Adolescents And Young Adults Population Research Articles

NCOG-23. CLINICIAN AND PATIENT REPORTED OUTCOMES IN YOUNG ADULTS WITH GLIOBLASTOMA: RESULTS FROM A MULTIMODAL PROSPECTIVE STUDY

Abstract The median age for glioblastoma (GBM) is 65 years old, however, younger patients have a similarly dismal prognosis. The adolescent and young adult (AYA) population (15-39 years) is a unique and understudied population. Our study aimed to identify survivorship needs in adult patients in AYA population (<40 yrs) with GBM through analysis of patient and clinician-reported outcomes (PROs and CROs). The Molecular, Imaging and Neurological assessment Database (MIND-CNS) captures Neurological Assessment in Neuro-Oncology (NANO) scores, MDASI-BT and FACIT-SP12 responses at first clinic visit and follow-ups for patients with GBM. We tested associations of the two age groups (18-39 vs. 40 years and older) with each domain of NANO, MDASI-BT and FACIT-SP12 at baseline and at follow-up visits using multivariate logistic regression models, adjusting for MGMT promoter methylation and extent of resection. There were 104 patients with GBM enrolled, including 11 young adults, (median =30 years) and 93 older adults (median =65 years). Young and older adults scored similarly in the domains of NANO, MDASI-BT, and FACIT-SP12 at baseline. MDASI domains at follow-up showed statistically significant lower scores on weakness, fatigue, distress, irritability, drowsiness, and disturbed sleep in younger vs. older adults (adjusted p<0.05). Younger adults had less difficulty with memory and concentration, and their symptoms interfered less with work, walking, and overall enjoyment of life. They also reported feeling more peaceful, finding greater comfort and strength in their faith and beliefs. A comparison of NANO score at baseline and progression will be performed at data maturation. While PROs were similar at baseline, young adults reported lower severity in their physical symptoms and higher spiritual well-being compared to older adults at follow-up visits, highlighting different survivorship experiences. Data maturation will allow for deeper analysis to better inform supportive strategies.

Adolescent microsurgical varicocelectomy and changes in sperm parameters: A matched cohort analysis.

Varicocele, a common vascular abnormality surrounding the testis, is known to be associated with impaired semen parameters and male infertility in adults. However, its impact on the adolescent and young adult (AYA) population is less well known. The study aimed to assess the improvement in sperm parameters following varicocelectomy in the AYA population, comparing them to matched adult counterparts, and investigating potential advantages of early intervention. A retrospective analysis was conducted using a comprehensive database at the University of Miami spanning from 2012 to 2023. We included AYA (under 25 years of age) men who underwent varicocelectomy. To ensure comparability, they were matched with adult patients (over 30 years of age) based on preoperative follicle-stimulating hormone (FSH) values and varicocele grade in a 1:2 ratio. Semen parameters were evaluated before and after surgery, including sperm count, motility, morphology, and overall semen quality. We included 45 patients in the Adolescents and Young Adults (AYA) category, and matched them with 116 adults based on FSH and varicocele grade, all of whom underwent microsurgical varicocelectomy. The AYA group exhibited greater improvements post-varicocelectomy compared to the matched cohort. Furthermore, postoperative sperm concentration in the AYA men demonstrated a remarkable increase, with a 1.7-fold increase in mean concentration compared to the adult group (p<0.001). Additionally, motility also displayed significant enhancement among the AYA men, with a final mean total motile sperm count (TMSC) improvement of 2.25-fold compared to the adult cohort (p=0.002). This study highlights the potential benefits of varicocelectomy as a viable treatment option for adolescents and young adults with varicocele, particularly those with impaired semen parameters. By intervening at an earlier stage of development, patients in this age group can achieve significant improvements in semen quality, as compared to their adult counterparts. These findings underscore the importance of considering varicocelectomy as a valuable therapeutic approach for the younger demographic, potentially alleviating future fertility concerns.

Adolescent and Young Adult Development in Transplant Recipients.

