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Brownlie and colleagues1in this issue of the NZMJhave reviewed the outcomes of the bulk of the New Zealand South Island cases of differentiated thyroid cancer (DTC) seen between 1984 and 2009; a total of 411 cases. Twenty-five patients or 6% of the total died, compromising twice as many women as men, with a mean age of 65 years. The patients were operated on by 19 different surgeons and no patient less than 45 years of age died. All deaths were in Caucasian patients, and 15 of the 25 were incurable from the outset as a result of locally advanced unresectable disease or metastatic disease at diagnosis.According to Table 1, local failure in the neck occurred in 9 or 36% of their patients. The ratio of females to males who died was similar to the gender ratio for all differentiated thyroid cancer (DTC) patients: 2.1:1 favouring females. Table 1. Prognostic effects of extra-thyroid extension and regional disease on outcome Variables T4A N0/n1a T4A N1b T1-3 N1b A&W N1 Rec AWD DOD 56% 11/18 66% 9/18 22% 4/18 0 40% 10/25 13% 2/25 50% 9/25* 20% 5/25* 77% 17/22 18% 4/22 9% 2/22 5% 1/22 N0 no regional disease, N/1a central compartment disease; N1b lateral neck disease, A&W alive & well;N1 Rec recurrence in lateral neck; AWD alive with disease; DOD dead of disease. *Significantly different to both the other groups p<0.04 or better; T4A extra-capsular spread. The editorial author has reviewed his personal experience of over 2000 thyroidectomies performed in Auckland between 1984 and 2012; 300 patients had differentiated thyroid cancer. The patients treated between 1984 and 2007 have been analysed. These data have been presented both nationally and internationally but never published. Statistical analysis utilised Chi-squared analysis. Patients were staged in accord with The Mayo Clinic staging MACIS,2 and also using the guidelines from the Joint American Staging System for Thyroid Cancer.3 Lymph node status (levels 1-7) was as described by Memorial Sloan Kettering Cancer Centre.4,5There were 127 DTC patients aged <45 years (97 papillary, 30 follicular), and 123 aged >45 years (94 papillary, 29 follicular). The ethnic distribution was similar for the two age groups with Europeans making up 61%, M ori 13%, Asian 15%, and Pacific 14%. Longest follow-up (FU) is 25 years with mean FU 13 years. The vast majority of patients were treated with total thyroidectomy. Over recent years central node dissection (level 6) has been almost universally performed for papillary cancer or follicular variant of papillary cancer in order to achieve lower recurrence rates in the central compartment and to have a higher percentage of patients with post-op thyroglobulin levels approximating zero.6 In addition for patients with lateral neck disease, neck dissection of levels 2-5 (after level 6 the commonest sites of involvement are in order levels 4,3 and 2 with level 5 being involved in >20% of patients) was employed for most patients.5 There are a number of differences in this Auckland experience when compared with the South Island report of Brownlie and colleagues;1 in particular the following. In Auckland, major prognostic factors governing outcome were similar to those from The Mayo Clinic,2 these included patient age, the presence of locally advanced disease, adequacy of resection, the status of regional disease, the completeness of the resection performed. In addition, in Auckland the ethnicity of the patient was significant with Asian patients having the best outcomes while Pacific patients had the worst outcome especially male Pacific patients aged >45 years.7 Age was a strong prognostic indicator for both recurrence and death in accord with Mazzaferri and Jhiang.8 Recurrence was frequent in young patients and in older patients with the lowest rate of recurrence in middle aged patients. In contrast, DOD and the presence of unfavourable bone mets were largely confined to patients over 60 years of age. See Figure 1. Abbreviations used in the following figures and tables N0 no regional disease, N1b lateral neck disease, N/1a central compartment disease Rec recurrence, N1 Rec Recurrence in lateral neck Mets metastatic disease, M1 Rec develop metastatic disease DOD dead of disease @ Dx at diagnosis NS not statistically significant AWD alive with disease, A&W alive & well * significance p<0.05 ** significance <0.03 or better Figure 1. Effect of age on outcome of papillary cancer Multifocal tumours were associated with less good outcome in patients < 45 years, but multifocality did not influence outcome in older patients. See Figure 2. Figure 2. Multifocal papillary primary: influence of age Progressive increase in tumour size had only a minor effect on outcome, but extra-thyroid spread (T4a) had a major effect on outcome. See Table 2. Table 2. Effect of tumour size and extra-capsular spread (T4A) on outcome Size CM T1 <2 cm T2 2-4 cm T3 >4 cm T4A A&W AWD DOD 96% 67/71 1% 1/71 0% 0/71 91% 78/80 0% 0/80 1% 1/80 80% 22/28 7% 2/28 0% 0/28 49% 21/43** 30% 13/43** 12% 5/43** ** Significant difference from other groups p<0.04 or better. In addition if there was lateral neck disease coupled with a locally