New research suggests a tool can identify childhood cancer survivors (CCSs) who have underlying cancer predisposition syndromes that increase their risk of subsequent malignant neoplasms beyond the risk conferred by anticancer treatment.

The tool, described in the Journal of Clinical Oncology, proved most effective in survivors of solid tumors or central nervous system (CNS) tumors and in CCSs who were not irradiated during treatment of their primary malignancy.

The researchers explained that the tool, the McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG), “incorporates clinical, family history, and tumor-specific features of each individual patient, inputting them into a tumor-specific algorithm.”


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MIPOGG identifies children with a genetic predisposition to cancer by guiding clinicians through a series of “yes” or “no” questions that generate a recommendation either for or against genetic evaluation for an underlying cancer predisposition syndrome.

In a population-based, nested case-control study, researchers sought to determine whether MIPOGG could help predict which CCSs are at risk of developing subsequent cancers.

Using a provincial cancer registry, the researchers identified 13,367 CCSs who were diagnosed and/or treated for a primary malignancy between 1986 and 2015, before they were 18 years of age.

CCSs who developed secondary malignant neoplasms were matched by primary cancer and year of diagnosis with CCSs who did not develop subsequent cancers over the same period.

In all, 317 patients (2.4%) developed subsequent cancer and were matched to 1,569 controls. At the time of their first malignancy, the median age of cases and controls was similar — 7.9 years and 7.6 years, respectively (P =.63).

The median age at the time of subsequent malignant neoplasm development was 18.3 years. The median follow-up was 17.1 years for cases and 16.0 years for controls.

In a multivariable model, a MIPOGG output recommending genetic evaluation was significantly associated with an increased risk of developing subsequent malignancy after the researchers controlled for exposure to chemotherapy, hematopoietic stem cell transplant (HSCT), and radiation during primary cancer therapy (hazard ratio, 1.53; 95% CI, 1.06-2.19).

There was a statistically significant correlation between an elevated risk for subsequent malignancy and exposure to HSCT, radiation, epipodophyllotoxins, and doxorubicin at doses of at least 200 mg/m2 during primary cancer therapy.  

A MIPOGG output recommending genetic evaluation was associated with a 2.9 times greater risk of developing subsequent malignancy in patients with a CNS tumor as their primary malignancy, a 1.63 times greater risk in patients with a primary solid tumor, and a 1.26 times greater risk in patients with a primary hematologic malignancy.

The researchers concluded that using MIPOGG in CCSs as a surrogate for cancer predisposition syndrome risk “has additional value” for predicting subsequent malignant neoplasms “over and above” its ability to screen for cancer predisposition syndromes.

“We recommend the incorporation of MIPOGG in the assessment of pediatric oncology patients at diagnosis or at any time in survivorship follow-up to assist in prioritizing patients for genetic evaluation and in planning individualized SMN [subsequent malignant neoplasm] surveillance strategies, including in health care settings where there is limited access to genetic testing.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Cullinan N, Schiller I, Di Giuseppe G, et al. Utility of a cancer predisposition screening tool for predicting subsequent malignant neoplasms in childhood cancer survivors. J Clin Oncol. Published online August 12, 2021. doi:10.1200/JCO.21.00018