Solid organ transplantation (SOT) is the gold standard of therapy for individuals with end-organ dysfunction. Improved survival outcomes after SOT can help adolescent and young adult (AYA) recipients lead long and healthy life. However, successful SOT during adolescence and young adulthood is often complicated by the innate developmental challenges of this age group. The psychosocial tasks of adolescence include identity development, autonomous decision-making, establishing social networks, educational and vocational preparation, and navigating romantic relationships. These goals may be amplified or delayed for pediatric SOT recipients. Adolescence is also marked by rapid physical changes in linear growth and the development of secondary sexual characteristics. Yet AYA may experience physical and pubertal delays related to transplantation, as well as exaggerated body image dissatisfaction due to medication side effects. Strict adherence to medication and post-transplant regimens may interfere with adolescents' desire for normalcy and fitting in with peers. Healthcare providers should be aware that AYA value education and self-empowerment in transplant care. Transplant success needs to be defined by both medical and psychosocial outcomes, particularly when it relates to the vulnerable AYA population. Fortunately, investment from the patient, family, and care team can aid in transplant recovery and success. This article will identify the developmental challenges faced by AYA undergoing solid organ transplantation as well as strategies to engage positive outcomes.

Trend analysis of hematological tumors in adolescents and young adults from 1990 to 2019 and predictive trends from 2020 to 2044: A Global Burden of Disease study.

Cancer constitutes the primary disease spectrum contributing to the Global Burden of Disease (GBD). Adolescents and young adults (AYA) aged 15-39 have received relatively less attention regarding tumor prevention, diagnosis, and treatment compared to older adults and children. This study aimed to analyze the changes in the disease burden of hematological malignancies among the global AYA over the past three decades based on the GBD database. The changes in the disease burden of hematological malignancies were analyzed among the AYA over the past three decades based on the information from the GBD database. The future trends were predicted using the Nordpred package in R. Our results showed that leukemia ranked first as the leading tumor burden among AYA in 2019, but the incidence rate and mortality rate of leukemia decreased year by year, with a projected age-standardized incidence rate (ASIR) of 1.65/100,000 for females and 2.40/100,000 for males by the year 2044. In addition, the incidence of non-Hodgkin's lymphoma has been gradually increasing in recent years, with an ASIR of 1.73/100,000 from 2020 to 2024. The results may serve as a basis for developing strategies to reduce the burden of hematological malignancies in the AYA population in different regions.

Treatment of Medulloblastoma in the Adolescent and Young Adult Population: A Systematic Review.

Medulloblastoma is the most frequent high-grade tumor of the central nervous system in children but accounts for less than 1% of these tumors in adults. Adolescent and young adult (AYA) patients are between both age groups, and different approaches are used to treat medulloblastoma in this population. We performed a systematic review of studies published between 2007 and 2023 that reported treatment approaches and survival data of AYA patients with medulloblastoma, defined as 15 to 39 years of age at diagnosis. Due to the heterogeneity of data, a meta-analysis was not possible. Except for the omission of chemotherapy after radiotherapy in a few adult studies, the treatment backbone is very similar between studies starting enrolment during childhood and older adolescence or adulthood. Despite indications for a higher rate of early treatment termination due to toxicity in adults, survival data remain comparable between studies starting enrolment earlier or later in life. However, molecular subtyping was missing in most studies, so the survival data must be interpreted cautiously. Nevertheless, pediatric-inspired strategies in the AYA population are feasible, but individual dose adjustments may be necessary during treatment and should be considered upfront. Collaborative studies investigating the best treatment approach for medulloblastoma in the AYA population are needed in the future.

Analyzing the gut microbiome in adolescent and young adult patients with melanoma receiving immune checkpoint blockade.

