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The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.
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The Children's Oncology Group AHOD0831 study used a positron emission tomography (PET) response-adapted approach in high-risk Hodgkin lymphoma, whereby slow early responders (SERs) received more intensive therapy than rapid early responders (RERs). We explored if baseline PET-based characteristics would improve risk stratification. Of 166 patients enrolled in the COG AHOD0831 study, 94 (57%) had baseline PET scans evaluable for quantitative analysis. For these patients, total body metabolic tumour volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax ) and peak SUV (SUVpeak ) were obtained. MTV/TLG thresholds were an SUV of 2.5 (MTV2.5 /TLG2.5 ) and 40% of the tumour SUVmax (MTV40% /TLG40% ). TLG2.5 was associated with event-free survival (EFS) in the complete cohort (p = 0.04) and in RERs (p = 0.01), but not in SERs (p = 0.8). The Youden index cut-off for TLG2.5 was 1841. Four-year EFS was 92% for RER/TLG2.5 up to 1841, 60% for RER/TLG2.5 greater than 1841, 74% for SER/TLG2.5 up to 1841 and 79% for SER/TLG2.5 greater than 1841. Second EFS for RER/TLG2.5 up to 1841 was 100%. Thus, RERs with a low baseline TLG2.5 experienced excellent EFS with less intensive therapy, whereas RERs with a high baseline TLG2.5 experienced poor EFS. These findings suggest that patients with a high upfront tumour burden may benefit from intensified therapy, even if they achieve a RER.
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Enfermedad de Hodgkin , Humanos , Niño , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Carga Tumoral , Fluorodesoxiglucosa F18/metabolismo , Tomografía de Emisión de Positrones/métodos , Medición de Riesgo , Pronóstico , Estudios Retrospectivos , Radiofármacos , Tomografía Computarizada por Tomografía de Emisión de Positrones , GlucólisisRESUMEN
PURPOSE: Radiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta-analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI). METHODS: After abstract screening, 25 studies (1995-2020) contained necessary patient, disease, and radiation treatment information (N = 96). All abstract, full text, and data capture were independently double-reviewed. The corresponding author was contacted for cases of insufficient information. Response to pre-radiation chemotherapy (N = 57) was categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Univariate and multivariate statistics were performed to investigate survival correlation. Patients with M4 disease were excluded. RESULTS: The 2- and 4-year overall survival (OS) was 63.8% and 45.7%, respectively, with a median follow-up of 2 years (range 0.3-13.5). The median age was 2 years (range 0.2-19.5), and 96% received chemotherapy. On univariate analysis, gross total resection (GTR, p = .0007), pre-radiation chemotherapy response (p < .001), and high-dose chemotherapy with stem cell recuse (HDSCT, p = .002) correlated with survival. On multivariate analysis, pre-radiation chemotherapy response (p = .02) and GTR (p = .012) retained survival significance as compared to a trend for HDSCT (p = .072). Comparisons of focal RT (vs. CSI) and greater than or equal to 5400 cGy primary dose were nonsignificant. Following CR or PR, a statistical trend favored focal radiation (p = .089) over CSI. CONCLUSION: Chemotherapy response prior to RT and GTR correlated with improved survival on multivariate analysis for ATRT M+ receiving RT. No benefit was observed for CSI compared to focal RT among all patients and following favorable chemotherapy response, inviting further study of focal RT for ATRT M+.
