Improving glioma drug delivery: A multifaceted approach for glioma drug development.

Glioma is one of the most common central nervous system (CNS) cancers that can be found within the brain and the spinal cord. One of the pressing issues plaguing the development of therapeutics for glioma originates from the selective and semipermeable CNS membranes: the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). It is difficult to bypass these membranes and target the desired cancerous tissue because the purpose of the BBB and BSCB is to filter toxins and foreign material from invading CNS spaces. There are currently four varieties of Food and Drug Administration (FDA)-approved drug treatment for glioma; yet these therapies have limitations including, but not limited to, relatively low transmission through the BBB/BSCB, despite pharmacokinetic characteristics that allow them to cross the barriers. Steps must be taken to improve the development of novel and repurposed glioma treatments through the consideration of pharmacological profiles and innovative drug delivery techniques. This review addresses current FDA-approved glioma treatments' gaps, shortcomings, and challenges. We then outline how incorporating computational BBB/BSCB models and innovative drug delivery mechanisms will help motivate clinical advancements in glioma drug delivery. Ultimately, considering these attributes will improve the process of novel and repurposed drug development in glioma and the efficacy of glioma treatment.

The State of Machine Learning in Outcomes Prediction of Transsphenoidal Surgery: A Systematic Review.

The purpose of this analysis is to assess the use of machine learning (ML) algorithms in the prediction of postoperative outcomes, including complications, recurrence, and death in transsphenoidal surgery. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed all papers that used at least one ML algorithm to predict outcomes after transsphenoidal surgery. We searched Scopus, PubMed, and Web of Science databases for studies published prior to May 12, 2021. We identified 13 studies enrolling 5,048 patients. We extracted the general characteristics of each study; the sensitivity, specificity, area under the curve (AUC) of the ML models developed as well as the features identified as important by the ML models. We identified 12 studies with 5,048 patients that included ML algorithms for adenomas, three with 1807 patients specifically for acromegaly, and five with 2105 patients specifically for Cushing's disease. Nearly all were single-institution studies. The studies used a heterogeneous mix of ML algorithms and features to build predictive models. All papers reported an AUC greater than 0.7, which indicates clinical utility. ML algorithms have the potential to predict postoperative outcomes of transsphenoidal surgery and can improve patient care. Ensemble algorithms and neural networks were often top performers when compared with other ML algorithms. Biochemical and preoperative features were most likely to be selected as important by ML models. Inexplicability remains a challenge, but algorithms such as local interpretable model-agnostic explanation or Shapley value can increase explainability of ML algorithms. Our analysis shows that ML algorithms have the potential to greatly assist surgeons in clinical decision making.

Management of brain metastasis. Surgical resection versus stereotactic radiotherapy: a meta-analysis.

Background: Treatment of metastatic brain tumors often involves radiotherapy with or without surgical resection as the first step. However, the indications for when to use surgery are not clearly defined for certain tumor sizes and multiplicity. This study seeks to determine whether resection of brain metastases versus exclusive radiotherapy provided improved survival and local control in cases where metastases are limited in number and diameter. Methods: According to PRISMA guidelines, this meta-analysis compares outcomes from treatment of a median number of brain metastases ≤ 4 with a median diameter ≤ 4 cm with exclusive radiotherapy versus surgery followed by radiotherapy. Four randomized control trials and 11 observational studies (1693 patients) met inclusion criteria. For analysis, studies were grouped based on whether radiation involved stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT). Results: In both analyses, there was no difference in survival between surgery ± SRS versus SRS alone two years after treatment (OR 1.89 (95% CI: 0.47-7.55, P = .23) or surgery + WBRT versus radiotherapy alone (either WBRT and/or SRS) (OR 1.18 (95% CI: 0.76-1.84, P = .46). However, surgical patients demonstrated greater risk for local tumor recurrence compared to SRS alone (OR 2.20 (95% CI: 1.49-3.25, P < .0001)) and compared to WBRT/SRS (OR 2.93; 95% CI: 1.68-5.13, P = .0002). Conclusion: The higher incidence of local tumor recurrence for surgical patients suggests that more prospective studies are needed to clarify outcomes for treatment of 1-4 metastasis less than 4 cm diameter.

Fluorescein-Guided Resection of High Grade Gliomas: A Meta-Analysis.

BACKGROUND: High-grade gliomas (HGGs) have a poor prognosis despite current standard of care of surgery, chemotherapy, and radiation therapy. Achieving gross total resection (GTR) has been found to prolong survival in these patients. Intraoperative fluorescent agents are often used to aid in the resection of HGGs. One commonly used fluorescent agent is fluorescein sodium, which is U.S. Food and Drug Administration-approved for ocular surgeries and has a better side effect profile and is less costly than 5-aminolevulinic acid (5-ALA). In this meta-analysis, we provide statistical evidence of the efficacy in using fluorescein for HGG resection. METHODS: Following the PRISMA framework, we assessed 119 reports from PubMed, Medline (Ovid), and BIOSIS Citation Index and found 21 eligible studies for meta-analysis, assessing the rates of GTR with fluorescein-guided resection of HGGs. RESULTS: A pooled cohort of 336 patients underwent fluorescein-guided HGG resection with a GTR rate of 81% (95% confidence interval 73%-89%; P < 0.001). Ten case-controlled studies were analyzed, showing a 29.5% increase in GTR rate in the fluorescein group compared with non-fluorescein-guided surgeries. CONCLUSIONS: This meta-analysis shows that fluorescein-guided surgery improves GTR rates of HGGs when compared with non-fluorescence guided surgery and has similar GTR rates when compared with reported 5-ALA-guided resection rates.

