Optimal management of a biochemical incomplete response to therapy in differentiated thyroid cancer: aggressive treatment or cautious observation?

Aim: The risk of differentiated thyroid cancer (DTC) recurrence is widely evaluated according to the 2015 ATA Risk Stratification System. Topography of malignant nodules has been previously reported as an additional risk factor but is not included in the ATA system. Thus, our study aimed to evaluate the relationship between DTC topography and response to initial therapy. Patients and Methods: We enrolled 401 low- to intermediate-risk patients with DTC who had undergone thyroidectomy and radioiodine therapy. DTC topography was recorded and compared with the response to therapy as assessed 12 months after end of therapy. Results: Overall, 366/401 (91.3%) patients had an excellent response to initial therapy while 22/401 (5.5%) and 13/401 (3.2%) had incomplete biochemical or structural response, respectively. Incomplete response occurred in 10/36 (27.8%), 5/125 (4.0%), and 4/111 (3.6%) patients whose unifocal malignant nodules were located in the isthmus, right lobe, or left lobe. Incomplete response was also observed in 4/54 (7.4%) and 12/75 (16%) patients carrying multifocal cancers in one or both lobes, respectively. Patients with isthmic cancer more frequently demonstrated incomplete response compared with those who had cancer in other locations (p=0.00). No significant relationship was found with age, gender, maximum size of malignant nodule, Hashimoto’s thyroiditis, vascular invasion, and extrathyroidal extension (p=0.78, p=0.77, p=0.52, p=0.19, p=0.73, and p=0.26, respectively). The risk of incomplete response was about 65% higher in patients with isthmic lesions compared with other patients (odds ratio=6.725). A log-rank test demonstrated that disease-free survival (DFS) of patients with isthmic lesions was significantly shorter than that of other patients (p=0.02). Conclusion: Our data show that isthmus topography of malignant thyroid nodules is a risk factor for having both persistent disease 12 months after primary treatment and reduced DFS.

Download Full-text

Differentiated Thyroid Cancer with Biochemical Incomplete Response: Clinico-Pathological Characteristics and Long Term Disease Outcomes

Cancers ◽

10.3390/cancers13215422 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5422

Author(s):

Miriam Steinschneider ◽

Jacob Pitaro ◽

Shlomit Koren ◽

Yuval Mizrakli ◽

Carlos Benbassat ◽

...

Keyword(s):

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Staging System ◽

Response To Therapy ◽

American Thyroid Association ◽

Incomplete Response ◽

Structural Disease ◽

Stratification System

Although most patients with differentiated thyroid cancer (DTC) and biochemical incomplete response (BIR) follow a good clinical outcome, progression to structural disease may occur in 8–17% of patients. We aimed to identify factors that could predict the long-term outcomes of BIR patients. To this end, we conducted a retrospective review study of 1049 charts from our Differential Thyroid Cancer registry of patients who were initially treated with total thyroidectomy between 1962 and 2019. BIR was defined as suppressed thyroglobulin (Tg) > 1 ng/mL, stimulated Tg > 10 ng/mL or rising anti-Tg antibodies, who did not have structural evidence of disease, and who were assessed 12–24 months after initial treatment. We found 83 patients (7.9%) matching the definition of BIR. During a mean follow-up of 12 ± 6.6 years, 49 (59%) patients remained in a state of BIR or reverted to no evidence of disease, while 34 (41%) progressed to structural disease. At the last follow-up, three cases (3.6%) were recorded as disease-related death. The American Thyroid Association (ATA) Initial Risk Stratification system and/or AJCC/TNM (8th ed.) staging system at diagnosis predicted the shift from BIR to structural disease, irrespective of their postoperative Tg levels. We conclude that albeit 41% of BIR patients may shift to structural disease, and most have a rather indolent disease. Specific new individual data enable the Response to Therapy reclassification to become a dynamic system to allow for the better management of BIR patients in the long term.

Download Full-text

Dynamic Risk Stratification in Patients with Differentiated Thyroid Cancer Treated Without Radioactive Iodine

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-4290 ◽

2016 ◽

Vol 101 (7) ◽

pp. 2692-2700 ◽

Cited By ~ 103

Author(s):

Denise P. Momesso ◽

Fernanda Vaisman ◽

Samantha P. Yang ◽

Daniel A. Bulzico ◽

Rossana Corbo ◽

...

