scholarly journals Identifying Childhood Cancer Survivors at Increased Genetic Risk for Second Malignant Neoplasms: Use of a Novel Screening Tool

2021 ◽  
pp. JCO.21.01817
Author(s):  
Roya M. Mostafavi ◽  
Kim E. Nichols
Author(s):  
Kathryn Tringale ◽  
Dana Casey ◽  
Gregory Niyazov ◽  
Jessica Lavery ◽  
Chaya Moskowitz ◽  
...  

Background It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. Procedure Patients aged 10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).


2020 ◽  
Vol 38 (15) ◽  
pp. 1711-1722 ◽  
Author(s):  
Adam P. Yan ◽  
Yan Chen ◽  
Tara O. Henderson ◽  
Kevin C. Oeffinger ◽  
Melissa M. Hudson ◽  
...  

PURPOSE To evaluate childhood cancer survivors’ adherence to surveillance protocols for late effects of treatment and to determine the factors affecting adherence. METHODS Between 2014 and 2016, 11,337 survivors and 2,146 siblings in the Childhood Cancer Survivor Study completed a survey ascertaining adherence to Children’s Oncology Group (COG) guidelines for survivors at high risk for second malignant neoplasms or cardiac dysfunction and to the American Cancer Society (ACS) cancer screening guidelines for average-risk populations. Adherence rates and factors affecting adherence were analyzed. RESULTS Median age at diagnosis was 7 years (range, 0-20.9 years), and median time from diagnosis was 29 years (range, 15-47 years). Among high-risk survivors, adherence to COG breast, colorectal, skin, and cardiac surveillance was 12.6% (95% CI, 10.0% to 15.3%), 37.0% (34.1% to 39.9%), 22.3% (21.2% to 23.4%), and 41.4% (40.1% to 42.7%), respectively. Among average-risk survivors, adherence to ACS breast, cervical, and colorectal screening was 57.1% (53.2% to 61.0%), 83.6% (82.7% to 84.5%), and 68.5% (64.7% to 72.2%), respectively. Twenty-seven percent of survivors and 20.0% of primary care providers (PCPs) had a survivorship care plan (SCP). For high-risk survivors, SCP possession was associated with increased adherence to COG breast (22.3% v. 8.1%; prevalence ratio [PR], 2.52; CI, 1.59 to 4.01), skin (34.8% v 23.0%; PR, 1.16; CI, 1.01 to 1.33), and cardiac (67.0% v 33.1%; PR, 1.73; CI, 1.55 to 1.92) surveillance. For high-risk survivors, PCP possession of a SCP was associated only with increased adherence to COG skin cancer surveillance (36.9% v 23.2%; PR, 1.24; CI, 1.08 to 1.43). CONCLUSION Guideline adherence is suboptimal. Although survivor SCP possession is associated with better adherence, few survivors and PCPs have one. New strategies to improve adherence are needed.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10569-10569
Author(s):  
Chu-Ling Yu ◽  
Emily S. Tonorezos ◽  
Chiung-Yu Huang ◽  
Brian C-H Chiu ◽  
Chun-Ju Chiang ◽  
...  

10569 Background: Childhood cancer survivors have excess risk of second malignant neoplasms, but data are limited in Asian populations. We established a nationwide retrospective cohort of childhood cancer survivors in Taiwan to study the risk of second malignant neoplasms in the population. Methods: Children and adolescents diagnosed with cancer before age 21 years between 1990 and 2011 were identified from the Taiwan Cancer Registry, the national cancer registry in Taiwan. One-year survivors of childhood cancer were ascertained through data linkage with the national death registry. Survivors were followed up through December 2012. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of second malignant neoplasms were calculated. Results: A total of 186 second malignant neoplasms occurred among 15,263 1-year survivors of childhood cancer after a mean follow-up time of 8.0 years (SIR = 5.4, 95% confidence interval [CI] = 4.6-6.2; AER = 12.4 per 10,000 person-years). The most common types of second malignant neoplasms were gastrointestinal cancers (n = 37), leukemia (n = 28), endocrine cancers (n = 18), and brain cancer (n = 17). Cancers in the liver (n = 11, including 9 hepatocellular carcinoma) and colorectum (n = 16) accounted for 73% of second gastrointestinal malignant neoplasms in this population. The cumulative incidence of second malignant neoplasms at 10 and 20 years from follow-up was 1.0% (95% CI = 0.8-1.2%) and 3.0% (95% CI = 2.3-3.6%), respectively. Conclusions: Childhood cancer survivors in Taiwan experience excess risk of second malignant neoplasms, in particular gastrointestinal cancers, compared with the general population.


2019 ◽  
Vol 37 (24) ◽  
pp. 2120-2130 ◽  
Author(s):  
Chaya S. Moskowitz ◽  
Joanne F. Chou ◽  
Joseph P. Neglia ◽  
Ann H. Partridge ◽  
Rebecca M. Howell ◽  
...  

