Risk of second primary malignancies after definitive treatment for esophageal cancer: A competing risk analysis.
Mitani Seiichiro,Kadowaki Shigenori,Oze Isao,Masuishi Toshiki,Narita Yukiya,Bando Hideaki,Oonishi Sachiyo,Hirayama Yutaka,Tanaka Tsutomu,Tajika Masahiro,Koide Yutaro,Kodaira Takeshi,Abe Tetsuya,Muro Kei
Cancer medicine
BACKGROUND:Esophageal cancer is associated with synchronous or metachronous cancer at other primary sites. However, few studies have evaluated the second malignancies after the treatment of esophageal cancer. The present study aimed to clarify the frequency of and risk factors for the second malignancies after definitive therapy for esophageal cancer. PATIENTS AND METHODS:We included patients with esophageal cancer who received definitive therapy between 2000 and 2010. Exclusion criteria were synchronous cancer or a past history of cancer. Standardized incidence rate (SIR) was calculated using age- and sex-specific incidence rates from the cancer registry data. To conduct risk analyses, we used the competing risk regression model, which defined death and the development of second malignancies as competing risks. RESULTS:A total of 758 patients were included, with 131 second malignancies occurring in 106 patients (14%), over a median follow-up of 3.7 years. Cumulative incidences of second malignancies after 3, 5, and 8 years were 4.0%, 7.6%, and 13.8%, respectively. The risk of second malignancy was significantly elevated [SIR = 1.83, 95% confidence interval (CI): 1.50-2.22]. The most common sites of primary tumor were the head and neck (20%), followed by the lung (17%), stomach (16%), colon and rectum (11%), and urinary tract (9%). Risk analyses revealed that age ≥ 65 years [subdistribution hazard ratio (sHR): 1.51, 95% CI: 1.01-2.24, vs age < 65] and clinical stages 0-I (sHR: 2.48, 95% CI: 1.46-4.22, vs stage III and IV) and II (sHR: 2.10, 95% CI: 1.23-3.58, vs stage III and IV) were significantly associated with second malignancies. CONCLUSIONS:Compared with the general population, an increased incidence of second malignancies was observed in the patients with esophageal cancer in the present study even after definitive treatment. Careful follow-up is required, especially in patients at a higher risk of second malignancies.
10.1002/cam4.2688
Analysis of prognosis and treatment decisions for patients with second primary lung cancer following esophageal cancer.
Frontiers in oncology
Introduction:As the long-term prognosis of esophageal cancer (EC) is improving, concerns of a second primary malignancy (SPM) have increased. However, research on lung cancer as the SPM after EC is limited. Therefore, we aimed to explore the prognostic factors and clinical treatment decisions of patients with second primary lung cancer following esophageal cancer (SPLC-EC). Materials and methods:We identified the data of 715 patients with SPLC-EC from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2016. We established a nomogram through Cox regression modelling to predict the prognosis of patients with SPLC-EC. We determined the association between factors and cancer-specific mortality using the Fine-Gray competing risk model. Then, we performed survival analysis to evaluate the benefits of different treatment methods for overall survival (OS). Results:The multivariate analysis indicated that sex, insurance recode, age, surgery and chemotherapy 0for first primary malignancy (FPM), primary site, stage, and surgery for SPM were independent prognostic factors for OS. Using concordance indices for OS, the nomogram of our cohort showed a higher value than the SEER historic-stage nomogram (0.8805 versus 0.7370). The Fine-Gray competing risk model indicated that surgery for FPM and SPM was the independent prognostic factor for EC-specific mortality (P=0.016, hazard ratio [HR] = 0.532) and LC-specific mortality (p=0.016, HR=0.457), respectively (p<0.001). Compared to the patient group having distant metastasis, patients with localized and regional metastasis benefitted from undergoing surgery for SPM (P<0.001, P<0.001, respectively). For patients without surgery for SPM, radiotherapy (P<0.001) and chemotherapy (P<0.001) could improve OS. Conclusions:Surgery remains the mainstay for managing SPLC-EC, especially for localized and regional tumors. However, chemotherapy and radiotherapy are recommended for patients who cannot undergo surgery. These findings can have implications in the treatment decision-making for patients with SPLC-EC.
10.3389/fonc.2022.777934
Excessive risk of second-cancer incidence and cancer mortality in patients with esophageal cancer.
