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Risk of Second Primary Malignancies Based on the Histological Subtypes of Colorectal Cancer.

ABSTRACT: Background: Previous studies have revealed an increased risk of second primary malignancies (SPMs) after colorectal cancer (CRC); however, no previous investigation has quantified differences in the risk of SPMs based on the histological subtypes of first primary CRC. Methods: Patients diagnosed with first primary CRC between 2000 and 2011 were identified from the Surveillance, Epidemiology, and End Results cancer registries. The patients were divided into three cohorts: classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC). Standardized incidence ratios were calculated to assess the risk of SPMs among the patients. Results: Overall risk of SPMs was significantly higher among patients with three histological subtypes of CRC than in the general population. The risk of esophagus cancer was significantly increased in SRCC. The risk of small intestine, colon and rectum, and corpus uteri cancers was high in three histological subtypes, with the highest risk observed in SRCC, followed by MA. Increased risks of second stomach, uterus, urinary bladder, kidney, and thyroid cancers were only observed in CA patients, while increased risk of second renal pelvis cancer was limited to MA patients. Furthermore, the high overall risk of SPMs in CA patients persisted regardless of clinicopathological factors. After surgery combined with chemotherapy treatment, CA patients were more prone to developing second small intestine, colon and rectum cancers than those treated with surgery only. A lower second prostate cancer risk was observed in rectal CA patients treated with surgery combined with radiotherapy than in patients treated with surgery only. Conclusion: The present study revealed that the risk of developing SPMs after CRC varied based on the histological subtypes of the first primary CRC. Although the mechanisms underlying the observed patterns of SPM risk remain unknown, the study provided insights into future cancer surveillance based on the histological subtypes of CRC.

SUBMITTER: Wu M

PROVIDER: S-EPMC7988191 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThis study aimed to profile the characteristics of patients with colorectal cancer (CRC) with a second primary malignancy (SPM) and to identify patients with CRC at high risk of developing SPMs.MethodsWe retrospectively reviewed data on patients with CRC aged 20-79 years from the Surveillance, Epidemiology, and End Results (SEER) database. Eligible patients were categorized into only one primary malignancy and SPM cohorts. A competing-risk model was used to quantify associations between SPM occurrence and the multiple traits of patients. Finally, a decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model by calculating net benefit.ResultsA total of 179,884 patients were identified, 18,285 (10.2%) of whom developed SPMs during a maximum follow-up of approximately 18 years. The median survival time after the second diagnosis was less than 4 years. The 3-year, 5-year, and 10-year cumulative risks of developing an SPM were 3.9%, 5.9%, and 10.0%, respectively. According to the multivariable competing-risk model, male colon cancer survivors, older in age, with a well-differentiated tumor and localized disease, who were treated with surgery were susceptible to SPMs. The DCA yielded a wide range of risk thresholds at which the net benefits would be obtained from our proposed model.ConclusionCRC survivors remain at high risk of developing SPMs. Patients with a second diagnosis of cancer showed not only significantly worse survival but also higher cancer-specific mortality. A web-based individualized predictive tool was also provided to assist clinicians in identifying patients at high risk of developing SPMs and planning their future care management.Implications for practiceColorectal cancer survivors remain at high risk of developing a second primary malignancy (SPM). This study aimed to profile the characteristics of patients with colorectal cancer with second primary malignancies and to further explore the risk factors related to the development of second primary malignancies, using a large population-based cohort. A clinically useful competing-risk nomogram was developed to predict the risk of SPMs based on individual clinical factors. According to the findings, older age, male sex, white or black race, localized disease, and treatment with surgery among patients with colon cancer were associated with an increased risk of developing an SPM. These findings and the proposed tool could be useful to clinicians and caregivers in the clinical counseling of patients with colorectal cancer and the development of long-term care management.

Project description:Background: Second primary malignancy (SPM) attracts a growing attention. However, the clinical features of colon cancer (CC) survivors with SPMs are not clear and could help guide clinicians to develop a better surveillance strategy. Methods: We reviewed 56,930 CC survivors treated with colectomy from the Surveillance, Epidemiology, and End Results (SEER) database during 1998-2011. Competing risk models and nomograms were conducted for predicting the risk of occurring SPMs. The clinical utility of the models was measured by decision curve analysis (DCA) using net benefit approaches. Results: Five thousand thirteen (17.1%) of male patients developed SPMs and sites of SPMs included prostate (32.2%), lung and bronchus (11.6%), urinary bladder and kidney (10.8%), colon (10.0%), and melanoma of the skin (3.9%), while 3,592 (13.0%) of female patients occurred SPMs and sites of SPMs involved breast (25.8%), lung and bronchus (13.6%), colon (11.6%), uterus (8.2%), urinary bladder, and kidney (5.6%). Survivors with a second carcinoma of lung and bronchus showed the worst prognosis. Older age increased the risk of SPMs in both male (Subdistribution hazard ratio =2.85 [95% confidence interval = 2.53-3.21]) and female (1.80 [1.59-2.04]) survivors, especially for the risk of a second prostate carcinoma in male (5.33 [4.03-7.03]). Compared with white race, black male survivors remained at higher risk to develop the second prostate carcinoma (1.98 [1.74-2.26]). Competing-risk nomograms for CC survivors were established to help clinicians predict the probabilities of overall SPMs and prostate carcinoma. Validation of nomograms showed good discrimination and accuracy, and DCAs revealed the clinical effectiveness. Conclusions: We profiled the clinical characteristics of a large population-based cohort of CC survivors with SPMs. These features may improve future follow-up management, especially for the surveillance of second prostate cancer in men and second breast cancer in women.

