Perineural Invasion of Cranial Nerves in Cutaneous Squamous Cell Carcinoma: Unraveling Its Complexities, Diagnostic Challenges, and Multifaceted Treatment Approaches.

Cutaneous squamous cell carcinoma is the second most common neoplasm among non-melanoma skin cancers. When associated with perineural invasion of the cranial nerves, with clinical features often observed in trigeminal and facial nerves due to their cutaneous extension, it may lead to a worse prognosis. This paper introduces a rare case of an 81-year-old male, with a history of a moderately differentiated invasive carcinoma of the left frontal region with perineural invasion on the left trigeminal cranial nerve. The case underscores the aggressive nature of the intraneural infiltration by squamous cell carcinoma and the challenges in managing such advanced malignancies.

Erratum: Single-center developing country analysis of radium-223 therapy in prostate cancer-preliminary results.

[This corrects the article on p. 352 in vol. 11, PMID: 34754606.].

Evaluation design of the patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard (InAdvance): a randomised controlled trial.

BACKGROUND: Palliative care aims to contribute to pain relief, improvement with regard to symptoms and enhancement of health-related quality of life (HRQoL) of patients with chronic conditions. Most of the palliative care protocols, programmes and units are predominantly focused on patients with cancer and their specific needs. Patients with non-cancer chronic conditions may also have significantly impaired HRQoL and poor survival, but do not yet receive appropriate and holistic care. The traditional focus of palliative care has been at the end-of-life stages instead of the relatively early phases of serious chronic conditions. The 'Patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard' (InAdvance) project implements and evaluates early palliative care in the daily clinical routine addressing patients with complex chronic conditions in the evolution towards advanced stages. The objective of the current study is to evaluate the acceptability, feasibility, effectiveness and cost-effectiveness of this novel model of palliative care in the relatively early phases in patients with chronic conditions. METHODS: In this study, a single blind randomised controlled trial design will be employed. A total of 320 participants (80 in each study site and 4 sites in total) will be randomised on a 1:1 basis to the Palliative Care Needs Assessment (PCNA) arm or the Care-as-Usual arm. This study includes a formative evaluation approach as well as a cost-effectiveness analysis with a within-trial horizon. Study outcomes will be assessed at baseline, 6 weeks, 6 months, 12 months and 18 months after the implementation of the interventions. Study outcomes include HRQoL, intensity of symptoms, functional status, emotional distress, caregiving burden, perceived quality of care, adherence to treatment, feasibility, acceptability, and appropriateness of the intervention, intervention costs, other healthcare costs and informal care costs. DISCUSSION: The InAdvance project will evaluate the effect of the implementation of the PCNA intervention on the target population in terms of effectiveness and cost-effectiveness in four European settings. The evidence of the project will provide step-wise guidance to contribute an increased evidence base for policy recommendations and clinical guidelines, in an effort to augment the supportive ecosystem for palliative care. TRIAL REGISTRATION: ISRCTN, ISRCTN24825698 . Registered 17/12/2020.

Validation of Convolutional Neural Networks for Fast Determination of Whole-Body Metabolic Tumor Burden in Pediatric Lymphoma.

