1. Conick, Hal

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Allen Ho, MD, noticed an increase in exotic types of thyroid cancer and wanted to dig deeper. The increase had put doctors in a conundrum, noted Ho, Director of the Head and Neck Cancer Program at Cedars-Sinai Medical Center. "The literature, the data, the prognosis, and the management of these rarer subtypes-they're not as robust as we would like."

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Ho and his fellow researchers looked at a cohort of data between the years 2000 and 2016 to see the growth of rare types of papillary thyroid carcinoma (PTC). The paper-titled Incidence and Mortality Risk Spectrum Across Aggressive Variants of Papillary Thyroid Carcinoma-was published in JAMA Oncology and found that the growth of aggressive papillary thyroid cancer variants outpaced the growth of well-differentiated types (2020; doi:10.1001/jamaoncol.2019.6851).


Not much is known about these rare subtypes of thyroid cancer, Ho said. One type-the diffuse sclerosing variant-has increased in incidence, he noted, but papers have gone back and forth for years on whether it's aggressive or indolent. "The rarer the disease, the less is known about it. And the less that can be extrapolated in larger scale studies."


That lack of knowing-in addition to the fact that most types of thyroid carcinoma are treated as an intermediate risk-led Ho and his fellow researchers to study the variance of thyroid cancers.


"We were clearly seeing different survival prognoses between [rare subtypes]," he stated. "And when we look at mortality risk and the risk of death, we found...that these patients had very different survival outcomes. However, because these subtypes are so rare, many guidelines just lump them all as one risk group."


Differences between the subtypes would mean that there's reason to stratify the study and treatment of differing types of papillary thyroid carcinoma, Ho explained. After digging in the data, the researchers found thousands of differences-different subtypes didn't fit on one curve, Ho noted, but a large variance.


"I think it surprised us in would expect to see what the guidelines suggest we would see, which is that there's one risk group and they all should have similar outcomes," Ho said. "But these are clearly morphologically distinct subtypes. And they turn out to have clinically different outcomes as well that match the different types. They're not all one in the same."


In all, the researchers found 5,447 aggressive variants of papillary thyroid carcinoma, according to the paper, with a substantial increase in the aggressive variant of this cancer.


"Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes," the researchers wrote in the paper's conclusion. "Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations."


Ho hopes that this study increases awareness that papillary thyroid carcinoma is not a binary disease, but one that has multiple layers. There are a range of types that vary in severity, he noted, and that means there should be a concerted effort to understand the exotic, aggressive subtypes. With better understanding, Ho believes that there can be better management, sub-stratification, and treatment of the disease.


The trend in treating thyroid cancer has been moving toward minimalist therapies, Ho said, but doctors who know that the patient whom they're treating has a more virulent subtype may want to instead increase treatment.


"Not all thyroid cancers are created equal," he stated. "We know that they don't all fit into the same bucket. Hopefully, we can stratify and tailor our treatment accordingly and recognize that some of these cancers can indeed be more aggressive, more lethal, and may be rising in incidence. The headlines often capture that thyroid cancer is a very common, well-behaved, and nonlethal disease. This [study] suggests that a subset of these cancers can be aggressive and can indeed be very dangerous."


As a next step from this study, Ho noted that researchers need to track the growing incidence of papillary thyroid cancers. "We note in the study that, while the relative incidence of aggressive cancers is rising, this comes just as the relative incidence of well-differentiated papillary thyroid cancers is starting to fall," he said. "That's an interesting reason to explore further."


Once the subtypes of thyroid cancer are better understood, Ho said that doctors could better tailor treatment for patients, potentially saving and extending lives. "That's one hope that comes out of the study."


Hal Conick is a contributing writer.


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