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INTRODUCTION: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy. METHODS: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center. Participants were divided into two groups: individuals treated with conventional chemotherapy ± radiation ("non-ASCR") (n = 32) or with chemotherapy ± radiation followed by myeloablative chemotherapy with ASCR ("ASCR") (n = 51). Ovarian dysfunction was defined as follicle-stimulating hormone ≥15 mU/mL, while premature ovarian insufficiency (POI) was defined as persistent ovarian dysfunction requiring hormone replacement therapy. Poisson models were used to determine prevalence ratios of ovarian dysfunction and POI. RESULTS: Among 83 females (median attained age: 19 years [range, 10-36]; median follow-up: 15 years [range, 7-36]), 49 (59%) had ovarian dysfunction, and 34 (41%) developed POI. Survivors treated with ASCR were 3.2-fold more likely to develop ovarian dysfunction (95% CI: 1.8-6.0; p < 0.001) and 4.5-fold more likely to develop POI (95% CI: 1.7-11.7; p = 0.002) when compared with those treated with conventional chemotherapy, after adjusting for attained age. Two participants in the non-ASCR group and six in the ASCR group achieved at least one spontaneous pregnancy. DISCUSSION: Ovarian dysfunction is prevalent in female high-risk neuroblastoma survivors, especially after ASCR. Longitudinal follow-up of larger cohorts is needed to inform counseling about the risk of impaired ovarian function after neuroblastoma therapy.
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Sobreviventes de Câncer , Neuroblastoma , Insuficiência Ovariana Primária , Humanos , Feminino , Neuroblastoma/terapia , Adolescente , Estudos Retrospectivos , Sobreviventes de Câncer/estatística & dados numéricos , Adulto , Criança , Adulto Jovem , Insuficiência Ovariana Primária/epidemiologia , Insuficiência Ovariana Primária/etiologia , Insuficiência Ovariana Primária/induzido quimicamente , Seguimentos , Ovário/efeitos dos fármacos , Ovário/fisiopatologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante AutólogoRESUMO
BACKGROUND: Approximately 1 in 10 adult survivors of childhood cancer is underweight. Although the consequences of being overweight or obese have been well described, outcomes among childhood cancer survivors who are underweight are unknown. OBJECTIVE: To determine whether underweight status increases the risk of mortality. PROCEDURE: Cohort study: Marginal models with generalized estimating equations to evaluate the associations between body mass index (BMI), serious or life-threatening chronic conditions, and death in the setting of long-term follow-up questionnaires and National Death Index search. PARTICIPANTS: Childhood cancer five-year survivors diagnosed during 1970-1986 in the Childhood Cancer Survivor Study Exposure: Underweight status, defined as body mass index (BMI) < 18.5 kg/m2 compared with ideal body weight. Based on available literature on body weight and mortality from the general population, ideal body weight was defined as BMI 22.0-24.9 kg/m2. MAIN OUTCOMES: Overall mortality and cancer-specific mortality. RESULTS: Of 9454 survivors (median age 35 years old (range, 17-58), an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline or follow-up questionnaire. Of 184 deaths, 29 were among underweight survivors. Underweight status was more common among females (9.1% vs. 4.5%, p < .01) and participants with younger age at diagnosis (8.2% for < 5 years vs. 6.1% for ≥5 years, p < .01), lower household income (8.9% for < $20,000 vs. 6.0% for ≥ $20,000, p < .01), or a history of serious chronic condition (p = .05). After adjustment for these factors, in addition to prior smoking and a history of radiation therapy, the risk of all-cause mortality within two years of BMI report was increased (OR 2.85; 95% CI: 1.63-4.97; p < .01) for underweight survivors, compared with ideal-weight survivors. CONCLUSIONS: Childhood cancer survivors who are underweight are at increased risk for late mortality that appears unrelated to smoking status, recognized chronic disease, or subsequent malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.
