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3/8/2018 18 th Multidisciplinary Management of Cancers: A Casebased Approach 18 th Multidisciplinary Management of Cancers: A Casebased Approach 18 th Multidisciplinary Management of Cancers: A Casebased Approach Panel Members Head and

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18th Multidisciplinary Management of Cancers: A Case‐based Approach 18th Multidisciplinary Management of Cancers: A Case‐based Approach

Head and Neck Oncology Tumor Board Focus on Thyroid Cancer

Session Chair

  • A. Dimitrios Colevas MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology ‐ Head and Neck Surgery, Stanford

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Panel Members

  • Tanaya Shree MD.

medical oncology fellow, Stanford

  • Chrysoula Dosiou MD, MS.

Clinical Associate Professor of Medicine, Stanford

  • Lisa Orloff MD. Professor of Otolaryngology ‐ Head and Neck Surgery, Stanford
  • Michael Campbell MD.

Assistant Professor of Surgery, UC Davis

  • Shyam Rao MD PhD. Assistant Professor of Radiation Oncology, UC Davis
  • Quan‐Yang Duh MD.

Professor of Surgery, UCSF

  • Alain Algazi MD. Associate Professor of Medicine, UCSF
  • Jed Katzel MD.

Medical Oncologist, The Permanente Medical Group

18th Multidisciplinary Management of Cancers: A Case‐based Approach

  • Presented in Taiwan with large right thyroid mass (cancer suspected)
  • Clinically staged T3N0M0
  • June 2011: total thyroidectomy, right neck dissection
  • Solitary tumor in right lobe, tracheal deviation, tight fixation to trachea, infiltration
  • f strap muscles
  • Residual tumor on trachea (R2 resection)
  • Pathology: 8.5cm papillary thyroid cancer in right lobe, extensive capsule invasion, margins

extensively positive, 0/5 LN positive.

  • AJCC T3N0M0 | Stage III

Case 1: 65 year old woman with papillary thyroid cancer

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1 / Question 1: How important is the completeness of resection for differentiated thyroid cancers?

  • A. Not important if radioactive iodine (RAI) ablation is planned

anyway

  • B. Not important if radiation is planned anyway
  • C. An important factor, significantly influencing risk of

recurrence

  • D. Important for papillary but not follicular thyroid cancers
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18th Multidisciplinary Management of Cancers: A Case‐based Approach

Incomplete tumor resection portends high risk for recurrence in DTCs

Incomplete resection is considered high risk for recurrence by both ATA and ETA

R0 R1 R2

5‐year DSS R0 – 94.4% R1 – 87.6% R2 – 67.9% p = 0.030 n = 153 MSKCC Operative Series Wang et al., Surgery (2016) ATA Guidelines 2015

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1: 65 year old woman with papillary thyroid cancer

  • Patient received postoperative RAI therapy with 200 mCi
  • Adjuvant radiotherapy recommended, but patient declined
  • Started on levothyroxine 100 mcg daily
  • Lost to follow‐up
  • Moved to the United States

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1: 65 year old woman with papillary thyroid cancer Question for the radiotherapists: What do medical oncologists need to know about 131I dosing? (Our patient received 200 mCi)

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1 / Question 2: What is the appropriate follow‐up of patients with locally advanced differentiated thyroid cancers after initial therapy?

  • A. Periodic thyroglobulin (Tg), anti‐Tg antibody, thyroid

stimulating hormone (TSH) and radioiodine scan

  • B. Periodic Tg, anti‐Tg antibody, TSH and neck ultrasound
  • C. Periodic Tg, anti‐Tg antibody, TSH and PET/CT
  • D. Clinical follow‐up only; no benefit to Tg measurements or

surveillance scans

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18th Multidisciplinary Management of Cancers: A Case‐based Approach

Follow‐up depends on estimation of recurrence risk

High risk patients:

  • Serum Tg, anti‐Tg antibody, TSH every 3‐6 months
  • Periodic neck ultrasound
  • Consider TSH‐stimulated 131I imaging
  • Additional imaging (CT, MRI, PET, extended

ultrasounds) as clinically indicated

ATA Guidelines 2015

Low risk patients:

