Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions.

Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies. Functional studies show that FUS-TFCP2 blocks myogenic differentiation, induces transcription of ALK and truncated TERT, and inhibits DNA repair. Unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibit genomic instability and signs of defective homologous recombination. DNA methylation profiling demonstrates a close relationship with undifferentiated sarcomas. In two patients, sarcoma was preceded by benign lesions carrying FUS-TFCP2, indicating stepwise sarcomagenesis. This study illustrates the potential of linking precision oncology with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers.

Sociodemographic Correlates of Low Health Literacy Skills Among Cancer Survivors: National Findings From BRFSS 2016.

PURPOSE: This study aimed to explore associations of sociodemographic factors with difficulties in three health literacy (HL) skills and the severity of low HL skills. DESIGN: Cross-sectional secondary data analysis. Subjects: Data came from 17,834 adults who responded to the HL module with a response rate of 47% in the 2016 Behavioral Risk Factor Surveillance System. MEASURES: Independent variables included sex, age, race/ethnicity, education, employment and income. Dependent variables are three HL skills: obtaining, understanding oral, and understanding written health information. ANALYSIS: We conducted weighted Chi-square tests and multinominal logistic regressions. RESULTS: Cancer survivors younger than 65 (aged 18-39: AOR = 4.46, P < .001; aged 40-64: AOR = 2.29, P < .001), Hispanic (AOR = 2.17, CI = 1.61-2.50, P < .01) had higher odds of difficulty obtaining health information. Female cancer survivors had lower odds of difficulty comprehending oral (AOR = .69, CI = .55-.87, P < .01) and written (AOR = .58, CI = .46-.74, P < .001) information. The relative risk ratio of having difficulties in three HL tasks was higher for those who were younger than 65 (aged 18-39: RRR = 10.18, CI = 2.41-4.3, P < .01; aged 40-64: RRR = 4.01, CI = 2.09-7.69, P < .001), Hispanic (RRR = 3.24, CI = 1.66-11.34, P < .01), unemployed (RRR = 6.1, CI = 2.88-12.76, P < .001), education levels lower than some college (some high school: RRR = 4.34, P < .01; high school: RRR = 2.62, P < .05) and household income under $25,000 (RRR = 6.99, CI = 2.8-17.5, P < .001). CONCLUSION: Intervention and communication materials need to be tailored for patients with different HL skills considering age, gender, socioeconomic status and cultural backgrounds.

Outcome of Children and Adolescents With Relapsed/Refractory/Progressive Malignancies Treated With Molecularly Informed Targeted Drugs in the Pediatric Precision Oncology Registry INFORM.

PURPOSE: INFORM is an international pediatric precision oncology registry, prospectively collecting molecular and clinical data of children with recurrent, progressive, or very high-risk malignancies. We have previously identified a subgroup of patients with improved outcomes on the basis of molecular profiling. The present analysis systematically investigates progression-free survival (PFS) and overall survival (OS) of patients receiving matching targeted treatment (MTT) with the most frequently applied drug classes and its correlation with underlying molecular alterations. METHODS: A cohort of 519 patients with relapsed or refractory high-risk malignancies who had completed a follow-up of at least 2 years or shorter in the case of death or loss to follow-up was analyzed. Survival times were compared using the log-rank test. RESULTS: MTT with anaplastic lymphoma kinase (ALK), neurotrophic tyrosine receptor kinase (NTRK), and B-RAF kinase (BRAF) inhibitors showed significantly improved PFS (P = .012) and OS (P = .036) in comparison with conventional treatment or no treatment. However, analysis of the four most commonly applied MTT groups, mitogen-activated protein kinase (MEK- n = 19), cyclin-dependent kinase (CDK- n = 23), other kinase (n = 62), and mammalian-target of rapamycin (mTOR- n = 20) inhibitors, did not reveal differences in PFS or OS compared with conventional treatment or no treatment in patients with similar molecular pathway alterations. We did not observe differences in the type of pathway alterations (eg, copy number alterations, single-nucleotide variants, InDels, gene fusions) addressed by MTT. CONCLUSION: Patients with respective molecular alterations benefit from treatment with ALK, NTRK, and BRAF inhibitors as previously described. No survival benefit was observed with MTT for mutations in the MEK, CDK, other kinase, or mTOR signaling pathways. The noninterventional character of a registry has to be taken into account when interpreting these data and underlines the need for innovative interventional biomarker-driven clinical trials in pediatric oncology.

Incidence and Outcomes of Non-Ventilator-Associated Hospital-Acquired Pneumonia in 284 US Hospitals Using Electronic Surveillance Criteria.

