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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 11563-11563
    Abstract: 11563 Background: Long-term survivors of neuroblastoma may be at risk for neurocognitive impairment due to young age at diagnosis and intensive multimodal therapies. Methods: 837 survivors of neuroblastoma (57% female; median [range] age 25 [17-58] years, age at diagnosis 1 [0-21] years) and 728 siblings (56% female; age 32[16-43] years) self-reported neurocognitive problems using a neurocognitive questionnaire. Impairment was defined as scores ≥90th percentile of siblings in emotional regulation (ER), organization, task efficiency (TE), and memory. Multivariable log-binomial models evaluated associations with treatment exposures, era and chronic conditions (Grade 2-4 CTCAE v5) adjusting for sex, age, and race. Analyses were stratified by age at diagnosis (≤1 and 〉 1 year) as proxy for risk group. Results: Rates of impairment were 19.7% (ER), 25.3% organization, 21.9% TE and 19.4% for memory. Survivors had 50% higher risk of impaired TE (≤1 year relative risk [RR] 1.48, 95% confidence interval [CI] 1.08-2.03; 〉 1 year: RR 1.58, CI 1.22-2.06) and ER (≤1 year RR 1.51, CI 1.07-2.12; 〉 1 year RR 1.44, CI 1.06-1.95) versussiblings. Among survivors ≤1 year at diagnosis, treatment with platinum (RR 1.74, CI 1.01-2.97), hearing loss (RR 1.95, CI 1.26-3.00), cardiovascular (RR 1.83, CI 1.15-2.89) and neurologic (RR 2.00, CI 1.32-3.03) conditions were associated with higher risk of impaired TE. Female sex (RR = 1.54, CI, 1.02-2.33), cardiovascular (RR 1.71, CI 1.08-2.70) and respiratory (RR 1.99, CI 1.14-3.49) conditions were associated with higher risk of impaired ER. Among survivors 〉 1 year at diagnosis those treated in 1970-79 vs. 1990-99 had 80% higher risk of impaired ER (RR 1.77, CI 1.02-3.06). Hearing loss (RR 1.56 (1.09-2.24), respiratory (RR 2.35, CI 1.60-3.45) and cardiovascular (RR 1.74, CI 1.12-2.69) conditions were associated with higher risk of impaired TE. Conclusions: Adult survivors of neuroblastoma are at-risk for neurocognitive impairment. Differences associated with age at diagnosis, chronic disease and treatment exposures may inform risk-stratified inventions to improve neurocognitive outcomes. Reduced risk in later eras may reflect improved supportive care and knowledge of late effects.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 10002-10002
    Abstract: 10002 Background: Aggressive therapies for high-risk neuroblastoma (HRNBL) have resulted in increased survival, but late effects have not been well-characterized. Methods: Comprehensive cross-sectional evaluation of health outcomes in HRNBL survivors enrolled on the COG Neuroblastoma Biology Study after 1/1/2000 and ≥ 5 years from primary diagnosis, using medical record abstraction and in-person clinical assessments. Descriptive and multivariable analyses identified extent of and risk factors for late toxicity. Results: There were 375 participants from 88 COG centers, 205 (55%) male; 92 (26%) non-white; 45 (13%) Hispanic. Median age at neuroblastoma diagnosis was 2.5 years (range: 0.2-15.8), at enrollment was 12.0 years (range: 5.0-24.0). All had received chemotherapy; 94% received cisplatin (median dose: 398 mg/m2). Other exposures included: radiation (95%), isotretinoin (91%), anti-GD2 antibody therapy (64%), MIBG (7%), single (79%) or tandem autologous transplantation (ASCT; 20%). ASCT conditioning included: Busulfan/Melphalan (BuMel) (18%), Carboplatin/Etoposide/Melphalan (CEM) (73%), Thiotepa/Cytoxan (19%), and total body irradiation (5%). Severe ototoxicity (requiring hearing aids) was observed in 58% of participants. Physician-reported late effects included hypothyroidism (17%), pulmonary hypertension (1%), congestive heart failure (2%), and hypertension (6%). Pulmonary Function Studies revealed restrictive lung disease [RLD - Total Lung Capacity 〈 70% predicted] in 8% of subjects. Laboratory study showed elevated creatinine in 7% and Hemoglobin A1c in 7%. Growth failure (height Z-score 〈 -1.7) was observed in 34%. Subsequent malignant neoplasms (SMN) developed in 15 participants (4%; 4 sarcomas, 3 MDS/t-AML, single instance of 8 other malignancies). Adjusting for sex, follow-up time, age, and race, there were no differences in risk of SMN, severe ototoxicity, growth failure, or RLD for participants who received BuMel vs. CEM-based condtioning, or among those who received anti-GD2 antibody therapy vs. those who did not. Use of carboplatin during ASCT was not assocoiated with increased ototoxicity risk for any category of