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Cancer Predisposition Screening Tool for Predicting Subsequent Malignancies in Childhood Cancer Survivors


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In a Canadian study reported in the Journal of Clinical Oncology, Cullinan et al found that the McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool provided predictive value for risk of subsequent malignant neoplasms in childhood cancer survivors beyond risk associated with treatment exposures.

Study Details

The MIPOGG tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome by guiding clinicians through yes or no questions that generate a recommendation for or against genetic evaluation. MIPOGG incorporates clinical, family history, and tumor-specific features of individual patients applied to tumor-specific algorithms. Each algorithm generates a recommendation for (output = yes) or against (output = no) genetic evaluation for an underlying cancer predisposition syndrome.

The study involved 13,367 childhood cancer survivors identified from the Ontario cancer registry who were diagnosed or treated for a primary malignancy before age 18 years between 1986 and 2015. Childhood cancer survivors who developed a subsequent malignant neoplasm (cases) were matched for primary cancer and year of diagnosis with childhood cancer survivors who did not develop a subsequent malignant neoplasm (controls) over the same period in a 1:5 ratio.

MIPOGG has additional value for subsequent malignant neoplasm prediction beyond treatment exposures and may be beneficial in decision-making for enhanced individualized subsequent malignant neoplasm surveillance strategies for childhood cancer survivors.
— Cullinan et al

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Key Findings

Among the 13,367 childhood cancer survivors, 317 (2.4%) developed a subsequent malignant neoplasm and were matched to 1,569 controls. A total of 298 (94%) of 317 cases and 1,457 (93%) of 1,569 controls had sufficient clinical data available to generate a MIPOGG output. Of these, 113 cases (38%) vs 421 controls (29%) were recommended for genetic evaluation by MIPOGG (P = .002).

On multivariate analysis, MIPOGG recommendation for genetic evaluation was significantly associated with an increased risk of subsequent malignant neoplasm after controlling for exposure to chemotherapy, hematopoietic stem cell transplantation (HSCT), and radiotherapy during primary cancer treatment (hazard ratio [HR] = 1.53, 95% confidence interval [CI] = 1.06–2.19).

Additional factors associated with an increased risk of subsequent malignant neoplasm on multivariate analysis were exposure to HSCT (HR = 1.83, 95% CI = 1.11–3.05), any exposure to radiation (HR = 2.12, 95% CI = 1.42–3.13), receipt of doxorubicin equivalent doses of ≥ 200 mg/m2 (HR = 1.85, 95% CI = 1.06­–3.24), and any exposure to epipodophyllotoxins (HR = 1.85, 95% CI = 1.15–2.98, for > 0 to ≤ 4,000 mg/m2; HR =  2.19, 95% CI = 1.07–4.46, for > 4,000 mg/m2) during primary cancer therapy.

MIPOGG showed more robust subsequent malignant neoplasm risk prediction in nonradiated patients relative to chemotherapy exposures. For example, a MIPOGG output of yes combined with a doxorubicin equivalent dose ≥ 200 mg/m2 and no radiation exposure was associated with a higher risk of subsequent malignant neoplasm vs MIPOGG output of no and similar treatment, with a hazard ratio of 4.01 (95% CI = 1.23–13.16). In contrast, for the same scenario, but with radiation exposure, the hazard ratio for subsequent malignant neoplasm was 1.24 (95% CI = 0.56–2.76).

In multivariate analysis across tumor types, MIPOGG output of yes vs no was associated with 2.9-fold greater risk of subsequent malignant neoplasm in patients with central nervous system tumors, 1.63-fold greater risk in those with solid tumors, and 1.26-fold greater risk in those with hematologic malignancies. 

The investigators concluded, “MIPOGG has additional value for subsequent malignant neoplasm prediction beyond treatment exposures and may be beneficial in decision-making for enhanced individualized subsequent malignant neoplasm surveillance strategies for childhood cancer survivors.”

Catherine Goudie, MD, of the Department of Pediatrics, Montreal Children’s Hospital, McGill University Health Centre, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by the Pediatric Oncology Group of Ontario Research Unit and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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