| Part 1 Clinicopathological characteristics in patients with cervical lymph node metastasis papillary thyroid carcinomatreated with early and delayed 131I therapyObjectivesTo compare the clinicopathologic features of the early and delayed 131I therapy after total thyroidectomy plus cervical lymph node dissection.Materials and MethodsThis study retrospectively analyzed patients who underwent the first radioactive iodine(RAI)treatment at the Department of Nuclear Medicine,Zhujiang Hospital of Southern Medical University from January 2014 to October 2018.These patients underwent total thyroidectomy(TT)with cervical lymph node dissection,and the postoperative pathology was papillary thyroid carcinoma(PTC)with cervical lymph node metastasis.The maximally selected rank statistics(MSRS)method was used to determine the optimal cutoff point for the time interval between surgery and the first RAI treatment.This cut-off point was used to divide the patients into the early delayed group,and the clinicopathological characteristics of the two groups were compared.ResultsA total of 853 patients with papillary thyroid carcinoma and cervical lymph node metastasis were included in this study,including 756(88.6%)patients<55 years old,97(11.4%)patients ≥55 years old,553(64.8%)females and 300(35.2%)males,with a male to female ratio of 1:1.8,mainly females.There were 704(82.5%)married patients and 149(17.5%)unmarried patients.The median BMI(P25-P75)was 22.4(20.3-24.8).There were 703(82.4)intermediate-risk patients with ATA stage,150(17.6%)low-risk patients.There were 266(31.2%)cases of Tla stage,374(43.8%)cases of T1b stage,138(16.2%)cases of T2 stage,75(8.8%)cases of T3 stage,78(9.1%)cases of primary tumor vascular invasion,73(8.6%)cases of nerve invasion,196(23.0%)cases of multiple lesions,556(65.2%)cases of BRAF gene positive.The size of lymph nodes was 0.7(0.4-1.2)cm,the number of lymphadenectomy was 14.0(6.0-27.0),the number of lymph node metastasis was 5.0(2.0-9.0),the stage of lymph node N1b was 465(54.5%),and the number of extranodal invasion was 309(36.2%).The median TSH(P25-P75)before iodine therapy was 65.8(52.1-79.3),stimulated thyroglobulin(Tg)levels was 4.5(1.1-14.5),and the first RAI dose was 150.0(125.5-155.0),the first RAI dose was 150.0(125.5-155.0).Patients in the unweighted cohort who received delayed RAI therapy were significantly more likely to have N1b disease(61.2%vs.52.5%;P=0.032),BRAFV600E mutation(70.9%vs.63.5%;P<0.001),and multifocal(32.7%vs.20.1%;P<0.001);they were less likely to have undergone a higher dose of RAI therapy(dose,90 vs.150 mCi;P<0.001)and had lower stimulated Tg levels(median 2.4 vs.4.9μg/L;P<0.001).ConclusionIn this study,we found that the factors affecting the timing of RAI treatment included lymph node metastasis(N)stage,BRAF V600E gene mutation,dorsalis,RAI treatment dose,and stimulated Tg level.Whether other socioeconomic factors exist,such as transportation conditions,educational level,income,etc.,needs further study.Part2 Optimal timing of 131I therapy after total thyroidectomy in patients with node-positive papillary thyroid cancerObjectivesThe baseline characteristics of the early and delayed group were balanced using an inverse probability weighting method based on propensity scores to determine the optimal timing of 131I therapy for predicting initial treatment response.Materials and MethodsWe retrospectively reviewed the clinical records of 853 patients with papillary thyroid carcinoma treated in our department(Department of Nuclear Medicine,Zhujiang Hospital of Southern Medical University)from January 2014 to October 2018.All patients underwent total thyroidectomy and radioiodine therapy,and the pathological diagnosis was papillary thyroid carcinoma with cervical lymph node metastasis.The maximum selected rank statistic(MSRS)method in the R package was used to estimate the optimal threshold for the time to first radioiodine therapy after surgery to predict the risk of developing non-ER.The patients were divided into early delayed group according to the threshold.Response to radioiodine therapy was assessed as excellent response(ER)and non-complete response(indeterminate response(IDR),biochemical incomplete response(BIR),structural incomplete response(SIR)).Continuous numerical variables are described by median(P25-P75)or mean±standard deviation,and categorical variables are described by frequency(percentage).Propensity scores were applied using inverse probability of treatment weighting(IPTW)to balance the baseline characteristics.The effect of time to radioactive iodine(TTR)on ER was tested using Kaplan-Meier analysis and Cox proportional hazards regression models.Several TTR thresholds were compared using the Akaike information criterion(AIC).Based on AIC analysis,the 173 day cut-off model was optimal for this study population(AIC=3956.099 for the 180 day cut-off,AIC=3987.385 for the 90 day cut-off,and AIC=3952.328 for the 173 day cut-off).ResultsAfter a median follow-up time of 37.4 months,there were 500 cases of ER(58.6%)and 353 cases of non-ER(41.4%)(including 158 cases of IDR,89 cases of BIR,and 106 cases of SIR).Patients receiving delayed RAI were at greater risk of non-ER than patients in the early RAI group.Cox regression analysis adjusted for IPTW showed a 133%(HR,2.33;95%confidence interval,1.48-3.66;P<0.001)increased risk of non-ER in the delayed RAI group compared with the early RAI group.In addition,the analysis showed that in patients with intermediate-risk recurrence and pN1b stage,delayed RAI therapy would increase the risk of non-ER,while in patients with low-risk recurrence and pN1a stage,delayed RAI therapy was not associated with the risk of non-ER.AIC revealed that the 173-day threshold model best predicted non-ER when compared with 90-and 180-day threshold models.ConclusionThe optimal time for initial RAI therapy for PTC with lymph node metastasis is within 173 days after TT.In patients with node-positive PTC,particularly those with intermediate risk of recurrence or lateral neck metastasis,delayed administration of indicative RAI therapy was associated with lower ER rates.Although preparation time is required for postoperative evaluation and radioiodine preparation in real situations,when possible,we should strive to reduce the time from total thyroidectomy to radioiodine therapy to improve the prognosis of such patients. |
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