Oncological outcomes for patients with well differentiated thyroid cancer Nixon, I.J.

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1 UvA-DARE (Digital Academic Repository) Oncological outcomes for patients with well differentiated thyroid cancer Nixon, I.J. Link to publication Citation for published version (APA): Nixon, I. J. (2013). Oncological outcomes for patients with well differentiated thyroid cancer General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 07 Jul 2018

2 Chapter 4 Thyroid Isthmusectomy for Well Differentiated Thyroid Cancer Iain J Nixon, MD, Frank L. Palmer, BA, Monica M Whitcher, BA, Ashok R Shaha, MD, Jatin P Shah, MD, Snehal G Patel, MD, Ian Ganly, MD, PhD Ann Surg Oncol 2011; 18(3):

3 Abstract Background The American Thyroid Association guidelines do not mention isthmusectomy as an appropriate procedure for thyroid cancer. Despite this, a small number of patients present with lesions isolated to the thyroid isthmus, which can be excised without exploring the trachesophageal grooves or total thyroidectomy. The aim of this study was to analyse outcomes in patients treated with isthmusectomy for small well differentiated thyroid cancer (WDTC) at our institution. Methods Nineteen patients with WDTC managed by isthmusectomy were identified from a database of 1810 patients (1%) with WDTC managed by surgery in Memorial Sloan Kettering Cancer Center, between Demographic, surgical, pathological and outcomes data were analyzed. Results Six patients were male and 13 female. The median age was 46 years (range years). All patients had a solitary nodule confined to the thyroid isthmus. The median size of lesion was 1cm (range 0.4-3cm). Eighteen patients had a pathologically T1 disease (pt1), 1 patient had a pt2 lesion. Two patients had papillary carcinoma detected in peri-thyroid lymph nodes (pn1a). There were no complications of recurrent laryngeal nerve palsy or hypocalcaemia. With a median follow up of 124 months (range ), the 10 year disease specific survival was 100% and 100% local and regional 10 year recurrence free survival. Conclusion 54 Our results suggest that isthmusectomy alone may be sufficient treatment in selected patients with small WDTC limited to the isthmus. This procedure has the benefit of avoiding dissection of the recurrent laryngeal nerve and parathyroid glands thus limiting post operative complications.

4 Cyclooxygenase-2 inhibition inhibits c-met kinase activity and Wnt activity in colon cancer. The place of thyroid isthmusectomy in the management of thyroid cancer is unclear. Neither the current American Thyroid Association1 nor the British Thyroid Association guidelines2 mention isthmusectomy as an appropriate procedure in the setting of thyroid cancer. Despite this, a small number of patients will present with malignant disease isolated to the thyroid isthmus, which can be excised without exploring the trachesophageal grooves. This approach has the attraction of reducing the potential for damage to the recurrent laryngeal nerves and parathyroid glands, as well as reducing operating time. Of the few reports in the literature on thyroid isthmusectomy3-6, most series include only small numbers of malignant lesions. Of the malignant lesions, most patients were treated with completion thyroidectomy after isthmusectomy. The aim of our study was to analyse the outcomes of patients treated with thyroid isthmusectomy alone for localized well differentiated thyroid cancer over a 20 year period at our institution. This is the largest series reporting on the role of isthmusectomy alone in the management of thyroid cancer confined to the isthmus. Chapter 4 Introduction 55

5 Methods and Patients Following approval by the Institutional Review Board, nineteen patients with well differentiated thyroid cancer managed by thyroid isthmusectomy alone were identified from a database of 1810 patients (1%) with well differentiated thyroid cancer managed by surgery in Memorial Sloan Kettering Cancer Center, between Patients who underwent initial treatment elsewhere prior to referral or those who were considered unresectable at the time of referral were excluded. Data was extracted from the electronic medical record and entered into an Excel spreadsheet for analysis. Data was collected on patient demographics, surgical details including extent of both thyroid and neck surgery, and the presence of gross extra-thyroid extension or residual disease on completion of surgery. Pathological details included tumor histology, size, and presence of extra-thyroid extension. Outcomes data included local, regional or distant recurrence. The presence of local or regional recurrence following treatment was based on cytological or histopathological evidence of disease. Distant disease was determined by imaging studies including radioiodine uptake scans and CT scans, or cytological and histopathological evidence where available. Biochemical evidence of recurrence was not accepted as definitive, as the use of thyroglobulin measurement was not routine practice during the early part of the study period, and may be difficult to interpret in the presence of normal thyroid lobes. Statistical analysis was performed using JMP statistical package (SAS Institute Inc. SAS Campus Drive, Cary, NC 27513). Survival outcomes were analyzed using the Kaplan-Meier method. 56

