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

Abstract

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.

Clinical Features of Patients with Esophageal and Second Primary Cancers

“…The difference could be attributed to the higher prevalence of HCC in Southeastern Asia. Additionally, Zhu et al (2012) observed that incidence of SPC in the EC patients was disproportionally higher in male than in female. The reason why SPC occurred in EC patients with male preponderance was not totally clarified yet, but it was generally deemed that tobacco and alcohol consumption played a crucial role in the prevalence of EC with the gender differences (Pandeya et al, 2013;Prabhu et al, 2014).…”

“…Also, it was reported that blood type could be a risk factor in the development of SPC in certain cancer (Lawniczak et al, 2014). Previous studies involving SPC had been enormously reported, but a limited number of subjects regarding EC and SPC were announced (Poon et al, 1998;Zhu et al, 2012). Therefore, we conducted this study to analyze the clinicopathological features in EC patients with or without SPC.…”

“…Although the preventive strategies of EC had been developed and the treatment such as surgical resection and adjuvant chemoradiotherapy had been improved, the post-therapeutic survival rate remained dismal in clinical practice (Ge et al, 2012;Jingu et al, 2012). What's worse, the development of secondary neoplasms after chemoradiotherapy was observed in several studies recently (Newhauser et al, 2009;Zhu et al, 2012). Hence, the incidence of second primary cancer (SPC) in posttherapeutic EC patients was a public health issue.…”

Risk of second primary malignancy after nasopharyngeal carcinoma in the United States: A population‐based study

“…Also, we used the SEER*Stat program latency exclusion period of 6 months when calculating incidence of second primaries that may still have included recurrences or metastases rather than true second primary malignancies. Finally, the standard incidence ratios reported may underestimate the true relative risk because of patient emigration from registries, particularly in younger patients …”

Risk of subsequent cancer following a primary CNS tumor

“…Though reports have implicated radiation therapy as a risk factor for development of a subsequent cancer [3, 4, 6,11–16], our study provided the first known large-scale comparison of subsequent cancer risk in patients who had radiation therapy for their primary CNS tumor to those that did not, separated by histological subtypes. Significantly elevated risks were found for patients diagnosed with an astrocytoma NOS, OII/III, ependymoma and MPNET and who had received radiotherapy (Table 2).…”