Published Ahead of Print on March 31, 2014 as 10.1200/JCO.2013.49.6596 The latest version is at http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2013.49.6596
JOURNAL OF CLINICAL ONCOLOGY
D I A G N O S I S
I N
O N C O L O G Y
low. Here we present the first report, to our knowledge, of an ATC with rearranged anaplastic lymphoma kinase (ALK) with an excellent response to crizotinib treatment.
Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase–Rearranged Anaplastic Thyroid Carcinoma
Case Report A 71-year-old woman with no history of exposure to ionizing radiation presented with a rapidly growing right cervical tumor that was associated with mild dysphagia. Ultrasound examination revealed concerning features, so treatment with total thyroidectomy with central dissection was planned. The gross examination of the surgical specimen revealed a 36 ⫻ 27 mm nonencapsulated nodule of the right thyroid lobe. On histologic examination, the nodule corresponded to a widely invasive, undifferentiated carcinoma with polygonal and polymorphic cells (Fig 1A), which merged from a minimal
Introduction Anaplastic thyroid cancers (ATCs) are rare, representing around 1% to 2% of all thyroid carcinomas.1 They are particularly aggressive malignancies, especially when metastatic. Prognosis after local progression or metastasis is poor, with only 20% survival at 1 year.2 Disseminated forms are essentially treated by an approach using doxorubicin-based chemotherapy or by targeted therapies within therapeutic protocols, but therapeutic response rates are generally
A
B
C
D
E
F
Fig 1. Journal of Clinical Oncology, Vol 32, 2014
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
Copyright 2014 by American Society of Clinical Oncology
1
Godbert et al
pulmonary lesions was observed (⬎ 20% according to RECIST version 1.1 criteria3). The patient was then referred to our institution (Institut Bergonie´). Additional histologic samples were obtained by bronchial fibroscopy and by mediastinoscopy. Histologic examination revealed an undifferentiated carcinoma. The anaplastic component of both lung and thyroid specimens was similar and showed minimal thyroglobulin reactivity, in favor of a thyroid origin. Given the poor prognosis of the disease and the lack of standard treatment in this setting, and after having obtained patient consent, we screened thyroid and lung tumor specimens for molecular alterations that could represent therapeutic targets. We found no aberrations of the EGFR, BRAF, RAS, ERBB2, PIK3CA, CTNNB1, PTEN, APC, or TP53 genes (Ion AmpliSeq cancer panel; Ion Torrent/Life Technologies, Guilford, CT). Strikingly, we found ALK1 overexpression (clone D5F3, dilution 1:50; Cell Signaling Technology, Danvers, MA) in the
component of papillary carcinoma of the follicular variant (Fig 1B). The tumor extended beyond the thyroid capsule infiltrating the adjacent muscle, and four regional lymph node metastases were observed at central node dissection (of nine dissected). They were stage pT4b N1a and stage IVB, according to the seventh edition of the TNM staging manual. Computed tomography (CT) of the thoraxabdomen-pelvis did not reveal any distant progression. Postoperative concomitant radiochemotherapy was administered with cisplatin (100 mg/m2), etoposide (50 mg/m2), and radiotherapy (45 Gy in conventional fractionation in the primary tumor bed, cervical nodes, and mediastinum, with a boost of 10 Gy in the primary tumor bed). Six months after completion of the initial treatment, multiple bilateral pulmonary recurrences were observed on a CT scan. Secondline chemotherapy treatment with carboplatin and etoposide was administered. After three cycles of chemotherapy, progression of the
Fig 2. 2
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
Diagnosis in Oncology
and tumor suppressor genes have been described, including BRAF, RAS, catenin, PIK3CA, P53, PTEN, AXIN1, and APC genes.7 A number of novel agents have been studied in ATC with, at best, only weak responses.8-10 ALK is an oncogene, a member of the insulin receptor subfamily of receptor tyrosine kinases.11 Since its initial identification within an oncogenic gene fusion product associated with anaplastic large-cell lymphoma, the number of ALK-rearranged neoplasms has continuously increased.12 The tyrosine kinase activities of ALK fusion proteins are aberrantly activated and promote cell proliferation and survival via various signaling pathways, among which are the phosphatidylinositol 3-kinase/Akt pathway and the MAP3 kinase pathway.13,14 ALK rearrangement has been recently described by Hamatani et al15 in 10 of 19 patients (atomic bomb survivors) with radiationexposed papillary thyroid carcinoma (PTC), with no detectable gene alterations in BRAF, RET, NTRK1, or RAS. The authors had previously reported an increased frequency of RET-PTC rearrangements in adult papillary carcinoma, with relatively higher radiation exposure compared with patients with lower radiation exposure, whereas point mutations such as BRAFV600E were less frequent.16 In this small series of patients with PTC, the authors note an association between solid/ trabecular-like architecture and the presence of ALK rearrangement, but do not describe an anaplastic component.15 