Significant increases seen in neuroendocrine tumors, survival

Reuters Health Information: Significant increases seen in neuroendocrine tumors, survival

Significant increases seen in neuroendocrine tumors, survival

Last Updated: 2017-05-01

By Marilynn Larkin

NEW YORK (Reuters Health) - Neuroendocrine tumors (NETs) are on the rise, but survival is improving as well, researchers in Texas say.

Dr. Arvind Dasari told Reuters Health that the annual incidence of NETs has increased “nearly seven-fold” since 1973, “making this tumor type the most commonly prevalent gastrointestinal malignancy, second only to colorectal cancer.”

Improvements in survival have been significant, however, “especially so for distant-stage gastrointestinal and pancreatic NETs, probably reflecting improvement in systemic therapies,” he said by email.

Although the findings “were somewhat expected,” he added, “the magnitude of change in incidence, prevalence and improvements in survival were surprising.”

As reported in JAMA Oncology, online April 27, Dr. Dasari of the University of Texas MD Anderson Cancer Center in Houston and colleagues analyzed SEER data from 1973 to 2012 on 64,971 patients diagnosed with NETs, about half of whom were women.

The age-adjusted incidence rate climbed 6.4-fold from 1973 (1.09 per 100,000) to 2012 (6.98 per 100,000) across all sites, stages, and grades.

In the SEER 18 database, covering 2000 to 2012, the highest incidence rates per 100,000 were 3.56 in gastroenteropancreatic sites, 1.49 in the lung, and 0.84 in NETs with an unknown primary site.

Rates rose most dramatically, the authors said, in patients over age 65, climbing more than eight-fold to 25.3 per 100,000, and in those ages 50 to 64, climbing to 14.3 per 100,000.

A three-fold rise to 1.75 per 100,000 was seen in those under age 50, and the annual percentage change for age-adjusted incidence from 2000 to 2012 was 3.2 per 100,000 individuals (P<0.001).

The median five-year overall survival rate varied significantly by stage, grade, age at diagnosis, primary site and time period of diagnosis.

After adjustment, overall survival was worse in regional NETs (hazard ratio, 1.73) and distant NETs (HR, 5.05) compared with localized NETs.

Compared to patients with NETs in the lung, those with NETs in the liver had the worst overall survival (HR, 1.85), followed by NETs in the stomach (HR, 1.20).

The overall survival rate for all NETs improved from 2000-2004 to 2009-2012 (HR, 0.79). Larger increases between these periods were seen in distant-stage gastrointestinal NETs (HR, 0.71) and distant-stage pancreatic NETs (HR, 0.56).

Dr. Dasari said, “The rise in prevalence is probably largely due to increased incidence of early stage, indolent tumors and to a lesser extent, improvements in imaging such as octreoscans and systemic therapies such as somatostatin analogues (which improve) survival for patients with advanced disease.”

“These data clearly show that NETs are no longer rare and in fact pose an important health care problem,” he affirmed. Therefore, “several questions need to be urgently answered.” These include:

- How to manage early stage NETs. “Whether all tumors need to be surgically removed irrespective of site/size/grade and other biological factors is unknown, especially in patients with competing co-morbidities,” Dr. Dasari noted.

- What risk factors are associated with recurrence after curative surgery and what are appropriate surveillance practices to detect such recurrences?

- What to do in the face of the “very sharp” rise in lung NETs, when there is only one FDA-approved drug to treat this subset of patients.

In addition, “In contrast to well differentiated NETs, poorly differentiated neuroendocrine carcinomas have dismal outcomes - and these patients desperately need novel therapies to improve survival,” Dr. Dasari concluded.

Editorialist Dr. Pamela Kunz of Stanford University School of Medicine in Palo Alto, California told Reuters Health, “The data . . . are quite striking, though it’s not the first time we learned of increasing incidence and high prevalence in NETs.”

“In fact,” she said by email, “the first large SEER-based epidemiologic study of NETs was conducted by the same research team at MD Anderson and published in 2008.” (http://bit.ly/2p1BKPt)

“At that time, NETs were infrequently the subject of clinical research and had few approved therapies,” she observed. “Perhaps a lack of awareness contributed to these trends going relatively unnoticed.”

Since then, “there has been exponential growth in the clinical and basic research of NETs,” she continued. “The NET research community is now better equipped to respond in full force - hopefully with more (and smarter) clinical trials, improved diagnostics, and NET-focused education for providers.”

“Given that NETs now represent a larger pubic health problem than previously recognized,” Dr. Kunz said, “I would especially like to see studies focused on economic burden, cost of therapies and comparative effectiveness.”

The study was funded by Novartis. Dr. Dasari and three coauthors have received fees from the company, as has Dr. Kunz.

SOURCE: http://bit.ly/2p1C5Sf and http://bit.ly/2oQjmNf

JAMA Oncol 2017.

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