RESUMEN
BACKGROUND: Eyes with Group D intraocular retinoblastoma have low salvage rates. A pilot study showed safety and efficacy of sub-Tenon's fascia carboplatin with systemic chemotherapy supporting further study. METHODS: Children with newly diagnosed bilateral intraocular retinoblastoma with at least one remaining Group C or D eye were treated with six courses of carboplatin/etoposide/vincristine (CEV) with sub-Tenon's fascia carboplatin for Group C/D eyes during courses 2-4. Local ophthalmic therapy started at course 3. The primary study objective was to determine the 1-year failure rate of Group D eyes. RESULTS: The study closed prematurely due to poor accrual and 22 of 30 patients were evaluable for failure rate, contributing 25 Group D and four Group C eyes. Among the 25 Group D eyes, there were 13 failures within the first year of study enrollment including eight needing external beam radiotherapy (EBR) and five needing enucleation, resulting in 1-year failure rate of 52%. The failure rate was significantly lower than the historical rate of 70% (P = .039). The 1-year eye preservation rate for Group D eyes was 80% (20/25). One-year failure rate for Group C eyes was 25% (1/4); 1-year preservation rate was 100% without need for EBR. Systemic toxicity included Grade 3 hearing loss in two subjects, infections, neutropenia, and thrombocytopenia. Ocular toxicities included periorbital fat atrophy (13/29 = 45% eyes), optic nerve atrophy (1/29 = 3% eyes), and restrictive fibrosis (1/29 = 3% eyes). CONCLUSIONS: Sub-Tenon's fascia carboplatin plus CEV was partially effective in Group D intraocular retinoblastoma but had unacceptable ocular toxicities.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Cápsula de Tenon , Adolescente , Adulto , Carboplatino/administración & dosificación , Niño , Preescolar , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pronóstico , Neoplasias de la Retina/patología , Retinoblastoma/patología , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations. METHODS: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow-up was 26.6 years. RESULTS: In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14-fold increased risk of developing an sSMN (95% confidence interval, 12.0-fold to 16.3-fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age <10 years were found to be at highest risk of developing lung cancer. Survivors of HL who were treated with abdominal/pelvic radiotherapy and high-dose alkylating agents were found to be at highest risk of developing colorectal cancer and females exposed to neck radiotherapy at age <10 years were at highest risk of thyroid cancer. By age 50 years, the cumulative incidence of breast, lung, colorectal, and thyroid cancer was 45.3%, 4.2%, 9.5%, and 17.3%, respectively, among those at highest risk. CONCLUSIONS: Survivors of childhood HL remain at an increased risk of developing sSMNs. In the current study, subgroups of survivors of HL at highest risk of specific sSMNs were identified, and evidence for screening provided.
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Enfermedad de Hodgkin/terapia , Neoplasias Primarias Secundarias/epidemiología , Adolescente , Adulto , Niño , Preescolar , Quimioterapia , Femenino , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Radioterapia , Medición de RiesgoRESUMEN
PURPOSE: To evaluate a chemoreduction regimen using systemic vincristine and carboplatin (VC) and local ophthalmic therapies to avoid external-beam radiotherapy (EBRT) or enucleation in patients with Group B intraocular retinoblastoma. PATIENTS AND METHODS: Twenty-one patients (25 eyes) were treated with six cycles of VC, accompanied by local ophthalmic therapies after cycle 1. The primary study objective was to determine the 2-year event-free survival (EFS) where an event was defined as the use of systemic chemotherapy in addition to vincristine or carboplatin, EBRT, and/or enucleation. RESULTS: All patients had tumor regression after the first cycle of VC and only two patients had progression during therapy. There were seven treatment failures within 2 years of study enrollment, resulting in 2-year EFS of 65% and early study closure in accordance with the statistical design. The 2-year cumulative incidence of enucleation was 15%; for external beam radiation therapy, it was 10%; and for chemotherapy to control progressive disease, it was 10%. All patients sustaining a treatment failure were salvaged with additional therapy. CONCLUSIONS: For the majority of patients with Group B intraocular retinoblastoma, chemoreduction with VC, without etoposide, in conjunction with local therapy provides excellent opportunity for ocular salvage. Local therapy given with every chemotherapy cycle and incorporation of etoposide may provide improved ocular salvage rates. Central review of group at diagnosis is critical in assigning appropriate therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Terapia Neoadyuvante/métodos , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Carboplatino/administración & dosificación , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Vincristina/administración & dosificaciónRESUMEN
Increases in the number of adult cancer survivors and other issues have forced the oncology community to examine, evaluate, and alter the cancer care paradigm. Pediatric oncologists are grappling with the task of transitioning a growing population of adult survivors of childhood cancer to adult medicine, while oncologists caring for adult cancer survivors are seeking models of follow-up care that are acceptable to patients and providers. Workforce and access-to-care issues suggest that primary care providers will see more cancer survivors in their practices across time, although it is unclear how prepared they are for this task. Translational research is needed to develop evidence-based clinical care and survivorship care plans. A broad picture of the evolving field of adult cancer survivorship is presented. The recent focus on young adult survivors of childhood cancer, an overview of translational research needed to inform the physical and psychosocial care of cancer survivors, and the roles of primary and specialty care providers managing this population is examined. Finally, an overview of evolving treatment summary and care plan initiatives is presented.
