bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphisms in genes OPRM1, β-arrestin 2, STAT6, and COMT and clinical outcome to opioid therapy.
Authors: Cros Sara , Buges Cristina , Ginés Alba , Martinez Cardús Anna , Ruiz de Porras Vicenç , Capdevila Laia , Carcereny Enric , Martinez-Balibrea Eva , Abad Albert
Published: March 2020

9129

Background: Morphine sulfate is the most widely used opioid in oncologic pain. There is a high variability in response between individuals. The objectives are to correlate the variability in response (R) and tolerability with polymorphisms within OPRM1, β-arrestin 2, STAT6 and COMT gene sequences. Methods: DNA from 44 oncologic patients (pts) with an EVA score > 6 was prospectively analyzed using allelic discrimination techniques and automatic sequencing. Pts (never treated with opioids) received morphine sulfate 10 mg per day. Pain was assessed by EVA score and toxicity was evaluated according to the most common opioid side effects. Symptomatology was reassessed after 72 hours. Chi-squared and Fisher’s tests where used to analyze data. Results: 17 pts (38.6%) responded with an EVA < 3. 6 pts (13.6%) did not experience toxicity, 36 pts (81.8%) had mild side effects and 2 pts (4.5%) had severe side effects. There was no relation between R rate (RR) and tolerance. 76.5% of pts responding to treatment had a CC/CT β-arrestin 2 genotype and this was associated with a better RR (CC/CT R = 46.4% vs. TT R = 25% p = 0.16). The 2 pts having severe side effects belonged to CC/CT group. COMT genotypes AA/GA were associated with a higher RR (83.3%pts) and better tolerance (100% pts with no toxicities). OPRM1 genotype GG was associated with both treatment failure (0% responded) and worse tolerance (any toxicity = 100%; severe side effects = 33%). Only 2,4% pts in the AA/GA genotype experienced some toxicity (p = 0.041). Although STAT6 genotypes were not associated with RR, tolerance was better in those pts with an AA or GA genotype with 97.5% pts showing either mild or no side effects (p = 0.007). Conclusions: Common variants in β-arrestin 2, COMT, OPRM1 and STAT6 genes have shown to predict for opioid-associated response and side effects in oncologic patients. Further studies are needed to assess factors determining the variability in response and tolerance to opioid treatment.
Cognitive symptoms in non-Hodgkin lymphoma survivors: Prevalence and discussion with doctors.
Authors: Arora Neeraj K , Jensen Roxanne E , Forsythe Laura Pence , Mitchell Sandra A. , Bellizzi Keith M , Aziz Noreen , Rowland Julia Howe , Hamilton Ann S. , Potosky Arnold L.
Published: March 2020

9130

Background: Several studies have documented the negative impact of chemotherapy on patients’ cognitive functioning. However, this concern has been understudied among non-Hodgkin Lymphoma (NHL) survivors. Methods: We analyzed survey data from a population-based study of survivors diagnosed with aggressive NHL in Los Angeles County 2-5 years prior to the study; data were collected between 2003-2005. We assessed prevalence of cognitive symptoms (CS) by a single item screener that asked if in the past 6 months survivors experienced problems with memory, attention, or concentration; if yes, we asked if they discussed the problem with a doctor. Frequency of CS was assessed by a 4 item scale that measured how often survivors experienced different CS in the past 4 weeks (none, a little, some, most, all the time). Logistic regression analyses identified correlates of reporting CS (yes/no) as well as discussion with a doctor (yes/no). Analyses were based on data from 358 survivors who had received chemotherapy and saw a doctor for follow-up care in the past year. Results: 134/358 survivors (37%) reported CS, many reporting difficulty some, most, or all the time with memory (64%), attention (58%), concentration (57%), and problem solving (46%). Survivors with higher education, who were not married/partnered, and who had more comorbidities were more likely to report CS (p<0.05 for all). Report of CS was not associated with age, NHL grade, time since completion of chemotherapy, or having been treated with radiation or bone marrow/stem cell transplant. Of the 134 survivors who reported CS, only 43% discussed them with a doctor. Survivors who reported being given information about late effects of treatment were more likely to discuss CS than those who were not (OR: 3.4, 95% CI 1.4-8.5, p<0.01). Conclusions: One in three NHL survivors reported CS following chemotherapy; however, a majority did not discuss these with a doctor. Periodic screening for CS in NHL survivors may be needed and would provide an opportunity to improve patient-clinician communication about this issue. Additionally, research that identifies mechanisms that cause CS in this population is warranted in order to develop targeted behavioral and medical interventions.
Prospective cohort study of chemotherapy-associated toxicity and supportive care in oncology practice.
Authors: Culakova Eva , Dale David C. , Poniewierski Marek S. , Kuderer Nicole Maria , Wogu Adane , Crawford Jeffrey , Lyman Gary H.
Published: March 2020

