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Younger Cancer Survivors at Risk for Polyposis

Younger Cancer Survivors at Risk for Polyposis


Undergoing cancer treatment at a younger age can put the survivors at risk of developing numerous gastrointestinal polyps, even if they do not have hereditary susceptibility to polyposis.

The acquired condition, therapy-associated polyposis (TAP), has only recently been discovered. Before the current study, TAP had been reported in only eight patients in the medical literature.

More details from another 34 patients are now described in an article published online February 12 in Cancer Prevention Research.

It reports that these patients with TAP had a median of 32 colorectal polyps, although some patients were found to have more than 50.

Polyposis is a known risk factor for gastrointestinal cancers, note the authors. From this series of 34 patients with TAP, nine patients developed colorectal cancer.

“It is well established that prior exposure to radiation and/or chemotherapy in childhood and young adult cancer (CYAC) survivors is associated with a broad range of late organ effects,” write the authors, led by Leah Biller, MD, Dana-Farber Cancer Institute, Boston, Massachusetts.

“This series demonstrates that TAP should be considered in patients with significant polyposis, no known pathologic germline variant and/or family history of gastrointestinal neoplasia, and a history of prior CYAC treatment,” they add.

Important Implications

Recognition of a nonhereditary form of polyposis has important implications for the diagnosis of patients and the subsequent management of family members, say the authors.

“Providers may not be aware that polyposis even exists as an acquired phenomenon — it is traditionally presumed to be hereditary, with inherited syndromes such as familial adenomatous polyposis,” Biller explained to Medscape Medical News in an email.

Patients who are diagnosed with polyposis, as well as their relatives, are typically advised to undergo increased screening with colonoscopy. Knowing that TAP is not a familial syndrome means that physicians can spare family members unnecessary colonoscopies.

Biller also suggested that physicians consider TAP for cancer survivors who have unexplained polyposis.

“We also think it would be reasonable to consider starting colonoscopies in survivors treated with prior chemotherapy and/or radiation at age 35 or 10 years after receiving treatment ― whichever occurs first,” Biller noted.

In addition, given that TAP patients may also have a predisposition for upper gastrointestinal polyps, “it would also be reasonable to consider at least a baseline esophagogastroduodenoscopy (EGD) in these patients,” she added.

Investigators also recommended that providers have a low threshold for recommending colonoscopy to any cancer survivor who is symptomatic with abdominal pain or bleeding, regardless of age, given the overall increased risk for polyps and CRC in these patients.

Cases Identified From Eight Registries

The team identified TAP cases from registries at eight cancer genetics programs.

“Each TAP case was assessed for clinical features of inherited CRC (colorectal cancer) predisposition syndromes, even though none of the cases…had a known personal diagnosis of any genetically defined syndrome,” the investigators explain.

For their analysis, polyposis was defined as a cumulative lifetime incidence of 10 or more gastrointestinal polyps of any type that occurred anywhere along the gastrointestinal tract.

The investigators included patients who had been diagnosed with cancer at age 30 years or younger or who had been diagnosed with CYAC between the ages of 31 and 45 if their first polyp was identified 10 years or more after their initial treatment.

From the eight cancer registries, 34 patients with TAP were identified. Of these, 28 had been previously treated for Hodgkin lymphoma, three for neuroblastoma, and one each for acute myeloid leukemia, medulloblastoma, nephroblastoma, and non-Hodgkin lymphoma.

Some 59% of patients had received an alkylating agent as their initial treatment; 62% had received abdominoplevic radiation; and 35% had received both.

The median age at which gastrointestinal polyposis was first detected was 49 years; the median time after initial cancer treatment was 27 years, the team notes.

For 24% of patients who received prior abdominopelvic radiotherapy, polyps were detected at a younger age than the age at which it is recommended that colonoscopy screening begin, the authors point out.

Current guidelines from the Children’s Oncology Group (COG) recommend initiation of colonoscopy for CYAC survivors who undergo abdominopelvic radiotherapy either at age 30 years or 5 years after they receive radiotherapy, whichever occurs later. Colonoscopy should then be repeated every 5 years.

It is currently recommended that for CYAC survivors, colonoscopy be initiated at age 45 years. For 30% of TAP patients who did not receive abdominopelvic radiotherapy, a polyp was detected at a younger age than 45.

For children and young adults who do not undergo abdominopelvic radiotherapy, COG guidelines recommend that screening colonoscopy begin at the age of 45. Colonoscopy should then be repeated every 10 years.

In the current analysis, nine patients who developed CRC had previously undergone radiotherapy. In this small group of patients, a third were diagnosed prior to the age at which current guidelines recommend that patients start screening colonoscopy.

Colorectal Polyps

“All TAP cases had colorectal polyps, with a median lifetime aggregate of 32 polyps,” the investigators report. More than two thirds of the group had a lifetime aggregate of 20 or more colorectal polyps; 35% of patients had 50 or more colorectal polyps, they add.

Some 30% of patients known to have undergone EGD had gastric or duodenal polyps or both. When fundic gland polyps were included in the analysis, almost three quarters of patients who underwent EGD were found to also have upper gastrointestinal polyps.

Almost all patients (94%) had more than one histologic type of colorectal polyp, the researchers note. This is in contrast to persons with hereditary polyposis syndromes; in those patients, all the polyps are generally of the same type.

Moreover, almost three quarters of patients with TAP displayed clinical features that were suggestive of one or more CRC predisposition syndromes.

“TAP appears to be an acquired condition that imitates various familial colorectal cancer syndromes but is biologically distinct from them,” senior author Matthew Yurgelun, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, said in a statement.

“The fact that it takes different forms and involves different types of polyps suggests that there may be multiple biological pathways involved in its development,” he added.

Biller and Yurgelun have disclosed no relevant financial relationships.

Cancer Prev Res. Published online February 12, 2020.

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