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Continuidad de la Atención al Paciente , Neoplasias/terapia , Sobrevivientes , Adulto , Niño , Conductas Relacionadas con la Salud , Educación en Salud , Humanos , Internet , Neoplasias/psicología , Planificación de Atención al PacienteRESUMEN
PURPOSE: We conducted a case-control study to examine the role of parents' nutrient intake before their child's conception in the child's risk of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation. METHODS: Parents of 206 cases from 9 North American institutions and 269 friend and relative controls participated; fathers of 182 cases and 223 controls and mothers of 202 cases and 260 controls provided useable information in telephone interviews on their diet in the year before the child's conception. We also asked parents about supplements, a significant source of nutrients in users. RESULTS: Father's intake of dairy-associated nutrients and his use of calcium supplements were associated with decreased risk, while his intake of copper, manganese, and vitamin E was associated with increased risk. Mother's use of multivitamins close to conception was associated with lower risk as was her intake of several micronutrients found in these supplements. In analyses to elucidate the primary factor from multiple correlated factors, the most robust findings were for father's calcium intake (adjusted OR = 0.46-0.63 for 700 mg increase) and calcium supplement use (OR = 0.35-0.41) and mother's multivitamin use (ORs 0.28-0.48). CONCLUSIONS: There are few directly relevant studies but some data indirectly support the biologic plausibility of the inverse associations with father's calcium intake and mother's use of multivitamins; however, we cannot rule out contributions of bias, confounding, or chance. Our findings provide a starting point for further investigation of diet in the etiology of retinoblastoma and new germline mutation generally.
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Dieta , Mutación de Línea Germinal , Proteína de Retinoblastoma/genética , Retinoblastoma/epidemiología , Adulto , Estudios de Casos y Controles , Padre , Femenino , Humanos , Masculino , Madres , Embarazo , Retinoblastoma/etiología , Retinoblastoma/genética , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Previous investigations of cancer survivors report that the cumulative incidence of subsequent leukemia plateaus between 10 and 15 years after primary therapy. Risk beyond 15 years has not been comprehensively assessed, primarily because of lack of long-term follow-up. Among 5-year survivors from the Childhood Cancer Survivor Study cohort, 13 pathologically confirmed cases of subsequent leukemia occurred ≥ 15 years after primary malignancy, with a mean latency of 21.6 years (range, 15-32 years). Seven were acute myeloid leukemia (2 acute promyelocytic leukemia with t(15;17), 2 with confirmed preceding myelodysplastic syndrome), 4 acute lymphoblastic leukemia (2 pre-B lineage, 1 T cell, 1 unknown), and 2 other. Two acute myeloid leukemia cases had the 7q- deletion. The standardized incidence ratio was 3.5 (95% confidence interval, 1.9-6.0). Median survival from diagnosis of subsequent leukemia was 2 years. This is the first description of a statistically significant increased risk of subsequent leukemia ≥ 15 years from primary diagnosis of childhood cancer.
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Leucemia/mortalidad , Adolescente , Canadá/epidemiología , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Leucemia/diagnóstico , Leucemia/terapia , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Children with solid tumors, most of which are malignant, have an excellent prognosis when treated on contemporary regimens. These regimens, which incorporate chemotherapeutic agents and treatment modalities used for many decades, have evolved to improve relapse-free survival and reduce long-term toxicity. This review discusses the evolution of the treatment regimens employed for management of the most common solid tumors, emphasizing the similarities between contemporary and historical regimens. These similarities allow the use of historical patient cohorts to identify the late effects of successful therapy and to evaluate remedial interventions for these adverse effects.