  • Serum Tg, anti‐Tg antibody, TSH at 6 and 12

months then annually

  • Periodic neck ultrasound (could be omitted in

very low risk patients)

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1: 65 year old woman with papillary thyroid cancer

  • April 2017: Patient presents with recurrent large right neck mass, difficulty swallowing,

inspiratory and expiratory sounds, and diffuse neck pain

  • Referred to a surgeon, who performs a fine needle aspiration (FNA) of the neck mass and
  • rders a neck MRI
  • FNA results: papillary thyroid carcinoma

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1: 65 year old woman with recurrent papillary thyroid cancer

  • 10 cm mass
  • Traversing midline
  • Completely encasing

right common carotid artery

  • Extending along C2

through C7 vertebrae

  • Infiltrating bilateral

cricoarytenoid complex

  • Narrowing airway to a 3

mm slit

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1: 65 year old woman with papillary thyroid cancer Question for the surgeons: What defines a resectable vs. an unresectable tumor?

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Case 1 / Question 3: What is the appropriate next step in management?

  • A. Evaluate for resection or debulking to facilitate retreatment

with radioactive iodine B.

68Ga‐DOTATATE PET/CT to complete staging

C.

18FDG PET/CT to complete staging

  • D. Blood thyroglobulin level, anti‐Tg antibodies, TSH
  • E. Tracheostomy

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1: 65 year old woman with recurrent papillary thyroid cancer

PET/CT June 2017

  • Large right neck mass
  • Extensive right neck

adenopathy

  • Many pulmonary nodules,

largest 1.7cm

  • Tg = 9432 ng/mL
  • TSH = 0.070 μIU/mL

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1 / Question 4:

18FDG‐PET‐avid differentiated thyroid cancer…

  • A. …is typically resistant to radioactive iodine therapy
  • B. …carries a better prognosis than PET‐negative DTC
  • C. …is likely to be negative for BRAF mutation
  • D. …is all of the above

18th Multidisciplinary Management of Cancers: A Case‐based Approach

FDG PET‐avid DTCs are generally resistant to radioiodine treatment

Salvatore et al., Q J Nucl Med Mol Imaging (2008) Wang et al., Thyroid (2001)

Retrospective study of 25 PET(+) and 22 PET(‐) patients with metastatic DTC given 131I therapy Retrospective study of 32 PET(+) and 13 PET(‐) patients with treated DTC but now rising Tg, who were then given 131I therapy

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18th Multidisciplinary Management of Cancers: A Case‐based Approach

BRAFV600E‐mutant DTCs are more likely to be FDG PET‐avid and have higher SUVs

Santhanam et al., Endoc Pract (2017) A review and metanalysis of PET‐avidity and BRAF mutation status in PTCs

7 studies 1144 patients

  • 843 BRAFV600E (+)
  • 301 BRAFV600E (‐)

Pooled odds ratio of having a positive FDG PET = 2.12 Likelihood of PET positivity 4 studies 338 patients

  • 268 BRAFV600E (+)
  • 70 BRAFV600E (‐)

Pooled mean difference in SUVMAX on FDG PET = 5.1 Mean SUV difference

18th Multidisciplinary Management of Cancers: A Case‐based Approach

FDG PET avidity is associated with worse prognosis in DTC

  • 125 patients with thyroid cancer
  • Volume of PET‐avid disease was single strongest predictor
  • 10 patients with PET(‐) distant metastatic disease

remained alive and well

Wang et al., J Endocrinol Metab (2000)

  • 76 patients with positive Tg and negative 131I scan
  • 5‐year survival:
  • 100% in PET‐negative group
  • 63% in PET‐positive group

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 1: 65 year old woman with recurrent papillary thyroid cancer

  • RAI re‐challenge deferred given large tumor that could not be debulked (and given PET

avidity, less likely to respond to RAI therapy)

  • Molecular testing and trial of targeted therapy recommended
  • If no response, recommended to consider radiation therapy
  • Started on lenvatinib 20mg daily (unclear if molecular testing ultimately performed)

