Intermediate-risk Papillary Thyroid Cancer Research Articles

Dynamic Risk Stratification Integrated with ATA Risk System for Predicting Long-Term Outcome in Papillary Thyroid Cancer.

In recent years, there has been a renewed interest in thyroid cancer management paradigms that use individualized risk assessments as the basis for treatment and follow-up recommendations. In this study, we assumed that the long-term follow-up of differentiated thyroid cancer patients might be better tailored by integrating the response to initial therapy with the America Thyroid Association (ATA) risk classes. This retrospective study included low- and intermediate-risk papillary thyroid cancer (PTC) patients followed up for a median time of 8 years and classified according to the response to initial therapy assessed 6-12 months after initial treatment. After a median follow-up of 8 years, in the initial excellent response subgroup of PTC patients (n = 522), the rate of recurrent disease was significantly higher in intermediate-risk patients than in low-risk PTC patients (6.9% versus 1.2%, p = 0.0005). Similarly, in the initial biochemical incomplete response subgroup (n = 82), the rate of excellent response was significantly higher in low-risk PTC patients (58.0%) than in intermediate-risk PTC patients (33.3%) (p = 0.007). Finally, in the initial structural incomplete response subgroup (n = 66), the rate of excellent response was higher in low-risk patients (80.0%) than in intermediate-risk patients (46.4%) (p = 0.08). Moreover, all patients with initial indeterminate response had an excellent response at the last follow-up visit. ATA risk classes were independently associated with long-term outcome in each subgroup of patients classified dynamically after initial therapy and the overall prognostic performance, defined via ROC curve analysis, of response to initial therapy integrated with the ATA risk system (AUC: 0.89; 95% CI: 0.86-0.92) was significantly higher compared to the ATA risk stratification (AUC 0.69; 95% CI: 0.65-0.74, p < 0.001) or the dynamic risk stratification (DRS) systems alone (AUC: 0.86 95% CI: 0.82-0.90, p = 0.007). This study of a large cohort of PTC patients showed that the initial ATA risk criteria may be useful for improving the risk-adapted management of PTC patients based on the response to initial therapy.

Early Post-operative Stimulated Serum Thyroglobulin: Role in Preventing Unnecessary Radioactive Iodine Treatment in Low to Intermediate Risk Papillary Thyroid Cancer.

The aims of the study are to evaluate the predictive value of early post-operative stimulated thyroglobulin (sTg) analysis on the recurrence risk, and to define a cut-off value that is related to recurrence risk in low to intermediate risk papillary thyroid cancer (PTC). This retrospective cohort study included individuals who were diagnosed with PTC aged 18 years or older and had been operated by experienced surgeons of a tertiary university hospital between the years 2011 and 2021. The American Thyroid Association thyroid cancer guidelines version 2015 was used as the risk stratification system. Early sTg measurement obtained at 3-4 weeks after surgery when TSH >30 µIU/mL. Data was collected from the hospital database. A total of 328 patients who had post-operative early sTg values with negative anti-Tg antibodies were included. The median age was 44 years. Of the 328 patients, 223 (68%) were women. The median tumor diameter was 11mm. One hundred ninety-one patients (58.2%) had low risk and 137 (41.8%) had intermediate risk for recurrent disease. Of the 328 patients, 4.0% had recurrent disease. In multivariate Cox regression, post-operative early sTg value [OR: 1.070 (1.038-1.116), P = .000], and the pre-operative malign cytology [OR: 1.483 (1.080-2.245), P = .042] were independent risk factors for recurrence. On the ROC curve analysis, the cut-off value of early sTg was 4.1ng/mL for those with recurrent disease. This study demonstrated that early sTg could predict recurrent disease in patients with low to intermediate risk PTC. A cut-off of 4.1ng/mL was identified with a high negative predictive value.

Factors Affecting Ablation Success After I-131 Radioactive Iodine Therapy in Low and Intermediate Risk Papillary Thyroid Cancer.