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Neoplasias/historia , Neoplasias/terapia , Niño , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
As more pediatric cancer patients survive for longer periods following treatment with cytotoxic agents, therapy-induced second malignant neoplasms (SMNs) have become a major concern. In this issue of Cancer Cell, Chao et al. report that mice carrying a mutation in Nf1, the gene responsible for neurofibromatosis type 1, treated with radiation and/or cyclophosphamide, developed tumors similar to human SMNs at a significantly higher rate than did wild-type controls treated similarly. This model provides efficient and rational means for testing procedures and agents that could inform clinicians regarding second cancer risks associated with treatment and, perhaps, reducing them.
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Modelos Animales de Enfermedad , Neoplasias Primarias Secundarias/etiología , Animales , Antineoplásicos Alquilantes/uso terapéutico , Ciclofosfamida/uso terapéutico , Humanos , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapiaRESUMEN
BACKGROUND: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. OBJECTIVE: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. DESIGN: Retrospective cohort study. SETTING: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. PATIENTS: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. MEASUREMENTS: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. RESULTS: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. LIMITATION: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. CONCLUSION: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. PRIMARY FUNDING SOURCE: National Cancer Institute.
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Neoplasias Gastrointestinales/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Sobrevivientes , Adolescente , Adulto , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Canadá/epidemiología , Niño , Neoplasias Colorrectales/epidemiología , Humanos , Incidencia , Compuestos de Platino/administración & dosificación , Compuestos de Platino/efectos adversos , Vigilancia de la Población , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Modelos de Riesgos Proporcionales , Radioterapia/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: To evaluate the occurrence of second malignant neoplasms (SMN) following chemoreduction (CRD) with carboplatin, vincristine, and etoposide (CEV) as frontline therapy in patients with retinoblastoma (RB). PRODECURE: We conducted a two-institution retrospective chart review of 245 patients with intraocular RB treated with six cycles of vincristine, carboplatin, and etoposide for treatment of intraocular retinoblastoma. Cumulative incidence of SMN was calculated with adjustment for the competing risk of death. RESULTS: There were 187 patients with germline retinoblastoma and 58 with non-germline disease. External beam radiotherapy was subsequently utilized in 46 (24%) of germline cases and six (10%) of non-germline cases. Mean follow-up of germline and non-germline patients was 80 and 70 months, respectively. Seven subsequent cancers were found in six patients for an overall incidence of 3% at a mean of 11 years. For germline cases, following CEV alone (n = 156), SMN were found in 4% following the RB diagnosis. We found no SMN in patients with non-germline RB. One patient developed pineoblastoma. SMN included osteosarcoma (n = 3), rhabdomyosarcoma (n = 1), orbital and conjunctival melanoma (n = 1), low-grade glioma (n = 1), and acute promyeloctic leukemia (n = 1). Five of the six patients with a second malignancy survive at mean of 46 months (range 15-71 months). CONCLUSIONS: At a mean of 11 years, 4% of children with germline RB treated with CEV as frontline therapy developed SMN's. No SMN was found in non-germline patients. Concerns regarding CEV-induced second cancers should not deter clinicians from using life and vision preserving therapy in patients with retinoblastoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Ojo/mortalidad , Neoplasias del Ojo/terapia , Neoplasias Primarias Secundarias/mortalidad , Retinoblastoma/mortalidad , Retinoblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Niño , Preescolar , Terapia Combinada/efectos adversos , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Neoplasias Primarias Secundarias/etiología , Estudios Retrospectivos , Tasa de Supervivencia , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
BACKGROUND: We previously developed a reliable and valid method for classifying the intensity of pediatric cancer treatment. The Intensity of Treatment Rating Scale (ITR-2.0) 1 classifies treatments into four operationally defined levels of intensity and is completed by pediatric oncology specialists based on diagnosis, stage, and treatment data from the medical record. Experience with the ITR-2.0 and recent changes in treatment protocols indicated the need for a minor revision and revalidation. METHODS: Five criterion raters reviewed the prior items, independently proposing additions and/or changes in the classification of diseases/treatments. Subsequent to a group discussion of the proposed changes, a revised 43-item ITR was evaluated. Pediatric oncologists (n = 47) completed a two-part online questionnaire. Validity of the classifications was determined by the oncologists classifying each disease/treatment into one of the four levels of intensity. Inter-rater reliability was calculated by having each oncologist classify the treatments of 12 sample patients using the new version which we call the ITR-3. RESULTS: Agreement between median ratings of the 43 items for the pediatric oncologists and the criterion raters was high (r = 0.88). The median of the raters was either identical (81%) with the criterion ratings or discrepant by one level. Inter-rater reliability was very high when using the ITR-3 to classify 12 sample patients, with a median agreement of 0.90 and an intraclass correlation coefficient (r(ICC) = 0.86). CONCLUSIONS: With these minor modifications and updates, the ITR-3 remains a reliable and valid method for classifying pediatric oncology treatment protocols.