9135

Background: Neutropenic complications remain important dose-limiting toxicities of cancer chemotherapy associated with considerable morbidity, mortality and cost. The risk of the initial neutropenic event is greatest in the first cycle when most patients are receiving full dose chemotherapy. Methods: A prospective cohort study of adult patients with solid tumors or lymphoma receiving a new chemotherapy regimen was conducted at 115 U.S. practice sites between 2002 and 2006. Chemotherapy-associated toxicities were captured in up to 4 cycles including severe neutropenia (SN), febrile neutropenia (FN), and infection. Documented interventions included colony-stimulating factor (CSF) and antibiotics use and reductions in chemotherapy relative dose intensity (RDI). Results: Results are available on 3,638 patients starting chemotherapy of which 3,301, 2,937, and 2,199 went on to cycles 2, 3, and 4, respectively. The majority of neutropenic and infection events occurred in cycle 1. A significant inverse relationship was observed between subsequent reductions in neutropenic and infectious events and efforts to reduce these complications (Table). Most patients with stage 4 solid tumors underwent reductions in chemotherapy RDI. Patients with lymphoma and stage 1-3 solid tumors were less likely to undergo dose reductions with half or more receiving prophylactic CSFs during treatment. Approximately 15% of patients also received prophylactic antibiotics. Conclusions: While the risk of neutropenic complications remains greatest during the initial cycle of chemotherapy, clinician efforts to reduce the risk of these events vary with cancer type and stage. Reduced dose intensity is evident in two-thirds of patients with advanced solid tumors whereas the CSFs are employed in half to two-thirds of patients with early stage solid tumors or lymphoma. [Table: see text]
Validation of the NCI patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in women receiving treatment for metastatic breast cancer.
Authors: Mitchell Sandra A. , Lang Kathy , Nichols Christine , Clauser Steven B. , Federico Victoria , Lalla Deepa , Tripathy Debu , Hurvitz Sara A. , Castro Kathleen M. , Reeve Bryce B. , Rogak Lauren J. , Denicoff Andrea , Chen Alice , Piekarz Richard , Bennett Antonia V , Atkinson Thomas Michael , O'Mara Ann M. , Minasian Lori M. , Basch Ethan M.
Published: March 2020

9144

Background: NCI PRO-CTCAE is designed to enhance adverse event reporting by integrating patients’ self-report of the frequency (F), severity (S) and interference (I) with usual activities of 78 symptomatic treatment toxicities. This study examined the construct validity of a subset of PRO-CTCAE items in women with metastatic breast cancer (MBC). Methods: 207 women (70% aged 45-59 years; 94% White;71% college-educated) with HER2+ MBC who had received treatment in the past month were recruited from 6 U.S. breast cancer support groups and completed a web survey that collected 18 PRO-CTCAE symptoms, and the Rotterdam Symptom Checklist (RSC). Pairwise concordance among PRO-CTCAE symptom dimensions was examined using weighted Kappa and Bowker’s test for symmetry. Results: Respondents were a median of 47 months since MBC diagnosis and 61% rated their health-related quality of life (HRQL) as good to excellent. Symptom prevalence was similar for PRO-CTCAE and RSC, with respondents more likely to endorse mood disturbance on PRO-CTCAE (Anxiety/Worry 90%; Sad/Unhappy Feelings 86%) vs. RSC (Anxiety 63%; Depressed Mood 61%). There was parallel rank-ordering of fatigue, anxiety, insomnia, depression, difficulty concentrating and neuropathy as the symptoms that were most severe, interfered most and caused the greatest bother. Within PRO-CTCAE, pairwise agreement among F, S and I was moderate for most symptoms (κw=.42 to .54). Agreement between F and S was highest for pain, nausea and arm/leg swelling (κw=.61 to .80), and lowest for anxiety/worry and sad/unhappy feelings (κw= .27-.37). Except for arm/leg swelling, endorsement patterns by the dimensions of F, S and I were distinct (Bowker’s p all <.002). Across PRO-CTCAE symptoms, S was consistently higher than I (mean differences .12 to .72, all p<.01]). Means for S were consistently and significantly higher for those with impaired versus preserved HRQL, providing evidence of construct validity. Conclusions: This study supports the construct validity of PRO-CTCAE, and suggests that F, S and I dimensions offer non-overlapping information relative to 17 /18 PRO-CTCAE symptomatic toxicities.
Health behaviors among testicular cancer survivors.
Authors: Palmer Steven C , Jacobs Linda A. , Coyne James C. , Vaughn David J.
Published: March 2020

9145

Background: Testicular cancer survivors (TCS) experience elevated risk for cardiovascular issues including coronary artery disease that present a greater threat to their long-term health than recurrence of cancer. These risks may be moderated by health behaviors (HBs), yet little is known about HBs or their barriers in this population. This is unfortunate, as these barriers may serve as intervention targets. This study examined HBs and their barriers in a population-based sample of TCS. Methods: TCS were recruited through the PA Cancer Registry. Eligible individuals were diagnosed with testicular cancer between 1990 - 2007 and provided informed consent. Participants completed measures of tobacco use, alcohol use, dietary habits, physical activity, BMI, quality of life (QOL), and barriers to performing HBs, as well as self-reported disease and treatment information. Results: 189 participants provided data. Participants were middle-aged (M=44 yrs. R=19-59), predominately white (95%), married (72%), parents (69%), 6.8 years post-diagnosis (R=1-19), and at normative levels for physical and psychosocial QOL. A substantial minority (31%) was unaware of their disease stage or histopathological type (27%), although 89% reported surgery, 32% chemotherapy, and 53% XRT. Almost 25% reported current tobacco use, and 35% reported “risky” alcohol use. Adequate aerobic activity was reported by half, but only 28% reported adequate strength and flexibility activities. 84% reported above normal BMI, with 35% in the obese range. Barriers to HBs included cancer-related problems (e.g., neuropathy, pain, hernia risk) and competing demands (e.g., work responsibility, time constraints). Cancer-related barriers were related to worse physical QOL and higher BMI. Competing demands predicted worse psychosocial QOL, unhealthy eating, and inadequate physical activities. Conclusions: Given the negative HBs in this sample and their potential cardiovascular risk, interventions aimed at reducing tobacco and risky alcohol use, as well as improving dietary and physical activity levels are needed. These interventions will likely need to overcome perceived barriers to adoption of HBs in order to be successful.
Lifetime traumas and their influence on advanced cancer patients’ illness understanding and likelihood of end-of-life discussions.
Authors: Kacel Elizabeth L , Maciejewski Paul K , Prigerson Holly Gwen
Published: March 2020

