Evaluating the Evidence SPECT/CT & Thyroid Cancer

The capability to obtain complementary functional and anatomic information through a single device during a single session makes SPECT/CT an attractive option for numerous applications. In recent years, researchers have shown that SPECT/CT significantly improved the interpretation of planar studies of patients with thyroid cancer in the post-therapy setting. SPECT/CT is now being incorporated in the diagnostic setting to help in the post-operative staging, risk stratification and management of thyroid cancer patients. But is the evidence sufficient to change practice?

In differentiated thyroid carcinoma, therapy usually begins with an initial partial, near-total or total thyroidectomy. Surgeons may choose to perform prophylactic or therapeutic neck compartment dissection as well. After surgery, the patient often is administered radioiodine therapy followed by I-131 scintigraphy to detect residual or metastatic disease.

But in thyroid cancer, evaluating the information on planar imaging is challenging. Scintigraphy scans lack anatomic landmarks, making it difficult to locate hot spots. Also, the physiologic uptake of radioiodine in saliva or organs such as the salivary glands or the liver that concentrate or secrete radioiodine may lead to false positives.

“Often, you see focal uptake [on planar images] and you can’t tell with certainty if, for instance, it’s a lymph node,” says Heiko Schöder, MD, clinical director of molecular imaging and therapy service at Memorial Sloan-Kettering Cancer Center in New York City. “Is it inside the liver or adjacent, or is it normal bowel activity? This has significant implications.”

Evaluating SPECT/CT, post-therapy

Reasoning that SPECT should improve the sensitivity of I-131 imaging, various researchers have been exploring the utility of SPECT/CT to determine whether a hybrid approach offers potential benefit in the post-therapy evaluation of patients with thyroid cancer.

In 2003, Yamamoto et al conducted a two-part study designed to validate an image fusion technique using SPECT and CT in 17 thyroid cancer patients and then demonstrated its clinical feasibility (J Nucl Med 2003;44:1905-1910). They found that I-131 SPECT/CT fusion imaging allowed researchers to precisely locate radioiodine uptake. Compared with a separate analysis using CT and scintigraphy alone, the information obtained from the fusion technique led to a change in the management of four patients and clarified scintigraphy findings in 11 other patients.

One year later, Tharp et al added to the evidence base using a sampling of 71 thyroid cancer patients. Researchers showed whole-body SPECT/CT had an incremental diagnostic value in 57 percent of patients (Eur J Med Mol Imaging 2004;31:1435-1442). SPECT/CT in the neck region had an incremental diagnostic value of 27 percent.

In thyroid cancer, the neck region is of particular interest after surgery. Surgeons often leave residual thyroid tissue to avoid complications such as damage to the laryngeal nerve or the parathyroid glands. Determining whether the cancer is still present in the remaining tissue and lymph nodes becomes important for staging the disease.

Post-surgery scintigraphy can be used for this purpose but provides poor anatomic information and is further limited by the high uptake of radioiodine in benign residual thyroid tissue at radioablation. In 2009, Daniela Schmidt, MD, of the nuclear medicine clinic at the University of Erlangen-Nurnberg in Erlangen, Germany, and colleagues wanted to compare the diagnostic value of SPECT/CT with planar scintigraphy for the staging of lymph nodes at radioablation to determine if SPECT/CT was more accurate.

“If you have iodine accumulation in the neck, you think maybe it could be in the thyroid remnant, but [instead it might be near] the thyroid remnant,” Schmidt says. “You need more anatomical information and this is given by the CT component of the SPECT/CT. You can see where the iodine focus is.”

Schmidt and colleagues took advantage of the clinic’s post-therapy protocol to perform SPECT/CT scans routinely on patients after their first radioablation. They identified 57 thyroid cancer patients who underwent whole-body planar scintigraphy and SPECT/CT of the neck (J Nucl Med 2009;50[1]:18-23). They reviewed the planar scans and SPECT/CT images independently from the clinical data and from each other for radioiodine uptake in the cervical nodes.