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Lenvatinib improves PFS in RAI‐refractory thyroid cancer

  • Lenvatinib inhibits VEGF receptors, FGF

receptors, PDGFRα, RET, and KIT

  • Lenvatinib significantly improved PFS over

placebo (18 months vs 4 months)

  • No overall survival difference, but many

patients crossed over

Schlumberger et al., NEJM (2015)

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Possible other issues to flesh out for case 1 / DTCs:

  • When if ever to reconsider surgery?
  • When to re‐challenge with RAI?
  • Strategies for increasing RAI uptake by malignant tissue?
  • What is adequate TSH suppression in RAI‐refractory patients?
  • Choices of systemic therapy?
  • Importance of molecular testing for BRAF, NKTR, VEGFR? Discussion of early results with

new kinase inhibitors?

  • Situations where we may use a kinase inhibitor before RAI?

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 2: 64‐year‐old woman with thyroid cancer

  • Early May 2017: New onset hoarseness, dysphagia, right otalgia, right mandibular

pain, 8 pound weight loss in 1 month. ECOG 3. Large right anterior neck mass noted

  • n physical exam.
  • May 31 2017 Neck US: “Multiple bilateral thyroid nodules are present. A large

complex heterogeneous nodule occupies the entire right lobe, with irregular margins and intranodular vascularity.”

  • June 7 2017 FNA: “malignant, significant degree of atypia, worrisome for anaplastic

thyroid cancer”

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 2: 64‐year‐old woman with thyroid cancer

Right thyroid mass has possible direct involvement with trachea, possible invasion at the right posterior contour. There is also concern for possible involvement with the right internal jugular vein and right common carotid artery as well. Lung with innumerable nodules, ranging from 1‐8 mm, suspicious for metastases

Noncontrast CT Neck & Chest

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 2 / Question 1: What additional information is needed prior to starting treatment?

  • A. Larger biopsy to confirm pathological diagnosis
  • B. Genomic profiling
  • C. Microsatellite instability status evaluation
  • D. PD‐L1 expression level
  • E. None
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Case 2: 64‐year‐old woman with thyroid cancer

  • Re‐biopsy of neck mass showed:
  • Anaplastic thyroid carcinoma
  • Intact expression of MLH1, MSH2, MSH6 PMS2 (mismatch repair proteins)
  • PD‐L1 expressed in 90% of tumor cells
  • “STAMP” (Solid tumor associated mutation panel) sent
  • Tracheotomy performed
  • FDG PET CT ordered to verify extent of disease
  • Thyroglobulin 4050 ng/ml

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 2: 64‐year‐old woman with anaplastic thyroid cancer

  • Staging PET/CT shows large anterior

neck/upper mediastinal mass, pulmonary nodules, suspicious left iliac lesion

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 2 / Question 2: What would be your initial choice of therapy?

  • A. Surgical resection
  • B. Immune checkpoint inhibitor
  • C. Chemotherapy
  • D. Radiation therapy
  • E. Chemoradiation

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 2: 64‐year‐old woman with metastatic anaplastic thyroid cancer

  • Recommended chemoradiation vs.

supportive care alone given incurable disease with poor prognosis

  • Received paclitaxel 80 mg/m2 weekly with

radiation

  • Response at 2 months excellent
  • Progressed at 4 months, but performance

status significantly improved

  • Mutation panel resulted:

– TP53 loss of function 6% VAF – TERT enhanced telomerase 7% VAF – NRAS activation 16% VAF

2 months 4 months

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18th Multidisciplinary Management of Cancers: A Case‐based Approach

Weekly paclitaxel for anaplastic thyroid cancer

  • Retrospective study by

Higashiyama et al., showed 31% response rate at a single institution

  • Prospective multicenter study by

Onoda et al., confirmed efficacy of weekly paclitaxel in anaplastic TC:

  • 0 CR
  • 21% PR
  • 52% SD
  • Median TTP still poor at 1.6

months

Onoda et al., Thyroid (2016)

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 2 / Question 3: What would be your next choice of therapy?