9563 Background: Melanoma is the third most common cancer in adolescent and young adults (AYA), a unique cohort defined as patients between 15-39 years of age per the National Cancer Institute. Immune checkpoint inhibitors (ICI) have changed the landscape for advanced melanoma treatment, and the gut microbiota has been shown to remodel the tumor microenvironment to improve ICI efficacy. There is a paucity of research in this cohort, however studies show that AYA patients, in general, have historically not seen the same survival gains as other age groups. Furthermore, literature shows that survival was much worse for AYA's with stage IV melanoma than observed among older adults. Methods: The AYA cohort in this retrospective review is from the 2021 Science publication entitled "Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response". This cohort was matched on a 2:1 basis with older non-AYA patients 50-70 years of age. We controlled for sex, BMI, race, treatment naivety, stage of disease, as well as smoking, drug, and alcohol status. Results: Our AYA cohort of 23 patients is comprised of 15 females, 22 Caucasians, 20 with primary cutaneous melanoma, 12 with stage III at the start of treatment and 11 with stage IV, 17 were BRAF positive, 8 received combined immunotherapy, 20 were treatment naïve, and 11 were responders. We found no difference in alpha or beta diversity in AYA and older non-AYA patients, however alpha diversity increased with age. This is consistent with literature regarding aging gut microbiomes. Furthermore, we noted the most common microbes found between these groups varied considerably. Using differential analyses, we found, for example, a higher abundance of Ruminococcaceae, at the family level, in older non-AYA patients and a higher abundance of Bacteroides stercoris in AYA patients. Literature shows the relative abundance of Ruminococcaceae increased with age and was significantly higher in older patients. Furthermore, Bacteroides stercoris correlates positively with fiber, grain, and vegetable intake. Additionally, Blautia massiliensia, Blautia obeum, and Dorea longicatena were found to be significantly more prevalent (p=0.010, p=0.34, and p=0.035, respectively)) in older non-AYA patients. These species are all known to be obesity biomarkers. Conclusions: We found that the gut microbiota of AYA and older non-AYA melanoma patients differ. Older non-AYA patients have bacterial species associated with negative biomarkers which may be due to an aging gut microbiome. Establishing microbial features in the AYA population can help with microbiome modulation as a therapeutic strategy. Enriching modalities include fecal microbiota transplantation, probiotics, and improving diet as well as fiber intake. Further research should explore if the gut microbiome influences worse outcomes in AYA's with late stage melanoma.

"God is going to help me get through this": spirituality perspectives from Hispanic adolescent and young adult cancer survivors.

Describe spirituality's role in a sample of Hispanic adolescent and young adult (AYA) cancer survivors. This phenomenology-informed convergent parallel mixed-methods study aimed to explore participants' lived experiences with hope during cancer treatments and cancer survivorship. A purposive sample of Hispanic AYAs who completed cancer treatments 2-5years ago were virtually recruited for participation. Participants completed virtual semi-structured interviews about their experiences with hope during cancer treatments and cancer survivorship and prepared narratives about their experiences. Thematic analyses were iteratively performed across the data set to identify final themes. Ten Hispanic AYA cancer survivors (mean age 30.2, SD = 4.5) years participated in this pilot study. Seven participants (70%) were female, and three participants (30%) were male. Six participants (60%) experienced non-hematologic malignancies, and four participants (40%) experienced hematologic malignancies. Eight (80%) participants' language preference was Spanish, while two (20%) participants' language preference was English. The theme spirituality and subthemes living by faith, god as a resource, and spiritual gratitude were identified as concepts participants linked to their conceptualization of hope during cancer treatment and survivorship. Hope and spirituality may be conceptually linked to coping behaviors among Hispanic AYA cancer survivors. Hope through faith may be a learned spiritual value in Hispanic AYAs and might play a role in their spiritual and cognitive development. Further research is needed to explore the potentially protective value of hope and spirituality for the Hispanic AYA population.

Abstract SY15-02: Health insurance and outcome disparities in adolescents and young adults with cancer

Abstract SY15-02: Health insurance and outcome disparities in adolescents and young adults with cancer

A Scoping Review of Oncosexology Policy and Practice Tools Focused on Adolescents and Young Adults.

Background: Despite being considered a key component of quality-of-life, sexual health concerns in adolescents and young adults (AYA) patients with cancer (aged 15-39 years old) are often unmet due to barriers from both patients and health care professionals (HCPs). Investigation into policy and practice tools in this scope of practice is also limited. Aim: To review the literature on policy and practice tools in AYA oncosexology. Method: A scoping review was conducted using four databases: Medline, EMCARE, EMBASE, and PsycINFO, based on the Joanna Briggs Institute Scoping Review methodology. Retrieved articles were extracted into Covidence, followed by two screening rounds. Descriptive and basic content analyses were performed for evidence synthesis. Results: Seventy-four articles were included after screening rounds and citation searches. Overall, oncosexology policy and practice tools were categorized into screening tools (11 articles), guidelines (38 articles), training programs (15 articles), service delivery initiatives (5 articles), and the evaluation of their feasibility/challenges to implementation (5 articles). Among these, only ten articles were specifically about the AYA population. They helped identify and resolve sexual health concerns in AYA patients with cancer by providing strategies to overcome communication barriers, treatment options, and information resources for patients, and by advocating for more HCP education on this topic. Conclusion: The results warrant the need for more research, implementation and expansion of policy and practice tools for sexual health issues in AYA patients with cancer.