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Neoplasias del Sistema Nervioso Central , Irradiación Craneoespinal , Tumor Rabdoide , Teratoma , Humanos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Tumor Rabdoide/patología , Terapia Combinada , Neoplasias del Sistema Nervioso Central/patología , Teratoma/patologíaRESUMEN
PURPOSE/OBJECTIVE: We compared the prognostic value of chest radiograph (CXR)- and computed tomography (CT)-derived definition of large mediastinal adenopathy (LMA) in pediatric Hodgkin lymphoma (HL). MATERIALS/METHODS: Total 143 patients treated for stage IIIB/IVB HL on COG AHOD0831 were included in this study. Six definitions of LMA were investigated: (i) mediastinal mass ratio on CXR (MRCXR ) > 1/3; (ii) mediastinal mass ratio on CT (MRCT ) > 1/3; (iii) mediastinal mass volume on CT (MVCT ) > 200 mL; (iv) normalized mediastinal mass volume (MVCT /thoracic diameter [TD]) > 1 mL/mm; (v) mediastinal mass diameter on CT (MDCT ) > 10 cm; and (vi) normalized mediastinal mass diameter (MDCT /TD) > 1/3. RESULTS: Median age at diagnosis was 15.8 years (range: 5.2-21.3 years). In patients with a slow early response (SER) to chemotherapy, MVCT > 200 mL, MDCT > 10 cm, and MDCT /TD > 1/3 were associated with worse relapse-free survival (RFS) on MVA, while MRCXR > 1/3, MRCT > 1/3, and MVCT /TD > 1 mL/mm trended toward worse RFS; MDCT /TD was the most strongly prognostic for inferior RFS, with a hazard ratio of 6.41 for MDCT /TD > 1/3 versus ≤1/3 on MVA (p = .02). CONCLUSION: LMA according to MVCT > 200 mL, MDCT > 10 cm, and MDCT /TD > 1/3 is associated with poor prognosis in advanced-stage HL patients with SER. The normalized mediastinal diameter, MDCT /TD > 1/3 appears to be the strongest predictor of inferior RFS.
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Enfermedad de Hodgkin , Linfadenopatía , Humanos , Niño , Preescolar , Adolescente , Adulto Joven , Adulto , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Pronóstico , Rayos X , Recurrencia Local de Neoplasia/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Low-grade diffusely infiltrative tumour (LGDIT), SMARCB1-mutant, is a histopathological distinct low-grade lesion encountered in older children and young adults that shows epigenetic similarity with ATRT-MYC and has the potential for malignant progression.
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Tumor Rabdoide , Teratoma , Niño , Epigénesis Genética , Humanos , Tumor Rabdoide/patología , Proteína SMARCB1/genética , Adulto JovenRESUMEN
Over the past century, classical Hodgkin lymphoma (HL) has been transformed from a uniformly fatal disease to one of the most curable cancers. Given the high cure rate, a major focus of classical HL management is reducing the use of radiation therapy (RT) and chemotherapy agents such as procarbazine and doxorubicin to minimize long-term toxicities. In both North America and Europe, an important philosophy in the management of classical HL is to guide the intensity of treatment according to the risk category of the disease. The main factors used for risk classification are tumor stage, bulk of disease, and the presence of B symptoms. Response to chemotherapy is an important factor guiding the utilization of RT in ongoing Children's Oncology Group (COG) and European Network Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials. Both trial groups have transitioned to reduced RT volumes that target the highest risk sites using highly conformal techniques, along with standard or intensified chemotherapy regimens to improve outcomes in higher risk patients. However, given the potential acute toxicities of intensified chemotherapy, immunoregulatory drugs are being investigated in upcoming trials. The purpose of this review is to summarize current approaches to treating pediatric classical HL according to the COG and EuroNet-PHL.
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Antineoplásicos/uso terapéutico , Quimioradioterapia/métodos , Enfermedad de Hodgkin/terapia , Niño , HumanosRESUMEN
PURPOSE: The purpose of this study is to describe the long-term toxicities of intracranial germ cell tumor (IGCT) in the adolescent and young adult (AYA) population. METHODS: We report late toxicities of a multi-center cohort of AYA patients treated for IGCT between 1975 and 2015. Charts were retrospectively reviewed for hormone deficiency, ototoxicity, seizure disorder, visual deterioration, cerebrovascular events, second neoplasm, psychiatric illness, and neurocognitive impairment. Statistical analysis was performed for late toxicities to evaluate the influence of select factors. RESULTS: Our patient cohort included 112 patients with IGCTs; 84% of patients had a germinoma as opposed to a non-germinomatous germ cell tumor (NGGCT), median age at radiotherapy (RT) was 19 years, and median follow-up was 8.3 years. Of the 94 patients with germinoma, 32 (34%) received both chemotherapy and RT as part of their upfront treatment, while 62 (66%) received RT alone. All 18 patients with NGGCT