  • A. Doxorubicin
  • B. Immune checkpoint inhibitor
  • C. TKI targeting NRAS pathway
  • D. Everolimus
  • E. Supportive care alone

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Immunotherapy for thyroid cancer : Current evidence

  • Thyroid cancers can contain many PD‐1+ T‐cells
  • Thyroid cancer cells frequently express PD‐L1, especially if BRAF mutant and especially when aggressive
  • One patient with an impressive response to

nivolumab (Kollipara et al., Oncologist 2017)

  • 64yo male with metastatic anaplastic

thyroid cancer, BRAF‐mutant, PD‐L1 positive

  • Had progressed on

Doxorubicin/Cisplatin and on Paclitaxel; mixed response to vemurafenib

  • Started on nivolumab; achieved CR;

received 12 cycles (~6 months); still in remission 20 months after starting nivolumab Pre‐treatment Post‐treatment

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Immunotherapy for thyroid cancer : Ongoing/planned studies

  • Nivolumab + Ipilimumab (NCT03246958, NCT02834013)
  • Pembrolizumab (NCT03072160, NCT02688608)
  • Pembrolizumab + Docetaxel (NCT03360890)
  • Pembrolizumab + Lenvatinib (NCT02973997)
  • Pembrolizumab +/‐ Surgery + Chemoradiation (NCT03211117)
  • Durvalumab + RAI (NCT03215095)
  • Tremelimumab + SBRT (NCT03122496)
  • Taxane induction + Atezolizumab + Vemurafenib‐OR‐Cometinib (NCT03181100)
  • Many other immunotherapy strategies being tested
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Case 2: 64‐year‐old woman with metastatic anaplastic thyroid cancer

  • Started on nivolumab 240 mg every two weeks
  • After two doses, complained of shadow over

right visual field

  • Ophthalmologist: mass in right eye
  • MRI: Sub‐centimeter nodule in the superior

nasal aspect of the right eye globe posteriorly without evidence of extraocular extension suspicious for metastatic disease.

  • Received radiation to eye metastasis with

improvement

  • Awaiting trametinib approval (given NRAS

mutation)

  • Has met with hospice

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 3: 28yo woman with palpable left neck mass

  • Presented with palpable neck mass; biopsy recommended but patient lost to follow‐up
  • 2 years later: Mass slowly growing, 20 lb weight loss in last year, increasing diarrhea,

anxiety, flushing

  • Recently diagnosed with diabetes and hypertension and started on medications for

both

  • Has a 9‐year old son, but 3 pregnancies in past two years ended prematurely
  • On evaluation: very thin, multiple anterior and lateral left neck masses palpable
  • Excisional left neck lymph node biopsy: metastatic medullary thyroid cancer, strongly

positive for TTF‐1, CEA, synaptophysin, chromogranin A, and CK‐7

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 3: CT Neck, labs

TSH 89, fT4 1.0, fT3 2.6 Calcitonin 148,568 CEA 2589

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 3 / Question 1: What additional work‐up is needed?

  • A. PET/CT to evaluate for metastases given Calcitonin > 500 and

extensive disease in neck B. Chest and abdominal imaging given extensive disease; RET mutation testing, then screen for pheochromocytoma and hyperparathyroidism only if positive; C. Plasma and urine metanephrines, then CT abdomen only if metanephrines positive in order to localize pheochromoctytoma

  • D. Plasma and urine metanephrines, PTH, RET mutation testing,

chest and abdominal imaging

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Case 3 / Question 1: What additional work‐up is needed?

