This is a retrospective observational study to examine the outcomes of thyroid cancer treated by surgery and radioactive iodine at the SQCCCRC. The study examines the effect of age, sex, body mass index, region, histopathology (tumor type and TNM status (primary tumor (T), regional lymph node (N), and distant metastasis (M) stage), iodine dose, baseline and follow up stimulated and unstimulated thyroglobulin Tg), thyroglobulin antibody (TgAb), and stimulated and unstimulated thyroid-stimulating hormone (TSH) levels), lymph node metastasis and distant metastasis on the patients’ outcomes.

This is a retrospective observational clinical study conducted at the Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC). The study aimed to evaluate the treatment outcomes of patients with DTC who underwent total thyroidectomy followed by RAI therapy.

The study included all patients diagnosed with DTC who were admitted to SQCCCRC between June 2021 and November 2023.

Demographic and clinical data were extracted from the hospital's electronic medical records. Collected variables were included:

Demographics: age, sex, region of residence, body mass index (BMI).

Clinical and pathological data: tumor histology, TNM staging (T: tumor size, N: lymph node involvement, M: distant metastasis), type of surgery, RAI dose.

Biochemical markers: pre- and post-treatment levels of stimulated and unstimulated thyroglobulin (Tg), thyroglobulin antibody (TgAb), and thyroid-stimulating hormone (TSH)

Disease status: presence or absence of local or distant metastasis, and recurrence status (new vs recurrent tumor).

The primary outcome is the biochemical response to treatment, defined as a stimulated Tg < 1 ng/mL or suppressed Tg < 0.2 ng/mL at either 6 months or 12 months following RAI therapy.

The secondary outcome is the presence of metastasis, categorized as:

Local persistence: residual thyroid tissue or cervical lymph node involvement detected by neck ultrasound 6 months post-treatment

Distant metastasis: identified through diagnostic whole-body I-131 scan and/or cross-sectional imaging (CT and PET/CT), as clinically indicated

Descriptive statistics were used to summarize patient characteristics: medians and interquartile ranges for continuous variables, and frequencies and percentages for categorical variables. Associations between demographic/clinical variables and the primary outcome (biochemical response) were analyzed using Chi-square tests and logistic regression models. A multivariate logistic regression was performed to identify independent predictors of treatment response, adjusting for potential confounders. A p-value < 0.05 was considered statistically significant.

A total of 255 patients met the inclusion criteria and were included in the analysis. Categorical variables and treatment response frequencies were compared between clinically and demographically defined subgroups, including lymph node involvement, administered radioactive iodine dose, and baseline thyroglobulin levels. All statistical tests were two sided, and a p value of ≤0.05 was considered statistically significant. Fisher’s exact test was used for comparisons of proportions. Continuous variables were summarized using descriptive statistics and compared between groups using the twosample ttest.

All statistical analyses were performed using R software (version 4.5.1; R Foundation for Statistical Computing, Vienna, Austria) and Stat version 19.0 BE (StataCorp, College Station, TX, USA).

A total of 255 patients diagnosed with DTC were included in the study. The mean age at diagnosis was 39.9 ± 12.4 years (range: 14–79), with 78% of patients being female. Geographically, the majority were from the Batinah (34.9%) and Muscat (21.8%) regions, with a small percentage from other governorates or outside Oman.

The mean BMI was 30.3 ± 6.4 kg/m^², with nearly half of the cohort (48.2%) classified as obese (BMI ≥ 30). Most patients had papillary thyroid carcinoma (93.3%), while follicular and Hürthle cell carcinoma accounted for 5.9% and 0.8% of cases, respectively.

Tumor size at diagnosis was less than 2 cm in 80.5% of patients, and the median maximum tumor diameter was 2 cm (IQR: 1.2–3 cm). Lymph node involvement (N1) was reported in 37.9% of cases, whereas in 31.5% of the cohort the LN status was unknown or Nx. Distant metastases were documented in 5.5% of patients. Features associated with more aggressive disease, including extrathyroidal extension and angio-vascular invasion, were present in 11.1% and 32.8% of patients, respectively. Multifocal disease was observed in 58.7%.

Based on the American Joint Committee on Cancer (AJCC) staging, 91.7% of the patients were classified as stage I and 4.2% as stage II. Six patients (2.5%) had stage IVB disease. According to American Thyroid Association (ATA) risk stratification, 49.8% were low-risk, 40% intermediate-risk, and 10.2% high-risk. The median duration of follow-up was 14 months (IQR: 12–24), ranging from 1 month to over 21 years. Demographic characteristics of the study cohort are presented in Table 1, Figure 1.

Patient age was strongly associated with disease stage (Table 2). Among patients younger than 45 years, the vast majority (98.8%) were classified as AJCC Stage I, with only 2 patients (1.2%) having Stage II disease and none with Stage III or IV. In contrast, older patients (≥45 years) exhibited a broader distribution of stages: 75% were Stage I, while the remaining 25% were diagnosed with Stage II–IV disease. This difference was statistically significant (p < 0.001, Fisher’s exact test). This relationship remained significant when age was analyzed as a continuous variable. Patients with Stage I disease had a significantly lower mean age compared to those with Stage II–IV disease (38.2 ± 10.3 vs. 57.1 ± 15.9 years, respectively; p < 0.001, two-sample t-test). No significant associations were observed between sex and disease stage in our cohort (p=.857). While the overall association between BMI and AJCC stage did not reach statistical significance (p = 0.059), a more focused analysis revealed a significant relationship between high BMI and advanced disease. Specifically, all patients with Stage IV disease had a BMI ≥30, and this association was statistically significant (p = 0.006).