received chemotherapy and RT. The most common late toxicity following IGCT treatments was physician-reported neurocognitive impairment, with a 10-year cumulative incidence (CI) of 38.5%. Ten-year CI of treatment-induced ototoxicity was 39.2% for patients who received cisplatin, compared to 3.6% for those who received carboplatin but no cisplatin (p < 0.005). Suprasellar/hypothalamic tumor location was associated with 10-year CI of treatment-induced hormone deficiency (36.1 vs 6.2%, p < 0.005). CONCLUSIONS: A significant proportion of AYAs treated for IGCTs experience late effects from treatment, including neurocognitive impairment, ototoxicity, and hormone deficiency. Suprasellar/hypothalamic tumor location and cisplatin were associated with a higher risk of treatment-induced hormone deficiency and ototoxicity, respectively.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/terapia , Quimioradioterapia/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Germinoma/terapia , Neoplasias de Células Germinales y Embrionarias/terapia , Traumatismos por Radiación/etiología , Adolescente , Adulto , Neoplasias Encefálicas/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Estudios de Seguimiento , Germinoma/patología , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , Traumatismos por Radiación/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Since their introduction to the International Neuroblastoma Risk Group (INRG) staging system in 2009, the role of Image-Defined Risk Factors (IDRFs) in predicting outcomes has been studied in heterogeneous populations with varying results. We conducted a systematic review and meta-analysis in order to determine quantitative measures of precisely how well pre-treatment IDRFs predict surgical outcomes and survival. METHODS: A systematic review was performed for studies between January 1990 and July 2019 that compared surgical outcomes and/or survival in pediatric neuroblastoma patients with one or more IDRFs to patients without IDRFs. Summary risk ratios (RR) and hazard ratios (HR) were calculated using a random-effects model. RESULTS: 19 retrospective cohort studies were included, representing data from 1132 patients. The risk ratio (RR) of incomplete surgical resection in IDRF-positive patients compared to IDRF-negative patients was 2.45 (95% CI 1.51-3.97). The RR of surgical complications was 2.30 (95% CI 1.46-3.61). The hazard ratio (HR) for 5-year EFS was 2.08 (95% CI 2.93-4.13) while the 5-year HR for OS was 2.44 (95% CI 1.46-4.08). CONCLUSION: IDRF-positive neuroblastoma patients have a higher risk of incomplete surgical resection, surgical complications, and 5-year mortality and/or relapse. Our results affirm that IDRFs remain a useful prognostic tool for neuroblastoma patients both for short and long-term outcomes. LEVEL OF EVIDENCE: II.
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Diagnóstico por Imagen , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estadificación de Neoplasias , Neuroblastoma/cirugía , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: The study objectives were to describe patterns of practice for intracranial germ cell tumors (IGCT) in adolescents and young adults (AYA) and to determine factors associated with practice patterns. METHODS: A survey was written containing questions on the management of two 17-year old males, one with localized pineal germinoma and the other with localized pineal non-germinomatous germ cell tumor (NGGCT). An invitation to participate anonymously in the survey was e-mailed to 119 oncologists who treat brain tumors across Canada. RESULTS: Seventy-two (61%) of the 119 oncologists participated in the study. For the germinoma case, the most common treatment approaches were whole ventricular radiotherapy (WVRT) and chemotherapy (CH) (56%), WVRT alone (15%), and craniospinal radiotherapy (CSRT) alone (10%); for physicians recommending WVRT + CH, most frequently selected whole ventricular doses were 24 Gy (57%) and 18 Gy (20%). Chemotherapy was included in the treatment of germinoma by 96% of pediatric physicians vs. 54% of adult physicians (P = 0.001). The most common treatment approaches for NGGCT were CSRT + CH (44%), WVRT + CH (21%), and pineal gland RT + CH (15%). The selection of craniospinal vs. smaller-volume RT was not associated with the physicians' specialty, percentage of practice treating brain tumors, number of IGCTs seen, or size of institution. CONCLUSIONS: There is wide variation in the management of IGCT in AYA across Canada. A 17-year old male with a localized pineal germinoma is highly likely to receive chemotherapy if managed by a pediatric oncologist, while the same patient is much less likely to receive chemotherapy if managed by an adult oncologist.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/terapia , Quimioradioterapia/métodos , Irradiación Craneana/métodos , Neoplasias de Células Germinales y Embrionarias/terapia , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adolescente , Adulto , Neoplasias Encefálicas/patología , Canadá , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , PronósticoAsunto(s)
