Risk of second primary cancer after treatment for esophageal cancer: A pooled analysis of nine cancer registries

ArticleinDiseases of the Esophagus 25(6):505-11 · November 2011with15 Reads
DOI: 10.1111/j.1442-2050.2011.01273.x · Source: PubMed
The introduction of new treatments for esophageal cancer including surgery, chemotherapy, radiotherapy, or a combination of these modalities has not only improved patient survival, but may also increase the risk of the second primary cancers. The available evidence is conflicting with most risk estimates based on sparse numbers. Here we estimated standardized incidence ratios (SIRs) of second cancer among 24,557 esophageal cancer survivors (at least 2 months) in the Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2007, who had been followed up for median 6.5 years (range 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.34, 95% confidence interval [CI]= 1.25-1.42) among the survivors compared with the general population; the SIRs for cancers of oral and pharynx, stomach, small intestine, larynx, lung and bronchus, thyroid and prostate cancer were 8.64 (95% CI = 7.36-10.07), 2.87 (95% CI = 2.10-3.82), 3.80 (95% CI = 1.82-7.00), 3.19 (95% CI = 2.12-4.61), 1.68 (95% CI = 1.46-1.93), 2.50 (95% CI = 1.25-4.47), and 0.77 (95% CI = 0.65-0.90), respectively. Radiotherapy raised cancer risk of larynx (SIR = 3.98, 95% CI = 2.43-6.14) and thyroid (SIR = 3.57, 95% CI = 1.54-7.03) among all esophageal cancer survivors. For patients who had 5-9 years of follow up after radiotherapy, the SIR for lung cancer was 3.46 (95% CI = 2.41-4.82). Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx, larynx, lung, and thyroid, while at a decreased risk for prostate cancer. These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx, lung, and thyroid. Thus, randomized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted.
    • "The results were controversial in previous studies. Matsubara et al. presented that both treatments were not correlated with SPM[14], but Zhu et al. stated that these treatments may increase risk[8]. This retrospective study has several limitations. "
    [Show abstract] [Hide abstract] ABSTRACT: To evaluate the risk and sites of metachronous secondary primary malignancies (SPMs) among patients with esophageal cancer. Newly diagnosed esophageal cancer patients between 1997 and 2011 were recruited. To avoid surveillance bias, SPMs that developed within one year were excluded. Standardized incidence ratios (SIRs) of metachronous SPMs in these patients were calculated by comparing to the cancer incidence in the general population. Risk factors for SPM development, included age, sex, comorbidities and cancer-related treatments, were estimated by Cox proportional hazards models. During the 15-year study period, 870 SPMs developed among 18,026 esophageal cancer patients, with a follow-up of 27,056 person-years. The SIR for all cancers was 3.53. The SIR of follow-up period ≥ 10 years was 3.56; 5-10 years, 3.14; and 1-5 years, 3.06. The cancer SIRs of head and neck (15.83), stomach (3.30), lung and mediastinum (2.10), kidney (2.24) and leukemia (2.72), were significantly increased. Multivariate analysis showed that age ≥ 60 years (hazard ratio [HR] 0.74), being male (HR 1.46) and liver cirrhosis (HR 1.46) were independent factors. According to the treatments, major surgery (HR 1.24) increased the risk, but chemotherapy was nearly significant. Patients with esophageal cancer were at increased risk of developing metachronous SPMs. The SIR remained high in follow-up > 10 years, so that close monitoring may be needed for early detection of SPM among these esophageal cancer patients.
    Full-text · Article · Jan 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Improvements in survival among central nervous system (CNS) tumor patients has made the risk of developing a subsequent cancer an important survivorship issue. Such a risk is likely influenced by histological and treatment differences between CNS tumors. De-identified data for 41,159 patients with a primary CNS tumor diagnosis from 9 Surveillance, Epidemiology and End Results (SEER) registries were used to calculate potential risk for subsequent cancer development. Relative risk (RR) and 95 % confidence interval (CI) of subsequent cancer was calculated using SEER*Stat 7.0.9, comparing observed number of subsequent cancers versus expected in the general United States population. For all CNS tumors studied, there were 830 subsequent cancers with a RR of 1.26 (95 % CI, 1.18-1.35). Subsequent cancers were observed in the CNS, digestive system, bones/joints, soft tissue, thyroid and leukemia. Radiotherapy was associated with an elevated risk, particularly in patients diagnosed with a medulloblastoma/primitive neuroectodermal tumor (MPNET). MPNET patients who received radiotherapy were at a significant risk for development of cancers of the digestive system, leukemia, bone/joint and cranial nerves. Glioblastoma multiforme patients who received radiotherapy were at lower risks for female breast and prostate cancers, though at an elevated risk for cancers of the thyroid and brain. Radiotherapy is associated with subsequent cancer development, particularly for sites within the field of radiation, though host susceptibility and post-treatment status underlie this risk. Variation in subsequent cancer risk among different CNS tumor histological subtypes indicate a complex interplay between risk factors in subsequent cancer development.
    Article · Feb 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Development of a second primary malignancy (SPM) after an index esophageal cancer is fairly rare, primarily due to decreased survival in patients with esophageal cancer. However, with advances in early detection and therapy, the number of long-term survivors is increasing, as is the incidence of SPMs in this population. Scope: We review herein the published literature on the incidence of SPMs after an index esophageal cancer as well as its associated risk factors, prognosis and surveillance. We discuss predisposing factors that may contribute to the development of SPMs, epidemiology and attempts at chemoprevention. Findings: Data from population-based studies, retrospective reviews and case reports indicate an increased risk of SPMs in patients with esophageal cancer with reported incidence rates between 8.3 and 27.1%. Index esophageal squamous cell carcinomas have a higher association with other tobacco-related cancers such as those of the head and neck and lung. They have also shown an association with second primary cancers of the breast, stomach, thyroid, and kidney. Individuals with esophageal adenocarcinomas are at a higher risk of developing second cancers of the stomach, oropharynx and lung/bronchus. Other primary cancer sites involved include the kidney, colorectum and pancreas. Common risk factors including lifestyle and genetic alterations may explain the increased incidence of second primary cancers in this patient population. Conclusions: Risk of developing a second malignancy should be anticipated after curative treatment of esophageal cancer, and raises concerns for optimal surveillance and therapy of these patients. Recent literature suggests similar survival rates in esophageal cancer patients with and without SPMs. With the increasing incidence of SPMs in subjects with esophageal cancer, there may be benefit to close screening for and aggressive therapy of SPMs. However, further studies are needed to elucidate optimal management strategies.
    Article · Jun 2013
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