Adolescent Young Adults Research Articles

Spirituality in Adolescents and Young Adults With Cancer: An Evolutionary Concept Analysis.

Background: Despite an increased focus on the importance of spirituality to human health, including adolescent health outcomes there remains an absence of evidence-based programs to address the spiritual needs of patients and families. A critical barrier is the absence of a clear conceptual understanding and operational definitions of spirituality for adolescents/young adults (AYAs) with cancer. The purposes of this concept analysis were to (a) clarify the concept of spirituality in the context of the AYAs' cancer experience and (b) generate a definition based on a review of the literature examining spiritual development and the role of spirituality in AYAs' health and cancer treatment. Method: We used Roger's evolutionary concept analysis method to identify antecedents, attributes, and consequences of spirituality in the context of AYAs' cancer using thematic analysis and included identification of case exemplars. Results: Of the 86 articles identified, 21 met our inclusion criteria. Analysis revealed four attributes of spirituality in AYAs with cancer: meaning and purpose, connectedness, life-long universal experience, and independent of or related to religion and faith traditions. Identified antecedents included the presence of spiritual resources, chronic illness, belief, or wonder about a higher power, and existential questions. Identified consequences included hope, meaning, feelings of peace, and enhanced well-being and illness acceptance. Based on the findings, we generated a definition of spirituality in AYAs with cancer. Discussion: Findings inform the development of measures and spiritual care interventions specific to AYAs with cancer. An important limitation to address in future research is the absence of AYAs' first-person accounts of their own spirituality.

Derangement of metabolic homeostasis, detoxifying ability and CA 15-3 in young adult female rats by fructose (15%) drinking is akin to known carcinogens: A missed fiend?

Objectives: Breast cancer (BC) has been the bane of peri-and post-menopausal women, but is now increasingly incident in adolescent/young adult (AYA) females. Pari-passu, there has been a >1000% increase in consumption of fructose as a caloric sweetener in soft drinks, whose top consumers are AYAs. The link between fructose consumption and mammary gland (MG) carcinogenesis is not well-established and the same is investigated and compared against known carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA) and electromagnetic radiations from mobile phone (EMF-MP). Materials and Methods: Weaned female Wistar rats were randomly grouped as normal control (NOR), fructose control (FRC), DMBA control (DMC), and exposure control (EXC). For 8 weeks, the NOR was provided chow and water, ad libitum, while FRC, DMC, and EXC additionally received 15% fructose drinking solution, ad libitum, DMBA (20 mg/Kg, p.o; at weaning) and EMF-MP (Global System for Mobile Communications [GSM]), 2 h/day daily), respectively. At the end of the study, the groups were compared for the biomarkers of insulin resistance (IR), carbohydrate and lipid metabolism, liver function, cardiometabolic function, oxidative stress, and MG carcinogenesis. Results: The serum markers of MG carcinogenesis (CA 15–3), IR (homeostasis model assessment-IR, area under the curve – oral glucose tolerance test), and liver and cardiometabolic function (serum glutamicoxaloacetic transaminase and homocysteine) were significantly raised (P < 0.05) in FRC versus NOR. The metabolic homeostasis (leptin, ghrelin, triglyceride-Glucose index, glucose-6-phosphatase, triglyceride, high-density lipoprotein, serum glutamic pyruvic transaminase, alkaline phosphatase, and glycogen) and detoxifying ability (free-radical scavenging activity [%] and superoxide dismutase) in FRC were not different from DMC, or EXC. Conclusion: The development of early indicators of MG carcinogenesis due to unhindered fructose drinking by AYA female rats is akin to exposure to DMBA or EMF-MPs that evidence the propensity of the former.

Cancer center-based follow-up among pediatric and adolescent/young adult cancer survivors: the role of a community-based organization and the social determinants of health.

Adherence to survivorship care is suboptimal among pediatric and adolescent/young adult (AYA) cancer survivors. We evaluated predictors of cancer center-based follow-up among pediatric/AYA cancer survivors, with an emphasis on social determinants of health (SDOH). This retrospective cohort study used electronic health record data at an academic medical center to identify patients aged 0-29years at last cancer treatment who completed treatment 2010-2019. Cancer center-based follow-up was defined by oncology or survivorship clinic visits through 12/31/2022. Multivariate logistic regression models (overall, ages 0-19 [pediatric], 20-29 [YA]) evaluated the association of demographics, clinical/treatment characteristics, and SDOH (insurance type, distance to cancer center, area deprivation index) with clinic attendance. Further modeling accounted for the service area of a community-based organization (CBO) that supports families of children with cancer. A total of 2210 survivors were included (56% pediatric, 44% YA; 66% non-White). Cancer center-based follow-up decreased from 94% 1-year post-treatment to 35% at > 5-7years. In adjusted analysis, AYAs had the lowest follow-up (5-7years post-treatment: OR 0.25 [0.15-0.41] for age 25-29; OR 0.25 [0.16-0.41] for age 20-24; OR 0.32 [0.20-0.52] for age 15-19). Survivors residing within the CBO service area were twice as likely to follow-up (OR 2.10 [1.34-3.29]). Among a diverse population, AYA survivors were vulnerable to loss to follow-up. Other SDOH were not consistently associated with follow-up. Support from a CBO may partly explain these findings. CBOs may strengthen survivorship follow-up within medically underserved communities. More research is needed to understand community support in survivorship.