invasive primary (Stage T4A N1B) then the outcome was significantly worse. See Table 2. This is in accord with the findings of Hay et al from The Mayo Clinic.2 Also Table 2 demonstrates the relatively good outcome for regional disease when there is no locally invasive primary, the relatively good outcome when a locally invasive primary was not coupled with regional disease. For younger patients, the number of nodes involved impacted on recurrence. See Table 3. This is in accord with Sugatani et al.9 Table 3. Papillary cancer in patients aged <45 years of age: effect of >5 involved nodes Variables Nil or <5 Nodes >5 Nodes A&W N1 Rec M1 Rec DOD 93 % 75/81 6% 5/81 1% 1/81 1% 1/81 57% 8/14 P<0.001 29% 4/14 P<0.01 36% 5/14 P<0.001 0% 0/14 NS In patients aged >45 years the size of nodes impacted significantly on both recurrence and survival. See Table 4. This finding is in agreement with Kitajiri et al.10 Table 4. Papillary cancer in patients aged >45 years: effect of nodes >3 cm diameter Variables No or nodes <3 cm Nodes >3 cm A&W N1 Rec M1 Rec DOD 79% 59/75 9% 7/75 11% 8/75 1% 1/75 38% 6/16 p<.001 19% 3/16 NS 43% 7/16 p<.001 25% 4/16 p<.003 Completeness of resection was a highly significant prognostic factor, as was the case at Mayo [Clinic].2 Patients with extensive disease necessitating borderline resection of cancer involving trachea, larynx, oesophagus did significantly less well than when complete resection could be performed. See Table 5. Table 5. Outcome: incomplete versus complete resection Variables Complete resection Incomplete resection A&W LR Rec AWMets DOD 74% 147/204 1% 2/204 1% 2/204 0.5% 1/205 12% 3/26 p<0.01 31% 8/26 p<0.01 62% 16/26 p<0.01 27% 7/26 P<0.01 Outcome as a function of race is shown in Table 6. The outcomes for Europeans, M ori, and Asians were similar irrespective of age, and the outcomes of Pacific patients aged <45 years were also similar to the above three ethnic groups. Asians were relatively over-represented (Asian population over the study period would have been much less than 50% of the M ori population7), and Asians had the best outcomes of any race with no patients either AWD or DOD. In contrast Polynesians aged >45 years fared significantly worse than other races largely due to the high proportion of males aged >65 years with T4A, N1b disease (6 patients), along with 4 Polynesian males with T4b disease, 3 of whom died of disease. Table 6. Differentiated thyroid cancer (DTC) in all ages: ethnicity versus outcome Variables European Asian M ori Pacific <45 Pacific >45 A&W AWD DOD 88% 127/144 10% 15/144 1% 2/144 100% 37/37 0% 0% 77% 14/18 22% 4/18 0% 73% 11/15 27% 4/15 0% 30% 6/20 p<0.03 45% 9/20 p<0.05 25% 5/20 p<0.03 MACIS score (based on presence of Metastases, Age, Completeness of resection, Invasion and Size2) stratified patients for outcome. See Table 7. Table 7. Outcome of DTC in all ages versus MACIS score MACIS Score <6 6-7 >7 A&W AWD DOD 99% 185/187 0.5% 1/187 0.5% 1/187 66%* 16/24 29%* 7/24 4%* 1/24 21%* 5/24 50%* 12/24 29%* 7/24 * Significantly different to preceding MACIS value p<0.04 or better. When survival as a function of MACIS score for patients treated in Auckland, Mayo [Clinic],2 and Sweden11 were compared, the survival data were similar. See Figure 3. In addition, the percentage of patients with high MACIS score seen in Auckland was double that seen at Mayo. Figure 3. DTC Outcomes of Mayo Clinic (USA) versus Sweden versus Auckland (NZ) Gender was unimportant in survival for any patient group. When all females were compared with all males the outcomes were virtually identical. See Table 8 below. Table 8. DTC effect of gender on outcome: all female patients versus all male patients Variables Females Males A&W AWD DOD 88% 168/192 8% 15/192 5% 9/192 83% 40/48 10% 5/48 6% 3/48 Overall there are a number of differences in outcome for South Island patients versus North Island patients. This is largely explained on the one hand by the higher percentage of good prognosis Asian patients in the North Island coupled on the other hand with a higher proportion of poor prognosis Polynesian patients seen in Auckland, many of whom were referred from Samoa. There is little doubt that most patients with differentiated thyroid cancer are best treated by total thyroidectomy and for papillary cancers a central neck dissection is also appropriate.6 An assessment of the roles of adjuvant radioiodine (RI) and external beam radiation (EBR) in the management of DTC is beyond the scope of this editorial. However it is this author\u2019s view that while RI is useful for treating metastatic thyroid cancer, data supporting its use as an adjuvant therapy in young patients with good prognosis lesions, is limited.12 Available World data indicate that RI may diminish recurrence in older patients with unfavourable prognostic factors.12 In contrast, the data supporting the use of EBR to diminish recurrence in patients with unfavourable central or lateral compartment disease is more compelling,12 and this modality is currently probably under-utilised in New Zealand for managing patients with locally advanced central and/or lateral neck disease.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

