Parent proxy assessment of sibling quality of life following pediatric hematopoietic cell transplantation.

BACKGROUND: When a child undergoes hematopoietic cell transplantation (HCT), the impact extends to the entire family, including siblings. Assessment of the quality of life (QoL) of siblings is challenged by their general lack of availability for regular assessment by clinical providers. Thus, the use of parent proxy reporting may be useful. Our aim was to describe the QoL of siblings of HCT survivors, as reported by their parents, as well as to identify parent and family factors associated with lower sibling QoL. METHODS: A cross-sectional study was utilized to assess parent-reported QoL of the HCT recipient's sibling (Short Form (SF)-10 Health Survey for Children and the Pediatric Symptom Checklist (PSC)-17). Parent QoL was assessed using the SF-12. Multivariable linear regression was used to explore hypothesized predictors of sibling QoL, including parent QoL, family impact/function (Impact on Family Scale, Family Adaptability and Cohesion Evaluation Scales, IV, and a question asking about financial problems) while adjusting for demographic and HCT characteristics. RESULTS: Ninety-seven siblings (55% males) with a mean age of 12 years (standard deviation [SD] 4 years) were assessed, representing HCT survivors, who were an average of 5 years (SD 4 years) post-HCT. Neither sibling psychosocial (mean 49.84, SD 10.70, p = 0.87) nor physical health scores (mean 51.54, SD 8.42, p = 0.08) differed from norms. Parent proxies reported behavioral/emotional problems (PSC-17 total score > 15) in 24% of siblings. While parental ratings of their own physical health (SF-12 were higher than norms (mean 53.04, SD 8.17, p = 0.0005), mental health scores were lower (mean 45.48, SD 10.45, p < 0.0001). In multivariable analysis, lower parent emotional functioning and adverse family function were associated with lower sibling QoL, as reported by parents. CONCLUSIONS: While proxy-reported QoL of siblings did not differ significantly from normative data, both parent QoL and family function were associated with sibling QoL. Future research is needed to understand how siblings themselves perceive their QoL following HCT.

The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Quality of Life Among Parents of Adolescent and Young Adult Brain Tumor Survivors.

We aimed to describe the quality of life (QOL) among parents of adolescent and young adult brain tumor survivors as well as parent, survivor, and diagnosis/treatment-related factors associated with adverse QOL. A cross-sectional study of 28 parents of adolescent and young adult brain tumor survivors (who were on average 10 y postdiagnosis) was used to assess QOL. Parent QOL was measured using the Patient-Reported Outcomes Measurement Information System Global Health measure. Factors associated with adverse parent QOL were explored using logistic regression including: parent, survivor, and diagnosis/treatment-related factors. Parent QOL was within the normal range; however, 40% scored below the clinical threshold of 0.5 SD below the mean for physical and mental health. Parent perceptions of greater family impact, survivor emotional/behavioral health problems, improved cognitive function, and recurrence were associated with adverse parent physical health. Parent anger/sorrow, uncertainty, survivor emotional/behavioral health problems, speech/language problems, and recurrence were associated with adverse parent mental health. Parental emotional resources and perceptions of improved survivor peer relationships were associated with greater parent physical and mental health. The impact of a brain tumor diagnosis and treatment on the QOL of parents may be significant. Interventions are needed to ensure that the needs of parents are met.

Successful Treatment of Genetically Profiled Pediatric Extranodal NK/T-Cell Lymphoma Targeting Oncogenic STAT3 Mutation.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is a distinct type of non-Hodgkin lymphoma predominantly observed in Asian and Latin American adult males. A 12-year-old Hispanic female diagnosed with ENKTCL was enrolled in our genomic profiling research protocol. We identified specific somatic alterations consistent with diagnosis of ENKTCL as well as oncogenic mutations in MAP2K1 and STAT3. To our knowledge, this is the first report of an immunophenotypically confirmed and genetically profiled case of ENKTCL in a female pediatric patient in the United States, including its unique treatment and favorable outcome.

Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation.

Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.

DNA-scaffolded multivalent ligands to modulate cell function.

We report a simple, versatile, multivalent ligand system that is capable of specifically and efficiently modulating cell-surface receptor clustering and function. The multivalent ligand is made of a polymeric DNA scaffold decorated with biorecognition ligands (i.e., antibodies) to interrogate and modulate cell receptor signaling and function. Using CD20 clustering-mediated apoptosis in B-cell cancer cells as a model system, we demonstrated that our multivalent ligand is significantly more effective at inducing apoptosis of target cancer cells than its monovalent counterpart. This multivalent DNA material approach represents a new chemical biology tool to interrogate cell receptor signaling and functions and to potentially manipulate such functions for the development of therapeutics.

Illness uncertainty and quality of life in children with cancer.

BACKGROUND: Illness uncertainty is prevalent in children with cancer and has been associated with increased psychological distress. The relationship between illness uncertainty and quality of life in pediatric cancer patients remains unclear. The aim of the present study was to examine illness uncertainty as a predictor of health-related quality of life in children diagnosed with cancer. It was hypothesized that child-reported illness uncertainty would be negatively associated with child health-related quality of life. PROCEDURE: Children aged 8 to 18 years old and receiving treatment for cancer were recruited to participate in this study. One hundred twenty children and their parent(s) completed measures of illness uncertainty, pain, anxiety, and quality of life during a routine visit to the Cancer Center at Children's Hospital of Orange County. RESULTS: Illness uncertainty was significantly associated with child age (P=0.02), overall health-related (P<0.001) and cancer-related (P<0.001) quality of life, but not with treatment status (on/off chemotherapy) or demographic variables including sex and household income. Regression analyses statistically controlling for age, anxiety, and pain revealed that illness uncertainty significantly predicted child-reported cancer-related and health-related quality of life (P<0.01) as well as parent-reported cancer-specific quality of life (P<0.01). CONCLUSIONS: Illness uncertainty is prevalent and associated with lower quality of life in children diagnosed with cancer. Improved communication with children regarding disease state, treatment expectations, and prognosis may alleviate uncertainty and improve functioning in this vulnerable patient population.

Multilevel socioeconomic effects on quality of life in adolescent and young adult survivors of leukemia and lymphoma.

PURPOSE: Cancer registry survival analyses have shown that adolescent and young adult patients with low socioeconomic status (SES) have reduced survival compared to those with higher SES. The objective of this study was to determine whether neighborhood- (nSES) and/or individual-level SES (iSES) also predicted current quality of life in adolescent and young adult survivors. METHODS: The Socioeconomics and Quality of Life study surveyed adolescent and young adult survivors of leukemia and lymphoma at least one year post-diagnosis using population-based ascertainment. Factor analysis was used to create a multidimensional age-relevant iSES score and compared with a preexisting census-block-group derived nSES score. Four quality of life domains were assessed: physical health, psychological and emotional well-being, social relationships, and life skills. Nested multivariable linear regression models were run to test the associations between both SES measures and quality of life and to compare the explanatory power of nSES and iSES. RESULTS: Data from 110 individuals aged 16-40 were included in the final analysis. After adjustment for sociodemographic confounders, low nSES was associated only with poorer physical health, whereas low iSES was related to poorer quality of life in all four domains with iSES accounting for an additional 14, 12, 25, and 10 % of the variance, respectively. CONCLUSIONS: Measures of SES at the individual as compared to the neighborhood level may be stronger indicators of outcomes in adolescents and young adults, which has important implications for SES measurement in the context of cancer surveillance.

Attitudes regarding analgesic use and pain expression in parents of children with cancer.

BACKGROUND: Children with cancer often experience significant levels of pain and their pain is generally undermanaged. Management of care to patients with cancer has shifted from the hospital to the home, and as such parents are charged with managing children's pain. However, parents may have misconceptions of analgesic use, which can lead to undertreatment of pain in children. The purpose of this study is to examine attitudes toward pain medication and perceptions of pain expression among parents of children undergoing cancer treatment. PROCEDURE: Parents of children who were undergoing cancer treatment at a hospital were recruited to take part in a survey study. A total of 187 parents completed a survey examining their attitudes toward medication and perceptions of pain expression in children. RESULTS: Many parents reported concerns regarding analgesic use to treat their children's pain and misconceptions about how children can express pain. Regression analyses noted that parental perceptions of pain expression were related to children's experience of chronic or recurring pain and the 2 dimensions of child temperament: emotionality and sociability. CONCLUSIONS: Many parents of children with cancer have misconceptions regarding issues of pain management; these misconceptions can potentially lead to undertreatment of pain in children. These misconceptions are associated with aspects of children's temperament.

"You're too young for this": adolescent and young adults' perspectives on cancer survivorship.

Adolescent and young adult cancer survivors face unique challenges not systematically addressed by cancer clinicians. Four focus groups and two individual interviews were conducted with 19 survivors to profile experiences and identify key concerns for future interventions. The resultant themes reflect cancer care continuum challenges (such as delays in diagnosis, problems with adherence), psychosocial concerns (such as infertility and reproductive concerns, changing social relationships, financial burden), and the paradox of being diagnosed with cancer as a young adult. Future intervention development for adolescent and young adult survivors should involve patient voices at each stage of the research process.

Peripheral blood stem cell support for multiple cycles of dose intensive induction therapy is feasible with little risk of tumor contamination in advanced stage neuroblastoma: a report from the Childrens Oncology Group.

BACKGROUND: Poor outcome in Stage 4 neuroblastoma may be improved with increased dose intensity of therapy. We investigated the feasibility of sequential collection and infusion of peripheral blood stem cells (PBSCs) as hematopoietic support for non-myeloablative dose intensive induction chemotherapy given every 21-28 days. METHODS: Twenty-two children with Stage 4 neuroblastoma (>or=1 year of age) received two cycles of high-dose cyclophosphamide (4 g/m(2)), doxorubicin (75 mg/m(2)), and vincristine (2 mg/m(2)) followed by three cycles of interpatient dose escalating carboplatin (Dose Level 0 = 800 mg/m(2); Dose Level 1 = 1,000 mg/m(2)), high-dose cyclophosphamide (4 g/m(2)), and etoposide (600 mg/m(2)). PBSC were harvested following cycle 2, 3, and 4 in Cohort 1 and infused after each subsequent cycle. In Cohort 2, PBSC were harvested after cycle 2 and split into three aliquots for infusion. Dose limiting toxicity (DLT) and ability to administer cycles within 28 days was assessed. RESULTS: Sufficient PBSC (>or=2 x 10(6) CD34 cells/kg per infusion) were collected from 17/21 eligible patients with minimal toxicity and no detectable neuroblastoma cells by immunocytology. Carboplatin at 1000 mg/m(2) resulted in DLT of delayed platelet recovery >28 days in 4/8 patients. Despite de-escalation to 800 mg/m(2), platelet DLT occurred in 4/7 Cohort 1 and 3/7 Cohort 2 patients. CONCLUSION: As defined in this protocol, doses of carboplatin were not tolerable with the PBSC dose administered. However, it was feasible to collect sufficient PBSC from small neuroblastoma patients to use as hematopoietic support with minimal risk of tumor contamination and toxicity.

Implementation and Validation of the Roche Light Cycler 480 96-Well Plate Platform as a Real-Time PCR Assay for the Quantitative Detection of Cytomegalovirus (CMV) in Clinical Specimens Using the Luminex MultiCode ASRs System.

Allogenic stem-cell therapies benefit patients in the treatment of multiple diseases; however, the side effects of stem-cell therapies (SCT) derived from the concomitant use of immune suppression agents often include triggering infection diseases. Thus, analysis is required to improve the detection of pathogen infections in SCT. We develop a polymerase chain reaction (PCR)-based methodology for the qualitative real-time DNA detection of cytomegalovirus (CMV), with reference to herpes simplex virus types 1 (HSVI), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV) in blood, urine, solid tissues, and cerebrospinal fluid. This real-time PCR of 96-well plate format provides a rapid framework as required by the Food and Drug Administration (FDA) for clinical settings, including the processing of specimens, reagent handling, special safety precautions, quality control criteria and analytical accuracy, precisely reportable range (analyst measurement range), reference range, limit of detection (LOD), analytical specificity established by interference study, and analyte stability. Specifically, we determined the reportable range (analyst measurement range) with the following criteria: CMV copies ≥200 copies/mL; report copy/mL value; CMV copies ≤199 copies/mL; report detected but below quantitative range; CMV copies = 0 with report <200 copies/mL. That is, with reference range, copy numbers (CN) per milliliter (mL) of the LOD were determined by standard curves that correlated Ct value and calibrated standard DNA panels. The three repeats determined that the measuring range was 1E2~1E6 copies/mL. The standard curves show the slopes were within the range -2.99 to -3.65 with R2 ≥ 0.98. High copy (HC) controls were within 0.17-0.18 log differences of DNA copy numbers; (2) low copy (LC) controls were within 0.17-0.18 log differences; (3) LOD was within 0.14-0.15 log differences. As such, we set up a fast, simple, inexpensive, sensitive, and reliable molecular approach for the qualitative detection of CMV pathogens. Conclusion: This real-time PCR of the 96-well plate format provides a rapid framework as required by the FDA for clinical settings.

Melanoma in pediatric, adolescent, and young adult patients.

The family practitioner, pediatrician, and dermatologist all have potential roles in the primary prevention, diagnosis, and treatment of localized thin melanomas. Surgical and medical oncologists are often involved when controversy arises over the nature of the skin lesion or whether sentinel lymph node (SLN) biopsies and adjuvant therapy are to be contemplated. This overview of melanoma will deal with the primary and nodal pathology, surgery, and medical therapy of melanoma in pediatric, adolescent, and young adult patients--and will raise areas of controversy that are only recently being addressed in databases of cases from this age group.

Leukemia survival in children, adolescents, and young adults: influence of socioeconomic status and other demographic factors.

OBJECTIVE: In California, leukemia represents ~35, 5, and 2% of all cancers in children (aged 0-14), adolescents (15-29), and young adults (30-39), respectively. Poorer survival has been previously noted in individuals residing in lower socioeconomic status (SES) neighborhoods. We explored the relationship between SES and survival as modified by age and race/ethnicity using data from the California Cancer Registry. METHODS: A total of 7,688 incident cases of first primary leukemia diagnosed during 1996-2005 in individuals aged 0-39 at diagnosis were included in this study. Univariate analyses of overall survival were conducted using the Kaplan-Meier method and multivariate survival analyses were performed using Cox proportional hazard regression to estimate hazard ratios. RESULTS: Multivariate analyses showed that overall survival and lymphoid cancer-specific survival was reduced in those individuals aged 15-39 compared to children aged 0-14. Although shorter survival was observed in non-whites, an association between lower-SES neighborhood and shorter survival was significant only for non-Hispanic whites (NHWs) (p value for trend <0.05). Lack of insurance was significantly associated with shorter survival for all race/ethnicities examined except Asian/Pacific Islanders (p value < 0.05). CONCLUSION: Lower survival in individuals diagnosed with leukemia was observed in adolescents and young adults compared to children and in non-whites compared to NHWs. Further, the independent effects on survival of both low SES and lack of insurance at diagnosis persisted after adjustment for demographic variables and varied across race/ethnicities.

Support and conflict in relationships and psychological health in adolescents and young adults with cancer.

Perceived support and conflict between adolescents and young adults with cancer and their primary caregivers, other family, close friends, and medical staff were examined in relation to adolescents and young adults' psychological health. Adolescents and young adults ( n = 115, 51% male, ages 12-24 years, M (standard deviation) = 16.07 (2.29)) in outpatient cancer treatment perceived more support and conflict within familial relationships than other relationships. Among familial relationships, perceived support and conflict were associated with psychological health; within other relationships, only support was associated with psychological health. Interactions among family were most strongly correlated with psychological distress; interactions with friends were stronger correlates of posttraumatic stress symptoms, positive affect, and posttraumatic growth.

Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer.

Importance: Pediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes. Objective: To evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer. Design, Setting, and Participants: This cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials. RNA sequencing (RNA-Seq) data were obtained from the following 4 clinical sites and analyzed at UCSC: British Columbia Children's Hospital (n = 31), Lucile Packard Children's Hospital at Stanford University (n = 80), CHOC Children's Hospital and Hyundai Cancer Institute (n = 46), and the Pacific Pediatric Neuro-Oncology Consortium (n = 24). The study dates were January 1, 2016, to March 22, 2017. Exposures: Participants underwent tumor RNA-Seq profiling as part of 4 separate clinical trials at partner hospitals. The UCSC either downloaded RNA-Seq data from a partner institution for analysis in the cloud or provided a Docker pipeline that performed the same analysis at a partner institution. The UCSC then compared each participant's tumor RNA-Seq profile with more than 11 000 uniformly analyzed tumor profiles from pediatric and young adult patients with cancer, downloaded from public data repositories. These comparisons were used to identify genes and pathways that are significantly overexpressed in each patient's tumor. Results of the UCSC analysis were presented to clinical partners. Main Outcomes and Measures: Feasibility of a third-party institution (UCSC Treehouse Childhood Cancer Initiative) to obtain tumor RNA-Seq data from patients, conduct comparative analysis, and present analysis results to clinicians; and proportion of patients for whom comparative tumor gene expression analysis provided useful clinical and biological information. Results: Among 144 samples from children and young adults (median age at diagnosis, 9 years; range, 0-26 years; 72 of 118 [61.0%] male [26 patients sex unknown]) with a relapsed, refractory, or rare cancer treated on precision medicine protocols, RNA-Seq-derived gene expression was potentially useful for 99 of 144 samples (68.8%) compared with DNA mutation information that was potentially useful for only 34 of 74 samples (45.9%). Conclusions and Relevance: This study's findings suggest that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into the clinical genomic interpretation framework for difficult-to-treat pediatric and young adult patients with cancer. The study also highlights for the first time to date the potential clinical utility of harmonized publicly available genomic data sets.