Patterns of Independence in Adolescent/Young Adult (AYA) Survivors of Childhood Cancer Having Received Radiotherapy (RT)

AYA cancer survivors are at risk for missed care opportunities due to transitions of care and movement towards independence. This study was undertaken to evaluate steps towards independence of AYA survivors voluntarily using a free, Internet-based tool for creation of survivorship care plans (SCP). A free, publicly accessible tool, Smart-ALACC (Smart Adult Living after Childhood Cancer) was made available on Oncolink.org. Analysis of convenience sample frame was performed with IRB approval. From 12/2017-12/2022, 676 AYA survivors utilized the tool; 55% (372) identified as female. Most (75%, 506) were white, 7% (48) Black, 7% (46) Asian, 6% (42) Hispanic, 5% other/ mixed race. Median age was 20y (R <16 - 46y) and median age at diagnosis was 11 y (R <1y - 21). Most common diagnoses were leukemia (31%, 212), lymphoma (21%, 140), sarcoma (14%, 95), CNS (9%, 54), and neuroblastoma (5%, 37). 311 pts (46%) reported having had RT, most commonly brain (PB) (19%, 60), "mantle" (14%, 43), craniospinal (CSI) (12%, 36), total body irradiation (TBI) (11%, 34), and head/ neck (8%, 26). Most (92%, 619) denied recurrence /secondary malignancy. Users reported being students (64%, 434) or working (24% (163)) full-time (20%) or part-time (4%); 4% (25) were neither. Most reported living with parents (71%, 482), 14% (92) with a partner/ spouse, 7% (46) alone, and 4% (30) with a roommate. Most reported using parental insurance (54%, 368), while 24% (163) had their own private insurance, 7% (49) public, and 2% uninsured. Of 466 users 18+ (466), more were employed (34%, 155, p = 0.04), living separately from parents (40%, 168, p < 0.001), and had independent insurance (52%, 184, p = 0.03). Of users 23+ (244), 141 (57%) were being employed (p < 0.001), 83% (153) living separately from parents (p < 0.001), and 165 (67%) had independent insurance (p < 0.001). Among users age 23+, survivors who had received brain RT (CSI, brain, or TBI) were less likely to live separately parents or with a spouse/ partner (p < 0.001), but equally likely to be employed (Table 1). AYA survivors choosing to use a SCP tool have diagnoses reflective of diagnostic patterns in pediatric oncology; many have had RT expected to be associated with cognitive and developmental late effects. Despite this, trends towards employment and independence were evident in young adult population compared to adolescent; somewhat less so in survivors having had brain RT. These data suggest that AYA survivors display independence from parents and require population directed survivorship support; future efforts should aim to include a more diverse body of users.

The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.

Evaluating the efficacy and toxicity of dose adjusted pegylated L-asparaginase in combination with therapeutic drug monitoring.

The incorporation of pediatric-inspired regimens in the adolescent-young-adult (AYA) and adult populations have resulted improved survival outcomes (Stock et al. Blood 133(14):1548-1559 2019; Dunsmore et al. J Clin Oncol 38(28):3282-3293 2020; DeAngelo et al. Leukemia 29(3):526-534 2015). Nonetheless incorporation of such regimens is limited by increased toxicity to asparaginase. Dosing strategies that reduce the weight-based dose of pegylated-L-asparaginase (PEG-asparaginase) utilizing activity monitoring have been shown to result in better tolerability of these regimens. The purpose of this study was to analyze the efficacy and safety of treating adults with Philadelphia chromosome negative (Ph-) ALL with pediatric-inspired regimens that incorporate PEG-asparaginase dose adjustments and asparaginase activity level monitoring. Patients aged 18-65 years initiated on pediatric-inspired regimens utilizing dose-reduced PEG-asparaginase with therapeutic drug monitoring-guided adjustments were included. The screening of 122 patients treated between 2015 and 2021 resulted in the inclusion of 54 patients. The median age of the cohort was 35 years (16-65 years), and median body mass index (BMI) was 30 kg/m2 (18.3-53.4 kg/m2). The 36-month survival estimate was 62.1% (95% CI 48.1-77.7%), and the median overall survival (OS) was 62.2 months (95% CI 35.1-89.3 months). In the AYA cohort, the 36-month survival was 71.2% (95% CI 55.8-91%) and the median overall survival was not reached. Survival was not significantly affected by immunophenotype or BMI. Discontinuation due to toxicity or hypersensitivity reactions was low at 11% and 9% respectively. The encouraging survival outcomes and favorable tolerability of this older population in the real-world setting support the use of individualized PEG-asparaginase dosing with PharmD-guided therapeutic drug monitoring.

Leveraging a community-academic partnership to evaluate the needs of Latinx AYA cancer survivors.