Linfoma Folicular/diagnóstico , Linfoma Folicular/radioterapia , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Linfoma Folicular/mortalidad , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Radioterapia/métodos , Dosificación Radioterapéutica , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Linfoma Folicular/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Estudios de Seguimiento , Humanos , Linfoma Folicular/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estadificación de Neoplasias , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The study objective was to describe radiation-induced vascular abnormalities, stroke prevalence, and stroke risk factors in survivors of childhood craniopharyngioma. PROCEDURE: Twenty survivors of childhood craniopharyngioma who received radiotherapy (RT) were included in the study. A clinical history, quality of life assessment, cognitive functioning assessment, magnetic resonance angiogram or computed tomography angiogram, fasting lipid profile, and fasting glucose or hemoglobin A1c test were obtained. RESULTS: Median age at diagnosis was 10.3 years and median age at time of study was 29.0 years. Vascular abnormalities were detected in six (32%) of 19 patients' angiograms (vascular stenosis, decreased artery size, aneurysm, cavernoma, and small vessel disease). Five (25%) of 20 patients experienced a stroke after RT. Median time since RT was 27.8 versus 9.1 years in patients with versus without vascular abnormalities (P = 0.02). A low level of high-density lipoproteiin (HDL) was present in 100% (5/5) of patients who had a post-RT stroke as compared with 13% (2/15) of patients who did not have any post-RT stroke (P = 0.02). Previous stroke had occurred in 0% (0/5) of patients receiving growth hormone (GH) replacement at the time of study, compared to 40% (6/15) of patients who were not receiving GH replacement (P = 0.09). CONCLUSIONS: Patients with craniopharyngioma treated with RT have a high prevalence of stroke and vascular abnormalities, particularly those with low HDL and longer duration of time since RT. There is a trend to suggest that continual GH replacement may reduce the risk of stroke. These patients should undergo careful monitoring and aggressive modification of stroke risk factors.
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Trastornos Cerebrovasculares , Craneofaringioma/radioterapia , Traumatismos por Radiación , Adolescente , Adulto , Factores de Edad , Angiografía Cerebral , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/epidemiología , Trastornos Cerebrovasculares/etiología , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/epidemiología , Radioterapia/efectos adversos , Factores de RiesgoRESUMEN
INTRODUCTION: We investigated the incidence of secondary bladder (BCa) and rectal cancers (RCa) after external beam radiotherapy (EBRT) for prostate cancer (PCa) compared to radical prostatectomy (RP) alone, and compared cancer-specific survival (CSS) of these secondary neoplasms to their primary counterparts. METHODS: This retrospective cohort study included men in the SEER cancer registry with a diagnosis of non-metastatic, clinically node-negative PCa treated with either RP or EBRT from 1995-2011 and allowed a minimum five-year lag period for the development of secondary BCa or RCa. Patients were divided into two eras, 1995-2002 and 2003-2011, to examine differences in incidence of secondary malignancies over time. Univariable and multivariable competing risk analyses with Fine-Gray subdistribution hazard and cause-specific hazard models were used to examine the risk of developing a secondary BCa or RCa. Competing risks analyses were used to compare CSS of primary vs. secondary BCa and RCa. RESULTS: A total of 198 184 men underwent RP and 190 536 underwent EBRT for PCa. The cumulative incidence of secondary BCa at 10 years was 1.71% for RP, and 3.7% for EBRT (p<0.001), while that of RCa was 0.52% for RP and 0.99% for EBRT (p<0.001). EBRT was associated with almost twice the risk of developing a secondary BCa and RCa compared to RP. The hazard of secondary BCa following EBRT delivered during 2003-2011 was 20% less than from 1995-2002 (p<0.09, Fine-Gray model), while that of secondary RCa was 31% less (p<0.001) (hazard ratio 0.78, p<0.001) for Fine-Gray and cause-specific hazard models. In the Fine-Gray model, the risk of death from BCa was 27% lower for secondary BCa after RP compared to primary BCa, while the risk of death was 9% lower for secondary BCa after EBRT compared to primary BCa. There was no difference in RCa-specific survival between primary or secondary RCa after RP or EBRT. CONCLUSIONS: The risk of BCa and RCa is almost twice as high for men undergoing EBRT for localized PCa vs. RP, but that risk is declining, likely reflecting advances in radiation delivery. The development of secondary RCa or BCa does not confer elevated risk of death compared to their primary counterparts.
