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Oncological outcomes for patients with well differentiated thyroid cancer

Nixon, I.J.

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Citation for published version (APA):Nixon, I. J. (2013). Oncological outcomes for patients with well differentiated thyroid cancer.

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Download date: 10 Mar 2020

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Chapter 7

Observation of Clinically Negative Central Compartment Lymph

Nodes in Papillary Thyroid Carcinoma

Iain J. Nixon MBChB, Ian Ganly MD,PhD, Snehal G. Patel MD, Luc G. Morris MD, Frank L. Palmer BA, Dorothy Thomas BA,

R. Michael Tuttle MD, Jatin P. Shah MD,PhD1, Ashok R. Shaha MD

Surgery 2013; in press

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Abstract

IntroductionThe role of propyhlactic central neck dissection (CND) in the management of papillary thyroid cancer (PTC) is controversial. We report our experience of an observational approach to the cN0 neck in PTC.

Methods1129 patients with PTC, who had total thyroidectomy between 1986-2005 were reviewed. 470 patients were pN1, 384 had benign nodes removed (pN0) and the remaining 275 had no nodes removed (pNx). The pNx group formed the cohort for this study.

ResultsWith a median follow-up of 70 months the 10year disease specific survival was 100%. Four patients had evidence of radioactive iodine (RAI) uptake on scans performed during follow-up without diagnostic cytology. All subsequently received RAI and are considered disease-free. Three patients had biopsy proven lateral-neck recurrence and underwent neck dissection. 1 patient developed a low-level thyroglobulin suspicious for recurrence. 1 patient has a sub-centimeter level-VI node suspicious for recurrence which has been observed. Therefore, the rate of structural recurrence in the central neck was 0.4% (1/275) and the rate of reoperation on the central neck was 0%.

ConclusionOur results suggest that properly selected patients can safely be managed with observation of the central neck rather than prophylactic CND, which has a higher complication rate.

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Introduction

Papillary thyroid cancer (PTC) metastasizes often and early (1-3). However unlike most human malignancies , spread of disease to regional lymph nodes is generally not associated with poor outcome (4). However, in older patients, such regional disease predicts both recurrence and survival (5, 6). Around 20-30% of patients with PTC will present with clinically palpable nodal disease (7, 8). Such patients require total thyroidectomy and appropriate neck dissection. In contrast, occult metastasis is much more common, particularly to the central neck (9). The incidence of occult metastases has been reported to be approximately 40% (9). The impact of occult metastases on outcome is unclear. As such, there is considerable controversy about the benefit of elective central compartment neck dissection in the cN0 central neck.

Clearly, there is no evidence that elective CND results in improved survival. However, proponents of the procedure argue that removal of occult disease may reduce post operative thyroglobulin (Tg) levels (10), allow improved selection of patients for adjuvant therapy (11) and reduce recurrence rates or need for reoperation (12). On the other hand, those who do not support elective CND cite low rates of identifiable persistent or recurrent central compartment disease during short term follow up of such patients (13). In addition, in those patients who do recur, after an initial central compartment elective dissection, disease is found in areas of the central compartment which are not normally dissected in the elective procedure (14). The long term outcome of observation of the central neck in cN0 patients is unknown. The American Thyroid Association (ATA) recently considered the feasibility of a prospective study to address this question (15), and calculated that over 5000 patients would have to be recruited, making such a trial impractical.

Our institutional approach has been to perform therapeutic CND only when disease is suspected based on pre-operative examination and imaging and intra-operative evaluation of the central neck. The aim of this study is to report the long-term outcomes of a large cohort of cN0 patients with PTC who underwent total thyroidectomy and post-operative observation of the central neck, in order to determine the rates of recurrence and reoperation in these patients.