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Índice de Massa Corporal , Sobreviventes de Câncer , Neoplasias , Magreza , Humanos , Magreza/mortalidade , Feminino , Masculino , Sobreviventes de Câncer/estatística & dados numéricos , Adolescente , Adulto , Neoplasias/mortalidade , Neoplasias/complicações , Adulto Jovem , Pessoa de Meia-Idade , Seguimentos , Criança , Pré-Escolar , Fatores de Risco , Taxa de Sobrevida , PrognósticoRESUMO
BACKGROUND: Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity. METHODS: In this phase 3 efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with body mass index (BMI)≥25 kg/m2 were randomized to a remotely-delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy (CRT). The primary endpoint was the difference in weight loss at 24-months in an intent-to-treat analysis. Analyses were performed using linear mixed effects models. RESULTS: Among 358 survivors (59% female, median attained age: 37 years, IQR: 33-43), baseline mean (SD) weight was 98.6 kg (24.0) for the intervention group (n=181) and 94.9 kg (20.3) for controls (n=177). Adherence to the intervention was poor; 15% of individuals in the intervention completed 24/30 planned coaching calls. Weight at 24-months was available for 274 (77%) participants. After controlling for CRT, sex, race/ethnicity, and age, the mean (SE) change in weight from baseline to 24-months was -0.4 kg (0.8) for intervention and 0.2 kg (0.6) for control participants (p=0.59). CONCLUSIONS: A remote weight-loss intervention that was successful among adults with CV conditions did not result in significant weight loss among adult survivors of childhood ALL. IMPACT: Future interventions in this population must be tailored to the unique needs of survivors to encourage engagement and adherence.
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BACKGROUND: Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described. METHODS: Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings. RESULTS: Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1]). CONCLUSION: Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes.
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Sobreviventes de Câncer , Neuroblastoma , Humanos , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Masculino , Feminino , Sobreviventes de Câncer/estatística & dados numéricos , Criança , Adolescente , Adulto , Adulto Jovem , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Fatores de Risco , Estados Unidos/epidemiologia , Modelos de Riscos Proporcionais , Incidência , Pré-EscolarRESUMO
Survivors of adolescent and young adult (AYA) cancers, defined as individuals diagnosed with a primary malignancy between age 15 and 39 years, are a growing population with unique developmental, psychosocial, and health-related needs. These individuals are at excess risk of developing a wide range of chronic comorbidities compared with the general population and, therefore, require lifelong, risk-based, survivorship care to optimize long-term health outcomes. The health care needs of survivors of AYA cancers are particularly complicated given the often heterogeneous and sometimes fragmented care they receive throughout the cancer care continuum. For example, AYA survivors are often treated in disparate settings (pediatric v adult) on dissimilar protocols that include different recommendations for longitudinal follow-up. Specialized tools and techniques are needed to ensure that AYA survivors move seamlessly from acute cancer care to survivorship care and, in many cases, from pediatric to adult clinics while still remaining engaged in long-term follow-up. Systematic, age-appropriate transitional practices involving well-established clinical models of care, survivorship care plans, and survivorship guidelines are needed to facilitate effective transitions between providers. Future studies are necessary to enhance and optimize the clinical effectiveness of transition processes in AYA cancer survivors.
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Sobreviventes de Câncer , Neoplasias , Transição para Assistência do Adulto , Humanos , Adolescente , Adulto Jovem , Criança , Adulto , Transferência de Pacientes , Neoplasias/psicologia , Sobreviventes , Sobreviventes de Câncer/psicologiaRESUMO
Cell free DNA (cfDNA) and circulating tumor cell free DNA (ctDNA) from blood (plasma) are increasingly being used in oncology for diagnosis, monitoring response, identifying cancer causing mutations and detecting recurrences. Circulating tumor RB1 DNA (ctDNA) is found in the blood (plasma) of retinoblastoma patients at diagnosis before instituting treatment (naïve). We investigated ctDNA in naïve unilateral patients before enucleation and during enucleation (6 patients/ 8 mutations with specimens collected 5-40 minutes from severing the optic nerve) In our cohort, following transection the optic nerve, ctDNA RB1 VAF was measurably lower than pre-enucleation levels within five minutes, 50% less within 15 minutes and 90% less by 40 minutes.
