients (DSC) for bladder/rectum of ⩾0.85/⩾0.81 performed better than CUT (⩾0.83/⩾0.76). A significantly lower DSC accuracy was observed for 15% and 10% sCTs. cycleGAN performed better than CUT for contouring, however both yielded comparable outcomes in other evaluations. ConclusionsCTs based on different CBCT doses using cycleGAN and CUT were investigated. Based on segmentation accuracy, 25% is the minimum imaging dose.