Young cancer survivors have increased risk of gastrointestinal polyposis

Last Updated: 2020-02-21

By Reuters Staff

NEW YORK (Reuters Health) - Survivors of childhood and young-adulthood cancer (CYAC) without known causative germline alterations or hereditary colorectal cancer predisposition syndrome can develop gastrointestinal polyposis presumably related to their cancer therapy, researchers report.

CYAC survivors face an increased risk for a variety of neoplastic and non-neoplastic adverse effects years after their original treatment, including colorectal adenomas and colorectal cancer. Previous reports have described eight cases of therapy-associated polyposis (TAP) that lacked identifiable germline variants in the high-risk polyposis genes adenomatous polyposis coli (APC) and MutY homolog (MUTYH).

Dr. Matthew B. Yurgelun of Dana-Farber Cancer Institute, in Boston, and colleagues further characterize the phenotypic spectrum of TAP in their report in Cancer Prevention Research.

They identified 34 TAP patients from eight institutions. The median age at the time of the original CYAC diagnosis was 18 years, and their gastrointestinal polyposis was first detected at a median age of 49 years and at a median of 27 years after their initial CYAC treatment.

Treatment for their initial cancer included alkylating chemotherapy (59%), abdominopelvic radiotherapy (62%), or both (35%).

A quarter of patients who received abdominopelvic radiotherapy and 30% of those who did not receive such radiotherapy had polyps detected prior to the age they would have been recommended to start colonoscopy screening by Children's Oncology Group (COG) guidelines.

Moreover, three of the nine patients who developed colorectal cancer and had known radiotherapy exposure were diagnosed prior to the recommended age to start colonoscopy screening.

Three-quarters of patients who underwent esophagogastroduodenoscopy (EGD) (19/23, 74%) also had upper gastrointestinal-polyp findings.

None of the 32 cases that had prior germline genetic testing had pathogenic or likely-pathogenic variants in any tested gene. Only one case had a first- or second-degree relatives with colorectal cancer diagnosed prior to age 50, and only two cases had a single first-degree relative with a reported history of 10 or more colorectal polyps.

In contrast, 25 of the 34 cases (74%) had clinical features suggesting an inherited gastrointestinal cancer syndrome.

"TAP appears to be an acquired phenomenon that may mimic biologically distinct forms of inherited colorectal cancer predisposition syndromes; this raises the potential for misdiagnosis, with concomitant implications for both patient- and family-specific cancer screening recommendations," the authors note.

Overall, 10 cases were diagnosed with colorectal cancer, seven with stage 0/I, one each with stage IIa and stage IIIa and one with unknown stage.

Seven cases underwent some degree of colorectal surgical resection for colorectal cancer, and seven more underwent resection for the management of polyposis.

The authors propose "that COG guidelines be expanded to include individuals who received chemotherapy (without abdominopelvic radiation), and that initiation of screening begin at age 35 or 10 years after age of chemotherapy, whichever occurs first. With these guidelines, none of the patients in this cohort would have been missed."

"Additionally," they write, "COG guidelines do not currently address upper gastrointestinal tract screening among CYAC survivors. Given that almost a third of TAP cases who underwent EGD screening had polyps in the stomach or duodenum, we would propose consideration of at least a baseline EGD at the age when colorectal polyposis is first identified."

"Further work is needed to better understand the underlying mechanisms for polyposis development, as this may in turn inform management of TAP and other treatment-related sequelae," the authors conclude.

Dr. Yurgelun did not respond to a request for comments.

SOURCE: https://bit.ly/2T733bs Cancer Prevention Research, online February 12, 2020.