anaplastic thyroid carcinoma : treatment outcome and prognostic factors

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Anaplastic Thyroid Carcinoma Treatment Outcome and Prognostic Factors Electron Kebebew, M.D. 1,2 Francis S. Greenspan, M.D. 3 Orlo H. Clark, M.D. 1,2 Kenneth A. Woeber, M.D. 3 Alex McMillan, Ph.D. 2 1 Department of Surgery, University of California– San Francisco, San Francisco, California. 2 University of California–San Francisco Compre- hensive Cancer Center, San Francisco, California. 3 Division of Endocrinology, University of Califor- nia–San Francisco, San Francisco, California. Presented in part at the 76th Annual Meeting of the American Thyroid Association, Vancouver, Canada, September 29 –October 3, 2004. Supported in part by the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation, a Hellman Family Grant, and the University of California Cancer Research Coor- dinating Committee. Address for reprints: Electron Kebebew, M.D., De- partment of Surgery, University of California–San Francisco, Box 1674, UCSF/Mount Zion Medical Center, San Francisco, CA 94143-1674; Fax: (415) 885-7617; E-mail: [email protected] Received September 27, 2004; revision received December 15, 2004; accepted December 15, 2004. BACKGROUND. Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive human malignancies. Several prognostic factors have been observed in patients with ATC, and some experts advocate aggressive multimodal therapy in selected patients. However, it is unclear whether such an approach significantly improves survival. The authors analyzed prognostic factors and treatment out- comes in patients with ATC reported in the National Cancer Institute’s Surveil- lance, Epidemiology, and End Results data base. METHODS. The cohort consisted of 516 patients with ATC reported to 12 popula- tion-based cancer registries between 1973 and 2000. Demographic, pathologic, and treatment data were used for univariate and multivariate survival analyses. RESULTS. The mean patient age at diagnosis was 71.3 years, and there were 171 men and 345 women. Eight percent of patients had intrathyroidal tumors, 38% had extrathyroidal tumors and/or lymph node invasion, and 43% of patients had distant metastasis. The average tumor size was 6.4 cm (range, 1–15 cm). Sixty-four percent of patients underwent surgical resection of their primary tumor, and 63% received external beam radiotherapy. The overall cause-specific mortality rate was 68.4% at 6 months and 80.7% at 12 months. Univariate analysis showed that age 60 years, female gender, intrathyroidal tumor, external beam radiotherapy, surgical resection, and combined surgical resection of tumor and radiotherapy were associated with a lower cause-specific mortality. On multivariate analysis, only age 60 years, an intrathyroidal tumor, and the combined use of surgical and external beam radiation therapy were identified as independent predictors of lower cause-specific mortality. CONCLUSIONS. Although most patients with ATC had an extremely poor prognosis, patients 60 years old with intrathyroidal tumors survived longer. Surgical resec- tion with external beam radiotherapy for ATC was associated with lower cause- specific mortality. Cancer 2005;103:1330 –5. © 2005 American Cancer Society. KEYWORDS: anaplastic thyroid carcinoma, survival, epidemiology, prognostic fac- tors, thyroidectomy, radiotherapy. A naplastic thyroid carcinoma (ATC), one of the most aggressive human malignancies, is associated with an almost uniformly rapid and lethal clinical course. Although 2% of all thyroid carci- nomas are ATC, it accounts for 14 –39% of thyroid carcinoma deaths. 1,2 Some investigators have advocated multimodal therapy for patients with ATC, including surgical resection or debulking, radio- therapy, and chemotherapy. 3–16 However, to our knowledge, few pub- lished data have shown any significant survival benefit from multi- modal therapy. 17,18 The aggressive nature and rarity of ATC make it difficult to de- termine patient outcome, especially in single-institution studies with small cohorts and short follow-up. In fact, ATC is classified as Stage IV 1330 © 2005 American Cancer Society DOI 10.1002/cncr.20936 Published online 28 February 2005 in Wiley InterScience (www.interscience.wiley.com).

