Tool May Predict Risk of Subsequent Malignancies in Childhood Cancer Survivors

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

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

The researchers explained that the tool, the McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG), “captures clinical, family history, and tumor-specific characteristics of each individual patient and inputs 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 for or against genetic evaluation of 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 for 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 old.

CCSs that developed secondary malignant neoplasms were compared with primary cancer and year of diagnosis with CCSs that did not develop subsequent cancers during the same period.

A total of 317 patients (2.4%) developed subsequent cancer and were compared with 1,569 controls. At the time of their first malignancy, the median age of the cases and controls was similar – 7.9 years and 7.6 years, respectively (P = 0.63).

The median age at the time of subsequent development of malignant neoplasm 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 malignancies 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 increased risk of subsequent malignancies 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-fold greater risk of developing a subsequent malignancy in patients with a CNS tumor as the primary malignancy, a 1.63-fold greater risk in patients with a primary solid tumor and a 1.26 times greater risk in patients with primary haematological malignancy.

The researchers concluded that the use of MIPOGG in CCSs as a surrogate for the risk of cancer predisposition syndrome has “added value” for predicting subsequent malignant neoplasms “on top of the ability to screen for cancer predisposition syndromes”.

“We recommend including MIPOGG in the assessment of pediatric oncology patients at diagnosis or at any time in survival rate follow-up to help prioritize patients for genetic evaluation and plan individualized SMN [subsequent malignant neoplasm] surveillance strategies, including in healthcare facilities where there is limited access to genetic testing.”

Disclosures: Some study authors stated that they have ties to biotech, pharmaceutical and/or device companies. See the original reference for a full list of disclosures.


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 Aug 12, 2021. doi:10.1200/JCO.21.00018

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