Adolescent And Young Adult Age Group Research Articles

Abatement of the Survival Cliff in Older Adolescents and Young Adults with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma in the United States.

Purpose: In 2018, a "survival cliff" in the United States was identified among older adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). This study reassessed the cliff and associated putative causes. Methods: Survival data were obtained using the U.S. Surveillance Research Program, National Cancer Institute (NCI) SEER 22 Registries. Accrual data on cancer treatment trials conducted by the NCI cooperative groups and NCI-designated cancer centers were obtained from the NCI Cancer Therapy Evaluation Program. Trend and average percent changes and statistical significances were identified with the NCI Joinpoint Regression Program. Results: A previous cliff-like decrement in the survival of 17- to 20-year-olds is no longer apparent, overall and in all racial and ethnic groups. The "survival cliff" age range was coincident with a clinical trial accrual cliff, and both diminished when more clinical trials were available to, and participated in by, young adult patients. Older AYA patients of ages 30-39 had minimal improvement in clinical trial accrual and least survival gain among the AYA age group. Conclusion: The survival cliff has abated, resulting in thousands of fewer premature deaths and tens of thousands of years of life saved-a remarkable achievement. The survival improvement may be attributed to improved clinical trial availability for and recruitment and participation of AYAs on treatment trials, application of pediatric-inspired ALL treatment regimens to AYAs, expanded national health insurance for -18 to 25 year olds, improved AYA cancer services, and a national focus on AYA oncology.

A retrospective machine learning–based analysis of nationwide cancer comprehensive genomic profiling data to identify features associated with recommendation of mutation-based therapy.

e13510 Background: Comprehensive genomic profiling (CGP) has played key roles in cancer precision medicine through optimization of therapeutic interventions based on genomic alterations in cancer cells. However, the probability of discovering mutation-based treatments through CGP remains low. To enhance the effectiveness and efficiency of cancer precision medicine, it is crucial to identify patients who are likely to benefit from CGP tests. This study aims to identify characteristics of patients in which mutation-based treatments are discovered by CGP tests. Methods: We retrospectively analyzed data from 60,655 patients who underwent CGP tests and were registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national data center for cancer CGP in Japan. The C-CAT database covers 99.7% of cancer patients who have undergone CGP tests in Japan. Major cancer types included 10,182 cases of bowel cancer, 8,691 pancreas cancer, 5,062 biliary tract cancer, and 3,777 breast cancer. We developed an eXtreme Gradient Boosting (XGBoost) model using machine learning, and used clinical information as input to predict whether one or more Japanese Pharmaceuticals and Medical Devices Agency (PMDA)-approved drugs are discovered through CGP tests or not. Shapley Additive Explanations (SHAP) was employed to extract significant features that contribute to the model prediction. Results: The prediction model achieved an area under the receiver operating characteristic curve of 0.826 for the overall cancer population. Positive SHAP values were observed for patients with breast (mean SHAP in breast cancer patients: 1.38), lung (1.08), bowel (0.75), and pancreas cancers (0.35), while negative SHAP values were associated with head and neck (-1.75), cervical cancers (-1.54), and brain (-1.33). Positive SHAP values were also associated with presence of liver or lymph node metastasis (0.23, 0.08), shorter intervals between diagnosis and CGP testing or specimen collection and CGP testing, and advanced age. Similar trends were observed in cancer-type-specific prediction models, which also identified their own unique features. In the adolescent and young adult (AYA) age group, primary brain tumors were strongly associated with negative SHAP values (-1.37). Conclusions: Our machine learning-based analysis of nationwide CGP data identified features that predict cases in which mutation-based treatments are discovered by CGP tests, both in the overall cancer population and within specific cancer types and the AYA age group. Expedited CGP testing is recommended for patients who match the identified profile to facilitate early targeted therapy interventions.

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.

Characteristics and Outcomes of Adolescent, Young Adults, and Adults 40-50 Years Old with Multiple Myeloma: A Single Center Experience