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Protocolos de Quimioterapia Combinada Antineoplásica/clasificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Adolescente , Preescolar , Femenino , Humanos , MasculinoRESUMEN
To combat the e-cigarette epidemic among young audiences, a federal law was passed in the US that raised the minimum legal sales age of tobacco to 21 years (commonly known as Tobacco 21). Little is known about sentiment toward this law. Thus, the purpose of our study was to systematically explore trends about Tobacco 21 discussions and comparisons to other age-restriction behaviors on Twitter. Twitter data (n = 4628) were collected from September to December of 2019 that were related to Tobacco 21. A random subsample of identified tweets was used to develop a codebook. Two trained coders independently coded all data, with strong inter-rater reliability (κ = 0.71 to 0.93) found for all content categories. Associations between sentiment and content categories were calculated using χ2 analyses. Among relevant tweets (n = 955), the most common themethe disjunction between ages for military enlistment and tobacco usewas found in 17.8% of all tweets. Anti-policy sentiment was strongly associated with the age of military enlistment, alcohol, voting, and adulthood (p < 0.001 for all). Opposition to Tobacco 21 propagates on social media because the US federal law does not exempt military members. However, the e-cigarette epidemic may have fueled some support for this law.
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Sistemas Electrónicos de Liberación de Nicotina , Medios de Comunicación Sociales , Adulto , Humanos , Políticas , Reproducibilidad de los Resultados , NicotianaRESUMEN
Although ionizing radiation induces germline mutations in animals, human studies of radiation-exposed populations have not detected an effect. We conducted a case-control study of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation, to investigate gonadal radiation exposure of parents from medical sources before their child's conception. Parents of 206 cases from nine North American institutions and 269 controls participated; fathers of 184 cases and 223 friend and relative controls and mothers of 204 cases and 260 controls provided information in telephone interviews on their medical radiation exposure. Cases provided DNA for RB1 mutation testing. Of common procedures, lower gastrointestinal (GI) series conferred the highest estimated dose to testes and ovaries. Paternal history of lower GI series was associated with increased risk of retinoblastoma in the child [matched odds ratio (OR) = 3.6, 95% confidence interval (CI) = 1.2-11.2, two-sided p = 0.02], as was estimated total testicular dose from all procedures combined (OR for highest dose=3.9, 95% CI = 1.2-14.4, p = 0.02). Maternal history of lower GI series was also associated with increased risk (OR = 7.6, 95% CI = 2.8-20.7, p < 0.001) as was the estimated total dose (OR for highest dose = 3.0, 95% CI = 1.4-7.0, p = 0.005). The RB1 mutation spectrum in cases of exposed parents did not differ from that of other cases. Some animal and human data support our findings of an association of gonadal radiation exposure in men and women with new germline RB1 mutation detectable in their children, although bias, confounding, and/or chance may also explain the results.
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Genes de Retinoblastoma , Mutación de Línea Germinal , Neoplasias Inducidas por Radiación/genética , Efectos Tardíos de la Exposición Prenatal , Dosis de Radiación , Retinoblastoma/genética , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Embarazo , Retinoblastoma/etiología , Rayos XRESUMEN
BACKGROUND: Women treated with therapeutic chest radiation may develop breast cancer. PURPOSE: To summarize breast cancer risk and breast cancer surveillance in women after chest radiation for pediatric or young adult cancer. DATA SOURCES: Studies from MEDLINE, EMBASE, the Cochrane Library, and CINAHL (1966 to December 2008). STUDY SELECTION: Articles were selected to answer any of 3 questions: What is the incidence and excess risk for breast cancer in women after chest radiation for pediatric or young adult cancer? For these women, are the clinical characteristics of breast cancer and the outcomes after therapy different from those of women with sporadic breast cancer in the general population? What are the potential benefits and harms associated with breast cancer surveillance among women exposed to chest radiation? DATA EXTRACTION: Three investigators independently extracted data and assessed study quality. DATA SYNTHESIS: Standardized incidence ratios ranged from 13.3 to 55.5; cumulative incidence of breast cancer by age 40 to 45 years ranged from 13% to 20%. Risk for breast cancer increased linearly with chest radiation dose. Available limited evidence suggests that the characteristics of breast cancer in these women and the outcomes after diagnosis are similar to those of women in the general population; mammography can detect breast cancer, although sensitivity is limited. LIMITATION: The quality of evidence for key questions 2 and 3 is limited by substantial study heterogeneity, variation in study design, and small sample size. CONCLUSION: Women treated with chest radiation have a substantially elevated risk for breast cancer at a young age, which does not seem to plateau. In this high-risk population, there seems to be a benefit associated with early detection. Further research is required to better define the harms and benefits of lifelong surveillance.