James H F Shaw, Head & Neck Surgeon, Clinical Professor of Surgery, Oncology Surgery Ltd, Remuera, Auckland

Acknowledgements

Correspondence

Professor James H F Shaw, Oncology Surgery Ltd, Level 1, 122 Remuera Road, Remuera, Auckland 1005, New Zealand. Fax: +64 (0)9 5292594

Correspondence Email

shawjhf@xtra.co.nz

Competing Interests

None known.

Brownlie B, Turner J, Adela AS. Deaths due to differentiated thyroid cancer: a New Zealand South Island experience: 1984-2009. N Z Med J 2012;125(1363). http://journal.nzma.org.nz/journal/125-1363/5366Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma at the Mayo clinic during 6 decades (1940-1999): temporal trends in initial therapy and long term outcome of 2444 consecutively treated patients. World Journal of Surgery 2002;26:879-85.Greene FLP, Fleming DC, Fritz ID, et al. Editors. Thyroid. In AJCC cancer staging manual. 6th Ed. New York. Springer; 2002.Shah JP. Surgical treatment of cervical lymph nodes for carcinoma. In colour atlas of head and neck surgery. Medical Wolfe Publications Ltd. 1987; pp 224-5.Roh JL, Kim JM, Park CL. Lateral cervical lymph node metastases from papillary thyroid cancer. Ann Surgeons. 2008;15:177-183.Alvarado R, Swank MS, Elbridge L, Sidcup SB. Central lymph node dissection as a secondary procedure for papillary thyroid cancer. Surgery 2009;145:514-8.Demographics of Auckland. Wikipedia 2012.Mazzaferri EL, Jhiang SM. Long term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418-428.Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. A novel classification system for patients with PTC: Addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow up period. Surgery 2004;135:139-148.Kitajiri S, Hiraumi H, Hirose T et al. The presence of large lymph node metastases is a prognostic factor in papillary thyroid cancer. Aurisn Nasus Larynx. 2003;30:169-74.Kjellman P, Zedenius J, Lundell G, et al. Predictors of outcome in patients with papillary thyroid cancer. European J Surgical Oncology. 2006;32:345-352.Wilson PC, Millar BM, Brierley JD. The management of advanced thyroid cancer. Clin Oncol.