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Page 1: Anaplastic thyroid carcinoma : Treatment outcome and prognostic factors

Anaplastic Thyroid CarcinomaTreatment Outcome and Prognostic Factors

Electron Kebebew, M.D.1,2

Francis S. Greenspan, M.D.3

Orlo H. Clark, M.D.1,2

Kenneth A. Woeber, M.D.3

Alex McMillan, Ph.D.2

1 Department of Surgery, University of California–San Francisco, San Francisco, California.

2 University of California–San Francisco Compre-hensive Cancer Center, San Francisco, California.

3 Division of Endocrinology, University of Califor-nia–San Francisco, San Francisco, California.

Presented in part at the 76th Annual Meeting of theAmerican Thyroid Association, Vancouver, Canada,September 29–October 3, 2004.

Supported in part by the Harold Amos MedicalFaculty Development Program of the Robert WoodJohnson Foundation, a Hellman Family Grant, andthe University of California Cancer Research Coor-dinating Committee.

Address for reprints: Electron Kebebew, M.D., De-partment of Surgery, University of California–SanFrancisco, Box 1674, UCSF/Mount Zion MedicalCenter, San Francisco, CA 94143-1674; Fax: (415)885-7617; E-mail: [email protected]

Received September 27, 2004; revision receivedDecember 15, 2004; accepted December 15,2004.

BACKGROUND. Anaplastic thyroid carcinoma (ATC) is rare but is one of the most

aggressive human malignancies. Several prognostic factors have been observed in

patients with ATC, and some experts advocate aggressive multimodal therapy in

selected patients. However, it is unclear whether such an approach significantly

improves survival. The authors analyzed prognostic factors and treatment out-

comes in patients with ATC reported in the National Cancer Institute’s Surveil-

lance, Epidemiology, and End Results data base.

METHODS. The cohort consisted of 516 patients with ATC reported to 12 popula-

tion-based cancer registries between 1973 and 2000. Demographic, pathologic, and

treatment data were used for univariate and multivariate survival analyses.

RESULTS. The mean patient age at diagnosis was 71.3 years, and there were 171

men and 345 women. Eight percent of patients had intrathyroidal tumors, 38% had

extrathyroidal tumors and/or lymph node invasion, and 43% of patients had

distant metastasis. The average tumor size was 6.4 cm (range, 1–15 cm). Sixty-four

percent of patients underwent surgical resection of their primary tumor, and 63%

received external beam radiotherapy. The overall cause-specific mortality rate was

68.4% at 6 months and 80.7% at 12 months. Univariate analysis showed that age

� 60 years, female gender, intrathyroidal tumor, external beam radiotherapy,

surgical resection, and combined surgical resection of tumor and radiotherapy

were associated with a lower cause-specific mortality. On multivariate analysis,

only age � 60 years, an intrathyroidal tumor, and the combined use of surgical and

external beam radiation therapy were identified as independent predictors of lower

cause-specific mortality.

CONCLUSIONS. Although most patients with ATC had an extremely poor prognosis,

patients � 60 years old with intrathyroidal tumors survived longer. Surgical resec-

tion with external beam radiotherapy for ATC was associated with lower cause-

specific mortality. Cancer 2005;103:1330 –5. © 2005 American Cancer Society.

KEYWORDS: anaplastic thyroid carcinoma, survival, epidemiology, prognostic fac-tors, thyroidectomy, radiotherapy.

Anaplastic thyroid carcinoma (ATC), one of the most aggressivehuman malignancies, is associated with an almost uniformly

rapid and lethal clinical course. Although � 2% of all thyroid carci-nomas are ATC, it accounts for 14 –39% of thyroid carcinomadeaths.1,2 Some investigators have advocated multimodal therapy forpatients with ATC, including surgical resection or debulking, radio-therapy, and chemotherapy.3–16 However, to our knowledge, few pub-lished data have shown any significant survival benefit from multi-modal therapy.17,18

The aggressive nature and rarity of ATC make it difficult to de-termine patient outcome, especially in single-institution studies withsmall cohorts and short follow-up. In fact, ATC is classified as Stage IV

1330

© 2005 American Cancer SocietyDOI 10.1002/cncr.20936Published online 28 February 2005 in Wiley InterScience (www.interscience.wiley.com).

Page 2: Anaplastic thyroid carcinoma : Treatment outcome and prognostic factors

thyroid carcinoma according to the American JointCommittee on Cancer, regardless of the tumor size orthe presence of lymph node or distant metastasis.19

Furthermore, assessing response to therapeutic ap-proaches in patients with ATC is complicated by itsaggressive clinical course and the inability to clinicallydistinguish differences in the disease course itselffrom small but real treatment effects. We evaluatedthe outcome and the effect of treatment on the sur-vival of patients with ATC reported in the NationalCancer Institute’s Surveillance, Epidemiology, andEnd Results (SEER) database.

