Summary
A recent study showed that childhood cancer survivors are at an increased risk for lung cancer. Risk factors include increased age at diagnosis, high doses of chest radiotherapy, and primary diagnoses of Hodgkin lymphoma, neuroblastoma, and bone cancer, according to data presented at the ASCO 2020 Annual Meeting (Abstract 10551).
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Original Article
Survivors of Childhood Malignancies Face Risk of Developing Lung Cancer
Oncology Times
By Catlin Nalley
A recent study showed that childhood cancer survivors are at an increased risk for lung cancer. Risk factors include increased age at diagnosis, high doses of chest radiotherapy, and primary diagnoses of Hodgkin lymphoma, neuroblastoma, and bone cancer, according to data presented at the ASCO 2020 Annual Meeting (Abstract 10551).
“There are a growing number of adults who are childhood cancer survivors. It is critical we recognize significant late effects, including subsequent neoplasms, and develop appropriate guidelines for surveillance,” noted study author Taumoha Ghosh, MD, a third-year pediatric oncology fellow at the University of Minnesota. “Lung cancer is the most common adult cancer in the general population. However, it has not been thoroughly investigated as a subsequent neoplasm in pediatric cancer survivors.
“Low-dose CT is a method for lung cancer surveillance in the general population, which could benefit subsets of survivors,” she continued. “The objective of this study was to evaluate risk factors, characteristics, and outcomes of lung cancer among childhood cancer survivors in the Childhood Cancer Survivor Study (CCSS).”
Methodology
Among individuals participating in the CCSS, 25,654 five-year survivors were analyzed. Diagnosis of subsequent lung cancer was self-reported and then confirmed by pathologic record review.
Demographic and diagnosis characteristics assessed included: sex, race, family history of cancer, smoking history, vital status, age at diagnosis, primary diagnosis, and diagnosis era, according to Ghosh.
“In particular, cancer treatment exposures were evaluated, including chemotherapy, which was anthracyclines, bleomycin, CCNU, alkylating agents, platinums, and epipodophyllotoxins, and radiation to the chest was also assessed by field size and dose group,” she explained.
The investigators calculated standardized incidence ratios (SIR) using rates from the SEER program. Hazard ratios (HR) were estimated for demographic and treatment variables using Cox proportional-hazards models.
Key Findings
Among all survivors assessed, 42 survivors developed 42 subsequent malignant lung cancers (SIR 4.0, 95% CI 2.9-5.4), according to Ghosh. This included 25 carcinomas (15 adenocarcinomas, one small cell, one squamous cell), seven mesotheliomas, and 10 others. The researchers identified two additional benign neoplasms.
“The cumulative incidence was 0.18 percent for subsequent lung cancers at 30 years,” Ghosh said, noting that the median time from primary diagnosis was 28 years (range 11-46) and median age at diagnosis was 45 years (range 15-65).
The researchers reported that at the end of follow-up, 65.9 percent of survivors with lung cancer were deceased compared to 14.1 percent of those without lung cancer.
“A multivariable analysis was performed using only covariates which had a p-value of less than 0.2 on univariate analysis,” Ghosh explained. “The variables included were age at diagnosis, smoking history, cancer diagnosis, bleomycin exposure, and radiotherapy exposure by dose and field in the multivariable model.
“Significant associations were noted between lung cancer and older age at diagnosis, specifically those 15-21 (HR 10.5, 95% CI 1.4-76.4), and those with primary diagnoses of Hodgkin lymphoma (HR 8.7, 95% CI 1.1-66.0), neuroblastoma (HR 20.7, 95% CI 1.3-331.0), and bone cancer (HR 21.4, 95% CI 2.3-202.7).”
Ghosh noted that radiation was not significant in this model. “This is thought to be due to the co-linearity between diagnosis and radiation variables that are included in the model,” she said. “Nevertheless, when trend for subsequent lung cancer after radiation was assessed in this model, there was a clear dose-dependent effect for maximum chest radiation dose where, for each increase in dose group, there was an increase in the hazard ratios of 1.5.”
To further assess the risk for lung cancer after radiation exposure, the researchers performed a treatment model with fixed radiation exposure. This model also included, sex, age at diagnosis, chemotherapy exposure, and smoking history.
“Maximum chest radiation dose (HR 4.1, 95% CI 1.4-11.7, for 30-40 Gy; and HR 8.1, 95% CI 3.0-22.2, for > 40 Gy, relative to 0-10 Gy), but not sex, smoking status, or chemotherapy exposures, was associated with lung cancer,” the study authors wrote. “Notably, six survivors who developed lung cancer received no radiation and of these, five had a primary bone cancer.”
“In conclusion, survivors of childhood cancer are at increased risk for developing subsequent lung cancer,” noted Ghosh, during her presentation. “Risk factors include older age at diagnosis, primary diagnosis of Hodgkin lymphoma, and high doses of chest radiotherapy.
“To our knowledge, this is the first study to describe associations with neuroblastoma and bone cancer. These newer findings suggest there may be survivor subsets who are at inherent risk of developing subsequent lung cancer due to their own genetics,” she concluded. “Future studies are needed to further develop rationale for screening guidelines.”
Catlin Nalley is a contributing writer.