Background Multiple myeloma (MM) is a malignant tumor with abnormal proliferation of plasma cells. Adolescent and Young Adult (AYA) patients are defined as patients between 15-39 years of age. Multiple myeloma is uncommon in non-elderly populations. Its prevalence is only 2% in AYA age group and only 10% in patients 40-50 years old. The feature of MM is not well known or understood in those two age groups. In this retrospective study we describe the clinical characteristics, cytogenetics, prognostic markers, treatments given and outcomes of MM in AYA and 40-50 years old patients. Methods We retrospectively analyzed data from the clinical database of our single tertiary hematology center, The National Center for Cancer Care and Research, Doha, Qatar. This center serves a country's population of about 2,8 million people. All patients diagnosed with MM between the age 50 or less during the period of January 2007 to December 2022 were included. Results Seventy-four patients were diagnosed at our centre with MM before the age of 50 years, total of all MM cases 222 (33%) Males was predominant 55/74 (74.3 %) with a median age of 41 years (range, 15-49). Most of the patients were from Asian 55%. At diagnosis patients had a median hemoglobin of 10.2 g/dl, creatinine 294 umol/L, total protein 90 gm/L, albumin 34.75 gm/L, calcium 2.7 mmol/L, LDH 255 U/L, IgG 2289.75 mg/dl, IgA 424.15 mg/dl, IgM 34.2 mg/dl, FLC-Kappa 1993 mg/L and FLC-Lambda 1177 mg/L. Median of bone marrow filtration by plasma cell was 51 %. Most of the patients presented at advance stages with 44 patient (59%) presented as IIIA Durie Salmon or stage III and IV by ISS 70 %. IgG Kappa most frequent type of MM 18 patients (24%), followed by Free light chain kappa (23%), IgG Lambda (18%) and others including two cases of plasmacytoma (Most recurrent cytogenetics were diploid cytogenetics in 42 patients (57%), while 7 patients (9%) had complex cytogenetics. Twenty-eight patients had spinal cord compression at single or multiple levels ( thoracic were most common site 20%) while 3 patients had pathological fractures. Bortezomib based regimen is most one used to treat our patients. Daratumumab- Velcade, Revlimid, and dexamethasone (D-VRD) was used for 35 patients (74%) and Velcade,Cyclophosphamide and Dexamethasone VCD in 20 patients (27%). The first response to treatment showed completed remission (CR) in 35 patients, very good partial remission in 10 patients, partial response in 9 patients, four patients either refractory or primary refractory disease and one patient with stable disease. Thirty -five patients (48%) underwent their first autologous bone marrow transplant ASCT. A total of 8 patients underwent second ASCT and one patient underwent third ASCT. After a median duration of follow up of 6.25 years and 72 % of the patients were still alive. We compared the characteristics and outcome for the AYA group (18-39) with patient age group 40 to 49 years. Although there was no statistical significance difference between the two groups regarding overall survival (p=0.21) , the older group had more cases of spinal cord compressions and more cases of refractory disease. Patient characteristics are described in Table 1. Conclusion One third of MM patients in our center are younger than 50 years. These patients tend to present with advanced stage and serious manifestation such as spinal cord compression. IgG kappa and free light chain are the most common myeloma type in this cohort. D-VRD is the most used protocol with a good response rate. Patient characteristics and treatment outcomes are the same for AYA patients compared with patients 40-49 years old (p=0.21). Patients who received first transplant had better OS compare the those who didn't (p0.01)

EBV Prevalence and Overall Survival in the Multi ethnic Study of Hodgkin Lymphoma (MESH)

Background: Classic Hodgkin Lymphoma (CHL) is a B-cell lymphoma characterized by rare Hodgkin Reed-Sternberg (HRS) cells surrounded by immune cell infiltrates that define histological subtypes. In 1987, Weiss discovered that a minority of CHL tumors harbored an Epstein-Barr virus (EBV) genome integrated into the genome of the HRS cell (EBV+ tumors) (Weiss, et al., Am J Pathol, 1987). A population-based study conducted in California reported 27% of CHL tumors were EBV+ with a higher prevalence in younger and older patients compared to adolescents and young adults (AYA), and in Hispanics compared to other racial/ethnic groups (Keegan, et al., JCO, 2005). We evaluated EBV tumor status and demographic characteristics and survival in a multiethnic set of CHL patients the Multi Ethnic Study of Hodgkin lymphoma (MESH). Methods: We collected 891 multiethnic cases of formalin-fixed paraffin-embedded tumor blocks of CHL diagnosed between 1978 and 2018. Patients were identified from cancer centers and hospitals in Atlanta, Los Angeles County, Mexico City, Philadelphia, Detroit, and the Residual Tissue Repositories from Hawai'i and Los Angeles County. CHL diagnosis and histological subtype were confirmed by hematopathologist review. Demographic and clinical information was collected from patient medical charts and state cancer registries. EBV tumor status was assigned based on EBER1 in situ hybridization performed using the Novocastra™ Epstein-Barr virus ISH Kit (Ready-to-use [RTU], Leica Microsystems, Inc. Buffalo Grove, IL) on 2mm cores arranged on tissue microarrays. EBV+ cases were defined by nuclear or cytoplasmic positivity in >5% of HRS cells, determined by a study hematopathologist (IS). We tested associations between EBV tumor status and age at diagnosis (pediatric [<15 years], adolescent/young adult [AYA, 15-39 years], older adults [40+ years]), sex, race/ethnicity (Hispanic, Black, Non-Hispanic White [NHW], Asian, and Hawaiian/Pacific Islander [HPI]), and histology (Nodular Sclerosis [NS]; Mixed Cellularity [MC]; Lymphocyte Rich [LR]; Lymphocyte Depleted [LD]) using χ-squared tests. We also assessed the association between EBV tumor status and overall survival (OS) right censored at 5 years using Kaplan-Meier and multivariable Cox regression analysis adjusted for age at diagnosis (continuous), sex, race/ethnicity, and histology (NS vs. other histologic subtypes). Results: To date, EBV results were available for 638 cases enrolled in the study. Frequency among those with EBV results was as follows: pediatric=45 (7%), AYA=373 (59%), older adults=217 (34%), male=347 (54%), Hispanic=246 (39%), Black=118 (19%), NHW=179 (28%), Asian=60 (9%), and HPI=20 (3%). Overall, 30% of the cases were EBV+. EBV positivity was higher in MC compared to NS cases across all age groups (p=<0.001). By histology and age, EBV positivity for both NS and MC was higher in pediatric (NS [45%]; MC [90%]) and older adult (NS [29%]; MC [64%]), compared to AYA cases (NS [16%]; MC [39%]). The AYA age group comprised the largest number of cases, the majority of which were EBV− (Figure 1). EBV+ cases were more common among males compared to females, with higher prevalence among males of pediatric (62%) and older ages (46%) compared to AYA males (24%), following the same pattern as histology. EBV positivity also differed by race/ethnicity (p=0.002), with the highest prevalence in Hispanics (38%) and lowest in HPI (10%). Survival analyses showed a statistically significantly different OS by EBV status (p<0.001), but after adjusting for age, sex, race/ethnicity, and histology, there was no statistically significant difference in OS between EBV+ and EBV− tumor patients (HR=1.08, p=0.744). Conclusion: Our results were largely consistent with the previous literature on EBV positivity prevalence in CHL by demographic characteristics. We report low EBV positivity in HPI for the first time, albeit with small numbers in that group. The difference in EBV tumor status by sex is noteworthy, with females having a higher EBV− AYA peak, and males having a higher EBV+ AYA peak. Unlike previous reports, we did not observe an association between EBV status and survival with adjustment for demographic and clinical variables. More studies with diverse populations and larger sample sizes are needed to better understand the complex interplay of EBV patterns in CHL tumors and their significance in different populations.