The distribution of metastatic cases varied by region (Table 3), with the highest proportion observed in Dhofar, accounting for 5 cases (38%) of all metastases. Other regions with notable proportions included Muscat and Al Batinah (2 cases; 15% each), followed by Al Dakhiliyah, Ash Sharqiyah, Non-Omani patients (1 case each). Statistical analysis showed a strong association between Dhofar region and the presence of distant metastasis (p = 0.003) (Figure 2).

At postoperative baseline, 43.2% of patients were biochemically hypothyroid (TSH > 4.3 mU/L). Median stimulated TSH was 100 mU/L (IQR: 75.7–100). The median thyroglobulin (TG) level was 0.6 ng/mL (IQR: 0.07–4.0), with 34.1% having TG < 0.2 ng/mL. Similarly, median stimulated TG was < 1ng/mL is 32.6% of the patients. Both suppressed and stimulated anti-thyroglobulin antibodies (TG-Abs) were negative (< 115 IU/mL) in 87.3% and 84.6% of cases. (Table 4)

Most patients underwent initial thyroidectomy at Sultan Qaboos University Hospital (47.1%) or Armed Forces Hospital (18.8%). Lymph node dissection was performed in 40.0% of cases.

Neck ultrasound conducted post-surgery revealed no residual findings in 78.1% of patients, while lymphadenopathy and residual thyroid tissue were seen in 13.7% and 8.2%, respectively. Postoperative whole-body scans indicated uptake limited to the neck in 89.4% of cases. Lymph node and distant uptake were observed in 5.5% and 5.1%, respectively.

Most patients (87.1%) received a single dose of radioactive iodine (RAI), with a median cumulative dose of 3.7 mCi (range: 1.1–23.3). Only 2.3% of patients required external beam radiotherapy, and 7.8% underwent a second surgical intervention, primarily for lymph node dissection.

At six months post-treatment, 71.3% of patients had a TG level < 0.2 ng/mL. This increased slightly to 73.3% by the last follow-up. TG-Abs remained negative (< 115 IU/mL) in over 91% of patients at both time points (Table 5, Figure 3).

We evaluated predictors of biochemical response (defined as TG < 0.2 ng/mL) at two key time points: 6 months post-RAI therapy and at the last follow-up.

At 6 months post-RAI, several variables were significantly associated with achieving a disease-free state. These included female sex (p = 0.006), absence of lymph node involvement (p = 0.001), no distant metastasis (p < 0.001), absence of extrathyroidal extension (p < 0.001), and lack of angio-vascular invasion (p < 0.001). Tumor size was also associated with early response, with T1 tumors showing better outcomes than T2–T4 tumors (p = 0.011). Patients classified as AJCC stage I or ATA low-risk had significantly higher rates of early response (p < 0.001 for both). While younger age (<45 years) appeared favorable, it only approached statistical significance (p = 0.050).

At last follow-up, the associations remained largely consistent. Female sex (p = 0.004), T1 tumor size (p = 0.032), absence of lymph node involvement (p = 0.003), absence of distant metastasis (p < 0.001), lack of extrathyroidal extension (p < 0.001), and absence of angio-vascular invasion (p = 0.003) continued to predict favorable response. Age <45 years achieved significance (p = 0.032). Notably, both age and tumor size, when treated as continuous variables, were not significantly associated with TG response at either time point (age: p = 0.325 at 6 months, p = 0.411 at last follow-up; tumor size: p = 0.107 at 6 months, p = 0.232 at last follow-up), suggesting a potential non-linear relationship.

Risk stratification continued to be predictive at both time points: patients with ATA low-risk disease were significantly more likely to achieve TG < 0.2 ng/mL at 6 months (85% vs. 33% in high-risk group; p < 0.001) and at last follow-up (85% vs. 40%; p < 0.001). Similarly, AJCC stage I was strongly associated with better outcomes (p < 0.001).

Follow-up duration also played a role. At 6 months, patients followed for ≤12 months had higher rates of biochemical response (p = 0.004), and this association remained significant at last follow-up (p < 0.001), although it may partially reflect lead-time bias.

In the multivariable logistic regression model for response at 6 months, tumor size (T1) was significantly associated with a favorable response, with patients having T1 tumors more likely to achieve TG < 0.2 ng/mL (p = 0.039; OR = 0.462, 95% CI: 0.222–0.963).

The presence of distant metastasis was excluded from the model due to perfect separation: all patients with distant metastasis had persistent disease, while none of the patients without metastasis achieved persistent disease. As a result, this variable was omitted due to perfect prediction and collinearity. At the last follow-up, the presence of distant metastasis remained a statistically significant independent predictor of persistent disease (p = 0.006; OR = 0.02, 95% CI: 0.001–0.315). Additionally, follow-up duration >12 months was independently associated with persistent disease at this time point (p = 0.039; OR = 0.404, 95% CI: 0.171–0.954) (Table 6, Figure 4).