The study was to evaluate the effect of radioactive iodine (RAI) treatment application time and clinical, histopathological factors on ablation success in patients with operated papillary thyroid cancer (PTC) in low and intermediate-risk. One hundred sixty-one patients with PTC in the low and intermediate-risk were evaluated. Most patients (89.4%) were in the low-risk, and 10.6% were in the intermediate-risk. When the patients were divided into two groups according to the date of receiving RAI treatment after surgery, those who received early treatment (≤3 months) constituted the majority of the patients (72.7%). Seventeen patients received 1.85 Gigabecquerel (GBq), 119 3.7 GBq, 25 5.55 GBq RAI. Most patients (82%) achieved ablation success after the first RAI treatment. The time interval between surgery and RAI treatment did not affect ablation success. Stimulated Tg level measured on the RAI treatment day was an independent predictive factor for successful ablation (p<0.001). The cut-off value of Tg found to predict ablation failure was 5.86 ng/ml. It was concluded that 5.55 GBq RAI treatment could predict ablation success compared to 1.85 GBq dose (p=0.017). It was concluded that having a T1 tumor may predict treatment success compared to a T2 or T3 tumor (p=0.001, p<0.001, retrospectively). The time interval does not affect ablation success in low and intermediate-risk PTC. The ablation success rate may decrease in patients who receive low-dose RAI and have high Tg levels before treatment. The most crucial factor in achieving ablation success is giving enough doses of RAI to ablate the residual tissue.

Outcomes of Patients with an Intermediate-Risk Group According to the Japanese Risk Classification of Papillary Thyroid Carcinoma

BackgroundThe management of intermediate-risk group of papillary thyroid cancer (PTC) is still vague, particularly regarding whether or not total thyroidectomy, postoperative radioactive iodine ablation (RAI-a), and postoperative TSH suppression are mandatory.MethodsThis retrospective study evaluated 680 PTC patients from 2010 to 2017, who were classified into the three risk groups as low, intermediate, and high-risk groups according to the criteria of the Japanese Association of Endocrine Surgeons (JAES) 2010 and underwent surgery according to the JAES guidelines. We retrospectively collected patient data for analyses of disease-free survivals in the intermediate-risk group patients.ResultsWe performed surgery on 680 PTC patients from 2010 to 2017. Of them, 297 were classified as the intermediate-risk group. DFS was not statistically significantly different in patients with/without total thyroidectomy and postoperative TSH suppression therapy. For RAI-a, DFS (95% confidence interval) at 3, 5, and 8 years were 93.2% (84.6 ~ 97.2), 81.6% (68,3 ~ 90.2), and 70.7% (51.4 ~ 84.6) in patients with postoperative RAI-a and 100%, 100%, and 100% in patients without postoperative RAI-a after total thyroidectomy, respectively. DFS of patients without RAI-a was superior to those with RAI-a (P < 0.0004). Multivariable analysis by stepwise selection method revealed that postoperative RAI-a was a risk factor with a hazard ratio of 5.69. (95% CI 1.998–16.21) (P = 0.001131).ConclusionsOur study did not show the efficacy of RAI-a in patients with intermediate-risk PTC. This study implies that judging the efficacy of adjuvant therapy such as RAI or TSh suppression in intermediate-risk patients is difficult.

Radioactive Iodine Therapy Decreases the Recurrence of Intermediate-Risk PTC With Low Thyroglobulin Levels.