18F-FDG PET/CT quantification of whole-body tumor burden in lymphoma is not routinely performed because of the lack of fast methods. Although the semiautomatic method is fast, it is not fast enough to quantify tumor burden in daily clinical practice. Our purpose was to evaluate the performance of convolutional neural network (CNN) software in localizing neoplastic lesions in whole-body 18F-FDG PET/CT images of pediatric lymphoma patients. Methods: The retrospective image dataset, derived from the data pool of the International Atomic Energy Agency (coordinated research project E12017), included 102 baseline staging 18F-FDG PET/CT studies of pediatric lymphoma patients (mean age, 11 y). The images were quantified to determine the whole-body tumor burden (whole-body metabolic tumor volume [wbMTV] and whole-body total lesion glycolysis [wbTLG]) using semiautomatic software and CNN-based software. Both were displayed as semiautomatic wbMTV and wbTLG and as CNN wbMTV and wbTLG. The intraclass correlation coefficient (ICC) was applied to evaluate concordance between the CNN-based software and the semiautomatic software. Results: Twenty-six patients were excluded from the analysis because the software was unable to perform calculations for them. In the remaining 76 patients, CNN and semiautomatic wbMTV tumor burden metrics correlated strongly (ICC, 0.993; 95% CI, 0.989 - 0.996; P < 0.0001), as did CNN and semiautomatic wbTLG (ICC, 0.999; 95% CI, 0.998-0.999; P < 0.0001). However, the time spent calculating these metrics was significantly (<0.0001) less by CNN (mean, 19 s; range, 11-50 s) than by the semiautomatic method (mean, 21.6 min; range, 3.2-62.1 min), especially in patients with advanced disease. Conclusion: Determining whole-body tumor burden in pediatric lymphoma patients using CNN is fast and feasible in clinical practice.

Involving Older Adults During COVID-19 Restrictions in Developing an Ecosystem Supporting Active Aging: Overview of Alternative Elicitation Methods and Common Requirements From Five European Countries.

Background: Information and communication technology solutions have the potential to support active and healthy aging and improve monitoring and treatment outcomes. To make such solutions acceptable, all stakeholders must be involved in the requirements elicitation process. Due to the COVID-19 situation, alternative approaches to commonly used face-to-face methods must often be used. One aim of the current article is to share a unique experience from the Pharaon project where due to the COVID-19 outbreak alternative elicitation methods were used. In addition, an overview of common functional, quality, and emotional goals identified by six pilot sites is presented to complement the knowledge about the needs of older adults. Methods: Originally planned face-to-face co-creation seminars were impossible to carry out, and all pilot sites chose alternative requirements elicitation methods that were most suitable in their situation. The elicited requirements were presented in the form of goal models. In one summary goal model, we provide an overview of common functional, quality, and emotional goals. Results: Different elicitation methods were combined based on the digital literacy of the target group and their access to digital tools. Methods applied without digital technologies were phone interviews, reviews of literature and previous projects, while by means of digital technologies online interviews, online questionnaires, and (semi-)virtual co-creation seminars were conducted. The combination of the methods allowed to involve all planned stakeholders. Virtual and semi-virtual co-creation seminars created collaborative environment comparable to face-to-face situations, while online participation helped to save the time of the participants. The most prevalent functional goals elicited were "Monitor health," "Receive advice," "Receive information." "Easy to use/comfortable," "personalized/tailored," "automatic/smart" were identified as most prevalent quality goals. Most frequently occurring emotional goals were "involved," "empowered," and "informed." Conclusion: There are alternative methods to face-to-face co-creation seminars, which effectively involve older adults and other stakeholders in the requirements elicitation process. Despite the used elicitation method, the requirements can be easily transformed into goal models to present the results in a uniform way. The common requirements across different pilots provided a strong foundation for representing detailed requirements and input for further software development processes.

Single-center developing country analysis of radium-223 therapy in prostate cancer-preliminary results.

We reviewed the records of mCRPC patients treated with off-label use of Ra-223. Ra-223 efficiency in this non-study population was correlated to outcome measures overall survival (OS), progression-free survival (PFS), bone event-free survival, bone marrow failure (BMF), and disease-related biomarkers. There were no limits regarding the number of prior hormonal agents or chemotherapy received before or during Ra-223. Exclusion criteria consisted of baseline platelet counts below 50,000/mm3 and/or absolute neutrophil counts below 1,500/mm3. Twenty-eight patients received 130 cycles of Ra-223 between 2017 and 2018. The overall median OS was 15.6 months. However, in patients submitted to 4 or fewer cycles, the median OS was 9.1 months; in contrast, the median OS was 18.5 months in patients submitted to 5 or 6 cycles. There was a significant inverse correlation between the number of cycles and the occurrence of bone events (76.2% of the patients that completed 6 cycles did not present bone events, while 71.4% of the patients that had skeletal-related events were submitted to less than 6 cycles). 82.1% of the patients were submitted to concomitant therapies with no significant side effects. There was also a decrease in ALP and LDH levels throughout treatment. Radium-223 increased OS and decreased bone events, especially when patients were able to complete 5-6 cycles. The proper selection of patients is crucial to improve outcomes.