10060 Background: Adult survivors of childhood cancer have an increased risk of late death and treatment-related comorbidities, yet &lt; 20% of survivors receive guideline concordant risk-based care. Individual-level disadvantages and population-level measures of deprivation contribute to unequal health outcomes among survivors. We aimed to explore the experiences of adolescent/young adult (AYA) cancer survivors and their parents in a region in California with low socioeconomic status and high rates of non-English language preference. Methods: We formed a community-academic partnership with Jacob’s Heart, a nonprofit organization that provides material/psychosocial support to predominantly Hispanic/Latino (Latinx) families of children with cancer. Between Feb-July 2022, we conducted semi-structured interviews in-person or by video or phone with English- or Spanish-speaking AYA survivors of childhood cancer (age ≥15 years, ≥5 years post-diagnosis), parents, and Jacob’s Heart staff members, with assistance from certified medical interpreters. Data were analyzed qualitatively using reflexive thematic analysis based on grounded theory and the constant comparative method. Themes were refined through team discussions with our community partners. Results: We interviewed 12 AYAs (11 Latinx and bilingual), 11 parents (8 Latinx, 7 non-English preferred), and 7 organization staff (5 Latinx and bilingual). AYAs (5 female, 7 male) were median age (min-max) 20 (16-32) and 9 (5-19) years post-diagnosis; parents (9 female, 2 male) were median age 48 (40-60) and 14 (6-23) years post-child’s diagnosis. Cancer types were leukemia (6 AYAs, 9 parents), CNS tumors (1 AYA, 2 parents), other solid tumors (3 AYAs), lymphoma (2 AYAs). Key themes across interviews included gratitude and trust in the pediatric cancer care team and Jacob’s Heart staff, challenges obtaining healthcare outside of the pediatric cancer setting, lasting effects of cancer on the family (e.g., parental job loss, financial strain, impact on siblings, prolonged fear of recurrence in parents, unmet mental health needs in parents and AYAs), and communication barriers between Latinx families and clinicians (e.g., hesitancy to ask questions, overwhelmed by medical information) and between AYAs and parents (e.g., avoidance of talking about cancer history, cancer-related stigma, differing language preferences of AYAs and parents). Conclusions: Childhood cancer has long-lasting effects on families and those with fewer socioeconomic resources face additional burdens. Communication gaps experienced by Latinx families may be a target for intervention to improve AYA survivorship care. Future steps include sharing results with participants and partnering with the community to co-design interventions to facilitate triadic communication among Latinx AYAs, parents, and clinicians.

Health insurance continuity and survival among children, adolescents, and young adults with blood cancer: An analysis based on SEER-Medicaid data.

6504 Background: Many previously uninsured patients do not receive Medicaid coverage until the point of, or after, cancer diagnosis, which may delay access to life-saving therapies. We examined whether continuous Medicaid coverage prior to diagnosis (vs. gaining Medicaid at, or after, diagnosis) provides a survival benefit in children and adolescents/young adults (AYAs) newly diagnosed with blood cancer. Methods: Using the linked SEER cancer registry-Medicaid enrollment data, we assessed coverage during the six months prior to, the month of, and the six months after cancer diagnosis (13-month window) in 29,873 children and AYAs (aged 0-39 years) diagnosed with blood cancer in 2006-2013. To measure insurance continuity, we categorized patients who had: (1) continuous Medicaid (enrolled for ≥6 months prior to through diagnosis), (2) newly gained Medicaid at/after diagnosis (enrollment only at or ≤6 months after diagnosis), (3) other patterns of noncontinuous Medicaid, (4) private insurance, (5) other insurance, or (6) uninsured/unknown insurance. The last three groups contain patients in SEER not linked to Medicaid enrollment data; these patients’ insurance at diagnosis was available in SEER. Kaplan-Meier (KM) survival curve of 5-year overall survival was stratified by insurance continuity category. Associations between insurance continuity and survival were examined using Cox proportional hazard models, for all blood cancers combined and by cancer type (leukemia, lymphoma, myeloma). Models also adjusted for age, sex, race/ethnicity, rurality, neighborhood socioeconomic status, and diagnosis year. Results: Of our sample, 44.1% had private insurance, followed by Medicaid (28.3%), other insurance (9.6%), and no insurance (3.9%) or unknown insurance (14.1%). Of Medicaid-insured patients, 44.9% had continuous Medicaid, 38.9% gained Medicaid at/after diagnosis, and 16.2% experienced other noncontinuous patterns. The KM-estimated 5-year survival probability was 89.3% for privately insured patients, followed by other insurance (88.1%), continuous Medicaid (78.2%), other patterns of noncontinuous Medicaid (74.3%), and newly gained Medicaid at/after diagnosis (70.6%; p&lt;0.001). In multivariable analysis, patients who newly gained Medicaid at/after diagnosis had a hazard ratio (HR) for death of 2.63 (95%CI=2.42-2.87), whereas patients with continuous Medicaid and those with other noncontinuous patterns had HRs of 2.08 (95%CI=1.90-2.28) and 2.31 (95%CI=2.04-2.60), respectively, compared to privately insured patients. This finding persisted across blood cancer types. Conclusions: Less than half of Medicaid-insured children and AYAs with blood cancer had continuous insurance coverage prior to and following cancer diagnosis. Lacking continuous Medicaid coverage was associated with inferior survival.