Whether radioactive iodine therapy (RAIT) is necessary for intermediate-risk papillary thyroid cancer (PTC) after total thyroidectomy is still lacking reliable evidence, especially for patients with low postoperative thyroglobulin (Tg) levels. This study conducted a propensity score matching (PSM) analysis to investigate whether RAIT is effective in reducing the recurrence of intermediate-risk PTC with low Tg levels. In total, 1487 patients with intermediate-risk PTC with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL after total thyroidectomy were enrolled retrospectively. The clinicopathological characteristics were compared between the non-RAIT and RAIT groups before and after PSM (1:4 matching). The impact of RAIT on biochemical recurrence and structural recurrence was evaluated. Overall, 1349 (90.7%) patients underwent RAIT, and 138 (9.3%) did not. After a median follow-up time of 51 months, 30 patients presented with recurrence, including 11 structural and 19 biochemical recurrences. After PSM, the non-RAIT group had a higher rate of structural recurrence (5/138 vs 5/552, P = .046) and biochemical recurrence (6/138 vs 4/552, P = .005) than the RAIT group. Multivariate analysis showed that not receiving RAIT was an independent risk factor for structural recurrence (hazard ratio [HR] 10.572, 95% CI 2.439-45.843, P = .002) and biochemical recurrence (HR 16.568, 95% CI 3.670-74.803, P < .001). Kaplan-Meier analysis showed that the non-RAIT group had more unfavorable recurrence-free survival (structural and biochemical, all P < .05). RAIT could decrease the recurrence risk of intermediate-risk PTC in patients with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL. Further prospective randomized studies are needed to confirm these findings.

A comparative analysis of treatment efficacy in intermediate-risk thyroid cancer.

This study aimed to evaluate the efficacy of different treatment combinations on patient survival in intermediate-risk differentiated thyroid cancer (DTC). The 2004-2017 National Cancer Database was queried for intermediate-risk papillary (PTC), follicular (FTC), or Hurthle cell (HTC) thyroid cancer patients. Four treatments were analyzed using Kaplan Meier and multivariable Cox regression: surgery, surgery with adjuvant radioiodine ablation (S + RAI), surgery with adjuvant thyroid-stimulating hormone suppression therapy (S + THST), and S + RAI + THST. Kaplan-Meier and multivariable Cox proportional-hazards analyses evaluated treatment-associated overall survival (OS). Of 65,736 patients, 72.2% were female and the average age was 45.4 ± 15.4years. The 10-year OS rates for PTC, FTC, and HTC were 93.2%, 85.2%, and 78.5%, respectively. S + RAI + THST exhibited higher OS than surgery alone and S + RAI (all p < 0.05). Compared to surgery alone, S + RAI + THST demonstrated reduced mortality in PTC (Hazard Ratio [HR]: 0.628, p < 0.001), FTC (HR: 0.490, p < 0.001), and HTC (HR: 0.520, p = 0.006). Similarly, adjuvant RAI + THST reduced mortality regardless of lymphovascular invasion (HR: 0.490, p < 0.001), N1a (HR: 0.570, p < 0.001) or N1b metastasis (HR: 0.621, p < 0.001), or positive margin status (HR: 0.572, p < 0.001). Treatment combinations demonstrated varying efficacies in intermediate-risk DTC depending on histology and tumor characteristics, with S + RAI + THST exhibiting the greatest treatment response.

Early Dynamic Risk Stratification Decreases Rate of Ablative and Adjuvant Radioiodine Use in ATA Low and Intermediate Risk Papillary Thyroid Cancer Patients.

In differentiated thyroid cancer (DTC), radioiodine (RAI) therapy is most frequently employed for remnant ablation or as adjuvant therapy for the remaining disease. The application of RAI to patients classified as intermediate risk (InR) is still a matter of debate. The aim of this study is to analyze the effect of early postoperative risk assessment on RAI use on papillary thyroid cancer patients who are classified as low risk (LoR) or InR. This is a single-center, prospective registry study. One-hundred-eighty-six patients operated between January 2012 and August 2021 and categorized as LoR or InR were included in this study. All patients had total thyroidectomy and central lymph node dissection by the same endocrine surgeon. An early dynamic risk assessment (EDRA) consisting of neck ultrasonography, serum thyroglobulin (Tg) and anti-Tg levels was performed 6 weeks after surgery. Most of the patients were either followed up without RAI or received ablative low activity (30-50 mCi) RAI based on predetermined criteria. Median follow-up was 63 months. Sixty-six (61%) patients in the LoR group and 43 (56%) patients in the InR group did not receive RAI treatment. Thirty-eight (35%) and 22 (29%) patients in LoR and InR groups received ablative (30-50 mCi) RAI therapy, respectively. In LoR group 5 (4.6%) patients and in InR group 12 (16%) patients received 100 mCi or more RAI activity. Only one patient in the InR group recurred during follow-up. No statistically significant difference regarding local recurrence was found between patients who didn't receive RAI or were treated with RAI within both LoR (p=0.152) and InR (p=0.272) groups. There is consensus for LoR patients about omitting RAI therapy after surgery. Indications for RAI treatment in InR DTC are still under debate. RAI use based on EDRA seems to be a better option than decisions solely made on histopathological risk factors and decreases adjuvant high-activity RAI use without increasing recurrence risk.