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias da Retina , Retinoblastoma , Humanos , DNA Tumoral Circulante/genética , Retinoblastoma/genética , Retinoblastoma/cirurgia , Projetos Piloto , Enucleação Ocular , Mutação , Neoplasias da Retina/genética , Neoplasias da Retina/cirurgia , Biomarcadores Tumorais/genética , Ubiquitina-Proteína Ligases/genética , Proteínas de Ligação a Retinoblastoma/genéticaRESUMO
PURPOSE: To describe the risk of late mortality, subsequent malignant neoplasms (SMNs), and chronic health conditions (CHCs) in survivors of neuroblastoma diagnosed in infancy by treatment era and exposures. METHODS: Among 5-year survivors of neuroblastoma in the Childhood Cancer Survivor Study diagnosed age < 1 year between 1970 and 1999, we examined the cumulative incidence of late (> 5 years from diagnosis) mortality, SMN, and CHCs (grades 2-5 and 3-5). Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs by decade and treatment (surgery-alone v chemotherapy with or without surgery [C ± S] v radiation with or without chemotherapy ± surgery [R ± C ± S]) among survivors and between survivors and 5,051 siblings. RESULTS: Among 1,397 eligible survivors, the 25-year cumulative incidence of late mortality was 2.1% (95% CI, 1.3 to 3.9) with no difference by treatment era. Among 990 participants who completed a baseline survey, fewer survivors received radiation in more recent eras (51.2% 1970s, 20.4% 1980s, and 10.1% 1990s; P < .001). Risk of SMN was elevated only among individuals treated with radiation-containing regimens compared with surgery alone (HR[C ± S], 3.2 [95% CI, 0.9 to 11.6]; HR[R ± C ± S], 5.7 [95% CI, 1.2 to 28.1]). In adjusted models, there was a 50% reduction in risk of grade 3-5 CHCs in the 1990s versus 1970s (HR, 0.5 [95% CI, 0.3 to 0.9]; P = .01); individuals treated with radiation had a 3.6-fold risk for grade 3-5 CHCs (95% CI, 2.1 to 6.2) versus those treated with surgery alone. When compared with siblings, risk of grade 3-5 CHCs for survivors was lowest in the most recent era (HR[1970s], 4.7 [95% CI, 3.4 to 6.5]; HR[1980s], 4.6 [95% CI, 3.3 to 6.4]; HR[1990s], 2.5 [95% CI, 1.7 to 3.9]). CONCLUSION: Neuroblastoma survivors treated during infancy have a relatively low absolute burden of late mortality and SMN. Encouragingly, risk of CHCs has declined in more recent eras with reduced exposure to radiation therapy.
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Sobreviventes de Câncer , Segunda Neoplasia Primária , Neuroblastoma , Criança , Lactente , Humanos , Estudos Retrospectivos , Sobreviventes , Neuroblastoma/epidemiologia , Neuroblastoma/terapia , Morbidade , Incidência , Segunda Neoplasia Primária/epidemiologiaRESUMO
PURPOSE: As the role of clinical ethics consultation in health care advances, there are calls to standardize the process of consultation. The Ethics Committee at Memorial Sloan Kettering Cancer Center (MSK) hypothesized that the process of requesting an ethics consultation could be improved by instituting an electronic health record (EHR) order for consultation requests. This report summarizes the impact of adopting an EHR order for ethics consultation requests at MSK. METHODS: This retrospective review of all clinical ethics consultations requested at a tertiary cancer center from May 2017 to February 2020 spans 17 months before and after implementation of an electronic order for consultation requests. Summary statistics are presented using Pearson chi-square analyses with a significance level of 0.05. RESULTS: There was a significant increase in the total number of consultation requests placed after implementation of the EHR order (n = 165, 0.08% of total patients) compared with before (n = 108, 0.05% of total patients; P = .007). The number of consults requested by providers from inpatient (P = .02) and outpatient (P = .04) settings significantly increased. The proportion of consults placed by medical versus nonmedical providers remained unchanged (P = .32). CONCLUSION: In this large single-institution retrospective study, implementation of an EHR order for ethics consultation requests was associated with a significant increase in the number of consultation requests. Implementation of an electronic order may decrease barriers to ethics consultation in diverse practice settings. Further longitudinal, multicenter studies are needed to assess strategies to improve access to clinical ethics consultation for oncology patients.