9146

Background: Research on posttraumatic stress in cancer patients has focused on patient reactions to their cancer diagnosis. Few studies have examined the impact of lifetime traumatic events prior to diagnosis on how advanced cancer patients understand the life-threatening nature of their illness and how likely they are to discuss their end-of-life (EOL) wishes with their oncology providers. Methods: The Coping with Cancer (CwC) is an NCI-funded prospective, multi-institutional cohort study of advanced cancer patients and their caregivers. Participants were recruited from September 2002 to February 2008 from six comprehensive cancer centers across the United States. Lifetime traumas were captured by the number of events reported in response to the Structured Clinical Interview for the DSM-IV (SCID) Lifetime Posttraumatic Stress Disorder question that probed for “extremely upsetting” life events. Associations between patient characteristics and number of lifetime traumas were estimated as odds ratios using ordinal logistic regression. Associations between number of lifetime traumatic exposures, controlling for confounding patient characteristics, and patient Terminal Illness Acknowledgement (TIA) and reports of EOL discussions were estimated as odds ratios using multiple logistic regression. Results: After adjusting for race, education, and recruitment site, the number of lifetime traumas patients reported remained significantly associated with TIA (OR = 1.25, p = .034) and discussion of EOL wishes (OR = 1.29, p = .013). Conclusions: The greater the number of traumatic experiences reported by cancer patients the more likely they are to acknowledge that they are terminally ill and discuss their end-of-life wishes with their oncology providers. The impact of witnessing or experiencing serious or life-threatening events in the past appears to improve advanced cancer patients’ abilities to understand the seriousness of their condition and increases the likelihood that they will discuss their preferences for care at the end of life with their doctors.
Vincristine (V), dactinomycin (A), and lower doses of cyclophosphamide (C) with or without radiation therapy for patients with newly diagnosed low-risk embryonal rhabdomyosarcoma (ERMS): A report from the Children’s Oncology Group (COG).
Authors: Walterhouse David , Pappo Alberto S. , Meza Jane L , Breneman John C. , Hayes-Jordan Andrea Anita , Parham David , Cripe Timothy P , Meyer William H. , Hawkins Douglas S.
Published: March 2020

9509

Background: Intergroup Rhabdomyosarcoma Study (IRS) trials showed improved survival with VAC compared with VA for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II ERMS (see table). In COG ARST0331, we hypothesized that VA in combination with lower doses of C (total cumulative dose=4.8 g/m2) would produce the benefit of IRS-IV VAC with less toxicity for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II low-risk ERMS. Methods: This single arm, non-inferiority, phase III study enrolled newly diagnosed patients with Stage 1 Group III (non-orbit) ERMS or Stage 3 Group I/II ERMS onto Subset 2. Therapy was 4 cycles of VAC followed by 12 cycles of VA over 46 weeks (total cumulative doses: V=54 mg/m2, A=21.6 mg/m2, C=4.8 g/m2). The radiation therapy dose was 36 Gy for Group IIA patients, 41.4 Gy for Group IIB/C patients, and 50.4 Gy for Group III patients. From 2004–2008 girls with Group III vaginal RMS did not receive radiotherapy if a complete response was achieved with chemotherapy with or without delayed resection. The primary endpoint was failure-free survival (FFS), and results were compared with a fixed expected outcome. Results: With a median follow-up of 3.0 yrs, we observed 16 failures vs. 7.8 expected failures. Estimated 3-yr FFS was 63% (95% CI: 46%, 75%) (n=60), and overall survival (OS) was 84% (95% CI: 68%, 93%). Estimated 3-yr FFS was 46% (95% CI: 23%, 67%) for girls with non-bladder genitourinary tract ERMS (n=21) and 75% (95% CI: 53%, 88%) for all other Subset 2 patients (n=39). Conclusions: We observed suboptimal FFS of patients with Subset 2 low-risk RMS using reduced total cyclophosphamide (4.8 g/m2). Results were complicated by the choice of no radiation therapy for girls with vaginal tumors. Future studies for low-risk RMS Subset 2 patients could investigate a dose of C between 4.8 and 26.4 g/m2 with VA and local radiotherapy. [Table: see text]
Effect of radiation on outcome of types II and III PPB: A report from the International Pleuropulmonary Blastoma Registry.
Authors: Williams Gretchen M , Priest John R. , Finkelstein Marsha J , Harris Anne , Doros Leslie Ann , Kratz Christian , Schultz Kris Ann Pinekenstein , Hill D Ashley , Dehner Louis P , Messinger Yoav H.
Published: March 2020