Response to Surgery Assessments for Sparing Radioiodine Remnant Ablation in Intermediate-Risk Papillary Thyroid Cancer.

Using response to surgery when tailoring radioiodine (RAI) therapy for papillary thyroid cancer (PTC) is valued but lacks prospective validation. To spare RAI thyroid remnant ablation among patients with intermediate-risk PTCs using 3-tiered assessments with response to surgery highlighted, in addition to the risk of the recurrence stratification and TNM staging. Patients with no evidence of disease (NED) identified as excellent response (ER) or indeterminate response (IDR) to surgery were spared from RAI thyroid remnant ablation after informed consent and prospectively enrolled under active surveillance. Those involved in other trials or without sufficient follow-up data were excluded. Dynamic responses were followed and compared longitudinally. The main outcome measures were NED presenting as durable ER or IDR for over 12 months. Of the enrolled 215 patients, 47.4% (102/215) ER and 52.6% (113/215) IDR were identified regarding RAI decision-making. After a median of 23.6 (interquartile range 13.8-31.6) months, the share of ER increased to 82.8% (178/215) and IDR decreased to 16.3% (35/215), with 85 patients shifting from IDR to ER over time, only 0.5% (1/215) structural incomplete response and 0.5% (1/215) biochemical incomplete response observed. Successful remnant ablation was observed in 27.7% (26/94) of the patients completing 2 diagnostic whole-body scans after a median interval of 13.0 months, indicating a theranostic effect. In the 173 patients followed for over 12 months, the NED rate did not differ between ER and IDR subgroups (100% vs 97.9%, P = .20). Through the 3-tiered assessments with response to surgery highlighted, postoperative ER and IDR spared from RAI remnant ablation may indicate similar favorable responses in intermediate-risk patients with PTC during 23.6 months of follow-up.

Radioactive iodine in low- to intermediate-risk papillary thyroid cancer.

It remains controversial whether papillary thyroid cancer (PTC) patients with low- to intermediate-risk disease should receive radioactive iodine (RAI) after total thyroidectomy (TT). We aim to identify those who might benefit from RAI treatment in PTC patients with cervical nodal metastasis after TT. Patients were divided into TT and TT+RAI groups from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2018). Overall survival (OS) and cancer-specific survival (CSS) were compared, and propensity score matching (PSM) was performed between groups. A total of 15,179 patients were enrolled, including 3,387 (22.3%) who underwent TT and 11,792 (77.7%) who received TT+RAI. The following characteristics were more likely to present in the TT+RAI group: multifocality, capsular extension, T3, N1b, and more metastatic cervical lymph nodes. RAI was associated with better OS in low- to intermediate-risk PTC patients in the multivariate Cox regression model. The subgroup analysis showed that RAI predicted better OS in patients ≥55 years, American Joint Committee on Cancer (AJCC) stage II, and capsular extension with a hazard ratio (HR) (95% CI) of 0.57 (0.45–0.72), 0.57 (0.45–0.72), and 0.68 (0.51–0.91), respectively. However, RAI failed to improve the prognoses of patients with age <55 years, AJCC stage I, PTC ≤1 cm, and capsular invasion. In the PSM cohort with 3,385 paired patients, TT+RAI treatment predicted better OS compared with TT alone. In addition, TT+RAI predicted better OS in patients with metastatic cervical lymph nodes ≥2, multifocality, extracapsular extension, and American Thyroid Association (ATA) intermediate risk. In conclusion, RAI was associated with better OS in low- to intermediate-risk PTC patients with age ≥55 years, multifocality, extrathyroidal extension, and ATA intermediate risk. However, the survival benefit from RAI may be limited in patients with AJCC stage I, PTC ≤1 cm, unifocality, capsular invasion, and ATA low-risk diseases; these patients even showed pathological cervical lymph node metastasis.

