This is a synthesis of data on thyroid diseases and (differentiated) thyroid cancer among Filipinos.

1. Thyroid Diseases &
Malignancies in the Philippines
Synthesis of Data regarding Filipinos with
(Differentiated) Thyroid Cancer
1
PSEDM 2019 Annual Convention: EndoFilipino
14 March 2019 EDSA Shangri La Hotel

2. hello!
I am Dr. Cecile A. Jimeno
Professor and Chair, UPCM Dep’t of Pharmacology & Toxicology
Clinical Associate Professor, Section of Endocrinology, Diabetes & Metabolism
You can find me on @ceciledoc or at cajimeno@up.edu.ph

3. DECLARATION OF CONFLICTS OF
INTEREST
NONE related to this presentation.
3

4. OUTLINE OF PRESENTATION
o Epidemiology of Thyroid Diseases
o Thyroid Cancer Epidemiology
o Outcomes Data: Recurrence and Mortality Rates
o Conclusions
4

5. Rationale for this Presentation
o Knowledge of epidemiology, risk factors for
diseases and outcomes that are unique for our
population will help us tailor fit our
recommendations & clinical decisions.
o Philippine recommendations based on data
about Filipinos.
5

6. 1a.
Epidemiology of Thyroid Diseases
in the Philippines
6

7. The Philippine Thyroid Disorders Study
(PhilTiDeS)
Philippine Society of Endocrinology and Metabolism
Food and Nutrition Research Institute-Department of Science and
Technology
PhilTiDeS Working Group
Josephine Carlos-Raboca, Gabriel Jasul Jr, Sjoberg Kho, Cecilia Jimeno,
Aimee Andag-Silva, Nemencio Nicodemus Jr, Elaine Cunanan
JAFES May 2012; 27: 1, 27-33.
7th National Nutrition Survey 2008

8. How many had goiter?
3.5%
6.7%
8.9%
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
NNS 1987 NNS 1993 PhilTiDeS
2010
Prevalence
N = 7227
Questionnaire (Thyroid history & PE)674 (8.9%)
had goiter
National Nutrition Survey, DOST-FNRI, 1987 and 1993
JAFES May 2012; 27: 1, 27-33.

9. Distribution of Goiters According to
WHO Grade and Morphology
0
100
200
300
400
500
600
Grade 1 Grade 2
frequency
WHO goiter grade
Nodular
Diffuse
55%
45%
62%
38%
JAFES May 2012; 27: 1, 27-33.

10. Distribution Based on Thyroid
Function Status
30 (0.6%)
258 (5.3%)
19 (0.4%)
110 (2.2%)
4480 (91.5%)
True hyperthyroid
Subclinical hyperthyroid
True hypothyroid
Subclinical hypothyroid
Normal
*Sample population with available thyroid function test results
JAFES May 2012; 27: 1, 27-33.

11. 1b.
Data on Iodine Sufficiency
From the Philippine NNHES- 2013

14. Zamboanga Peninsula
Palawan, Capiz, Guimaras, Zamboanga Peninsula (del Norte, del
Sur, Zamboanga Sibugay, Isabela City), Bukidnon, Misamis
Occidental, Davao Oriental, Lanao del Sur, Abra, Mountain Province

15. Conclusions-1
o There is significant burden of thyroid diseases
in the Philippines (9% goiters, 9% thyroid
dysfunction)
o Another survey is probably needed to further
elucidate the “subclinical thyroid disease”
burden seen in the 2008 PhilTiDeS
o Generally the country is already “iodine
sufficient” but there are still provinces with IDD
15

16. 2.
Epidemiology of Thyroid Cancer
Among Filipinos
Incidence
Mortality
Comparisons with other Populations

17. 106,512,067 ++
Total number of new cancer cases (ALL): 141,021
Total number of deaths: 86,337
Thyroid Cancer new cases: 5,926
Total Population

18. Data Sources Philippines
o Country-specific data source: Cebu Cancer
Registry, Manilla Cancer Registry, Rizal Cancer
Registry
o Method: Weighted/simple average of the most
recent local rates applied to 2018 population
18

19. Cancer Statistics Philippines
19

20. Top Ten Cancers in the Philippines
20

21. THYROID CANCER EPIDEMIOLOGY
21
NEW CASES DEATHS 5-Yr
Prevalence
(all ages)Number Rank % Cum
Risk
Number Rank % Cum
Risk
PHILS 5,926 7 4.57 1.03 715 22 0.92 0.37 18,135
ASIA 340,245 8 4.15 0.83 23,847 24 0.46 0.15 1,146 682
WORLD 567,233 10 3.52 0.86 41,071 25 0.46 0.14 1,997 846
INDONESIA 11,470 11 3.78 1.08 2,119 19 1.19 0.52 34,249
North
AMERICA
70 547 8 3.90 1.76 2,337 25 0.37 0.10 290,445
GLOBOCAN 2018 (WHO)

