A Series Of Studies On The Efficacy And Response Of ¹³¹I Therapy In Papillary Thyroid Carcinoma Based On Pathological And Molecular Features

Part I:Unfavorable Responses to Radioiodine Therapy in N1b Papillary Thyroid Cancer:A Propensity Score Matching StudyObjective:Regional nodal metastases carry prognostic significance in papillary thyroid cancer(PTC).However,whether different locational nodal metastases correlate with different therapeutic responses remains controversial.We innovatively utilized the propensity score matching(PSM)to balance the bias between the two study groups,and applied the response to therapy re-stratification system(RTRS)to evaluate the dynamic disease status after surgery and radioiodine(RAI)therapy in PTC patients with different locational nodal metastases.Methods:A total of 585 non-distant-metastatic PTC patients who underwent total thyroidectomy and RAI therapy were retrospectively enrolled.Patients with nodal metastases were categorized into N1a and N1b groups.PSM was used to balance the bias caused by the different baseline clinicopathological characteristics between two groups.Therapeutic responses were dynamically evaluated,and responses to RAI therapy were classified into excellent(ER),indeterminate(IDR),biochemical incomplete(BIR)and structural incomplete response(SIR).Results:N1b group patients showed a significantly higher pre-ablation stimulated thyroglobulin(Ps-Tg)level than N1a group patients(7.4ng/mL vs 3.2ng/mL,P<0.001).After RAI therapy,with a median follow-up time 23.04 months,N1b group patients took longer time to achieve ER(9.86 months vs 3.29 months,P<0.001)and exhibited a higher proportion of non-ER(IDR,BIR and SIR)(39.15%vs 17.46%,P<0.001)compared to N1a group patients.In logistic regression,N1 b and Ps-Tg≥10ng/mL were confirmed to be independent factors predicting non-ER(Odds Ratio,2.591,9.196,respectively).In Cox regression,patients with N1b disease and Ps-Tg≥10ng/mL showed significantly lower hazards for achieving ER(Hazard Ratio,0.564,0.223,respectively).Conclusion:N1b PTC patients showed inferior responses to surgery and RAI therapy compared to N1a patients.N1b was confirmed to be an independent factor predicting unfavorable responses to RAI therapy.Part II:BRAFV600E Mutant PTC Patients with N1b or Extra-thyroid Extension:Adjuvant RAI Therapy Couldn’t Promise Better ResponsesObjective:BRAFV600E mutant papillary thyroid cancer(PTC)patients with lateral lymph node metastasis(N1b)or extra-thyroid extension(ETE)carry worrying prognoses.While,for those patients,whether a high-dose adjuvant radioactive iodine(RAI)therapy(100-150mCi)could promise a better outcome than low-dose RAI remnant ablation(30mCi)remains controversial.In this study,we innovatively applied the response to therapy re-stratification system(RTRS)to evaluate the dynamic responses to remnant ablation and adjuvant RAI therapy in BRAFV600E mutant PTC patients with N1b or ETE.We aimed to guide a more personalized RAI therapy dose based on patients’ pathological and genetic features.Methods:Without demonstrative persistent/metastatic disease according to pre-RAI therapy assessments,a total of 265 BRAFV600E mutant PTC patients who underwent total thyroidectomy and RAI therapy were retrospectively enrolled.Patients were divided into 5 subgroups based on the pathologic features,including N1b,microscopic ETE(micro-ETE),gross ETE(gross-ETE),N1b+micro-ETE and N1b+gross-ETE groups.Responses to RAI therapy were dynamically evaluated and classified into excellent(ER),indeterminate(IDR),biochemical incomplete(BIR)and structural incomplete response(SIR).Kaplan-Meier analysis and chi-square test were utilized to compare the responses to RAI therapy between adjuvant therapy and remnant ablation groups.Results:There were no statistic differences in the baseline characteristics(including age,gender,tumor size,multifocality and pre-ablation stimulated thyroglobulin)between adjuvant therapy and remnant ablation groups in each pathological subgroup.Defining the first detection of ER as the endpoint,in Kaplan-Meier analysis,adjuvant therapy group patients didn’t show less time to achieve the initial ER compared to remnant ablation group patients in each subgroup(remnant ablation vs.adjuvant therapy):N1b group(4.9 vs.4.7 months,p=0.611),micro-ETE group(3.0 vs.4.4 months,p=0.130),gross-ETE group(2.5 vs.3.8 months,p=0.027),N1b+micro-ETE group(3.1 vs 4.4 months,p=0.526)and N1b+gross-ETE group(2.8 vs 4.6 months,p=0.237)subgroups.At the end of follow-up(median 31.8 months),patients receiving adjuvant therapy didn’t show higher ER rates than patients who underwent remnant ablation in each subgroup(adjuvant therapy vs.remnant ablation):N1b group(73.9%vs.72.5%,p=0.602),micro-ETE group(83.5%vs.69.3%,p=0.006),gross-ETE(100%vs.81.0%,p=0.195),N1b+micro-ETE(70%vs.70.6%,p=0.924),and N1b+gross-ETE group(100%vs.75%,p=0.310).Conclusion:For BRAFV600E mutant PTC patients with N1b or ETE but without demonstrative persistent/metastatic disease,high-dose RAI adjuvant therapy couldn’t promise better responses than low-dose remnant ablation.To balance the benefit of therapeutic efficacy and radiation side effects,low-dose remnant ablation might be a better choice for such patients.