Evaluation of potential socioeconomic and racial/ethnic disparities in all-cause mortality in adolescent and young adult patients with cancer.

6501 Background: Adolescent Young Adult (AYA) cancer patients, aged 15-39, have historically been understudied. For older adults, socioeconomic (SES) and racial/ethnic disparities in mortality have been demonstrated, but less is known about survival disparities for AYA patients. Most existing studies do not account for the influence of insurance status and access to care. To address this gap, we evaluated the association of SES and race/ethnicity with overall mortality for AYA cancer patients who were members of an integrated health delivery system with relatively equal access to care. Methods: Patients diagnosed with cancer at age 15-39 years old in Kaiser Permanente Southern California between 2010-2018 were included. The fourteen most common AYA cancer types within our cohort were included (excluding thyroid cancer due to low mortality rate). The Neighborhood Deprivation Index (NDI) was used as a marker of SES. Patients were placed into NDI quartiles (Q1: least deprived-Q4: most deprived). Mortality rate per 1,000 patient years was calculated for each racial/ethnic group and NDI quartile. Multivariable cox model was used to estimate hazard ratios (HRs) for all-cause mortality. Models included race/ethnicity and NDI subgroup simultaneously, adjusting for sex, age and stage at diagnosis, and cancer type. Results: A total of 6,380 patients (59% female, median age: 33) were followed for a maximum of ten years. Racial/ethnic distribution was 45% Hispanic, 36% non-Hispanic White, 10% non-Hispanic Asian/Pacific Islander, 7% non-Hispanic Black, 2% Other/Unknown. Overall mortality was 21.8 deaths per 1,000 person years. Crude mortality rates were higher among Non-White racial/ethnic groups (Asian/Pacific Islander: 26.7, Black: 26.2, Hispanic: 25.6, Other/Unknown: 30.3) compared to White patients (16.4). In the adjusted model, Hispanic (HR=1.32, 95% confidence interval [CI] 1.03-1.50, p=0.004) and Black (HR=1.35, 95% CI 1.00-1.83, p=0.05) patients experienced significantly higher risk of all-cause mortality compared to White patients. No mortality differences were observed between Asian/Pacific Islander and White patients. Patients from more deprived neighborhoods had higher mortality risk (Q1: 19.9, Q2: 19.8, Q3: 24.1, Q4: 27.4). In the adjusted model, there was no significant difference in all-cause mortality between Q1 and Q2-Q4 [Q2 (HR=0.88, 95% CI 0.71-1.10), Q3 (HR=0.94, 95% CI 0.75-1.17), Q4 (HR=0.96, 95% CI 0.76-1.22)]. Conclusions: Our study suggests that for insured AYA cancer patients with similar access to care, Hispanic and Black patients have increased risk of all-cause mortality as compared to White patients, while no significant SES survival disparities were observed. These findings warrant further investigation, awareness, and intervention to address inequities in cancer care among vulnerable populations.

Predictors of cancer center-based follow-up among pediatric and adolescent/young adult cancer survivors.

10055 Background: Though guidelines recommend lifelong follow-up for pediatric and adolescent/young adult (AYA) cancer survivors, this has been challenging to implement in clinical practice. We constructed an institutional cohort of pediatric/AYA cancer survivors in order to evaluate follow-up patterns and identify predictors of cancer center-based follow-up. We hypothesized that follow-up would be lower for patients with greater individual- and area-level socioeconomic disadvantage and longer time since treatment. Methods: This retrospective cohort study used EHR data at an academic medical center. We included all patients who completed cancer treatment between 2010-2019 and were aged 0-29 years at last treatment date. Treatment was defined by diagnosis/procedure codes and medication records for chemotherapy, radiation, stem cell transplant, and cancer surgery. The primary outcome of cancer center-based follow-up was defined by clinic visits in an oncology department through 12/31/2022. Patients who died were excluded after the date of death. Multivariate logistic regression models (overall, age 0-19, age 20-29) evaluated the association of follow-up with age, sex, race/ethnicity, treatment intensity, insurance type, primary language, distance to cancer center, and area deprivation index (ADI, a composite measure of socioeconomic disadvantage). Results: 2210 patients were included with an overall rate of cancer center-based follow-up that decreased from 94% 1 year after treatment to 61% at 2-3 years, 45% at 4-5 years, and 35% at 6-7 years. Follow-up was not significantly associated with race/ethnicity, insurance type, primary language, or ADI for overall or age-specific cohorts. Patients &gt;100 miles away had lower odds of follow-up. Increasing age was associated with decreased odds of follow-up, and this trend persisted over time since treatment (Table). Conclusions: Patterns of decreased pediatric/AYA cancer survivor follow-up were largely predicted by age and time since treatment. Further work is ongoing to understand drivers of follow-up disparities, including transfers of care and insurance type among AYA patients and the role of community support and telemedicine in healthcare access and health promotion. [Table: see text]

Bad to the Bone: Emerging Approaches to Aggressive Bone Sarcomas.