Importance: Non-ventilator-associated hospital-acquired pneumonia (NV-HAP) is a common and deadly hospital-acquired infection. However, inconsistent surveillance methods and unclear estimates of attributable mortality challenge prevention. Objective: To estimate the incidence, variability, outcomes, and population attributable mortality of NV-HAP. Design, Setting, and Participants: This cohort study retrospectively applied clinical surveillance criteria for NV-HAP to electronic health record data from 284 US hospitals. Adult patients admitted to the Veterans Health Administration hospital from 2015 to 2020 and HCA Healthcare hospitals from 2018 to 2020 were included. The medical records of 250 patients who met the surveillance criteria were reviewed for accuracy. Exposures: NV-HAP, defined as sustained deterioration in oxygenation for 2 or more days in a patient who was not ventilated concurrent with abnormal temperature or white blood cell count, performance of chest imaging, and 3 or more days of new antibiotics. Main Outcomes and Measures: NV-HAP incidence, length-of-stay, and crude inpatient mortality. Attributable inpatient mortality by 60 days follow-up was estimated using inverse probability weighting, accounting for both baseline and time-varying confounding. Results: Among 6 022 185 hospitalizations (median [IQR] age, 66 [54-75] years; 1 829 475 [26.1%] female), there were 32 797 NV-HAP events (0.55 per 100 admissions [95% CI, 0.54-0.55] per 100 admissions and 0.96 per 1000 patient-days [95% CI, 0.95-0.97] per 1000 patient-days). Patients with NV-HAP had multiple comorbidities (median [IQR], 6 [4-7]), including congestive heart failure (9680 [29.5%]), neurologic conditions (8255 [25.2%]), chronic lung disease (6439 [19.6%]), and cancer (5,467 [16.7%]); 24 568 cases (74.9%) occurred outside intensive care units. Crude inpatient mortality was 22.4% (7361 of 32 797) for NV-HAP vs 1.9% (115 530 of 6 022 185) for all hospitalizations; 12 449 (8.0%) were discharged to hospice. Median [IQR] length-of-stay was 16 (11-26) days vs 4 (3-6) days. On medical record review, pneumonia was confirmed by reviewers or bedside clinicians in 202 of 250 patients (81%). It was estimated that NV-HAP accounted for 7.3% (95% CI, 7.1%-7.5%) of all hospital deaths (total hospital population inpatient death risk of 1.87% with NV-HAP events included vs 1.73% with NV-HAP events excluded; risk ratio, 0.927; 95% CI, 0.925-0.929). Conclusions and Relevance: In this cohort study, NV-HAP, which was defined using electronic surveillance criteria, was present in approximately 1 in 200 hospitalizations, of whom 1 in 5 died in the hospital. NV-HAP may account for up to 7% of all hospital deaths. These findings underscore the need to systematically monitor NV-HAP, define best practices for prevention, and track their impact.

Immunocompromised Host Pneumonia: Definitions and Diagnostic Criteria: An Official American Thoracic Society Workshop Report.

Pneumonia imposes a significant clinical burden on people with immunocompromising conditions. Millions of individuals live with compromised immunity because of cytotoxic cancer treatments, biological therapies, organ transplants, inherited and acquired immunodeficiencies, and other immune disorders. Despite broad awareness among clinicians that these patients are at increased risk for developing infectious pneumonia, immunocompromised people are often excluded from pneumonia clinical guidelines and treatment trials. The absence of a widely accepted definition for immunocompromised host pneumonia is a significant knowledge gap that hampers consistent clinical care and research for infectious pneumonia in these vulnerable populations. To address this gap, the American Thoracic Society convened a workshop whose participants had expertise in pulmonary disease, infectious diseases, immunology, genetics, and laboratory medicine, with the goal of defining the entity of immunocompromised host pneumonia and its diagnostic criteria.

Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology.

The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.

Genomic ALK alterations in primary and relapsed neuroblastoma.