Chronic Myeloid Leukemia in Adolescents and Young Adults: A SEER-Based Analysis of Characteristics and Survival Outcomes of 1565 Patients

Introduction: Adolescents and Young Adults (AYA) are individuals between 15-39 years old. There are an estimated 1 million new cases of cancers in this age group yearly [1]. Although Chronic Myeloid Leukemia (CML) is typically a disease of middle-aged and elder patients, with a median age of 62 years [1], AYA accounts for about 22.1% of all CML cases [2]. There has been little focus directed towards this age group and most studies focus on the middle-aged and elderly. Despite the remarkable improvement in the survival of CML over the years, the largest study to date [3] suggested poor survival outcomes for patients in underserved populations and with low income. We aimed to determine whether sociodemographic differences exist in the AYA age group. Method: The Surveillance, Epidemiology, and End-Result (SEER) registry research plus database 17 (2000 -2020) was used to assess and compare the survival outcomes in the AYA group and older population diagnosed with CML. Both univariate and multivariate analyses were performed. Cox proportional hazards regression was used to determine prognostic factors for survival. A two-sided p-value ≤0.05 was considered significant. Results: A total of 6,319 patients with CML were identified, of which 75.2% (n= 4754) were adults ≥40 years, and 24.8% (n= 1565) were AYAs . Amongst the AYA, 51.4% (n=804) were Non-Hispanic White (NHW), 25 % (n=390) were Hispanics, 12.1% (n=189) were Non-Hispanic Black (NHB), 10.5% (n=164) were Non-Hispanic Asian or Pacific Islander (NHAPI) and 1.2% (n=18) were Non-Hispanic American Indian/Alaska Native (NHAIA) [Table 1]. The frequency of Hispanics in the AYA group was more compared to adults ≥40 years (25% vs 12.9%). NHWs had a lower frequency in the AYA group compared to adults ≥40 years (51.4% vs 67.5%) and NHBs had a similar distribution in both age groups (12.1% vs 11.6%). The proportion of mortality attributed to CML was lower in the AYA group compared to older adults ≥40 years (7.7% vs 11.9%). The results for individual Cox regression for each racial group show that AYA Hispanic males had a worse prognosis than females (HR= 2.930, 95% CI: 1.234-6.960), such observation was not seen in other AYA races [Table 2] but it was seen in Hispanic adult males ≥40 years (HR= 1.583, 95% CI: 1.074-2.334). Also, we identified that for patients aged ≥40 years, male sex was an independent poor prognostic factor for NHW (HR= 1.259, 95% CI: 1.074-1.476) and NWB (HR=1.879, 95% CI: 1.232-2.864) [Table 2]. Conclusion: Our study shows similar demographic characteristics between AYA and adults ≥40 years old. However, AYAs are less likely to die from CML compared to adults ≥40 years. Hispanic males appear to have a worse outcome than females, an observation seen in both age groups, and is independent of other analyzed prognostic factors. More research is needed to examine and identify other prognostic factors of CML in AYA with the aim of improving their survival outcomes.