MATERIALS AND METHODSStudy Design and Data SourceA retrospective cohort design was used to analyze datafrom the SEER 12-registry database. The study wasexempted from review by the University of Califor-nia—San Francisco Committee on Human Research.The database consists of cases diagnosed from 1973through 2000 from the states of Connecticut, NewMexico, Hawaii, Iowa, and Utah and from the metro-politan areas of Atlanta, Detroit, San Francisco-Oak-land, and Seattle-Puget Sound. The database also in-cludes cases diagnosed from 1992 through 2000 fromthe Los Angeles and San Jose-Monterey metropolitanareas and the Alaska Native region. The SEER databaseincludes information on demographics, pathology,treatment, and survival.

Variable DefinitionsPatients with anaplastic thyroid carcinoma were se-lected from the SEER database for public use (SEER12-registry database).20 Tumors that were diagnosedonly at autopsy or by death certificate and tumorswithout pathologic confirmation of ATC were ex-cluded from the survival analyses. The cut-off date forfollow-up was December 31, 2000. Classification ofstage of disease at diagnosis, tumor size, treatment,and race/ethnicity followed SEER definitions.21 Dis-ease stage was defined as local (confined to the thy-roid gland), regional (extension into adjacent tissue orlymph node involvement), distant (metastasis), andunstaged.

Data AnalysisWe used the SEER Stat software (version 5.0.20) toabstract patients with ATC into the StatView statisticalsoftware package (version 4.51; SAS Institute Inc.,Cary, NC) according to the International Classifica-tions of Diseases for Oncology, third revision codes forsite and histology (C739 and 8020/8021). The data arereported as means � standard deviations or as num-bers and percentages. For the univariate survival anal-

ysis, the log-rank test was used to compare theKaplan–Meier events. For the multivariate survivalanalysis, a Cox proportional hazards model was devel-oped by forward, stepwise regression for all predictorvariables that were identified as significant in the uni-variate analysis. The specific variables studied wereage (per decade), gender, race/ethnicity, era of diag-nosis (per decade), tumor size (in 1-cm incrementsfrom 1 cm to 12 cm), extent of disease (local, regional,and distant), surgical resection of tumor, and radia-tion treatment. It was assumed that the observed dif-ferences were statistically significant if the probabilityof chance occurrence was � 0.05.

RESULTSIn total, 516 patients with ATC were reported from1973 to 2000 to the SEER Program (Table 1). Themajority of patients were white (84.6%) and female(66.9%). ATC was the first primary tumor in 90.3% ofpatients. Only 39 patients (7.5%) had an intrathyroidalATC, whereas 194 patients (37.6%) had extrathyroidalinvasion and/or regional lymph node metastasis, and222 patients (43.0%) had distant metastasis. Half of allpatients with ATC underwent surgical resection, and326 patients (63.2%) underwent radiation treatment(Table 2), which consisted of external beam radiationin 305 patients (59.1%) and radioisotopes in 12 pa-tients (2.3%) (Table 2). Most patients were treated withexternal beam radiation after surgical resection. Un-fortunately, data regarding chemotherapy for ATC arenot collected in the SEER database.

The overall cause-specific mortality was 69.4% at6 months and 80.7% at 12 months (Fig. 1). On univar-iate analysis, patient age � 60 years, gender, primarytumor size (� 5cm), SEER extent of disease, surgicalresection, external beam radiation, era of diagnosis,and combined surgical resection with external beamradiation were significant prognostic factors; however,race/ethnicity, first malignant primary tumor, and pri-mary tumor size were not (Table 3). On multivariateanalysis, age � 60 years, SEER extent of disease, andcombined surgical resection with external beam radi-ation treatment were independent prognostic factors(Table 3, Fig. 2). In a subgroup analysis, combinedsurgical resection with external beam radiation de-creased the cause-specific mortality rate significantlyin patients with regional and distant disease, but notin patients with only intrathyroidal ATC (Fig. 3).