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Combinatorial therapies consisting of radiation therapy (RT) with systemic therapies, particularly chemotherapy and targeted therapies, have moved the needle to augment disease control across nearly all disease sites for locally advanced disease. Evaluating these important combinations to incorporate more potent therapies with RT will aid our understanding of toxicity and efficacy for patients. This article discusses multiple disease sites and includes a compilation of contributions from expert Red Journal editors from each disease site. Leveraging improved systemic control with novel agents, we must continue efforts to study novel treatment combinations with RT.
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Atención al Paciente , Humanos , Terapia CombinadaRESUMEN
Importance: Contemporary North American trials for children with Hodgkin lymphoma (HL) have decreased radiation therapy (RT) use and increased pharmacologic cardioprotection but also increased the cumulative doxorubicin dose, making overall treatment consequences for late cardiac toxic effects uncertain. Objective: To estimate the risk of cardiac toxic effects associated with treatments used in modern pediatric HL clinical trials. Design, Setting, and Participants: For this cohort study, Fine and Gray models were fitted using survivors in the Childhood Cancer Survivor Study who were diagnosed with HL between January 1, 1970, and December 31, 1999, and were followed for a median of 23.5 (range, 5.0-46.3) years. These models were applied to the exposures in the study population to estimate the 30-year cumulative incidence of cardiac disease. The study population comprised patients with intermediate-risk or high-risk HL treated in 4 consecutive Children's Oncology Group clinical trials from September 2002 to October 2022: AHOD0031, AHOD0831, AHOD1331, and S1826. Data analysis was performed from April 2020 to February 2023. Exposures: All patients received chemotherapy including doxorubicin, and some patients received mediastinal RT, dexrazoxane, or mediastinal RT and dexrazoxane. Main Outcomes and Measures: Estimated 30-year cumulative incidence of grade 3 to 5 cardiac disease. Results: The study cohort comprised 2563 patients, with a median age at diagnosis of 15 (range, 1-22) years. More than half of the patients were male (1357 [52.9%]). All 2563 patients received doxorubicin, 1362 patients (53.1%) received mediastinal RT, and 307 patients (12.0%) received dexrazoxane. Radiation therapy use and the median mean heart dose among patients receiving RT decreased, whereas the planned cumulative dose of doxorubicin and use of dexrazoxane cardioprotection increased. For patients treated at age 15 years, the estimated 30-year cumulative incidence of severe or fatal cardiac disease was 9.6% (95% CI, 4.2%-16.4%) in the AHOD0031 standard treatment group (enrolled 2002-2009), 8.6% (95% CI, 3.8%-14.9%) in the AHOD0831 trial (enrolled 2009-2012), 8.2% (95% CI, 3.6%-14.3%) in the AHOD1331 trial (enrolled 2015-2019), and 6.2% (95% CI, 2.7%-10.9%) in the S1826 trial (enrolled 2019-2022), whereas the expected rate in an untreated population was 5.0% (95% CI, 2.1%-9.3%). Despite the estimated reduction in late cardiac morbidity, the frequency of recommended echocardiographic screening among survivors will increase based on current guidelines. Conclusions and Relevance: In this cohort study of sequential HL trials, reductions in the proportion of children receiving mediastinal RT and increases in dexrazoxane use were estimated to offset the increased doxorubicin dose and produce a net reduction in late cardiac disease. Further studies on dexrazoxane are warranted to confirm whether its role in reducing cardiac toxic effects is maintained long term. These findings suggest that survivorship follow-up guidelines should be refined to align with the risks associated with treatment.
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Dexrazoxano , Cardiopatías , Enfermedad de Hodgkin , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Adulto Joven , Cardiotoxicidad/epidemiología , Cardiotoxicidad/etiología , Protocolos Clínicos , Estudios de Cohortes , Dexrazoxano/uso terapéutico , Doxorrubicina/efectos adversos , Cardiopatías/inducido químicamente , Cardiopatías/epidemiología , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/radioterapiaRESUMEN
BACKGROUND: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. STUDY DESIGN: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. RESULTS: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. CONCLUSIONS: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.
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Neoplasias Renales , Tumor de Wilms , Niño , Humanos , Anaplasia , Etnicidad , Hispánicos o Latinos , Neoplasias Renales/terapia , Neoplasias Renales/patología , Tumor de Wilms/genética , Tumor de Wilms/terapia , Negro o Afroamericano , Grupos Raciales , Tasa de SupervivenciaRESUMEN
The objective was to assess the cost-effectiveness of staging PET/CT in early-stage follicular lymphoma (FL) from the Canadian health-care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding staging PET/CT versus using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a noncurative approach, or no change in RT treatment as planned. The subsequent disease course was described using a state-transition cohort model over a 30-y time horizon. Diagnostic characteristics, probabilities, utilities, and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars), and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs) and was cost-effective in 89% of simulations (i.e., either saved costs or had an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis showed that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT before curative-intent RT.