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Neoplasias de la Mama/epidemiología , Neoplasias Inducidas por Radiación/epidemiología , Adolescente , Factores de Edad , Niño , Femenino , Enfermedad de Hodgkin/radioterapia , Humanos , Incidencia , Oportunidad Relativa , Dosificación Radioterapéutica , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition. RESULTS: Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition. CONCLUSIONS: Survivors of childhood cancer have a high rate of illness owing to chronic health conditions.
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Enfermedad Crónica/epidemiología , Neoplasias/complicaciones , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , HermanosRESUMEN
PURPOSE: To evaluate chemoreduction (CRD) for group E retinoblastoma. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Seventy-six eyes of 56 patients with group E retinoblastoma were treated with CRD alone or CRD plus low-dose prophylactic external beam radiotherapy (CRD+P-EBR). The CRD included vincristine, etoposide, and carboplatin (6 cycles). The P-EBR was given routinely 2 months after completion of CRD at a suggested dose of 2600 cGy. Therapeutic EBR (T-EBR) was only given at the time of extensive tumor recurrence at a suggested dose of 3800 cGy. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Globe salvage. RESULTS: Of the 76 eyes, 64 received CRD alone and 12 received CRD+P-EBR. At the 2-year follow-up, globe salvage was achieved in 29 (53%) of 55 eyes in the CRD group and in 10 (91%) of 11 eyes in the CRD+P-EBR group. At 5 years, globe salvage was achieved in 20 (48%) of 42 eyes in the CRD group and in 4 (80%) of 5 eyes in the CRD+P-EBR group (P=0.347). Of the 64 eyes in the CRD group, 16 (25%) were salvaged with CRD alone and 13 (20%) with CRD+T-EBR, whereas 22 (34%) were enucleated after CRD alone and 13 (20%) were enucleated after CRD+T-EBR. Of the 12 eyes in the CRD+P-EBR group, 10 (83%) were salvaged with CRD+P-EBR, whereas 2 (17%) were enucleated and none required T-EBR. The median dose for T-EBR was 3800 cGy, and that for P-EBR was 2600 cGy. Eyes treated with CRD+P-EBR showed significantly less recurrence, leading to less chance of enucleation or therapeutic radiotherapy than that for CRD alone (P<0.001). Visual acuity was 20/100 or better or fix and follow in 9 (32%) of 28 salvaged eyes in the CRD group and in 4 (40%) of 10 in the CRD+P-EBR group. At 5 years, there were no patients in either group with metastasis of pinealoblastoma or who had died. In one patient in the CRD group, a second cancer developed. CONCLUSIONS: Group E retinoblastoma managed with CRD+P-EBR showed significantly less need for enucleation or therapeutic radiotherapy than eyes treated with CRD alone. These findings merit further study and consideration.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Radioterapia de Alta Energía , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Carboplatino/uso terapéutico , Niño , Preescolar , Terapia Combinada , Etopósido/uso terapéutico , Enucleación del Ojo , Femenino , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia , Neoplasias de la Retina/clasificación , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/radioterapia , Retinoblastoma/clasificación , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/radioterapia , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/uso terapéutico , Agudeza VisualRESUMEN
PURPOSE: To prospectively determine the prevalence of high-risk histopathologic features (HRFs) in patients with unilateral retinoblastoma who undergo enucleation and to evaluate the role of chemotherapy in preventing recurrences. PATIENTS AND METHODS: Children newly diagnosed with enucleated unilateral retinoblastoma were enrolled prospectively. After central histopathology review, patients with specific HRFs received chemotherapy; others were observed. Primary end points were event-free survivals (EFS). RESULTS: Of the 331 patients enrolled during 2005 to 2010, 321 eligible patients had central histopathologic review. Discordance between central review and contributing institutions occurred in 23% of patients with HRFs and in 17% of patients without HRFs. Postlaminar optic nerve involvement was present in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary 3 mm or greater choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal concomitant with lamina or prelamina optic nerve involvement. Two-year EFS for patients with HRFs requiring adjuvant chemotherapy was 0.96 (95% CI, 0.89 to 0.98), and 2-year EFS for patients without HRFs for which observation was indicated was 0.99 (95% CI, 0.96 to 1.0). The 2-year EFS for all patients was 0.98 (95% CI, 0.96 to 0.99). CONCLUSION: Adequate handling and interpretation of histopathology of eyes with retinoblastoma is necessary to assign metastatic risk. Concomitant less than 3 mm choroidal and any prelaminar/laminar optic nerve invasion show no recurrence and may warrant no adjuvant chemotherapy. In contrast, concomitant greater than 3 mm peripapillary choroidal invasion and 1.5 mm or greater of postlaminar optic nerve invasion have the poorest outcomes, supporting the need for a more intensive adjuvant chemotherapy regimen for this subgroup. Strict criteria for adjuvant therapy may improve outcomes of children who undergo enucleation at diagnosis and may avoid unnecessary adjuvant chemotherapy for those who are not at risk for recurrence.