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Patients and Methods

Following approval by the Institutional Review Board, we analyzed patients with papillary thyroid carcinoma undergoing total thyroidectomy. From an institutional database of 1810 consecutive patients who underwent surgery for differentiated thyroid cancer in MSKCC, 62 were excluded with non-papillary histology, 44 had distant metastases at presentation and 575 had less than total thyroidectomy. Therefore, we identified 1129 consecutive patients with PTC, who were considered free of distant metastases and had total thyroidectomy for resectable disease between 1986 and 2005.

The whole group was stratified by nodal status. 470 patients (42%) had pathological nodal metastases (pN1), 384 (34%) had nodes removed without metastases (pN0) and the remaining 275 patients (24%) had no nodal tissue removed (Nx). Twenty-two percent of our pN0 cohort and 76% of the pN1 cohort had neck dissection, whereas he remaining patients had nodal tissue removed without formal neck dissection. The surgical details were extracted from the operative report. The pathological details were extracted from the pathology report. The group of patients who had nodes removed without formal neck dissection consists both of patients who had nodal tissue excised inadvertently as part of the total thyroidectomy, and also those who had node sampling during the procedure. In an attempt to avoid ambiguity in terms of lymph node removal, only those patients who did not undergo neck dissection, and had no nodes removed during surgery (Nx group) and so had no sampling of the central neck nodes were chosen as the study cohort.Data collected included patient demographics and surgical details including the presence of gross extra-thyroid extension. Histopathological details recorded included tumor histology, primary tumor size and presence of extra-thyroid extension. Post-operative treatment details recorded included use of RAI and post-operative structural and functional imaging.

In the cohort of patients from 1986 to 2005, ultrasound was not routinely used for pre-operative assessment of the central or lateral compartment lymph nodes. The assessment of the lateral neck nodes was based on preoperative clinical examination. Assessment of the central compartment for all patients was by intraoperative evaluation and palpation of the lymph nodes at the time of thyroidectomy. If no suspicious nodes were present in the central compartment, then no elective central compartment neck dissection was done. If suspicious nodes were noted, then a central compartment neck dissection was carried out. Frozen section of the lymph nodes was generously used. Post operative thyroid stimulating hormone (TSH) suppression is practiced for all patients, aiming for a level of between 0.1-0.5mcUnits/ml.

Outcomes data included local, regional and distant recurrence as well as details of death. In order to encompass all potential events, local, regional and distant recurrences were determined by clinical examination, ultrasound, radioiodine scan or biochemical assay with or without cytological confirmation. Local recurrence was considered as disease suspected

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or proven in the thyroid bed. Regional recurrence included disease suspected or proven in the regional lymphatics (either central or lateral with additional information on all recurrences provided). Distant recurrence included disease in any site beyond the thyroid bed and regional lymhpatics.

Disease specific outcomes were calculated using the date of last follow up with the treating surgeon or endocrinologist at MSKCC. Details of death were determined from death certificates and hospital records where available. All patients who had evidence of active structural disease at the time of last follow-up and died during follow up were considered to have died of disease. The median follow-up for the entire patient cohort was 70 months (range 1-275 months).

Initially all surgical patients were followed by the attending surgeon in MSKCC, with input from the endocrinologists and nuclear medicine physicians as required. The majority of patients are now followed by both the surgeon and endocrinologist at MSKCC, all of whom are specialized in the management of thyroid cancer. A minority of patients were followed by local endocrinologists.

During the time period of the study from 1986 to 2000, serum thyroglobulin was not routinely used to detect recurrence. Similarly, annual ultrasound was not uniformly used as a tool for detection of clinically occult recurrent disease during the majority of the study period. Both ultrasound and thyroglobulin measurement have become routine in the past 10 years for follow up of patients with PTC within our institution. A total of 114 patients (41%) underwent ultrasound examination during follow up. Of those who had ultrasound the median number of examinations during follow up was 4 (range 1-14). A total of 167 patients (61%) had Tg monitoring during follow up. Of those who had Tg monitoring, the median number of Tg levels analyzed was 6 (range 1-34). Three of the 11 recurrences (27%) were detected in patients who were operated up to 2000, the remaining 8 recurrences (78%) were detected in patients operated on after 2000.