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contact nzmj@nzma.org.nz

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Brownlie and colleagues1in this issue of the NZMJhave reviewed the outcomes of the bulk of the New Zealand South Island cases of differentiated thyroid cancer (DTC) seen between 1984 and 2009; a total of 411 cases. Twenty-five patients or 6% of the total died, compromising twice as many women as men, with a mean age of 65 years. The patients were operated on by 19 different surgeons and no patient less than 45 years of age died. All deaths were in Caucasian patients, and 15 of the 25 were incurable from the outset as a result of locally advanced unresectable disease or metastatic disease at diagnosis.According to Table 1, local failure in the neck occurred in 9 or 36% of their patients. The ratio of females to males who died was similar to the gender ratio for all differentiated thyroid cancer (DTC) patients: 2.1:1 favouring females. Table 1. Prognostic effects of extra-thyroid extension and regional disease on outcome Variables T4A N0/n1a T4A N1b T1-3 N1b A&W N1 Rec AWD DOD 56% 11/18 66% 9/18 22% 4/18 0 40% 10/25 13% 2/25 50% 9/25* 20% 5/25* 77% 17/22 18% 4/22 9% 2/22 5% 1/22 N0 no regional disease, N/1a central compartment disease; N1b lateral neck disease, A&W alive & well;N1 Rec recurrence in lateral neck; AWD alive with disease; DOD dead of disease. *Significantly different to both the other groups p<0.04 or better; T4A extra-capsular spread. The editorial author has reviewed his personal experience of over 2000 thyroidectomies performed in Auckland between 1984 and 2012; 300 patients had differentiated thyroid cancer. The patients treated between 1984 and 2007 have been analysed. These data have been presented both nationally and internationally but never published. Statistical analysis utilised Chi-squared analysis. Patients were staged in accord with The Mayo Clinic staging MACIS,2 and also using the guidelines from the Joint American Staging System for Thyroid Cancer.3 Lymph node status (levels 1-7) was as described by Memorial Sloan Kettering Cancer Centre.4,5There were 127 DTC patients aged <45 years (97 papillary, 30 follicular), and 123 aged >45 years (94 papillary, 29 follicular). The ethnic distribution was similar for the two age groups with Europeans making up 61%, M ori 13%, Asian 15%, and Pacific 14%. Longest follow-up (FU) is 25 years with mean FU 13 years. The vast majority of patients were treated with total thyroidectomy. Over recent years central node dissection (level 6) has been almost universally performed for papillary cancer or follicular variant of papillary cancer in order to achieve lower recurrence rates in the central compartment and to have a higher percentage of patients with post-op thyroglobulin levels approximating zero.6 In addition for patients with lateral neck disease, neck dissection of levels 2-5 (after level 6 the commonest sites of involvement are in order levels 4,3 and 2 with level 5 being involved in >20% of patients) was employed for most patients.5 There are a number of differences in this Auckland experience when compared with the South Island report of Brownlie and colleagues;1 in particular the following. In Auckland, major prognostic factors governing outcome were similar to those from The Mayo Clinic,2 these included patient age, the presence of locally advanced disease, adequacy of resection, the status of regional disease, the completeness of the resection performed. In addition, in Auckland the ethnicity of the patient was significant with Asian patients having the best outcomes while Pacific patients had the worst outcome especially male Pacific patients aged >45 years.7 Age was a strong prognostic indicator for both recurrence and death in accord with Mazzaferri and Jhiang.8 Recurrence was frequent in young patients and in older patients with the lowest rate of recurrence in middle aged patients. In contrast, DOD and the presence of unfavourable bone mets were largely confined to patients over 60 years of age. See Figure 1. Abbreviations used in the following figures and tables N0 no regional disease, N1b lateral neck disease, N/1a central compartment disease Rec recurrence, N1 Rec Recurrence in lateral neck Mets metastatic disease, M1 Rec develop metastatic disease DOD dead of disease @ Dx at diagnosis NS not statistically significant AWD alive with disease, A&W alive & well * significance p<0.05 ** significance <0.03 or better Figure 1. Effect of age on outcome of papillary cancer Multifocal tumours were associated with less good outcome in patients < 45 years, but multifocality did not influence outcome in older patients. See Figure 2. Figure 2. Multifocal papillary primary: influence of age Progressive increase in tumour size had only a minor effect on outcome, but extra-thyroid spread (T4a) had a major effect on outcome. See Table 2. Table 2. Effect of tumour size and extra-capsular spread (T4A) on outcome Size CM T1 <2 cm T2 2-4 cm T3 >4 cm T4A A&W AWD DOD 96% 67/71 1% 1/71 0% 0/71 91% 78/80 0% 0/80 1% 1/80 80% 22/28 7% 2/28 0% 0/28 49% 21/43** 30% 13/43** 12% 5/43** ** Significant difference from other groups p<0.04 or better. In addition if there was