cisplatin induction dose. Comparing subjects who received CEM as a component of tandem ASCT (vs. single CEM), there was increased risk of growth failure [OR (95%CI) = 4.2(2.1, 8.4); p 〈 0.0001], but not RLD. Exposure to isotretinoin was not associated with increased risk of growth failure. Further multivariable analyses will be presented, exploring risks for late toxicity associated with conditioning regimens, radiation therapy, surgical approaches, and acute and chronic complications of therapy. Conclusions: The burden of late toxicity in HRNBL survivors is substantial. Anti-GD2 immunotherapy and isotretinoin do not appear to be associated with SMN, ototoxicity, growth failure, or RLD.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 6565-6565
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 18_suppl ( 2012-06-20), p. CRA9513-CRA9513
    Abstract: CRA9513 Background: The risk of breast cancer (BC) by age 50 among women treated for childhood cancer with chest radiation therapy (RT) and how this risk compares with that of BRCA1 and BRCA2 (BRCA1/2) mutation carriers is unknown. Methods: We evaluated the risk of BC in a cohort of 1268 female 5-yr childhood cancer survivors treated with chest RT and estimated the cumulative incidence of BC non-parametrically treating death as a competing risk. The cumulative incidence of BC in BRCA1/2 mutation carriers was estimated with the kin-cohort method using data from 4570 female first-degree relatives of women diagnosed with unilateral BC (probands) participating in the WECARE Study. Absolute Excess Risks (AERs) were estimated using population-based data from the SEER program. Results: With a median follow-up of 26 yrs (range 5-39) for the CCSS cohort, 175 women were diagnosed with BC at a median age of 38 yrs (range 24-53) and a median latency of 23 yrs (range 7-38); the overall cumulative incidence of BC by age 50 was 24% (95% confidence interval [CI] 20-28%) and among Hodgkin lymphoma survivors was 30% (95% CI 25-35%). In comparison, among first-degree relatives of WECARE Study probands 324 were diagnosed with BC (median age at diagnosis, 55 yrs (range 26-90)). The estimated cumulative incidence by age 50 was 31% (95% CI 16-47%) and 10% (95% CI 2-23%) in carriers of BRCA1 and BRCA2 mutations, respectively. The population cumulative incidence of BC is 4% by age 50. Among the childhood cancer survivors, AERs for BCs diagnosed per 10,000 person-years of observation were respectively 34 (95% CI 18-52), 27 (95% CI 11-45), and 95 (95% CI 78-112) among women treated with 10-19 Gy (23%), 20-29 Gy (17%), and 30+ Gy (56%) of chest RT. Conclusions: Women treated for childhood cancer with chest RT have a substantial risk of BC comparable to BRCA1/2 mutation carriers and considerably greater than that of the general population. Women treated with 10-19 Gy RT had an increased excess risk warranting consideration of breast cancer surveillance strategies similar to the current recommendations for women treated with 〉 20 Gy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 6593-6593
    Abstract: 6593 Background: Female childhood HL survivors treated with ≥10 Gy of chest radiation are at high risk of developing BC. The Children’s Oncology Group (COG) guidelines recommend lifetime annual mammography (MAM) and breast Magnetic Resonance Imaging (MRI) starting 8y after chest radiation or age 25, whichever is later, and clinical breast examination (CBE) annually from puberty and semiannually from age 25. Initial model results suggest that CBE adds no survival benefit in this cohort. Digital breast tomosynthesis (DBT) is increasingly replacing digital MAM in clinical practice. Here, we present the efficacy and cost-effectiveness of COG’s imaging-based screening recommendations. Methods: Life-years (LYs), quality-adjusted LYs (QALYs), BC mortality, and costs (2017 U.S.$) were estimated from simulating the lifetimes of 5-million chest-irradiated 25y old HL survivors who underwent BC screening with each of the following strategies: annual digital MAM, MRI, MAM+MRI, annual DBT or DBT+MRI from age 25 onward. Treatment-related BC risk (in-situ and invasive) and non-BC mortality were estimated from female 5y HL survivors in the Childhood Cancer Survivor Study and from U.S. population rates. Test sensitivity was 70-74% for MAM (based on prior HL studies) and 89% for DBT and MRI (based on women at high risk of de novo BC). Costs and quality of life weights were obtained from medical literature. Results: For HL survivors with no screening, lifetime BC risk was 42.7% and BC mortality was 18.1%. BC risk and non-BC