DISCUSSIONMultimodal therapy for patients with ATC has beenadvocated by some investigators, because most pa-tients present with metastatic disease and die withinmonths of diagnosis. The evidence that supports such

Anaplastic Thyroid Carcinoma/Kebebew et al. 1331

Page 3: Anaplastic thyroid carcinoma : Treatment outcome and prognostic factors

an approach, however, is based on single-institutionstudies of select groups of patients.5,7,9,10,13,16,22–26 Ourcurrent study of the population-based SEER datademonstrates that patients � 60 years old who haveintrathyroidal ATC have a better prognosis comparedwith older patients who have distant metastasis. Sur-gical resection with external beam radiation in pa-tients with regional and distant ATC was associatedwith lower cause-specific cancer mortality.

The mean patient age at diagnosis and the genderdistribution in the current report were similar to thosereported in other, smaller cohort studies.5,16,24,27–30

Intrathyroidal ATC was uncommon, and most patientspresented with regional disease and distant metasta-sis. Coexisting thyroid diseases such as differentiatedthyroid carcinoma and multinodular goiter are com-mon in patients with ATC and some studies suggestedthat these factors may influence the clinical course ofpatients with ATC.28 –32 Unfortunately, because theSEER database does not contain information regard-ing the presence of other thyroid diseases, we couldnot evaluate the effect of these factors. Although tu-mor histology was not reexamined in the currentstudy, and patients with medullary thyroid carcinoma,thyroid non-Hodgkin lymphoma, and the insular vari-ant of follicular thyroid carcinoma may be diagnosedincorrectly with ATC, we do not believe this accountsfor all 10.6% of patients who survived for � 2 years.27

This is because the misdiagnosis of ATC has beenuncommon since the 1970s, when immunohisto-chemical techniques were implemented, and the

TABLE 1Demographic, Clinical, and Pathologic Characteristics in 516 Patientswith Anaplastic Thyroid Carcinoma, 1973–2000

Characteristic No. of patients

DemographicsMale:female ratio 171:345Age (yrs)

Mean � SD 71.3 � 12.7Range 15–95

RaceWhite 437Black 26Othera 51Unknown 2

Era of diagnosis and treatment1973–1980 831981–1990 1231991–2000 310

PathologyDiagnostic confirmationPositive histology 454Positive cytology 58Clinical 1Radiographic 2Unknown 1

First malignant primary tumorYes 466No 50

No. of primary malignanciesOne 453Two 54Three 6Four 3

Tumor size (cm)b

Mean � SD 6.4 � 2.6Range 1.0–15.0

SEER extent of diseasec

Local 39Regional 194Distant 222Unstaged 61

SD: standard deviation; SEER: Surveillance, Epidemiology, and End Results Program.a Other refers to 2 Native Americans and 49 Asian and Pacific Islanders.b Tumor size data were collected beginning in 1988 and were available for 37% of patients.c Specific sites of distant metastasis are not reported in the SEER database.

TABLE 2Treatment Modalities in Patients with Anaplastic Thyroid Carcinoma,1973–2000

Treatment modality No. of patients

Surgical resectiona

Yes 253No 141Unknown 122

Extent of thyroidectomya

Total thyroidectomy 12Subtotal or near total thyroidectomy 37Lobectomy and/or isthmusectomy 23Removal of less than a lobe 8Thyroidectomy, NOS 2Surgery, NOS 171

Radiation treatmentExternal beam 305Radioisotopeb 12Unspecified 9None 177Unknown 13

External beam radiation sequence tosurgical resection

Before surgery 4After surgery 147Before and after surgery 4No surgery 143Unknown sequence 7

NOS: not otherwise specified.a No details concerning the extent of surgical resection (e.g., radical en bloc, limited, debulking with

respect to contiguous structures) are included in the Surveillance, Epidemiology, and End Results

(SEER) database except for the extent of thyroidectomy used, which was collected beginning in 1989.b The type of radioisotope used is not specified in the SEER database, but these patients most likely

represent radioiodine ablation. These patients were censored in the survival analysis when evaluating

the effect of external beam radiation treatment.

1332 CANCER April 1, 2005 / Volume 103 / Number 7

Page 4: Anaplastic thyroid carcinoma : Treatment outcome and prognostic factors

SEER database consists of patients with ATC reportedsince 1973.

