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ORIGINAL ARTICLE
Year : 2020  |  Volume : 17  |  Issue : 3  |  Page : 123-127

Retrospective evaluation of clinicopathological characteristics of differentiated thyroid cancer patients with iodine-131-avid distant metastasis: A tertiary care centre experience


Department of Nuclear Medicine, NIMS, Hyderabad, Telangana, India

Date of Submission03-Apr-2020
Date of Acceptance25-Jun-2020
Date of Web Publication20-Jan-2021

Correspondence Address:
Dr. Kavitha Nallapareddy
Room No. 40, Department of Nuclear Medicine, NIMS, Hyderabad - 500 082, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_23_20

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  Abstract 


Introduction: Among various prognostic indicators, distant metastases have a strong impact on the overall survival of differentiated thyroid cancer (DTC) patients.
Aim: The aim of this study was to know the incidence, pattern of iodine-131-avid distant metastases in DTC patients at presentation, long-term survival probability in DTC patients with distant metastases and also to know the relationship between the distant metastases and clinicopathological variables such as age, gender, and histopathological subtypes.
Materials and Methods: Retrospective evaluation of case records and whole-body iodine scans of DTC patients referred to our hospital between January 2013 and December 2018 was done.
Results: A total of 1336 DTC patients' case records were analyzed. Among them, 157 patients (11.7%) had distant metastases at presentation. Majority were female patients (63%). The mean age of patients in the study group was 48.4 years. Most of the patients had papillary histopathology (58.6%), followed by follicular (34.4%), poorly differentiated (5.73%), and Hurthle cell carcinoma (1.27%). Bone was the most common site of metastases in 49% of patients, followed by the lung in 25% of patients. Two (1.27%) patients had an unusual site of metastases involving the kidney and adrenal gland. Nearly one-third patients (25.5%) had multi-organ metastases. The 5 years specific survival probability of DTC patients with distant metastases at presentation was 47.3%.
Conclusion: The incidence of distant metastases in our study is similar to the incidence rate reported in the literature. Distant metastasis is higher in female patients and in the age group of 45 years and above. Bone is the most common organ site of metastases rather than lung in the present study, which is pointing towards the high incidence of skeletal metastases in Indian patients. The specific survival probability at 5 years is 47.3%.

Keywords: Differentiated thyroid cancer, iodine-131-avid distant metastases, radioactive iodine therapy


How to cite this article:
Manohar P R, Nallapareddy K, Srivastava MK, Kendarla VK. Retrospective evaluation of clinicopathological characteristics of differentiated thyroid cancer patients with iodine-131-avid distant metastasis: A tertiary care centre experience. Thyroid Res Pract 2020;17:123-7

How to cite this URL:
Manohar P R, Nallapareddy K, Srivastava MK, Kendarla VK. Retrospective evaluation of clinicopathological characteristics of differentiated thyroid cancer patients with iodine-131-avid distant metastasis: A tertiary care centre experience. Thyroid Res Pract [serial online] 2020 [cited 2021 Oct 28];17:123-7. Available from: https://www.thetrp.net/text.asp?2020/17/3/123/307554




  Introduction Top


Thyroid cancer is the most common endocrine cancer. Its incidence rate is increasing for the last three decades. Now it is the fifth-most diagnosed cancer in women.[1],[2] Thyroid cancer is three times more common in women. Its peak age incidence between 45–49 years in women and 65–69 years in men.[3],[4] Differentiated thyroid cancer (DTC) includes papillary and follicular thyroid cancer accounts for 90% of all thyroid cancer subtypes. Standard treatment for thyroid cancer is total thyroidectomy, followed by adjuvant radioactive iodine-131 (I-131) therapy and suppressive doses of thyroxin supplementation. The incidence of distant metastases in DTC is around 10%–15%. DTC without distant metastases has a better overall survival around 80%–100% at 5 years; it reduces to 40% in patients having distant metastases.[5] It is important to detect the distant metastases in patients with DTC because it is associated with poor cause-specific and overall survival rates. This study was conducted to know the incidence, site and extent of I-131-avid distant metastases in DTC patients at presentation, long-term survival probability in patients with distant metastases and also to find out the relationship between the distant metastases and other parameters like age, gender, histopathological subtypes in the metastatic subgroup.


  Materials and Methods Top


This is a retrospective study conducted at the Department of Nuclear Medicine, Nizam's Institute of Medical Sciences (NIMS) Hyderabad, a tertiary care teaching hospital, which represents a different patient population referred from different regions the southern part of India. The study was approved by the institutional ethics committee with reference letter number EC/NIMS/2541/2020.

In this study, we retrospectively analyze all case records and available whole-body radioiodine scans of DTC patients who were referred for I-131 therapy from January 2013 to December 2018 (6 years period).

A total of 1336 histologically proven DTC patients were referred for I-131 therapy during the study period. Available postoperative diagnostic whole-body radioiodine scans (I-131 Dx WBS) and I-131 posttherapy whole-body scans (I-131 Rx WBS) of these patients were reviewed separately by two nuclear medicine physicians and only those scans having concordance were included in the study. Any nonphysiological radioiodine uptake sites other than the neck on I-131 Dx/I-131 Rx WBS were interpreted as distant metastases. Of the 1336 patients with DTC, 157 patients had distant metastases at presentation were included for further analysis in this study.

