|Year : 2020 | Volume
| Issue : 4 | Page : 206-212
Incremental value of post-high dose therapy I-131 scan over pre.therapy diagnostic I-131 scan in patients with differentiated thyroid cancer: Experience from a tertiary care centre in South India
Chandra Teja Reddy Singareddy1, Ranadheer Gupta Manthri1, VS Krishnamohan1, KB Sricharan1, Tekchand Kalawat1, Narendra Hulikal2
1 Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India
2 Department of Surgical Oncology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India
|Date of Submission||04-Dec-2019|
|Date of Decision||05-Jun-2020|
|Date of Acceptance||14-Jul-2020|
|Date of Web Publication||5-Jan-2021|
Professor and Head, Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Objective: Objective of this study is to establish the incremental value of post-high dose therapy I-131 whole body scintigraphy (WBS) over diagnostic pre-therapy I-131 WBS in the detection of radioiodine avid foci, staging and change in the management in patients with differentiated thyroid carcinoma post-total thyroidectomy.
Methods: We retrospectively studied 93 post-total thyroidectomy patients with well differentiated thyroid cancer (mean age 47 [range 18–78] years; 72 females) who underwent diagnostic dose pre-therapy? I-131 WBS and post-high dose therapy? I-131 WBS from January 2017 to June 2018 were included. Discordance rate of pre-therapy? I-131 WBS findings with post-therapy? I-131 WBS was calculated.
Results: Post-therapy I-131 WBS revealed additional radioiodine avid foci not detected on pre-therapy? I-131 WBS in 16 (17.2%) patients. Upstaging was more common in patients =55 years (8 of 23, 34.8%) when compared to patients <55 years (1 of 70, 0.014%). In 13/93 patients (13.9%) who were considered as low risk on pre-therapy? I-131 WBS, 10 patients (10.7%) were found to be intermediate risk and 3 patients as high risk on post-therapy I-131 WBS.
Conclusion: Post-therapy? I-131 WBS revealed new foci in 17.2% patients and clinical upstaging occurred in 9.6% of patients compared to pre-therapy I-131 WBS. There is a significant improvement in the detection of radioiodine avid foci overall and also metastatic lymph nodes by doing post-therapy? I-131 WBS. We suggest that post-therapy? I-131 WBS should be routinely done as it had an incremental role over pre-therapy? I-131 WBS in establishing the true extent of tumour burden, in upstaging the disease and thereby planning adequate hormone suppression to attain target thyroid stimulating hormone levels.
Keywords: Discordance, post-therapy I-131 scan, pre-therapy I-131 scan, thyroid cancer
|How to cite this article:|
Reddy Singareddy CT, Manthri RG, Krishnamohan V S, Sricharan K B, Kalawat T, Hulikal N. Incremental value of post-high dose therapy I-131 scan over pre.therapy diagnostic I-131 scan in patients with differentiated thyroid cancer: Experience from a tertiary care centre in South India. J Clin Sci Res 2020;9:206-12
|How to cite this URL:|
Reddy Singareddy CT, Manthri RG, Krishnamohan V S, Sricharan K B, Kalawat T, Hulikal N. Incremental value of post-high dose therapy I-131 scan over pre.therapy diagnostic I-131 scan in patients with differentiated thyroid cancer: Experience from a tertiary care centre in South India. J Clin Sci Res [serial online] 2020 [cited 2021 Jan 27];9:206-12. Available from: https://www.jcsr.co.in/text.asp?2020/9/4/206/306187
| Introduction|| |
Thyroid cancer is the most common malignancy of the endocrine glands with an annual incidence of 1.1%. Differentiated thyroid carcinoma (DTC) includes papillary carcinoma, follicular carcinoma and their variants. Early stages of disease have extremely favourable survival results, whereas advanced stages have a less favourable prognosis. Standard treatment for DTC includes total thyroidectomy followed by adjuvant therapy with? I-131. This combined approach resulted in 5 years' survival rate exceeding 90%.