6 The clinical and pathological characteristics are shown in Table 1. Pathology In 18 patients (95%) the diagnosis was papillary carcinoma. The remaining 1 patient (5%) had follicular carcinoma. The median size of lesion was 1cm (range 0.4-3cm). Eighteen patients had a pathologically T1 disease (pt1), 1 patient had a pt2 lesion. Two patients had papillary carcinoma detected in peri-thyroid lymph nodes, making them pn1a. In two patients the surgical margin was microscopically positive. Two patients had microscopic extra thyroid extension noted on histopathology with no evidence of extension seen during surgery. Following surgical excision 8 patients (42%) were classified as low risk, 9 as intermediate (47%) and 2 were classified as high risk (11%) using the GAMES criteria. Outcomes There were no complications of recurrent laryngeal nerve palsy or hypocalcaemia. One patient had a wound hematoma managed at the bedside without return to the operating room. The median follow up was 124 months (range ). During this time there were no disease specific deaths (10 year disease specific survival 100%). The 10 year overall survival was 94%, one patient died at 65 months of unrelated causes. There were no regional or distant recurrences. One patient had a papillary carcinoma removed from the right thyroid lobe at 124 months by uncomplicated completion thyroidectomy. That patient was a low risk female, with a 1cm tumor without extra thyroid extension. No patient with positive margins or microscopic extra thyroid extension had a local or regional recurrence. Cyclooxygenase-2 inhibition inhibits c-met kinase activity and Wnt activity in colon cancer. Patient and Treatment Characteristics Six patients were male and 13 female. The median age was 46 years (range years). All patients had a solitary nodule confined to the thyroid isthmus. Eighteen patients (95%) were T1 and 1 patient (5%) was T2. Eighteen patients (95%) were clinically N0 and 1 patient (5%) was clinically N1b. All patients were free of distant metastases. Nine patients (47%) were first diagnosed with malignancy on pre-operative fine needle aspiration (FNA), a further 3 patients (16%) were diagnosed at frozen section in the operating room. Seven patients (37%) were diagnosed on final histopathological analysis. The 1 patient with a palpable cervical lymph node had failed to respond to chemoradiotherapy for an oropharyngeal cancer, and had a suspicious nodule in the thyroid isthmus on CT scan, which was positive for papillary carcinoma. The cervical node was found to contain squamous cell carcinoma on histopathological analysis. This patient had isthmusectomy and modified radical neck dissection. All remaining patients underwent thyroid isthmusectomy alone. No patients received post-operative radio-iodine treatment. Chapter 4 Results 57

7 Discussion 58 Outcomes for patients with well differentiated thyroid cancers are excellent with 20 year survival rates of around 90%7-10. Current guidelines do not support surgical management of thyroid cancer with procedures other than thyroid lobectomy, near-total and total thyroidectomy1,2. There are no specific guidelines for management of thyroid cancers confined to the thyroid isthmus. Although the majority of thyroid nodules present within the body of the lobes, a small minority of patients will present with disease limited to the isthmus11. Lesions of the thyroid isthmus occur in less than 10% of patients presenting with thyroid cancer, and may have a higher incidence of both multifocality and capsular invasion than cancers presenting in the lobes11. If, in this situation, the nodule is solitary, confined to the isthmus without evidence of extra glandular extension, the patient may be suitable for thyroid isthmusectomy or wide field isthmusectomy. Unlike excision of a thyroid lobe, isthmusectomy does not require exploration of the trachesophageal groove or formal identification of the recurrent laryngeal nerve, which may reduce risk to the parathyroid glands and the recurrent laryngeal nerve. Although thyroid isthmusectomy is a recognised surgical procedure, few groups have reported their experience with the procedure for thyroid cancer 3-6,12. In the majority of reports in which a cancer is found after isthmusectomy, completion thyroidectomy is normally performed. Perez-Ruiz et al report a series of 31 isthmusectomies including only 1 papillary carcinoma, who proceeded to completion thyroidectomy 1 week later4. Similarly, Skilbeck et al report their experience of 9 isthmusectomies for isolated isthmic lesions with indeterminate cytology5. Two of their patients were finally diagnosed with malignancy and both patients again proceeded to completion thyroidectomy. Maser et al report on 8 patients with benign or indeterminate cytology from an isthmic nodule. Three of their patients were diagnosed with malignancy on histopathology and all went on to completion thyroidectomy3. In Sugenoya et al s report on 19 well differentiated thyroid isthmus malignancies, four patients were treated with isthmusectomy alone and all were alive with no evidence of recurrence 20 years following surgery. This finding prompted the authors to recommend isthmusectomy as an appropriate treatment for malignant lesions of the thyroid isthmus6. We advocate isthmusectomy for an isolated lesion of the thyroid isthmus without evidence of extraglandular spread on imaging or assessment in the operating room. Using these criteria only 19 of 1811 patients (1%) were deemed suitable for isthmusectomy between 1986 and All patients in this study had clinically apparent disease limited to the thyroid isthmus. In 1 patient suspected of having metastasis to the lateral neck, the metastatic malignancy was from an aerodigestive tract primary rather than from the thyroid. With a median follow up of over 10 years, disease specific survival and both regional and distant recurrence free survival in our group was 100%. One patient died of unrelated causes during the study period. One patient developed a papillary cancer in the residual thyroid tissue and underwent uneventful completion thyroidectomy over 10 years following initial surgery. We encountered no cases of hypocalcaemia or recurrent laryngeal nerve damage.