Ohmori Masayasu,Ishihara Ryu,Morishima Toshitaka,Tabuchi Takahiro,Okada Hiroyuki,Ohno Yuko,Sobue Tomotaka,Miyashiro Isao
Journal of gastroenterology
BACKGROUND:Second primary cancers have impact on survival in patients who achieved cure for the first esophageal cancer. We, therefore, assessed the risk of incidence and mortality for second primary cancer by calculating standardized incidence ratio (SIR) and standardized mortality ratio (SMR) in patients with superficial or localized esophageal cancer without lymph node metastases as the first cancer (index cancer). METHODS:Data on cancer development and subsequent causes of deaths were collected from integrated database of the Osaka Cancer Registry and the Vital Statistics of Japan. Records with information on patients with index esophageal cancer diagnosed between 2004 and 2013 were extracted from the database. Then, SIR and SMR for second primary cancers that developed in other organ were calculated with the reference to the general population during the same period. All probability values are two-tailed. RESULTS:Of 473,784 case records, 3022 cases of patients with index esophageal cancer were identified. Significantly higher SMRs/SIRs for cancers in mouth/pharynx, larynx, pancreas, and leukemia were confirmed with the values of 10.78/16.16, 8.56/6.44, 2.33/2.31, and 3.96/4.42, respectively. Significantly, higher SIRs for stomach, lung, and skin cancers were confirmed with the values of 2.84, 2.36, and 3.38, respectively, while SMRs were not significantly higher in these cancers. CONCLUSIONS:Significantly higher risks for mouth/pharynx, larynx, pancreas, and leukemia as second cancers were clarified. Careful surveillance for these cancers is required for esophageal cancer patients.
10.1007/s00535-021-01767-2
Correlation between second and first primary cancer: systematic review and meta-analysis of 9 million cancer patients.
The British journal of surgery
BACKGROUND:Many survivors of a first primary cancer (FPCs) are at risk of developing a second primary cancer (SPC), with effects on patient prognosis. Primary cancers have different frequencies of specific SPC development and the development of SPCs may be closely related to the FPC. The aim of this study was to explore possible correlations between SPCs and FPCs. METHODS:Relevant literature on SPCs was retrospectively searched and screened from four databases, namely, PubMed, EMBASE, Web of Science, and PMC. Data on the number of patients with SPC in 28 different organ sites were also collected from The Surveillance, Epidemiology, and End Results (SEER) 8 Registry and NHANES database. RESULTS:A total of 9 617 643 patients with an FPC and 677 430 patients with an SPC were included in the meta-analysis. Patients with a first primary gynaecological cancer and thyroid cancer frequently developed a second primary breast cancer and colorectal cancer. Moreover, those with a first primary head and neck cancer, anal cancer and oesophageal cancer developed a second primary lung cancer more frequently. A second primary lung cancer and prostate cancer was also common among patients with first primary bladder cancer and penile cancer. Patients with second primary bladder cancer accounted for 56% of first primary ureteral cancer patients with SPCs. CONCLUSIONS:This study recommends close clinical follow-up, monitoring and appropriate interventions in patients with relevant FPCs for better screening and early diagnosis of SPCs.
10.1093/bjs/znad377
Prevalence of lung tumors in patients with esophageal squamous cell carcinoma and vice versa: a systematic review and meta-analysis.
Journal of cancer research and clinical oncology
PURPOSE:Recent reports suggest an increased prevalence of lung second primary tumors (LSPTs) in esophageal squamous cell carcinoma (ESCC) patients and vice versa. However, the exact prevalence of SPTs remains unclear and screening for these SPTs is currently not routinely performed in western countries. We aimed to report on the prevalence of LSPTs in patients with ESCC and esophageal second primary tumors (ESPTs) in patients with lung cancer (LC). METHODS:Databases were searched until 25 March 2021 for studies reporting the prevalence of LSPTs in ESCC or vice versa. Pooled prevalences with 95% confidence intervals (CI) of SPTs were calculated with inverse variance, random-effects models and Clopper-Pearson. RESULTS:Nineteen studies in ESCC patients and 20 studies in LC patients were included. The pooled prevalence of LSPTs in patients with ESCC was 1.8% (95% CI 1.4-2.3%). For ESPTs in LC patients, the pooled prevalence was 0.2% (95% CI 0.1-0.4%). The prevalence of LSPTs in ESCC patients was significantly higher in patients treated curatively compared to studies also including palliative patients (median 2.5% versus 1.3%). This difference was consistent for the ESPT prevalence in LC patients (treated curatively median 1.3% versus 0.1% for all treatments). Over 50% of the detected SPTs were squamous cell carcinomas and were diagnosed metachronously. CONCLUSION:Patients with ESCC and LC have an increased risk of developing SPTs in the lungs and esophagus. However, the relatively low SPT prevalence rates do not justify screening in these patients. Further research should focus on risk stratification to identify subgroups of patients at highest risk of SPT development.
10.1007/s00432-022-04103-0
Risk of second cancer in esophageal squamous cell carcinoma and adenocarcinoma survivors: a population-based analysis in SEER dataset.
Translational gastroenterology and hepatology
Background:Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients. Methods:This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992-2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients' characteristics. Results:After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51-1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02-1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87-15.79), stomach (SIR: 3.03, 95% CI: 1.77-4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47-8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96-2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52-0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23-5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02-1.54), and kidney (SIR: 1.57, 95% CI: 1.05-2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11-1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50-0.76 for regional stage; sHR: 0.27, 95% CI: 0.20-0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40-0.56 for regional stage; sHR: 0.10, 95% CI: 0.07-0.13 for distant stage). Conclusions:Both ESCC and EAC patients are at considerable risk of certain types of second cancer.