lateral neck disease coupled with a locally invasive primary (Stage T4A N1B) then the outcome was significantly worse. See Table 2. This is in accord with the findings of Hay et al from The Mayo Clinic.2 Also Table 2 demonstrates the relatively good outcome for regional disease when there is no locally invasive primary, the relatively good outcome when a locally invasive primary was not coupled with regional disease. For younger patients, the number of nodes involved impacted on recurrence. See Table 3. This is in accord with Sugatani et al.9 Table 3. Papillary cancer in patients aged <45 years of age: effect of >5 involved nodes Variables Nil or <5 Nodes >5 Nodes A&W N1 Rec M1 Rec DOD 93 % 75/81 6% 5/81 1% 1/81 1% 1/81 57% 8/14 P<0.001 29% 4/14 P<0.01 36% 5/14 P<0.001 0% 0/14 NS In patients aged >45 years the size of nodes impacted significantly on both recurrence and survival. See Table 4. This finding is in agreement with Kitajiri et al.10 Table 4. Papillary cancer in patients aged >45 years: effect of nodes >3 cm diameter Variables No or nodes <3 cm Nodes >3 cm A&W N1 Rec M1 Rec DOD 79% 59/75 9% 7/75 11% 8/75 1% 1/75 38% 6/16 p<.001 19% 3/16 NS 43% 7/16 p<.001 25% 4/16 p<.003 Completeness of resection was a highly significant prognostic factor, as was the case at Mayo [Clinic].2 Patients with extensive disease necessitating borderline resection of cancer involving trachea, larynx, oesophagus did significantly less well than when complete resection could be performed. See Table 5. Table 5. Outcome: incomplete versus complete resection Variables Complete resection Incomplete resection A&W LR Rec AWMets DOD 74% 147/204 1% 2/204 1% 2/204 0.5% 1/205 12% 3/26 p<0.01 31% 8/26 p<0.01 62% 16/26 p<0.01 27% 7/26 P<0.01 Outcome as a function of race is shown in Table 6. The outcomes for Europeans, M ori, and Asians were similar irrespective of age, and the outcomes of Pacific patients aged <45 years were also similar to the above three ethnic groups. Asians were relatively over-represented (Asian population over the study period would have been much less than 50% of the M ori population7), and Asians had the best outcomes of any race with no patients either AWD or DOD. In contrast Polynesians aged >45 years fared significantly worse than other races largely due to the high proportion of males aged >65 years with T4A, N1b disease (6 patients), along with 4 Polynesian males with T4b disease, 3 of whom died of disease. Table 6. Differentiated thyroid cancer (DTC) in all ages: ethnicity versus outcome Variables European Asian M ori Pacific <45 Pacific >45 A&W AWD DOD 88% 127/144 10% 15/144 1% 2/144 100% 37/37 0% 0% 77% 14/18 22% 4/18 0% 73% 11/15 27% 4/15 0% 30% 6/20 p<0.03 45% 9/20 p<0.05 25% 5/20 p<0.03 MACIS score (based on presence of Metastases, Age, Completeness of resection, Invasion and Size2) stratified patients for outcome. See Table 7. Table 7. Outcome of DTC in all ages versus MACIS score MACIS Score <6 6-7 >7 A&W AWD DOD 99% 185/187 0.5% 1/187 0.5% 1/187 66%* 16/24 29%* 7/24 4%* 1/24 21%* 5/24 50%* 12/24 29%* 7/24 * Significantly different to preceding MACIS value p<0.04 or better. When survival as a function of MACIS score for patients treated in Auckland, Mayo [Clinic],2 and Sweden11 were compared, the survival data were similar. See Figure 3. In addition, the percentage of patients with high MACIS score seen in Auckland was double that seen at Mayo. Figure 3. DTC Outcomes of Mayo Clinic (USA) versus Sweden versus Auckland (NZ) Gender was unimportant in survival for any patient group. When all females were compared with all males the outcomes were virtually identical. See Table 8 below. Table 8. DTC effect of gender on outcome: all female patients versus all male patients Variables Females Males A&W AWD DOD 88% 168/192 8% 15/192 5% 9/192 83% 40/48 10% 5/48 6% 3/48 Overall there are a number of differences in outcome for South Island patients versus North Island patients. This is largely explained on the one hand by the higher percentage of good prognosis Asian patients in the North Island coupled on the other hand with a higher proportion of poor prognosis Polynesian patients seen in Auckland, many of whom were referred from Samoa. There is little doubt that most patients with differentiated thyroid cancer are best treated by total thyroidectomy and for papillary cancers a central neck dissection is also appropriate.6 An assessment of the roles of adjuvant radioiodine (RI) and external beam radiation (EBR) in the management of DTC is beyond the scope of this editorial. However it is this author\u2019s view that while RI is useful for treating metastatic thyroid cancer, data supporting its use as an adjuvant therapy in young patients with good prognosis lesions, is limited.12 Available World data indicate that RI may diminish recurrence in older patients with unfavourable prognostic factors.12 In contrast, the data supporting the use of EBR to diminish recurrence in patients with unfavourable central or lateral compartment disease is more compelling,12 and this modality is currently probably under-utilised in New Zealand for managing patients with locally advanced central and/or lateral neck disease.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