PSMA whole-body tumor burden in primary staging and biochemical recurrence of prostate cancer.

PURPOSE: The objective of this study was to evaluate whether 68Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients. METHODS: We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purposes or due to biochemical recurrence (BR). PSMAwbtb metrics (total volume of PSMA-avid tumor (PSMA-TV)) and total uptake of PSMA-avid lesions (PSMA-TL) were calculated semi-automatically. Spearman's rank correlations between PSMAwbtb metrics and clinical, laboratory parameters (age, time-to-BR, years of diagnosis of prostate cancer, free and total serum PSA levels, and the Gleason score) and with the highest SUVmax of a lesion (hSUVmax) were analyzed. RESULTS: Among the 257 PSMA PET/CT studies, there were 46 scans (17.9%) performed for primary staging and 211 (82.1%) for BR. PSMA-TV and PSMA-TL were calculated for the 157 positive scans (58.8%), which were 43 patients (93.5%) in the primary staging group and 114 patients (54.0%) in the BR group. In the primary staging group, we observed a significant correlation between PSMA-TL and hSUVmax (p = 0.0021). In the BR group, there was a significant direct correlation between PSMA-TL and the variables age (p = 0.0031), total serum PSA values (p = < 0.0001), free serum PSA values (p = < 0.0001), and the hSUVmax (p = < 0.0001). Similar results were obtained for PSMA-TV. CONCLUSION: PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.

Validation of a Multifocal Segmentation Method for Measuring Metabolic Tumor Volume in Hodgkin Lymphoma.

Quantification of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) can be time-consuming. We evaluated the performance of an automatic multifocal segmentation (MFS) method of quantification in patients with different stages of Hodgkin lymphoma, using the multiple VOI (MV) method as reference. Methods: This prospective bicentric study included 50 patients with Hodgkin lymphoma who underwent staging 18F-FGD PET/CT. The examinations were centrally reviewed and processed with commercial MFS software to obtain MTV and TLG using 2 fixed relative thresholds (40% and 20% of SUVmax) for each lesion. All PET/CT scans were processed using the MV and MFS methods. Interclass correlation coefficients and Bland-Altman plots were used for statistical analysis. Repeated calculations of MTV and TLG values by 2 observers with different degrees of PET/CT imaging experience were used to ascertain interobserver agreement on the MFS method. Results: The means and SDs obtained for the MTV with MV and MFS were, respectively, 736 ± 856 mL and 660 ± 699 mL for the 20% threshold and 313 ± 359 mL and 372 ± 434 mL for the 40% threshold. The time spent calculating the MTV was much shorter with the MFS method than with the MV method (median time, 11.6 min [range, 1-30 min] and 64.4 min [range, 1-240 min], respectively), especially in patients with advanced disease. Time spent was similar in patients with localized disease. There were no statistical differences between the MFS values obtained by the 2 different observers. Conclusion: MTV and TLG calculations using MFS are reproducible, generate similar results to those obtained with MV, and are much less timing-consuming. Main differences between the 2 methods were related to difficulties in avoiding overlay of VOIs in the MV technique. MV and MFS perform equally well in patients with a small number of lesions.

Proposal for a Quantitative 18F-FDG PET/CT Metabolic Parameter to Assess the Intensity of Bone Involvement in Multiple Myeloma.

Many efforts have been made to standardize the interpretation of 18F-FDG PET/CT in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of 18F-FDG PET/CT considering the extent and intensity of bone 18F-FDG uptake: Intensity of Bone Involvement (IBI). Whole body 18F-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with 18F-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement - PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00-1.35). Visual analysis categorized PET exams into three groups (negative/mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients' hemoglobin values and IBI (r = -0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting.