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81 Background: Up to 20% of childhood cancer survivors suffer from a significant physical function impairment due to cancer or cancer treatment. Early intervention with Occupational Therapy (OT) and Physical Therapy (PT) increases engagement in personal care, leisure interests, school-based tasks, return to work, and prevents cognitive decline. Despite this, less than 30% of childhood cancer survivors receive PT services. To date, facilitators and barriers to implementing cancer rehabilitation (CR) for pediatric cancer survivors have not been adequately explored. Thus, the aim of this research was to identify system-level barriers and facilitators to CR delivery based on surveys completed by hospital administrators, oncology physicians, advanced practice providers, and OT/PT therapists. Methods: A cross-sectional method was employed. Three previously published cardiac rehabilitation delivery instruments specific for administrators, OT/PT therapists and clinical providers respectively were adapted to evaluate CR delivery. All surveys used a 5-point Likert-type response format (e.g., 1 = strongly disagree to 5 = strongly agree). Surveys ranged from 12 items (therapist survey) to 23 items (administrator survey). Questions pertained to knowledge, attitudes, and perceptions regarding CR. Results: A total of 20 administrators (mean age, 49.95 years old, 65% non-Hispanic White, 65% female), 20 providers (mean age, 43.4 years old, 71.4% non-Hispanic White, 67% female), and 20 therapists (mean age, 38.3 years old, 70% non-Hispanic white, 84% female) completed surveys. Administrators’ results indicated mid-range CR knowledge (median: 3.5; IQR 2,5), and all perceived CR as important or extremely important to outpatient care (median: 5; IQR 4,5). Limited insurance coverage and lack of space were the top barriers identified by administrators. Eighty percent of providers endorsed that clinical practice guidelines promote CR referral (median 4; IQR 4,5) and none reported being skeptical of CR benefits. Provider-identified barriers included an inconvenient referral process, lack of CR patient-education materials, and inadequate information on external CR resources. Therapists identified rate of absenteeism and referral rates as barriers to CR. Ninety percent of therapists reported hybrid CR delivery (supervised and unsupervised exercise) could facilitate CR participation (median 4; IQR 4,4). Conclusions: System-wide, there was adequate knowledge and positive perceptions and attitudes regarding CR. However, we identified multiple barriers presenting opportunities for multilevel interventions. These included: insurance coverage advocacy, streamlining referral processes to CR services, providing information on external CR programs, providing patient education materials, and leveraging hybrid CR delivery to optimize participation.

280 Background: The COVID-19 pandemic has negatively impacted morbidity, mortality, and economic status globally. Adolescents and young adults (AYAs, age 15-39) with cancer may experience disparities in access to health care, compounded by social distancing and stay-at-home orders aimed at reducing the spread of COVID-19. The use of telehealth platforms for clinical visits has accelerated rapidly due to policy changes during the pandemic. Telehealth may provide an avenue for accessing healthcare services among AYAs with cancer; yet, there are few data on AYAs’ preferences and satisfaction relating to telehealth. Our study examined telehealth utilization, satisfaction, preferences and future recommendations among AYAs with a cancer diagnosis. Methods: AYAs in active cancer treatment or in post-treatment survivorship completed an online questionnaire that assessed their experience with telehealth, including: satisfaction with the telehealth visit, likelihood of participating in a future telehealth visit, topics participants would like to discuss via telehealth, and open-ended comments regarding suggestions for improving future telehealth visits. Participants were recruited in two cohorts: a pre-vaccine cohort (September 2020 - January 2021) prior to availability of COVID-19 vaccines in Texas; and, a post-vaccine cohort (April 2021 - May 2021) after vaccine availability. Descriptive statistics were used to summarize preliminary findings. Results: Participants included 273 AYAs with cancer (mean age, 33.8 years old, 26% male, 73% non-Hispanic White, 11% in active treatment, 53% in post-vaccine cohort). Of 71.7% who participated in at least one telehealth visit, 50.9% were somewhat or very satisfied with their visit(s). Topics that all participants preferred to address via telehealth included: stress management (34%); sleep quality (31.7%); diet/nutrition (32.1%); and mental health (29.5%).Topics least preferred for telehealth included fertility counseling (16.7%) and sexual health (13.7%). Open-ended comments from participants highlighted the importance of healthcare providers taking time to listen to their concerns during their visits. Participants suggested that telehealth encounters can be improved by ensuring adequate time for the visit plus good video and audio quality, and using telehealth for follow-up visits rather than initial consultations. Conclusions: About half of AYAs who had participated in a telehealth visit indicated satisfaction with the visit(s). Findings indicated AYAs’ preferences for the types of topics that are most and least preferred to address in telehealth visits, as well as specific recommendations for improving the quality of visits. Consideration of AYAs’ preferences and recommendations in the ongoing implementation of telehealth may help improve patient satisfaction.

Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten survival in glioblastoma. Dexamethasone-induced anti-proliferative effects may confer protection from radiotherapy- and chemotherapy-induced genotoxic stress. This study highlights the importance of identifying alternative agents such as vascular endothelial growth factor antagonists for managing oedema in glioblastoma patients. Beyond the established adverse effect profile of protracted corticosteroid use, this analysis substantiates the request for prudent and restricted use of corticosteroids in glioblastoma.

The prevalence of overweight and obesity is increasing worldwide, and the evidence base for a link between obesity and cancer is growing. In the United States, approximately 85,000 new cancer cases per year are related to obesity. Recent research has found that as the body mass index increases by 5 kg/m2, cancer mortality increases by 10%. Additionally, studies of patients who have had bariatric surgery for weight loss report reductions in cancer incidence and mortality, particularly for women. The goal of this review is to provide an update of recent research, with a focus on epidemiologic studies on the link between obesity and cancer. In addition, we will briefly review hypothesized mechanisms underlying the relationship between obesity and cancer. High priorities for future research involve additional work on the underlying mechanisms, and trials to examine the effect of lifestyle behavior change and weight loss interventions on cancer and intermediate biomarkers.

MYC overexpression has been implicated in the pathogenesis of most types of human cancers. MYC is likely to contribute to tumorigenesis by its effects on global gene expression. Previously, we have shown that the loss of MYC overexpression is sufficient to reverse tumorigenesis. Here, we show that there is a precise threshold level of MYC expression required for maintaining the tumor phenotype, whereupon there is a switch from a gene expression program of proliferation to a state of proliferative arrest and apoptosis. Oligonucleotide microarray analysis and quantitative PCR were used to identify changes in expression in 3,921 genes, of which 2,348 were down-regulated and 1,573 were up-regulated. Critical changes in gene expression occurred at or near the MYC threshold, including genes implicated in the regulation of the G1-S and G2-M cell cycle checkpoints and death receptor/apoptosis signaling. Using two-dimensional protein analysis followed by mass spectrometry, phospho-flow fluorescence-activated cell sorting, and antibody arrays, we also identified changes at the protein level that contributed to MYC-dependent tumor regression. Proteins involved in mRNA translation decreased below threshold levels of MYC. Thus, at the MYC threshold, there is a loss of its ability to maintain tumorigenesis, with associated shifts in gene and protein expression that reestablish cell cycle checkpoints, halt protein translation, and promote apoptosis. [Cancer Res 2008;68(13):5132–42]

Background. Anaplastic astrocytoma (AA) represents 7% of primary brain tumors in adults. Patient-, tumor-, and treatment-related factors are thought to be predictive of survival. We retrospectively assessed the association of patient-, tumor-, and treatment-related factors with survival in AA treated with radiotherapy (RT) at our institution. Patients and methods. Medical records of patients with AA treated with RT between 1987 and 2007 were reviewed. Patient-, tumor-, and treatment-related variables were recorded and used to assign patients to a Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification. First use of chemotherapy was recorded. Log-rank tests and Cox regression models were used to assess for an association of patient-, tumor- and treatment-related factors with survival. Results. One-hundred twenty-six patients were eligible for study. Median age, Karnofsky performance status, and duration of symptoms were 43 years, 90, and 8 weeks. Median radiation dose was 59.4 Gy; 61% of patients underwent tumor resection, and 17% and 41% of patients received temozolomide during and after RT. Median survival was 31 months, and 2-year survival was 58%. RTOG RPA class was associated with survival (p < 0.001), but use of temozolomide during or after RT was not (p > 0.05). Conclusions. In this retrospective study with inherent limitations, RTOG RPA classification was associated with survival. Further studies are necessary to confirm or refute this finding