22. Number of
Cases:
1983-2008
22
Generated through
http://ci5.iarc.fr/CI5plus/

23. Age-
Standardized
Incidence Rate
23
Generated through
http://ci5.iarc.fr/CI5plus/

24. 26
Generated through
http://www-
dep.iarc.fr/WHOdb/WHOdb.htm
Selected
GLOBAL
Registries

25. Asian
Registries
27
Generated through
http://ci5.iarc.fr/CI5plus/

26. How
about
FilAms?
28
Generated through
http://www-dep.iarc.fr/
WHOdb/WHOdb.htm

27. Filipinos Abroad
o Hawaii: highest rate of thyroid malignancy is
found in Filipino women, with an age-adjusted
incidence of 18.2 per 100,000.
o Ontario, Canada: OR for malignancy in Filipinos
was 3.57 (95% CI, 1.79–7.12).
Muir CS. International patterns of cancer. In: Greenwald P, Kramer BS, Weed DL, editors. Cancer
prevention and control. New York: Marcel Dekker; 1995. p 37–68. Cancer epidemiology and prevention.
Philadelphia: WB Saunders; 1982. p 837–854. Clark JR. HEAD & NECK—DOI 10.1002/hed May 2006

28. Mortality Data
30

29. Crude Death
Rate
31

30. Crude Death
Rate
32

31. Crude Death
Rate
33

32. ASR
Mortality
34
http://www-dep.iarc.fr/WHOdb

33. 3.
How well are we doing in terms of
screening and diagnosis?
36

34. Abelardo AD. Thyroid Fine-Needle Aspiration Practice in the
Philippine. J Pathol Transl Med. 2017 Nov; 51(6): 555–559.
Bethesda Classification
2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

35. The Bethesda System for Reporting
Thyroid Cytopathology (TBSRTC)
CATEGORY DESCRIPTION
I Non-diagnostic aspirates/unsatisfactory (bloody
smears, blood & colloid, paucicellular smears with
< 6 follicular cell groups of ten cells each, and
poorly prepared smears.
II Benign
III Atypia of Undetermined significance or follicular
lesion of undetermined signfiicance
IV Follicular neoplasm or suspicious for a Follicular
neoplasm
V Suspicious for malignancy
VI Malignant
38

36. o Abelardo summarised the current status of thyroid
cytology in the Philippines, where there are only
10 trained & practicing cytopathologists.
o Analysed publications on cytological & histological
correlation studies from the Philippines.
39

37. 40
Abelardo AD. Journal of Pathology and Translational Medicine 2017; 51: 555-559
https://doi.org/10.4132/jptm.2017.07.14

38. ACCURACY OF FNAB
o Cytohistologic correlations: wide range of
sensitivity from 30.7% to 73% & specificity from
83% to 100%.
o Low sensitivity is due to poor tissue sampling
since most of the FNAB are done by palpation
only: can be improved with UTZ-guidance
o Overall, FNA of the thyroid has enabled the
accurate diagnosis of thyroid disorders and it
correlates well with histopathology.
Abelardo AD. Journal of Pathology and Translational Medicine 2017; 51: 555-559
https://doi.org/10.4132/jptm.2017.07.14

39. ACCURACY OF FNAB
o The risk of malignancy for category III ranges
from 35.3% to 50%, which is higher than
TBSRTC reference rate.
o Conveying these rates to our clinical colleagues
with the recommendation to do a repeat FNA
should be reconsidered for optimal patient care
42
Abelardo AD. Journal of Pathology and Translational Medicine 2017; 51: 555-559
https://doi.org/10.4132/jptm.2017.07.14

40. 43
ULTRASOUND-
GUIDED FNAB (N=118)
PALPATION-GUIDED
FNAB (N=57)
Sensitivity 78.6% 30.7%
Specificity 91.67 100
PPV 86.84 100
NPV 85.94 81.25
Accuracy 86.2 82.69
Non-dx yield 4% 12%

41. o N = 2,239 nodules underwent USG-FNAB with
9.7% inadequate specimens.
o 251 were excised with 27% malignant
o Sensitivity of USG-FNAB: 70.3%
o Specificity: 92.8
o PPV: 76.5% NPV: 90.4%
o Accuracy rate: 87.2%
Young JK, J of ASEAN Fed of Endcorine Soc. 26 No. 1 May 2011