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Consultoria Ética , Atenção à Saúde , Registros Eletrônicos de Saúde , Comissão de Ética , Humanos , Estudos RetrospectivosAssuntos
Neoplasias , Sobreviventes , Adolescente , Humanos , Neoplasias/mortalidade , Neoplasias/terapia , Adulto JovemRESUMO
BACKGROUNDChildhood cancer survivors who received abdominal radiotherapy (RT) or total body irradiation (TBI) are at increased risk for cardiometabolic disease, but the underlying mechanisms are unknown. We hypothesize that RT-induced adipose tissue dysfunction contributes to the development of cardiometabolic disease in the expanding population of childhood cancer survivors.METHODSWe performed clinical metabolic profiling of adult childhood cancer survivors previously exposed to TBI, abdominal RT, or chemotherapy alone, alongside a group of healthy controls. Study participants underwent abdominal s.c. adipose biopsies to obtain tissue for bulk RNA sequencing. Transcriptional signatures were analyzed using pathway and network analyses and cellular deconvolution.RESULTSIrradiated adipose tissue is characterized by a gene expression signature indicative of a complex macrophage expansion. This signature includes activation of the TREM2-TYROBP network, a pathway described in diseases of chronic tissue injury. Radiation exposure of adipose is further associated with dysregulated adipokine secretion, specifically a decrease in insulin-sensitizing adiponectin and an increase in insulin resistance-promoting plasminogen activator inhibitor-1. Accordingly, survivors exhibiting these changes have early signs of clinical metabolic derangement, such as increased fasting glucose and hemoglobin A1c.CONCLUSIONChildhood cancer survivors exposed to abdominal RT or TBI during treatment exhibit signs of chronic s.c. adipose tissue dysfunction, manifested as dysregulated adipokine secretion that may negatively impact their systemic metabolic health.FUNDINGThis study was supported by Rockefeller University Hospital; National Institute of General Medical Sciences (T32GM007739); National Center for Advancing Translational Sciences (UL1 TR001866); National Cancer Institute (P30CA008748); American Cancer Society (133831-CSDG-19-117-01-CPHPS); American Diabetes Association (1-17-ACE-17); and an anonymous donor (MSKCC).
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Abdome/efeitos da radiação , Tecido Adiposo/efeitos da radiação , Exposição à Radiação/efeitos adversos , Adulto , Sobreviventes de Câncer , Doença Crônica , Feminino , Humanos , MasculinoRESUMO
PURPOSE: Women treated with chest radiation for childhood cancer have one of the highest risks of breast cancer. Models producing personalized breast cancer risk estimates applicable to this population do not exist. We sought to develop and validate a breast cancer risk prediction model for childhood cancer survivors treated with chest radiation incorporating treatment-related factors, family history, and reproductive factors. METHODS: Analyses were based on multinational cohorts of female 5-year survivors of cancer diagnosed younger than age 21 years and treated with chest radiation. Model derivation was based on 1,120 participants in the Childhood Cancer Survivor Study diagnosed between 1970 and 1986, with median attained age 42 years (range 20-64) and 242 with breast cancer. Model validation included 1,027 participants from three cohorts, with median age 32 years (range 20-66) and 105 with breast cancer. RESULTS: The model included current age, chest radiation field, whether chest radiation was delivered within 1 year of menarche, anthracycline exposure, age at menopause, and history of a first-degree relative with breast cancer. Ten-year risk estimates ranged from 2% to 23% for 30-year-old women (area under the curve, 0.63; 95% CI, 0.50 to 0.73) and from 5% to 34% for 40-year-old women (area under the curve, 0.67; 95% CI, 0.54 to 0.84). The highest risks were among premenopausal women older than age 40 years treated with mantle field radiation within a year of menarche who had a first-degree relative with breast cancer. It showed good calibration with an expected-to-observed ratio of the number of breast cancers of 0.92 (95% CI, 0.74 to 1.16). CONCLUSION: Breast cancer risk varies among childhood cancer survivors treated with chest radiation. Accurate risk prediction may aid in refining surveillance, counseling, and preventive strategies in this population.
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Neoplasias da Mama/etiologia , Neoplasias Induzidas por Radiação/epidemiologia , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Sobreviventes de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
We assessed breast, cervical, and colorectal cancer screening practices in adult retinoblastoma (Rb) survivors and non-Rb controls. We found that most Rb survivors adhered to general population cancer screening recommendations. Rates did not differ among Rb survivors and non-Rb controls, or among survivors by laterality, even though bilateral survivors reported higher levels of concern about future health and cancer risk. Older age, being overweight/obese, and lack of recent contact with medical personnel were independently associated with decreased utilization of Pap smear among female Rb survivors. Future studies are warranted to determine whether these associations might provide an opportunity for intervention.