9521

Background: Pleuropulmonary blastoma (PPB) is a rare dysembryonic lung neoplasm of early childhood with progression from a purely cystic (Type I) lesion to a solid high-grade sarcoma Type III (T-III), or a mixed solid/cystic stage Type II (T-II). Surgery and chemotherapy are required for T-II and T-III PPB, but the benefit of radiation therapy for T-II and T-III PPB is debated and is being evaluated in this study. Methods: This is a retrospective analysis of central pathology-reviewed Types II and III PPB from the IPPBR. Treatments were chosen by physician, were not randomized, and included surgery and chemotherapy. The outcome of patients treated with upfront radiation (before progression or relapse) was compared to patients who did not receive radiation. Event-free survival (EFS) and overall survival (OS) were determined to last follow-up, using the Kaplan-Meier analysis, with log-rank test. Results: Outcome for 212 patients (117 Type-II and 95 Type III) was significantly better for T-II than T-III: EFS for T-II was 68.1% vs. T-III 45.7% (P=0.002), and OS for T-II was 75.2% vs. T-III 57.9% (p=0.01). Excluding patients with incomplete therapy information, 174 were treated with surgery and chemotherapy. Of these 44 (25%) also received radiation therapy; 130 patients did not. The table below shows comparison of radiated vs. non-radiated. Radiation provided no additional survival benefit, overall or by tumor Type. Multivariate analysis showed that gender and extent of primary tumor resection (biopsy vs. gross total resection) had no effect on outcome, however T-II vs. T-III retained prognostic significance. Conclusions: For this collection of advanced-type PPB, outcome is significantly better for T-II than T-III. For patients treated initially with surgery and chemotherapy, adding radiation therapy offered no improvement in event-free or overall survival. Limitations of this study include its retrospective nature and non-uniform treatment regimens. [Table: see text]
Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults (AYA): A population-based study.
Authors: Vergamini Lucas B. , Frazier A. Lindsay , Abrantes Fernanda L. , Ribeiro Karina Braga , Rodriguez-Galindo Carlos
Published: March 2020

9523

Background: Studies have shown an increase in thyroid cancer incidence among adults since the 1990s. However, few studies have evaluated this occurrence among children and AYA. Increases resulting from enhanced detection are most likely to involve small tumors. The objective of this study is to investigate trends in incidence of differentiated thyroid carcinomas in children and AYA by size and sex. Methods: This is an ecological time-trend study. Cases of differentiated thyroid cancer (1984-2008) in patients younger than 30 years old were selected from SEER 9 cancer registries using International Classification of Diseases for Oncology 3rd edition (ICD-O-3) codes for papillary and follicular cancers (codes 8050/3, 8052/3, 8130/3, 8260/3, 8290/3, 8330-8332/3, 8335/3, 8340-8344/3, 8450/3 and 8452/3). Patients who had multiple primary tumors were excluded from the study. SEER*Stat software was used to calculate age-standardized rates (estimated per 1,000,000 persons; World Standard Population) and annual percentage changes (APC) were calculated using Joinpoint model. Results: Rates ranged from 2.77 (1990) to 7.45 (2002) for males and from 17.19 (1987) to 41.3 (2008) for females. Overall, a significant increasing trend in incidence was observed for females (APC=3.20, 95%CI 2.80, 3.60). When a stratified analysis based on tumor size was performed, significant increasing trends were noted for the following categories: 0.5-0.9 cm (Males: APC=3.50, 95%CI 1.50, 5.40; Females: APC=7.30, 95%CI 5.90, 8.80), 1.0-1.9 cm (Males: APC=3.20, 95%CI 1.00, 5.40; Females: APC=2.90, 95%CI 2.20, 3.70), and ≥ 2cm (Males: APC=1.30, 95%CI 0.30, 2.40; Females: APC=2.50, 95%CI 1.70, 3.20). However, no statistically significant trends were noted for tumors <0.5 cm (Males: APC=2.50, 95%CI -0.30, 5.40; Females: APC=2.0, 95%CI -6.90, 11.80). Conclusions: Incidence rates for differentiated thyroid carcinoma are also increasing among children and AYA in the United States. The absence of increasing trends for small tumors (< 0.5cm) rules out diagnostic scrutiny as the only explanation for the observed results. Environmental, dietary and genetic factors should be investigated.
Association of bone mineral density with incidental renal stone in long-term survivors of childhood acute lymphoblastic leukemia.
Authors: Gawade Prasad Laxman , Ness Kirsten K. , Sharma Shelly , Li Zhenghong , Srivastava Deo Kumar , Spunt Sheri L. , Nottage Kerri , Hudson Melissa M. , Kaste Sue
Published: March 2020