Planar imaging and SPECT/CT both identified 143 foci of radioiodine uptake in cervical nodes, but based on SPECT/CT, 28 foci in the original diagnosis were then revised. Six lesions evaluated as lymph node metastases on scintigraphy and 11 lesions considered to be indeterminate on scintigraphy were reclassified as benign on SPECT/CT. Beyond that, SPECT/CT allowed evaluators to identify 11 lymph node metastases that had been classified as thyroid remnant or indeterminate through planar scans.

SPECT/CT added information on the nodal stage in 35 percent of patients, Schmidt et al calculated, with two patients reclassified from no nodal involvement to NI (cancer present in nodes) and six patients reclassified from indeterminate to NI.

“We found that the information of the SPECT/CT helps to interpret the planar imaging better,” Schmidt says. They concluded that the use of SPECT/CT would have altered management of 25 percent of patients with thyroid cancer.

Risk & recurrence

Physicians use staging and risk stratification to determine the prognosis and management of a patient. The American Joint Committee on Cancer and the International Union Against Cancer developed a staging system that is based on information about the tumor, lymph node involvement and distant metastases to predict risk of death. In 2005, the American Thyroid Association revised its guidelines to include three levels of the risk of recurrence. To determine risk stratification scores, physicians assess information on distant metastases, resection of the tumor (complete or incomplete), invasion of the tumor to locoregional tissue or structures, aggressive histology or vascular invasion and uptake of I-131 outside the thyroid bed. Patients 45 years old and younger are considered lower risk than older patients.

Applying the new risk criteria system, Schöder and colleagues designed a retrospective comparison study to determine if post-therapy SPECT/CT modified risk of recurrence classification and changed the need for additional cross-sectional imaging (J Nucl Med 2010;51[9]:1361-1367). They performed planar imaging and SPECT/CT scans in 148 consecutive patients with thyroid cancer treated with I-131 between April 2006 and December 2007 at the cancer center. Patients were primarily intermediate to high risk; the hospital typically does not treat low-risk patients with I-131 after total thyroidectomy.

They found that characterization of radioiodine uptake in the neck was significantly better with SPECT/CT and characterization of uptake in the lung, liver and bone also was more accurate with SPECT/CT compared with planar imaging. They noted significantly more nodal metastases with SPECT/CT compared with planar imaging. Of 11 patients who had equivocal distant uptake on planar scans, nine were shown to be benign, one malignant and one remained equivocal on SPECT/CT.

Due to the improved accuracy, additional scans were avoided in 48 percent of patients. SPECT/CT significantly altered the estimates for risk of recurrence in 6.4 percent of patients. Applied to patient management, post-therapy I-131 SPECT/CT helped physicians determine the appropriate frequency and intensity of follow-up studies, the authors concluded.

“We use SPECT/CT routinely now in post-therapy scans,” says Schöder, adding that it streamlines patient management and avoids the need for additional scans.

Post-op opportunity

Given SPECT/CT’s superiority over planar imaging in the post-therapy setting, can it also provide useful information in the diagnostic setting, before I-131 therapy is administered? Anca M. Avram, MD, director of the nuclear endocrinology and radiotherapy section at the University of Michigan Medical Center in Ann Arbor, and colleagues proposed that the addition of SPECT/CT information to histopathologic data might further refine staging and risk stratification. That knowledge, in turn, might help inform post-operative therapy.

“Management decisions are based more on surgical pathology results that give you lots of information about the primary tumor but partial information about lymph nodes and no information about distant metastases,” Avram says.

In a retrospective study, Avram and colleagues demonstrated the feasibility of staging thyroid cancer before initiation of radioiodine therapy using I-131 scintigraphy with SPECT/CT (AJR 2010;195:730-736). A total of 48 patients underwent diagnostic I-131 planar imaging (37 MBq of I-131) and SPECT/CT. They were staged and scored based on three levels of sequential information: histopathological analysis and chest radiography data, planar images and SPECT/CT data. The patients were restaged based on findings on the I-131 scintigraphy (planar and then planar and SPECT/CT information).