Statistical analysis was carried out using SPSS 19 (IBM Corporation). Variables were compared within groups using Pearson’s chi squared test. Survival outcomes were analyzed using the Kaplan-Meier method. Univariate analysis was carried out by the log rank test. A p value less than 0.05 was considered significant.

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Results

The median age of the Nx group was 51 years (range 20-83 years), and 73% were female. The age distribution and year of surgery for the cohort is displayed in Figure 1 and Figure 2. pT stage was T1 in 149 patients (54%) ,T2 in 59 (21%),T3 in 61 (22%)and T4 in 6 patients (3%). One hundred and thirty-three patients (48%) were treated with adjuvant RAI based on patient and primary tumor characteristics (Table 1). Table 1 shows comparison of patient and tumor characteristics of the observed group (Nx) compared to the patients who had CND (pN0 and pN1). As expected, the patient and tumor characteristics of the Nx and pN0 patients were very similar. However, in comparison with those patients who had pN1 disease, the pNx group was more likely to be older, female and have a lower pT stage. This Nx group was less likely to receive adjuvant RAI.When stratified by the use of RAI (Table 2), those selected for RAI were more likely to be male (35% versus 19%, p<0.001) and have advanced (pT3/T4) primary tumors (39% versus 11%, p<0.001).With a median follow up of 70 months (range 1-275 months), the 10 year disease specific survival and recurrence free survival in the Nx group were 100% and 94% respectively (Figure 3). Four patients did have suspicion of recurrence in the thyroid bed on subsequent imaging. Three patients had an RAI scan which showed uptake in the central neck, either normal thyroid tissue or recurrence. All were treated with RAI, and therefore despite the absence of diagnostic cytology, these were considered local recurrences for the purposes of coding in this study. One patient had a non specific thyroid bed nodule on ultrasound which was found to be RAI avid on subsequent imaging. He was also treated with RAI and therefore coded as having local recurrence. All 4 of these patients are still alive and have subsequently been free of disease for a median follow up of 124 months (range 116-161 months). No patients within this cohort (0%) required further surgery to the central neck for recurrence to central compartment neck nodes or the thyroid bed.Five patients (5/275, 1.8%) were considered to have evidence of regional disease during follow up. Three of these had biopsy proven lateral neck disease and underwent neck dissection, one of whom also recurred in the lung. Of the remaining 2 patients 1 had a low level detectable thyroglobulin (4ng/ml) without demonstrable structural disease and 1 had a sub-centimeter level VI neck node suspicious for recurrence which has been observed. Overall therefore, only 1 patient had true nodal recurrence in the central neck (1/275, 0.4%). Two patients developed pulmonary metastases. When all patients with suspicion of disease (proven by biopsy, or suspected based upon Tg or RAI imaging) were included in the analysis, the 10 year local, regional and distant recurrence rates were 2%, 3% and 2% respectively. The staging, treatment and recurrence details of these 11 patients are shown in Table 3. The median age of this group was 60 years (range 24-76). Six patients (55%) received post operative RAI.Factors predictive or outcome are shown in Table 4. Male gender and advanced pT stage both

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showed an association with regional recurrence on univariate analysis. However, there were insufficient events to support a multivariate analysis.Those patients who did not receive RAI were found to have higher rates of recurrent local disease than those who did receive RAI (5% versus 0% at 5 years, p=0.018). All of these 4 local recurrences were characterized by a delayed RAI scan which showed residual uptake in the thyroid bed rather than any cytological or histological demonstration of disease. Of the 133 patients managed without RAI, only 1 had a structural recurrence. This patient developed disease in the lateral neck 13 years after initial thyroidectomy, which was treated with selective lateral neck dissection and post operative RAI. This patient went on to die of bronchial carcinoma at the age of 92 years.

