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Article ; Online: Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk B ALL: A Children's Oncology Group Study.

Alexander, Sarah / Kairalla, John A / Gupta, Sumit / Hibbitts, Emily / Weisman, Hannah / Anghelescu, Doralina / Winick, Naomi J / Krull, Kevin R / Salzer, Wanda L / Burke, Michael J / Gore, Lia / Devidas, Meenakshi / Embry, Leanne / Raetz, Elizabeth A / Hunger, Stephen P / Loh, Mignon L / Hardy, Kristina K

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2024 , Page(s) JCO2301989

Abstract: Purpose: Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study ... ...

Abstract	Purpose: Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study evaluated the impact of cumulative exposure to anesthesia on neurocognitive outcomes among a multicenter cohort of children with ALL. Methods: This study was embedded in AALL1131, a Children's Oncology Group phase III trial for patients with high-risk B-ALL. In consenting patients age 6-12 years, prospective uniform assessments of neurocognitive function were performed during and at 1 year after completion of therapy. Exposure to all episodes of anesthetic agents was abstracted. Multivariable linear regression models determined associations of cumulative anesthetic agents with the primary neurocognitive outcome reaction time/processing speed (age-normed) at 1 year off therapy, adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status (as a proxy for socioeconomic status), and leukemia risk group. Results: One hundred and forty-four children, 76 (52.8%) males, mean age of 9.1 (min-max, 6.0-12.0) years at diagnosis, underwent a median of 27 anesthetic episodes (min-max, 1-37). Almost all patients were exposed to propofol (140/144, 97.2%), with a mean cumulative dose of 112.3 mg/kg. One year after therapy, the proportion of children with impairment ( Conclusion: In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.23.01989
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article ; Online: Impaired neurocognitive functioning 3 months following diagnosis of high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group.

Hardy, Kristina K / Kairalla, John A / Gioia, Anthony R / Weisman, Hannah S / Gurung, Meera / Noll, Robert B / Hinds, Pamela S / Hibbitts, Emily / Salzer, Wanda L / Burke, Michael J / Winick, Naomi J / Embry, Leanne

Pediatric blood & cancer

2023 Volume 70, Issue 7, Page(s) e30350

Abstract: Purpose: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, ...

Abstract	Purpose: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, and its association with patient-reported outcomes, early in treatment. Patients and methods: A total of 483 children with high-risk ALL, aged 6-12 years at diagnosis, consented to the neurocognitive study embedded in a prospective therapeutic trial, Children's Oncology Group (COG) AALL1131. A computerized neurocognitive battery (Cogstate) was administered 3 months post diagnosis assessing reaction time, visual attention, working memory, visual learning, and executive functioning. Parent-reported executive functioning and patient-reported physical symptoms were also collected. Results: Data from 390 participants (mean age at diagnosis = 9.2 years, 55.4% male) were obtained. Relatively few patients reported pain (16.0%) or nausea (22.6%), but a majority (68.5%) reported feeling at least some fatigue at testing. Mean Cogstate Z-scores were within normal limits across tasks; however, rates of impairment (Z-scores ≤ -1.5) for reaction time, working memory, visual learning, and visual attention were all higher than expected compared to the standardization sample. Patients reporting fatigue were significantly more likely to have impaired reaction time and visual attention compared to those reporting no fatigue. Conclusion: Findings support feasibility of computerized cognitive assessments and suggest higher-than-expected rates of impaired cognitive performance early during treatment for pediatric ALL, notably within 3 months of diagnosis, suggesting intervention efforts may be indicated. These results also highlight acute factors that may impact reliability of "baseline" assessments conducted soon after diagnosis.
MeSH term(s)	Child ; Humans ; Male ; Female ; Reproducibility of Results ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Executive Function ; Cognition ; Memory, Short-Term ; Neuropsychological Tests
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30350
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Article ; Online: Impact of Genomic and Clinical Factors on Outcome of Children ≥18 Months of Age with Stage 3 Neuroblastoma with Unfavorable Histology and without MYCN Amplification: A Children's Oncology Group (COG) Report.