After I-131 therapy, these patients were followed – up at 6 months and 1 year interval period with clinical examination, radioiodine whole-body scan, stimulated serum thyroglobulin and Anti thyroglobulin antibody levels.

Statistical analysis

All continuous variables of the study have been described by descriptive statistics such as mean and standard deviation. Categorical variables described by frequency and percentages. Kaplan–Meier method was used to draw the survival curves from the initial presentation to the last follow-up or time of death due to DTC. Survival time was censored for patients who were alive at the end of the study period, lost during follow-up, and died due to other causes. The data were analyzed using GraphPad Prism version 8.4.2 for Windows, GraphPad Software, San Diego, California, USA.


  Results Top


A total of 1336 DTC patients' case records was analyzed. Among them, 157 patients (11.7%) had distant metastases at presentation [Table 1]. Most of the patients 155 (98.7%) underwent total/near-total thyroidectomy, and 2 (1.27%) patients had incomplete surgeries.
Table 1: Incidence of distant metastases in 6 years retrospective group

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Of 157 DTC patients with distant metastases, 99 (63%) female patients with a mean age of 44.5 years (range 11–75 years), and 58 (37%) male patients with a mean age of 56.2 years (range 17–78 years). The mean age of the total number of patients in the study group was 48.4 years (range 11–78 years) [Table 2]. There were 49 patients (31.2%) in the age group of <45 years. One hundred and eight patients (68.8%) were in the age group of 45 years or more [Table 2].
Table 2: Clinical characteristics of the patients with distant metastases (n=157)

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Among 157 DTC patients with distant metastases, 92 (58.6%) patients had papillary thyroid carcinoma (PTC), 54 (34.4%) patients had follicular thyroid carcinoma (FTC). Poorly DTC (PDTC) and hurthle cell carcinoma (HTC) were seen 9 (5.73%) and 2 (1.27%) patients, respectively [Table 3]. Bone was the most common site of metastases in 77 (49%) patients. Lung was the next most common site of metastases in 39 (25%) patients. One patient (0.63%) had brain metastasis. Multiple organ metastases observed in 32 (20.4%) patients involving bone and lung, 3 (1.9%) patients had bone and brain metastases, 2 (1.27%) patients had lung and liver metastases. Only one patient (0.6%) had multi-organ metastases involving bone, lung, and brain. In the study group, we observed unusual sites of metastases involving the renal and adrenal gland in one patient each, respectively [Table 4]. Single-organ metastasis was observed in 117 (74.5%) patients and multi-organ metastases were seen in 40 (25.5%) patients [Table 5].
Table 3: Histopathological characteristics of patients (n=157)

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Table 4: Metastatic sites in differentiated thyroid cancer patients with distant metastases (n=157)

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Table 5: Organ wise total metastatic sites (n=157)

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Out of 92 patients of PTC, 32 (34.7%) patients had bone metastases, 37 (40.2%) patients had lung metastases, 17 (18.5%) patients had multi-organ metastases involving lung and bone, 2 (2.17%) patients had bone and brain metastases. Two (2.17%) patients had lung and liver metastases. Unusual sites of metastases involving renal and adrenal glands observed in 2 (2.17%) patients. Among the 54 patients with FTC, bone metastases seen in 37 (68.5%) patients. Two (3.7%) patients had lung metastases, one patient (1.85%) had brain metastases, 12 (22.2%) patients had lung and bone metastases, one patient (1.85%) had metastases in bone and brain. One patient (1.85%) had metastases involving the bone, brain, and lung. Of 9 patients with PDTC, 6 patients (66.6%) had bone metastases and 3 (33.3%) patients had lung and bone metastases. Two patients with HTC had bone metastases [Table 6]. One hundred and fifty four (98%) patients were treated with multiple doses of I-131 therapy.
Table 6: Metastatic sites and histopathology sub types

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During the 6 years study period, 99 (63%) censures, and 58 (37%) deaths due to DTC were observed. The censored group included 95 living patients at the end of the study period, four patients lost to follow-up. The median follow-up of living patients was 3.2 years. Kaplan–Meier derived median survival for the study group (n = 157) was about 5 years. The 5 years specific survival probability of DTC patients with distant metastases at presentation was 47.3% [Figure 1]. We also analyzed the survival probabilities of papillary and follicular thyroid cancer patients with distant metastases of our study group. Of 92 PTC patients, 33 (35.8%) patients died during the study period due to thyroid cancer. Among 54 FTC patients, 23 (42.5%) patients died during the study period due to thyroid cancer. The 5 years specific survival probabilities of PTC and FTC patients were 54% and 34%, respectively [Figure 2] and [Figure 3].
Figure 1: Kaplan–Meier plot of 5 years specific survival in differentiated thyroid cancer patients with distant metastases at presentation

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Figure 2: Kaplan–Meier plot of 5 years specific survival in papillary thyroid cancer patients with distant metastases at presentation