The role of neck ultrasound in the follow-up of low- and intermediate- risk papillary thyroid cancer.

The optimal time for a neck ultrasound (US) in the follow-up of papillary thyroid cancer (PTC) after the first year is undetermined. We aimed to verify the utility of routine neck US in the surveillance of patients diagnosed with low- and intermediate-risk PTC with no evidence of disease at the one-year assessment. We conducted a retrospective longitudinal study of patients with low- and intermediate-risk PTC with normal neck US, unstimulated serum thyroglobulin (Tg) < 1 ng/mL and negative anti-Tg antibodies at the one-year follow-up. Patients were divided into group 1 [undetectable Tg (<0.20 ng/mL)] and group 2 [detectable Tg but < 1 ng/mL]. The negative predictive value (NPV) of the one-year unstimulated Tg at the five-year and last follow-up visits was calculated. We included n = 88 patients in group 1 and n = 8 patients in group 2. No patient from group 1 presented suspicious US findings at the five-year evaluation [NPV: 100.0% (95% confidence interval (CI): 95.5%-100.0%)], and at the last visit, only one patient had developed a lymph node classified as suspicious [NPV: 98.8% (95% CI: 93.2%-100.0%); mean follow-up: 6.7 years]. In group 2, two patients' USs presented suspicious findings at the five-year evaluation [NPV: 75.0% (95% CI: 34.9%-96.8%)]. At the last visit, only one patient persisted with suspicious findings in the US [NPV: 87.5% (95% CI: 47.4%-99.7%); mean follow-up: 6.5 years]. Low- and intermediaterisk PTC with an excellent response to treatment at the one-year assessment can be safely monitored with regular unstimulated Tg assessments. Conclusions should not be drawn for Tg levels between 0.20-0.99 ng/mL.

Lymph Node Metastases Identified at the Post-Ablation 131I SPECT/CT Scan Is a Prognostic Factor of Intermediate-Risk Papillary Thyroid Cancer.

The intermediate-risk category of papillary thyroid cancer (PTC) comprises heterogeneous patients within a wide range of stages and varied care management. Understanding the risk features of recurrence observed after the initial therapy should be emphasized. We aimed to evaluate the prognostic significance of radioactive iodine-avid lymph nodes observed during the initial treatment of patients with PTC that were considered to be at intermediate risk. Data on patients with intermediate-risk PTC treated from 2012 to 2018 were retrospectively reviewed. Post-therapeutic SPECT/CT (Rx SPECT/CT) was evaluated in the enrolled patients. The clinical, pathologic, and incidence of radioiodine-avid (RAI-avid) lymph node metastasis (mLN) on Rx SPECT/CT were reviewed, and risk factors related to recurrent disease were analyzed. After a median follow-up of 37.26 (30.90, 46.33) months, structural persistent/recurrent disease was detected in 9.81% (36/367) of patients with intermediate-risk tumors. The incidence of recurrence was higher in patients who demonstrated RAI-avid mLN after the initial therapy than in those who did not (p < 0.001). In a multivariate Cox proportional hazard regression analysis, RAI-avid mLN appeared to be a robust risk factor for recurrent disease after the initial therapy (HR: 8.967, 95% CI: 3.433–23.421, p = 0.000). RAI-avid mLN is a significant risk factor for recurrent intermediate-risk PTC after the initial treatment.