Project description:OBJECTIVE:To evaluate the risk of a second primary cancer after endometrial cancer according to histological subtype. METHODS:Using data from the 13 National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries we identified women diagnosed with a primary endometrial cancer between 1992 and 2014. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for second primary cancer risk (all anatomical sites combined and for individual anatomical sites) among patients with endometrial cancer compared with the general population, in the overall study population and according to histological subtype. RESULTS:Among 96 256 women diagnosed with endometrial cancer, 8.4% (n=8083) developed a second primary cancer. The risk of second primary cancer was higher among patients with endometrial cancer than in the general population (SIR=1.05, 95% CI 1.03 to 1.07). We observed significantly higher second primary cancer risk among women with high grade endometrioid (SIR=1.12, 95% CI 1.05 to 1.19), serous (SIR=1.24, 95% CI 1.11 to 1.38), carcinosarcoma (SIR=1.18, 95% CI 1.02 to 1.35), mixed epithelial (SIR=1.22, 95% CI 1.06 to 1.40), and sarcoma (SIR=1.28, 95% CI 1.12 to 1.45) compared with the general population, but not for women with low grade endometrioid (SIR=1.01, 95% CI 0.98 to 1.03) or clear cell (SIR=1.09, 95% CI 0.88 to 1.33) endometrial cancer. Women with low grade endometrioid endometrial cancer had significantly lower second primary cancer risks in the gum and other mouth (SIR=0.57, 95% CI 0.30 to 0.97), lung and bronchus (SIR=0.72, 95% CI 0.66 to 0.77), and lymphocytic leukemia (SIR=0.71, 95% CI 0.54 to 0.93) while women with high risk endometrial cancer histological subtypes experienced significantly higher second primary cancer risk at several anatomical sites. CONCLUSIONS:Risk of developing second primary cancersat all anatomic sites combined and at individual anatomical sites varied according to histological subtype. Clinicians should be aware that women with different histological subtypes carry different second primary cancer risks .

Project description:Background The most common form of treatment for non-metastatic lung cancer is surgery-based combination therapy, which may also include adjuvant radiotherapy or chemotherapy. Second primary malignancies (SPMs) are uncommon but significant radiation side effects in patients with resectable lung cancer, and SPMs have not been adequately investigated. Our study aims to assess the correlations of radiotherapy with the development of SPMs in patients with resectable lung cancer. Methods We screened for any primary malignancy that occurred more than five years after the diagnosis of resectable lung cancer. Based on the large cohort of the Surveillance, Epidemiology and End Results database, radiotherapy-correlated risks were estimated using the Poisson regression analysis and the cumulative incidence of SPMs was calculated using Fine-Gray competing risk regression analysis. Results Among the 62,435 patients with non-metastatic lung cancer undergoing surgery, a total of 11,341 (18.16%) patients have received radiotherapy. Our findings indicated that radiotherapy was substantially related to a high risk of main second solid malignancies (RR = 1.21; 95%CI, 1.08 to 1.35) and a negligible risk of main second hematologic malignancies (RR = 1.08; 95%CI, 0.84 to 1.37). With the greatest number of patients, the risk of acquiring a second primary gastrointestinal cancer was the highest overall (RR = 1.77; 95 percent CI, 1.44 to 2.15). The cumulative incidence and standardized incidence ratios of SPMs revealed similar findings. Furthermore, the young and the elderly may be more vulnerable, and the highest risk of acquiring most SPMs was seen more than ten years after lung cancer diagnosis. Additionally, more attention should be paid to the second primary gastrointestinal cancer in young individuals with resectable lung cancer. Conclusion After receiving radiotherapy, an increased risk of developing second primary solid and gastrointestinal cancers was observed for patients with resectable lung cancer. The prevention of SPMs associated with radiotherapy requires further attention. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-022-03857-y.

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Risk of Second Primary Malignancies Based on the Histological Subtypes of Colorectal Cancer.

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