The iodide avidity of these tumours and their metastases, allow staging of the disease non-invasively through I-131 whole-body scintigraphy (WBS). Furthermore, because of their iodide avidity, residual malignant tissue and metastases can be effectively treated after total thyroidectomy with localized internal radiation from? I-131. The goals of high-dose radioactive iodine therapy with I-131 are to ablate the post-surgical thyroid remnant tissue, to reduce the chance of local recurrence, to treat any local or distant metastases and to facilitate long-term follow-up using serum thyroglobulin and/or? I-131 WBS.
Diagnostic and post-therapy radioiodine WBS has been established as an effective way to indicate residual and metastatic disease burden after thyroidectomy in patients with DTC because of the expression of sodium-iodide symporter (NIS) by well-differentiated tumour tissue.
After surgery and before? I-131 administration, a pre-therapy diagnostic WBS is performed with radioiodine either? I-123 or? I-131 to identify remnant thyroid tissue and residual local or distant metastatic thyroid cancer. Post-therapy? I-131 WBS is primarily done to look for localisation of I-131, to identify metastatic disease not seen by the pre-therapy scan, and it should be routinely done. At times, post-therapy? I-131 WBS was not performed because of affordability of patients and feasibility in spite of counselling them regarding its incremental role in the management.
We conducted this study to to evaluate the incremental value of post-high dose therapy I-131 WBS over diagnostic pre-therapy? I-131 WBS in the detection of radioiodine avid foci, staging and change in the management of patients with DTC post-total thyroidectomy.
| Material and Methods|| |
In this retrospective analytical study, consecutive DTC patients' post-total thyroidectomy who underwent diagnostic dose pre-therapy? I-131 WBS and post-high dose therapy? I-131 WBS from January 2017 to June 2018 were included. Patients in whom high-dose I-131 was administered without prior diagnostic? I-131 WBS and in patients without recent diagnostic pre-therapy? I-131 WBS (<6 months of therapy) for the comparison were excluded from the study.
Ninety three patients (mean age 47 [range 18–78] years; 72 females) were studied [Table 1]. All patients were prepared for high-dose radioiodine therapy in the form of withdrawal from levothyroxine suppression therapy for at least 3 weeks. Patients were instructed to follow a low-iodine diet for 2–3 weeks before the administration of I-131. All patients were questioned about possible ingestion of substances with high-iodine content and other drugs that could interfere with? I-131 localisation?. I-131 WBS was performed in hypothyroid state in all patients with either a thyroid-stimulating hormone (TSH) level of >30 mIU/L or clinically symptomatic due to local or distant metastases such as bone pain and dyspnoea in whom TSH fails to rise because of widespread functioning metastases.
I-131 WBS was performed with images acquired in anterior and posterior projections sweep view at a rate of 8cm/min by using a dual head gamma camera (Siemens symbia E) equipped with high energy, high-resolution collimator and peaked at 364 KeV with 15% window. Pre-therapy I-131 WBS was performed 2 days after the oral administration of I-131 over a dose range of 1.8-2.6 mCi (66.6–96.2 MBq) with a mean dose of 2.1 mCi (77.7 MBq). Post-therapy I-131 WBS was performed 6–8 days after giving high dose I-131 therapy over a dose range of 30–200 mCi (1110–7400 MBq) with a mean dose of 79.2 mCi (2930.4 MBq).
Scintigraphic images were reported by experienced nuclear medicine physicians in the form of number and location of abnormal radioiodine avid foci on pre- and post-therapy I-131 WBS. They were not blinded to the results of pre-therapy I-131 WBS when reporting post-therapy I-131 WBS. Discordance rate of pre-therapy I-131 WBS findings with post-therapy I-131 WBS was calculated. To assess the signi?cance of differences in the numbers of radioiodine avid foci, Wilcoxon signed-rank test for paired data was used. All statistical computations were performed using the Statistical Package for Social Sciences (SPSS) statistical software, Version 22? (IBM Corp. Somers NY, USA).
| Results|| |
Eighty five of the 93 patients (91.3%) showed radioiodine avid foci in pre-therapy I-131 WBS, whereas post-therapy I-131 WBS showed radioiodine avid foci in 90/93 patients (96.7%) and remaining were labelled as thyroglobulin-elevated negative iodine scintigraphy [Table 2].