  • A. PET/CT to evaluate for metastases given Calcitonin > 500 and

extensive disease in neck B. Chest and abdominal imaging given extensive disease; RET mutation testing, then screen for pheochromocytoma and hyperparathyroidism only if positive; C. Plasma and urine metanephrines, then CT abdomen only if metanephrines positive in order to localize pheochromoctytoma

  • D. Plasma and urine metanephrines, PTH, RET mutation testing,

chest and abdominal imaging NCCN ATA, UpToDate

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 3: 28yo woman with metastatic medullary thyroid cancer

  • 24h urine metanephrines 9208 [<222]
  • 24h urine normetanephrines 7311 [<412]
  • Plasma metanephrine 2343
  • Plasma normetanephrine 3057
  • Plasma total metanephrine 5400
  • PTH 41 [10‐80], Ca 9.9, Alb 4.3
  • MRI Abdomen: Bilateral adrenal masses

(left 5.9 x 5.3 x 5.9; right 3.3 x 2.8 x 2.2), innumerable liver lesions, bony lesions

  • Heterozygous for RET Cys634Arg

mutation (germline)

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Mulligan LM. Nat Rev Cancer (2014)

RET protein

MEN2A

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 3: 28yo woman with MEN2A with metastatic MTC and bilateral PHEOs

  • Started on phenoxybenzamine for alpha blockade
  • Must start at least two weeks prior to surgery
  • Underwent open bilateral adrenalectomy & liver biopsy
  • Findings: 6cm left adrenal mass, 2.5cm right adrenal mass, liver mets
  • Pathology: adrenal masses both pheochromocytomas; liver metastasis consistent with

metastatic medullary thyroid cancer

  • Underwent total thyroidectomy for debulking
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18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 3 / Question 2: What next?

  • A. Observation
  • B. Dabrafenib and trametinib
  • C. Vandetanib
  • D. Cabozantinib
  • E. Immune checkpoint inhibitor

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Tyrosine Kinase Inhibitors for Medullary Thyroid Cancer

Vandetanib approved for metastatic MTC in April 2011 Cabozantinib approved for metastatic MTC in Nov 2012

Pappa & Alevizaki. Endocrine (2016)

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Tyrosine Kinase Inhibitors for Medullary Thyroid Cancer

Elisei et al., J. Clin. Oncol. (2013) Wells et al., J. Clin. Oncol. (2012)

Vandetanib vs. Placebo, PFS Cabozantinib vs. Placebo, PFS

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 3: 28yo woman with MEN2A with metastatic MTC and bilateral PHEOs

  • Started on Cabozantinib
  • Great response
  • Progression after 1.5 years
  • Started on Vandetanib
  • Responded but discontinued due to toxicity
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Thyroidectomy Cabozantinib 140mg/d Cabozantinib 120mg/d Cabozantinib 100mg/d Vandetanib 300 mg/d Discontinued Cabozantinib Discontinued vandetanib

Felt good Felt bad Felt good Felt OK

140,000 160,000 100,000 120,000 60,000 80,000 20,000 40,000 180,000 5/19/15 11/25/14 5/3/16 11/10/15 4/18/17 10/25/16

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 3: 28yo woman with MEN2A with metastatic MTC and bilateral PHEOs

“BLU‐667 is a potent and selective inhibitor of RET mutations, fusions, and predicted resistant mutants.” Phase 1 Study of BLU‐667 in Patients With Thyroid Cancer, Non‐Small Cell Lung Cancer, and Other Advanced Solid Tumors NCT03037385 Dr Matthew Taylor, OHSU

BLU‐667

Feels great.

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 3 / Question 3: What about her family?

  • A. If no family history suggestive of MEN2A, recommend RET

mutation testing only for son

  • B. Recommend RET mutation testing of all first degree relatives
  • C. Recommend RET mutation testing and neck ultrasound for all

first‐degree relatives

  • D. Recommend RET mutation testing, neck ultrasound, plasma

and urine metanephrines, and PTH for all first degree relatives

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 3: 28yo woman with MEN2A with metastatic MTC and bilateral PHEOs

  • 30‐year‐old brother,

18‐year‐old sister, and 9‐year‐old son all tested for RET mutations

  • Son tested positive for

RET Cys634Arg mutation (same as patient)

Adapted from ATA Guidelines 2015 Figure from Van der Tuin et al., Cancer Research Frontiers (2015)

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Case 4: 52 yo woman with a right thyroid nodule

  • 52‐year‐old female; physician palpated right thyroid mass
  • Ultrasound shows 1.8 cm hypoechoic solid nodule in right thyroid; left

lobe homogenous and free of nodules

Fine needle aspirate revealed “Follicular Lesion of Undetermined Significance” (“FLUS”)

ATA guidelines, Thyroid (2016)

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 4 / Question 1: What is the next step in management?