Venetoclax Combination Treatment of Acute Myeloid Leukemia in Adolescents and Young Adult Patients.

Over the past two decades, the prognosis in adolescents and young adults (AYAs) diagnosed with acute myeloid leukemia (AML) has significantly improved. The standard intensive cytotoxic treatment approach for AYAs with AML, consisting of induction chemotherapy with anthracycline/cytarabine combination followed by consolidation chemotherapy or stem cell transplantation, has lately been shifting toward novel targeted therapies, mostly in the fields of clinical trials. One of the most recent advances in treating AML is the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax with hypomethylating agents, which has been studied in elderly populations and was approved by the Food and Drug Administration (FDA) for patients over 75 years of age or patients excluded from intensive chemotherapy induction schemas due to comorbidities. Regarding the AYA population, venetoclax combination therapy could be a therapeutic option for patients with refractory/relapsed (R/R) AML, although data from real-world studies are currently limited. Venetoclax is frequently used by AYAs diagnosed with advanced hematologic malignancies, mainly acute lymphoblastic leukemia and myelodysplastic syndromes, as a salvage therapeutic option with considerable efficacy and safety. Herein, we aim to summarize the evidence obtained from clinical trials and observational studies on venetoclax use in AYAs with AML. Based on the available evidence, venetoclax is a safe and effective therapeutic option for R/R AML AYA patients. However, further research in larger cohorts is needed to confirm these data, establishing the benefits of a venetoclax-based regimen for this special population.

Abstract 3955: A proteogenomic study of high-grade glioma among adolescents and young adults

Abstract To unravel the molecular mechanisms underlying high-grade glioma (HGG) in adolescent and young adult (AYA) patients, we conducted a comprehensive proteogenomic analysis for 34 AYA (age 15-40) and 59 pediatric (age 0-15) HGG cases. Our approach involved whole genome sequencing, methylation profiling, RNA sequencing, and a suite of mass spectrometry-based proteomic experiments, including global proteomic, phosphoproteomic, and glycoproteomic profiling. The proteomics study successfully identified and quantified approximately 11,000 proteins, 33,000 phosphosites, and 3000 glycopeptides with a 50% missing filtering threshold. To identify the unique characteristics of AYA HGG in contrast to both pediatric and adult HGG, we further integrated a proteogenomic dataset of 99 adult GBM tumors previously published by CPTAC and collaborators (PMID: 33577785). Our study unveiled a collection of mutations, copy number variations, epigenetic modifications and gene fusions that exhibited different frequencies across tumors from pediatric, AYA, and adult patients. Moreover, the influence of these genetic variations on RNA/protein activities also varied across different age groups. Clustering analysis using age-dependent molecular profiles revealed striking differences in RNA/protein/phosphosite activities between patients aged 15-26 and 26-40. Additionally, significantly better overall survival (OS) was observed in the 26-40 age group compared to all other age groups, highlighting distinct biological characteristics within the AYA category that differentiate adolescents from young adults.By leveraging proteogenomic datasets from normal brain tissues (PMID: 30518843), we identified genes, proteins, and pathways with differential age-dependent molecular profiles between tumor and normal brain tissues. Notably, this analysis highlighted significant alterations in proteins from the oxidative phosphorylation, tricarboxylic acid (TCA) cycle, and myelin sheath pathways in tumors compared to normal tissues, some of which were found to be sex-specific.To search for prognostic markers, we introduced a novel approach called Trans-Population Survival Analysis through Interpolation of Age-Dependent Tumor Molecular Profiles. Applying this method on the kinase activity scores derived from the phosphoproteomic data, we identified 150 kinases whose activities were significantly associated with OS among AYA patients. Additionally, employing a causal network analysis tool, we pinpointed six kinases causally linked to OS, suggesting their potential as treatment targets. This study not only characterizes the molecular landscape of AYA HGG but also explores the disease trajectory across the lifespan. Our findings shed light on the intricate interplay of various factors influencing glioma etiology and patient outcomes, paving the way for a deeper understanding of HGG in the AYA population. Citation Format: Nicole Tignor, Mateusz P. Koptyra, Shrabanti Chowdhury, Weiping Ma, Jo Lynne Rokita, Marina Gritsenko, Xiaoyu Song, Giacomo B. Marino, Eden Z. Deng, Francesca Petralia, Azra Krek, Dmitry Rykunov, Felipe da Veiga Leprevost, Noshad Hosseini, Komal S. Rathi, Yingwei Hu, Simona Migliozzi, Tomer Yaron, Weijia Fu, Bo Zhang, Yuankun Zhu, Miguel A. Brown, Jeffrey R. Whiteaker, Clinical Proteomics Tumor Analysis Consortium (CPTAC), Children’s Brain Tumor Network (CBTN), Mehdi Mesri, Ana I. Robles, Karin Rodland, Lewis C. Cantley, Antonio Iavarone, Kenneth Aldape, Marcin Cieślik, Alexey I. Nesvizhskii, Joseph E. Ippolito, Joshua B. Rubin, Amanda G. Paulovich, Hui Zhang, Avi Ma'ayan, Tao Liu, Phillip B. Storm, Adam C. Resnick, Brian R. Rood, Pei Wang. A proteogenomic study of high-grade glioma among adolescents and young adults [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 3955.