"She Was a Little Social Butterfly": A Qualitative Analysis of Parent Perception of Social Functioning in Adolescent and Young Adult Brain Tumor Survivors.

Psychosocial sequelae of diagnosis and treatment for childhood brain tumor survivors are significant, yet little is known about their impact on adolescent and young adult (AYA) brain tumor survivors. Interviews were conducted with parents of AYA brain tumor survivors with a focus on social functioning. Semistructured interviews were conducted with English- and Spanish-speaking parents of AYA brain tumor survivors ≥10 years of age who were >2 years postdiagnosis, and analyzed using emergent themes theoretically integrated with a social neuroscience model of social competence. Twenty parents representing 19 survivors with a survivor mean age 15.7 ± 3.3 years and 10.1 ± 4.8 years postdiagnosis were interviewed. Several themes relevant to the social neuroscience social competence model emerged. First, parents' perceptions of their children's impaired social functioning corroborated the model, particularly with regard to poor social adjustment, social withdrawal, impaired social information processing, and developmentally inappropriate peer communication. Second, ongoing physical and emotional sequelae of central nervous system insults were seen by parents as adversely affecting social functioning among survivors. Third, a disrupted family environment and ongoing parent psychosocial distress were experienced as salient features of daily life. We document that the aforementioned framework is useful for understanding the social impact of diagnosis and treatment on AYA brain tumor survivorship. Moreover, the framework highlights areas of intervention that may enhance social functioning for AYA brain tumor survivors.

Cognitive Impairment in Survivors of Adolescent and Early Young Adult Onset Non-CNS Cancers: Does Chemotherapy Play a Role?

INTRODUCTION: The development of complex cognitive functions including executive functions occurs during adolescence and early young adulthood. Survivors of cancers diagnosed during adolescence and young adulthood (AYA) may be at specific risk for chemotherapy-associated cognitive impairment; however, little data are available that specifically examine long-term cognitive outcomes in the AYA-onset cancer survivor population. METHODS: A literature search was conducted between January 1991 to December 2015 using a variety of search terms pertaining to the AYA-onset cancer population and cognitive outcomes. Articles that described cognitive outcomes in AYA-onset cancer survivors without primary or secondary central nervous system lesions diagnosed at ages 14-25 years old were examined and reported. RESULTS: Three articles fulfilled the inclusion criteria. All three evaluated cognitive outcomes in AYA-onset cancer survivors at varying time points after receipt of systemic chemotherapy. Target groups and neuropsychological evaluation techniques differ across studies. All studies reported increased rates of objective or self-reported cognitive impairment in AYA-onset cancer survivors. DISCUSSION: AYA-onset cancer survivors experience cognitive impairment. Despite the nature of normal adolescent neurodevelopment, chemotherapy exposure during the AYA years may not significantly contribute to cognitive impairment. Chronic cognitive impairment may be associated with chronic complications of cancer therapy. Large-scale standardized, prospective, and longitudinal evaluations of cognitive outcomes specific to AYA-onset cancer survivor population are needed to better understand associated risk factors.

Molecular Genetic Profiling of Adolescent Glassy Cell Carcinoma of the Cervix Reveals Targetable EGFR Amplification with Potential Therapeutic Implications.

Glassy cell carcinoma of the cervix (GCCC) is a very rare and aggressive form of cervical cancer. An adolescent female with advanced metastatic disease was enrolled in our genomic profiling research protocol. We identified high-level amplification of epidermal growth factor receptor (EGFR) and Yes-associated protein-1 (YAP1), which led to the addition of EGFR inhibitors to the chemotherapy regimen. Here, we report the first genetically profiled case of GCCC with potential therapeutic implications.