Serious dermatologic adverse events such as erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported in patients receiving antiepileptic drugs (AEDs) and cranial radiotherapy (RT). Given the frequency of AED-associated rashes and the infrequency of serious dermatologic adverse events after cranial RT, we sought to further assess the prevalence of cutaneous eruptions in patients receiving an AED before and after cranial RT. We reviewed medical records of patients taking AEDs while undergoing RT for a high-grade glioma and recorded demographic, disease, and treatment parameters, as well as the development of rashes. Rashes were found in 19 % of patients taking AEDs. Phenytoin was most commonly implicated (93 %) in rash formation compared with other AEDs (P < 0.0001), both before and during RT. Most rashes (76 %) occurred before starting RT (P < 0.0001). However, of those during RT, most were associated with phenytoin compared with other AEDs (P = 0.002). One case of SJS was noted in a patient receiving phenytoin prior to RT. While rashes were slightly less prevalent in patients receiving temozolomide compared with those not receiving temozolomide (3.4 vs 4.8 %), this difference was not statistically significant (P = 0.65). Rashes are relatively common in patients receiving AEDs, with the highest incidence associated with phenytoin. However, the risk of serious dermatologic events is low. There did not appear to be an association between the receipt of cranial radiotherapy and the development of AED-associated rash with phenytoin or other AEDs.

Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS).Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS.Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), independently of RTOG RPA class and seizure history.VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

Survival of elderly patients with glioblastoma (GBM) is poor, but improves with tumor resection and radiotherapy (RT). Concurrent temozolomide (TMZ) chemotherapy during RT improves the survival of younger patients with GBM, but the benefit in elderly patients is unclear. Medical records of patients ≥65 years old with primary GBM, histologically confirmed at Memorial Sloan-Kettering Cancer Center and treated with RT, were reviewed. Survival was associated with patient (age, performance status), tumor (single or multiple), and treatment (extent of surgery, RT field, technique, fractionation and use of concurrent TMZ) characteristics in a multivariable Cox regression model. Grade ≥3 hematologic toxicity rates were compared to reported rates in younger patients. Median age of the 291 patients studied was 71 years. Longer survival was associated with younger age, tumor resection, and concomitant TMZ and RT (p < 0.01). Concurrent TMZ and RT improved median survival of patients with favorable prognostic factors from 12 to 21 months and from 10 to 13 months in patients 65–70 and ≥71 years old, respectively. Concomitant TMZ and RT increased the 2 year OS rate from 14 to 41 % and from 5 to 24 % in patients 65–70 and ≥71 years old, respectively. Grade 3–4 thrombocytopenia was significantly more frequent in the present cohort. Survival of elderly patients with GBM may be prolonged with the use of concomitant TMZ during RT. An ongoing randomized study will determine the benefit of this approach in a prospective fashion.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) survivors are at a higher risk for obesity and overweight than even the general pediatric population. Obesity risk has been linked to certain parenting (permissive and authoritarian) styles and to lack of parental support for weight-related behaviors. We thus sought to evaluate the potential contribution of parenting behaviors and styles to weight related issues and depression among overweight and obese children who have survived ALL. METHODS: Surveys on parenting styles, behaviors, communication styles, and parental support for weight management behaviors were performed by the primary parents of overweight and obese youth recruited for a clinical trial of a weight management program among childhood ALL survivors aged 8-18 years at three tertiary care pediatric institutions. In addition, the Childhood Depression Inventory was performed by the recruited children and baseline demographics from both children and parents were collected. Distribution and correlation analyses of survey results and collected baseline data were performed. RESULTS: Thirty five overweight (20%) and obese (80%) children recruited to date comprised 43% male, median (IQR) age of 13 (10,16) years, median BMI % of 98 (95,99)% and 89% Hispanic. The corresponding primary parent population consisted of 89% women, median age of 42 (38,48) years, median BMI of 33 (28,40) kg/m2 (60% obese, 26% overweight), and 89% Hispanic. While the majority (97%) of parents reported an authoritative parenting style, there were variations in the amount of permissive and dysfunctional parenting reported. Parenting verbosity in reaction to misbehavior was moderately associated with increased baseline child BMI percentile (r=0.37, p=0.03). Authoritarian parenting style moderately correlated with parental support for physical activity (specifically walking and biking) for the entire cohort (r=0.36, p=0.03). However, overall, parenting styles did not specifically correlate with support for weight management behaviors or with age and gender-matched child BMI percentiles. Parental over-reactivity correlated with higher child depression rating scores (r=0.35, p=0.04) while parental granting of autonomy was associated with lower depression rating scores (r=-0.35, p DISCUSSION: We did not observe a preponderance of parenting styles associated with greater weight status in children among overweight and obese youth with ALL. However, specific parenting styles and behaviors were related to child weight status, parental weight management support, and depression ratings among overweight and obese ALL child survivors. These data confirm the important role of parents in weight management among young childhood ALL survivors. Citation Format: Jeannie S. Huang, Laura Terrones, Maria Chang, Lindsay Dillon. Parenting considerations in the management of overweight and obese childhood ALL survivors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1368. doi:10.1158/1538-7445.AM2013-1368