Bone sarcomas are rare heterogeneous tumors that affect patients of all ages including children, adolescent young adults, and older adults. They include many aggressive subtypes and patient groups with poor outcomes, poor access to clinical trials, and lack of defined standard therapeutic strategies. Conventional chondrosarcoma remains a surgical disease, with no defined role for cytotoxic therapy and no approved targeted systemic therapies. Here, we discuss promising novel targets and strategies undergoing evaluation in clinical trials. Multiagent chemotherapy has greatly improved outcomes for patients with Ewing sarcoma (ES) and osteosarcoma, but management of those with high-risk or recurrent disease remains challenging and controversial. We describe the impact of international collaborative trials, such as the rEECur study, that aim to define optimal treatment strategies for those with recurrent, refractory ES, and evidence for high-dose chemotherapy with stem-cell support. We also discuss current and emerging strategies for other small round cell sarcomas, such as CIC-rearranged, BCOR-rearranged tumors, and the evaluation of emerging novel therapeutics and trial designs that may offer a new paradigm to improve survival in these aggressive tumors with notoriously bad (to the bone) outcomes.

Adolescent Young Adult Acute Lymphoblastic Leukemia Survivors Develop Innovative Solutions for Unmet Needs.

Adolescent young adult (AYA) cancer survivors continue to have substantive unmet needs. Literature and insights from a task force of survivors, caregivers, and survivor advocates convened by Servier Pharmaceuticals indicate desires for peer created and provided support. This secondary data analysis of information from the task force identified unmet needs in five domains and solutions explored for four prioritized needs. Ultimately, four actionable solution concepts were selected by the task force for further development. Through their work, many key insights about including survivors in creating solutions and the many approaches for best serving AYAs with cancer were revealed.

Abstract B042: Understanding unmet needs of adult survivors of childhood cancer in California’s Salinas Valley: A community-academic partnership to develop programs for families after cancer treatment

Abstract Childhood cancer survivors are at elevated risk of poor health outcomes as they age due to late effects from past cancer treatments. Lifelong risk-based survivorship care is recommended; however, those who lack insurance, have lower income and education, or live in a socioeconomically disadvantaged area are less likely to receive this care, contributing to health disparities. Working toward the goal of improving equitable access to care for cancer survivors, the Stanford Cancer Survivorship Program has partnered with Jacob’s Heart, a nonprofit community organization that supports families of children with cancer in California’s Salinas Valley, a socioeconomically disadvantaged region with a large Latinx farmworker population and high rates of limited English proficiency. Jacob’s Heart provides material resources (financial, food, transportation) and psychosocial support (1:1 and group counseling, social activities) to families during treatment. Together with Jacob’s Heart, we are conducting a needs assessment in accordance with community-based participatory research principles. We present preliminary findings of a qualitative study designed to identify post-treatment concerns, needs, and barriers to cancer survivorship care in the Salinas Valley communities. Semi-structured interviews were conducted with Jacob’s Heart staff, adolescent/young adult (AYA) cancer survivors, and parents of cancer survivors. Eligible participants were ≥5 years post cancer diagnosis, ≥15 years of age, spoke English or Spanish, and received services from Jacob’s Heart during their treatment. The Jacob’s Heart team led recruitment using purposive sampling; 7 staff members, 19 AYA cancer survivors and 13 parents of cancer survivors were recruited. Interviews were conducted in-person or by video or telephone, in English or Spanish with professional interpreters if needed, and transcribed verbatim. Interview topics included demographics, post-treatment healthcare experiences, challenges and concerns related to prior treatment, sources of support, and suggestions for resources. Data were analyzed qualitatively using reflexive thematic analysis based on grounded theory and the constant comparative method. Preliminary findings indicate concerns among the staff around helping families adjust to life post-treatment and helping AYAs transition to independence as young adults. AYAs voiced communication challenges around survivorship topics (overwhelmed by too much information, worried about future health problems, yet hesitant to discuss with healthcare teams) and expressed the need for age-specific social connections and peer support. Further analysis of AYA and parent interviews is ongoing and will be presented at the time of the meeting. This study highlights the strength of a community-academic partnership to understand the lived experiences of AYA cancer survivors and their families and to identify opportunities to improve care. Findings will inform future collaborative interventions and projects that can be implemented in the community to address the unmet needs. Citation Format: Stephanie M. Smith, Caroline Pecos-Duarte, Evelyn Tolamatl Ariceaga, Elle Billman, Anmol Teer, Catherine Benedict, Mary Smith, Sandy Montes, Esmeralda Rivera, Daniela Ramirez, Heidi Boynton, Lidia Schapira. Understanding unmet needs of adult survivors of childhood cancer in California’s Salinas Valley: A community-academic partnership to develop programs for families after cancer treatment [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B042.