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Neoplasias da Mama/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Fatores Etários , Idoso , Sobreviventes de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Retina/epidemiologia , Retinoblastoma/epidemiologia , Adulto JovemRESUMO
Childhood cancer survivors are a growing population with high morbidity and many healthcare needs. As time from treatment lengthens, these patients are more and more likely to be followed in community primary care. Yet, studies suggest that primary care providers are unprepared (although not unwilling) to care for childhood cancer survivors. The 1-year fellowship in childhood cancer survivorship presented herein represents an educational intervention designed to prepare clinical leaders in survivorship. Ultimately, this effort may help address current gaps in care for childhood cancer survivors.
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Sobreviventes de Câncer , Neoplasias , Criança , Atenção à Saúde , Bolsas de Estudo , Humanos , Neoplasias/terapia , SobrevivênciaRESUMO
Purpose: Analysis of circulating tumor DNA (ctDNA) in the plasma of patients with retinoblastoma and simulating lesions. Design: Retrospective cross-sectional study of the association of plasma ctDNA from retinoblastoma and simulating lesions with disease course. Participants: Fifty-eight Memorial Sloan Kettering Cancer Center patients with retinoblastoma comprising 68 plasma ctDNA samples and 5 with retinoblastoma-simulating lesions. Methods: The ctDNA analyzed with hybridization capture and next-generation sequencing in blood (plasma) of patients who had retinoblastoma or simulating lesions were evaluated for association with clinical course of the disease. Main Outcome Measures: Presence or absence of molecular aberrations in the RB1 gene and correlations with clinical features. Results: RB1 cell-free DNA (cfDNA) was detected in 16 of 19 patients with newly diagnosed, untreated intraocular retinoblastoma and in 3 of 3 patients with newly diagnosed, untreated metastatic disease. It was also present in 3 patients with recurrent intraocular disease before therapy, but was not present in patients with recurrent disease who received intra-arterial chemotherapy, nor in 21 patients who had undergone enucleation for unilateral disease. In 1 patient who had delayed treatment (insurance reasons) and showed rapid growth of the intraocular tumor, the variant allele frequency increased in 1 month from 0.34% to 2.48%. No RB1 mutations were detected in the cfDNA from plasma of patients with simulating lesions (3 with Coats disease and 1 with persistent fetal vasculature [PFV]). In 2 patients, we identified 2 independent RB1 mutations in plasma. Conclusions: Mutations in RB1 were found in the cfDNA from blood of patients with newly diagnosed, untreated retinoblastoma and in patients who showed disease recurrence in the eye after prior treatment, but not in unilateral retinoblastoma after enucleation Levels of ctDNA increase in patients with progressive disease who did not receive any treatment. High plasma cfDNA levels were detected in patients with newly diagnosed metastatic disease, and these levels decreased after systemic chemotherapy was administered. Further validation is needed for measuring the somatic alterations in cfDNA from blood in retinoblastoma that could provide a promising method of monitoring patients in the future.
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PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has raised a variety of ethical dilemmas for health care providers. Limited data are available on how a patient's concomitant cancer diagnosis affected ethical concerns raised during the early stages of the pandemic. METHODS: We performed a retrospective review of all COVID-related ethics consultations registered in a prospectively collected ethics database at a tertiary cancer center between March 14, 2020, and April 28, 2020. Primary and secondary ethical issues, as well as important contextual factors, were identified. RESULTS: Twenty-six clinical ethics consultations were performed on 24 patients with cancer (58.3% male; median age, 65.5 years). The most common primary ethical issues were code status (n = 11), obligation to provide nonbeneficial treatment (n = 3), patient autonomy (n = 3), resource allocation (n = 3), and delivery of care wherein the risk to staff might outweigh the potential benefit to the patient (n = 3). An additional nine consultations raised concerns about staff safety in the context of likely nonbeneficial treatment as a secondary issue. Unique contextual issues identified included concerns about public safety for patients requesting discharge against medical advice (n = 3) and difficulties around decision making, especially with regard to code status because of an inability to reach surrogates (n = 3). CONCLUSION: During the early pandemic, the care of patients with cancer and COVID-19 spurred a number of ethics consultations, which were largely focused on code status. Most cases also raised concerns about staff safety in the context of limited benefit to patients, a highly unusual scenario at our institution that may have been triggered by critical supply shortages.