Abstract P4-06-06: Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population

Abstract Background: Neoadjuvant chemotherapy (NACT) is the standard early-stage triple-negative breast cancer (TNBC) treatment. Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. Younger patients have with poorer prognosis in breast cancer. To date, few studies are comparing the prognosis of AYA and older women (≥40) with breast cancer subtypes, specifically Triple-negative breast cancer (TNBC), as AYAs had higher proportions of this subtype. Method: Retrospective review was performed on female patients who received NACT at a King Hussien Cancer Center from January 2014 to June 2020. Data were collected from patients’ electronic medical records. TNBC was histopathologically confirmed. Logistic regression analysis of predictors of pathologic complete response (pCR). Survival curves were estimated with the Kaplan-Meier method. Multivariate analysis for EFS was performed using Cox’s proportional hazards regression model, covariates included age at diagnosis (AYA vs. ≥40), tumor size, nodal status LVI and pCR Result: We analyzed 211 women with stage I-III TNBC, including 62 (29.4%) women aged 18 to 39 years (AYA) and 149 (70.6%) ≥40 years. 138 (68.3%) were node positive, and 71 (34.8%) were T3/4 disease. Median follow-up was 28.1 months, median number of ER visit during NAC is 1 (0-11), 23 (10.9 %) patients had admission during neoadjuvant chemotherapy, most commonly due to febrile neutropenia 13 (56.9%). 37 (17.5%) patients did not complete NAC, due to disease progression in 22 (10.4%), and toxicity in 15 (7.1%) patients. 195 (92.4%) patients had surgery, including 75 (35.5%) had breast-conserving surgery (BCS). 166 (76.3%) patients had objective response, and 64 (30.3%) had pCR. 170 (80.6%) received adjuvant radiotherapy, and 38 (18%) received adjuvant capecitabine. No significant differences between the AYA and the ≥40 group in terms of clinicopathological, toxicity, pCR rate, and the rate of BCS. In univariate analysis, the LVI, nodal status, pCR, and age group were significant predictors of DFS. In multivariate analysis, only PCR and age are the only independent predictor of DFS. The median DFS was worse in the AYA population 47.8 (31.21-64.39) months vs. NR in ≥40 (p-value 0.013). In patients who achieved pCR, the estimated 5-years DFS for the AYA group was 56.1% versus 86.8% for the ≥40 group, (p-value 0.71). In patients with residual disease, PFS for AYA was 34.2 (95%CI 11.5-57) months vs. 59.5 months in the ≥40 group, (p 0.009). Conclusion: Although there is no difference in pCR between the AYA age group patient treated with NACT for TNBC and the older age group, the DFS is significantly worse in the AYA than the ≥40 age group in patients with residual disease. As well, DFS is numerically worse in the AYA age vs. the ≥40 age group in patients who achieved pCR. Citation Format: Faris Tamimi, Baha’ Sharaf, Suhaib Khater, Suhaib Al-Sawajneh, Malek Horani, Khalid M. Elrabii, Anas Zayed, Hikmat Abdel-Razeq. Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-06.

Chronic Myeloid Leukemia in Adolescents and Youngadults: Clinicopathological Variables and Outcomes

Introduction Adolescents and young adults (AYAs) are defined as those diagnosed with cancer at ages 15 through 39. [1] In Qatar we have a large number of patients that fall under the category of AYA, reflecting the fact that most of the population are relatively young working force, where the statistics confirm that the median age of the population of Qatar in 2021 is 32.5 [2]. Objective We conducted this study to find out if AYA age group differ from older age group in clinicopathological variables or outcome, which could indicate a unique disease pathology. We also compared different risk scores to find out which one is more representative of real outcome in AYA. Methodology We conducted a retrospective analysis of the files of 224 patients being treated in our center for CML. Patients' management and response assessment was done based on ELN 2013 guidelines. The analysis is done based on age at diagnosis: < 40 years (AYA) or ≥ 40 years. Results Our study included 224 patients of diverse ethnicities. Baseline characteristics for the study cohort are summarized on the attached table. Patients in the AYA group had a better prognosis based on Sokal score. Same applies for Euro/Hasfold scores. Whereas EUTOS and ELTS scores showed more comparable risk stratification between age groups (see the attached table). When comparing the outcome at 1 year, 24 patients (35.8%) from AYA group vs. 10 (14.4%) from the other group failed to achieve optimal response or had disease progression. The patients who achieved CCyR were comparable (AYA group = 21 (31.3%) vs 20 (29.0%) in the other group). With regards to MMR or deeper response the number was 22 (32.9%) in AYA group vs 39 (56.3%) in the other group. The cumulative MMR was significantly lower in AYA group compared with the older patients' group: 55 (56.7%) vs 69 (73.4%) p=0.016. However, there was no significant difference with regards to DMR: 36 (37.1%) vs 44 (46.8%) p = 0.175 (but still with higher percentage of patients achieving DMR in older age group). Discussion AYA are an important patient population which is underrepresented in the studies done in CML. Most recommendations for CML management are extracted from studies including patients who are much older with a small fraction qualifying as AYA. Some unique challenges for this population include fertility issues, access to health care, and survivorship concerns. Treatment free remissions are more important and more relevant for this age group. Our study shows that AYA patients present more aggressively with higher WBC count, lower Hb lever, and bigger spleens. Additionally, more patients in AYA group were diagnosed in blast phase. However, Sokal/Euro risk scores classified more patients in this group as lower risk; whereas EUTOS and ELTS risk scores placed the patients in comparable risk groups; despite that, outcome was worse both at 1 year and at last follow up. This may suggest that this patient population may have different underlying disease biology which may warrant different risk stratification and different approach to management. In conclusion, AYA present a unique age group, and more studies are needed to clarify the differences in disease biology and possible effect on outcome, as well as possibly formulate a new risk score for this age group.