BACKGROUND: Genomic alterations of the anaplastic lymphoma kinase gene (ALK) occur recurrently in neuroblastoma, a pediatric malignancy of the sympathetic nervous system. However, information on their development over time has remained sparse. METHODS: ALK alterations were assessed in neuroblastomas at diagnosis and/or relapse from a total of 943 patients, covering all stages of disease. Longitudinal information on diagnostic and relapsed samples from individual patients was available in 101 and 102 cases for mutation and amplification status, respectively. RESULTS: At diagnosis, ALK point mutations occurred in 10.5% of all cases, with highest frequencies in stage 4 patients <18 months. At relapse, ALK alteration frequency increased by 70%, both in high-risk and non-high-risk cases. The increase was most likely due to de novo mutations, frequently leading to R1275Q substitutions, which are sensitive to pharmacological ALK inhibition. By contrast, the frequency of ALK amplifications did not change over the course of the disease. ALK amplifications, but not mutations, were associated with poor patient outcome. CONCLUSIONS: The considerably increased frequency of ALK mutations at relapse and their high prevalence in young stage 4 patients suggest surveying the genomic ALK status regularly in these patient cohorts, and to evaluate ALK-targeted treatment also in intermediate-risk patients.

Comprehensive analysis of mutational signatures reveals distinct patterns and molecular processes across 27 pediatric cancers.

Analysis of mutational signatures can reveal underlying molecular mechanisms of the processes that have imprinted the somatic mutations found in cancer genomes. Here, we analyze single base substitutions and small insertions and deletions in pediatric cancers encompassing 785 whole-genome sequenced tumors from 27 molecularly defined cancer subtypes. We identified only a small number of mutational signatures active in pediatric cancers, compared with previously analyzed adult cancers. Further, we report a significant difference in the proportion of pediatric tumors showing homologous recombination repair defect signatures compared with previous analyses. In pediatric leukemias, we identified an indel signature, not previously reported, characterized by long insertions in nonrepeat regions, affecting mainly intronic and intergenic regions, but also exons of known cancer genes. We provide a systematic overview of COSMIC v.3 mutational signatures active across pediatric cancers, which is highly relevant for understanding tumor biology and enabling future research in defining biomarkers of treatment response.

An exploration of financial toxicity among low-income patients with cancer in Central Texas: A mixed methods analysis.

OBJECTIVE: Financial toxicity is of increasing concern in the United States. The Comprehensive Score for Financial Toxicity (COST) is a validated measure; however, it has not been widely utilized among low-income patients and may not fully capture financial toxicity in this population. Furthermore, the relationships between financial toxicity, quality of life (QOL), and patient well-being are poorly understood. We describe the experience of financial toxicity among low-income adults receiving cancer care. We hypothesized that higher financial toxicity would be associated with less income and lower quality of life. Qualitative interviews focused on the financial impact of cancer treatment. METHOD: This study was conducted at a cancer clinic in Central Texas. Quantitative and qualitative data were collected in Fall and Spring 2018, respectively. The quantitative sample (N = 115) was dichotomized by annual income (<$15,000 vs. >$15,000). Outcomes included financial toxicity (COST), quality of life (FACT-G), and patient well-being (PROMIS measures: Anxiety, Depression, Fatigue, Pain Interference, and Physical Function). Associations between quality of life, patient well-being, and financial toxicity were evaluated using linear regression. Sequential qualitative interviews were conducted with a subsample of 12 participants. RESULTS: Patients with <$15k had significantly lower levels of QOL and patient well-being such as depression and anxiety compared to patients with >$15k across multiple measures. A multivariate linear regression found QOL (Β = 0.17, 95% CI = 0.05, 0.29, p = 0.008) and insurance status (Β = -3.79, 95% CI = -7.42, -0.16, p = 0.04), but not income, were significantly associated with financial toxicity. Three qualitative themes regarding patient's access to cancer care were identified: obtaining healthcare coverage, maintaining financial stability, and receiving social support. SIGNIFICANCE OF RESULTS: Low-income patients with cancer face unique access barriers and are at risk for forgoing treatment or increased symptom burdens. Comprehensive assessment and financial navigation may improve access to care, symptom management, and reduce strain on social support systems.

Navigating Financial Barriers to Papanicolaou Tests and Mammograms for Young Adult Women Residing in Rural and Border Areas of Texas.