42. Insights & Future Directions
o There are few cytopathologists in the country
who perform FNAB as well as read them.
o Endocrinologists with proper training can do
USG-guided FNAB which improves the yield of
the specimen.
o Recognize that with Bethesda category 1-3, the
risk for malignancy is not zero – need for repeat
FNAB.
45

43. Other Insights
o The current treatment algorithm at Mount Sinai
Hospital is that all Filipino pts with palpable (>1
cm) thyroid nodules undergo thyroidectomy.
o This is based on the very high rate of thyroid
cancer (approximately 70%) observed in Filipino
pts with thyroid nodules regardless of FNAB
findings.
Clark JR. HEAD & NECK—DOI 10.1002/hed May 2006

44. Opinion of A Canadian Surgeon
In Filipino pts, we have not found FNA biopsy to
be a helpful investigation, and it may provide a
false sense security in patients with benign
cytologic findings.
Among Filipinos with benign cytologic findings,
56% were ultimately found to have malignancy
compared with 18% of non-Filipino patients with
benign cytologic findings.
Total thyroidectomy for nodules > 1 cm should be
done for Filipinos regardless of FNAB results.
47 Clark JR. HEAD & NECK—DOI 10.1002/hed May 2006
“
“

45. INSIGHTS
o Results of FNAB must be correlated with clinical
& USG findings in order to guide decision making
o What are the clinical & sonographic features
predictive of thyroid malignancy among Filipinos?
48

46. o P: 837 of 1,670 patients (50.1%) were enrolled
in the study, which included 417 benign and 420
malignant tumors. [retrospective cohort]
49

47. Factors Predictive of Malignancy
o Clinical, biochemical & USG characteristics
predictive of thyroid malignancy
o Outcome/Results:
○ Age at diagnosis: X= 38±11 years, with
female predominance.
○ Size, gender were not predictive
o Multiple logistic regression:
○ Hard or firm nodule OR 58.8 / OR 12.82 (P<0.001)
○ Microcalcifications OR, 11.1; P<0.001),
○ Irregular margins on ultrasound OR, 4.5; P<0.001,
○ Absence of associated symptoms OR, 2.3; P<0.002.
50

48. Factors Predictive of Malignancy
o Other factors also associated with an increased
likelihood of malignancy, but did not reach
statistical significance in a multivariate analysis:
○ presence of rapidly enlarging thyroid nodule,
○ fixation of the nodule on the surrounding
tissue, and the
○ composition and hypoechogenicity of the
thyroid nodule on ultrasound.
51

49. 4.
Results of Outcome Studies
Recurrences
52

50. o N= 649 pts with papillary thyroid cancer (PTC) &
79 pts with follicular thyroid cancer (FTC)
o Mean follow-up: 53±12 (PTCA) and 83±23 months
[Retrospective cohort]

51. Baseline Characteristics
54

52. Criteria for Recurrence
(assessed after thyroidectomy)
(1) elevated stimulated (>2 μg/L) or unstimulated
(>1 μg/L) serum thyroglobulin after
thyroidectomy and radioactive ablation;
(2) recurrent or new-onset lymphadenopathies
proven to be thyroid cancer by biopsy or
radioiodine scan; and
(3) recurrent or new-onset distant metastases
proven to be thyroid cancer by biopsy or
radioiodine scan.
55

53. Outcomes: % with Recurrence
o 214/649 pts (32.9%) with PTC: 13±6 months
o 23/79 pts (29.1%) with FTC : 26±15 months
developed a recurrence after thyroidectomy
Endocrinol Metab. 2016; 31(1):72.doi: 10.3803/EnM.2016.31.1.72

54. Predictors of Recurrence in
Differentiated Thyroid Cancer
Risk Factors Odds Ratio (95% CI) p-value
PTCA: Age > 45 years 1.44 (1.09-1.89) 0.010
Lymph node mets at pres’n (N1) 4.0 (2.99- 5.34) < 0.001
Distant mets at presentation (M1) 2.78 (1.59- 4.84) < 0.001
Multifocality 1.43 (1.05-1.95) 0.023
Follicular variant histology 0.60 (0.37-0.97) 0.037
Postsurgical RAI 0.31 (0.24-0.42) < 0.001
FTCA: Distant mets at pres’n 19.4 (6.28-59.96) < 0.001
FTCA: Post-surgical RAI 0.41 (0.17-0.98) 0.044
Endocrinol Metab. 2016; 31(1):72.doi: 10.3803/EnM.2016.31.1.72