8 Chapter 4 Cyclooxygenase-2 inhibition inhibits c-met kinase activity and Wnt activity in colon cancer. Using our previously published risk stratification scheme, GAMES, 58% of patients were classified as intermediate or high risk. Despite this, our results suggest that in carefully selected patients, thyroid isthmusectomy can be effective treatment for well differentiated thyroid cancer. Thyroid isthmusectomy should be reserved for selected patients with a small thyroid tumor with no major extrathyroidal extension or adherence to the surrounding structures. It should be recognized that this is not a nodulectomy, it is an oncologic procedure with wide-field isthmusectomy which encompasses all gross tumor and a surrounding portion of normal thyroid tissue. Most of these patients are low or intermediate risk thyroid cancer patients who do not require postoperative radioactive iodine ablation. The preoperative ultrasound should be reviewed carefully to ensure there is no nodularity involving either lobe of the thyroid. Postoperative follow-up is generally clinical follow-up along with sonographic evaluation and thyroid function tests, etc. In our experience, this is a sound oncologic surgical procedure for small tumors involving the isthmus of the thyroid. 59

9 Conclusion Our results suggest that isthmusectomy alone may be sufficient treatment in selected patients with small, well differentiated cancer limited to the thyroid isthmus. This procedure has the added benefit of avoiding dissection of the recurrent laryngeal nerve and parathyroid glands thus limiting post-operative complications of hoarseness and hypocalcaemia. 60

10 Cyclooxygenase-2 inhibition inhibits c-met kinase activity and Wnt activity in colon cancer. 1. Cooper, D.S., G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L. Mazzaferri, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, (11): Watkinson, J.C. The British Thyroid Association guidelines for the management of thyroid cancer in adults.nucl Med Commun, (9): Maser, C., P. Donovan, and R. Udelsman. Thyroid isthmusectomy: a rarely used but simple, safe, and efficacious operation. J Am Coll Surg, (3): Perez-Ruiz, L., S. Ros-Lopez, M. Gudelis, J.A. LatasaGimeno, C. Artigas-Marco, and A. Pelayo-Salas. Isthmectomy: a conservative operation for solitary nodule of the thyroid isthmus. Acta Chir Belg, (6): Skilbeck, C., A. Leslie, and R. Simo. Thyroid isthmusectomy: a critical appraisal. J Laryngol Otol, (10): Sugenoya, A., K. Shingu, S. Kobayashi, H. Masuda, S. Takahashi, T. Shimizu, H. Onuma, et al. Surgical strategies for differentiated carcinoma of the thyroid isthmus. Head Neck, (2): Hay, I.D., E.J. Bergstralh, J.R. Goellner, J.R. Ebersold, and C.S. Grant. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through Surgery, (6): ; discussion Mazzaferri, E.L. and S.M. Jhiang. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer.the American journal of medicine, (5): Lin, H.W. and N. Bhattacharyya. Survival impact of treatment options for papillary microcarcinoma of the thyroid. Laryngoscope, (10): Shaha, A.R., J.P. Shah, and T.R. Loree. Risk group stratification and prognostic factors in papillary carcinoma of thyroid. Ann Surg Oncol, (6): Lee, Y.S., J.J. Jeong, K.H. Nam, W.Y. Chung, H.S. Chang, and C.S. Park. Papillary carcinoma located in the thyroid isthmus. World J Surg, (1): Saadi, H., P. Kleidermacher, and C. Esselstyn, Jr. Conservative management of patients with intrathyroidal well-differentiated follicular thyroid carcinoma. Surgery, (1): Chapter 4 References 61

11 Table 1. Clinical and pathological characteristics Variables N (%) Age <45y 9 (47%) >45y 10 (53%) Gender Male 6 (32%) Female 13 (68%) N0 18 (95%) N1b 1 (5%) (Ultimately SCC) M0 19 (100%) M1 0 cn Stage M Stage Histology Papillary Ca 18 (95%) Follicular Ca 1 (5%) Negative 17 (89%) Positive 2 (11%) T1 18 (95%) T2 1 (5%) Margins pt Stage 62 Extra Thyroid Extension None 17 (89%) Microscopic 2 (11%) pn Stage N0 17 (89%) N1a 2 (11%) GAMES Criteria Low 8 (42%) Intermediate 9 (47%) High 2 (11%) GAMES is the method of risk stratification used in Memorial Sloan Kettering Cancer Center10

Oncological outcomes for patients with well differentiated thyroid cancer Nixon, I.J.

UvA-DARE (Digital Academic Repository) Oncological outcomes for patients with well differentiated thyroid cancer Nixon, I.J. Link to publication Citation for published version (APA): Nixon, I. J. (2013).