Epidemiological analysis of second primary malignant neoplasms in cancer survivors aged 85 years and older: a SEER data analysis (1975-2016).
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SUBMITTER: Zhao X
PROVIDER: S-EPMC9270446 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The cancer burden in the oldest old has increased rapidly. This study aimed to investigate the epidemiology of second primary malignancy (SPM) in malignant solid tumor survivors aged 85 years and older utilizing the Surveillance, Epidemiology, and End Results (SEER) database. A total of 128,466 malignant solid tumor patients had been identified between 2000 and 2011, including 6774 patients who developed a SPM. The overall crude incidence of developing a SPM was 5.3%. Considering death as a competing event, the 3, 5, and 10-year cumulative incidence was 1.9%, 3.2%, and 5.4%, respectively. Relative younger age, male gender, surgery history, local stage and first primary malignancy (FPM) site located in the urinary system were related to higher cumulative incidence. A median time interval of 24.0 months was found between diagnosis of FPM and SPM. The most common SPM site was digestive system, whereas the least common was oral cavity and pharynx. The median overall survival (OS) was 49.0 months, and the median survival after SPM was 13.0 months. Relative older age, male gender and black race were associated with worse OS and survival after SPM, as well as higher hazard ratios of death. In conclusions, this study performed a comprehensive analysis of SPM among malignant solid tumor survivors aged 85 years and older. Additional studies are needed to characterize the specific cancer type of interest.
| S-EPMC8492691 | biostudies-literature
Project description:This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing.
| S-EPMC5899852 | biostudies-literature
Project description:ImportanceAlthough the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age.ObjectiveTo assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 years) and older adult (≥40 years) patients with the same SPMs.Design, setting, and participantsThis was a population-based, retrospective cohort study of patients with cancer in 13 Surveillance, Epidemiology and End Results regions in the United States diagnosed from 1992 to 2008 and followed through 2013. Data analysis was performed between June 2016 and January 2017.Main outcomes and measuresFive-year relative survival was calculated overall and for each cancer occurring as a PM or SPM by age at diagnosis. The impact of SPM status on cancer-specific death was examined using multivariable Cox proportional hazards regression.ResultsA total of 15 954 pediatric, 125 750 AYAs, and 878 370 older adult patients diagnosed as having 14 cancers occurring as a PM or SPM were included. Overall, 5-year survival after an SPM was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older adults compared with a PM at the same age. For the most common SPMs in AYAs, the absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid carcinoma, and 13% for secondary soft-tissue sarcoma. Survival by SPM status was significantly worse in younger vs older patients for thyroid, Hodgkin lymphoma, non-Hodgkin lymphoma, acute myeloid leukemia, soft-tissue sarcoma, and central nervous system cancer. Adolescents and young adults with secondary Hodgkin lymphoma (hazard ratio [95% CI], 3.5 [1.7-7.1]); soft-tissue sarcoma (2.8 [2.1-3.9]); breast carcinoma (2.1 [1.8-2.4]); acute myeloid leukemia (1.9 [1.5-2.4]); and central nervous system cancer (1.8 [1.2-2.8]) experienced worse survival compared with AYAs with the same PMs.Conclusion and relevanceThe adverse impact of SPMs on survival is substantial for AYAs and may partially explain the relative lack of survival improvement in AYAs compared with other age groups. The impact of a particular SPM diagnosis on survival may inform age-specific prevention, screening, treatment, and survivorship recommendations.
| S-EPMC5824209 | biostudies-literature
Project description:Purpose: Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants, we analyzed germline and SMN samples from pediatric cancer survivors.Experimental Design: We performed whole-exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in 37 pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without any history of a familial cancer predisposition syndrome but known to have developed SMNs.Results: WES revealed TP53 mutations involving p53's DNA-binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53-mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53-coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in 6 patients and a synonymous SNP A639G in 4 others, resulting in 10 of 37 evaluable patients (27%) harboring a germline TP53 variant.Conclusions: Currently, germline TP53 is not routinely assessed in patients with pediatric cancer. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive posttreatment monitoring. Clin Cancer Res; 23(7); 1852-61. ©2016 AACR.
| S-EPMC5570538 | biostudies-literature
Project description:BackgroundThe principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background.Patients and methodsA total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients.ResultsOf all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively.ConclusionThis retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis.
| S-EPMC6331079 | biostudies-literature
Project description:Survival and second malignancy prediction models can aid clinical decision making. Most commonly, survival analysis studies are performed using traditional proportional hazards models, which require strong assumptions and can lead to biased estimates if violated. Therefore, this study aims to implement an alternative, machine learning (ML) model for survival analysis: Random Survival Forest (RSF). In this study, RSFs were built using the U.S. Surveillance Epidemiology and End Results to (1) predict 30-year survival in pediatric, adolescent, and young adult cancer survivors; and (2) predict risk and site of a second tumor within 30 years of the first tumor diagnosis in these age groups. The final RSF model for pediatric, adolescent, and young adult survival has an average Concordance index (C-index) of 92.9%, 94.2%, and 94.4% and average time-dependent area under the receiver operating characteristic curve (AUC) at 30-years since first diagnosis of 90.8%, 93.6%, 96.1% respectively. The final RSF model for pediatric, adolescent, and young adult second malignancy has an average C-index of 86.8%, 85.2%, and 88.6% and average time-dependent AUC at 30-years since first diagnosis of 76.5%, 88.1%, and 99.0% respectively. This study suggests the robustness and potential clinical value of ML models to alleviate physician burden by quickly identifying highest risk individuals.