Six of their patients had rearrangement with EML4, which was apparently not the case in our patient’s tumor. The FISH pattern that we observed is similar to that described in some patients with ALK-positive lung carcinomas and corresponds to a deletion in the ALK gene. Research is in progress to attempt to identify the partner gene. To our knowledge, this is the first case of an ATC with ALK rearrangement to be described in the literature. In contrast to the patients described by Hamatani et al,15 our patient was not exposed to radiation. Murugan et al17 identified two gain-of-function point mutations (C3592T and G3602A) in exon 23 of the ALK gene in two of 18 patients with ATC, but found no mutations in well-differentiated thyroid cancers. From a medico-economic point of view, our patient case raises the problem of the prescription of off-label drugs for patients with cancer. Although our article suggests efficacy of crizotinib in thyroid tumors bearing an aberration of the ALK gene, a well-designed proofof-concept phase II study would represent the best proof of evidence of crizotinib’s efficacy in this setting. Given the rarity of the disease, such a clinical trial would be feasible only in the context of an international collaborative effort.
differentiated papillary carcinoma component (Fig 1C), the anaplastic component of the thyroid specimen (Fig 1D), and the metastatic tumor (Fig 1E). To understand the mechanisms involved in this overexpression, we analyzed the status of the ALK1 gene using fluorescent in situ hybridization (FISH; Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe; Abbott Molecular, Abbott Park, IL). As shown in Figure 1F, we found a rearrangement of the ALK1 gene (arrows show one fusion signal and one red signal with loss of the green signal) in more than 50% of cells among the well-differentiated papillary carcinoma components of the thyroid as well as in the anaplastic component of both specimens, the primary tumor and the pulmonary metastasis. Real-time polymerase chain reaction analysis with Taqman Gene Expression Assays (Applied Biosystems, Foster City, CA), testing for the 10 most frequent echinoderm microtubule-associated protein-like 4 (EML4)/ALK transcripts, was negative. This was in accordance with comparative genomic hybridization array analysis (Agilent Technologies, Santa Clara, CA), which confirmed the FISH pattern, showing a partial deletion in region 2p23 corresponding to the ALK gene (Fig 2, arrow) and with the distal break-point into the ALK gene. We did not observe any corresponding breakages in the EML4 gene. Comparative genomic hybridization array profiles were similar in both localizations (data not shown). On the basis of our molecular findings, we initiated crizotinib (250 mg per day). The treatment was well tolerated and the patient maintained an excellent performance status (Eastern Cooperative Oncology Group [ECOG] score of 0) 2 years after the initial diagnosis. CT examination at baseline (Fig 3A) and at 3 months after crizotinib (Fig 3B) showed an exceptional response of more than 90% across all pulmonary lesions (RECIST version 1.1 criteria). CT examination 6 months after therapy initiation confirmed this excellent response. Discussion ATC is a rare cancer with a poor prognosis. Median overall survival is less than 6 months after initial diagnosis, and 1-year survival is approximately 20%.2 However, several cases of prolonged survival have been described, especially in patients with limited thyroid extension with complete cytoreductive surgery.4 Patients with metastatic ATC (stage IVC) have short survival and no prospects for a curative outcome. The administration of cytotoxic treatment has not demonstrated clear therapeutic efficacy or improvement in quality of life.1,5,6 In parallel with the recent development of inducible tyrosine kinase targeted therapies, interest in the molecular pathogenesis of ATC has grown over the last few years. Mutations in several oncogenes
A
B
Fig 3. www.jco.org
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
3
Godbert et al
Our case is remarkable in that the ALK rearrangement was present both in the well-differentiated component, which was a follicular variant of the papillary type, and in the anaplastic component. This is in favor of an early and likely driver event in the carcinogenesis of this patient’s disease, as is the excellent and durable response to crizotinib. It is difficult to know whether the ALK rearrangement played a role or not in the anaplastic transformation. We did not find any other mutations, even using powerful techniques such as next-generation sequencing. To our knowledge, this is also the first case to be described of an ALK-positive thyroid carcinoma treated by an ALK-specific inhibitor (crizotinib). To our knowledge, this is the first patient to be reported with an ALK rearrangement in ATC who has demonstrated an excellent response to crizotinib. This opens the door to new therapeutic possibilities for these poor-prognosis carcinomas, and potentially for undifferentiated thyroid carcinomas. However, to clearly understand the potential of crizotinib in ATC treatment, the prevalence of this rearrangement needs to be assessed in a larger group.