Modified dynamic risk stratification system further predicts individual outcome in patients with intermediate-risk papillary thyroid cancer

ObjectiveWe assessed the contribution of initial treatment response to further refining prediction of individual outcomes in intermediate-risk papillary thyroid cancer (PTC) on the American Thyroid Association (ATA) risk stratification system. Dynamic risk stratification (DRS) as originally proposed by Tuttle et al. in 2010 was modified to also include serum antithyroglobulin antibodies (TgAb) as a surrogate marker of the likelihood of persistent disease, specifically in patients with thyroglobulin assay interference by TgAb. MethodsThree hundred and seventy-three patients with ATA intermediate-risk PTC were enrolled retrospectively upon reviewing medical records. Patients were followed at the National Cancer Institute in Bogota, Colombia after being treated with total thyroidectomy and I-131 therapy between 2009 and 2013. Best response to initial therapy was classified as excellent, indeterminate, biochemically incomplete or structurally incomplete. Final disease status after a median follow-up of 7.1 years was classified as no evidence of disease (NED), indeterminate, or persistent disease (either biochemically or structurally). The rate of recurrence was determined in excellent responders. ResultsExcellent response was achieved by 164 patients (43.9%). At a median follow-up of 42 months, 19 (11.6%) had experienced recurrence. 87.4% of initially excellent responders available at the final checkpoint were NED, compared to 28% of those with biochemically or structurally incomplete response and to 60.2% of all ATA intermediate-risk PTC patients in our cohort. ConclusionsModified DRS further predicted individual outcomes in intermediate-risk PTC, potentially allowing ongoing management to be tailored accordingly.

Abstract 730: Annual hazard rate of recurrence in Middle-Eastern papillary thyroid cancer over a long-term follow-up

Abstract Predicting the pattern of recurrence is necessary to establish optimal surveillance and treatment strategies. We identified patient population that remain at risk for an event and clarify changes in the hazard rate (HR) for tumor recurrence overtime in Middle Eastern patients with Papillary Thyroid Cancer (PTC). Data for 1201 PTC patients from single institute with median follow-up of 9.5 years were analyzed. Estimated HR were plotted overtime for the entire cohort, as well as for radioactive iodine (RAI) ablation in patients separately. The changes in risk were further analyzed according to clinical variable and factors predictive of early (≤ 5years) and late (&amp;gt;5 years) recurrence were explored using Cox regression analysis. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 - 2 years (3.7%), with a second smaller peak between 13 - 14 years (3.2%). Patients receiving RAI therapy had a lower hazard of recurrence compared to those who did not receive RAI therapy (1.5% vs 2.7%, p = 0.0001). Importantly, this difference was significant even in the intermediate-risk PTC patients (0.7% vs 2.3%; p = 0.0001). Interestingly, PTC patients who were male, aged ≥ 55 years, with lymph node involvement and advanced stage disease were still at high risk for late recurrence. In conclusion, we confirmed the validity of double-peaked time-varying pattern for risk of recurrence in Middle-Eastern PTC patients. Furthermore, according to the time distribution of recurrence hazard, we could formulate individualized treatment and surveillance plans in PTC patients. Citation Format: Abdul K. Siraj, Sandeep K. Parvathareddy, Zeeshan Qadri, Saud Azam, Felisa De Vera, Maha Al-Rasheed, Wael Haqawi, Hassan AlDossari, Khawla S. Al-Kuraya. Annual hazard rate of recurrence in Middle-Eastern papillary thyroid cancer over a long-term follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 730.

Is Postoperative Adjuvant Radioactive Iodine Ablation Therapy Always Necessary for Intermediate-Risk Papillary Thyroid Cancer Patients With Central Neck Metastasis?