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COVID-19 , Institutos de Câncer , Consultoria Ética/tendências , Neoplasias , Ordens quanto à Conduta (Ética Médica)/ética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais , Reanimação Cardiopulmonar/ética , Criança , Tomada de Decisões , Comitês de Ética Clínica , Feminino , Alocação de Recursos para a Atenção à Saúde/ética , Neoplasias Hematológicas , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/ética , Neoplasias Renais , Neoplasias Pulmonares , Masculino , Futilidade Médica , Competência Mental , Pessoa de Meia-Idade , Mieloma Múltiplo , Cidade de Nova Iorque , Saúde Ocupacional/ética , Quartos de Pacientes , Autonomia Pessoal , Procurador , SARS-CoV-2 , Sarcoma , Adulto JovemRESUMO
Childhood cancer survivors are at increased risk for treatment-related late effects; data are lacking on how coronavirus disease 2019 (COVID-19) infection impacts this cohort. We assessed COVID-19-related symptoms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG seroprevalence, and rate of COVID-19-related hospitalization among 321 asymptomatic survivors of childhood cancer or transplantation seen for routine long-term follow-up between May and September 2020 in a New York City tertiary cancer center. While 10.9% (n = 35) reported possible COVID-19-related symptoms, 7.8% (n = 20) of those tested had positive SARS-CoV-2 IgG, and one patient (0.3%) required COVID-19-related hospitalization. This report suggests that childhood cancer survivors appear to be at relatively low risk for COVID-19 complications.
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Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias Hematológicas/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Cidade de Nova Iorque/epidemiologia , Estudos Retrospectivos , Risco , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificaçãoRESUMO
Importance: Persistent radiation-induced alopecia (pRIA) and its management have not been systematically described. Objective: To characterize pRIA in patients with primary central nervous system (CNS) tumors or head and neck sarcoma. Design, Setting, and Participants: A retrospective cohort study of patients from January 1, 2011, to January 30, 2019, was conducted at 2 large tertiary care hospitals and comprehensive cancer centers. Seventy-one children and adults diagnosed with primary CNS tumors or head and neck sarcomas were evaluated for pRIA. Main Outcomes and Measures: The clinical and trichoscopic features, scalp radiation dose-response relationship, and response to topical minoxidil were assessed using standardized clinical photographs of the scalp, trichoscopic images, and radiotherapy treatment plans. Results: Of the 71 patients included (median [range] age, 27 [4-75] years; 51 female [72%]), 64 (90%) had a CNS tumor and 7 (10%) had head and neck sarcoma. Alopecia severity was grade 1 in 40 of 70 patients (56%), with localized (29 of 54 [54%]), diffuse (13 of 54 [24%]), or mixed (12 of 54 [22%]) patterns. The median (range) estimated scalp radiation dose was 39.6 (15.1-50.0) Gy; higher dose (odds ratio [OR], 1.15; 95% CI, 1.04-1.28) and proton irradiation (OR, 5.7; 95% CI, 1.05-30.8) were associated with greater alopecia severity (P < .001), and the dose at which 50% of patients were estimated to have severe (grade 2) alopecia was 36.1 Gy (95% CI, 33.7-39.6 Gy). Predominant trichoscopic features included white patches (16 of 28 [57%]); in 15 patients, hair-shaft caliber negatively correlated with scalp dose (correlation coefficient, -0.624; P = .01). The association between hair density and scalp radiation dose was not statistically significant (-0.381; P = .16). Twenty-eight of 34 patients (82%) responded to topical minoxidil, 5% (median follow-up, 61 [interquartile range, 21-105] weeks); 4 of 25 (16%) topical minoxidil recipients with clinical images improved in severity grade. Two patients responded to hair transplantation and 1 patient responded to plastic surgical reconstruction. Conclusions and Relevance: Persistent radiation-induced alopecia among patients with primary CNS tumors or head and neck sarcomas represents a dose-dependent phenomenon that has distinctive clinical and trichoscopic features. The findings of this study suggest that topical minoxidil and procedural interventions may have benefit in the treatment of pRIA.
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Alopecia/diagnóstico , Irradiação Craniana/efeitos adversos , Minoxidil/administração & dosagem , Lesões por Radiação/diagnóstico , Couro Cabeludo/cirurgia , Administração Tópica , Adolescente , Adulto , Idoso , Alopecia/etiologia , Alopecia/terapia , Neoplasias do Sistema Nervoso Central/radioterapia , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Feminino , Cabelo/efeitos da radiação , Cabelo/transplante , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Estudos Retrospectivos , Couro Cabeludo/efeitos da radiação , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
We describe utilization of clinical genetic services among survivors of childhood and young adult cancer after participation in a genetic registry. Clinical genetic counselors flagged 162 out of 1069 pedigrees (15.2%) as suggestive of inheritable cancer susceptibility, resulting in 126 (11.8%) referral letters. Following delivery of the referral letters, 19 (15.1%) participants completed clinical genetic counseling, 16 (12.7%) received testing, and four (3.2%) were found to have actionable results. Our results suggest a discordance between reported willingness to undergo genetic counseling and real-world utilization.