Keyword(s):

Thyroid Cancer ◽

Risk Stratification ◽

Differentiated Thyroid Cancer ◽

Radioactive Iodine ◽

Response To Therapy ◽

Therapy Assessment ◽

Dynamic Risk ◽

Incomplete Response ◽

Risk Estimates ◽

Negative Imaging

Context: Although response to therapy assessment is a validated tool for dynamic risk stratification in patients with differentiated thyroid cancer (DTC) treated with total thyroidectomy (TT) and radioactive iodine therapy (RAI), it has not been well studied in patients treated with lobectomy or TT without RAI. Because these responses to therapy definitions are heavily dependent on serum thyroglobulin (Tg) levels, modifications of the original definitions were needed to appropriately classify patients treated without RAI. Objective: This study aimed to validate the response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI. Design and Setting: This was a retrospective study, which took place at a referral center. Patients: A total of 507 adults with DTC were treated with lobectomy (n = 187) or TT (n = 320) without RAI. They had a median age of 43.7 y, 88% were female, 85.4% had low risk, and 14.6% intermediate risk. Main Outcome Measure: Main outcome measured was recurrent/persistent structural evidence of disease (SED) during a median followup period of 100.5 months (24–510). Results: Recurrent/persistent SED was observed in 0% of the patients with excellent response to therapy (nonstimulated Tg for TT < 0.2 ng/mL and for lobectomy < 30 ng/mL, undetectable Tg antibodies [TgAb] and negative imaging; n = 326); 1.3% with indeterminate response (nonstimulated Tg for TT 0.2–5 ng/mL, stable or declining TgAb and/or nonspecific imaging findings; n = 2/152); 31.6% of the patients with biochemical incomplete response (nonstimulated Tg for TT > 5 ng/mL and for lobectomy > 30 ng/mL and/or increasing Tg with similar TSH levels and/or increasing TgAb and negative imaging; n = 6/19) and all (100%) patients with structural incomplete response (n = 10/10) (P < .0001). Initial American Thyroid Association risk estimates were significantly modified based on response to therapy assessment. Conclusions: Our data validate the newly proposed response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI as an effective tool to modify initial risk estimates of recurrent/persistent SED and better tailor followup and future therapeutic approaches. This study provides further evidence to support a selective use of RAI in DTC.

Download Full-text

A New Dynamic Response to Therapy Assessment in Postoperative Patients With Low-Risk Differentiated Thyroid Cancer Treated Without Radioactive Iodine

Frontiers in Oncology ◽

10.3389/fonc.2021.764258 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ping Dong ◽

Li Wang ◽

Liu Xiao ◽

Liu Yang ◽

Rui Huang ◽

...

Keyword(s):

Thyroid Cancer ◽

Dynamic Response ◽

Differentiated Thyroid Cancer ◽

Radioactive Iodine ◽

Response To Therapy ◽

Low Risk ◽

Therapy Assessment ◽

Incomplete Response ◽

Increasing Trend

BackgroundTotal thyroidectomy (TT) or lobectomy without radioactive iodine (RAI) is becoming a common management for patients with low-risk differentiated thyroid cancer (DTC). However, the assessment of response to therapy for these patients remains controversial. The aim of this study was to propose and validate a new dynamic evaluation strategy to assess the response to therapy in patients with low-risk DTC treated with TT or lobectomy but without RAI.MethodsWe performed a retrospective analysis of 543 adult patients with low-risk DTC who underwent TT or lobectomy without RAI therapy. Follow-up consisted of trends of serum thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb) levels and neck ultrasonography (US) were conducted every 6–24 months. Response to therapy assessments were defined as excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response according to the follow-up findings.ResultsAt a median follow-up of 51 months (range 33–66 months), 517 (95%) had excellent response, while the other 26 had either biochemical incomplete response (an increasing trend of suppressed serum Tg levels, n=9; an increasing trend of TgAb levels, n=3) or indeterminate response (a stable or decreasing trend of suppressed serum Tg levels, but a stable positive trend of TgAb levels, n=14). No patients had structural incomplete response or no deaths related to thyroid cancer. The risk of incomplete response was significantly higher in lobectomy than in TT (p<0.001).ConclusionOur study proposed and validated a new dynamic response to therapy assessment depending on trends of suppressed serum Tg, TgAb levels, and neck US findings which could be an appropriate tool for postoperative follow-up in low-risk DTC patients without RAI therapy. Our findings provided further evidence to support no routine recommendation of RAI after surgery in low-risk DTC.

Download Full-text

Predictive factors determining incomplete response to radioiodine therapy in patients with differentiated thyroid cancer

The Quarterly Journal of Nuclear Medicine and Molecular Imaging ◽

10.23736/s1824-4785.18.03026-1 ◽

2020 ◽

Vol 64 (1) ◽

Author(s):

Ewelina Szczepanek-Parulska ◽

Magdalena Wojewoda-Korbelak ◽

Martyna Borowczyk ◽

Malgorzata Kaluzna ◽

Barbara Brominska ◽

...