Papillary thyroid cancer (PTC) is commonly associated with neck lymph node metastasis (LNM), and recurrence does occur after radioactive iodine (RAI) ablation therapy. This study aimed to analyze the effectiveness of RAI ablation with regard to disease recurrence in intermediate-risk PTC patients with neck LNM. In addition, the study identified possible predisposing risk factors that might benefit from RAI ablation and analyzed common RAI therapy complications among these patients. A retrospective analysis of 349 intermediate-risk PTC patients with neck LNM who underwent thyroidectomy with neck dissection was performed. The oncologic results and clinicopathologic characteristics of these patients together with the incidence of postoperative RAI therapy complications were evaluated. Of the 349 patients, disease recurrence after treatment occurred for 27 patients (8%) during a mean follow-up period of 58.7 months (range 7-133 months). The recurrence-free survival curve of the patients who received postoperative RAI therapy (n = 208) did not differ significantly from that of the patients who did not receive it (n = 141) (P = 0.567). Nine patients without adjuvant RAI therapy (6%, 9/141) had recurrence. The recurrence rate for the central LNM patients without RAI therapy was only 2% (2/106). Both of these patients with recurrence had pathologic extranodal spread (ENS) and a high number (> 5) of metastatic central LNs. Postoperative RAI-related complications were observed in 24 patients (12%). Postoperative RAI is not necessary for intermediate-risk papillary thyroid cancer patients with central LNM, especially for patients with negative ENS and low number (< 5) of metastatic lymph nodes.

Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up.

Simple SummaryTumor recurrence is a relatively common event in papillary thyroid cancer (PTC). The aim of this study was to analyze the time-varying pattern of recurrence in PTC using annual hazard function and establish a predictive model for early and late recurrences. We found a double-peaked pattern of annual hazard of recurrence, with the risk being highest during the first 5 years after surgery. We also found distinct clinico-pathological parameters that could independently predict the occurrence of early recurrence (first 5 years) as compared to late recurrence (after 5 years). Overall, this study highlights the importance of long-term follow-up of PTC patients. Furthermore, the findings of our study could help in establishing individualized treatment and surveillance plans in PTC patients.Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.

The benefits of radioactive iodine ablation for patients with intermediate-risk papillary thyroid cancer.

BackgroundThe beneficial effects of radioactive iodine (RAI) ablation for intermediate-risk papillary thyroid cancer (PTC) patients are still controversial.Materials and methodsTo determine the impact of RAI therapy on disease-specific survival (DSS) in patients with intermediate-risk PTC, we retrospectively analyzed the data of 23107 intermediate-risk PTC patients who underwent primary thyroidectomy with or without RAI in the Surveillance, Epidemiology, and End Results (SEER) database.ResultsRAI therapy was significantly associated with improved DSS (adjusted HR = 0.65, P = 0.017) in intermediate-risk PTC patients after multivariate adjusting for clinicopathological characteristics. However, subgroup analyses demonstrated that RAI ablation was only associated with improved DSS in patients with male gender (adjusted HR = 0.47, P = 0.005), age ≥ 45 years (adjusted HR = 0.34, P < 0.001) and tumor size > 20 mm (adjusted HR = 0.58, P = 0.007).ConclusionRAI decision-making should be considered on an individual basis rather than “one size fits all” in intermediate-risk PTC patients; only patients with male gender, age ≥ 45 years, and tumor size > 20 mm may benefit from RAI therapy.

Lymphocyte-to-monocyte ratio prior to radioiodine ablation in low- and intermediate-risk, papillary thyroid cancer.

We aimed to investigate inflammation indices based on preablation hematological parameter of the lymphocyte-to-monocyte ratio (LMR) to predict the clinical outcome in papillary thyroid cancer (PTC) patients with low- and intermediate-risk stratification. This retrospective study analyzed 772 patients with low- and intermediate-risk PTC who underwent total thyroidectomy followed by radioiodine therapy between July 2005 and July 2009 with a median of 10 years. Kaplan-Meier statistics were used to test differences in recurrence-free survival (RFS) between groups based on the optimal cutoff point of biomarkers identified using receiver operating characteristic curves. With an optimal cutoff point of 7.05, 215 patients (29.8%) were classified as having low LMR and 557 patients (71.2%) were classified as having high LMR. High LMR was significantly associated with a prolonged RFS (hazard ratio [HR]: 2.048, 95% confidence interval [CI]: 1.062-4.359, p = 0.001). Multivariate analysis showed that low LMR (HR = 2.035, 95% CI: 1.011-4.095, p = 0.012), tumor size over 2 cm (HR = 2.762, 95% CI: 1.303-5.852, p = 0.008), and high preablative simulated thyroglobulin level over 10 ng/ml (HR = 7.826, 95% CI: 2.353-26.033, p < 0.001) were independent prognostic markers for worse RFS in the enrolled PTC patients. LMR at the time of radioiodine therapy has comparable predictor for the clinical outcome with both tumor size and preablative simulated thyroglobulin level in low- to intermediate-risk PTC patients.