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enucleación del Ojo , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Quimioterapia Adyuvante , Niño , Preescolar , Progresión de la Enfermedad , Etopósido/administración & dosificación , Enucleación del Ojo/efectos adversos , Enucleación del Ojo/mortalidad , Femenino , Humanos , India , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia , Supervivencia sin Progresión , Estudios Prospectivos , Neoplasias de la Retina/mortalidad , Neoplasias de la Retina/patología , Retinoblastoma/mortalidad , Retinoblastoma/secundario , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Retinoblastoma occurs in approximately 4 per million children per year in the United States, usually before 2 years of age. In developed countries, 95% of children with tumor in one eye can be cured with enucleation, while children with tumor in both eyes require individualized therapy to preserve vision. Although enucleation and radiation are very effective therapies for children with bilateral disease, the resultant visual impairment, cosmetic deformity and risk for new tumors result in morbidity to these children who otherwise have a near normal lifespan. Therefore, since 1994, chemoreduction with vincristine, carboplatin, and etoposide combined with focal treatment, have been used successfully. However, a major concern with the use of carboplatin has been ototoxicity. PROCEDURES: To determine whether carboplatin, in the doses and schedule used by us and others to treat retinoblastoma (18.6 mg/kg q 4 weeks for six cycles) results in hearing impairment, we reviewed the records of 248 children with retinoblastoma, 164 of whom had received carboplatin. Children generally received carboplatin, vincristine, and etoposide (CEV) for six cycles of chemotherapy. RESULTS: Hearing evaluations prior to initiating therapy were abnormal in 14 patients (5.6%). No patients with normal initial audiograms were found to have abnormal studies following repeated evaluations. CONCLUSION: While ototoxicity is a potential concern in this young patient population, carboplatin in the treatment of retinoblastoma does not appear to produce impairment. Screening can identify children who require frequent audiologic follow-up, but children whose hearing is normal prior to therapy do not require routine surveillance following six cycles of standard CEV therapy.
Asunto(s)
Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Audición/efectos de los fármacos , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carboplatino/administración & dosificación , Niño , Preescolar , Etopósido/administración & dosificación , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Pérdida Auditiva/inducido químicamente , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Infertility is often a complication for adolescent and young adult males who receive cancer therapy, a problem that might be averted through using cryopreserved sperm. We aim to evaluate feasibility of offering newly diagnosed patients the opportunity to bank sperm and, to determine the beliefs and decision-making processes of patients and their parents who considered sperm banking. PROCEDURE: Eligible patients and parents were approached and offered sperm cryopreservation. Semen samples from patients who sequentially attempted sperm banking were analyzed. Questionnaires were then administered to patients and parents who had been approached about sperm banking. RESULTS: Semen samples from 68 patients were analyzed. Nine patients were azoospermic; all had been pre-treated with chemotherapy. Fifty patients completed the questionnaire. Parent and patient made the decision together to bank 80% of the time. All sons who attempted to bank and their parents felt they had made the right decision, including those who attempted but failed. CONCLUSIONS: Viable sperm can be collected successfully from adolescent and young adults who are newly diagnosed with cancer. Semen quality was dramatically reduced by one course of gonadotoxic therapy. Parents and patients want information regarding sperm cryopreservation early. Parents appear to play an important role in the decision to sperm bank. We recommend sperm banking be offered to all eligible patients.