Excessive risk of second primary cancers in young-onset colorectal cancer survivors.
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ABSTRACT:
SUBMITTER: He X
PROVIDER: S-EPMC5911632 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
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Project description:To assess etiological and clinical consequences of second primary cancers (SPCs) in prostate cancer (PC) patients, we followed newly diagnosed patients to identify men who were diagnosed with a SPC and recorded their causes of death. We used the Swedish Family-Cancer Database to assess relative risks (RRs) and causes of death in SPCs until the year 2015 in patients with a PC diagnosis between 2001 and 2010. Among a total of 4.26 million men, 76 614 were diagnosed with PC at the median age of 71 years. Among them, 8659 (11.3%) received a subsequent diagnosis of SPC after a median follow-up of 4 years. The most common SPCs were colorectal, skin, bladder, and lung cancers, melanoma, and non-Hodgkin lymphoma. The ranking was almost identical with first cancers among elderly men in Sweden. The RR for SPCs in prostate-specific antigen-detected PC was approximately equal to RR in other PC. Mortality patterns of PC patients were distinct depending on the presence or absence of SPC. Among patients with SPC, 47.8% died as a result of the corresponding SPC, followed by other causes (22.2%) and PC (18.1%). For patients without SPC, PC and non-neoplastic causes almost matched each other as the main causes of death (48.5% and 47.8%). The results suggest that SPCs appear autonomous from primary PC and reflect incidence and mortality of first cancers in general. SPC was the most common cause of death in patients with SPC; close to half of the patients died due to SPC. For improved survival in PC patients, prevention and early detection of SPCs would be important, and the present results suggest that risk factors for SPC in PC are the same as those for first cancer in general.
| S-EPMC6246949 | biostudies-literature
Project description:Purpose: The current study explored the risk of developing second primary cancers (SPCs) among long-term early-stage breast cancer survivors and identified risk factors to build an externally validated clinical prediction model. Methods: The cumulative incidence of SPCs was calculated by Gray method among survivors of early-stage initial primary breast cancer (IPBC). Comparisons of treatment-related risk by selected organ sites were performed. A nomogram was established to estimate the individual risk of developing SPCs based on the multivariate Fine and Gray risk model. Decision curve analysis (DCA) was used to evaluate clinical usefulness of the model. Results: The cumulative incidence of developing SPCs after early-stage IPBC was 7.43% at 10 years, 14.41% at 15 years, and 20.08% at 20 years. Radiotherapy was associated with elevated risks of any SPCs and with elevated risks of lung cancer (SHR: 1.109; P = 0.045), breast cancer (SHR: 1.389; P < 0.001), and AML (SHR: 1.298; P = 0.045). Chemotherapy was significantly associated with a declined risk of any SPCs, with decreased risks of lung (SHR: 0.895; P = 0.015) and breast cancers (SHR: 0.891; P < 0.001), as well as elevated risks of other leukemias (SHR: 1.408; P = 0.002). HR-positive status was associated with decreased risks of any SPCs; with decreased risks of breast (SHR: 0.842; P < 0.001) and ovarian cancers (SHR: 0.483; P < 0.001); and with elevated risks of urinary tract cancers (SHR: 1.214; P = 0.029). Conclusion: We found that the cumulative incidence of developing SPCs increased over time and did not plateau. Risk factors for developing SPCs identified by our study were not consistent with those of previous studies. The prediction model can help identify individuals at higher risk of SPCs.