  • A. Hemithyroidectomy
  • B. Total thyroidectomy
  • C. Repeat US‐FNA
  • D. Repeat US‐FNA with molecular testing

18th Multidisciplinary Management of Cancers: A Case‐based Approach Case 4: 52 yo woman with a right thyroid nodule Bethesda 2017

5-11% 55-74% 2-18% 2-25% 1-6% 2-5% Overall: About 25% of FNAs are indeterminate-- 10-40% of these are malignant Frequency Diagnostic category Risk of malignancy “AUS” and “FLUS” “FN”

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 4: 52 yo woman with a right thyroid nodule

Molecular Testing for Indeterminate FNAs

  • Gene expression classifier test (Afirma)
  • Analyzes mRNA expression of 167 genes
  • Results: benign vs suspicious
  • PPV = 37‐44%
  • NPV = 93‐95%
  • Panel testing for mutations (e.g. Thyroseq)
  • Includes BRAF, RAS, RET/PTC, PAX8/PPAR
  • PPV = 87‐95%
  • NPV = 72‐94%

FNA Result Afirma Result Malignancy rate Suspicious for malignancy Benign 15‐28% AUS/FLUS or FN Benign 6‐7% AUS/FLUS or FN Suspicious 37‐44% Our patient undergoes Afirma testing: “suspicious”

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Case 4: 52 yo woman with a right thyroid nodule

  • Patient undergoes right

hemithyroidectomy

  • Pathology: “Papillary thyroid

carcinoma, follicular variant”

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Case 4 / Question 2: What is the next step in management?

  • A. Completion thyroidectomy
  • B. Completion thyroidectomy and radioiodine ablation
  • C. Observation with periodic neck ultrasounds
  • D. No further intervention needed
  • E. Need to review pathology in greater detail to decide

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Follicular Variant Papillary Thyroid Cancer (FVPTC)

Non-encapsulated FVPTC (infiltrative/diffuse), very close to classical PTC Classical PTC FVPTC Follicular adenoma/ carcinoma Encapsulated FVPTC (close to follicular adenoma/carcinoma

Cancer Volume 107, Issue 6, pages 1255-1264, 9 AUG 2006 DOI: 10.1002/cncr.22138 http://onlinelibrary.wiley.com/doi/10.1002/cncr.22138/full#fig3

Characteristic Classic PTC FVPTC Follicular CA Extrathyroidal Extension 25% 15% 9% LN metastases 34% 16% 2% Distant metastases 1% 2% 4% 15 year Disease‐ Specific Survival 97% 98% 92% Yu, X‐M. et al., Thyroid (2013)

18th Multidisciplinary Management of Cancers: A Case‐based Approach

Follicular Variant Papillary Thyroid Cancer (FVPTC)

Characteristic Encapsulated FVPTC Non‐encapsulated FVPTC Number1 61 17 Extrathyroidal extension1 5% 65% Positive margins1 2% 50% Lymph node metastases1 5% 65% Tumor fibrosis1 18% 88% BRAF2 0% 26% RAS2 36% 10% 70% of cases noninvasive (n=42) At 11 years follow-up: NO recurrences NO metastatic disease NO deaths

1Liu et al., 2006, Cancer 107: 1255 2Rivera et al., 2010, Mol Pathol 23:1191

 Noninvasive encapsulated FVPTC renamed “Non‐Invasive Follicular Thyroid Neoplasm with Papillary‐like Nuclear Features” or NIFTP  about 19% of PTCs

8/2016

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Case 4: 52 yo woman with a right thyroid nodule

  • Detailed examined of histology revealed NIFTP
  • Observation recommended
  • 73% of malignancies identified after suspicious Afirma1,2 and 74% of malignancies

identified after positive Thyroseq3 testing in AUS/FLUS or FN FNAs were FVPTC

1Lastra et al., 2014 2Wong et al., 2016 3Nikiforov et al., 2011