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Discussion

Few topics in the management of PTC are as controversial as the elective management of the central neck in patients with clinically uninvolved central neck nodes. The reason that this debate remains unresolved is that outcomes in these patients are excellent (16). Deaths are rare and recurrence is uncommon. With such low potential for improving outcomes in this group, prospective randomized trials are not feasible (15). A number of factors have led to a divergence of opinions amongst experts within the field. Identification of nodal metastases in the central neck is challenging without histological analysis. Although ultrasound allows accurate identification of metastatic disease in the lateral neck, it is less useful in the central compartment when the thyroid gland is still present (17). Intra-operative clinical assessment of lymph nodes is also inaccurate (11), and can be confounded by the presence of enlarged nodes related to Hashimoto’s thyroiditis. Those who argue for elective CND highlight the high rates of histologically identified metastatic nodes within the elective CND specimens (9). The presence of this occult nodal disease contributes to an upstaging of older patients by AJCC criteria (18, 19). This in turn may influence decisions regarding adjuvant radioactive iodine (RAI) therapy in up to one third of patients (11).An argument has also been made that elective CND results in lower post operative Tg levels (10). Reducing the Tg, and by inference the burden of disease, within this patient group may improve outcome and facilitate follow up, although this finding has not been widely reproduced (11). Whether elective CND results in reduced recurrence rates is controversial. Elective CND has never been shown to improve survival. Microscopic metastases, which are present in around 40% of such patients, rarely progress to become clinically meaningful disease. Therefore, the excellent outcomes enjoyed by cN0 patients managed with surgery alone questions the clinical utility of upstaging these patients and exposing them to the side effects and associated risks of RAI. In addition, the rarity of recurrence in this patient group casts doubt on the need for additional surgery in order to facilitate post operative surveillance. Given the lack of evidence in outcome from elective CND, one must carefully weigh up any potential benefit from surgery with the potential risks associated with CND such as damage to the recurrent laryngeal nerves (RLN) and inadvertent removal of parathyroid glands resulting in hypoparathyroidism. There is no doubt that removal of tissue from the para tracheal region places the parathyroid glands and recurrent laryngeal nerve (RLN) at risk (19). Although a number of expert groups have demonstrated that elective CND can be performed with low rates of complication (9, 11), such evidence is lacking for patients managed outside centers of excellence where the majority of patients are managed.A further surgical issue relating to the role of elective CND is the impact of primary surgery on the hazards of re-operating on the central neck. Re-operation has been associated with higher rates of hypoparathyroidism and RLN injury (20), and therefore clinicians must balance the increased risks of additional primary surgery against the potential for increased risk during

