Aggressive Approach to Anaplastic Thyroid Cancer Shows Benefit

Nancy A Melville

October 20, 2015

ORLANDO, Florida — Survival rates of the rare anaplastic thyroid carcinoma, which has a very poor prognosis, show significant improvement when patients are treated with an aggressive combined-modality therapy, although the toxicities associated with such therapies can take their toll, according to research describing experience with the approach at the Mayo Clinic, in Rochester, Minnesota.

"Aggressive, combined-modality therapy appears to be associated with improved overall survival in anaplastic thyroid carcinoma, especially among patients with lower-stage disease," coauthor Keith C Bible, MD, PhD, chair of the endocrine malignancies disease-oriented group with the Mayo Clinic Cancer Center, told Medscape Medical News.

"This apparently improved longer-term survival, however, comes at the cost of heightened therapy-related toxicities that may or may not make an aggressive approach acceptable to individual patients," he added.

Median overall survival rates of anaplastic thyroid carcinoma are only approximately 5 months, and 1-year survival rates are less than 20%. Fifty-year data from the Mayo Clinic on 134 cases from 1949 to 1999 showed even poorer outcomes, with median survival of only 3 months and only a 9.7% chance of survival beyond 1 year.

But in a previous pilot study, Dr Bible and colleagues showed exceptionally improved overall survival of 60 months in patients with locoregionally confined disease who were treated with the aggressive approach. The 1- and 2-year Kaplan Meier overall survival in the pilot series was 70% and 60%, respectively.

The multimodal approach involves surgery, chemotherapy, and , and individualized intensity-modulated radiation therapy (IMRT) and radio sensitizing, in which radiation is tailored according to the size, shape and location of the tumor and the amount of radiation is minimized to surrounding structures.

While the approach is highly intensive, it is also highly toxic, but with such a poor prognosis with anaplastic thyroid carcinoma, patients often opt for the treatment nonetheless.

"Many, but not all, patients prioritize longevity over toxic effects, hoping that they will tolerate therapy well and also gain benefit," Dr Bible said.

Asked to comment, session moderator Duncan J Topliss, MD, of Monash University, Melbourne, Australia, said: "Anaplastic thyroid carcinoma has a very poor prognosis, as the authors cite. Thus, a regimen that improves survival from these very grim figures is important to examine.

"Many studies report improved survival with surgery and radiotherapy with/without chemotherapy," he added. "This abstract reports an apparent good response similar to some other reports."

Treating Aggressively Lessens Severity of Recurring Disease

An updated report on an expanded series of 29 anaplastic thyroid carcinoma patients treated with the aggressive approach was presented here at the 2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association (ITC/ATA).

The patients, who had a median age of 60, had a median Kaplan Meier overall survival of 22.4 months. Their 1-year overall survival was 61%, 3-year survival was 48%, and 5-year survival was 43%.

Ten patients (34%) were still alive at a median follow-up of 24.5 months (range, 6.8 months to 8.5 years). Among patients who died, 74% (14 patients) had distant metastases or distant as well as locoregional disease (10%, two patients).

Anaplastic thyroid carcinoma is, by nature, indicative of stage IV disease. At the time of diagnosis, two of the patients were stage IVa (7%), representing intrathyroidal disease, 20 were stage IVb (69%), with gross extrathyroidal disease but no distant metastases, and seven were stage IVc (24%), indicative of distant metastases.

Most (93%) had surgery, with R0 (no residual tumor) achieved in 24% of patients and R1 (microscopic residual tumor) resection achieved in 52%.

The patients were all treated with chemotherapy, including 24 (83%) with taxanes and 19 (66%) with docetaxel/doxorubicin, which is the center's standard of care if patients are able to tolerate the treatment.

The patients all also received definitive-intention locoregional radiation (median, 66 Gy; range, 46–70 Gy; median fractions, 33). Among them, 24 (83%) completed the treatment, while five (17%) did not complete due either to toxicity (four) or death (one).

There were no significant differences in patient overall survival according to factors including cancer stage, the extent of surgery, or age above or below 60.

Notably, the aggressive approach appears to have a benefit of lessening the severity of recurrent disease in some patients, Dr Bible noted.

"We have been struck that recurrent disease in patients treated with this aggressive approach is sometimes of lesser aggressiveness and more indolent than their presenting disease, thereby allowing for the application of additional salvage approaches to address disease recurrences."

Fact That Study Is Small Doesn't Diminish Findings

The differences in survival rates between the first and second reported series likely underscore the effect of different cancer stages, Dr Bible noted.

"This approach was elected initially because we were wishing to optimize the chances that improved outcomes might be observed, thinking that IVc patients were likely to have such poor survival as to make such aggressive interventions of less likely benefit," he explained.

But with the encouraging preliminary results in the initial IVa and IVb population, the authors in their next series included patients also with IVc disease and those who were less robust, likely explaining the different pooled outcomes.

"In our experience, IVa patients do better than IVb patients, who do better than those in IVc. Our update is thus entirely consistent with our prior report on a stage-adjusted basis," he observed.

Despite the study's small size, the findings are nevertheless valuable, Dr Topliss commented to Medscape Medical News.

"Yes, the study is small, but in anaplastic thyroid carcinoma this study is not so small," he said. "It is difficult even in large centers to collect substantial case series."

"The size of the study does mean that differences in the patient population compared with other studies may occur and lead to apparently different results — for example, if by chance a study was made up of younger patients with smaller tumors."

The findings in general are consistent with other studies reporting on outcomes of a multimodal approach to anaplastic thyroid carcinoma, he concluded.

Dr Bible, the coauthors, and Dr Topliss had no relevant financial relationships.

2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association; Orlando, Florida. Abstract 72, presented October 20, 2015.


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