9527

Background: With 5-year survival of childhood acute lymphoblastic leukemia (ALL) now exceeding 90%, long term morbidities are of growing concern. Both low bone mineral density (BMD) and renal dysfunction have been reported in ALL survivors. Our objective was to evaluate the association between low BMD and incidental renal stones, a known predictor of renal dysfunction. Methods: Adult participants who were 10+ year survivors of childhood ALL and members of St. Jude Lifetime Cohort study were recruited between 12/2007 and 3/2011. During their risk-based medical evaluations they underwent quantitative computed tomography (QCT) to evaluate BMD. Incidental renal stones were identified by radiologists’ review of axial QCT source images. Demographic information was abstracted from responses to health surveys and dietary intake from a Block food frequency questionnaire. Association between BMD and renal stones was evaluated in a multivariable logistic regression model. Confounding variables were selected using directed acyclic graphs and change in effect estimates strategy. Results: At a median of 26.1 years from diagnosis, BMD Z score of > 1 standard deviation (SD) was detected in 77/662 (11.6%) and renal stones in 73/662 (11%) participants. In a multivariable model adjusted for age, dietary vitamin D and renal radiation, when compared to BMD Z score > 1 SD, the risk of renal stones increased with a decrease in BMD Z-score; 1 to 0 SD (Odds Ratio (OR), 1.93; 95% confidence interval (CI), 0.69 to 5.41), 0 to -1 SD (OR, 1.46; 95% CI, 0.52 to 4.05), -1 to -2 SD (OR, 2.72; 95% CI, 0.81 to 6.41), and ≤ -2 SD (OR, 4.96; 95% CI, 1.43 to 17.13). Older age (45-54 vs.18-24 y; OR, 3.66; 95% CI, 1.10 to 12.15), renal radiation (OR, 1.97; 95% CI, 0.59 to 6.50) and > 141.5 IU intake of vitamin D (OR, 1.65; 95% CI, 0.98 to 2.77) were also associated with renal stone formation. Conclusions: Our results not only help us recognize survivors at risk, but also informs radiologists to be vigilant of incidental renal stones among older ALL survivors with low BMD.
A longitudinal study of anthracycline cardiotoxicity in pediatric Ewing sarcoma.
Authors: Brown Tanya Renae , Vijarnsorn Chodchanok , Potts James , Milner Ruth , Sandor George , Fryer Christopher
Published: March 2020

9529

Background: Trends in cardiac function over time have not been previously described in Ewing sarcoma. Our cohort is unique as all the cardiac evaluations occurred systematically in one tertiary cardiology unit during a 28 year period. Objectives: 1.To evaluate the cardiac functional trends in the cohort at baseline, during treatment and in surveillance. 2.To evaluate the risk factors associated with cardiac toxicity. Design: Received ethics approval for a retrospective chart review of all patients less than 17 years, diagnosed with Ewing sarcoma from 1978-2006, treated initially at British Columbia Children’s Hospital . Methods: There was complete data on 71/79 eligible patients. Echocardiograms were recorded at 5 time points: pre treatment, worst function during treatment, on therapy completion, worst function during surveillance and the most recent echocardiogram. Cardiac toxicity was graded using CTCAE v 4.0. The statistical analysis with SAS software v 9.2 calculated the chi square and odds ratios to explore a possible association between exposure and outcome. Results: Median age at diagnosis 11.1 yrs (2.2-16.1 yrs), 52% female, metastatic in 17, overall survival 74% at 10yrs. A total of 397 echocardiograms were performed with 244 (61%) being normal and 153 (39%) being abnormal. The median cumulative dose of anthracyclines was 365mg/m2. Grade 1-5 cardiomyopathy occurred in 42 (59%) patients. Grade 3-5 toxicity occurred in 11 (15%) patients on chemotherapy completion increasing to 23 (32%) 120 months post diagnosis. The median time to the worst cardiac function was 51months (2-183). Four of 19 (20%) deaths were cardiac related including 2/3 cardiac transplants. Conclusions: Symptomatic cardiac toxicity increased from 20% noted in our earlier Ewings cohort (Kakader et al. 1997) to 32% with longitudinal evaluation assessments. Significant and progressive cardiac toxicity occurred after completion of chemotherapy.
Parent-reported cognition and its clinical applications in pediatric oncology.
Authors: Lai Jin-Shei , Krull Kevin R. , Zelko Frank , Wagner Lynne I. , Cella David , Goldman Stewart
Published: March 2020

9532

Background: Parent-reported cognitive function (PCF) of their child's cognitive abilities is often used to trigger referral for comprehensive neuropsychological evaluation. The purpose of this study was to evaluate the clinical utility of PCF to predict impairment as measured by neuropsychological assessment and to identify factors associated with PCF. Methods: 565 patients (53% brain tumor, BT; 47% other types of cancer, non-BT) aged 7-21 (mean=14 yrs; 56% males) and their parents were recruited. 34% received radiation therapy, 72% chemotherapy and 71% surgery. Mean years since diagnosis= 5.7 yrs. PCF was measured using a 43-item pediatric perceived cognitive function item bank (pedsPCF). Parents completed the pedsPCF and a single item to rate their child's quality of life (QOL). Patients completed NINDS-NeuroQOL Depression, PedsQL Fatigue scales and neuropsychological tests (NPT) of psychomotor function, attention, learning and working memory using the CogState. K-Means clustering was used to group patients based on scores of depression, fatigue and pedsPCF. Results: PedsPCF significantly differentiated BT from non-BT, t=5.65, p<.01. Correlations between pedsPCF and NPT ranged from 0-0.66 (BT, < 1 yr diagnosis, psychomotor), depending on BT (vs non-BT), yrs since diagnosis and treatment, and NPT. Three clusters were identified with its own unique characteristics. Specifically, pedsPCF was significantly correlated w/ depression & fatigue for cluster 1; correlated w/ NPT scores for non-BT for cluster 2; and correlated w/ NPT for BT for cluster 3. Cluster membership of patients were significantly differentiated by Karnofsky rating, surgery (yes/no), QOL, parent education, child age, and child gender, but not types of treatment, and grade repetition (yes/no). Conclusions: This is one of the first studies to report an association between perceived cognitive function, using parent ratings, and neuropsychological performance. PedsPCF demonstrated clinical utility in differentiating between children with a brain tumor from children with other cancer types. PedsPCF has the potential to serve as a screening tool to facilitate efficient referral for comprehensive neurocognitive assessment.
Conservative treatment of intraocular retinoblastoma: A prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy.
Authors: Aerts Isabelle , Lumbroso-Le Rouic Livia , Hajage David , Levy-Gabriel Christine , Savignoni Alexia , Algret Nathalie , Doz Francois P. , Desjardins Laurence
Published: March 2020