Co-delivery of HIV pre-exposure prophylaxis (PrEP) and HIV testing among publicly insured adolescents and young adults (AYA) receiving medication for opioid use disorder (MOUD)

BackgroundLow rates of HIV pre-exposure prophylaxis (PrEP) prescribing contribute to the disproportionate burden of HIV in the United States. Among adolescent and young adults (AYA) with opioid use disorder, HIV testing and PrEP co-prescription rates are poorly characterized. MethodsWe performed a retrospective analysis involving deidentified data from Philadelphia’s Medicaid beneficiaries ages 16–29 years who were prescribed medication for opioid use disorder (MOUD) from 2015 to 2020 and continuously Medicaid-enrolled for ≥6 months prior to that prescription. After identifying the presence of a qualifying diagnosis signifying a PrEP indication, we examined the outcome of appropriate PrEP co-prescriptions and HIV testing using generalized estimating equations (GEE) modeling. ResultsWe identified 795 AYA Medicaid beneficiaries with 1269 qualified treatment episodes. We calculated a PrEP prescribing rate of 29.47 per 1000 person-years among AYA receiving MOUD. The HIV testing rate was 63.47 per 1000 person-years among AYA receiving MOUD. GEE modeling revealed that individuals receiving methadone were more likely (aOR=2.62, 95% CI=1.06–6.49) to receive HIV testing within 6 months after a PrEP-qualifying diagnosis compared to those receiving other MOUD medications. Those who only saw outpatient behavioral health providers were less likely (aOR=0.48, 95% CI=0.24–0.99) to have received an HIV test within 6 months after the PrEP-qualifying diagnosis compared to those receiving inpatient behavioral health services. ConclusionsCo-prescription of PrEP and HIV testing among AYA receiving MOUD was rare in this large urban publicly insured population. Interventions are needed to increase HIV prevention services for this key population of AYA at risk for HIV infection.

Brain Tumor Imaging in Adolescents and Young Adults: 2021 WHO Updates for Molecular-based Tumor Types.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric-type and adult-type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult-type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

Examining the prevalence of nicotine vaping and association of major depressive episodes among adolescents and young adults by disability type in 2021

BackgroundNicotine vaping is more prevalent among U.S. adults with disabilities compared to those without disabilities. However, less is known about nicotine vaping among adolescents (12–17 years) and young adults (18–25 years) by disability status. MethodsUsing data from a sample of 24,722 adolescents and young adults (AYAs) from the 2021 National Survey on Drug Use and Health, we conducted descriptive and multivariable analyses to estimate the national prevalence of nicotine vaping by disability type and examined major depressive episodes (MDEs) as a risk factor for nicotine vaping. ResultsA greater proportion of AYAs with disabilities engaged in past-month nicotine vaping compared to those without a disability (13.9 % vs 9.6 %, p = 0.0001). Also, when MDE was excluded from the model, AYAs with any disability had higher odds of nicotine vaping (AOR = 1.41; 95 % CI 1.15, 1.74) than those without a disability. However, disability status was no longer significant when MDE was included (AOR = 1.16; 95 % CI 0.91, 1.46) in the model. ConclusionsThe higher prevalence of nicotine vaping among AYAs with disabilities suggests that tailored messages may be needed to communicate health risks and adverse outcomes of e-cigarette use. Also, MDE is associated with nicotine vaping among AYA populations. This information can be helpful to school nurses, counselors, and mental health professionals in their screening of major depression as a risk factor for e-cigarette use.