Pinto, Navin / Naranjo, Arlene / Ding, Xiangming / Zhang, Fan F / Hibbitts, Emily / Kennedy, Rebekah / Tibbetts, Rachelle / Wong-Michalak, Shannon / Craig, David W / Manojlovic, Zarko / Hogarty, Michael D / Kreissman, Susan / Bagatell, Rochelle / Irwin, Meredith S / Park, Julie R / Asgharzadeh, Shahab

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 8, Page(s) 1546–1556

Abstract: Purpose: Patients ≥18 months of age with International Neuroblastoma Staging System (INSS) stage 3 unfavorable histology (UH), MYCN-nonamplified (MYCN-NA) tumors have favorable survival rates compared with other high-risk neuroblastoma populations. The ... ...

Abstract	Purpose: Patients ≥18 months of age with International Neuroblastoma Staging System (INSS) stage 3 unfavorable histology (UH), MYCN-nonamplified (MYCN-NA) tumors have favorable survival rates compared with other high-risk neuroblastoma populations. The impact of select clinical and biological factors on overall survival (OS) and event-free survival (EFS) were evaluated. Experimental design: Patients enrolled on Children's Oncology Group (COG) A3973 (n = 34), ANBL0532 (n = 27), and/or biology protocol ANBL00B1 (n = 72) were analyzed. Tumors with available DNA (n = 65) and RNA (n = 42) were subjected to whole-exome sequencing (WES) and RNA sequencing. WES analyses and gene expression profiling were evaluated for their impact on survival. Multivariate analyses of EFS/OS using significant factors from univariate analyses were performed. Results: 5-year EFS/OS for patients treated with high-risk therapy on A3973 and ANBL0532 were 73.0% ± 8.1%/87.9% ± 5.9% and 61.4% ± 10.2%/73.0% ± 9.2%, respectively (P = 0.1286 and P = 0.2180). In the A3973/ANBL0532 cohort, patients with less than partial response (PR; n = 5) at end-induction had poor outcomes (5-year EFS/OS: 0%/20.0% ± 17.9%. Univariate analyses of WES data revealed that subjects whose tumors had chromosome 1p or 11q loss/LOH and chromosome 5 or 9 segmental chromosomal aberrations had inferior EFS compared with those with tumors without these aberrations. Multivariate analysis revealed that 11q loss/LOH was an independent predictor of inferior OS [HR, 3.116 (95% confidence interval, 1.034-9.389), P = 0.0435]. Conclusions: Patients ≥18 months of age at diagnosis who had tumors with UH and MYCN-NA INSS stage 3 neuroblastoma assigned to high-risk therapy had an 81.6% ± 5.3% 5-year OS. Less than PR to induction therapy and chromosome 11q loss/LOH are independent predictors of inferior outcome and identify patients who should be eligible for future high-risk clinical trials.
MeSH term(s)	Humans ; Child ; Infant ; Neoplasm Staging ; N-Myc Proto-Oncogene Protein/genetics ; Neuroblastoma/therapy ; Neuroblastoma/drug therapy ; Genes, myc ; Chromosome Deletion ; Genomics ; Gene Amplification ; Prognosis
Chemical Substances	N-Myc Proto-Oncogene Protein ; MYCN protein, human
Language	English
Publishing date	2023-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-3032
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Zs.A 4223: Show issues

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Article ; Online: Persistence of Chemotherapy-Induced Peripheral Neuropathy Despite Vincristine Reduction in Childhood B-Acute Lymphoblastic Leukemia.

Rodwin, Rozalyn L / Kairalla, John A / Hibbitts, Emily / Devidas, Meenakshi / Whitley, Moira K / Mohrmann, Caroline E / Schore, Reuven J / Raetz, Elizabeth / Winick, Naomi J / Hunger, Stephen P / Loh, Mignon L / Hockenberry, Marilyn J / Angiolillo, Anne L / Ness, Kirsten K / Kadan-Lottick, Nina S

Journal of the National Cancer Institute

2022 Volume 114, Issue 8, Page(s) 1167–1175

Abstract: Background: Children with B-acute lymphoblastic leukemia (B-ALL) are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Children's Oncology Group AALL0932 randomized reduction in vincristine and dexamethasone (every 4 weeks vs 12 weeks ... ...