James H F Shaw, Head & Neck Surgeon, Clinical Professor of Surgery, Oncology Surgery Ltd, Remuera, Auckland

Acknowledgements

Correspondence

Professor James H F Shaw, Oncology Surgery Ltd, Level 1, 122 Remuera Road, Remuera, Auckland 1005, New Zealand. Fax: +64 (0)9 5292594

Correspondence Email

shawjhf@xtra.co.nz

Competing Interests

None known.

Brownlie B, Turner J, Adela AS. Deaths due to differentiated thyroid cancer: a New Zealand South Island experience: 1984-2009. N Z Med J 2012;125(1363). http://journal.nzma.org.nz/journal/125-1363/5366Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma at the Mayo clinic during 6 decades (1940-1999): temporal trends in initial therapy and long term outcome of 2444 consecutively treated patients. World Journal of Surgery 2002;26:879-85.Greene FLP, Fleming DC, Fritz ID, et al. Editors. Thyroid. In AJCC cancer staging manual. 6th Ed. New York. Springer; 2002.Shah JP. Surgical treatment of cervical lymph nodes for carcinoma. In colour atlas of head and neck surgery. Medical Wolfe Publications Ltd. 1987; pp 224-5.Roh JL, Kim JM, Park CL. Lateral cervical lymph node metastases from papillary thyroid cancer. Ann Surgeons. 2008;15:177-183.Alvarado R, Swank MS, Elbridge L, Sidcup SB. Central lymph node dissection as a secondary procedure for papillary thyroid cancer. Surgery 2009;145:514-8.Demographics of Auckland. Wikipedia 2012.Mazzaferri EL, Jhiang SM. Long term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418-428.Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. A novel classification system for patients with PTC: Addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow up period. Surgery 2004;135:139-148.Kitajiri S, Hiraumi H, Hirose T et al. The presence of large lymph node metastases is a prognostic factor in papillary thyroid cancer. Aurisn Nasus Larynx. 2003;30:169-74.Kjellman P, Zedenius J, Lundell G, et al. Predictors of outcome in patients with papillary thyroid cancer. European J Surgical Oncology. 2006;32:345-352.Wilson PC, Millar BM, Brierley JD. The management of advanced thyroid cancer. Clin Oncol.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Brownlie and colleagues1in this issue of the NZMJhave reviewed the outcomes of the bulk of the New Zealand South Island cases of differentiated thyroid cancer (DTC) seen between 1984 and 2009; a total of 411 cases. Twenty-five patients or 6% of the total died, compromising twice as many women as men, with a mean age of 65 years. The patients were operated on by 19 different surgeons and no patient less than 45 years of age died. All deaths were in Caucasian patients, and 15 of the 25 were incurable from the outset as a result of locally advanced unresectable disease or metastatic disease at diagnosis.According to Table 1, local failure in the neck occurred in 9 or 36% of their patients. The ratio of females to males who died was similar to the gender ratio for all differentiated thyroid cancer (DTC) patients: 2.1:1 favouring females. Table 1. Prognostic effects of extra-thyroid extension and regional disease on outcome Variables T4A N0/n1a T4A N1b T1-3 N1b A&W N1 Rec AWD DOD 56% 11/18 66% 9/18 22% 4/18 0 40% 10/25 13% 2/25 50% 9/25* 20% 5/25* 77% 17/22 18% 4/22 9% 2/22 5% 1/22 N0 no regional disease, N/1a central compartment disease; N1b lateral neck disease, A&W alive & well;N1 Rec recurrence in lateral neck; AWD alive with disease; DOD dead of disease. *Significantly different to both the other groups p<0.04 or better; T4A extra-capsular spread. The editorial author has reviewed his personal experience of over 2000 thyroidectomies performed in Auckland between 1984 and 2012; 300 patients had differentiated thyroid cancer. The patients treated between 1984 and 2007 have been analysed. These data have been presented both nationally and internationally but never published. Statistical analysis utilised Chi-squared analysis. Patients were staged in accord with The Mayo Clinic staging MACIS,2 and also using the guidelines from the Joint American Staging System for Thyroid Cancer.3 Lymph node status (levels 1-7) was as described by Memorial Sloan Kettering Cancer Centre.4,5There were 127 DTC patients aged <45 years (97 papillary, 30 follicular), and 123 aged >45 years (94 papillary, 29 follicular). The ethnic distribution was similar for the two age groups with Europeans making up 61%, M ori 13%, Asian 15%, and Pacific 14%. Longest follow-up (FU) is 25 years with mean FU 13 years. The vast majority of patients were treated with total thyroidectomy. Over recent years central node dissection (level 6) has been almost universally performed for papillary cancer or follicular variant of papillary cancer in order to achieve lower recurrence rates in the central compartment and to have a higher percentage of patients with post-op thyroglobulin levels approximating zero.6 In addition for patients with lateral neck disease, neck dissection of levels 2-5 (after level 6 the commonest sites of involvement are in order levels 4,3 and 2 with level 5 being involved in >20% of patients) was employed for most patients.5 There are a number of differences in this Auckland experience when compared with the South Island report of Brownlie and colleagues;1 in particular the following. In Auckland, major prognostic factors governing outcome were similar to those from The Mayo Clinic,2 these included patient age, the presence of locally advanced disease, adequacy of resection, the status of regional disease, the completeness of the resection performed. In addition, in Auckland the ethnicity of the patient was significant with Asian patients having the best outcomes while Pacific patients had the worst outcome especially male Pacific patients aged >45 years.7 Age was a strong prognostic indicator for both recurrence and death in accord with Mazzaferri and Jhiang.8 Recurrence was frequent in young patients and in older patients with the lowest rate of recurrence in middle aged patients. In contrast, DOD and the presence of unfavourable bone mets were largely confined to patients over 60 years of age. See Figure 1. Abbreviations used in the following figures and tables N0 no regional disease, N1b lateral neck disease, N/1a central compartment disease Rec