Risk of venous thromboembolism and major bleeding in the clinical course of osteosarcoma and Ewing sarcoma

BackgroundPatients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under-researched in general as well as in relevant age groups. AimsTo study the impact of VTE and major bleeding (MB) in OS and ES patients, subdivided in children, Adolescents Young Adults (AYAs; aged 18–39) and older adults. MethodsRetrospective single-center chart review in 519 OS and 165 ES patients treated between 1980 and 2018. Patients were followed from sarcoma diagnosis until an outcome of interest (VTE, MB) or death occurred. Cumulative incidences were estimated with death as competing risk. Cox models were used to determine prognostic impact. ResultsFive-year cumulative incidences of VTE were 12 % (95%CI 9.1–15) for OS and 6.7 % (95%CI 3.5–11) for ES patients, mostly happening in patients ≥18 years; the most frequent VTE presentation was catheter-related upper-extremity thrombosis (OS: 18/65, ES: 7/11). Five-year cumulative incidences for MB were 5.8 % (95%CI 4.0–8.1) in OS and 5.4 % (95%CI 2.5–9.8) in ES patients. 192 OS and 77 ES AYAs were included, who faced similar VTE and MB incidences as older adults. In OS, VTE and MB were both associated with mortality (adjusted HRs 2.0 [95%CI 1.4–2.9] and 2.4 [95%CI 1.4–4.0], respectively), whereas in ES this association was only present for MB (aHR 3.4 [95%CI 1.2–9.6]). ConclusionsVTE is a frequent complication in adult OS and to a lesser extent in ES patients, while the rate of MB was comparably high in both sarcoma types.

Updated Outcomes of the University of Southern California (USC) ALL Frontline Regimen (based on CCG-1882) after Protocol Modification in the Era of Novel Agents in Ph-Negative ALL Patients

INTRODUCTION: Pediatric inspired regimens in adolescent young adults and adults have improved outcomes in acute lymphoblastic leukemia (ALL). CALGB 10403 was prospectively tested in patients 17-39 years and achieved a 3-year event free survival of 59%. In 2007, we reported outcomes after incorporating peg-asparaginase (PEG) dosed at 2000mg/m in induction for patients aged 17- 55 years. This was well tolerated and achieved a complete remission (CR) rate of 96%. In 2014, we reported experience with the use of multiple doses of PEG (CCG-1882) for newly diagnosed ALL adult patients achieving a 7-year overall survival (OS) of 51%. Since then, the USC ALL regimen consisting of 2 induction phases, was further modified with a goal of maintaining good outcomes and improving compliance and toxicities. Fractionated doses of cytarabine were changed to a single dose, the methotrexate dose of 1g/ m2 (2.5 g/m2 if T cell) given D1,15 in intensification phases was changed to 3g/ m2 (B and T cell) given in single doses, and consolidation was increased to six cycles allowing for PEG holidays. Moreover, the approval and incorporation of novel agents such as blinatumomab and inotuzumab also changed outcomes in ALL. Therefore, this study reports an update of outcomes since further modification of the USC ALL pediatric-based regimen in the era of novel agents. METHODS: This is a retrospective review which included adults aged 18 years with newly diagnosed Philadelphia negative ALL (2016-2020) treated at the USC/Norris Comprehensive Cancer Center and the Los Angeles County Hospital (LAC). Primary objectives were over-all survival (OS), event-free survival (EFS), disease-free survival (DFS) at 3 years. Secondary outcomes were complete remission/complete remission with incomplete recovery (CR/CRi) and minimal residual disease (MRD) by flow cytometry rates. OS, DFS, EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p value ≤0.05 was significant. RESULTS: 121 patients with Ph-negative ALL were reviewed (49.6% Ph-negative B-ALL, 23.9% Ph-like B-ALL, 0.8% B cell lymphoblastic leukemia (LBL), 9.1% T cell ALL, 4.1% T cell LBL, 4.1% early T-cell, 5.8% mixed phenotype acute leukemia (MPAL). Median age at diagnosis was 39.3 years. There were 71.9% Hispanic, 15.7% White, 9.9% Asian, 2.5% African Americans. 57.9% males, 42.1% females. In terms of risk stratification, the majority were unfavorable at 54.6% and 37.8% unknown. Median BMI was 29.6 kg/ m2. 52.5% had hepatic steatosis and 5% had CNS disease pre-induction. 68.7% received PEG during induction 1, and 67.9% during induction 2. Post-induction 1, 83.5% patients achieved CR/Cri with 49% MRD negativity by flow. Post-induction 2, 75% achieved CR/Cri with 57.1% MRD negativity by flow. 26.4% received blinatumomab but not allo-HSCT. 20% received blinatumomab and underwent allo-HSCT. 34.7% received blinatumomab for MRD flow positivity, median 2 cycles, only 5.8% received inotuzumab, 35.5% underwent allogenic stem cell transplant. 28.9% and 9.1% had any relapse and refractory disease, respectively. Mortality rate was at 14.9%. 3y OS was at 80.7%, 3y EFS at 54.3% and 3y DFS 61.3%. When stratified by MRD flow negativity after induction 1 and 2, 3y OS was 83.7% vs 91.1% (p=0.55), 3y DFS was 68% vs 64.1%(p=0.98) and 3y EFS was 68% vs 59.5% (p=0.84). When stratified by blinatumomab use, 3y OS 72.5% vs 85.1% (p=0.15), 3y EFS was 31.6% vs 67.5% (p=0.001), 3y DFS was 40.1% vs 73.1% (p=0.001) (Fig 1-2). Use of PEG resulted in grade 3/4 toxicities including hypersensitivity (4.1%), transaminitis (21.5%), pancreatitis (5.4%), hypertriglyceridemia (49.5%), hypofibrinogenemia (45.5%), hyperbilirubinemia (21.5%) and thrombosis (16.5%). CONCLUSIONS: The modified pediatric-based USC ALL induction regimen using PEG maintained a high 3y OS at 85.3% and appreciable 3y EFS at 54.3% and 3y DFS at 61.3%, with tolerable toxicities in an era of novel agents like blinatumomab. This compares favorably with the original USC ALL regimen, CALGB 10407 and GRAALL 2005. Of note, 3y EFS and 3y DFS were significantly lower in those who underwent blinatumomab since these patients were MRD flow positive and lacked deeper remissions, but 3y OS (72.5%) remained high regardless, even though 26.4% who received blinatumomab were not able to go for allo-HSCT. This suggests the beneficial effect of blinatumomab. Further follow-up is necessary to provide a more robust and mature survival data. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Exportin, XPO2, Is a Novel Therapeutic Target in Pediatric, Adolescent and Young Adult AML