Abstract	Background: Children with B-acute lymphoblastic leukemia (B-ALL) are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Children's Oncology Group AALL0932 randomized reduction in vincristine and dexamethasone (every 4 weeks vs 12 weeks during maintenance in the average-risk subset of National Cancer Institute standard-B-ALL (SR AR B-ALL). We longitudinally measured CIPN, overall and by treatment group. Methods: AALL0932 standard-B-ALL patients aged 3 years and older were evaluated at T1-T4 (end consolidation, maintenance month 1, maintenance month 18, 12 months posttherapy). Physical and occupational therapists (PT/OT) measured motor CIPN (hand and ankle strength, dorsiflexion and plantarflexion range of motion), sensory CIPN (finger and toe vibration and touch), function (dexterity [Purdue Pegboard], and walking efficiency [Six-Minute Walk]). Proxy-reported function (Pediatric Outcome Data Collection Instrument) and quality of life (Pediatric Quality of Life Inventory) were assessed. Age- and sex-matched z scores and proportion impaired were measured longitudinally and compared between groups. Results: Consent and data were obtained from 150 participants (mean age = 5.1 years [SD = 1.7], 48.7% female). Among participants with completed evaluations, 81.8% had CIPN at T1 (74.5% motor, 34.1% sensory). When examining severity of PT/OT outcomes, only handgrip strength (P < .001) and walking efficiency (P = .02) improved from T1-T4, and only dorsiflexion range of motion (46.7% vs 14.7%; P = .008) and handgrip strength (22.2% vs 37.1%; P = .03) differed in vincristine and dexamethasone every 4 weeks vs vincristine and dexamethasone 12 weeks at T4. Proxy-reported outcomes improved from T1 to T4 (P < .001), and most did not differ between groups. Conclusions: CIPN is prevalent early in B-ALL therapy and persists at least 12 months posttherapy. Most outcomes did not differ between treatment groups despite reduction in vincristine frequency. Children with B-ALL should be monitored for CIPN, even with reduced vincristine frequency.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Child ; Child, Preschool ; Dexamethasone/therapeutic use ; Female ; Hand Strength ; Humans ; Longitudinal Studies ; Male ; Peripheral Nervous System Diseases/chemically induced ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Quality of Life ; Vincristine/adverse effects
Chemical Substances	Antineoplastic Agents ; Vincristine (5J49Q6B70F) ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2022-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djac095
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Uh III Zs.131: Show issues

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Article ; Online: The ganglioside G

Balis, Frank Milton / Busch, Christine Maria / Desai, Ami Vijay / Hibbitts, Emily / Naranjo, Arlene / Bagatell, Rochelle / Irwin, Meredith / Fox, Elizabeth

Pediatric blood & cancer

2019 Volume 67, Issue 1, Page(s) e28031

Abstract: Background: G: Procedure: G: Results: The C: Conclusions: Circulating ... ...

Abstract	Background: G Procedure: G Results: The C Conclusions: Circulating G
MeSH term(s)	Biomarkers, Tumor/blood ; Case-Control Studies ; Child ; Follow-Up Studies ; Gangliosides/blood ; Humans ; Neuroblastoma/blood ; Neuroblastoma/diagnosis ; Prognosis ; Retrospective Studies
Chemical Substances	Biomarkers, Tumor ; Gangliosides ; ganglioside, GD2 (65988-71-8)
Language	English
Publishing date	2019-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.28031
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Zs.A 1131: Show issues

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Article ; Online: Assessment of proxy-reported responses as predictors of motor and sensory peripheral neuropathy in children with B-lymphoblastic leukemia.

Rodwin, Rozalyn L / DelRocco, Natalie J / Hibbitts, Emily / Devidas, Meenakshi / Whitley, Moira K / Mohrmann, Caroline E / Schore, Reuven J / Raetz, Elizabeth / Winick, Naomi J / Hunger, Stephen P / Loh, Mignon L / Hockenberry, Marilyn J / Ma, Xiaomei / Angiolillo, Anne L / Ness, Kirsten K / Kairalla, John A / Kadan-Lottick, Nina S

Pediatric blood & cancer

2023 Volume 70, Issue 11, Page(s) e30634

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children's Oncology Group AALL0932 physical function study, we sought to determine if ... ...

