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Background: Escalation of prescribed dose in prostate cancer (PCa) radiotherapy enables improvement in tumor control at the expense of increased toxicity. Opportunities for reduction of treatment toxicity may emerge if more efficient dose escalation can be achieved by redistributing the prescribed dose distribution according to the known heterogeneous, spatially‐varying characteristics of the disease. Purpose: To examine the potential benefits, limitations and characteristics of heterogeneous boost dose redistribution in PCa radiotherapy based on patient‐specific and population‐based spatial maps of tumor biological features. Method: High‐resolution prostate histology images, from a cohort of 63 patients, annotated with tumor location and grade, provided patient‐specific "maps" and a population‐based "atlas" of cell density and tumor probability. Dose prescriptions were derived for each patient based on a heterogeneous redistribution of the boost dose to the intraprostatic lesions, with the prescription maximizing patient tumor control probability (TCP). The impact on TCP was assessed under scenarios where the distribution of population‐based biological data was ignored, partially included, or fully included in prescription generation. Heterogeneous dose prescriptions were generated for three combinations of maps and atlas, and for conventional fractionation (CF), extreme hypo‐fractionation (EH), moderate hypo‐fractionation (MH), and whole Pelvic RT + SBRT Boost (WPRT + SBRT). The predicted efficacy of the heterogeneous prescriptions was compared with equivalent homogeneous dose prescriptions. Results: TCPs for heterogeneous dose prescriptions were generally higher than those for homogeneous dose prescriptions. TCP escalation by heterogeneous dose prescription was the largest for CF. When only using population‐based atlas data, the generated heterogeneous dose prescriptions of 55 to 58 patients (out of 63) had a higher TCP than for the corresponding homogeneous dose prescriptions. The TCPs of the heterogeneous dose prescriptions generated with the population‐based atlas and tumor probability maps did not differ significantly from those using patient‐specific biological information. The generated heterogeneous dose prescriptions achieved significantly higher TCP than homogeneous dose prescriptions in the posterior section of the prostate. Conclusion: Heterogeneous dose prescriptions generated via biologically‐optimized dose redistribution can produce higher TCP than the homogeneous dose prescriptions for the majority of the patients in the studied cohort. For scenarios where patient‐specific biological information was unavailable or partially available, the generated heterogeneous dose prescriptions can still achieve TCP improvement relative to homogeneous dose prescriptions. [ABSTRACT FROM AUTHOR]

Congenital myasthenic syndrome (CMS) is a group of 32 disorders involving genetic dysfunction at the neuromuscular junction resulting in skeletal muscle weakness that worsens with physical activity. Precise diagnosis and molecular subtype identification are critical for treatment as medication for one subtype may exacerbate disease in another (Engel et al., Lancet Neurol 14: 420 [2015]; Finsterer, Orphanet J Rare Dis 14: 57 [2019]; Prior and Ghosh, J Child Neurol 36: 610 [2021]). The SNAP25-related CMS subtype (congenital myasthenic syndrome 18, CMS18; MIM #616330) is a rare disorder characterized by muscle fatigability, delayed psychomotor development, and ataxia. Herein, we performed rapid whole-genome sequencing (rWGS) on a critically ill newborn leading to the discovery of an unreported pathogenic de novo SNAP25 c.529C > T; p.Gln177Ter variant. In this report, we present a novel case of CMS18 with complex neonatal consequence. This discovery offers unique insight into the extent of phenotypic severity in CMS18, expands the reported SNAP25 variant phenotype, and paves a foundation for personalized management for CMS18. [ABSTRACT FROM AUTHOR]

Background: Lymphatic drainage from the arm may be altered after axillary lymph node dissection (ALND). Understanding these alterations is important as they may change standard surgical and radiation treatment in recurrent breast cancer or upper extremity skin cancers, including melanoma., Methods: Utilizing a single-institution planar and single photon emission computed tomography/computed tomography lymphoscintigraphy database, we identified patients with a diagnosis of upper extremity cutaneous melanoma from 2008 to 2023 who previously underwent ALND for cancer treatment and did not develop upper extremity cancer-related lymphedema. ALND patients were matched to control patients presenting with cutaneous melanomas at the same anatomic sites. Sentinel lymph nodes (SLNs) were compared between both groups., Results: Of 3628 upper extremity melanoma cutaneous patients, 934 met inclusion criteria, including 22 ALND and 912 control patients. Level I axillary SLN drainage was observed in 98% of controls and 27% of ALND patients (p < 0.001). Level II axillary SLN drainage was observed in 3% of controls and 27% of ALND patients (p < 0.001). Level III axillary SLN drainage was observed in 1% of controls and 32% of ALND patients (p < 0.001). Epitrochlear SLN drainage was observed in 9% of controls and 32% of ALND patients, respectively (p < 0.046). Brachial SLN drainage was observed in 4% of controls and 23% of ALND patients (p < 0.001)., Conclusions: Distinct changes in functional lymphatic drainage were seen between the arms of patients who previously underwent ALND versus control patients. Levels II and III axillary, epitrochlear, and brachial nodes are possible sites of metastatic disease that should be considered in patients with a prior ALND., (© 2024 Wiley Periodicals LLC.)