recurrence, N1 Rec Recurrence in lateral neck Mets metastatic disease, M1 Rec develop metastatic disease DOD dead of disease @ Dx at diagnosis NS not statistically significant AWD alive with disease, A&W alive & well * significance p<0.05 ** significance <0.03 or better Figure 1. Effect of age on outcome of papillary cancer Multifocal tumours were associated with less good outcome in patients < 45 years, but multifocality did not influence outcome in older patients. See Figure 2. Figure 2. Multifocal papillary primary: influence of age Progressive increase in tumour size had only a minor effect on outcome, but extra-thyroid spread (T4a) had a major effect on outcome. See Table 2. Table 2. Effect of tumour size and extra-capsular spread (T4A) on outcome Size CM T1 <2 cm T2 2-4 cm T3 >4 cm T4A A&W AWD DOD 96% 67/71 1% 1/71 0% 0/71 91% 78/80 0% 0/80 1% 1/80 80% 22/28 7% 2/28 0% 0/28 49% 21/43** 30% 13/43** 12% 5/43** ** Significant difference from other groups p<0.04 or better. In addition if there was lateral neck disease coupled with a locally invasive primary (Stage T4A N1B) then the outcome was significantly worse. See Table 2. This is in accord with the findings of Hay et al from The Mayo Clinic.2 Also Table 2 demonstrates the relatively good outcome for regional disease when there is no locally invasive primary, the relatively good outcome when a locally invasive primary was not coupled with regional disease. For younger patients, the number of nodes involved impacted on recurrence. See Table 3. This is in accord with Sugatani et al.9 Table 3. Papillary cancer in patients aged <45 years of age: effect of >5 involved nodes Variables Nil or <5 Nodes >5 Nodes A&W N1 Rec M1 Rec DOD 93 % 75/81 6% 5/81 1% 1/81 1% 1/81 57% 8/14 P<0.001 29% 4/14 P<0.01 36% 5/14 P<0.001 0% 0/14 NS In patients aged >45 years the size of nodes impacted significantly on both recurrence and survival. See Table 4. This finding is in agreement with Kitajiri et al.10 Table 4. Papillary cancer in patients aged >45 years: effect of nodes >3 cm diameter Variables No or nodes <3 cm Nodes >3 cm A&W N1 Rec M1 Rec DOD 79% 59/75 9% 7/75 11% 8/75 1% 1/75 38% 6/16 p<.001 19% 3/16 NS 43% 7/16 p<.001 25% 4/16 p<.003 Completeness of resection was a highly significant prognostic factor, as was the case at Mayo [Clinic].2 Patients with extensive disease necessitating borderline resection of cancer involving trachea, larynx, oesophagus did significantly less well than when complete resection could be performed. See Table 5. Table 5. Outcome: incomplete versus complete resection Variables Complete resection Incomplete resection A&W LR Rec AWMets DOD 74% 147/204 1% 2/204 1% 2/204 0.5% 1/205 12% 3/26 p<0.01 31% 8/26 p<0.01 62% 16/26 p<0.01 27% 7/26 P<0.01 Outcome as a function of race is shown in Table 6. The outcomes for Europeans, M ori, and Asians were similar irrespective of age, and the outcomes of Pacific patients aged <45 years were also similar to the above three ethnic groups. Asians were relatively over-represented (Asian population over the study period would have been much less than 50% of the M ori population7), and Asians had the best outcomes of any race with no patients either AWD or DOD. In contrast Polynesians aged >45 years fared significantly worse than other races largely due to the high proportion of males aged >65 years with T4A, N1b disease (6 patients), along with 4 Polynesian males with T4b disease, 3 of whom died of disease. Table 6. Differentiated thyroid cancer (DTC) in all ages: ethnicity versus outcome Variables European Asian M ori Pacific <45 Pacific >45 A&W AWD DOD 88% 127/144 10% 15/144 1% 2/144 100% 37/37 0% 0% 77% 14/18 22% 4/18 0% 73% 11/15 27% 4/15 0% 30% 6/20 p<0.03 45% 9/20 p<0.05 25% 5/20 p<0.03 MACIS score (based on presence of Metastases, Age, Completeness of resection, Invasion and Size2) stratified patients for outcome. See Table 7. Table 7. Outcome of DTC in all ages versus MACIS score MACIS Score <6 6-7 >7 A&W AWD DOD 99% 185/187 0.5% 1/187 0.5% 1/187 66%* 16/24 29%* 7/24 4%* 1/24 21%* 5/24 50%* 12/24 29%* 7/24 * Significantly different to preceding MACIS value p<0.04 or better. When survival as a function of MACIS score for patients treated in Auckland, Mayo [Clinic],2 and Sweden11 were compared, the survival data were similar. See Figure 3. In addition, the percentage of patients with high MACIS score seen in Auckland was double that seen at Mayo. Figure 3. DTC Outcomes of Mayo Clinic (USA) versus Sweden versus Auckland (NZ) Gender was unimportant in survival for any patient group. When all females were compared with all males the outcomes were virtually identical. See Table 8 below. Table 8. DTC effect of gender on outcome: all female patients versus all male patients Variables Females Males A&W AWD DOD 88% 168/192 8% 15/192 5% 9/192 83% 40/48 10% 5/48 6% 3/48 Overall there are a number of differences in outcome for South Island patients versus North Island patients. This is largely explained on the one hand by the higher percentage of good prognosis Asian patients in the North Island coupled on the other hand with a higher proportion of poor prognosis Polynesian patients seen in Auckland, many of whom were referred from Samoa. There is little doubt that most patients with differentiated thyroid cancer are best treated by total thyroidectomy and for papillary cancers a central neck dissection is also appropriate.6 An assessment of the roles of adjuvant radioiodine (RI) and external beam radiation (EBR) in the management of DTC is beyond the scope of this editorial. However it is this author\u2019s view that while RI is useful for treating metastatic thyroid cancer, data supporting its use as an adjuvant therapy in young patients with good prognosis lesions, is limited.12 Available World data indicate that RI may diminish recurrence in older patients with unfavourable prognostic factors.12 In contrast, the data supporting the use of EBR to diminish recurrence in patients with unfavourable central or lateral compartment disease is more compelling,12 and this modality is currently probably under-utilised in New Zealand for managing patients with locally advanced central and/or lateral neck disease.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