Abstract	Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children's Oncology Group AALL0932 physical function study, we sought to determine if parent/guardian proxy-reported responses from the Pediatric Outcomes Data Collection Instrument could identify children with motor or sensory CIPN diagnosed by physical/occupational therapists (PT/OT). Four variables moderately discriminated between children with and without motor CIPN (c-index 0.76, 95% confidence interval [CI]: 0.64-0.84), but sensory and optimism-corrected models had weak discrimination (c-index sensory models 0.65, 95% CI: 0.54-0.74). New proxy-report measures are needed to identify children with PT/OT diagnosed CIPN.
MeSH term(s)	Humans ; Child ; Peripheral Nervous System Diseases/chemically induced ; Peripheral Nervous System Diseases/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Physical Examination ; Quality of Life ; Antineoplastic Agents/therapeutic use
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30634
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Zs.A 1131: Show issues

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Article ; Online: Association of heterogeneous MYCN amplification with clinical features, biological characteristics and outcomes in neuroblastoma: A report from the Children's Oncology Group.

Campbell, Kevin / Naranjo, Arlene / Hibbitts, Emily / Gastier-Foster, Julie M / Bagatell, Rochelle / Irwin, Meredith S / Shimada, Hiroyuki / Hogarty, Michael / Park, Julie R / DuBois, Steven G

European journal of cancer (Oxford, England : 1990)

2020 Volume 133, Page(s) 112–119

Abstract: Purpose: MYCN amplification (MNA) is associated with poor outcomes in neuroblastoma. Less is known about heterogeneous MNA within a tumour. We compared clinical characteristics, biologic features and clinical outcomes of patients with heterogeneous MNA ... ...

Abstract	Purpose: MYCN amplification (MNA) is associated with poor outcomes in neuroblastoma. Less is known about heterogeneous MNA within a tumour. We compared clinical characteristics, biologic features and clinical outcomes of patients with heterogeneous MNA to patients with either homogeneous MNA or MYCN wild-type tumours. Patients and methods: In this retrospective cohort study, we categorized patients as having tumours with MYCN wild-type, homogeneous MNA (>20% amplified tumour cells) or heterogeneous MNA (≤20% amplified tumour cells). We used chi-squared or Fisher's exact tests to compare features between groups. We used log-rank tests and Cox models to compare event-free survival (EFS) and overall survival (OS) between groups. Results: MYCN status and heterogeneity status (if amplified) could be ascertained in diagnostic tumour samples from 5975 patients, including 57 (1%) with heterogeneous MNA, 981 (16.4%) with homogeneous MNA, and 4937 (82.6%) with MYCN wild-type tumours. Multiple clinical and biological features differed between patients with heterogeneous vs. homogeneous MNA, including enrichment for thoracic primary sites and paucity of 1p loss of heterozygosity with heterogeneous MNA (p < 0.0001). Importantly, EFS and OS were not significantly different between patients with heterogeneous vs. homogeneous MNA. Further, EFS and OS for patients with heterogeneous MNA were significantly inferior to patients with wild-type MYCN. Conclusion: Although neuroblastomas with heterogeneous MNA demonstrate significantly different biological and clinical patterns compared with homogeneous MNA, prognosis is similar between the two groups. These results support current practice that treats patients with heterogeneous MNA similarly to patients with homogeneous MNA.
MeSH term(s)	Child ; Child, Preschool ; Cohort Studies ; Female ; Gene Amplification ; Genetic Association Studies ; Genetic Heterogeneity ; Humans ; Infant ; Male ; N-Myc Proto-Oncogene Protein/genetics ; Neuroblastoma/diagnosis ; Neuroblastoma/genetics ; Neuroblastoma/mortality ; Prognosis ; Retrospective Studies ; Survival Analysis
Chemical Substances	MYCN protein, human ; N-Myc Proto-Oncogene Protein
Language	English
Publishing date	2020-05-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2020.04.007
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Refinement of risk stratification for childhood rhabdomyosarcoma using FOXO1 fusion status in addition to established clinical outcome predictors: A report from the Children's Oncology Group.