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Figure 3: Kaplan–Meier plot of 5 years specific survival in follicular thyroid cancer patients with distant metastases at presentation

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  Discussion Top


Thyroid cancer is classified based on the cell of origin, cancers arise from follicular epithelium are further classified into DTC, PDTC, and undifferentiated thyroid cancer. DTC and some of the PDTC subtypes show radioactive iodine avidity. Standard treatment protocol for these subtypes of thyroid cancer includes total thyroidectomy followed by adjuvant I-131 therapy and suppressive doses of thyroxin supplementation.[5],[6] Compared to other types of thyroid cancer, DTC has a better prognosis in terms of cause-specific survival (CSS) and disease-free survival.[7],[8]

There are various prognostic indicators age, gender, tumor size, functioning metastases, and distant metastases to predict the disease outcome in DTC patients. Among them, the presence of distant metastasis has a strong impact on the overall survival of DTC patients.[9] The overall incidence of distant metastases varies from 4% to 15%.[10] The presence of distant metastases in DTC patients reduces a 5-year survival by 39%–53% and 10 years survival by 13%–33%. The lung is the most common site of metastases, followed by the bone, brain, and liver. Distant metastases involving multiple organs associated with a high mortality rate of nearly 92% at 5 years.[10],[11],[12],[13]

Distant metastases at presentation in DTC patients related to other clinicopathological features such as age, extrathyroid extension, and tumor size. Age (>45 years), presence of extrathyroid extension, and tumor size >4 cm are the independent prognostic factors for CSS of DTC patients with distant metastases.[9]

Published data from different regions of the world reported the relationship between clinicopathological features and distant metastases in DTC patients.[12],[13],[14],[15] We have made an attempt to know the incidence, pattern, extent of I-131-avid distant metastases in DTC patients at presentation, long-term survival probability in patients with distant metastases and also to know the relationship between the distant metastases and clinicopathological variables such as age, gender, and histopathological subtypes.

In this study, 11.7% of DTC patients had distant metastases at presentation. This finding is almost similar when compared to the overall incidence of distant metastases (12.4%–14.6%) reported in other studies.[16],[17],[18] The mean age of the study population was 48.4 years, which is in agreement with most of the studies (>45 years).[17],[18] Female patients (63%) were also more common than males (37%), as observed in previous reports (females 60.60%; males 39.9%).[18] Bone (49%) was the most common site of metastases followed by the lung (25%) in our study, similar findings observed in other studies based on Indian patients.[18],[19] However, this is in contrast to observations made in most of the studies from different regions of the world, which reported that the lung is the most common metastatic site followed by the bone.[14],[15],[20]

In patients with papillary thyroid cancer variant, 39.1% of patients had lung metastases and 35.9% of patients had bone metastases which are similar when compared to 45.5% (lung) and 37.5% (bone) in a study from the southern part of India.[18] On the other hand, we observed 66.6% of patients with FTC had skeletal metastases in the present study. This finding is almost similar when compared to 63.3% reported in a study from the northern part of India.[19] In this study, 25.5% of patients had distant metastases involving multiple organs, which was similar when compared to 22.5% in a study from the southern part of India.[18] The incidence of multi organ metastases (25.5%) in the present study was more when compared to 19% and 16% reported in studies from the UK and US, respectively,[14],[15] which may indicate aggressive behavior of DTC in Indian patients. The 5 years specific survival probability of DTC patients with distant metastases at presentation was 47.3%. This was almost similar when compared to 39% and 42% observed in studies from the UK and US, respectively.[14],[15] the 5-year survival rate of 47.3% in the present study was less when compared to 74.3% reported in a study from the northern part of India.[19] The difference is maybe due to the study sample size mismatch (157 patients vs. 35 patients).

In the present study, 11.7% of the patients had distant metastases; the majority of the patients (68.8%) were in the age group of 45 years and above, indicating that distant metastasis is more common in the age group of 45 years and above. Female patients outnumbering the male patients. In our study, we found that the incidence of bone metastases is more than lung metastases. Nearly one-third patients had multi-organ metastases. In addition to common sites of metastases, we observed uncommon sites of metastases involving the kidney and adrenal gland. Median survival for the study group (n = 157) was about 5 years. The 5-year specific survival probability of DTC patients with distant metastases at presentation was 47.3%. Specific survival probabilities of PTC and FTC patient subgroups with distant metastases at 5 years were 54% and 34%, respectively. However, there are some limitations in our study, first, it is a retrospective study. The second, it is an institutional-based study likely to have a selection bias. The third, variants of histopathological types of DTC were not mentioned.


  Conclusion Top


We conclude that the overall incidence of distant metastases in our study based on the Indian population is similar to an incidence rate reported in the literature. Bone is the most common organ site of metastases rather than lung in the present study, which is pointing toward the high incidence of skeletal metastases in Indian patients. Distant metastasis is higher in female patients and in the age group of 45 years and above. Median survival time for DTC patients with distant metastases is about 5 years. The specific survival probability at 5 years is 47.3%.

Acknowledgement

We are thankful to Dr. Namala Balakrishna, Regional Medical Advisor- Global Medical Affairs (IF,MEA), Glenmark, Mumbai for his help in data analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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