Purpose: Costs of Papanicolaou (Pap) tests and mammograms are a primary barrier for women aged 18-39 seeking screening and diagnostic services. Race/ethnicity and rural/border resident status compound their risks for delayed diagnosis, possibly resulting in higher mortality. Methods: We analyzed cross-sectional data from young adult (YA) women (aged 18-39) from a cancer education and patient navigation (PN) program in rural and border Texas from 2012 to 2016. Descriptive statistics, Chi-square tests, and logistic regressions summarized sociodemographic variables and receipt of PN, Pap tests, and mammograms. Results: The sample consisted of 1181 women aged 31.8 years (standard deviation 5.5) on average. A total of 795 (67.3%) received PN, 494 (41.8%) received a Pap test, and 121 (10.3%) received a mammogram. The YA women attending the program due to cost (odds ratio [OR]: 7.24; confidence interval [CI]: 4.74-11.05) and reporting 1 (OR: 3.84; CI: 2.40-6.14) or 2+ barriers (OR: 6.00; CI: 3.61-9.99) had higher odds of being navigated than those not concerned about cost and not identifying a barrier. The YA women attending due to cost (OR: 2.22, CI: 1.61-3.05) and receiving navigation (OR: 1.92; CI: 1.29-2.84) had higher odds of receiving a Pap test than their counterparts. The majority receiving a mammogram were worried about cost (85.1%); 40.5% had a family history of breast cancer, and a doctor or nurse recommended a mammogram for 15.7%. Conclusion: Detection of cervical and breast cancer in YA women residing in rural and border Texas may be improved with PN to assist with financial barriers to care and service coordination.

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM.

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival.

Reflections of Moral Suffering, Resilience, and Wisdom of Pediatric Oncology Social Workers during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has significantly altered the lives of pediatric oncology social workers. Challenges include difficulty building rapport with the use of telephone/computers, lack of clarity around who is designated as "essential", structural challenges, isolation, and witnessing distress. This study aimed to describe the ways that the pandemic has personally impacted pediatric oncology social workers. METHODS: Participants were recruited through the Association of Pediatric Oncology Social Workers (APOSW) listserv. In total, 101 participants from 31 states and the District of Columbia completed an online survey containing quantitative and open-ended questions. Qualitative data analysis included thematic analysis of participants' optional survey responses to three open-ended questions. RESULTS: Fifty-seven of the participants provided responses that revealed 3 first level codes and 11 second level codes. First level codes were developed a priori from the questions: Experiences that stay with you, Wisdom gained and Impact on your work. Pandemic-related challenges caused moral suffering and professional challenges for participants but also created opportunities to find meaning in their work. CONCLUSION: Data illuminated moral suffering, unrecognized resilience, new ways of maintaining self-and family care, and creative approaches to care of children with cancer and their families at diagnosis, during treatments and at the end of life.

Wonders & Worries: A randomized clinical trial of a psychosocial intervention for children who have a parent with cancer.

OBJECTIVE: The aim of this study was to test the effectiveness of Wonders & Worries, a psychosocial intervention for children who have a parent with cancer. Primary goals were to improve family quality of life, functioning and communication skills as reported by parent and child, enhance children's emotional/behavioral adjustment and parenting efficacy, while decreasing parenting concerns and ill parents' depression and anxiety. METHODS: Sixty families were recruited from a community based non-profit agency. Parents diagnosed with Stage I-III cancer and their children ages 5-14 years were enrolled and randomized into intervention (n = 32) or wait-list control groups (n = 28). Families received 2 parent consults, six weekly 1-h individual child sessions, and 1 treatment center tour. The intervention was comprised of an age-appropriate understanding of cancer and expression of feelings, coping skills to ease feelings related to parent's cancer and enhanced ability to communicate about the disease. Controls received parent consult and access to W & W resources. Data were obtained from standardized measures at baseline; 6 and 10 weeks follow up. RESULTS: Intervention group significantly improved on parenting concerns, parenting self-efficacy, and family quality of life. Children in the intervention group had significantly lower emotional and behavioral problems and worries related to cancer compared to controls. The intervention failed to significantly affect ill parent's anxiety, depressed mood, family functioning and child's anxiety. CONCLUSIONS: The Wonders & Worries intervention promoted positive adaptation for ill parents and their children. This intervention is promising enough to warrant further refinement and testing with larger, more diverse samples.

County-Level Poverty and Barriers to Breast and Cervical Cancer Screening in a Health Education and Patient Navigation Program for Rural and Border Texas Residents.

The study examined the impact of (1) county-level poverty rates and (2) patient navigation on breast and cervical cancer screening outcomes for women in rural and border counties in Texas reporting barriers to screening.Univariate analyses described the distribution and screening prevalence rates in the sample, while a series of random intercept logistic regression models analyzed mammogram (N = 2326 women aged 40+) and Papanicolaou (Pap; N = 2959 women aged 21-64) screening separately.Mammogram and Pap screening prevalence rates were highest among women who were aged 40-64, Spanish-speaking Latinas, lower educated, attending cancer education events because of the cost of the screenings, patient navigation recipients, living in the south region of Texas, and in counties with high poverty. Although models indicated significant variability in screening rates by county, county-level poverty was only significantly associated with odds of getting Pap screening in adjusted models. Not receiving patient navigation vs. receiving it was associated with lower odds for both mammogram (OR: 0.51, CI: 0.38-0.70) and Pap (OR: 0.69, CI: 0.50-0.94) screenings.County-level variation in screening rates exists for both mammogram and Pap tests and should be considered in the development and implementation of screening interventions in rural and border areas. However, other factors beyond poverty levels may explain the variation.