Many studies have documented the lethal courseof patients with ATC, but the important prognosticfactors that determine survival and the effect of mul-timodal treatment remain unclear. Patient age, gen-der, tumor size, extent of disease, leukocytosis, pres-ence of acute local symptoms, coexisting multinodulargoiter and well differentiated thyroid carcinoma, sur-gical resection, and multimodal therapy all reportedlyinfluence patient survival according to some (but not

all) studies.11,16,23,25,28 –30,32,33 In the current study,which we believe includes the largest cohort analyzedto date, we found that only patient age at diagnosisand the presence of intrathyroidal ATC were indepen-dent predictors of lower cause-specific mortality.There was a 28.3% difference in the cause-specificmortality between patients � 60 years and patients� 60 years, and there was a 44.9% difference in thecause-specific mortality at 1-year follow-up betweenpatients who had distant metastasis and patients whohad intrathyroidal ATC. Although it was reported pre-viously that tumor size (microscopic foci or size � 5– 6cm) was a predictor of mortality, it was not found to be

FIGURE 1. Overall cause-specific mortality in patients with anaplastic thyroid

carcinoma. The mean cause-specific survival was 12 months (median, 3

months).

TABLE 3Univariate and Multivariate Analyses of Prognostic Factors forAnaplastic Thyroid Carcinoma

VariableUnivariateP value

Multivariate HR(95% CI)

Age (� 60 yrs) 0.0009a 0.482 (0.268–0.867)a

Gender (female) 0.0028a 1.089 (0.746–1.590)Race/ethnicityb 0.0682 NAFirst primary malignancy 0.7859 NATumor size (� 5 cm)c 0.0203a 1.245 (0.854–1.816)SEER stage � 0.0001a

Local 0.572 (0.366–0.893)a

Regional 0.831 (0.611–1.130)Distant 1.492 (1.113–2.000)a

Surgical resection � 0.0001a 0.779 (0.312–1.946)External beam radiation 0.0064a 0.534 (0.147–1.940)Combined surgical resection with

external beam radiation � 0.0001a 0.722 (0.587–0.889)a

HR: hazard ratio; 95% CI: 95% confidence interval; NA: not applicable; SEER: Surveillance, Epidemiol-

ogy, and End Results Program.a Significant prognostic variable.b Survival analysis compared between whites, blacks, and others.c Tumor size increased by 1-cm increments from 1 cm to the first significant value.

FIGURE 2. Cause-specific mortality in patients with anaplastic thyroid

carcinoma by (A) age, (B) Surveillance, Epidemiology, and End Results

extent of disease, and (C) combined surgical resection with external beam

radiation.

Anaplastic Thyroid Carcinoma/Kebebew et al. 1333

Page 5: Anaplastic thyroid carcinoma : Treatment outcome and prognostic factors

an independent predictor of lower cause-specific mor-tality in the current study.25,26,30,31

In patients with ATC, the effects of surgical resec-tion, radiation treatment, and chemotherapy on localcontrol or improved survival are unclear. Althoughsome studies have shown no survival benefit fromresection, radiation therapy, or chemotherapy, otherstudies suggested that multimodal therapy may bebeneficial in some patients with ATC.5,7,9,10,13,16,22–26 Amajor confounding factor in determining the effect oftreatment on outcome has been selection bias, be-cause patients who undergo surgical resection andradiation treatment often have less extensive dis-ease.18 Although it is impossible to control for suchfactors in a retrospective study, our subgroup compar-ison of patients with regional and distant ATC stilldemonstrates a significant survival advantage for pa-tients who underwent both surgical resection and ex-ternal beam radiation therapy. Given the small num-ber of patients who had intrathyroidal ATC, it was notsurprising to find no significant decrease in the cause-specific mortality rate with combined surgical resec-tion and external beam radiation. Unfortunately, nodata regarding the precise extent of surgical resectionand chemotherapy are collected in the SEER database.One of the most studied chemotherapy agents in pa-tients with ATC has been the radiosensitizing agentdoxorubicin, but no significant survival benefit hasbeen observed.14,34 In a multicenter Phase II trial thatevaluated the effects of paclitaxel in 19 evaluable pa-tients, a 53% response rate to treatment was reportedwith no significant effect on survival.35 Although aneffect from chemotherapy could not be excluded as aconfounding factor in the current study, recent studiesusing paclitaxel monotherapy or a combination ofcisplatin, bleomycin, 5-fluorouracil, and cyclophosph-amide resulted in no significant survival benefit.36 –38

Patients � 60 years old with intrathyroidal ATCappear to have a better prognosis than older patientswith distant metastasis. In the current study, surgicalresection with external beam radiation in patientswith ATC was associated with a lower cause-specificmortality.