Five Year Survival Rate of Adolescents and Young Adults (AYA) Cancer Patients: A Prospective Fixed Cohort Study in Bangladesh

Background: Survivors of adolescent and young adult cancers (AYA) often live 50 to 60 years beyond their diagnosis. Cancer incidence increased in all AYA age groups during the most recent decades, but there were little clinical and epidemiological data from developing countries. There are 7,20,06,601(44.2%) people in Bangladesh under this AYA age group (15-39 years). This study aimed to determine the five-year survival rate of AYA cancer patients. &#x0D; Methods: The study was a prospective fixed cohort study. The study period was from 2016 to 2021. &#x0D; Results: Of the total 593 patients, the male and female ratio was 1:1.01. After a follow-up of 5 years, it was documented that 278(46.88%) patients dropped out from follow-up. Among the remaining patients, 185(31.19%) died, and 130(21.92%) were alive. The alive male was 52(40.00%), the female was 78(60.00%), and the ratio was M: F=1:1.5. Highest survival were in germ cell tumour at 80% &#x0D; followed by gestational trophoblastic tumour 77.77%, lymphoma 73.68%, breast cancer 63.64%, ovarian malignancies 57.14%, testicular cancer 50.00% and skin cancer 50.00%. None had insurance coverage, and 92% were dependent on treatment costs. &#x0D; Conclusion: Evidence-based guidelines for AYA have not been developed for evidence-based late effects screening and care guidelines for AYA cancer patients. The high death (31.19%) occurrence is dangerously alarming for Bangladesh as youth are the majority of the total population. So methods should be searched to reduce the AYA death occurrences.

Updated Trends in Hematopoietic Cell Transplantation in the United States with an Additional Focus on Adolescent and Young Adult Transplantation Activity and Outcomes

Hematopoietic cell transplantation (HCT) has been successfully used to treat many malignant and nonmalignant conditions. As supportive care, donor selection, and treatment modalities evolve, documenting HCT trends and outcomes is critical. This report from the Center for International Blood and Marrow Transplant Research (CIBMTR) provides an update on current transplantation activity and survival rates in the United States. Additional data on the use and outcomes of HCT in the adolescent and young adult (AYA) population are included. AYA patients more frequently receive peripheral blood stem cell grafts than pediatric patients, which may reflect differences in practice in pediatric versus adult treatment centers. The proportions of donor types also differ those in adult and pediatric populations. Outcomes for patients in the AYA age range are similar to those of pediatric patients for acute myelogenous leukemia but worse for acute lymphoblastic leukemia. Outcomes for both leukemias are better in AYA patients compared with older adults. Comparing the time periods 2000 to 2009 and 2010 to 2019 revealed significant improvement in overall survival across the age spectrum, but the greatest improvement in the AYA age group.

Non-Private Health Insurance Predicts Advanced Stage at Presentation and Amputation in Lower Extremity High Grade Bone Sarcoma: A National Cancer Database Study : Amputation Predicts Survival: An Effect Most Pronounced in Pediatric and AYA Age Group.

Advances in diagnostic and treatment modalities for high grade bone sarcomas (HGBS) of lower extremity (LE) have enabled limb salvage resections as a feasible first-line surgical option. However, amputations are still performed. Impact of amputation on survival and predictive factors for amputation and the stage at presentation for HGBS of LE remain unknown. National Cancer Database was used to extract 5781 cases of high-grade bone sarcoma of the LE from 2004 to 2017. Kaplan-Meier and Cox regression were used to determine the impact of amputation on survival. Chi square test and logistic regression were used to assess the correlation of predictive factors with amputation and stage at presentation. Amputation [hazard ratio (HR) 1.516; 95% confidence interval (CI) 1.259-1.826; p < 0.001] and advanced stage (HR 0.248; 95% CI 0.176-0.351; p < 0.001) were independent predictors of poor overall survival. The impact of amputation on survival was most pronounced for pediatric and adolescents and young adults (AYA) age groups (18% decrease in 10-year survival). Amputation was more likely to be performed among those with nonprivate insurance (HR 1.736; 95% CI 1.191-2.531; p = 0.004), a finding that was mirrored for advanced stage at presentation (HR 0.611; 95% CI 0.414-0.902; p = 0.013). Amputation is an independent predictor of poor outcomes among patients with HGBS of LE. The impact of amputation on survival is the highest for the pediatric and AYA age group. Nonprivate insurance is associated with increased likelihood of amputation and an advanced stage at presentation among patients with high-grade bone sarcoma of the LE. This is the largest study highlighting insurance-related disparities in this cohort.

Molecular landscape of IDH-wild-type, H3-wild-type glioblastomas of adolescents and young adults.