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subsequent procedures for recurrent disease. Indeed, the morbidity of surgery has resulted in the ATA guidelines recommending that elective lateral neck dissection should not be performed, despite a known risk of occult disease of around 23% (9). A more subtle argument in relation to recurrent disease in the central neck is related to the exact anatomical location of recurrence Clayman et al. in their report on 210 patients who underwent surgery on the central neck for persistent or recurrent nodal disease, found that up to 60% of patients had disease dorsal to the RLN (14). Additionally, high rates of disease were reported at the inlet of the RLN, at the cricopharyngeus muscle and in relation to the vertebral artery. Because of thepotential for complications related to dissection in these areas during primary surgery , they are not routinely addressed in elective CND. Therefore elective CND may not prevent the manifestation of disease in such high risk sites.In 2006, the ATA published guidelines stating “Routine central-compartment (level VI) neck dissection should be considered for patients with PTC” (21). This statement resulted in significant controversy, due to the lack of any definitive evidence. In their most current guidelines, published in 2009, the ATA changed their recommendations:, stating “Prophylactic central-compartment neck dissection may be performed in patients with PTC, especially for advanced primary tumors (T3 or T4)”. They go on to comment that the approach to the central neck should take in to consideration surgical expertise, recognizing that in low volume units, the risk benefit ratio may favor total thyroidectomy alone with observation of the central neck. This change reflected the ongoing debate over the role of prophylactic central nodal dissection. In our study, we report on 275 cN0 patients selected for observation of the central neck. No patient died during follow up and no patients required additional surgery to the central compartment. Only 11 patients (11/275, 4%) were suspected of having recurrent disease at some point during follow up. Of these, only 1 patient had proven recurrent structural disease in the central neck (1/275, 0.4%) which currently remains under observation. Three patients developed biopsy proven disease in the lateral neck (3/275, 1%), all of who underwent lateral neck dissection. Two patients developed distant metastases (2/275, 1%). The remaining 5 patients had either the suspicion of disease in the central neck on RAI scanning which was treated with RAI and are now considered disease free (4/275, 1%) or a raised Tg without structural evidence of disease (1/275, 0.4%). Around half of this cohort received adjuvant RAI. Of the 133 patients (48%) who were managed without RAI, only 1 patient had a recurrence. Our results therefore provide compelling evidence that patients with cN0 PTC can be managed safely with observation of the central neck. Such patients undoubtedly benefit from avoidance of any iatrogenic injury to RLNs and parathyroid glands. We do recognize that our study has limitations due to the retrospective nature of the study design. Our patient group was managed over a 20 year period, and although in the early stages of the study ultrasound was not used, in later years it became a routine part of pre operative clinical assessment. It is therefore likely that an increasing number of the latter patients will have suspicious disease identified prior to surgery. If anything this strengthens our results, as even in the older patients, who were likely to have had disease which today would be identified and resected, outcomes were excellent.

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The introduction of routine serial ultrasound and Tg in the follow up of these patients has also impacted on post-operative outcomes in patients with PTC. Such studies were not available during the early stages of this study, and it is conceivable that patients lost to follow up prior to the routine use of such investigations may have harbored occult persistent nodal disease. These highly sensitive investigations have allowed the identification of increasingly low volume disease. However, whether this will result in improved patient outcomes, or simply added anxiety and side effects related to intervention is not clear. Despite this, our study adds follow-up data to more contemporary cohorts, such as that reported by Monchik et al (13). This group concluded that elective CND is not required in selected low risk patients with PTC. They report that only 1.8% of 192 patients selected not to undergo elective CND had biopsy proven persistent disease in the central compartment 4-6 months following surgery.

In conclusion, we have shown that those patients without pre- or intra-operative evidence of nodal disease, who are observed, have low rates of recurrence and excellent outcome, including regional recurrence and survival. Despite the fact that these patients are likely to have a significant rate of occult micrometastasis, such patients can safely be managed with observation rather than elective central neck dissection.

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2. Roh JL, Park JY, Park CI. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone. Ann Surg. 2007 Apr;245(4):604-10. PubMed PMID: 17414610. Pubmed Central PMCID: 1877043.

3. Randolph G, Duh QY, Heller KS, Livolsi VA, Mandel SJ, Steward D, et al. The Prognostic Significance of Nodal Metastases from Papillary Thyroid Carcinoma can be Stratified Based on the Size and Number of Metastatic Lymph Nodes, as Well as the Presence of Extranodal Extension ATA Surgical Affairs Committee’s Taskforce on Thyroid Cancer Nodal Surgery. Thyroid.2012 Aug 10. PubMed PMID: 22881837.

4. Cady B, Sedgwick CE, Meissner WA, Bookwalter JR, Romagosa V, Werber J. Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma. Ann Surg. 1976 Nov;184(5):541-53. PubMed PMID: 984923. Pubmed Central PMCID: 1345475. Epub 1976/11/01.eng.

5. Hughes CJ, Shaha AR, Shah JP, Loree TR. Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis. Head Neck. 1996 Mar-Apr;18(2):127-32. PubMed PMID: 8647677. Epub 1996/03/01.eng.

6. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov;19(11):1167-214. PubMed PMID: 19860577. Epub 2009/10/29.eng.

7. Bardet S, Malville E, Rame JP, Babin E, Samama G, De Raucourt D, et al. Macroscopic lymph-node involvement and neck dissection predict lymph-node recurrence in papillary thyroid carcinoma. Eur J Endocrinol. 2008 Apr;158(4):551-60. PubMed PMID: 18362303.

8. Gemsenjager E, Perren A, Seifert B, Schuler G, Schweizer I, Heitz PU. Lymph node surgery in papillary thyroid carcinoma. J Am Coll Surg. 2003 Aug;197(2):182-90. PubMed PMID: 12892795.

9. Hartl DM, Leboulleux S, Al Ghuzlan A, Baudin E, Chami L, Schlumberger M, et al. Optimization of staging of the neck with prophylactic central and lateral neck dissection for papillary thyroid carcinoma. Ann Surg. 2012 Apr;255(4):777-83. PubMed PMID: 22418010.

10. Popadich A, Levin O, Lee JC, Smooke-Praw S, Ro K, Fazel M, et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer.Surgery. 2011 Dec;150(6):1048-57. PubMed PMID: 22136820.

11. Hughes DT, White ML, Miller BS, Gauger PG, Burney RE, Doherty GM. Influence of prophylactic central lymph node dissection on postoperative thyroglobulin levels and radioiodine treatment in papillary thyroid cancer. Surgery. 2010 Dec;148(6):1100-6; discussion 006-7. PubMed PMID: 21134539.

12. Scheumann GF, Gimm O, Wegener G, Hundeshagen H, Dralle H. Prognostic significance and surgical management of locoregional lymph node metastases in papillary thyroid cancer. World J Surg. 1994 Jul-Aug;18(4):559-67; discussion 67-8. PubMed PMID: 7725745. Epub 1994/07/01.eng.

13. Monchik JM, Simon CJ, Caragacianu DL, Thomay AA, Tsai V, Cohen J, et al. Does failure to perform prophylactic level VI node dissection leave persistent disease detectable by ultrasonography in patients with low-risk papillary carcinoma of the thyroid? Surgery. 2009 Dec;146(6):1182-7. PubMed PMID: 19958947. Epub 2009/12/05.eng.

14. Clayman GL, Agarwal G, Edeiken BS, Waguespack SG, Roberts DB, Sherman SI.Long-term outcome of comprehensive central compartment dissection in patients with recurrent/persistent papillary thyroid carcinoma.Thyroid. 2011 Dec;21(12):1309-16. PubMed PMID: 22136266.

15. Carling T, Carty SE, Ciarleglio MM, Cooper DS, Doherty G, Kim LT, et al. American Thyroid Association (ATA) - Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma. Thyroid.2011 Dec 9. PubMed PMID: 22150591. Epub 2011/12/14. Eng.

16. Nixon IJ, Ganly I, Patel SG, Palmer FL, Whitcher MM, Tuttle RM, et al. Thyroid lobectomy for treatment of well differentiated intrathyroid malignancy.Surgery. 2012 Apr;151(4):571-9. PubMed PMID: 22001636. Epub 2011/10/18.eng.

17. Hwang HS, Orloff LA. Efficacy of preoperative neck ultrasound in the detection of cervical lymph node metastasis from thyroid cancer.Laryngoscope. 2011 Mar;121(3):487-91. PubMed PMID: 21344423.

18. Edge SB, American Joint Committee on Cancer. AJCC cancer staging manual. 7th ed. New York: Springer; 2010. xiv, 648 p. p.

19. Bozec A, Dassonville O, Chamorey E, Poissonnet G, Sudaka A, Peyrottes I, et al. Clinical impact of cervical lymph node involvement and central neck dissection in patients with papillary thyroid carcinoma: a retrospective analysis of 368 cases. Eur Arch Otorhinolaryngol. 2011 Aug;268(8):1205-

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12. PubMed PMID: 21607578. Epub 2011/05/25.eng.