55. Comparisons with International Data
o Koreans (17.5%) & Japanese (9.6%)
o US data (Mazzaferri et al): N = 1,355 in the U.S.
Air Force or Ohio State University hospitals
followed prospectively (1994)
○ Median follow: 15.7 yrs.
○ After 30 yrs: survival rate was 76%,
○ Recurrence rate: 30%,
○ Cancer death rate: 8%.
58
Mazzaferri et al. November 1994 The American Journal of Medicine” Volume 97

56. o A moderate surgical approach of bilateral thyroid
resection, with usual central neck nodal clearance,
and lateral internal jugular lymphadenectomy for
node-positive disease, including preoperative US
for detection & mapping of LNM.
o 1999-2006, 420 pts were treated with this
comprehensive approach, & excluded only the few
pts found intraoperatively to be unresectable.
59
NEWER DATA
Grant CS. Gland Surgery 2015;4(1):52-62

57. Outcomes of Mayo Clinic Data
o 40% multicentric, ave 1.7 cm in size, 30% bilateral,
17% extrathyroidal extension, 51% had C-VI LNM
& lateral LNMs in 20%, and MACIS low-risk
prognostic scores in 84%.
o RAI given in 40% of patients.
o Relapse of LNM in previously operated fields in
5% of patients; 3% had true local recurrence or
distant metastasis, with complications limited to
1.2% hypoparathyroidism and only a single patient
suffered unintentional RLN paralysis.
60

58. Filipinos in Canada
o N= 499 pts with thyroid cancer (36 Filipinos)
treated at Mount Sinai Hospital from 1984 to
2003, with a minimum 5-year follow-up and a
minimum 1.0-cm tumor size.
o 78% of Filipino pts were Stage 1 (vs 65% NF),
83% papillary, 22% were >4 cm (vs 15% NF)
o Recurrence: Filipinos 25% vs Non-Filipino 9.5%
o Odds ratio, 3.20; 95% CI, 1.23-7.49; P=.004.
61
Kus LH Arch Otolaryngol Head Neck Surg. 2010;136(2):138-142

59. Filipinos in Canada
o Multivariate analysis after adjustment for
confounding factors i.e. gender, age, history of
head & neck radiation therapy, and type of
thyroid surgery: OR 6.99, 95% CI 2.31–21.1
o No significant differences between Filipino
patients & non-Filipino pts regarding the rate of
death from ThyCA (5.6% vs 1.9%) and the time
to recurrence (52.6 vs 53.1 months), likely due to
small sample size.
Kus LH Arch Otolaryngol Head Neck Surg. 2010;136(2):138-142

60. Insights
o Recurrence rates for Filipinos are higher than
international cohorts.
o Predictors of recurrence: age > 45, LN mets (N1)
& distant mets (M1) at presentation, with RAI
being protective
o Mortality rates are low in the PGH cohort = int’l
cohorts but data from the national databases
indicate that mortality rates are higher
o Similar to some of the international guidelines:
optimal surgery + routine RAI remnant ablation.
63

61. Management Principles for Differentiated
Thyroid Cancer
1. Remove primary tumor, disease extending beyond
thyroid capsule, lymph node metastases (adequate
surgery).
2. Minimize risk of disease recurrence, metastatic
spread (adequate surgery, RAI therapy, TSH
suppression).
3. Accurate staging and risk stratification 
prognostication, follow-up
4. Long-term surveillance
64
Haugen BR, et al Thyroid. Volume 26, Number 1, 2016.
Acta Medica Philippina VOL. 42 N0. 1 2008

62. Preoperative or Intraoperative Decision-
making (American Thyroid Association):
Indications for TOTAL THYROIDECTOMY: (any present)
o Known distant metastases
o Extrathyroidal extension
o Tumor > 4 cm in diameter
o Cervical lymph node metastases
o Poorly differentiated
o Consider prior radiation exposure (Cat 2B)
o Consider bilateral nodularity
65 Haugen BR, et al Thyroid. Volume 26, Number 1, 2016

63. Preoperative or Intraoperative
Decision-making:
Indications for Total Thyroidectomy OR Lobectomy:
(all criteria present)
o No prior radiation exposure
o No distant metastases
o No cervical lymph node metastases
o No extrathyroidal extension
o Tumor < 4 cm in diameter
66
Haugen BR, et al Thyroid. Volume 26, Number 1, 2016