Keyword(s):

Thyroid Cancer ◽

Predictive Factors ◽

Differentiated Thyroid Cancer ◽

Radioiodine Therapy ◽

Incomplete Response

Download Full-text

Evaluation of the response levels of non-metastatic thyroid cancer patients in the postoperative twelfth month

Medical Science and Discovery ◽

10.36472/msd.v7i8.401 ◽

2020 ◽

Vol 7 (8) ◽

pp. 584-588

Author(s):

Hasan İkbal Atılgan ◽

Hülya Yalçın

Keyword(s):

Thyroid Cancer ◽

Cancer Patients ◽

Radioactive Iodine ◽

Thyroid Tissue ◽

Thyroid Stimulating Hormone ◽

Response To Therapy ◽

Response Level ◽

Excellent Response ◽

Incomplete Response

Objective: Radioactive iodine (RAI) is used to ablate residual thyroid tissue after total thyroidectomy. The aim of this study was to evaluate the response according to the12th-month results of thyroid cancer patients and to investigate the changes in response level during follow-up. Materials and Methods: The study included 97 patients, comprising 88 (90.7%) females and 9 (9.3%) males, with a mean age of 41.68±13.25 years. None of the patients had lymph node or distant metastasis and all received RAI therapy. Thyroid-stimulating hormone (TSH), thyroglobulin (TG), and anti-TG levels and neck USG were examined in the 12th-month. Response to therapy was evaluated as an excellent response, biochemical incomplete response, structural incomplete response, or indeterminate response. Results: In the 12th month, 80 patients (82.47%) had excellent response, 13 patients (13.40%) had an indeterminate response, 3 patients (3.09%) had structural incomplete response and 1 patient (1.03 %) had biochemical incomplete response. Of the 80 patients with excellent response, 15 had no follow-up after the 12th month. The remaining 65 patients were followed up for 31.11±9.58 months. The response changed to indeterminate in the 18th month in 1 (1.54%) patient and to structural incomplete response in the 35th month in 1 (1.54%) patient. The 13 patients with indeterminate responses were followed up for 20.61±6.28 months. Conclusion: The TG level at 12th months provides accurate data about the course of the disease especially in patients with excellent responses. Patients with excellent response in the 12th month may be followed up less often and those with the indeterminate or incomplete responses should be followed up more often.

Download Full-text

The Influence of Age on Disease Outcome in 2015 ATA High Risk Differentiated Thyroid Cancer Patients

Acta Endocrinologica ◽

10.1530/eje-21-0365 ◽

2021 ◽

Author(s):

Evert F.s. van Velsen ◽

Robin P. Peeters ◽

Merel T. Stegenga ◽

F.j. van Kemenade ◽

Tessa M. van Ginhoven ◽

...

Keyword(s):

Thyroid Cancer ◽

High Risk ◽

Risk Stratification ◽

Differentiated Thyroid Cancer ◽

Response To Therapy ◽

Disease Outcome ◽

High Risk Patients ◽

Risk Patients ◽

Stratification System ◽

Risk Stratification System

Objective Recent research suggests that the addition of age improves the 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC). The aim of our study was to investigate the influence of age on disease outcome in ATA High Risk patients with a focus on differences between patients with papillary (PTC) and follicular thyroid cancer (FTC). Methods We retrospectively studied adult patients with High Risk DTC from a Dutch university hospital. Logistic regression and Cox proportional hazards models were used to estimate the effects of age (at diagnosis) and several age cutoffs (per five years increment between 20 and 80 years) on (i) response to therapy, (ii) developing no evidence of disease (NED), (iii) recurrence, and (iv) disease specific mortality (DSM). Results We included 236 ATA High Risk patients (32% FTC) with a median follow-up of 6 years. Age, either continuously or dichotomously, had a significant influence on having an excellent response after initial therapy, developing NED, recurrence, and DSM for PTC and FTC. For FTC, an age cutoff of 65 or 70 years showed the best statistical model performance, while this was 50 or 60 years for PTC. Conclusions In a population of patients with High Risk DTC, older age has a significant negative influence on disease outcomes. Slightly different optimal age cutoffs were identified for the different outcomes, and these cutoffs differed between PTC and FTC. Therefore, the ATA Risk Stratification System may further improve should age be incorporated as an additional risk factor.

Download Full-text