An Evaluation of Breast and Cervical Cancer Screening Outcomes in an Education and Patient Navigation Program in Rural and Border Texas.

This study examines breast and cervical cancer screening uptake in a cancer education and patient navigation (PN) program for residents of rural and border counties in Texas by level of participation (education only, PN only, or education and PN). Data collected from March 1, 2012, to November 5, 2016, included 6663 follow-up surveys from participants aged 21-74. Logistic regression models assessed program participation on the odds of completing breast or cervical cancer screening. For women aged 40-74 years (N = 4942; mean age = 52 years), 58.4% reported a mammogram within 6 months on average from initial contact. In the breast cancer screening model, women who only received PN (OR: 6.06, CI: 4.87-7.53) or who participated in both the education plus PN program (OR: 3.33, CI: 2.77-4.02) had higher odds of mammogram screening compared to women who only received education. For women aged 21-64 years (N = 6169; mean age = 46 years), 37.7% received a Papanicolaou (Pap) test within 6 months on average from initial contact. In the Pap screening model, both education and PN (OR: 3.23, CI: 2.66-3.91) and PN only (OR: 2.35, CI: 1.88-2.93) groups had higher odds of screening for cervical cancer compared to those only receiving education. Graphed predicted probabilities examined significant interactions between race/ethnicity/language and program participation (P < 0.0001) for both screenings. PN, solely or in combination with education, is an effective strategy to increase screening for breast and cervical cancer, beyond educational outreach efforts alone, among un-/underserved, racially/ethnically diverse women in rural and border Texas counties.

Patient reported outcomes affecting quality of life in socioeconomically disadvantaged cancer patients.

PURPOSE: The aim of this study was to identify correlates of quality of life (QOL) for socioeconomically disadvantaged cancer patients receiving care in the "safety net" health system. DESIGN: This cross-sectional study used linear regressions to determine the effect of patient reported outcome measures (PRO) on QOL.Sample/Methods: Cancer patients (n = 115) receiving drug therapy completed a series of PROs including: Functional Assessment of Cancer Therapy (FACT-G), PROMIS (Anxiety, Depression, Fatigue, Pain Interference, and Physical Function), and the Comprehensive Score for Financial Toxicity. FINDINGS: More than 60% of patients reported an annual income below $24,999. Forty-five percent of patients were either uninsured or county-funded. Depression, pain, and financial toxicity were found to be consistently significant correlates of QOL.Implications: Cancer patients with existing financial strain have unique psychosocial stressors. This study provides insight into the relationship between these stressors, and the need for targeted screening and intervention that address such aspects of care.

"When Will I Feel Normal?": Disorienting Grief Responses Among Young Adults With Advanced Cancer.

BACKGROUND: The diagnosis of an advanced cancer during young adulthood frequently entails the loss of confidence in physical function, as well as the certainty of achieving future social, vocational, and existential aspirations. These losses leave young adults with tenuous holds on facets of their life that foster hope and meaning. OBJECTIVE: The aim of this study was to explore the unique physical and psychosocial-spiritual losses and patterns of grief responses among young adults living with advanced cancer. INTERVENTIONS/METHODS: Theoretical sampling led to the recruitment of 13 young adults, ages 23 to 38 years, diagnosed with stage III or IV cancer. Participants completed 1 semistructured interview, a timeline of pivotal moments throughout their illness, and a sociodemographic survey. Glaser's grounded theory methods informed the study design and analysis. RESULTS: Young adults displayed patterns of disorienting grief, which left them bereft of almost all familiar facets of their pretrauma lives and identities. Disorienting physical and psychosocial-spiritual losses presented in the following subcategories: disorientation to all aspects of former life, lost identity, and isolation. CONCLUSIONS: Findings from this study reveal a novel framework from which to interpret grief experiences among young adults living with advanced cancer. IMPLICATIONS FOR NURSING PRACTICE: The implementation of grief assessments and interventions during pivotal stages in young adults' cancer treatment and recovery may ameliorate psychological distress and normalize perceptions of life disruptions. Nursing education before treatment initiation and termination can reduce young adults' fears surrounding unfamiliar symptoms and prepare them for the physical and emotional uncertainties that often accompany remission or end-of-life.

Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B.

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.