64. Asia Pacific Region Expert
consensus
o Thyroid lobectomy and isthmusectomy is an
appropriate approach for some patients with
cytologically indeterminate lesions, but bilateral
total or near-total thyroidectomy is generally
performed when papillary, follicular, or Hürthle
cellcancer is known or suspected preoperatively
67
Sundram et al. THYROID Volume 16, Number 5, 2006

65. Asia Pacific Region Expert consensus
68

66. PGH Consensus: Total
thyroidectomy for most patients
Total thyroidectomy for ALL pts with DTCA &
nodule size > 1 cm
o For low-risk pts, in light of the varying surgical
expertise, decision making about lobectomy versus
thyroidectomy must be weighed vs the minimally lower
risk of disease recurrence versus higher rates of
postoperative hypoparathyroidism and recurrent
laryngeal nerve injury.
o Lobectomy may be sufficient for DTCA < 1 cm,
isolated, intrathyroidal and without cervical lymph
metastases on pre-operative ultrasound (Grade B)
Acta Medica Philippina Vol. 42 N0. 1 2008
69
Sison CM. JAFES. Vol. 27 No. 1 May 2012

67. Management Principles for Differentiated
Thyroid Cancer
1. Remove primary tumor, disease extending beyond
thyroid capsule, lymph node metastases (adequate
surgery).
2. Minimize risk of disease recurrence, metastatic
spread (adequate surgery, RAI therapy, TSH
suppression).
3. Accurate staging and risk stratification 
prognostication, follow-up
4. Long-term surveillance
70
Haugen BR, et al Thyroid. Volume 26, Number 1, 2016.
Acta Medica Philippina VOL. 42 N0. 1 2008

68. PGH Consensus: Total thyroidectomy,
and RAI for most patients
o “Ablative radioactive iodine-131 therapy shall be
given postoperatively to all patients with well
differentiated thyroid carcinoma assessed to be
at high risk for disease morbidity and mortality
o Lower risk patients do not show evidence for
benefit. “
o ? More recent data seem to point to benefit of
RAI even for low risk DTCA among Filipinos in
decreasing recurrence rates.
Acta Medica Philippina VOL. 42 N0. 1 2008
71

69. 5.
Outcomes after surgery for
low risk cancers
72

70. ATA 2009 with Proposed Modifications:
ATA Low Risk Category
Papillary thyroid cancer (with all of the following):
o No local or distant metastases;
o All macroscopic tumor has been resected
o No tumor invasion of loco-regional tissues/structures
o No aggressive histology (e.g., tall cell, hobnail variant,
columnar cell carcinoma)
o If 131 I is given, no RAI-avid metastatic foci outside the
thyroid bed on the 1st post-treatment whole-body scan
o No vascular invasion
o Clinical N0 or < 5 pathologic N1 micrometastases
(< 0.2 cm in largest dimension) *
Haugen BR, ATA 2015. THYROID Vo26, Number 1, 2016

71. ATA 2009 with Proposed Modifications:
ATA Low Risk Category
o Intrathyroidal, encapsulated follicular variant of
papillary thyroid cancer *
o Intrathyroidal, well differentiated follicular thyroid
cancer with capsular invasion and no or minimal
(< 4 foci) vascular invasion *
o Intrathyroidal, papillary microcarcinoma, unifocal
or multifocal, including BRAFV600E mutated (if
known)*
Haugen BR, ATA 2015. THYROID Vo26, Number 1, 2016

72. Why it Matters
o RAI remnant ablation is currently not routinely
recommended for low risk DTCA, whether the
initially therapy is total thyroidectomy or
lobectomy (ATA).
“RAI remnant ablation is not routinely recommended
after thyroidectomy for ATA low-risk DTC pts.
Consideration of specific features of the individual
patient that could modulate recurrence risk, disease
follow-up implications, and pt preferences are
relevant to RAI decision-making. “
(Weak recommendation, Low-quality evidence)
Haugen BR, ATA 2015. THYROID Vo26, Number 1, 2016

73. 76
Routine RAI
Consider RAI
RAI not routinely
recommended

74. o Retrospective cohort
o N= 906 PTC patients in the outpatient database;
649 charts (72%) were available for review, and
188 patients (29%) were considered low-risk.
77

75. Criteria for Low Risk (ATA 2009)
o Absence of local or distant metastases,
o resection of all macroscopic tumors,
o absence of tumor invasion of locoregional
tissues,
o absence of aggressive tumor histology (tall cells,
insular cells, columnar cells) or vascular
invasion, and
o uptake of 131I (if given) limited to the thyroid bed
on the first post-treatment whole-body
radioactive iodine (RAI) scan.
78 Jauculan. Endocrinol Metab 2016;31:113-119