Hibbitts, Emily / Chi, Yueh-Yun / Hawkins, Douglas S / Barr, Frederic G / Bradley, Julie A / Dasgupta, Roshni / Meyer, William H / Rodeberg, David A / Rudzinski, Erin R / Spunt, Sheri L / Skapek, Stephen X / Wolden, Suzanne L / Arndt, Carola A S

Cancer medicine

2019 Volume 8, Issue 14, Page(s) 6437–6448

Abstract: Background: Previous studies of the prognostic importance of FOXO1 fusion status in patients with rhabdomyosarcoma (RMS) have had conflicting results. We re-examined risk stratification by adding FOXO1 status to traditional clinical prognostic factors ... ...

Abstract	Background: Previous studies of the prognostic importance of FOXO1 fusion status in patients with rhabdomyosarcoma (RMS) have had conflicting results. We re-examined risk stratification by adding FOXO1 status to traditional clinical prognostic factors in children with localized or metastatic RMS. Methods: Data from six COG clinical trials (D9602, D9802, D9803, ARST0331, ARTS0431, ARST0531; two studies each for low-, intermediate- and high-risk patients) accruing previously untreated patients with RMS from 1997 to 2013 yielded 1727 evaluable patients. Survival tree regression for event-free survival (EFS) was conducted to recursively select prognostic factors for branching and split. Factors included were age, FOXO1, clinical group, histology, nodal status, number of metastatic sites, primary site, sex, tumor size, and presence of metastases in bone/bone marrow, soft tissue, effusions, lung, distant lymph nodes, and other sites. Definition and outcome of the proposed risk groups were compared to existing systems and cross-validated results. Results: The 5-year EFS and overall survival (OS) for evaluable patients were 69% and 79%, respectively. Extent of disease (localized versus metastatic) was the first split (EFS 73% vs 30%; OS 84% vs. 42%). FOXO1 status (positive vs negative) was significant in the second split both for localized (EFS 52% vs 78%; OS 65% vs 88%) and metastatic disease (EFS 6% vs 46%; OS 19% vs 58%). Conclusions: After metastatic status, FOXO1 status is the most important prognostic factor in patients with RMS and improves risk stratification of patients with localized RMS. Our findings support incorporation of FOXO1 status in risk stratified clinical trials.
MeSH term(s)	Adolescent ; Age Factors ; Biomarkers, Tumor ; Child ; Child, Preschool ; Disease Progression ; Female ; Forkhead Box Protein O1/genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Oncogene Proteins, Fusion/genetics ; Prognosis ; Rhabdomyosarcoma/diagnosis ; Rhabdomyosarcoma/etiology ; Rhabdomyosarcoma/mortality ; Rhabdomyosarcoma/therapy ; Risk Assessment ; Risk Factors
Chemical Substances	Biomarkers, Tumor ; FOXO1 protein, human ; Forkhead Box Protein O1 ; Oncogene Proteins, Fusion
Language	English
Publishing date	2019-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2045-7634
ISSN (online)	2045-7634
DOI	10.1002/cam4.2504
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Article ; Online: Predictors of differential response to induction therapy in high-risk neuroblastoma: A report from the Children's Oncology Group (COG).

Pinto, Navin / Naranjo, Arlene / Hibbitts, Emily / Kreissman, Susan G / Granger, M Meaghan / Irwin, Meredith S / Bagatell, Rochelle / London, Wendy B / Greengard, Emily G / Park, Julie R / DuBois, Steven G

European journal of cancer (Oxford, England : 1990)

2019 Volume 112, Page(s) 66–79

Abstract: Background: Induction chemotherapy plays an important role in the management of patients with high-risk neuroblastoma. Predictors of response to induction therapy are largely lacking. We sought to describe clinical and biological features associated ... ...