9538

Background: intraocular retinoblastoma treatments often associate chemotherapy and focal treatments. The protocols vary and may combine two or three drugs, and different number of cycles associated to the local adjuvant treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin, as a single agent. In order to decrease the possible long term toxicity of chemotherapy due to etoposide, a prospective randomized phase II chemo reduction protocol was conducted, using vincristine and carboplatin vs. etoposide carboplatin. Methods: the study was proposed when initial tumour size or location did not allow the use of front-line local treatments. The phase II randomized study of reduction chemotherapy used vincristin carboplatin or etoposide carboplatin, followed by local treatment including chemothermotherapy using the combination carboplatin and laser diode hyperthermia. Primary endpoint was the need for secondary enucleation or EBRT not exceeding 40% at 2 years. The new treatment was considered sufficiently effective if 10 events or less were observed among 33 eyes. Results: 55 children, 65 eyes were included in the study (May 2004- August 2009).32 eyes (27 children) were treated conservatively in the arm etoposide-carboplatin and 33 (28 children) eyes in the arm vincristin carboplatin.At two years after treatment 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin-carboplatin and 26/32 (81.3%) in the arm etoposide and carboplatin. Conclusions: neoadjuvant chemotherapy by two cycles of vincristine and carboplatin followed by chemothermotherapy (using the combination carboplatin, as a single drug, and laser diode hyperthermia) does not seem to offer an optimal local control.
Serial assessment of humoral immunity in pediatric AML: A prospective study.
Authors: Bakhshi Sameer , Bansal Anuj Kumar , Sharawat Surender Kumar , Gupta Ritu , Sreenivas Vishnu kumar
Published: March 2020

9551

Background: Humoral immunity has been evaluated in pediatric ALL; data in pediatric AML is lacking. The objectives of this study were to assess humoral immunity on follow-up in pediatric AML patients. Methods: From April 2010-May 2011, 45 consecutive AML patients 1-18 years old were prospectively enrolled with 7 healthy controls. Immunoglobulin (Ig) levels in 45 patients and B-lymphocytes (CD19+) in 29 patients were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow-up and relapse. Results: At diagnosis, Ig levels were higher in patients as compared to healthy controls (IgG, p=0.041; IgA, p=0.07; IgM, p=0.16) while B-cells were lower (p=0.001). Patients with gum hypertrophy had low Ig levels (IgG, p=0.007; IgA, p=0.003; IgM, p=0.06). CR rate was 84.4% (38/45); EFS 40% and OS 58% at 20 months follow-up. Post-induction, there was reduction in IgM (p<0.001) and IgA (p=0.048) levels and increase in B cells (p<0.001). Using generalized estimating equation regression model, average reduction from post-induction till 3 month follow-up was 36.9 units/visit (IgG); 10.3 units/visit (IgA); 0.32 units/visit (IgM) in those with continuous CR (group-1, n=24) and 91 units/visit (IgG); 8.9 units/visit (IgA); 1.5 units/visit (IgM) in those who relapsed (group-2, n=14). Difference between these two groups was significant for IgA (p=0.017). There was increase in IgG (p=0.52) and IgA levels (0.21) at relapse when compared with post-consolidation values. B-cells had an average increase of 3.6 units/visit (p=0.012) in group 1 and decrease of 0.58 units/visit (p=0.82) in group 2; (group-1 vs group-2, p=0.10). There was no significant correlation of baseline Ig and B cells with CR rate, EFS and OS. Conclusions: This is the first study to evaluate humoral immunity serially in pediatric AML. AML patients with gum hypertrophy have low IgG and IgA at diagnosis. On serial monitoring, B cells show an increase in patients who are in continuous CR while those who relapse tend to show a reduction on follow-up. Further, on follow-up, although all Ig decrease, but the reduction in IgA is significantly lower in patients who relapse suggesting their possible role in disease biology.
Treatment outcomes of pediatric oncology patients in Zambia.
Authors: Slone Jeremy , Chunda-Liyoka Catherine , Perez Marta , Mutalima Nora , Newton Robert , Chintu Chifumbe , Kankasa Chipepo , Chipeta James , Heimburger Douglas C. , Vermund Sten H. , Friedman Debra L.
Published: March 2020

9558

Background: Due to challenges in the delivery of pediatric oncology care in low-middle income countries (LMIC), diagnosis and treatment remains inadequate for the majority of patients. The University of Zambia School of Medicine/University Teaching Hospital (UTH) and Vanderbilt University School of Medicine/Vanderbilt Institute for Global Health established a partnership to investigate treatment outcomes at UTH, the only institution providing pediatric oncology care in Zambia, and assess risk factors associated with treatment abandonment. Methods: A retrospective study was conducted in a cohort of patients, presenting from July 2008 – June 2010, using an established database and medical record review. Results: Of the 230 children enrolled in the database, 162 met the inclusion criteria. The average age at diagnosis was 6.0 years; males comprised 55.6% of the cohort; 51.6% had a histopathological diagnosis and 10.5% of the cohort was HIV positive. The most common diagnoses were lymphoma (25.9%), Wilms tumor (22.8%), and retinoblastoma (17.9%). Leukemia and Kaposi sarcoma accounted for 7.4% each. Death (46.3%) and abandonment of treatment (45.7%) were the most common outcomes with only 8.0% having completed treatment or currently undergoing treatment, including palliative regimens, at the time of data acquisition. Residence in Lusaka or Central provinces, closest in proximity to UTH, was associated with a decreased risk for abandonment of treatment (Odds Ratio (OR) 0.41 (95% CI 0.21-0.81, p = 0.009) while maternal education less than secondary school (OR 2.73 95% CI 1.2-6.6, p = 0.03) was associated with an increased risk for abandonment of treatment. Conclusions: At the only pediatric cancer center in Zambia, treatment outcomes are dire with the majority of the cohort abandoning treatment or dying during therapy. Challenges include access to cancer chemotherapy, logistical facilitation, fiscal support of radiotherapy, and community engagement. Further investigation is required to inform effective intervention strategies to improve outcomes.
Demographics, treatment, and outcome of retinoblastoma: A large series with protocol-based management.
Authors: Reddy Vijay Anand Palkonda , Honavar Santosh , Fairooz Puthiyapurayil M , Ali Mohammed Javed , Vemuganti Geeta K
Published: March 2020