76. Exclusion Criteria
o Patients for whom data were lacking in terms of
either initial Tg or anti-Tg antibody levels or post-
therapy whole-body scans were excluded.
79 Jauculan. Endocrinol Metab 2016;31:113-119

77. 80
Recurrence:
51 pts (35.17%) at
a median interval of
60 ± 65.28 months
after thyroidectomy

78. 81

79. Factors Associated with recurrence among
low risk patients with PTCA

80. Comparisons with International Data
o Shaha et al. N= 465 pts with low risk DTCA
o Median follow-up of 20 years, the 10- and 20-
year survival in this select group was 99%.
o Local, regional, & distant recurrence rates were
5, 9, and 2% in this series.
o No statistical difference in the overall failure rate
between total lobectomy & total thyroidectomy
(13 vs. 8%; p = 0.06).
83
Ann Surg Oncol. 1997 Jun;4(4):328-33

81. Comparisons with International Data
Filiz Hatipoğlu et al (Turkey):
o N = 217 pts with DTC with > 3 years follow up.
o Recurrence in a group of pts who had RAI tx with
no signs of residual thyroid tissue or metastasis
with diagnostic WBS that was performed at 6-12
months after therapy & had Tg level < 2 ng/dl
o Recurrence: 12 (7.5%) of the 160 patients who
were considered as “successful ablation”
84 Mol Imaging Radionucl Ther. 2016 Jun; 25(2): 85–90.

82. INSIGHTS
o It appears that our risk of recurrence even for low
risk DTCA is higher than international cohorts.
o RAI therapy was protective & proved
advantageous esp since the non-RAI group had
a higher baseline post-thyroidectomy Tg
o RAI therapy may have benefit for preventing
recurrences/persistent disease.
o LN clearance and dissection
o Future studies to determine the optimal RAI
activity for treatment of low risk DTCA
85

83. How about the lowest risk
patients?
Papillary Thyroid Microcarcinoma (PTMC)
86

84. Outcomes for Micropapillary Thyroid Ca
USTH
Guerrero R
MMC
G Silva et al
TMC
Lazaro K
UP PGH
Co M
Number of
cases
75 (22% of
DTCA)
22 (10% of
DTCA)
90 (30% of
DTCA)
115
(~ 13%)
Mean age 47 years 46 48 43.63 ± 10.9
Follow up
Mean, range
Not
mentioned
6 yrs
(1-11 yrs)
42 mos
(12-129)
ongoing
Recurrence
rate
5.3%
(all had TT)
1/22
(4.5%)
6/90
(6.67%)
26/115
(22.61%)
Mortality rate 1.3% 0 0 0
Determinants Male
gender *
----- None ** pending
Silva G Phil J Int Med 47:237-244, Nov-Dec 2009; Guerrero R. J of the AFES. Vol. 29 No. 1 May 2014; Lazaro
KD Phil J of Int Med, Volume 56 Number 3 July - Sept., 2018. Co MI, Unpublished (personal communication).

85. INSIGHTS: Papillary Microcarcinoma
o Locations of recurrences: thyroid bed & lymph
nodes, most were classical histology, unifocal, >
95% total thyroidectomy or NTT, RAI in 45-53%
o Median: 18 mos (12-70 mos ), 6-12 mos in USTH
o In the UST & MMC reports, there were 3 who had
distant mets (bone) < 45 years old; PGH 3
o RAI did not seem to alter outcomes
Data set is small; need to understand the
implications of recurrences to long term outcomes.
88

86. 6.
Studies Investigating Underlying
Reasons for Poorer Outcomes
(mortality, recurrence)
89

87. Why is this Important?
o Identifying demographic indicators of poor
prognosis in thyroid cancer is vital to making
general guidelines for treatment but are also
crucial to effective, personalized clinical
decision-making.
o Well-differentiated thyroid carcinoma has a
favorable prognosis, but patients with multiple
recurrences have drastically lower survival.
Nguyen L. Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

88. o Filipinos in the US are known to have high
thyroid cancer incidence & recurrence rates.
o It is unknown whether Filipinos also have higher
thyroid cancer mortality rates.
91