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BACKGROUND: Germline retinoblastoma (Rb) survivors are at lifelong risk for developing subsequent malignancies (SMNs). Optimal surveillance modalities are needed to detect SMN at an early stage in this high-risk cohort. We investigated the use of rapid whole-body magnetic resonance imaging (WB-MRI) as a noninvasive screening modality in this cohort. PROCEDURE: WB-MRI was performed in asymptomatic preadolescent, adolescent, or young adult survivors of germline Rb from February 1, 2008 to December 31, 2018 at a tertiary cancer center. We calculated sensitivity and specificity of WB-MRI and rate of false-positive findings requiring additional evaluation. RESULTS: Overall, 110 WB-MRI were performed in 47 germline Rb survivors (51% female; median age at initial WB-MRI: 15.5 years [range 8-25.3]). Patients received 1-10 annual WB-MRI examinations (median: two). Thirteen patients had an abnormal WB-MRI; three findings were deemed to be likely benign and were not evaluated further. Ten patients required dedicated imaging and three required biopsy; two patients were diagnosed with localized high-grade osteosarcoma, while the other eight had benign findings. One patient was diagnosed with secondary osteosarcoma 3 months after normal WB-MRI. In total, there were 96 true negatives, 11 false positives, two true positives, and one false negative. The sensitivity of WB-MRI in this cohort was 66.7% (95% confidence interval [CI], 14.2-96.0) and the specificity was 89.7% (95% CI, 83.6-93.7). CONCLUSIONS: Based on our 10-year experience, surveillance WB-MRI appears to have limited utility as a surveillance modality for SMN in germline Rb survivors. Alternate screening modalities should be investigated.
Assuntos
Imageamento por Ressonância Magnética/métodos , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Imagem Corporal Total/métodos , Adolescente , Adulto , Sobreviventes de Câncer , Criança , Feminino , Seguimentos , Células Germinativas , Humanos , Incidência , Masculino , Segunda Neoplasia Primária/diagnóstico por imagem , Segunda Neoplasia Primária/epidemiologia , New York/epidemiologia , Vigilância da População , Prognóstico , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: To generate recommendations for long-term follow-up of adult survivors of heritable retinoblastoma. DESIGN: We convened a meeting of providers from retinoblastoma centers around the world to review the state of the science and to evaluate the published evidence. PARTICIPANTS: Retinoblastoma is a rare childhood cancer of the retina. Approximately 40% of retinoblastoma cases are heritable, resulting from a germline mutation in RB1. Dramatic improvements in treatment and supportive care have resulted in a growing adult survivor population. However, survivors of heritable retinoblastoma have a significantly increased risk of subsequent malignant neoplasms, particularly bone and soft tissue sarcomas, uterine leiomyosarcoma, melanomas, and radiotherapy-related central nervous system tumors, which are associated with excess morbidity and mortality. Despite these risks, no surveillance recommendations for this population currently are in place, and surveillance practices vary widely by center. METHODS: Following the Institute of Medicine procedure for clinical practice guideline development, a PubMed, EMBASE, and Web of Science search was performed, resulting in 139 articles; after abstract and full-text review, 37 articles underwent detailed data abstraction to quantify risk and evidence regarding surveillance, if available. During an in-person meeting, evidence was presented and discussed, resulting in consensus recommendations. MAIN OUTCOME MEASURES: Diagnosis and mortality from subsequent neoplasm. RESULTS: Although evidence for risk of subsequent neoplasm, especially sarcoma and melanoma, was significant, evidence supporting routine testing of asymptomatic survivors was not identified. Skin examination for melanoma and prompt evaluation of signs and symptoms of head and neck disease were determined to be prudent. CONCLUSIONS: This review of the literature confirmed some of the common second cancers in retinoblastoma survivors but found little evidence for a benefit from currently available surveillance for these malignancies. Future research should incorporate international partners, patients, and family members.