The active transport of proteins across the nuclear membrane is regulated by nuclear transport receptors termed importins and exportins, depending on their direction of transport. Nuclear transport receptors contribute to cancer development, through abnormal localization of protein cargos. Increased expression of the exportin, exportin-1/chromosome region maintenance 1 (XPO1/CRM1), has been associated with high risk AML and shorter survival times and XPO1 inhibitors show signs of efficacy in AML. While previous data demonstrate a functional role for XPO1 in AML, less is known about the exportin, XPO2, (alias CSE1L). Despite XPO2 RNAi depletion screens demonstrating a higher genetic dependence in leukemia versus solid tumors/non-hematologic malignancies (p = 0.0394), the functional impact of inhibiting XPO2 has never been studied in leukemia. We analyzed a public database of CRISPR/Cas9 depletion screens in 26 AML cell lines. XPO2 ranked in the top 1.4% of essential genes in AML, along with KPNB1 and XPO1 (DepMap 22Q2 Public+Score, Chronos, www.depmap.org). An RNAi depletion screen confirmed these findings, with XPO2 identified within the top 0.2% of essential genes in AML (Achilles+DRIVE+Marcotte, DEMETER2, www.depmap.org). Gene dependency scores indicated a greater reliance on XPO2, compared to XPO1 (p <0.0001). Increased expression of XPO2 mRNA was associated with decreased event free survival (p = 0.0014) and overall survival (p = 0.00091) in pediatric and adolescent/young adult (AYA) AML patients from the TARGET dataset. Analyzing the BeatAML dataset, increased XPO2 mRNA expression was also associated with decreased overall survival in AML patients <40 years, but not in patients >40 years (p <0.0001). We analyzed protein expression databases and identified XPO2 as the highest expressed member of the exportin family in AML cells lines and AML primary patient samples. By immunoblot analysis, increased expression of XPO2 was detected in 7/7 primary AML samples and 8 AML cell lines (HL60, MV4-11, MOML13, NB4, OCI-AML2, OCI-M2, TEX and U937), compared to normal hematopoietic cells. XPO2 mRNA was also increased in 5/5 primary AML samples and 8/8 AML cell lines, compared to normal hematopoietic cells, as measured by qRT-PCR. To confirm the functional importance of XPO2 in AML, we knocked down XPO2 with shRNA in AML cell lines. Genetic silencing of XPO2 decreased growth and viability of OCI-AML2, TEX and NB4 cells. Gambogic acid (GA), a natural product from Garcinia hanburyi, has been identified as a covalent inhibitor of XPO2-mediated nuclear transportation. In OCI-AML2, TEX and NB4 cell lines, gambogic acid decreased growth and viability of AML cell lines at nanomolar concentrations (TEX cells IC50 = 369nM, OCI-AML2 cells IC50 = 433nM, NB4 cells IC50 = 161nM). To uncover the mechanism of how XPO2 mediates cell death in AML we interrogated a publicly available BioID database (PXD007976) and performed gene set enrichment analysis on XPO2 targets using gprofiler. Processes related to ribosome biogenesis were significantly enriched in XPO2 cargo, whereas XPO1 cargo were enriched for processes related to snRNA transcription and transport (p <0.05). In summary, we identified XPO2 as an essential gene for AML. XPO2 is preferentially increased in AML cell lines and primary patient samples compared to normal hematopoietic cells. Increased XPO2 expression is associated with worse clinical outcomes in pediatric and AYA patients with AML. XPO2 may function to enhance ribosomal biogenesis, demonstrating a critical role in leukemia initiation and progression. Thus, this work demonstrates a new dependency of AML on XPO2, as well as highlights a new therapeutic target for this disease.