REFERENCES1. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A Na-

tional Cancer Data Base report on 53,856 cases of thyroidcarcinoma treated in the U.S., 1985–1995 [see comments].Cancer. 1998;83:2638 –2648.

2. Kitamura Y, Shimizu K, Nagahama M, et al. Immediatecauses of death in thyroid carcinoma: clinicopathologicalanalysis of 161 fatal cases. J Clin Endocrinol Metab. 1999;84:4043– 4049.

3. Aldinger KA, Samaan NA, Ibanez M, Hill CS Jr. Anaplasticcarcinoma of the thyroid: a review of 84 cases of spindle andgiant cell carcinoma of the thyroid. Cancer. 1978;41:2267–2275.

4. Besic N. The role of initial debulking surgery in the man-agement of anaplastic thyroid carcinoma. Surgery. 2003;133:453– 454; author reply, 454 – 455.

5. Busnardo B, Daniele O, Pelizzo MR, et al. A multimodalitytherapeutic approach in anaplastic thyroid carcinoma:study on 39 patients. J Endocrinol Invest. 2000;23:755–761.

6. Goldman JM, Goren EN, Cohen MH, Webber BL, BrennanMF, Robbins J. Anaplastic thyroid carcinoma: long-termsurvival after radical surgery. J Surg Oncol. 1980;14:389 –394.

7. Kasai N, Sakamoto A, Uchida M. A combined modality foranaplastic large-cell carcinoma of the thyroid. Auris NasusLarynx. 1985;12(Suppl 2):S72–S74.

8. Kim JH, Leeper RD. Treatment of locally advanced thyroidcarcinoma with combination doxorubicin and radiationtherapy. Cancer. 1987;60:2372–2375.

9. Pierie JP, Muzikansky A, Gaz RD, Faquin WC, Ott MJ. Theeffect of surgery and radiotherapy on outcome of anaplasticthyroid carcinoma. Ann Surg Oncol. 2002;9:57– 64.

10. Schlumberger M, Parmentier C, Delisle MJ, Couette JE, DrozJP, Sarrazin D. Combination therapy for anaplastic giant cellthyroid carcinoma. Cancer. 1991;67:564 –566.

11. Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. Prognosticfactors and therapeutic strategy for anaplastic carcinoma ofthe thyroid. World J Surg. 2001;25:617– 622.

12. Tallroth E, Wallin G, Lundell G, Lowhagen T, Einhorn J.Multimodality treatment in anaplastic giant cell thyroid car-cinoma. Cancer. 1987;60:1428 –1431.

13. Tennvall J, Lundell G, Hallquist A, Wahlberg P, Wallin G,Tibblin S. Combined doxorubicin, hyperfractionated radio-therapy, and surgery in anaplastic thyroid carcinoma. Re-port on two protocols. The Swedish Anaplastic Thyroid Can-cer Group. Cancer. 1994;74:1348 –1354.

14. Tennvall J, Lundell G, Wahlberg P, et al. Anaplastic thyroidcarcinoma: three protocols combining doxorubicin, hyper-fractionated radiotherapy and surgery. Br J Cancer. 2002;86:1848 –1853.

15. Werner B, Abele J, Alveryd A, et al. Multimodal therapy inanaplastic giant cell thyroid carcinoma. World J Surg. 1984;8:64 –70.

16. Haigh PI, Ituarte PH, Wu HS, et al. Completely resectedanaplastic thyroid carcinoma combined with adjuvant che-motherapy and irradiation is associated with prolonged sur-vival. Cancer. 2001;91:2335–2342.

FIGURE 3. Cause-specific survival in patients with anaplastic thyroid carci-

noma (excluding patients with local disease only) who treated with combined

surgical resection and external beam radiation.

1334 CANCER April 1, 2005 / Volume 103 / Number 7

Page 6: Anaplastic thyroid carcinoma : Treatment outcome and prognostic factors

17. Sherman SI. Thyroid carcinoma. Lancet. 2003;361:501–511.18. Pasieka JL. Anaplastic thyroid cancer. Curr Opin Oncol.

2003;15:78 – 83.19. Greene FL, Page DL, Fleming ID, et al., editors. Thyroid.