| S-EPMC6970432 | biostudies-literature
Project description:Disparities exist in breast cancer (BC) outcomes between racial and ethnic groups in the United States. Reasons for these disparities are multifactorial including differences in genetics, stage at presentation, access to care, and socioeconomic factors. Less is documented on racial/ethnic differences in subsequent risk of second primary cancers (SPC). The purpose of this study is to evaluate the risk of SPC among different racial/ethnic groups of women with BC. We conducted a retrospective cohort study of 134,868 Non-Hispanic White, 17,484 Black, 18,034 Hispanic, and 19,802 Asian/Pacific Islander (API) women with stages I-III BC in twelve Surveillance, Epidemiology and End Results Program registries between 2001 and 2010. Standardized incidence ratios (SIR), 95 % confidence intervals (CI), and absolute excess risks were calculated by comparing incidence of SPC in the cohort to incidence in the general population for specific cancer sites by race/ethnicity and stratified by index BC characteristics. All women were at increased risks of second primary BC and acute myeloid leukemia (AML), with higher risk among more advanced stage index BC. Black and API women had higher SIRs for AML [4.86 (95 % CI 3.05-7.36) and 5.00 (95 % CI 3.26-7.32)], respectively] which remained elevated among early-stage (I) BC cases. Women with a history of invasive BC have increased risk of SPC, most notable for second primary BC and AML. These risks for secondary cancers differ by race/ethnicity. Studies evaluating possible genetic and biobehavioral mechanisms underlying these differences are warranted. Strategies for BC adjuvant treatment and survivorship care may require further individualization with consideration given to race/ethnicity.
| S-EPMC4501770 | biostudies-literature
Project description:Excess sarcoma risks after childhood cancer are well established, but risks among young adulthood cancer survivors are poorly understood. Using US population-based cancer registry data, we compared bone and soft-tissue sarcoma risk vs the general population among 186 351 individuals who were diagnosed with nonsarcoma first primary malignancies at ages 20-39 years from 1975 to 2014 (follow-up through 2015) and survived at least 1 year. Bone sarcomas were rare (n = 50), but risk was statistically significantly elevated overall (2.9-fold) and greater than fivefold after Hodgkin lymphoma, non-Hodgkin lymphoma, and central nervous system tumors. Soft-tissue sarcomas were more common (n = 284) and risks were statistically significantly elevated approximately twofold overall and after melanoma and carcinomas of the breast, thyroid, and testis, and greater than fourfold after Hodgkin lymphoma and central nervous system tumors. Risks varied markedly by subtype, with the highest risks (greater than fourfold) for osteosarcoma and the soft-tissue subtypes of rhabdomyosarcoma and blood vessel and nerve sheath sarcomas. These data demonstrate elevated risk for sarcoma after a range of young adulthood cancers.
| S-EPMC7049991 | biostudies-literature
Project description:PurposeConcerns have been raised that modern intensity modulated radiotherapy (IMRT) may be associated with increased second primary cancer risks (SPC) compared to previous three-dimensional conformal radiation techniques (3DCRT), due to increased low dose volumes and more out-of-field ionizing dose to peripheral tissue further away from the target. We assessed the impact of treatment technique on SPC risks in a cohort of prostate cancer (PCa) survivors.Material and methodsThe study cohort comprised 1,561 PCa survivors aged 50-79 years at time of radiotherapy, treated between 2006-2013 (N=707 IMRT, N=854 3DCRT). Treatment details were extracted from radiotherapy systems and merged with longitudinal data of the Netherlands Cancer Registry to identify SPCs. Primary endpoint was the development of a solid SPC (excluding skin cancer) in peripheral anatomical regions, i.e. non-pelvic. Applied latency period was 12 months. SPC rates in the IMRT cohort (total cohort and age subgroups) were compared to 1) the 3DCRT cohort by calculating Sub-Hazard Ratios (sHR) using a competing risk model, and 2) to the general male population by calculating Standardized Incidence Ratios (SIR). Models were adjusted for calendar period and age.ResultsMedian follow-up was 8.0 years (accumulated 11,664 person-years at-risk) with 159 cases developing ≥1 non-pelvic SPC. For IMRT vs 3DCRT we observed a significantly (p=0.03) increased risk (sHR=1.56, 95% Confidence Interval (CI) 1.03-2.36, corresponding estimated excess absolute risk (EAR) of +7 cases per 10,000 person-years). At explorative analysis, IMRT was in particular associated with increased risks within the subgroup of active smokers (sHR 2.94, p=0.01). Within the age subgroups 50-69 and 70-79 years, the sHR for non-pelvic SPC was 3.27 (p=0.001) and 0.96 (p=0.9), respectively. For pelvic SPC no increase was observed (sHR=0.8, p=0.4). Compared to the general population, IMRT was associated with significantly increased risks for non-pelvic SPC in the 50-69 year age group (SIR=1.90, p<0.05) but not in the 70-79 years group (SIR=1.08).ConclusionIMRT is associated with increased SPC risks for subjects who are relatively young at time of treatment. Additional research on aspects of IMRT that may cause this effect is essential to minimize risks for future patients receiving modern radiotherapy.
