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Study Connects Lymphoma Stage at Diagnosis to Risk of Secondary Cancer


The findings have implications for survivorship care, as more patients are living longer due to the availability of immunotherapies.

Researchers from the University of Colorado Cancer Center have found that the stage of cancer when lymphoma is diagnosed can be a key factor in whether the patient later develops a secondary primary cancer.

Findings that appeared recently in the journal Cancer have important implications for survivorship care, as more and more patients who are diagnosed with diffuse large B-cell lymphoma (DLBCL) survive thanks to the arrival of modern immunotherapies.

“We have made tremendous progress in this field, and as a result, patients are living longer,” Manali Kamdar, MD, investigator at the University of Colorado Cancer Center and clinical director, Lymphoma Services at UCHealth University of Colorado Hospital, said in a statement. "Thus, survivorship has taken center stage in the management of these lymphomas. Given that these patients are at an increased risk of developing second primary cancers, our goal is to identify risk factors that can predict or mitigate this risk."

The study examines records from 26,038 patients over 18 years of age who were diagnosed with DLBCL from 1973 to 2010. The patients were categories as having either early-stage (stage I or II) or advanced (stage III or IV) disease. Differences in overall and location-specific secondary primary malignancies (SPMs) were assessed in 5-year intervals, according to the abstract.

“We’ve known that, genetically, early and late stage disease is different, and our hypothesis was that the type and timing of secondary primary cancers may thus be different as well,” Kamdar said.

Of the patients studied, 14,724 had early stage disease and 11,314 had advanced disease. Median follow-up was 13.3 years, and 13% of the patients developed an SPM. A higher but nonsignificant increased risk of SPM development occurred in those with early-stage disease compared with those with advanced disease (14% vs 11.6%, P = .14).

During the 5 years after diagnosis, the patients with early-stage DLBCL had a higher risk of SPM than those with advanced disease at diagnosis; the secondary cancers tended to be solid tumors, specifically colorectal, pancreas, breast, and prostate tumors. During the period 10 to 15 years after diagnosis, patients who had advanced disease had a higher risk of SPM than those with early-stage disease; these secondary cancers tended to be hematologic SPMs, such as leukemia.

“This is a first step toward identifying tools in survivorship clinics to better suveil survivors. It benefits patients because we may be able to better identify risk,” Kamdar said.

Low blood counts 10 years after treatment for late-stage DLBCL would set off alarms, given these findings, for example. And the results reinforce current recommendations for age-based screenings, including colonoscopies.

All patients who developed SPM were at higher risk of death, regardless of the stage of cancer at diagnosis.


Major A, Smith DE, Ghosh D, Rabinovitch R, Kamdar M. Risk and subtypes of secondary primary malignancies in diffuse large B-cell lymphoma survivors change over time based on stage at diagnosis [published online September 11, 2019]. Cancer 2019; doi:10.1002/cncr.32513.

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