PURPOSE Female survivors of childhood cancer have a high risk of subsequent breast cancer. We describe the ensuing risk for mortality and additional breast cancers. PATIENTS AND METHODS Female participants in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of cancer diagnosed between 1970 and 1986 before age 21 years, and subsequently diagnosed with breast cancer (n = 274; median age at breast cancer diagnosis, 38 years; range, 20 to 58 years) were matched to a control group (n = 1,095) with de novo breast cancer. Hazard ratios (HRs) and 95% CIs were estimated from cause-specific proportional hazards models. RESULTS Ninety-two childhood cancer survivors died, 49 as a result of breast cancer. Overall survival after breast cancer was 73% by 10 years. Subsequent risk of death as a result of any cause was higher among childhood cancer survivors than among controls (HR, 2.2; 95% CI, 1.7 to 3.0) and remained elevated after adjusting for breast cancer treatment (HR, 2.4; 95% CI, 1.7 to 3.2). Although breast cancer–specific mortality was modestly elevated among childhood cancer survivors (HR, 1.3; 95% CI, 0.9 to 2.0), survivors were five times more likely to die as a result of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (HR, 5.5; 95% CI, 3.4 to 9.0). The cumulative incidence of a second asynchronous breast cancer also was elevated significantly compared with controls ( P < .001). CONCLUSION Mortality after breast cancer was higher in childhood cancer survivors than in women with de novo breast cancer. This increased mortality reflects the burden of comorbidity and highlights the need for risk-reducing interventions.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24180-e24180
Author(s):  
Jenna Sopfe ◽  
Rebekah Marsh ◽  
Leslie C. Appiah ◽  
James L. Klosky ◽  
Pamela N Peterson ◽  
...  

e24180 Background: Up to half of adolescent and young adult (AYA) childhood cancer survivors (CCS) experience sexual dysfunction (SD) as a result cancer or its treatment. SD in CCS is under-recognized, with low levels of routine screening due to barriers such as discomfort, time, and awareness. This study explores solutions to these barriers by describing AYA CCS preferences for implementation of screening for SD and evaluating the utility of a validated adult screening tool (PROMIS SexFS Brief) in this population. Methods: 16 AYA CCS (aged 15-24 years) completed semi-structured interviews followed by questionnaire completion. Interviews explored patients’ prior experiences with SD screening, along with preferences for screening type (e.g., discussion, screening tool), delivery modality, and timing. Patients then completed the PROMIS SexFS Brief while verbalizing their thoughts and providing open-ended responses to each item. Transcribed interviews were inductively coded and analyzed, guided by content analysis methodology. Results: This analysis represents 2/3 of planned interviews, and all will be completed by April 1, 2020. Interviews were performed with 11 females and 5 males (median age 21). Preliminary analysis demonstrates that participants had minimal experience with SD conversations, but had preferences regarding by whom, how, and when screening/education should occur. Who: Participants felt providers should have preexisting rapport with their patients; preferences existed for provider role and sex/age. How: A combination of written materials and in-person conversations was preferred. Several acknowledged a desire to have a “warning” that the conversation would happen, such as through a questionnaire. Participants did not have a preference regarding delivery modality (paper vs. online). The PROMIS SexFS Brief appeared to demonstrate content validity and acceptability in AYA CCS. When: Participants wanted education and screening to occur regularly throughout cancer therapy and survivorship. SD conversations should be tailored developmentally to the patient. Conclusions: Our results demonstrate a theme throughout interviews of the importance of patient/provider rapport. Further, while AYA CCS prefer in-person conversations about SD, conversations should be preceded by written information or a questionnaire to increase patient preparedness/comfort. Preliminary findings suggest that the PROMIS SexFS Brief is a promising tool for screening SD in this population; further studies evaluating use in clinical settings is warranted.


2021 ◽  
Author(s):  
Oliver Zolk ◽  
Annika von dem Knesebeck ◽  
Norbert Graf ◽  
Thorsten Simon ◽  
Barbara Hero ◽  
...  

BACKGROUND Cardiac toxicity is the most common non-malignant cause of death in childhood cancer survivors attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. Genetic markers have been proposed to be used together with clinical risk factors to predict the individual risk of cardiac toxicity from cancer therapies such as doxorubicin. OBJECTIVE The primary aim is to replicate the previously described associations of doxorubicin-induced cardiotoxicity with RARG rs2229774, SLC28A3 rs7853758 and UGT1A6 rs17863783 variants and to evaluate the predictive value of the multimarker genetic test. The secondary aim is to evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors and to replicate the association of doxorubicin-related cardiotoxicity with other candidate genes. METHODS This is the pharmacogenetic sub-study of the research project Structural Optimization for Children with Cancer after Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblasoma or nephroblastoma who were treated with doxorubicin according to the trial protocols of SIOP 9/GPOH, SIOP 93-01/GPOH, SIOP 2001/GPOH, NB 90, NB 97, or NB 2004 to participate in this prospective cross-sectional cohort study. The study participants underwent a cardiological examination and were asked to provide a blood or saliva sample for genotyping. The health status and cardiovascular diagnoses of the study participants were recorded using a questionnaire completed by the cardiologist. Digital echocardographic data were centrally evaluated to determine the contractile function parameters. Medical data on tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants in several candidate genes by TaqMan genotyping. RESULTS This study included 657 survivors treated with doxorubicin for childhood cancer, resulting in the largest German cohort assembled for investigation of cardiovascular late effects to date. Data analyses are yet to be completed. CONCLUSIONS The study will define the genetic risk related to three marker genes proposed for risk assessment in a pharmacogenetic guideline. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma treated with doxorubicin. The results will help to improve primary treatment and follow-up care to reduce cardiovascular late effects in the growing population of childhood cancer survivors. CLINICALTRIAL German clinical trials register ID: DRKS00015084


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