| S-EPMC7691574 | biostudies-literature
Project description:ImportanceThe number of cancer survivors who develop new cancers is projected to increase, but comprehensive data on the risk of subsequent primary cancers (SPCs) among survivors of adult-onset cancers are limited.ObjectiveTo quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types and sex.Design, setting, and participantsA retrospective cohort study from 12 Surveillance, Epidemiology, and End Results registries in the United States, that included 1 537 101 persons aged 20 to 84 years diagnosed with FPCs from 1992-2011 (followed up until December 31, 2017) and who survived at least 5 years.ExposuresFirst primary cancer.Main outcomes and measuresIncidence and mortality of SPCs per 10 000 person-years; standardized incidence ratio (SIR) and standardized mortality ratio (SMR) compared with those expected in the general population.ResultsAmong 1 537 101 survivors (mean age, 60.4 years; 48.8% women), 156 442 SPC cases and 88 818 SPC deaths occurred during 11 197 890 person-years of follow-up (mean, 7.3 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 18 of the 30 FPC types, and risk of dying from any SPCs was statistically significantly higher for 27 of 30 FPC types as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 21 of the 31 FPC types, and risk of dying from any SPCs was statistically significantly higher for 28 of 31 FPC types as compared with risks in the general population. The highest overall SIR and SMR were estimated among survivors of laryngeal cancer (SIR, 1.75 [95% CI, 1.68-1.83]; incidence, 373 per 10 000 person-years) and gallbladder cancer (SMR, 3.82 [95% CI, 3.31-4.39]; mortality, 341 per 10 000 person-years) among men, and among survivors of laryngeal cancer (SIR, 2.48 [95% CI, 2.27-2.72]; incidence, 336 per 10 000 person-years; SMR, 4.56 [95% CI, 4.11-5.06]; mortality, 268 per 10 000 person-years) among women. Substantial variation existed in the associations of specific types of FPCs with specific types of SPC risk; however, only a few smoking- or obesity-associated SPCs, such as lung, urinary bladder, oral cavity/pharynx, colorectal, pancreatic, uterine corpus, and liver cancers constituted considerable proportions of the total incidence and mortality, with lung cancer alone accounting for 31% to 33% of mortality from all SPCs.Conclusions and relevanceAmong survivors of adult-onset cancers in the United States, several types of primary cancer were significantly associated with greater risk of developing and dying from an SPC, compared with the general population. Cancers associated with smoking or obesity comprised substantial proportions of overall SPC incidence and mortality among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.