9568

Background: Retinoblastoma is the most common primary intraocular malignancy of childhood with incidence of 1 in 20,000 and the third most common pediatric cancer. In the previous decades, early diagnosis and treatment of retinoblastoma have improved survival rates in developed countries. Nevertheless, protocol based management help reduce the mortality rate associated with advanced tumors. The purpose of the study is to report demographics, management, and outcome of retinoblastoma in the Ocular oncology centre of South India. Methods: Consecutive case series of 1,543 eyes of 1,067 patients with 22 years of follow-up. Demographics, clinical features, treatment and outcome (survival, organ salvage and function salvage) were analyzed. Management comprised of focal therapy for small tumors, standard triple drug chemoreduction for larger (>4mm) tumors, high dose chemoreduction and periocular chemotherapy for vitreous seeds, and enucleation for advanced tumors. Adjuvant therapy was provided in patients with histopathologic high-risk factors for systemic metastasis. Orbital retinoblastoma was managed with a multimodal treatment protocol. Results: Sixty-six percent were <3 years of age. Forty-five percent were bilateral. Symptoms were leucocoria (33%), vision loss (10%), proptosis (6%), and squint (6%). The tumor was intraocular in 94% and orbital in 6%. Management was by protocol and included enucleation (52%), chemoreduction (26%), focal therapy (11%), and external beam radiation (5%). Fifty-five percent of enucleated patients had histopathologic risk factors for metastasis and received adjuvant chemotherapy. Chemoreduction with focal therapy resulted in eye and vision salvage in 92%. Overall, 94% survived. Conclusions: Protocol-based management of retinoblastoma provides excellent prognosis for survival, eye salvage and vision salvage.
Preclinical study of a PARP inhibitor in neuroblastoma.
Authors: Addioui Anissa , Belounis Assila , Cournoyer Sonia , Nyalendo Carine , Brito Rose- Marie , Beaunoyer Mona , Teira Pierre , Sartelet Hervé
Published: March 2020

9570

Background: Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In spite of many therapeutic improvements, only 60% survive long term despite aggressive combinations of multi-agent chemotherapy. In previous studies, we have demonstrated that tumor initiating cells (TIC) expressing CD133 (CD133high) in NB are more resistant to chemotherapy. Moreover, these cells express higher levels of PARP-1, a central protein involved in DNA repair. PARP-1 expression is significantly lower in NB usually showing spontaneous regression than in standard NB, suggesting an implication of PARP-1 in NB progression. The objective of this study is to determine the efficacy in vitro of AG-014699 (AG), a PARP- inhibitor, used in monotherapy or in combination to cisplatine (CP) and doxorubicine (DR), classical chemotherapeutic agents used in NB treatment, on NB cell survival. Methods: Six NB cell lines (parental or CD133high purified by flow cytometry (FACS)) were treated with AG alone or in association to CP or DR. PARP-1 ELISA protein assay was used to determine the optimal drug concentration needed to inhibit the protein. Cell survival was measured by MTT test. Western Blots were done to evaluate any apoptotic or autophagic pathway modulations. Quantification of DNA damage in treated cell was done by immunofluorescence of H2A-X protein. Results: We showed that a 4µM concentration of AG is sufficient for PARP-1 inhibition. One third of celllines presented a sensitivity to AG when used in monotherapy with an IC50 lower than 5µM. However, AG demonstrated synergistic effects when associated to DR, decreasing the IC50 by half, although none is observed when combined to CP. Sentitivity of the TIC did not appear to be more important than the bulk cells. With increasing concentration of AG, our WB showed no increase in cleaved Caspase-3 suggesting no modulation of the apoptotic pathway. However, autophagy seemed to be upregulated confirmed by an increase in cleaved LC3 II protein. Double strand breaks increased 2.5 folds when 4µM AG is added to the IC50 of DR. Conclusions: AG used in combination at potentially therapeutic doses shows promising results in NB. These results will allow for the improvement of NB treatments by introducing a new therapeutic strategy.
Substitution of cisplatin for etoposide in 2 of 3 induction cycles of CAV/IE with subsequent irinotecan and vincristine for relapse in adults with Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET).
Authors: Rushing Daniel A. , Ezewuiro Obiageli , Staehler Sandra S. , Potter Kristin , Rojas Luis , Wagner Stephanie Glacy
Published: March 2020