Post-therapy? I-131 WBS revealed additional radi (oiodine avid foci not detected on pre-therapy I-131 WBS in 16 (17.2%) patients. Of these 16 patients with discordant scans, radioiodine avid foci at new sites [Figure 1] were identified on post-therapy I-131 WBS in 14 patients, whereas more additional radioiodine avid foci in already established sites [Figure 2] were identified in two patients.
|Figure 1: Pre-therapy I-131 WBS (a) of a 58-year-old female showing negative scan but post-therapy I-131 WBS (b) reveals radiotracer uptake at new sites in thyroid bed (black arrow) and lymph node metastases (red arrows). R = Right side WBS=Whole body scan|
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|Figure 2: Pre-therapy I-131 WBS (a) of a 63-year-old male patient showing increased tracer uptake in thyroid bed (black arrow) and post-therapy I-131 WBS (b) revealing additional radioiodine avid remnant in thyroid bed (red arrow) WBS=Whole body scan|
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New radioiodine avid foci were identified in 5 patients with negative pre-therapy? I-131 WBS, whereas additional radioiodine avid foci at new sites are identified in 11 patients with positive pre-therapy? I-131 WBS. Discordance was more common in patients =55 years (8 of 23, 34.8%) when compared to patients <55 years (8 of 70, 11.4%) [Table 3].
|Table 3: Discordance of pre- and post-therapy I-131 whole body scan (n=16)|
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There was a significant improvement in the detection of metastatic lymph nodes and overall radioiodine avid foci on post-therapy I-131 WBS compared to pre-therapy? I-131 WBS. Although there was improved detection of radioiodine avid foci at other locations also, it was not statistically significant [Table 4] and [Table 5] and [Figure 3].
|Table 4: Radioiodine avid foci identified by pre- and post-therapy I-131 whole body scan at different individual sites|
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|Table 5: Distribution of discordant foci in patients with discordant results (n=16)|
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|Figure 3: Venn diagram showing distribution of discordant metastatic sites in 16 patients|
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Staging of DTC according to American Joint Commission on Cancer (AJCC 8) is in?uenced by patients' age. Therefore, patients were divided into two age cohorts, those <55 years (70 patients [75.2%]) and those =55 years (23 patients [24.8%]).
Nine (9.6%) of these 16 patients with discordant findings had radioiodine avid foci in new locations (lymph nodes, bones and lungs) resulting in upstaging of thyroid cancer [Figure 4]. The remaining 7 (7.5%) had additional radioiodine avid foci that were not enough to alter the staging due to age <55 years [Figure 5] or additional foci in the same region. Upstaging was more common in patients =55 years (8 of 23, 34.8%) when compared to patients <55 years (1 of 70, 0.014%) as the single criterion for upstaging in patients <55 years is the presence of distant metastasis. All patients with age =55 years with discordant scans were upstaged in this study [Table 6].