Rising Breast Cancer Rates in Younger Women: Could Dietary Advanced Glycation End Products Be the Missing Link?

Abstract The incidence of breast cancer is increasing among young women, who are at higher risk of aggressive cancer-related deaths. Lifestyle factors, especially diet, are known to be changeable risk factors that can affect cancer development. This review focuses on the published literature connecting dietary advanced glycation end products (AGEs) and the risk of breast cancer, particularly in the adolescent and young adult (AYA) population. To support our analysis, we collected and synthesized data from sources such as PubMed, the SEER database, the American Association of Food and Nutrition Guidelines, and the World Health Organization publications within the last 15 years. AGEs are mainly found in ultra-processed foods, as well as in foods high in fat and sugar, which are common in the Western diet. AGEs are also created through nonenzymatic glycoxidation during food cooking at high temperatures. AGEs have been linked to cancer progression through the receptor for AGE, which can activate inflammatory and oxidative stress pathways that support tumor formation. Epidemiological studies and preclinical models have indicated that a high dietary intake of AGEs is correlated with an elevated risk of developing breast cancer and poorer survival outcomes for women. While the connection between AGEs and breast cancer risk is evident, there is a lack of research focusing on the AYA population. This highlights the necessity for further investigation to fully comprehend the impact of dietary AGE consumption during formative years on the rising incidence of breast cancer in the AYA population. We want to highlight the significance of cancer prevention methods. This includes initiatives to decrease the intake of dietary AGEs during puberty, when simultaneously raising awareness and providing education on the significance of adopting healthy dietary practices and engaging in regular physical activity. These measures could be effective in reducing the risk of breast cancer among young women worldwide.

BRCA Mutations and Fertility Preservation.

Hereditary cancers mostly affect the adolescent and young adult population (AYA) at reproductive age. Mutations in BReast CAncer (BRCA) genes are responsible for the majority of cases of hereditary breast and ovarian cancer. BRCA1 and BRCA2 act as tumor suppressor genes as they are key regulators of DNA repair through homologous recombination. Evidence of the accumulation of DNA double-strand break has been reported in aging oocytes, while BRCA expression decreases, leading to the hypothesis that BRCA mutation may impact fertility. Moreover, patients exposed to anticancer treatments are at higher risk of fertility-related issues, and BRCA mutations could exacerbate the treatment-induced depletion of the ovarian reserve. In this review, we summarized the functions of both genes and reported the current knowledge on the impact of BRCA mutations on ovarian ageing, premature ovarian insufficiency, female fertility preservation strategies and insights about male infertility. Altogether, this review provides relevant up-to-date information on the impact of BRCA1/2 mutations on fertility. Notably, BRCA-mutated patients should be adequately counselled for fertility preservation strategies, considering their higher sensitivity to chemotherapy gonadotoxic effects.

Challenges and limitations of clinical trials in the adolescent and young adult CNS cancer population: A systematic review.

The adolescent and young adult (AYA) cancer population, aged 15-39, carries significant morbidity and mortality. Despite growing recognition of unique challenges with this age group, there has been little documentation of unmet needs in their care, trial participation, and quality of life, particularly in those with primary brain tumors. A systematic literature review of 4 databases was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Studies included editorials, reviews, and practice guidelines on the challenges and limitations faced by the AYA population. Papers had to address CNS tumors. Sixty-eight studies met the inclusion criteria. The challenges and limitations in clinical trials in the AYA population were synthesized into 11 categories: molecular heterogeneity, tumor biology, diagnostic delay, access to care, physician factors, patient factors, primary brain tumor (PBT) factors, accrual, limited trials, long term follow up, and trial design. The published papers' recommendations were categorized based on the target of the recommendation: providers, coordination of care, organizations, accrual, and trial design. The AYA cancer population was found to suffer from unique challenges and barriers to care and the construction of trials. The AYA CNS cancer population suffers from unique challenges and barriers to care and construction of trials that make it critical to acknowledge AYAs as a distinct patient population. In addition, AYAs with primary brain tumors are underrecognized and underreported in current literature. More studies in the AYA primary brain tumor patient population are needed to improve their care and participation in trials.