Yann Godbert, Be´ne´dicte Henriques de Figueiredo, and Franc¸oise Bonichon Institut Bergonie´, Bordeaux, France
Fre´de´ric Chibon Institut Bergonie´; and Institut National de la Sante´ et de la Recherche Me´dicale U916, Bordeaux, France
Isabelle Hostein and Gae¨lle Pe´rot Institut Bergonie´, Bordeaux, France
Camille Dupin Laboratoire d’Anatomie et de Cytologie Pathologiques, Bordeaux, France
Agne`s Daubech Cabinet d’Histo Cyto Pathologie, Le Bouscat, France
Genevieve Belleanne´e and Audrey Gros University Hospital, Pessac, France
Antoine Italiano and Isabelle Soubeyran Institut Bergonie´, Bordeaux, France
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Smallridge RC, Ain KB, Asa SL, et al: American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 22:1104-1139, 2012 2. Kebebew E, Greenspan FS, Clark OH, et al: Anaplastic thyroid carcinoma: Treatment outcome and prognostic factors. Cancer 103:1330-1335, 2005 3. Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247, 2009 4. Lim SM, Shin SJ, Chung WY, et al: Treatment outcome of patients with anaplastic thyroid cancer: A single center experience. Yonsei Med J 53:352-357, 2012 5. Ain KB, Egorin MJ, DeSimone PA: Treatment of anaplastic thyroid carcinoma with paclitaxel: Phase 2 trial using ninety-six-hour infusion—Collaborative Anaplastic Thyroid Cancer Health Intervention Trials (CATCHIT) Group. Thyroid 10:587-594, 2000 6. Shimaoka K, Schoenfeld DA, DeWys WD, et al: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56:2155-2160, 1985 7. Smallridge RC, Marlow LA, Copland JA: Anaplastic thyroid cancer: Molecular pathogenesis and emerging therapies. Endocr Relat Cancer 16:17-44, 2009 8. Mooney CJ, Nagaiah G, Fu P, et al: A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid 19:233-240, 2009 9. Kloos RT, Ringel MD, Knopp MV, et al: Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 27:1675-1684, 2009 10. Pennell NA, Daniels GH, Haddad RI, et al: A phase II study of gefitinib in patients with advanced thyroid cancer. Thyroid 18:317-323, 2008 11. Morris SW, Kirstein MN, Valentine MB, et al: Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 263: 1281-1284, 1994 12. Minoo P, Wang HY: ALK-immunoreactive neoplasms. Int J Clin Exp Pathol 5:397-410, 2012 13. Allouche M: ALK is a novel dependence receptor: Potential implications in development and cancer. Cell Cycle 6:1533-1538, 2007 14. Mourali J, Be´nard A, Lourenc¸o FC, et al: Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage. Mol Cell Biol 26:6209-6222, 2006 15. Hamatani K, Mukai M, Takahashi K, et al: Rearranged anaplastic lymphoma kinase (ALK) gene in adult-onset papillary thyroid cancer amongst atomic bomb survivors. Thyroid 22:1153-1159, 2012 16. Hamatani K, Eguchi H, Ito R, et al: RET/PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose. Cancer Res 68:7176-7182, 2008 17. Murugan AK, Xing M: Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res 71:4403-4411, 2011
ACKNOWLEDGMENT
We thank Pippa McKelvie-Sebileau of Institut Bergonie´ for medical editorial assistance in English.