89. Methods & Results
o Thyroid cancer mortality in Filipino, non-Filipino
Asian (NFA), & non-Hispanic White (NHW)
adults using US death records (2003–2012) and
US Census data.
o N= 19,940,952 deaths.
o AMR due to thyroid cancer:
○ Highest in Filipinos (1.72 deaths per 100,000,
95% CI 1.51–1.95)
○ NFAs: 1.03 per 100,000, 95% CI 0.95–1.12
○ NHWs: 1.17 per 100,000, 95% CI 1.16–1.18.
92
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

90. Proportional Mortality Ratios (PMR)
93

91. o Compared to NHWs, higher proportionate
mortality was observed in Filipino women (3–5
times higher) across all age groups, and
o Filipino men had 2–3 times higher PMR in the
subgroup over the age of 55.
o Filipinos that completed higher education had
notably higher PMR (5.0) than their counterparts
who had not (3.5)
Proportional Mortality Ratios (PMR)
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

92. Conclusions
o Negative prognostic factors for thyroid cancer
traditionally include “age greater than 45 years”
and “male gender.”
o Filipinos die of thyroid cancer at higher rates
than NFAs and NHWs of similar ages.
o Highly-educated Filipinos & Filipino women were
esp at risk for poor thyroid cancer outcomes.
o Filipino ethnicity should be factored into clinical
decision-making in the mgt of thyroid cancer.
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

93. Why Filipinos?
o Dietary or Nutritional Influences
○ Scarce studies
○ Cohort of Korean females: did not know that
many of their foods were contained high levels of
iodine & consumed these while on low iodine diet
o ? Filipino pts have similar misunderstandings & a
higher intake of iodine-rich foods, ie seafood
and dairy, than other patients preparing for RAI
treatment, which may render the treatment less
effective, or may modulate tumor behavior.
96
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

94. Thyroid Ca and iodine sufficiency
o There was a trend towards having more
malignant thyroid nodules (55.8%) among iodine-
deficient cases compared with iodine sufficient
cases (40%).
o Counter-intuitive because iodine excess is
known to be associated with the development of
PTCA
97
Ejercito-de Jesus RE, Fojas MC, Buenaluz-Sedurente.
Philipp J Intern Med 2008;46:27–34.

95. Why Filipinos?
o Highly-educated Filipinos had higher
proportionate mortality due to thyroid cancer
o 1970s-80s: Filipino immigrants who arrived to the
US were health professionals
o Until mid-1980s: Filipino nurses represented 75%
of all foreign nurses in the U.S nurse workforce.
o ? Occupational exposures such as radiation, or
o ? Higher education may be a proxy for other
factors that influence clinical outcome i.e.
different approaches to accessing healthcare
98
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

96. Why Filipinos?
o Study did not find a scientific difference in the
proportionate mortality between Philippine-born
Filipinos and their US-born Filipino counterparts.
o This makes environmental exposures present in
the Philippines, such as carcinogenic volcanic
lava unlikely to explain the differential outcomes
we observed.
No difference between Filipinos & FilAms
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

97. Why Filipinos?
o ? Genetic predisposition in the host and/or tumor
o Recent work at Cancer Genome Atlas Research
Network drastically increased our understanding
of the genetic basis of thyroid cancer behavior.
o Alterations & gene expression patterns of
specific genes (i.e. TERT, CHEK2, and ATM)
and sets of functionally-related genes have been
shown to define clinical sub-classes of thyroid
cancer & may contribute to loss of differentiation
and tumor progression
Cell 2014; 159(3):676–690. DOI: 10.1016/j.cell.2014.09.050

98. Why Filipinos?
o Filipinos may carry an allele that predisposes
them as a population to the somatic mutations
that drive thyroid tumor aggressiveness.
101
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

99. Gender & Prognosis
o Within both Filipinos and NFAs, women had higher
PMRs than men at all ages.
o Filipino women had especially high PMR compared
to other racial/ethnic/gender groups at all ages.
o Given the gender differences in this study, it is
plausible that an X-linked allele could be
predisposing Filipino women to more aggressive
thyroid cancer.
102
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

100. Future Directions
o “To investigate pathophysiology, future studies
should also examine whether aggressive
histopathological subtypes, such as anaplastic
thyroid cancer or tall cell variant PTC, and
genetic alterations associated with thyroid de-
differentiation and tumor progression, such as
TERT promoter mutations, are more common in
thyroid cancers surgically removed from
Filipinos. “
103
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

101. Future Directions
o Genetic epidemiology studies should investigate
whether Filipinos as a population carry a higher
proportion of any specific allele that predisposes
them to aggressive thyroid tumors.
o Such investigations would provide invaluable
information on the pathophysiology of aggressive
thyroid cancer, could support clinical decision-
making, and could lead to more targeted thyroid
cancer treatment plans for this population.
104
Cancer. 2017 December 15; 123(24): 4860–4867. doi:10.1002/cncr.30958

102. Genetic Epidemiology
What have we done so far?
105

103. o N= 65 pts with 38.46% BRAF V600E mutation
o Those with mutations were predominantly female,
young (mean age 36 years), with tumour size < 4
cm, and late-stage disease. All classical PTCA.
o Extra-thyroidal extension (60%), significant
sclerosis (96%), and subcapsular tumour location
(72%) were the most frequent findings.