Volumetric Modulated Arc Therapy Total Body Irradiation (VMAT-TBI) in Pediatric and Adolescent/Young Adult Patients Undergoing Stem Cell Transplantation: Early Outcomes and Toxicities

<h3>Purpose/Objective(s)</h3> Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy (VMAT-TBI). <h3>Materials/Methods</h3> We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019-2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse free survival (RFS) were analyzed using the Kaplan-Meier method. <h3>Results</h3> Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with non-myeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs D_mean was 7.3±0.3 Gy for myeloablative regimens (range: 6.8–7.8). Kidneys were spared to average mean dose of 71.4±4.8% of prescription dose. Gonadal sparing was achieved for patients treated for non-malignant diseases to D_mean of 0.7±0.1 Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI. <h3>Conclusion</h3> VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.

Impact of COVID-19 on Adolescent HIV Prevention and Treatment Research in the AHISA Network

Members of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) network conduct research aiming to close gaps between what is known to be impactful across the HIV prevention and treatment cascade, and services delivered to optimize outcomes for adolescents/young adults (AYA) in high HIV-prevalence settings. The COVID-19 pandemic introduced new challenges which threaten to exacerbate care and access disparities. We report results of a survey among AHISA teams with active AYA HIV research programs in African countries to determine how the pandemic has impacted their efforts. Results highlighted the detrimental impact of the pandemic on research efforts and the expanded need for implementation research to help provide evidence-based, context-specific pandemic recovery support. Key lessons learned included the viability of remote service delivery strategies and other innovations, the need for adaptive systems that respond to evolving contextual needs, and the need for organized documentation plans, within empathic and flexible environments.

Seeking virtual support: Digital technology use in adolescent and young adults with advanced cancer.

A cancer diagnosis, especially advanced cancer, interferes with adolescent/young adult (AYA) peer relationships. AYAs increasingly use digital technologies (i.e., social media, video games) as a social instrument; little is known about the role of digital technologies in the AYA cancer experience. The objective of this analysis was to describe the use and impact of digital technologies among AYAs with advanced cancer. As part of the "Exploring the Concept of a 'Good Death'" study, semi-structured interviews were conducted with 32 English-speaking AYAs (14-25 years) with advanced cancer (relapsed/refractory disease, estimated survival &lt;50%). Interviews were audio recorded, deidentified, and transcribed verbatim. Questions focused on communication and sources of psychosocial support. Directed content analysis was used for codebook creation. Three reviewers completed transcript coding and reconciled discrepancies. Thematic analysis identified hierarchical themes. The present analysis focused on the specific theme of "digital technologies as a support mechanism." When asked about sources of support, social media and multiplayer online games were most often recognized by AYAs. Three themes emerged regarding the role of digital technologies: distraction, maintaining existing peer support, and connecting with peers with cancer. Two AYAs acknowledged negative consequences of social media. AYAs with advanced cancer cite digital technologies as a mechanism for maintaining and seeking peer support. Digital technologies may be leveraged to provide psychosocial support for AYAs with advanced cancer.

National Ovarian and Testicular Tissue Transport and Cryopreservation Service (NOTTCS)

Background: Recognised female fertility preservation strategies include oocyte and embryo cryopreservation. Ovarian tissue cryopreservation is no longer experimental, and the only option for children and pre-pubertal girls. Although testicular cryopreservation remains experimental for boys, it has the potential to evolve and provide a realistic opportunity for fertility in the future. The RWH/MIVF fertility preservation service has been preserving ovarian tissue since 1995. This service has been available to children, adolescent young adults (AYA) and adults about to receive gonadotoxic treatment for malignant and non-malignant conditions. In 2013, this service was extended to freezing testicular tissue for pre-pubertal and peri-pubertal males. Until 2019 these fertility preservation options have only been available to those undergoing procedures at Melbourne metropolitan hospitals. Young cancer patients seeking fertility preservation in regional or interstate areas, did not have this opportunity due to lack of access and resources. One approach to increasing patient access to Gonadal Tissue Cryopreservation (GTC), was to establish a national tissue retrieval and transport service. Aim: This paper describes the uptake of a GTC transport program at RWH, allowing rural and interstate oncology referral for transport, processing and storage of gonadal tissue in an acknowledged centre of excellence. Method: An information/education/instruction resource package was developed for fertility units Australia-wide, supported by a centralised GTC program coordinator. Referrals are fast tracked to eliminate any delay in treatment. Gonadal tissue is harvested at the referring hospital and transported to RWH for cryopreservation and storage, following methods established in other countries with a centralised service 1 – 3 . Results: To date, 40 ovarian and testicular tissue has been transported from all Australian states, and Northern Territory to RWH, including semen transported from a regional hospital where no fertility service was available. This service was made possible, and free of charge to those patients 13–30 yo with a cancer diagnosis, through a generous donation by Sony Foundation. Conclusion: Provision of a comprehensive fertility preservation service, including GTC, for young people, was not widely available until 2019. Gonadal tissue transport facilitates engagement and upskilling in oncofertility with extensive support from a centre of excellence, allowing expansion of patient and provider access to best-practice fertility preservation options, regardless of their geographic location and socio-economic status.