Intrauterine Device Placement Success for Adolescents and Young Adults at Community-Based Reproductive Health Clinics

BackgroundDespite the endorsement of intrauterine device (IUD) use in adolescents and young adults (AYA) by leading professional organizations and demonstrated acceptance and desirability by AYA, clinicians may worry about procedural difficulty of IUD device placement in younger patients. ObjectiveThe aim of this study was to evaluate the clinical outcomes of first-attempt IUD placement in an AYA population by vaginal delivery (VD) history. Study DesignWe performed a retrospective cohort study of patients <25 years at reproductive health clinics with an IUD placement attempt between January 1-August 31, 2017. We abstracted sociodemographic characteristics, pregnancy history, and procedural characteristics including complications. Bivariate analyses compared successful first attempt IUD placement by VD history. We also assessed frequency of secondary clinical outcomes including ancillary measures used, provider type, symptoms reported during the procedure, and complications. ResultsWe included 1,325 participants (median age=21.3 years) including 42 (3.2%) with a prior VD. Nearly all IUD placements were successful at first attempt (n=1,301, 98.2%) and performed by advanced practice clinicians (n=1,314, 99.2%). First-attempt IUD placement success was similar in those participants with and without VD (p>0.999). Ancillary measures other than NSAIDS were used infrequently (n=16, 3.6%.) .(Among participants with an unsuccessful placement, 66.7% returned, and all had a successful IUD placement on the second attempt. Documented complications within six months of placement were rare (n=29) and mostly comprised of expulsions (n=27, 93.1%). ConclusionIUD placement success among AYA at community-based reproductive health clinics is very high and is not associated with a history of prior vaginal delivery.

Chronic Lymphocytic Leukemia (CLL) in Adolescents and Young Adults (AYA): Clinical Characteristics, Prognostic Factors and Survival for 498 Patients

Background Chronic lymphocytic leukemia (CLL) is primarily a disease of the elderly; however, it can also present in Adolescents and Young Adults (AYA) aged 15 to 39 years. Recent information of case series no larger than 227 patients each described clinical outcomes such as a 5-year Overall Survival (OS) of 90% and a 10-year OS of 78% for AYA 1-4. Data on the effect of age on OS in CLL is conflictive among studies 2,3. A higher proportion of males with CLL have been reported in the younger ages compared with olders in some series 2,4 but not in others 3. Sociodemographic characteristics and distribution between younger and older CLL patients have not been extensively reported 2-4. The objective of our study is to describe the clinical and sociodemographic characteristics, prognostic factors and survival in AYA diagnosed with CLL. Materials and Methods Cases of CLL were obtained from the Surveillance, Epidemiology, and End Results (SEER) Database from 2000 to 2020. Statistical analyses were conducted with SPSS® version 25. Patient characteristics were reported in frequencies and compared with the Chi-squared test. The Kaplan-Meier method was used to estimate the median Overall Survival (OS). Cox Regression was done to identify independent prognostic factors of survival. Results A total of 51,992 cases of CLL were identified. The median age of diagnosis was 69 years (interquartile range: 18 years). 498 AYA cases (1% of total population) were found (Table 1). For them, 66.1% were males, 70.3% were non-Hispanic whites and 90.2% lived in metropolitan areas. A median income of ≥$75,000 was noted in 45.6% of the patients. Chemotherapy was received by 32.7% and radiation therapy was given to 1.6%. The median OS for AYA population was not reached (Figure 1), with a 5-year and 10-year OS of 91% and 84%, respectively. OS was different between AYA vs older population, and age was found to be an independent prognostic factor for survival in the entire population of CLL (p&amp;lt;0.001, Figure 1). The age group comparison also found more proportion of males in AYA vs olders (66.1% vs 58.5%, p&amp;lt;0.001), more proportion of non-white patients in AYA group (29.6% vs 15.3%, p&amp;lt;0.001) and that AYA patients were more prone to receive chemotherapy (32.7% vs 14.8%, p&amp;lt;0.001). The multivariate analysis specific for AYA population found that American Indian/Alaska Native Non-Hispanic patients had poor prognosis compared with other races (HR=19.1, CI 95%: 2.2-166.5, p=0.008). Also, receiving radiotherapy (Beam radiation) was associated with poor prognosis (HR=5.5, CI 95%: 1.6-19.6, p=0.008). Compared to people with income &amp;lt;$35,000, all patients with higher income had better prognosis (for patients with ≥$75,000 median income the HR was 0.01, 95% IC: 0.001-0.11, p&amp;lt;0.001). Chemotherapy was not found to be an independent prognostic factor in this population (p=0.8). Conclusions To the best of our knowledge, this is the largest epidemiological study available for CLL in AYA to this date. Sociodemographic differences and epidemiologic prognostic factors described in this research contribute to understand this disease. Interventional studies are required to identify possible targeted therapies that could improve survival outcomes in this population. We believe that the differences in distribution and prognosis for the described variables in our study can contribute towards optimizing the randomization in interventional trials in the future.