| S-EPMC7756242 | 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:BackgroundInitial primary colorectal cancer (IPCRC) has a high risk of developing into second primary colorectal cancer (SPCRC). Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) have different characteristics and are considered to be two different entities. However, the different risks for SPCRC in categorized tumor sites and SPCRC subcategorized sites have not been fully elucidated to date. We aimed to compare incidence and survival of IPCRC and SPCRC and characterize the risk factors of SPCRC while also comparing the different SPCRC characteristics.MethodsWe used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data to compute standardized incidence ratios (SIR) in order to estimate risk of SPCRC after IPCRC diagnosis. The most prominent risk factors for SPCRC were measured by multivariate regression analysis and the temporal trend of SPCRC incidence was assessed with Joinpoint regression. Survival of patients with SPCRC and IPCRC was compared by Kaplan-Meier analysis.ResultsPatients with IPCRC were 1.73 times more likely to develop SPCRC (SIR?=?1.73, 95% CI 1.69-1.78). SPCRC incidence declined since the first 8 years of IPCRC diagnosis to baseline. We demonstrated poorer survival with SPCRC compared with IPCRC while second RCC resulted in better survival compared with second LCC. Black ethnicity, age range 70-79, and LCC were associated with the highest risk of developing SPCRC.ConclusionThe characteristic differences between second LCC and RCC were relatively narrow. Furthermore, in those with SPCRC, RCC had the best survival outcome.
| S-EPMC6161401 | biostudies-literature
Project description:This study aimed to investigate the risk factors of second primary cancer among female breast cancer (BC) survivors, with emphasis on the prediction of the individual risk conditioned on the patient's characteristics. We identified 208,474 BC patients diagnosed between 2004 and 2010 from the Surveillance, Epidemiology and End Results (SEER) database. Subdistribution proportional hazard model and competing-risk nomogram were used to explore the risk factors of second primary BC and non-BC, and to predict the 5- and 10-year probabilities of second primary BC. Model performance was evaluated via calibration curves and decision curve analysis. The overall 3-, 5-, and 10-year cumulative incidences for second primary BC were 0.9%, 1.6% and 4.4%, and for second primary non-BC were 2.3%, 3.9%, and 7.8%, respectively. Age over 70 years at diagnosis, black race, tumor size over 2 cm, negative hormone receptor, mixed histology, localized tumor, lumpectomy alone, and surgeries plus radiotherapy were significantly associated with increased risk of second BC. The risk of second non-BC was only related to age, race and tumor size. The proposed risk model as well as its nomogram was clinically beneficial to identify patients at high risk of developing second primary breast cancer.
| S-EPMC7732282 | biostudies-literature
Project description:BACKGROUND:Patients with history of colorectal cancer (CRC) are at increased risk for developing a second primary colorectal cancer (SPCRC) as compared to the general population. However, the degree of risk is uncertain. Here, we attempt to quantify the risk, using data from the large population-based California Cancer Registry (CCR). MATERIALS AND METHODS:We analyzed the CCR data for cases with surgically-treated colon and rectal cancer diagnosed during the period 1990-2005 and followed through up to January 2008. We excluded those patients diagnosed with metastatic disease and those in whom SPCRC was diagnosed within 6 months of the diagnosis of the primary CRC. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to evaluate risk as compared to the underlying population after taking into account age, sex, ethnicity, and time at risk. RESULTS:The study cohort consisted of 69809 cases with colon cancer and 34448 with rectal cancer. Among these patients there were 1443 cases of SPCRCs. The SIR for developing SPCRC was higher in colon cancer survivors (SIR=1.4; 95% CI: 1.3 to 1.5) as compared to the underlying population. The incidence of SPCRC was also higher in females (SIR=1.5; 95% CI: 1.3 to 1.6) and Hispanics (SIR=2.0; 95% CI: 1.7 to 2.4) with primary colon cancer. The SIR for developing an SPCRC was higher only among those whose initial tumor was located in the descending colon (SIR=1.6; 95% CI: 1.3 to 2.0) and proximal colon (SIR=1.4; 95% CI: 1.3 to 1.6). CONCLUSIONS:Our results confirm that CRC patients, especially females and Hispanics, are at a higher risk of developing SPCRC than the general population. Differential SPCRC risk by colorectal tumor subsite is dependent on gender and ethnicity, underscoring the heterogeneous nature of CRC.
| S-EPMC3072650 | biostudies-literature