Background: Variations of hand and forearm lymphatic drainage to upper-arm lymphatic pathways may impact the route of melanoma metastasis. This study compared rates of lymphatic drainage to epitrochlear nodes between anatomic divisions of the hand and forearm to determine whether the anatomic distribution of hand and forearm melanomas affects the likelihood of drainage to epitrochlear lymph nodes., Methods: Using a single-institution lymphoscintigraphy database, we identified all patients with cutaneous melanoma on the hand and forearm. A body-map two-dimensional coordinate system was used to classify cutaneous melanoma sites between radial-ulnar and dorsal-volar divisions. Sentinel lymph nodes (SLNs) visualized on lymphoscintigraphy were recorded. Proportions of patients with epitrochlear SLNs were compared between anatomic divisions using χ 2 analysis., Results: Of 3628 upper extremity cutaneous melanoma patients who underwent lymphatic mapping with lymphoscintigraphy, 1400 met inclusion criteria. Twenty-one percent of patients demonstrated epitrochlear SLNs. Epitrochlear SLNs were observed in 27% of dorsal forearm melanomas and 15% of volar forearm melanomas (p < 0.001). Epitrochlear SLNs were observed in 31% of ulnar forearm melanomas and 17% of radial forearm melanomas (p < 0.001)., Conclusions: Higher proportions of dorsal and ulnar forearm melanomas have epitrochlear SLNs. Metastasis to epitrochlear SLNs may be more likely from melanomas in these respective forearm regions., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Purpose: Radiomic features from MRI and PET are an emerging tool with potential to improve prostate cancer outcomes. However, feature robustness due to image segmentation variations is currently unknown. Therefore, this study aimed to evaluate the robustness of radiomic features with segmentation variations and their impact on predicting biochemical recurrence (BCR)., Materials and Methods: Multi-scanner, pre-radiation therapy imaging from 142 patients with localised prostate cancer was used. Imaging included T2-weighted (T2), apparent diffusion coefficient (ADC) MRI, and prostate-specific membrane antigen (PSMA)-PET. The prostate gland and intraprostatic tumours were manually and automatically segmented, and differences were quantified using Dice Coefficient (DC). Radiomic features including shape, first-order, and texture features were extracted for each segmentation from original and filtered images. Intraclass Correlation Coefficient (ICC) and Mean Absolute Percentage Difference (MAPD) were used to assess feature robustness. Random forest (RF) models were developed for each segmentation using robust features to predict BCR., Results: Prostate gland segmentations were more consistent (mean DC = 0.78) than tumour segmentations (mean DC = 0.46). 112 (3.6 %) radiomic features demonstrated 'excellent' robustness (ICC > 0.9 and MAPD < 1 %), and 480 features (15.4 %) demonstrated 'good' robustness (ICC > 0.75 and MAPD < 5 %). PET imaging provided more features with excellent robustness than T2 and ADC. RF models showed strong predictive power for BCR with a mean area under the receiver-operator-characteristics curve (AUC) of 0.89 (range 0.85-0.93)., Conclusion: When using radiomic features for predictive modelling, segmentation variability should be considered. To develop BCR predictive models, radiomic features from the entire prostate gland are preferable over tumour segmentation-based features., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Lymphoedema is a debilitating disease that results in chronic swelling of a body region due to a dysfunctional lymphatic system. Since a cure is yet to be identified for this disease, management is currently the best option for preventing disease progression and improving patient outcomes. Fluorescence lymphography is a popular approach for mapping the lymphatic vessels to provide information about the underlying lymphatic dysfunction. However, current clinical fluorescence lymphography tools do not enable the creation of comprehensive 3D maps of lymphatics throughout affected limbs. This work presents the development toward multi-camera 3D reconstruction with fluorescence imaging to overcome the current limitations in clinical tools. Pilot studies have been performed that identify suitable instrumentation for this multi-camera approach and techniques for creating a 3D fluorescence lymphography device are discussed.Clinical Relevance- This paper presents development toward new low-cost and portable clinical tools for lymphoedema diagnosis and to facilitate personalised treatment and self-management of this disease.