Comparable Outcomes of Relapsed Acute Lymphoblastic Leukemia in Adolescents and Young Adults (AYA) Patients Treated with Pediatric-Inspired Chemotherapy (R3 protocol) Versus Adult-Based Salvage (FA) Protocol

Background Although the survival rate of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved by using pediatric-based treatment protocols, those who experience a relapse still have poor outcomes when treated with adult chemotherapy salvage-regimens, which have traditionally included high doses of Ara-C. The long-term survival rate for patients treated with these salvage-regimens is less than 10%. Salvage treatment with blinatumomab for adults with relapsed B-cell ALL results in a complete remission (CR) rate of 34%, a median survival of 7.7 months, and an overall survival (OS) of less than 30% at 18 months. In contrast, the ALLR3 protocol for relapsed ALL in patients up to the age of 18 years achieved a CR rate of 97% and an overall survival rate of 72%. Therefore, this study aims to compare the outcomes of AYA patients treated with pediatric-inspired regimen (R3 regimen) to those treated with adult-based regimen (FA (Fludarabine/Cytarabine) protocol). Methods The R3 protocol treated 17 AYA patients with relapsed Philadelphia-negative ALL, aged between 14 to 40 years old, who had received first-line therapy. Patients who achieved CR underwent allogenic transplant. The protocol included vincristine, mitoxantrone, asparaginase, dexamethasone, and intrathecal methotrexate. In comparison, 60 patients were treated with FA protocol, with patients achieved CR proceeded to allogeneic stem cell transplantation. Relapses were classified as very early (&amp;lt; 18 months from diagnosis), early (&amp;gt;18 months from diagnosis and &amp;lt;6 months from the end of therapy), and late (&amp;gt;6 months from the end of therapy). Patients' characteristics, response rate (RR) and overall survival (OS) were analyzed. Results The two arms had comparable characteristics. The median age in the R3 arm was 16 years (range: 14-40 years) compared to 22 years (range: 18-32 years) in the FA protocol arm. In the R3 arm, 88.2% of patients had B-cell ALL, while in the FA protocol arm, 92.2% had B-cell ALL. CNS involvement was seen in 28.8% and 17.6% of cases in the R3 and FA protocol arms, respectively. Relapses were classified as very early, early, or late in 2 (12%), 5 (29%), and 7 (41%) of cases in the R3 arm and were mostly late (25.2%) in the FA protocol arm. Relapses in the R3 arm were isolated bone marrow (BM), isolated extramedullary (EMD), or combined BM and EMD in 14 (82%), 1 (6%), and 2 (12%) cases, respectively, while EMD was around three times higher (16.9%) in the FA arm. The overall CR rate was 60% at the end of R3 induction, with negative MRD (&amp;lt;10 −4 cells) in 47.1% of patients. The overall CR rate was higher in the FA arm (76.3%), but the difference with the R3 arm was not statistically significant (p-value 0.1). The disease was refractory to subsequent salvage therapy in 42% of cases in both arms. About half of the patients who responded to R3 proceeded to allogeneic stem cell transplant (52.3%), while 78% of the patients post-FA underwent transplantation. Eight patients died (47%) in R3 arm, but only one patient died due to treatment-related sepsis, while the other seven patients died due to disease-related causes. At a median follow-up of 4 years, OS was 53% in the R3 arm compared to 30.8% in the FA arm, but the difference was not significant (p-value=0.8). The post-FA mortality was mainly due to infections (15.3% in FA vs. 5.9% in R3). Conclusion Pediatric-inspired protocols that have shown significant benefits in the front-line setting for ALL in the AYA population did not demonstrate a significant difference when compared to traditional adult-based salvage chemotherapy regimens in relapsed disease.