Understanding how adolescents and young adults with cancer talk about needs in online and face-to-face support groups.

We compared adolescent and young adult cancer patient and survivor language between mediated and face-to-face support communities in order to understand how the use of certain words frame conversations about family, friends, health, work, achievement, and leisure. We analyzed transcripts from an online discussion board ( N = 360) and face-to-face support group ( N = 569) for adolescent and young adults using Linguistic Inquiry and Word Count, a word-based computerized text analysis software that counts the frequency of words and word stems. There were significant differences between the online and face-to-face support groups in terms of content (e.g. friends, health) and style words (e.g. verb tense, negative emotion, and cognitive process).

The need to be Superman: the psychosocial support challenges of young men affected by cancer.

PURPOSE/OBJECTIVES: To investigate how gender-specific issues shape the experiences of young adult men with cancer and what they report to be problematic. RESEARCH APPROACH: A qualitative, descriptive approach. SETTING: Website, focus group in the southwestern United States, and phone interviews throughout the United States. PARTICIPANTS: Text from an online forum (N=3,000 posts), focus group of six men, and separate interviews with four men. METHODOLOGIC APPROACH: Data analysis took place over two months through constant comparison of online text as well as a focus group and interview transcripts. FINDINGS: Men face challenges being both a receiver and provider of support in relationships with their peers, romantic partners, and children. Cultural expectations to "be strong" drive their support-seeking beliefs and behaviors. CONCLUSIONS: Men report conflict between desires to show strength and to be honest that present a barrier to support, as well as contribute to inadequate relationships with male peers and greater difficulty in exchanging support with romantic partners. INTERPRETATION: The authors identified attitudes about and barriers to men's experiences with social support, which healthcare providers, such as nurses, should be sensitive to when developing and providing support.

Mother-teen communication about weight management.

Although research shows family members can influence each other's diet and exercise behaviors, the specific strategies that most effectively motivate individuals to enact healthy behaviors have not been revealed. Toward this goal, this study employed confirmation theory to assess how the quality of weight management (WM) communication between 107 mother-teen dyads was related to their diet and exercise behaviors as well as their subjective perceptions of the productivity of WM conversations. Confirmation theory proposes two components of confirmation: acceptance and challenge. Analyses revealed that accepting and challenging communication were both positively related to the perceived productivity of WM conversations. However, more complex associations emerged for diet and exercise. Acceptance was more helpful in motivating better eating habits for mothers with low health motivation and teens with high health motivation. For exercise, challenge was helpful in motivating teens with higher sensitivity about communicating about weight issues; however, counter to predictions, challenge was negatively related to exercise for teens with low health motivation and low sensitivity. These interactions, however, explained less variance than analyses for perceived effectiveness and satisfaction.

Defining adolescent and young adult (AYA) exercise and nutrition needs: concerns communicated in an online cancer support community.

OBJECTIVE: To describe topics, needs, and concerns related to nutrition and exercise that adolescents and young adults affected by a serious illness (cancer) discuss online. METHODS: Investigators conducted a qualitative content analysis of messages related to nutrition and exercise posted on an online young adult cancer forum. RESULTS: AYAs described several functions achieved through nutrition and exercise, such as fighting cancer, losing weight, obtaining nutrients despite side effects of treatment, promoting general health, enjoyment, and promoting mental/emotional health. AYAs also discussed several problems that interfere with nutrition and exercise goals, such as side effects of steroids, physiological problems with eating, safety concerns or physical limitations due to treatment, poor follow through with behavioral change, stress, and low energy. CONCLUSION: AYAs discuss specific ways nutrition and exercise help achieve a variety of functions that may be physical or psychological, cancer-specific or general. AYAs describe several concerns and barriers that impede their nutrition and exercise goals. PRACTICE IMPLICATIONS: Clinicians should also consider relevant medical and personal variables that partly determine nutrition and exercise concerns. Clinicians can anticipate barriers to desired nutrition/exercise change and develop interventions that address these barriers in appropriately tailored ways, including using digital media.

Exploring psychosocial support online: a content analysis of messages in an adolescent and young adult cancer community.

The increased usage of online cancer support groups as a resource for health-related information and social support has sparked numerous discussions about the role of online support in healthcare. However, little is known about the role of social-networking groups focused on supporting adolescents and young adults (AYAs) dealing with cancer. The current investigation report findings from a content analysis designed to explore how AYAs use an online support group to meet their psychosocial needs. Overall, members of the community focused on exchanging emotional and informational support, coping with difficult emotions through expression, describing experiences of being an AYA dealing with cancer through language (metaphors), enacting identity through evaluations of the new normal (life with and after cancer), and communicating membership as an AYA with cancer. This study highlights the unique needs of the AYA cancer community and offers a preliminary roadmap for practitioners, and network members, such as family and friends, to attempt to meet the needs of this unique community.