mortality were, respectively, 7.4- and 5.2-fold higher at age 50 in HL survivors relative to the general population. Screening at ages 25-74 had similar LY gain and BC mortality reduction compared to lifetime screening; hence, we focused on screening for ages 25-74. For all strategies screening provided LY gain of 0.34-0.47 and reduced BC mortality by 6.7-9.8% compared with no screening; incremental cost-effectiveness ratio (ICER), or cost per QALY gained, for MAM alone was $58,726 and for DBT alone was $62,989. ICER of adding MRI to MAM ($385,285) or to DBT ($513,358) indicated lower cost-effectiveness of supplemental MRI (Table). Conclusions: Annual screening at ages 25-74y in chest-irradiated HL survivors appears beneficial. Using $100K per QALY gained as cost-effectiveness threshold, annual MAM or DBT are more cost-effective, whereas adding MRI to MAM is less cost-effective.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 7504-7504
    Abstract: 7504 Background: The anti-CD30 antibody drug conjugate, Brentuximab vedotin (Bv) is approved for adults with advanced stage HL but its use has not been established in children or adolescents. We compared the efficacy and safety of Bv with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVE-PC) to the standard pediatric dose intensive regimen ABVE-PC, inclusive of bleomycin. Methods: This multicenter randomized, open-label phase 3 study enrolled patients 2-21 years (yrs) with previously untreated HL, stages IIB + bulk, IIIB, IVA, IVB. Patients were randomized to 5 cycles of either ABVE-PC or Bv-AVE-PC given every 21 days with granulocyte colony-stimulating factor support. Centrally reviewed PET-CT after 2 cycles (PET2) identified slow responding lesions (SRL) defined as Deauville score 〉 3. Involved site radiotherapy (ISRT) was given to bulky mediastinal adenopathy and SRL. The primary objective was 3-year EFS; events include relapse/progression, second malignant neoplasm (SMN) or death. Final data cutoff was 31 December 2021. Results: 600 participants were enrolled across 151 institutions from March 2015 to August 2019; 587 were eligible. Median age was 15.6 yrs (range 3.4-21). Patient and disease characteristics were balanced across study arms. Histology was nodular sclerosing in 76.5%. Stage distribution: 20.6% IIB-bulk; 19.3% IIIB; 28.5% IVA; 31.7% IVB. At a median follow-up of 42.1 mos (0.1-80.9), 3-year EFS (95%CI) by intent-to-treat analyses was 82.5% (77.4, 86.5) with ABVE-PC and 92.1% (88.4, 94.7) with Bv-AVE-PC (HR 0.41 (0.25, 0.67), p = 0.0002). Median time to 1st event was 9.4 months for both arms but the range differs by arm (3.6-57.8 ABVE-PC; 1.3, 25.8 Bv-AVE-PC). Relapse rate was 17% following ABVE-PC and 7% with Bv-AVE-PC. One SMN is noted in each arm: thyroid cancer at 57.8 mos and acute myeloid leukemia at 20.3 mos. 3-year overall survival (95%CI) was 98.5% (96.0, 99.4) for ABVE-PC and 99.3% (97.3, 99.8) for Bv-AVE-PC (p = 0.38). PET2 SRL rates were comparable (ABVE-PC 19% vs. Bv-AVE-PC 18%, p = 0.8). As-treated ISRT receipt did not differ (ABVE-PC 55.7% vs. Bv-AVE-PC 52.7%, p = 0.69). No difference in grade 3/4 adverse events was observed; myelosuppression, reflected in a 32% incidence of 〉 grade 3 febrile neutropenia, did not differ by arm (p = 0.67). Only 19% of patients experienced 〉 grade 2 neuropathy by the Balis pediatric neuropathy scale, with no difference between arms (p = 0.86). Conclusions: Brentuximab vedotin with AVE-PC in a dose intensive regimen has superior efficacy to ABVE-PC for pediatric patients with high-risk HL. A 59% risk reduction in EFS was achieved with no increase in toxicity and with fewer patients receiving ISRT compared to prior pediatric trials for high-risk HL. Clinical trial information: 02166463.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 10047-10047
    Abstract: 10047 Background: Pediatric Hodgkin lymphoma (HL) is a highly curable disease. However, survivors are at high risk for long-term complications of therapy. The impact of sociodemographic and clinical factors on adherence to late effects surveillance guidelines is unknown. Methods: The CCSS is a retrospective cohort with prospective follow-up of survivors diagnosed from 1970-1999. HL survivors enrolled in CCSS who responded to a 2017 questionnaire were included. We assessed adherence to the Children’s Oncology Group surveillance guidelines for cardiomyopathy, breast cancer, colorectal cancer, and skin cancer. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals (aOR [95% CI]) for sociodemographic and clinical risk factors associated with adherence. Estimates were adjusted for area deprivation index (ADI); chronic health conditions; recent (≤2 years) routine check-up, cancer center or survivorship clinic visit; and possession of a survivorship care plan (SCP). Results: 1,380 HL survivors (45.6% male; median age 43.6 years, range 21.6-65.9 years) responded, of whom 55.5% were at elevated risk for cardiac dysfunction, 71.0% for breast cancer, 83.5% for skin cancer, and 39.4% for colorectal cancer. Of those at elevated risk, 42.7%, 19.9%, 31.3% and 48.9% were adherent to the guidelines for cardiac, breast, skin, and colorectal screening, respectively. Predictors of adherence to cardiac dysfunction guidelines were male sex (aOR 1.7 [1.1-2.6] ), having children (aOR 1.6 [1.1-2.4]), recent routine checkup (aOR 4.0 [1.3-13.1] ), recent visit to a cancer center or survivorship clinic (aOR 6.2 [3.9-10.0]), and possession of a SCP (aOR 3.1 [1.9-5.0] ). Adherence to breast cancer guidelines was higher in those who were unmarried (aOR 2.1 [1.0-4.1]), had a recent visit to a cancer center or survivorship clinic (aOR 3.7 [2.0-7.0] ), and possessed a SCP (aOR 3.5 [1.5-8.3]). Adherence to skin cancer guidelines was higher in those 〉 14 years at diagnosis (aOR 1.8 [1.3-2.4]), living in a low deprivation area (ADI 1-24.9) compared to a high deprivation area (ADI 75-100) (aOR 3.4 [1.9-5.9] ), employed (aOR 1.8 [1.1-2.9]), 〉 30 years from diagnosis (aOR 2.4 [1.6-3.6]), with a recent routine check-up (aOR 3.6 [1.1-12.5] ), and recent cancer care (aOR 2.4 [1.6-3.5]). Adherence to colorectal cancer guidelines was higher in those with grade 3-4 chronic health conditions (aOR 1.9 [1.1-3.3] ). Conclusions: Less than 50% of HL survivors are adherent to screening guidelines. Sociodemographic risk factors are significant predictors of non-adherence, particularly to skin cancer screening guidelines. This threatens to potentiate outcome disparities among HL survivors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 8
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 33 ( 2015-11-20), p. 3849-3850
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 33 ( 2015-11-20), p. 3849-3850
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 10051-10051
    Abstract: 10051 Background: Infants with neuroblastoma typically have low-risk disease with excellent survival. Therapy has been de-intensified over time to minimize late effects, however the impact on survivors’ risk of late mortality, subsequent malignant neoplasms (SMN), and chronic health conditions (CHC) is unclear. Methods: We evaluated late mortality, SMNs and CHCs (graded according to CTCAE v4.03), overall and by diagnosis era, among 990 5-year neuroblastoma survivors diagnosed at 〈 1 year of age between 1970-1999. Cumulative mortality, standardized mortality ratios (SMR), and standardized incidence ratios (SIR) of SMNs were estimated using the National Death Index and SEER rates, respectively. Cox proportional hazards estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC, compared to 5,051 CCSS siblings. Results: Among survivors (48% female; median attained age: 24 years, range 6-46), there was increased treatment with surgery alone across the 1970s, 1980s and 1990s (21.5%, 35.3%, 41.1%, respectively), but decreased treatment with combination surgery + radiation (22.5%, 5.3%, 0.3%, respectively) and surgery + radiation + chemotherapy (28.7%, 14.7%, 9.3%, respectively). The 20-year cumulative mortality was 2.3% (95% CI, 1.4-3.8), primarily due to SMNs (SMR SMN = 10.0, 95% CI, 4.5-22.3). The 20-year cumulative incidence of SMN was 1.2% (95% CI, 0.3-3.2), 2.5% (95% CI, 1.3-4.4), and zero for those diagnosed in the 1970s, 1980s, and 1990s, respectively. SIR was highest for renal SMNs (SIR 12.5, 95% CI, 1.7-89.4). Compared to siblings, survivors were at increased risk for grade 1-5 CHC (HR 2.1, 95% CI, 1.9-2.3) with similar HR across eras (HR 1970s = 1.9, 95% CI, 1.6-2.2; HR 1980s = 2.2, 95% CI, 1.9-2.6; HR 1990s = 2.0, 95% CI, 1.7-2.4). The HR of severe, disabling, life-threatening and fatal CHC (grades 3-5) decreased in more recent eras (HR 1970s = 4.7, 95% CI, 3.4-6.6; HR 1980s = 4.4, 95% CI, 3.2-6.2; HR 1990s = 2.9, 95% CI, 2.0-4.3). Conclusions: Survivors of infant neuroblastoma remain at increased risk for late mortality, SMN, and CHCs many years after diagnosis. However, the risk of grade 3-5 CHCs has declined in more recent eras, likely reflecting de-intensification of therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. CRA9513-CRA9513
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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