104. Critique of the Paper
o Considering that all the tumours were classic
PTC, such rate is unexpectedly low.
o This poses an interesting question about other
genetic events, which could drive thyroid cancer
development in the studied cohort.
o PTC classic variant is typically initiated by BRAF
mutation (up to 75%), while mutually exclusive
gene fusions (mainly RET/PTC ) are found less
frequently
107 Nat Rev Cancer. 2013; 13: 184-99.

105. o 12/17 (70.59%) pts had BRAF V600E mutation
o 13 women, median age of 46 yrs (25 -74 years)
o 14 patients had conventional subtype PTC;
o Tumor size from 0.8 to 7.0 cm (median, 2.4 cm);
extrathyroidal extension in 7 pts (38.9%),
multifocality in 6 , and LNM in 8 pts.
108 Journal of Global Oncology

106. o Retrospective analysis
o 31/37 (83.8%) of our pts harbored the BRAF
mutation & were exclusively the V600E1 variant.
o 5-year survival: 84.2%.
o Mean age 47 years old (range 21–87) and
female gender 28/37 (76%).
o All pts had the conventional subtype of PTC.
109

107. Braf V600E Mutations among Filipinos
in Hawaii
o Average tumor size: 2.1 cm (range 0.4–6.0);
o Extrathyroidal extension in 62%, multifocality in
49%, lymph node involvement 46%,
o Presence of distant metastasis in only 2/37 (5%).
o AJCC stage distribution: I=19/37 (51%), II=4/37
(11%), III=11/37 (30%), and IV=3/37 (8%).
o No association between extrathyroidal extension
and BRAF mutation (p-value 0.65).
110

108. Discordant Data?
o The controversy may be explained by technical
issues, low sample number, selection bias, or
specific characteristics of the studied population.
o Andrey Bychkov MD, PhD:
“ However…. the main issue learned from the
Filipino study is that despite significant research
interest and practical promises, BRAF mutation
remains largely underexplored in Southeast
Asian patients with thyroid cancer. “
111 Nat Rev Cancer. 2013; 13: 184-99.

109. 112

110. Lessons Learned
“More efforts are needed to set up large multi-
institutional studies with the aim to establish the
national prevalence of BRAF mutation in thyroid
cancer across ASEAN countries.”
113 Nat Rev Cancer. 2013; 13: 184-99.

111. Insights
o We need a better understanding of our genetic
epidemiology – this will help us to better
understand our pathophysiology & ultimately
help us to be more definite in our
recommendations for the population as a whole
& for each pt.
114

112. 7.
Auditing how well we have done
115
Survival outcomes

113. Cancer survival Compared to
European Cohorts
116
European Journal of Public Health, Vol. 21, No. 2, 221–228, 2010

114. 1995-1999
European Countries & Manila and Rizal Cancer Registries
European Journal of Public Health, Vol. 21, No. 2, 221–228

115. Philippine residents vs Fil-Ams vs
Americans
118
Redaniel MT. British Journal of Cancer (2009) 100, 858 – 862

116. Reasons for the Differences in
Outcomes?
o Access to health care.
“The very large differences in the survival estimates
of Filipino-Americans and the Philippine resident
population highlight the importance of the access to
and utilisation of diagnostic and therapeutic facilities
in developing countries.
Redaniel MT. British Journal of Cancer (2009) 100, 858 – 862; Jpn J Clin Oncol 2010;40(7)603–612

117. Conclusions
o Comprehensive review of the available data
o We need to improve thyroid cancer detection by
FNAB, that should ideally be USG guided
o Our recurrence/persistence rates are high even
for DTCA, even for low risk cancers
o Our data for micropapillary CA is small: need a
registry for these cases
o Our mortality rates though not as high as other
cancers are still higher than global rates
120

118. Thyroid Cancer
EndoFilipino
We have the data, let’s do better.
“True Patriotism is loving your country and countrymen
enough to want to make it better.”
Malcolm Jenkins