20. Pai SI, Tufano RP. Reoperation for recurrent/persistent well-differentiated thyroid cancer. Otolaryngol Clin North Am. 2010 Apr;43(2):353-63, ix. PubMed PMID: 20510718.

21. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006 Feb;16(2):109-42. PubMed PMID: 16420177. Epub 2006/01/20.eng.

Table 1: Comparison of group stratified by pN0/N1/Nx

Variable pN0 (n=384) pN1 (n=470) Nx (n=275) p Value

Age <=45y 153 (40%) 272 (58%) 101 (37%) <0.001

>45y 231 (60%) 198 (42%) 174 (63%)

Gender Female 326 (85%) 301 (64%) 201 (73%) <0.001

Male 58 (15%) 169 (36%) 74 (27%)

pT T1 227 (59%) 130 (28%) 149 (54%) <0.001

T2 55 (14%) 63 (13%) 59 (21%)

T3 90 (23%) 205 (43%) 61 (22%)

T4 11 (3%) 71 (15%) 6 (3%)

Tx 1 (1%) 1 (1%) 0

cN N0 301 (78%) 115 (24%) 273 (99%) <0.001

N1a 57 (15%) 84 (18%) 2 (1%)

N1b 26 (7%) 271 (58) 0 (0%)

pN N1a 204 (43%)

N1b 239 (51%)

N1x 27 (6%)

RAI Yes 212 (55%) 386 (82%) 142 (52%) <0.001

No 172 (45%) 84 (18%) 133 (48%)

Neck Surgery Neck Dissection 83 (22%) 355 (76%) <0.001

Node Sampling 301 (78%) 115 (24%)

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Table 2. Demographics of the Nx Group Stratified by RAI

Variable RAI (n=133)No RAI

(n=142)p

Age <=45y 55 (41%) 54 (38%) 0.573

>45y 78 (59%) 88 (62%)

Gender Female 86 (65%) 115 (81%) 0.002

Male 47 (35%) 27 (19%)

pT T1 45 (34%) 104 (73%) <0.001

T2 36 (27%) 23 (16%)

T3 46 (35%) 15 (11%)

T4 6 (4%) 0 (0%)

Table 3. Treatment and recurrence details of patients who recurred during follow up

AgepT

StageRAI LR

Time to recurrence

RRTime to

recurrenceDR

Time to Recurrence

Total Follow

up

24 T2 No Yes 15 No No 130




76 T2 No No Yes 72 No 178

38 T3 Yes No Yes 4 No 78



69 T3 Yes No Yes 81 Yes 57 142

60 T1 Yes No No Yes 10 59

71 T3 Yes No No Yes 62 64

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Table 4. Factors predictive of recurrence free survival for the pNx group

Variable5y Regional Recurrence

Ratep

5y Local Recurrence

Ratep

5yDistant

Recurrence Ratep

>45y 1% 1% 2%

Gender Female 0% 0.007 2% 0.921 1% 0.783

Male 3% 2% 2%

pT T1 0% 0.029 1% 0.579 1% 0.402

T2 0% 5% 0%

T3 4% 2% 3%

T4 0% 0% 0%

RAI Yes 2% 0.505 0% 0.018 0% 0.134

No 0% 5% 2%

Figure 1 Age Distribution of the Cohort by Decade

20-29 30-39 40-49 50-59 60-69 70+

Age by Decade

30%

25%

20%

15%

10%

5%

0%

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Figure 2Year of Surgery

70%

60%

50%

40%

30%

20%

10%

0 1985-1990 1991-1995 1996-2000 2001-2005

Figure 3Disease specific and recurrence free survival

uva-dare (digital academic repository) oncological ... · 1129 patients with ptc, who had total...

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