We aimed to characterise glioblastomas of adolescents and young adults (AYAs) that were isocitrate dehydrogenase (IDH) wild type (wt) and H3wt. Fifty such patients (aged 16-32) were studied by methylation profiling, targeted sequencing and targeted RNA-seq. Tumours predominantly clustered into three methylation classes according to the terminology of Capper et al. (2018): (anaplastic) pleomorphic xanthoastrocytoma (PXA) (21 cases), GBM_midline (15 cases) and glioblastoma RTK/mesenchymal (seven cases). Two cases clustered with ANA_PA, four cases with LGG classes and one with GBM_MYCN. Only fifteen cases reached a calibrated score >0.84 when the cases were uploaded to DKFZ Classifier. GBM_midline-clustered tumours had a poorer overall survival (OS) compared with the PXA-clustered tumours (p = 0.030). LGG-clustered cases had a significantly better survival than GBM_midline-clustered tumours and glioblastoma RTK/mesenchymal-clustered tumours. Only 13/21 (62%) of PXA-clustered cases were BRAF V600E mutated. Most GBM_midline-clustered cases were not located in the midline. GBM_midline-clustered cases were characterised by PDGFRA amplification/mutation (73.3%), mutations of mismatch repair genes (40.0%), and all showed H3K27me3 and EZH1P loss, and an unmethylated MGMT promoter. Across the whole cohort, MGMT promoter methylation and wt TERT promoter were favourable prognosticators. Mismatch repair gene mutations were poor prognosticators and together with methylation class and MGMT methylation, maintained their significance in multivariate analyses. BRAF mutation was a good prognosticator in the PXA-clustered tumours. Methylation profiling is a useful tool in the diagnosis and prognostication of AYA glioblastomas, and the methylation classes have distinct molecular characteristics. The usual molecular diagnostic criteria for adult IDHwt glioblastoma should be applied with caution within the AYA age group.

Adolescent and young adult cancers in India–Findings from the National Cancer Registry Programme

BackgroundThe adolescent and young adult (AYA) age group is a bridge between pediatric and adult age groups. The present study describes the epidemiology of cancers in the AYA age group in India. MethodsThe data of primary site cancers in the age group of 15–39 years from the 28 Population Based Cancer Registries (PBCRs') and 58 Hospital Based Cancer Registries under the National Cancer Registry Programme for the reporting year 2012–2016 was analysed. ResultsThe median age adjusted incidence rate (AAR) was 22.2 per 100,000 among males and 29.2 per 100,000 among females. The age-specific incidence rate increased with increasing age in both genders with the highest recorded numbers in the 35–39 age group. The proportion of myeloid leukaemia and non-Hodgkin's lymphoma was highest in the 15–24 age group. Cancers of the breast, thyroid, mouth and tongue constituted the leading sites between 30 and 39 years. There was a significant increase in the incidence among AYA males (APC=0.9) between 1985 and 2015, while a decline in incidence was observed for females, which was not significant (APC=−0.2). The majority of patients had locoregional spread of cancer at the time of diagnosis. The projected number of cancer cases in both genders are expected to increase to 178,617 in 2025. ConclusionCancers in the AYA population are a concern in India. Since AYA oncology appears to be evolving in India, a robust health care system and suitable AYA cancer care policies and programmes are strongly needed to improve disease outcomes and survival.

PSYCHOTHERAPY WITH MEDICALLY ILL CHILDREN: EARLY CHILDHOOD TO TRANSITIONAL-AGE YOUTH IN 2021

This session aims to equip attendees with selected psychotherapeutic tools for the mental health assessment and treatment of medically ill children and adolescents situated in a developmental framework. Participants will have an opportunity to discuss the effects of medical illness on development from early childhood through adolescent and young adult (AYA) age groups. They will learn about therapeutic interventions with young medically ill children aged 0-6 years and their families. Presenters will share experiences on establishing remote services on the pediatric unit and emergency service with medically ill children during the pandemic and discuss bedside psychotherapy strategies. Participants will also have an opportunity to learn about psychotherapeutic strategies regarding chronic illness themes in the AYA age group, leading up to and including end-of-life care. Participants will gain a new understanding of the effects of medical illness on development from early childhood through AYA age groups. Methods of psychotherapeutic engagement are evolving, whether due to forced adaptations during the COVID-19 pandemic or through recently developed psychotherapeutic tools from parent-child interaction, dignity, and meaning-centered psychotherapies for patients and families. Effective psychotherapeutic applications across the pediatric continuum of care are essential for optimal implementation and outcomes. Children and adolescents remain subject to chronic and terminal medical illnesses with comorbid mental health conditions and considerations. Even as medical advances have extended life expectancies, the need for relevant, practical, and effective delivery of psychotherapeutic interventions—both in person and virtual—has also increased. Child and adolescent psychiatrists are advised to be current with helpful treatment modalities in their roles as psychotherapists and multidisciplinary treatment team leaders working in settings with medically ill youth.

