Fresh Focus on Second Primary Cancers

Tony Hagen @oncobiz
Published: Thursday, Apr 05, 2018
Sudipto Mukherjee, MD, MPH
Sudipto Mukherjee, MD, MPH
When investigators looked at roughly 150,000 cases of well-differentiated thyroid cancer (WDTC) using the SEER database of the National Cancer Institute, they knew that the use of radioactive iodine (RAI) in conjunction with surgery and other treatments for thyroid cancer had increased dramatically over the years. This was concerning because RAI is a risk factor in second hematologic malignancies (SHMs), and its use is largely unnecessary in many cases of low-risk WDTC, according to Sudipto Mukherjee, MD, MPH, an associate staff member of the Department of Hematology and Oncology at Cleveland Clinic in Ohio.1 Mukherjee and colleagues sought to determine whether oncologists and hematologists were overtreating with RAI in cases of WDTC, and thus putting their patients at risk for SHMs. The answer was a disheartening “yes.“

Of the 148,215 patients with WDTC, 53% received surgery and 47% received RAI. The RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; HR, 1.79; 95% CI, 1.13-2.82; P = .01) and chronic myeloid leukemia (CML; HR, 3.44; 95% CI, 1.87- 6.36; P <.001). The increased risk of AML and CML after RAI was seen even in the aftermath of low- and intermediate-risk WDTC tumors, which Mukherjee said would not have been the case had RAI been avoided as a treatment option.

“What we have noticed is that there has been a signal of increased second cancers in these patients. Most of them have involved solid tumors, a few have been hematologic malignancies, and in the recognition of these second cancers occurring as a late complication, the American Thyroid Association guidelines have started to emphasize a clinical and judicious application of RAI on a case-by-case basis,” said Mukherjee in an interview with OncologyLive®. The numbers already give hope that clinical practices are changing toward conservative use of RAI, he explained, noting that although use of RAI rose from 6% of cases in 1973 to 50% in 2006, it had declined to 41% by 2014.

For Mukherjee and his fellow investigators, it was important to gain greater insight into the use of RAI and its implications for a broad spectrum of SHMs. Second cancers that result from initial cancer therapy or are caused by other factors are a growing concern, given that cancer survivors are living longer, which makes it important to think about the longer-term consequences of anticancer therapy options. In addition, having individualized survivorship care plans and communicating adequately with patients, primary care providers, and primary care nurse practitioners are vital to ensuring appropriate follow-up care years after an experience of treatment for cancer, said providers interviewed for this article.

“It is projected that by 2020, there will be almost 18 million long-term cancer survivors, and out of that we are expecting probably more than a half a million long-term thyroid cancer survivors,” Mukherjee said. “A substantial majority—probably two-thirds—would have been exposed to RAI, and thus are at risk of AML and CML. That’s a large population who are at risk.”

Concerns about second primary malignancies (SPMs) in patients who have been treated successfully for thyroid cancer are reflected in similar trends in other tumor types. In an analysis of the cancer profiles of patients in SEER registries published in JAMA Oncology in November, investigators found that 18.4% of the 765,843 cancers diagnosed in the study population—or 141,021 malignancies—represented a second order or higher primary cancer.2

Broadly speaking, the National Cancer Institute defines an SPM as a new cancer occurring in a patient with a previous diagnosis of cancer (as opposed to a metastasis). Although the precise reasons for the development of these cancers are not fully understand, investigators have identified 3 major areas of risk: treatment-related causes; genetic susceptibility; and lifestyle, environmental, or medical history factors.3

Thyroid Cancer Example

Although thyroid cancers are a fraction of the new malignancies diagnosed annually in the United States, the link between second cancers and prior therapy is a striking example of the implications of prior therapy and the need for early intervention in cases of secondary cancer.


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