| S-EPMC9894907 | biostudies-literature
Project description:Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
| S-EPMC3295744 | biostudies-literature
Project description:ImportanceDetailed data describing the epidemiology of second malignant neoplasms (SMN) are needed for survivors of adolescent and young adult (AYA) cancer to inform the development of age-appropriate survivorship care guidelines.ObjectiveTo describe the incidence, risk factors, and mortality for SMN in survivors of AYA cancer.Design, setting, and participantsThis retrospective matched cohort study included 10 574 two-year survivors diagnosed with cancer between January 1, 1990, and December 31, 2012, at age 15 to 39 years in an integrated health care delivery system in Southern California. A comparison cohort without a history of cancer was individually matched 13:1 to survivors of AYA cancer by age, sex, and calendar year. Data analysis was completed in July 2018.ExposuresSecondary malignant neoplasm risk factors of interest included age, stage, and calendar year at first cancer diagnosis; sex; race/ethnicity; radiation therapy; and chemotherapy.Main outcomes and measuresDiagnoses of SMN were ascertained using cancer registries from the National Cancer Institute Surveillance, Epidemiology, and End Results Program through December 31, 2014. Poisson regression was used to evaluate the association between cancer survivor status and developing SMN and risk factors for SMN, while risk of all-cause mortality by SMN status was examined in Cox regression.ResultsA total of 10 574 survivors of AYA cancer (6853 [64.8%] female; median [range] age, 33 [15-39] years; 622 with SMN) and 136 683 participants in the comparison cohort (88 513 [64.8%] female; median [range] age, 33 [15-39] years; 3437 with first cancer) were included. In survivors of AYA cancer, 20-year cumulative incidence of SMN was 12.5%. The incidence rate ratio (IRR) of developing SMN in survivors of AYA cancer was 2.6 (95% CI, 2.4-2.9) compared with the comparison cohort. Survivors of breast cancer, melanoma, and testicular cancer had substantially elevated risk for SMN of the same organ (IRR, 5.6 [95% CI, 4.6-6.8], 11.2 [95% CI, 7.3-17.2], and 16.2 [95% CI, 6.8-38.4], respectively). Among survivors of AYA cancer, older age (IRR for age 30-39 years, 1.79 [95% CI, 1.21-2.65]), female sex (IRR, 1.31 [95% CI, 1.09-1.57]), white race/ethnicity (IRR for Asian race, 0.61 [95% CI, 0.43-0.87]), advanced stage at first cancer diagnosis (IRR for stage II, 1.29 [95% CI, 1.11-1.65]), and use of radiotherapy (IRR, 1.50 [95% CI, 1.26-1.79]) were associated with increased risk of SMN. Survivors of AYA cancer who developed SMN had an all-cause mortality rate 7.2 (95% CI, 6.1-8.5) times greater than survivors without SMN.Conclusions and relevanceThis study suggests that SMN risk is elevated in survivors of AYA cancer and varies across survivor subgroups. Survival following SMN may be significantly compromised. These data may form the basis for identifying individuals at high risk, as well as informing screening for SMN.
| S-EPMC6563559 | biostudies-literature
Project description:PurposeThe association between post-resection radiotherapy for primary gynecological malignant neoplasms (GMNs) and the development of secondary primary malignancies (SPMs) remains a subject of debate. This study represents the first population-based analysis employing a multivariate competitive risk model to assess risk factors for this relationship and to develop a comprehensive competing-risk nomogram for quantitatively predicting SPM probabilities.Materials and methodsIn our study, data on patients with primary GMNs were retrospectively collected from the Epidemiology, Surveillance and End Results (SEER) database from 1973 to 2015. The incidence of secondary malignant tumors diagnosed at least six months after GMN diagnosis was compared to determine potential risk factors for SPMs in GMN patients using the Fine and Gray proportional sub-distribution hazard model. A competing-risk nomogram was constructed to quantify SPM probabilities.ResultsA total of 109,537 patients with GMNs were included in the study, with 76,675 and 32,862 GMN patients in the training and verification sets, respectively. The competing-risk model analysis identified age, primary tumor location, tumor grade, disease stage, chemotherapy, and radiation as risk factors for SPMs in GMN patients. Calibration curves and ROC curves in both training and verification cohorts demonstrated the predictive accuracy of the established nomogram, which exhibited a good ability to predict SPM occurrence.ConclusionsThis study presents the nomogram developed for quantitatively predicting SPM probabilities in GMN patients for the first time. The constructed nomogram can assist clinicians in designing personalized treatment strategies and facilitate clinical decision-making processes.
| S-EPMC10587290 | biostudies-literature
Project description:PurposeTo evaluate childhood cancer survivors' adherence to surveillance protocols for late effects of treatment and to determine the factors affecting adherence.MethodsBetween 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.ResultsMedian 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).ConclusionGuideline 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.
| S-EPMC7357338 | biostudies-literature