Planar images detected previously unsuspected metastases in four patients, regional nodal metastases in four patients and clarified equivocal neck findings in 15 patients. The use of SPECT/CT changed the stage in 21 percent of the patients. Based on information from the diagnostic planar and SPECT/CT scans, the prescribed radioactivity was changed in 58 percent of the patients.

“Having an accurate diagnosis will lead to better treatment decisions,” Avram says. “It is essential to fully characterize the focal activity or unusual foci of radioactive iodine distribution in order to develop an accurate plan to manage the patient. SPECT/CT is very important in diagnosing, managing and deciding steps for treating the patient.”

Avram’s institution, which is a tertiary referral center, routinely has thyroid cancer patients undergo diagnostic I-131 scans after total thyroidectomy and before their first radioablation. Information from the scans complements the histopathological analysis and chest radiography data, which are all used to develop a management plan for the patient. The institution also uses the information to determine the prescribed dose.

“In the case of distant metastases, we also do a full body dosimetry calculation to be able to maximize the therapeutic dose,” she says. “With distant metastases the idea is to give them maximum tolerated dose to try to eliminate distant disease.”
Avram emphasizes that SPECT/CT adds information that better serves the patient. “The major impact is you will tell the patient where exactly he or she stands and have complete information on which to base a management decision,” she says.

Linking benefits & outcomes

While SPECT/CT in the diagnostic setting may add information that then allows a more targeted therapy, it is unknown if it changes survival. The incidence rate for thyroid cancer in the U.S. is 11.6 per 100,000 men and women per year, according the U.S. National Cancer Institute. In the U.S., the five-year survival rate for patients with localized, regional and distant thyroid cancer is 99.8 percent, 97 percent and 57.3 percent, respectively (CA Cancer J Clin 2012;62[2]:118-128). The prognosis is especially good for patients who are younger than 45 years old, which is reflected in staging and risk stratification systems.

“The argument that nodal metastases do not have a major impact on the survival of thyroid cancer patients should be balanced by the fact that the discovery of regional metastases on post-operative diagnostic 131-I scans impacts treatment decisions—radioiodine therapy for elimination of small metastatic foci or surgical re-intervention for resection of bulky residual metastases—which can decrease the risk of recurrence,” Avram says.

Avram and colleagues observed that the restaging in their study led to both increases and decreases in prescribed doses. Patients accurately identified as low risk might avoid unnecessary exposure to radiation, a concern for younger patients.

The relatively low incidence rate for differentiated thyroid carcinoma and the fact that it is a slow-growing cancer make linking practice to long-term outcomes challenging. “For recurrence, the problem is there is not enough [follow-up] time,” Schmidt says. “Recurrence can come in two or 10 years.”

A study comparing the effectiveness of different imaging modalities would require a 30-year follow-up, according to Avram. While a resource similar to the National Oncology PET Registry likely would shed light on the issue, building and maintaining a SPECT/CT database would take money and time, Schöder says.  

Nonetheless, SPECT/CT is making inroads. Schöder notes that the trend at large institutions is to swap out planar nuclear medicine cameras with SPECT/CT. Marketing analysts at Frost & Sullivan observed a similar pattern in 2011 in its “Emerging Technology Developments in Hybrid Imaging,” report, which found the increasing use of SPECT/CT was beginning to dampen sales of standalone CT systems.

And the use of SPECT/CT also impacts some practices. SPECT/CT is used routinely in thyroid cancer imaging at all three researchers’ institutions, be it before the first radioiodine therapy at the University of Michigan Medical Center or in the post-therapy setting at Memorial Sloan-Kettering and University of Erlangen-Nurnberg. The addition of SPECT/CT has yet to be recommended in guidelines, but Schöder says evidence is accumulating in its favor.

“The guidelines are quite conservative,” he says. “They [guideline committee members] want to see sufficient amount of evidence before they put anything in the guidelines. However, several groups are now collecting such evidence, and the benefit eventually will be clear.”