AJCC cancer staging manual. 6th edition. New York: Spring-er-Verlag, 2002:77.

20. Surveillance, Epidemiology, and End Results Program. Serialonline. Available at URL: http://www.seer.cancer.gov/publicdata/ [accessed November 11, 2003].

21. Surveillance, Epidemiology, and End Results Program.Monograph online. Available at URL: http://seer.cancer-.gov/tools/codingmanuals/ [accessed November 11, 2003].

22. Besic N, Auersperg M, Us-Krasovec M, Golouh R, Frkovic-Grazio S, Vodnik A. Effect of primary treatment on survivalin anaplastic thyroid carcinoma. Eur J Surg Oncol. 2001;27:260 –264.

23. Jereb B, Stjernsward J, Lowhagen T. Anaplastic giant-cellcarcinoma of the thyroid. A study of treatment and progno-sis. Cancer. 1975;35:1293–1295.

24. Junor EJ, Paul J, Reed NS. Anaplastic thyroid carcinoma: 91patients treated by surgery and radiotherapy. Eur J SurgOncol. 1992;18:83– 88.

25. Kobayashi T, Asakawa H, Umeshita K, et al. Treatment of 37patients with anaplastic carcinoma of the thyroid. HeadNeck. 1996;18:36 – 41.

26. Nilsson O, Lindeberg J, Zedenius J, et al. Anaplastic giant cellcarcinoma of the thyroid gland: treatment and survival overa 25-year period. World J Surg. 1998;22:725–730.

27. Carcangiu ML, Steeper T, Zampi G, Rosai J. Anaplastic thy-roid carcinoma. A study of 70 cases. Am J Clin Pathol.1985;83:135–158.

28. McIver B, Hay ID, Giuffrida DF, et al. Anaplastic thyroidcarcinoma: a 50-year experience at a single institution. Sur-gery. 2001;130:1028 –1034.

29. Pacheco-Ojeda LA, Martinez AL, Alvarez M. Anaplastic thy-

roid carcinoma in Ecuador: analysis of prognostic factors.Int Surg. 2001;86:117–121.

30. Tan RK, Finley RK 3rd, Driscoll D, Bakamjian V, Hicks WLJr., Shedd DP. Anaplastic carcinoma of the thyroid: a24-year experience. Head Neck. 1995;17:41– 47; discus-sion, 47– 48.

31. Demeter JG, De Jong SA, Lawrence AM, Paloyan E. Anaplas-tic thyroid carcinoma: risk factors and outcome. Surgery.1991;110:956 –961; discussion, 961–963.

32. Venkatesh YS, Ordonez NG, Schultz PN, Hickey RC, Go-epfert H, Samaan NA. Anaplastic carcinoma of the thyroid.A clinicopathologic study of 121 cases. Cancer. 1990;66:321–330.

33. Lo CY, Lam KY, Wan KY. Anaplastic carcinoma of the thy-roid. Am J Surg. 1999;177:337–339.

34. Haigh PI. Anaplastic thyroid carcinoma. Curr Treat OptionsOncol. 2000;1:353–357.

35. Ain KB, Egorin MJ, DeSimone PA. Treatment of anaplasticthyroid carcinoma with paclitaxel: Phase 2 trial using nine-ty-six-hour infusion. Collaborative Anaplastic Thyroid Can-cer Health Intervention Trials (CATCHIT) Group. Thyroid.2000;10:587–594.

36. [No authors listed.] Intensive chemotherapy for anaplasticthyroid carcinoma: combination of cisplatin, doxorubicin,etoposide and peplomycin with granulocyte colony-stimu-lating factor support. Chemotherapy Committee, The Japa-nese Society of Thyroid Surgery. Jpn J Clin Oncol. 1995;25:203–207.

37. De Besi P, Busnardo B, Toso S, et al. Combined chemother-apy with bleomycin, Adriamycin, and platinum in advancedthyroid cancer. J Endocrinol Invest. 1991;14:475– 480.

38. Williams SD, Birch R, Einhorn LH. Phase II evaluation ofdoxorubicin plus cisplatin in advanced thyroid cancer: aSoutheastern Cancer Study Group trial. Cancer Treat Rep.1986;70:405– 407.

Anaplastic Thyroid Carcinoma/Kebebew et al. 1335