Increased Toxicity Among Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia at U.S. Children's Hospitals

Introduction: Adolescent and Young Adult (AYA) patients with cancer are known to experience disparities in access to care along with delays in diagnosis and treatment. AYA patients with acute lymphoblastic leukemia (ALL) have poorer outcomes as compared to children with ALL. As a result, AYA patients with ALL are increasingly being treated in children's hospitals on pediatric protocols. However, minimal data exist regarding how well AYA patients tolerate the intensity of chemotherapy at doses and regimens designed for children. Our study aims to compare toxicities between pediatric and AYA populations treated for ALL in children's hospitals in the United States.Methods: With IRB approval, the Pediatric Health Information Systems (PHIS) database was queried to analyze healthcare outcomes in pediatric and AYA patients with ALL (ICD-9 code 204.00) admitted between January 1999 and December 2014. We chose to utilize the PHIS database, as these AYA patients with ALL were more likely to have been treated on pediatric protocols. AYA was defined as patients between the ages of 15 and 39 according to the National Cancer Institute (NCI) definition. We extracted relevant ICD-9 diagnoses and procedure codes for each patient related to grades 3 or 4 toxicities as outlined by the NCI, including: infections, cardiac, gastrointestinal, neurological, pulmonary, psychological, and renal complications, thrombosis, avascular necrosis, sepsis, and procedures performed. We focused primarily on various drug-related toxicities specific to therapeutic agents used in pediatric protocols. Admission age, sex, race, ICU stay, and mortality were also analyzed. Nominal data were described with percents and continuous data with medians . Nominal variables were compared using Chi squared analysis; continuous variables were compared using Wilcoxon rank sum tests. All statistical analyses were performed using SAS v. 9.4 (SAS Institute, Cary, NC).Results: A total of 18,095 admissions met inclusion criteria, representing 13,720 patients. Of these, 2,348 admissions (13.0%) were in the AYA age group. 10,896 patients (79%) had one admission and the remaining 2,824 (21%) had two or more admissions. 55% of children and 66% of AYA patients were male. AYA patients had a significantly higher incidence of ICU stay [16.3% vs 13.3%; p<0.0001], longer median length of hospital stay [9.0 vs 8.0 days; p=0.002], and increased mortality [3.9% vs 1.6%; p<0.0001]. The following table (Table 1) describes our key findings. The latter show statistically significant differences among the two groups, with AYA patients showing markedly increased toxicities.Conclusions: In this large multicenter database study, we found overall increased number of toxicities among AYA patients with ALL. Compared to children, AYA patients developed disproportionately higher toxicities from drugs commonly used in pediatric protocols for ALL. Prospective studies are needed to assess whether dose modifications for certain chemotherapeutics may improve the toxicity profile and health care burden of AYA patients with ALL treated in children's hospitals. [Display omitted] DisclosuresAhuja:Shire: Speakers Bureau; Shire: Honoraria; CSL Behring: Honoraria; Bayer: Honoraria.

Glioblastoma in adolescents and young adults: An age-based comparative study from Jordan over a 17-year period

BackgroundGlioblastoma (GBM) is the most common primary brain tumor. Epidemiologic studies on GBM are rarely reported in the special age group of adolescents and young adults (AYA) in comparison to other age groups. We aim to present data on GBM in Jordan, with a focus on the AYA age, including the incidence, gender, location and outcome, as well as long term survival (LTS). MethodsData on GBM was requested from the Jordan Cancer Registry (JCR), and statistical analysis was performed. All data were retrospective and anonymized. ResultsEight hundred GBM cases were analyzed from 2000 to 2016 including 505 males (63.1 %). Males outnumbered females across are studied years (p-value <0.001). There were 49 pediatrics (0−14 years, 6.1 %), 125 AYA (15−39 years, 15.6 %), 358 adults (40−59 years, 44.8 %) and 268 elderly (60+ years, 33.5 %) cases. Supratentorial location predominated across all age groups (p-value <0.001). The preponderance of males and supratentorial tumors remained across the AYA age group in comparison to others. The median overall survival (OS) was 23.61 months. AYA age group had a better outcome in comparison to the adults/elderly age group (p-value< 0.001). LTS appear to be more common in the AYA age group (p-value 0.021). ConclusionsThis is the first comparative epidemiologic study of GBM in Jordan, focusing on the AYA age group. The AYA age group appears to be associated with a better outcome compared to older age groups, with more LTS compared to others.

Otorhinolaryngologists/head and neck surgeons' knowledge, attitudes, and practices regarding fertility preservation in young cancer patients treated with chemotherapy: an anonymous questionnaire survey.

It is well known that chemotherapy for adolescent and young adult (AYA) patients with cancer can reduce fertility regardless of the regimen. A decline in fertility greatly affects the quality of life of cancer survivors in the AYA age group; however, few patients are thought to be receiving fertility preservation measures. A questionnaire survey was conducted to assess the current understanding and consideration of fertility among otorhinolaryngologists/head and neck surgeons who treat AYA patients with cancer, and to inform them of the guidelines for fertility preservation. A total of 275 otorhinolaryngologists/head and neck surgeons working at our hospital in Ehime, Japan, six neighboring universities, and their affiliated facilities were included in this study. The questionnaire was mailed and requested to be returned by fax. Twenty questions were asked about respondents' years of experience as physicians, specialties, experience in medical care and chemotherapy for AYA patients with cancer, and knowledge and experience in fertility reduction measures. Although 58.7% of the physicians were aware that cryopreservation of eggs and sperm prior to chemotherapy was recommended, only 7 out of 40 physicians (17.5%) had referred AYA patients with cancer to an appropriate medical facility (department) after obtaining informed consent for chemotherapy. Although fertility preservation has been discussed at professional conferences and seminars, consideration and actions in the field of otorhinolaryngology/head and neck surgery have not been sufficient. We hope that the results of this survey will help raise awareness of fertility preservation.