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Linfoma Folicular , Tomografía Computarizada por Tomografía de Emisión de Positrones , Canadá , Análisis Costo-Beneficio , Humanos , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/radioterapia , Años de Vida Ajustados por Calidad de VidaRESUMEN
PURPOSE: The study objective was to assess the discussion of late effects (LEs) and screening recommendations (SRs) for adolescent and young adults (AYAs) treated for lymphoma. METHODS: A retrospective study was conducted on AYA lymphoma survivors aged 15-24 years at diagnosis who received radiation therapy (RT) ± chemotherapy between 1984 and 2010 at any of the six British Columbia (BC) Cancer treatment centers across the province. Charts were reviewed to evaluate discussion of LEs and SRs. Susceptibility to specific LEs was determined by reviewing treatment details. RESULTS: Of 305 patients, 212 (70%) had documented discussion of at least one specific LE, 39 (13%) had non-specific documentation only, and 54 (18%) had no documented discussion of LEs. Accounting only for patients susceptible to each LEs, the most frequently discussed LEs was radiation-induced (RI) neoplasm (42%), and the least frequently discussed LEs was carotid artery stenosis (0.4%). The most common SRs discussed in susceptible patients was for RI breast cancer (43%). Of patients discharged between 1985 and 1999 vs 2000 and 2014, LEs were discussed in 63 vs 93% (P < 0.0005), and SRs were discussed in 30 vs 65%, respectively (P < 0.0005). Older age at discharge, presence of a discharge note, and occurrence of a discharge appointment were associated with increased discussion of SRs. CONCLUSIONS: Most survivors of AYA lymphoma received some discussion of LEs and SRs, but each relevant LEs and SRs was discussed in only a minority of susceptible patients. IMPLICATIONS FOR CANCER SURVIVORS: Survivors of AYA lymphoma and their primary care professionals may not be appropriately informed of health risks and how to screen for them.
Asunto(s)
Linfoma , Adolescente , Anciano , Colombia Británica/epidemiología , Progresión de la Enfermedad , Humanos , Linfoma/epidemiología , Estudios Retrospectivos , Sobrevivientes , Adulto JovenRESUMEN
PURPOSE: The study objective is to describe and quantify the incidence of treatment-induced late effects in AYA lymphoma patients. METHODS: Consecutive patients diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) at 15-24 years of age were identified. All patients in British Columbia who received radiation therapy (RT) from 1974 to 2014 with ≥ 5-year survival post-RT were included. Late effects' analyses included only survivors who received RT to the relevant anatomical site(s) and/or relevant chemotherapy, and were reported as cumulative incidence (CI) ± standard error. RESULTS: Three hundred and five patients were identified (74% HL). Median age of diagnosis was 21 years. Median follow-up was 19.1 years for secondary malignancy and 7.2 years for other endpoints. Hypothyroidism was the most prevalent late effect, with a CI of 22.4 ± 2.8% and 35.1 ± 4% at 5 and 10 years, respectively. CI of in-field secondary malignancy was 0.4 ± 0.4% at 10 years and 2.8 ± 1.2% at 20 years. CI of symptomatic pulmonary toxicity was 4.6 ± 1.5% and 6.8 ± 2.0% at 5 and 10 years, respectively, and was higher in patients receiving multiple RT courses (p = 0.009). Esophageal complications occurred at a CI of 1.4 ± 0.8% at 5 years and 2.2 ± 1.1% at 10 years. CI of xerostomia/dental decay was 2.6 ± 1.3% at 5 years and 4.9 ± 2.1% at 10 years. CI of cardiac disease was at 2.3 ± 0.9% at 5 years and 4.4 ± 1.5% at 10 years. CI of infertility was 6.5 ± 1.6% at 5 years and 9.4 ± 2.1% at 10 years. CONCLUSION: Survivors of AYA lymphoma have a high incidence and diverse presentation of late effects. IMPLICATIONS FOR CANCER SURVIVORS: AYA lymphoma survivors should be educated about their risks of late effects and offered screening and follow-up when appropriate.