DOI: 10.1200/JCO.2013.49.6596; published online ahead of print at www.jco.org on March 31, 2014 ■ ■ ■
4
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
JOURNAL OF CLINICAL ONCOLOGY
D I A G N O S I S
I N
O N C O L O G Y
low. Here we present the first report, to our knowledge, of an ATC with rearranged anaplastic lymphoma kinase (ALK) with an excellent response to crizotinib treatment.
Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase–Rearranged Anaplastic Thyroid Carcinoma
Case Report A 71-year-old woman with no history of exposure to ionizing radiation presented with a rapidly growing right cervical tumor that was associated with mild dysphagia. Ultrasound examination revealed concerning features, so treatment with total thyroidectomy with central dissection was planned. The gross examination of the surgical specimen revealed a 36 ⫻ 27 mm nonencapsulated nodule of the right thyroid lobe. On histologic examination, the nodule corresponded to a widely invasive, undifferentiated carcinoma with polygonal and polymorphic cells (Fig 1A), which merged from a minimal
Introduction Anaplastic thyroid cancers (ATCs) are rare, representing around 1% to 2% of all thyroid carcinomas.1 They are particularly aggressive malignancies, especially when metastatic. Prognosis after local progression or metastasis is poor, with only 20% survival at 1 year.2 Disseminated forms are essentially treated by an approach using doxorubicin-based chemotherapy or by targeted therapies within therapeutic protocols, but therapeutic response rates are generally
A
B
C
D
E
F
Fig 1. Journal of Clinical Oncology, Vol 32, 2014
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
Copyright 2014 by American Society of Clinical Oncology
1
Godbert et al
pulmonary lesions was observed (⬎ 20% according to RECIST version 1.1 criteria3). The patient was then referred to our institution (Institut Bergonie´). Additional histologic samples were obtained by bronchial fibroscopy and by mediastinoscopy. Histologic examination revealed an undifferentiated carcinoma. The anaplastic component of both lung and thyroid specimens was similar and showed minimal thyroglobulin reactivity, in favor of a thyroid origin. Given the poor prognosis of the disease and the lack of standard treatment in this setting, and after having obtained patient consent, we screened thyroid and lung tumor specimens for molecular alterations that could represent therapeutic targets. We found no aberrations of the EGFR, BRAF, RAS, ERBB2, PIK3CA, CTNNB1, PTEN, APC, or TP53 genes (Ion AmpliSeq cancer panel; Ion Torrent/Life Technologies, Guilford, CT). Strikingly, we found ALK1 overexpression (clone D5F3, dilution 1:50; Cell Signaling Technology, Danvers, MA) in the
component of papillary carcinoma of the follicular variant (Fig 1B). The tumor extended beyond the thyroid capsule infiltrating the adjacent muscle, and four regional lymph node metastases were observed at central node dissection (of nine dissected). They were stage pT4b N1a and stage IVB, according to the seventh edition of the TNM staging manual. Computed tomography (CT) of the thoraxabdomen-pelvis did not reveal any distant progression. Postoperative concomitant radiochemotherapy was administered with cisplatin (100 mg/m2), etoposide (50 mg/m2), and radiotherapy (45 Gy in conventional fractionation in the primary tumor bed, cervical nodes, and mediastinum, with a boost of 10 Gy in the primary tumor bed). Six months after completion of the initial treatment, multiple bilateral pulmonary recurrences were observed on a CT scan. Secondline chemotherapy treatment with carboplatin and etoposide was administered. After three cycles of chemotherapy, progression of the
Fig 2. 2
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
Diagnosis in Oncology
and tumor suppressor genes have been described, including BRAF, RAS, catenin, PIK3CA, P53, PTEN, AXIN1, and APC genes.7 A number of novel agents have been studied in ATC with, at best, only weak responses.8-10 ALK is an oncogene, a member of the insulin receptor subfamily of receptor tyrosine kinases.11 Since its initial identification within an oncogenic gene fusion product associated with anaplastic large-cell lymphoma, the number of ALK-rearranged neoplasms has continuously increased.12 The tyrosine kinase activities of ALK fusion proteins are aberrantly activated and promote cell proliferation and survival via various signaling pathways, among which are the phosphatidylinositol 3-kinase/Akt pathway and the MAP3 kinase pathway.13,14 ALK rearrangement has been recently described by Hamatani et al15 in 10 of 19 patients (atomic bomb survivors) with radiationexposed papillary thyroid carcinoma (PTC), with no detectable gene alterations in BRAF, RET, NTRK1, or RAS. The authors had previously reported an increased frequency of RET-PTC rearrangements in adult papillary carcinoma, with relatively higher radiation exposure compared with patients with lower radiation exposure, whereas point mutations such as BRAFV600E were less frequent.16 In this small series of patients with PTC, the authors note an association between solid/ trabecular-like architecture and the presence of ALK rearrangement, but do not describe an anaplastic component.15 