Positive Lymph Node Counts in American Thyroid Association Low-Risk Papillary Thyroid Carcinoma Patients.

Current American Thyroid Association (ATA) guidelines state that patients with intermediate-risk papillary thyroid cancer (PTC) may benefit from remnant ablation. One criterion for intermediate-risk classification is >5 positive lymph nodes (LNs). We investigate whether performing step-sectioning of LNs increases the metastatic detection rate, thereby influencing ATA risk of recurrence (ROR) classification. A retrospective review was conducted of cases in which ≥ 5 LNs were removed during thyroidectomy and ≤5 LNs were found positive for PTC. Step-sectioning was performed on the original tissue blocks. All slides were re-reviewed by a senior pathologist. Twenty patients met study criteria. Step-sectioning significantly increased LN yield compared to standard sectioning. In total, we found 12 new positive lymph nodes; seven (58%) were in totally new lymph nodes, while five (42%) were in lymph nodes previously read as negative. All newly discovered metastases were classified as micrometastases (≤2mm). Of the 15 patients originally classified as low-risk, the step-sectioning protocol impacted two patients (13%), increasing ROR stratification. Intensive step-sectioning reveals additional micrometastases. More detailed analysis did not identify clinically significant nodal disease likely to impact the clinical course of patients in this study. Our study supports current standards of pathology specimen handling related to LN assessment and the impact on ATA ROR classification. Nonetheless, it is important for clinicians to understand their institution's sectioning protocol utilized to report positive and total LN counts, which could impact ATA risk stratification and denote the comprehensive nature of the LN dissection that was performed.

Total vs hemithyroidectomy for intermediate risk papillary thyroid cancer: A 23 year retrospective study in a tertiary center.

There is much debate in the literature over the extent of surgery for patients with intermediate risk papillary thyroid cancer. We herein report our results in a local tertiary hospital. We identify from our database patients with papillary thyroid cancer who underwent surgery in our hospital and were stratified to be of intermediate risk from the GAMES stratification system. Patients' demographic data, surgical and pathological details were recorded. Primary end points were disease specific survival (DSS) and recurrence free survival (RFS). From January 1993 to December 2016, 231 patients with papillary thyroid cancer underwent surgery of which 137 (59%) were of intermediate risk. 45 (33%) patients had hemithyroidectomy and 92 (67%) patients had total thyroidectomy. In the total thyroidectomy group, patients had a higher tumor (T) (p value = 0.009) and nodal (N) staging (p value = 0.001). They were also predicted to have a higher risk of recurrence according to the American Thyroid Association (ATA) classification (p value = 0.005). The 5 year DSS in both groups were 100%. The 5 year RFS in the total thyroidectomy and hemithyroidectomy groups were 92% and 100% respectively and were significantly different by the log rank test (p value = 0.02). The median follow up time was 54 months (range 4-276 months). The 5 year survival in intermediate risk papillary thyroid cancer is favorable. Hemithyroidectomy is an acceptable choice of operation in intermediate risk patients with a better risk profile.

Is it Worth Suppressing Tsh in low- and Intermediate-Risk Papillary Thyroid Cancer Patients Before the First Disease Assessment?

Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment. A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 μUI/mL; group 2, TSH 0.1 to 0.5 μUI/mL; group 3, 0.5 to 2 μUI/mL; and group 4 >2 μUI/mL. This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups. TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment. ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography.