Trimodal Therapy Best for Operable Anaplastic Thyroid Cancer

Veronica Hackethal, MD

May 15, 2017

Patients with operable anaplastic thyroid cancer have improved overall survival when treated with an aggressive trimodal approach using a combination of surgery followed by radiation and radio-sensitizing chemotherapy, according to a new study published in the May issue of Thyroid.

In the study, patients who received trimodal therapy had significantly longer overall survival (median, 22.1 months), compared with radiation and chemotherapy without surgery (median 6.5 months; HR, 0.2; P = .0008).

The results support current guideline recommendations and confirm findings from past studies that aggressive trimodal therapy is the best approach for patients with resectable anaplastic thyroid cancer.

A key point is that the study included only patients with complete resections or those for whom surgery reduced their cancer to microscopic disease. It did not include patients for whom surgery left behind gross disease.

And this underscores the importance of a complete surgical resection in prolonging survival, stresses senior author Maria Cabanillas, MD, of the University of Texas MD Anderson Cancer Center, Houston.

"If you can get a good surgery on these patients, they have better survival and better locoregional control," she told Medscape Medical News.

"Early referral to determine whether patients can have a resection is critical because it really can extend overall survival," she added.

Anaplastic Thyroid Cancer Is Extremely Lethal; Refer to Expert Center

Anaplastic thyroid cancer is one of the most lethal forms of cancer, with a median overall survival of only 3 to 5 months. Almost all patients have stage IV disease at diagnosis, and only about 20% remain alive at 1 year. (In this study, median overall survival was 11.9 months, and 39% of participants were alive at 1 year.)

Patients with advanced-stage, inoperable tumors are often referred straight to palliative care, but Dr Cabanillas thinks these patients should also be evaluated for whether they can go on therapy.

So referral to centers with expertise in this form of cancer is imperative, she reiterates.

"Patients who might be marginally operable also need early referral to institutions with expertise. They need a higher level of care that usually cannot be provided in smaller hospitals," she added.

And patients with good performance status should also be considered for inclusion in clinical trials.

Dr Cabanillas suggests physicians reach out to centers with expertise for help in managing these patients, although there is the problem that there are only a few centers with sufficient experience managing this type of cancer and that are running clinical trials, she noted.

Surgeons Thought Most Were Undifferentiated Thyroid Cancers

The retrospective study included patients with pathologically confirmed anaplastic thyroid cancer who received care at MD Anderson Cancer Center between January 2013 and October 2015.

Of 54 patients included in the study, initial treatment was surgery in 23 patients, radiation with or without radio-sensitizing chemotherapy in 29 patients, and systemic chemotherapy alone in two.

Interestingly, "the overwhelming majority of patients who had surgeries were not known to have anaplastic thyroid cancer prior to their operation — known as "incidental [anaplastic thyroid cancer] phenomenon" — suggesting that surgeons were more willing to undertake a complicated surgery because the [original] diagnosis was of a more differentiated thyroid cancer," note the authors.

Nineteen overall had trimodal therapy with complete surgical resection followed by radiation and radio-sensitizing chemotherapy. Patients' median age was 63, 54% were women, and 78% were non-Hispanic white. Half had stage IVc disease (distant metastases) at diagnosis.

Results showed that patients with stage IVa disease (confined to the neck and considered resectable) had the longest time to treatment failure (median, 8.5 months). Those with stage IVc disease (distant metastases and not resectable) had a much shorter time to treatment failure (median 3.8 months).

Opportunity to Move Toward Adjuvant, Neoadjuvant Therapy?

This short time to treatment failure for those with distant metastatic disease highlights a potential opportunity for improved outcomes, which could perhaps be achieved with earlier initiation of systemic therapy, including adjuvant or neoadjuvant therapy, say the researchers.

And "we still need to do a lot of work in patients who are not resectable," noted Dr Cabanillas, "because the truth is most patients are not resectable."

This study is also the first to include genetic testing to evaluate the influence of certain mutations on survival and time to treatment failure in anaplastic thyroid cancer.

The results showed a nonsignificant trend toward shorter time to treatment failure for patients with TP53 mutations. Such patients may need closer follow-up, because they may be more likely to fail early, Dr Cabanillas explained.

Dr Cabanillas reports research funding from Roche and Eisai. The coauthors report no relevant financial relationships.

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Thyroid. 2017;27:672-681. Article


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