James H F Shaw, Head & Neck Surgeon, Clinical Professor of Surgery, Oncology Surgery Ltd, Remuera, Auckland

Acknowledgements

Correspondence

Professor James H F Shaw, Oncology Surgery Ltd, Level 1, 122 Remuera Road, Remuera, Auckland 1005, New Zealand. Fax: +64 (0)9 5292594

Correspondence Email

shawjhf@xtra.co.nz

Competing Interests

None known.

Brownlie B, Turner J, Adela AS. Deaths due to differentiated thyroid cancer: a New Zealand South Island experience: 1984-2009. N Z Med J 2012;125(1363). http://journal.nzma.org.nz/journal/125-1363/5366Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma at the Mayo clinic during 6 decades (1940-1999): temporal trends in initial therapy and long term outcome of 2444 consecutively treated patients. World Journal of Surgery 2002;26:879-85.Greene FLP, Fleming DC, Fritz ID, et al. Editors. Thyroid. In AJCC cancer staging manual. 6th Ed. New York. Springer; 2002.Shah JP. Surgical treatment of cervical lymph nodes for carcinoma. In colour atlas of head and neck surgery. Medical Wolfe Publications Ltd. 1987; pp 224-5.Roh JL, Kim JM, Park CL. Lateral cervical lymph node metastases from papillary thyroid cancer. Ann Surgeons. 2008;15:177-183.Alvarado R, Swank MS, Elbridge L, Sidcup SB. Central lymph node dissection as a secondary procedure for papillary thyroid cancer. Surgery 2009;145:514-8.Demographics of Auckland. Wikipedia 2012.Mazzaferri EL, Jhiang SM. Long term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418-428.Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. A novel classification system for patients with PTC: Addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow up period. Surgery 2004;135:139-148.Kitajiri S, Hiraumi H, Hirose T et al. The presence of large lymph node metastases is a prognostic factor in papillary thyroid cancer. Aurisn Nasus Larynx. 2003;30:169-74.Kjellman P, Zedenius J, Lundell G, et al. Predictors of outcome in patients with papillary thyroid cancer. European J Surgical Oncology. 2006;32:345-352.Wilson PC, Millar BM, Brierley JD. The management of advanced thyroid cancer. Clin Oncol.

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