10.21037/tgh-23-29
Survival outcomes in esophageal cancer patients with a prior cancer.
Medicine
ABSTRACT:To achieve a deeper understanding of patients who developed esophageal cancer (EC) as a second primary malignancy, which may help guide in clinical practice for these patients in the future.In the primary cohort, EC patients with a prior malignancy were identified from the surveillance, epidemiology, and end result 18 database. The 5 most common types of prior cancers were picked out based on the frequency of occurrence. In addition, Kaplan-Meier and log-rank tests were performed to investigate the survival impacts of prior cancers on EC patients. Besides, a competing-risk model was constructed to explore the relationship between EC-treatment and EC-specific mortality. In the secondary cohort, patients with stage I-III (N0M0) EC from 2004 to 2014 were enrolled. After propensity score matching, univariate and multivariate Cox analyses were developed to determine the prognostic factors for EC patients.A total of 1199 EC patients with a prior cancer were identified in the primary cohort. The 5 most common sites of prior cancers were prostate, female breast, bladder, lung and bronchus, and larynx. Kaplan-Meier analyses revealed that EC patients with prior prostate cancer and bladder cancer had the best overall survival (OS), while those with prior cancers of larynx and lung and bronchus had the worst OS. Fine and Gray competing risks analysis indicated that the administration of surgery was closely associated with better EC-specific survival (P < .001). In the secondary cohort, multivariate Cox analyses found that age at diagnosis, race, tumor grade, tumor extent, nodal status and metastasis stage, histology, and the administration of surgery were prognostic factors for OS and cancer-specific survival in EC patients. Besides, the existence of a prior cancer was an independent prognostic factor for cancer-specific survival.EC remains to be the most important cause of death in EC patients with a prior cancer. EC related treatment should be actively adopted in patients with a prior cancer, as they were more likely to die from EC than the prior cancer. EC patients with a prior cancer had comparable OS than those without.
10.1097/MD.0000000000024798
Secondary primary lung cancer after esophageal cancer: a population-based study of 44,172 patients.
Scandinavian journal of gastroenterology
BACKGROUND:The present study aimed to assess the survival, incidence, and characteristics of secondary primary lung cancer (SPLC) after esophageal cancer (EC-LC). METHODS:The patients with esophageal cancer (EC) who developed SPLC and patients with first primary lung cancer (LC-1) were retrospectively reviewed in the Surveillance, Epidemiology, and End Results 18 registries covering 2000-2016. Overall survival and characteristics were compared between patients with EC-LC and patients with LC-1. The independent relation between a history of EC and death was evaluated by calculating hazard ratios in multivariate Cox regression analysis propensity score-matching analysis, and multiple imputation for cases with missing information. RESULTS:In comparison with the general population, the patients with EC had a higher risk for developing secondary primary lung cancer (SIR =1.86, 95% confidence interval (CI): 1.69-2.05). A history of EC was found to be an independent risk factor of death for lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients in localized stage based on multivariate Cox regression analysis, propensity score-matching analysis and multiple imputation. CONCLUSIONS:There is a significantly increased risk of secondary primary lung cancer in EC survivors and a history of EC adversely affects overall survival in individuals who subsequently develop localized LUSC and LUAD. Clinicians should moderately strengthen lung tissue protection during the management of EC patients.
10.1080/00365521.2021.1994639
Causal relationship between lung diseases and risk of esophageal cancer: insights from Mendelian randomization.
Journal of cancer research and clinical oncology
BACKGROUND:An increasing number of cohort studies have indicated a correlation between lung diseases and esophageal cancer, but the exact causal relationship has not been definitively established. Therefore, the objective of this study is to assess the causal relationship between lung diseases and esophageal cancer. METHODS:Single-nucleotide polymorphisms (SNPs) related to lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF), along with outcomes data on esophageal cancer, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse-variance-weighted method. RESULTS:Totally, 81 SNPs related to asthma among 218,792 participants in GWAS. Based on the primary causal effects model using MR analyses with the inverse variance weighted (IVW) method, asthma was demonstrated a significantly related to the risk of esophageal cancer (OR 1.0006; 95% CI 1.0003-1.0010, p = 0.001), while COPD (OR 1.0306; 95% CI 0.9504-1.1176, p = 0.466), lung cancer (OR 1.0003, 95% CI 0.9998-1.0008, p = 0.305), as well as IPF (OR 0.9999, 95% CI 0.9998-1.0000, p = 0.147), showed no significant correlation with esophageal cancer. CONCLUSIONS:The two-sample MR analysis conducted in this study revealed a positive causal relationship between asthma and esophageal cancer. In contrast, esophageal cancer demonstrated no significant correlation with COPD, lung cancer, or IPF. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding esophageal cancer screening among patients with asthma.
10.1007/s00432-023-05324-7