9571

Background: Treatment for adults with cyclophosphamide, doxorubicin and vincristine alternating with ifosfamide and etoposide (CAV/IE) for ES/PNET is based on the success reported in children however the same treatment in adults is less effective. 50% of relapsed disease is expected to occur in the lungs with median survival of 12.5 months (mo) after relapse. Since Cisplatin is used for relapse, we initially substituted cisplatin for etoposide in courses # 2 and # 3 of IE for 2 patients (pts) who were not responding to IE as determined by serial CT scanning and then used it for all pts. Relapsed pts were treated with irinotecan + vincristine (IRI-V) for at least 2 cycles as salvage therapy. We report the effect of cisplatin on influencing the relapse pattern and the effect of IRI-V on survival for pts after relapse Methods: A retrospective chart review of 19 consecutive adult pts (July 2004 to June 2011), with newly diagnosed ES /PNET were treated with CAV/IE as per H. Grier NEJM 2003 and modified as a 14 day cycle. Cisplatin 20 mg/m2 I.V. q d X4 was substituted for etoposide for courses # 2 and 3 of IE and combined with ifosfamide as above (IC) followed by surgery or RT. For pts with relapse Irinotecan was given I.V. 20mg/m2 days 1-5 & 8-12 + vcr I.V. 2mg days 1 & 8 q21 days for 2 or more cycles. Repeat treatment with CAV, IE or IC was also utilized for relapse. We evaluated the toxicities, the pattern of relapse and the survival after relapse with these treatments Results: Grade IV hematologic toxicity occurred in 11 of 19 pts treated with CAV vs. 7of 19 pts treated with IE vs. 7 of 19 pts treated with IC and 1 of 11 pts treated with IRI-V but 3 of those 11 pts had Grade IV diarrhea. Median survival was 44.8+ mo for 10 pts with non- metastatic and 23 mo for 9 pts with metastatic disease respectively. More importantly median survival from the time of relapse was 22.5+ mo, (range 12.7 to 31+ mo). 11 pts relapsed: 2 pts only in bone, 9 pts Local only, 0 pts had distant lung recurrence Conclusions: Cisplatin appears to markedly alter the relapse pattern in adults with ES/PNET and Irinotecan +vcr appears to prolong survival in relapsed pts previously treated with cisplatin.
Insurance retention in adolescent and young adult survivors of malignancies in a vertically integrated health care system.
Authors: Cooper Robert Michael
Published: March 2020

9588

Background: Adolescents and Young Adults (AYA) with cancer are a unique population of patients. This group is afflicted with a wide range of cancer types. AYA patients often have delays in diagnosis due to issues related to insurance and continuity of care and have less participation clinical trials related to other age groups. Survivors are at risk of late effects of treatment. A vertically integrated health care system with a comprehensive electronic medical record provides an ideal opportunity to care for adolescent and young adult (AYA) cancer survivors and conduct survivorship research. In this system, patients who complete oncology care return to primary medical care but can be tracked in a systematic fashion. Methods: We evaluated the insurance retention of survivors of AYA malignancies by querying the Cancer Registry and identified 13,240 known survivors of malignancies diagnosed within the system between 1990 and 2005. We looked at the percentage of survivors who were still cared for in our system at certain time points after diagnosis. We then reanalyzed the group by ethnicity, disease, and age at diagnosis. Results: The retention rate for all patients was 88% at 1 year, 64 % at 5 years, and 52% at 10 years. The retention rates were similar regardless of ethnicity. When we looked at the influence of age at time of diagnosis we noted that the younger the patients were at diagnosis the lower the percentage of those retaining insurance at the 10 year time point. We analyzed the group by the more common cancers and noted that patients diagnosed with breast cancer had greatest retention at 10 years of 68%. Conclusions: The lengthy insurance retention of adolescent and young adult cancer survivors makes a vertically integrated medical care system an ideal population laboratory for cancer survivorship research in this understudied population of cancer survivors.
Quality of cancer family history and referral for genetic counseling and testing among oncology practices: A pilot test of quality measures as part of the ASCO Quality Oncology Practice Initiative (QOPI).
Authors: Wood Marie , Kadlubek Pamela , Lu Karen H. , Wollins Dana , Weitzel Jeffrey N. , Neuss Michael N. , Hughes Kevin S.
Published: March 2020

CRA1505

The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Outcome in adolescent and young adult (AYA) patients compared with younger patients treated for high-risk B-precursor acute lymphoblastic leukemia (HR-ALL): A report from the Children’s Oncology Group study AALL0232.
Authors: Larsen Eric , Raetz Elizabeth A. , Winick Naomi Joan , Salzer Wanda L. , Nachman James B. , Devidas Meenakshi , Hunger Stephen , Carroll William L.
Published: March 2020

CRA9508

The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
New insights into the risk of breast cancer in childhood cancer survivors treated with chest radiation: A report from the Childhood Cancer Survivor Study (CCSS) and the Women's Environmental Cancer and Radiation Epidemiology(WECARE) Study.
Authors: Moskowitz Chaya S. , Chou Joanne F. , Wolden Suzanne L. , Bernstein Jonine L. , Malhotra Jyoti , Friedman Danielle Novetsky , Mubdi Nidha Z. , Henderson Tara O. , Leisenring Wendy M. , Stovall Marilyn , Hammond Sue , Boice John D. , Hudson Melissa M. , Diller Lisa , Bhatia Smita , Neglia Joseph Philip , Begg Colin B. , Robison Leslie L. , Oeffinger Kevin C. ,   WECARE Study Collaborative
Published: March 2020

CRA9513

The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.