Six of their patients had rearrangement with EML4, which was apparently not the case in our patient’s tumor. The FISH pattern that we observed is similar to that described in some patients with ALK-positive lung carcinomas and corresponds to a deletion in the ALK gene. Research is in progress to attempt to identify the partner gene. To our knowledge, this is the first case of an ATC with ALK rearrangement to be described in the literature. In contrast to the patients described by Hamatani et al,15 our patient was not exposed to radiation. Murugan et al17 identified two gain-of-function point mutations (C3592T and G3602A) in exon 23 of the ALK gene in two of 18 patients with ATC, but found no mutations in well-differentiated thyroid cancers. From a medico-economic point of view, our patient case raises the problem of the prescription of off-label drugs for patients with cancer. Although our article suggests efficacy of crizotinib in thyroid tumors bearing an aberration of the ALK gene, a well-designed proofof-concept phase II study would represent the best proof of evidence of crizotinib’s efficacy in this setting. Given the rarity of the disease, such a clinical trial would be feasible only in the context of an international collaborative effort.
differentiated papillary carcinoma component (Fig 1C), the anaplastic component of the thyroid specimen (Fig 1D), and the metastatic tumor (Fig 1E). To understand the mechanisms involved in this overexpression, we analyzed the status of the ALK1 gene using fluorescent in situ hybridization (FISH; Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe; Abbott Molecular, Abbott Park, IL). As shown in Figure 1F, we found a rearrangement of the ALK1 gene (arrows show one fusion signal and one red signal with loss of the green signal) in more than 50% of cells among the well-differentiated papillary carcinoma components of the thyroid as well as in the anaplastic component of both specimens, the primary tumor and the pulmonary metastasis. Real-time polymerase chain reaction analysis with Taqman Gene Expression Assays (Applied Biosystems, Foster City, CA), testing for the 10 most frequent echinoderm microtubule-associated protein-like 4 (EML4)/ALK transcripts, was negative. This was in accordance with comparative genomic hybridization array analysis (Agilent Technologies, Santa Clara, CA), which confirmed the FISH pattern, showing a partial deletion in region 2p23 corresponding to the ALK gene (Fig 2, arrow) and with the distal break-point into the ALK gene. We did not observe any corresponding breakages in the EML4 gene. Comparative genomic hybridization array profiles were similar in both localizations (data not shown). On the basis of our molecular findings, we initiated crizotinib (250 mg per day). The treatment was well tolerated and the patient maintained an excellent performance status (Eastern Cooperative Oncology Group [ECOG] score of 0) 2 years after the initial diagnosis. CT examination at baseline (Fig 3A) and at 3 months after crizotinib (Fig 3B) showed an exceptional response of more than 90% across all pulmonary lesions (RECIST version 1.1 criteria). CT examination 6 months after therapy initiation confirmed this excellent response. Discussion ATC is a rare cancer with a poor prognosis. Median overall survival is less than 6 months after initial diagnosis, and 1-year survival is approximately 20%.2 However, several cases of prolonged survival have been described, especially in patients with limited thyroid extension with complete cytoreductive surgery.4 Patients with metastatic ATC (stage IVC) have short survival and no prospects for a curative outcome. The administration of cytotoxic treatment has not demonstrated clear therapeutic efficacy or improvement in quality of life.1,5,6 In parallel with the recent development of inducible tyrosine kinase targeted therapies, interest in the molecular pathogenesis of ATC has grown over the last few years. Mutations in several oncogenes
A
B
Fig 3. www.jco.org
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
3
Godbert et al
Our case is remarkable in that the ALK rearrangement was present both in the well-differentiated component, which was a follicular variant of the papillary type, and in the anaplastic component. This is in favor of an early and likely driver event in the carcinogenesis of this patient’s disease, as is the excellent and durable response to crizotinib. It is difficult to know whether the ALK rearrangement played a role or not in the anaplastic transformation. We did not find any other mutations, even using powerful techniques such as next-generation sequencing. To our knowledge, this is also the first case to be described of an ALK-positive thyroid carcinoma treated by an ALK-specific inhibitor (crizotinib). To our knowledge, this is the first patient to be reported with an ALK rearrangement in ATC who has demonstrated an excellent response to crizotinib. This opens the door to new therapeutic possibilities for these poor-prognosis carcinomas, and potentially for undifferentiated thyroid carcinomas. However, to clearly understand the potential of crizotinib in ATC treatment, the prevalence of this rearrangement needs to be assessed in a larger group.