Increased Toxicity Among Adolescents and Young Adults Compared with Children Hospitalized with Acute Lymphoblastic Leukemia at Children's Hospitals in the United States.

Purpose: Adolescent and young adult (AYA) patients (15-39 years old) with acute lymphoblastic leukemia (ALL) have less favorable outcomes and higher treatment-related mortality as compared with older children with ALL. Minimal data exist regarding how well AYA patients tolerate the intensity of chemotherapy at doses and regimens designed for children, and the toxicities suffered by this population at children's hospitals have not been thoroughly characterized. Methods: Pediatric Health Information Systems database was queried to analyze health care outcomes in pediatric (ages 10-14) and AYA patients (ages 15-39) with ALL hospitalized between January 1999 and December 2014. We extracted relevant ICD-9 data for each patient related to grades 3 or 4 toxicities as outlined by the NCI. Results: A total of 5345 hospital admissions met inclusion criteria, representing 4046 unique patients. Of these admissions, 2195 (41.1%) were in the AYA age group, and the remainder were in the 10-14-year-old group. AYA patients had a significantly higher incidence of intensive care unit stay but no difference in median hospital stay nor mortality. AYA patients had increased toxicities in almost every organ system as compared with older children. Conclusions: In this large multicenter US database study, we found an overall increased number of toxicities among AYA patients with ALL in children's hospitals. Compared with children between the ages of 10 and 15, AYA patients developed disproportionately higher toxicities from drugs commonly used in pediatric protocols for ALL. Prospective studies are needed to assess whether dose modifications for certain chemotherapeutics may improve the toxicity profile and health care burden of AYA patients with ALL treated in children's hospitals.

Central Nervous System Tumors in Adolescents and Young Adults: An Epidemiological Study from Jordan

Background: The adolescent and young adult (AYA) age group lacks targeted epidemiologic studies that assess the prevalence and outcome of tumors. We aim to provide deep analysis of the epidemiology of central nervous system (CNS) tumors in AYA in Jordan. Methodology: This is a retrospective study for all CNS tumors in the AYA group patients diagnosed and managed at King Hussein Cancer Center in 2007–2016. A patient list was retrieved from the Center’s Cancer Registry, and clinicopathologic data were reviewed individually from the patients’ records. Results: A total of 370 cases of primary CNS tumors were retrieved, with a median age of 28.5 years. Males outnumbered females; 57.6 and 42.4%, respectively. Most tumors occurred in the cerebrum (62.2%, n = 230), the frontal lobe was the most commonly affected (29%). Glioma was the most common histologic category (58.9%, n = 218), with high-grade tumors, including glioblastoma and anaplastic astrocytoma, prevailing. Embryonal tumors comprised the second most common group (16.8%, n = 62). Medulloblastoma was the prototype of embryonal tumors (91.9%; n = 57). Glioma tended to affect the older age group than embryonal tumors (p value = 0.002). On last available follow-up, 29.5% were lost to follow-up, 36% were alive, and 34.6% were deceased. The median overall survival (OS) for all tumors was 47.6 months. Embryonal tumors had a better outcome than glioma (median OS 76.3 vs. 30.3 months, respectively; p value = 0.001). Conclusions: High-grade glioma affecting the cerebrum was the most common tumor among AYA age group and was associated with a less favorable outcome compared to embryonal tumors. More research is needed to address this special age group.

The Outcome of Autologous Stem Cell Transplantation in Adolescent and Young Adult Patients with Multiple Myeloma

Objectives: Multiple myeloma (MM) is a disease of the elderly and peaks at 60-to-70 years of age. The disease is rarely observed in young age groups. The incidence of MM is 2% among the patients under 40 years of age. Methods: In this retrospective study, we analyzed the results of MM patients in the adolescents and young adults (AYA) age group who were treated in our center between January 2010 and July 2018. Results: Of the 212 MM patients, 7% (15/212) were in the AYA age group. The median progression-free survival (PFS) was 20.3 months, and the median overall survival (OS) was 41.5 months among patients in the AYA age group. In the group of patients who were over 40 years of age, the median PFS was 19.07 months, and the median OS was 30.1 months. At the time of diagnosis, the patients in the group that was 40 years of age or older were, more frequently International Staging System (ISS) 2 and ISS 3, while patients in the AYA group were more often ISS 1. Conclusion: As the goal is to achieve longer OS, and the incidence of comorbidities in younger patients is low, augmented treatments should be considered. Keywords: Autologous hematopoietic stem cell transplantation, adolescent young adult, multiple myeloma