Abstract	Background: Induction chemotherapy plays an important role in the management of patients with high-risk neuroblastoma. Predictors of response to induction therapy are largely lacking. We sought to describe clinical and biological features associated with induction response. Methods: Patients from four consecutive COG high-risk trials were included. Response was evaluated by the 1993 International Neuroblastoma Response Criteria. The primary end-point was end-induction partial response (PR) or better. Univariate analyses were performed to compare response as a function of clinical or biologic predictors. A multivariate logistic regression model using significant predictors from univariate analyses was constructed to model PR or better. Results: The analytic cohort included 1242 patients. End-induction response ≥PR was significantly associated with higher event-free and overall survival. Baseline factors associated with ≥PR included age <18 months (87.4% with ≥PR vs. 78.7% if older; p = 0.0103), International Neuroblastoma Staging System non-stage 4 (89.0% vs. 78.4% if stage 4; p = 0.0016), MYCN amplification (85.5% vs. 77.1% if non-amplified; p = 0.0006), 1p loss of heterozygosity (LOH; 85.6% vs. 76.0% if no LOH; p = 0.0085), no 11q LOH (84.8% vs. 70.9% if 11q LOH; p = 0.0004) and high mitosis-karyorrhexis index (MKI; 84.5% vs. 77.5% if low-intermediate MKI; p = 0.0098). On multivariable analysis (n = 407), the absence of 11q LOH was the only factor that remained significantly associated with ≥PR (odds ratio: 1.962 vs. 11q LOH; 95% confidence interval 1.104-3.487; p = 0.0216). Conclusions: Improved end-induction response in high-risk neuroblastoma is associated with longer survival. Patients with 11q LOH are less likely to respond to induction therapies and should be prioritised for novel approaches in future trials.
MeSH term(s)	Child, Preschool ; Cohort Studies ; Disease-Free Survival ; Female ; Gene Amplification/drug effects ; Gene Amplification/genetics ; Humans ; Infant ; Logistic Models ; Loss of Heterozygosity/drug effects ; Loss of Heterozygosity/genetics ; Male ; N-Myc Proto-Oncogene Protein/genetics ; Neoadjuvant Therapy/methods ; Neoplasm Staging/methods ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Neuroblastoma/pathology ; Nuclear Proteins/genetics ; Prognosis ; Risk Factors
Chemical Substances	N-Myc Proto-Oncogene Protein ; Nuclear Proteins
Language	English
Publishing date	2019-04-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2019.02.003
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Article ; Online: Impact of Surveillance Imaging Modality on Survival After Recurrence in Patients With Favorable-Histology Wilms Tumor: A Report From the Children's Oncology Group.

Mullen, Elizabeth A / Chi, Yueh-Yun / Hibbitts, Emily / Anderson, James R / Steacy, Katarina J / Geller, James I / Green, Daniel M / Khanna, Geetika / Malogolowkin, Marcio H / Grundy, Paul E / Fernandez, Conrad V / Dome, Jeffrey S

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2018 , Page(s) JCO1800076

Abstract: Purpose: The use of computed tomography (CT) for routine surveillance to detect recurrence in patients with Wilms tumor (WT) has increased in recent years. The utility of CT, despite increased risk and cost, to improve outcome for these patients is ... ...

Abstract	Purpose: The use of computed tomography (CT) for routine surveillance to detect recurrence in patients with Wilms tumor (WT) has increased in recent years. The utility of CT, despite increased risk and cost, to improve outcome for these patients is unknown. We conducted a retrospective analysis with patients enrolled in the fifth National Wilms Tumor Study (NWTS-5) to determine if surveillance with CT correlates with improved overall survival (OS) after recurrence compared with chest x-ray (CXR) and abdominal ultrasound (US). Patients and methods: Overall, 281 patients with recurrent unilateral favorable-histology WT were reviewed to assess how WT recurrence was detected: sign/symptoms (SS), surveillance imaging (SI) with CT scan, or SI with CXR/US. Results: The estimated 5-year OS rate after relapse was 67% (95% CI, 61% to 72%). Twenty-five percent of recurrences were detected with SS; 48.5%, with CXR/US; and 26.5%, with CT. Patients with SS had a 5-year OS rate of 59% (95% CI, 46% to 72%) compared with 70% (95% CI, 63% to 77%; P = .23) for those detected by SI. Recurrences detected by CT had a shorter median time from diagnosis to recurrence (0.60 years) compared with SS (0.91 years) or CXR/US (0.86 years; P = .003). For recurrences detected by SI, more tumor foci at relapse ( P < .001) and size of the largest focus greater than 2 cm ( P = .02) were associated with inferior OS. However, there was no difference in OS after relapse when recurrence was detected by CT versus CXR/US (5-year OS rate, 65% v 73%; P = .20). Conclusion: In patients with favorable-histology WT, elimination of CT scans from surveillance programs is unlikely to compromise survival but would result in substantial reduction in radiation exposure and health care costs.
Language	English
Publishing date	2018-10-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.18.00076
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