Yann Godbert, Be´ne´dicte Henriques de Figueiredo, and Franc¸oise Bonichon Institut Bergonie´, Bordeaux, France
Fre´de´ric Chibon Institut Bergonie´; and Institut National de la Sante´ et de la Recherche Me´dicale U916, Bordeaux, France
Isabelle Hostein and Gae¨lle Pe´rot Institut Bergonie´, Bordeaux, France
Camille Dupin Laboratoire d’Anatomie et de Cytologie Pathologiques, Bordeaux, France
Agne`s Daubech Cabinet d’Histo Cyto Pathologie, Le Bouscat, France
Genevieve Belleanne´e and Audrey Gros University Hospital, Pessac, France
Antoine Italiano and Isabelle Soubeyran Institut Bergonie´, Bordeaux, France
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Smallridge RC, Ain KB, Asa SL, et al: American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 22:1104-1139, 2012 2. Kebebew E, Greenspan FS, Clark OH, et al: Anaplastic thyroid carcinoma: Treatment outcome and prognostic factors. Cancer 103:1330-1335, 2005 3. Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247, 2009 4. Lim SM, Shin SJ, Chung WY, et al: Treatment outcome of patients with anaplastic thyroid cancer: A single center experience. Yonsei Med J 53:352-357, 2012 5. Ain KB, Egorin MJ, DeSimone PA: Treatment of anaplastic thyroid carcinoma with paclitaxel: Phase 2 trial using ninety-six-hour infusion—Collaborative Anaplastic Thyroid Cancer Health Intervention Trials (CATCHIT) Group. Thyroid 10:587-594, 2000 6. Shimaoka K, Schoenfeld DA, DeWys WD, et al: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56:2155-2160, 1985 7. Smallridge RC, Marlow LA, Copland JA: Anaplastic thyroid cancer: Molecular pathogenesis and emerging therapies. Endocr Relat Cancer 16:17-44, 2009 8. Mooney CJ, Nagaiah G, Fu P, et al: A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid 19:233-240, 2009 9. Kloos RT, Ringel MD, Knopp MV, et al: Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 27:1675-1684, 2009 10. Pennell NA, Daniels GH, Haddad RI, et al: A phase II study of gefitinib in patients with advanced thyroid cancer. Thyroid 18:317-323, 2008 11. Morris SW, Kirstein MN, Valentine MB, et al: Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 263: 1281-1284, 1994 12. Minoo P, Wang HY: ALK-immunoreactive neoplasms. Int J Clin Exp Pathol 5:397-410, 2012 13. Allouche M: ALK is a novel dependence receptor: Potential implications in development and cancer. Cell Cycle 6:1533-1538, 2007 14. Mourali J, Be´nard A, Lourenc¸o FC, et al: Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage. Mol Cell Biol 26:6209-6222, 2006 15. Hamatani K, Mukai M, Takahashi K, et al: Rearranged anaplastic lymphoma kinase (ALK) gene in adult-onset papillary thyroid cancer amongst atomic bomb survivors. Thyroid 22:1153-1159, 2012 16. Hamatani K, Eguchi H, Ito R, et al: RET/PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose. Cancer Res 68:7176-7182, 2008 17. Murugan AK, Xing M: Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res 71:4403-4411, 2011
ACKNOWLEDGMENT
We thank Pippa McKelvie-Sebileau of Institut Bergonie´ for medical editorial assistance in English.
DOI: 10.1200/JCO.2013.49.6596; published online ahead of print at www.jco.org on March 31, 2014 ■ ■ ■
4
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at University of Queensland on July 15, 2015 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.102.42.98