|Figure 4: Pre-therapy I-131 WBS (a) of a 63-year-old male patient showing increased tracer uptake in thyroid bed (black arrow) and post-therapy I-131 WBS (b) revealing additional radioiodine avid lymph nodes (red arrows). The patient was upstaged to Stage II WBS=Whole body scan|
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|Figure 5: Pre-therapy I-131 WBS (a) of a 39-year-old female patient showing increased tracer uptake in thyroid bed and post-therapy I-131 WBS (b) revealing additional radioiodine avid lymph nodes (red arrows). But stage was unaltered as age of patient is <55 years WBS=Whole body scan|
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TSH suppression post-total thyroidectomy is done based on the risk category of the patient. In 13/93 patients, who were considered as low risk on pre-therapy I-131 WBS, 10 patients were found to be intermediate risk and 3 patients as high risk by post-therapy I-131 WBS [Figure 6]. Subsequently, the dose of Levothyroxine to these 13 patients was increased to maintain target TSH of 0.1-0.5 and <0.1 mIU/L for intermediate and high-risk patients, respectively. Follow-up of these patients was done by stimulated serum thyroglobulin, serum anti-thyroglobulin, diagnostic I-131 WBS and high-resolution ultrasonogram of the neck for a mean duration of 272 ± 47 days. No new lesions were detected in 9 of these 13 patients who came for follow-up. Of these 9 patients, 1 attained excellent response, 3 had structural incomplete response, 4 had biochemical incomplete response and 1 had indeterminate response. Comparison of discordance rate between pre- and post-therapy I-131 whole body scan in different studies is shown in [Table 7].,,,, Risk of skeletal-related events is shown in [Figure 7].
|Figure 6: Pre-therapy I-131 WBS (a) of a 61-year-old male patient showing negative scan but post-therapy I-131 WBS (b) reveals foci of radiotracer concentration in thyroid bed (black arrows), lymph nodes (red arrows) and bilateral lung metastases more prominent on posterio images (blue arrows). The patient was upstaged to Stage IV and risk category was changed from low to high risk WBS=Whole body scan|
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|Table 6: Upstaging on post-therapy I-131 whole body scan in patients showing discordant foci|
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|Figure 7: Pre-therapy I-131 WBS (a) of a 65-year-old male patient showing two foci of increased tracer uptake in thyroid bed (black arrows) and post-therapy I-131 WBS (b) revealing another focus in the centre of neck which on correlation with ultrasonogram neck suggestive of central compartment lymph node metastases (red arrows). Also post-therapy I-131 WBS revealing another focus in head of left Femur (green arrow). To decrease the risk of skeletal related events, the patient was treated with bisphosphonates WBS=Whole body scan|
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| Discussion|| |
Empirical chosen range of therapeutic activities, from 1.1 to 7.4 GBq (30–200 mCi), is in practice for many years than using dosimetry. Diagnostic? I-131 scanning plays an important role in decision-making about? I-131 therapy. However, diagnostic? I-131 WBS tend to underestimate the disease burden in comparison to? I-131 post-therapy WBS.
In this study, we evaluated the differences in the detection of radioiodine avid foci between pre-therapy and post-therapy? I-131 WBS and found a signi?cant difference (P < 0.05) in the detection of total radioiodine avid foci and radioiodine avid lymph nodes. Of 16 patients with discordant pre- and post-therapy? I-131 WBS, 9 were found to be clinically upstaged on the basis of a post-therapy? I-131 WBS that showed additional radioiodine avid foci in new locations. While the number of discordant scans was equal between the two age cohorts, the incidence of upstaging was not and was more common in patients =55 years which is in line with more staging options available for individuals =55 years as compared to those individuals <55 years in whom the single criterion for upstaging is the presence of distant metastasis.
Possible explanations for this discrepancy between pre- and post-therapy I-131 WBS are many. Differences in imaging time: the pre-therapy diagnostic? I-131 WBS was acquired 48 h after I-131 dosing in contrast to nearly 1 week delay in the acquisition of post-therapy? I-131 WBS following therapy. A longer delay increases the target to background ratio and improves lesion detection. Very small metastases, although accumulating iodine, may not reach the sensitivity threshold needed for visualisation when low I-131 doses (74–185 MBq) were used, but they may appear after a therapeutic dose (>1110 MBq). The lower iodine avidity of tissues such as lymph nodes impair tracer uptake at lower doses, but may be overcome by administering higher doses. Tissue with a high uptake capacity like residue in thyroid bed might sequester the radiotracer more and impair visualisation of less iodine avid metastases, which can be detected by greater iodine availability after the administration of high doses.
Inadequate history and improper patient preparation regarding food and drug intake that can potentially interfere? I-131 uptake can lead to discrepancy between the two scan findings. Differential rates of radioiodine turnover. Metastases from thyroid carcinoma have a slow radioiodine metabolism compared to tissue in thyroid bed. Hence, they might not be able to concentrate an adequate amount of radioiodine on earlier imaging. Therefore, post-therapy scanning has been suggested by many nuclear medicine? physicians as it can reveal lesions not apparent on diagnostic scans and that are clinically important.
Although radioiodine uptake is specific for tissues which express NIS, image interpretation may be confounded by multiple factors diminishing the specificity of RAI imaging. Single photon-emission computed tomography (SPECT)/computed tomography (CT) is a useful modality for assessing radioiodine uptake resulting from benign uptake in organs with NIS expression, radioactive secretions or other mechanisms of uptake.,, The use of I-124, a positron emitting tracer for positron emission tomography/CT detects thyroid cancer lesions with high sensitivity and resolution, providing three-dimensional data.,
Some authors reported that diagnostic imaging with? I-131 scan damage thyroid tissue sufficiently to impair uptake and thus limits the effectiveness of subsequent I-131 treatment, an effect referred to as stunning. However, many argued against possibility of stunning by lower doses of less than 185 MBq of I-131. In our study, no discordance in the form of stunning was reported as we routinely perform pre-therapy? I-131 WBS with a dose of approximately 74 MBq.
Studies comparing pre-therapy scan with radioiodine and post-therapy I-131 WBS have reported concordance rates ranging from 72% to 94%. In a study more thyroid remnants (77 vs. 69), twice as many lymph node metastases (32 vs. 16) and four times more distant metastases (12 vs. 3) were reported on post-therapy? I-131 WBS than on pre-therapy I-131 WBS. A higher discordance rate has been reported in patients undergoing a second cycle of high dose I-131 (18%) than in those receiving their first high dose I-131 (6%). Post-therapy I-131 WBS had revealed either additional findings, such as, unsuspected cervical nodes or pulmonary uptake on post-therapy? I-131 WBS or more accurate localization of lesions seen on the diagnostic study in 18 cases (46.2%) and in additional 6 cases (15.4%), questionable new findings were noted. The results of our study with a discordance rate of 17.2% have been similar to other studies (Table 7).,,,,
In the presence of bone metastases, risk of skeletal-related events is increased. In our? study there were? three patients in whom post-therapy? I-131 WBS detected additional bone metastases which were not appreciated on pre-therapy I-131 WBS. The risk of skeletal-related events is further increased in weight-bearing areas of skeleton such as head of Femur (Figure 7). Denosumab (by inhibiting? RANKL) or bisphosphonates (by inhibiting osteoclasts) had to be administered in such patients to decrease the risk of skeletal-related events and thus helping in decreasing their morbidity.
Limitations of the study
Three-dimensional? single photon emission computed tomography (SPECT) was not done in this study, but all the above findings were confirmed with morphological imaging, such as, ultrasonography or CT neck. The correlation of results with serum thyroglobulin and anti-thyroglobulin was not done as it was our practice to advise them only during follow-up visits and not during initial therapy.
Post-therapy I-131 WBS revealed new foci in 17.2% patients and clinical upstaging occurred in 9.6% of patients compared to pre-therapy? I-131 WBS. There is significant improvement in the detection of radioiodine avid foci overall and also metastatic lymph nodes by doing post-therapy? I-131 WBS. To conclude, post-therapy? I-131 WBS should be routinely done as it had an incremental role over pre-therapy? I-131 WBS in establishing the true extent of tumour burden, in upstaging the disease and thereby planning adequate hormone suppression to attain target TSH.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]