3/8/2018 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Panel Members Head and Neck Oncology Tumor • Tanaya Shree MD. medical oncology fellow, Stanford Board • Chrysoula Dosiou MD, MS. Clinical Associate Professor of Medicine, Stanford Focus on Thyroid Cancer • 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 Session Chair • Quan‐Yang Duh MD. Professor of Surgery, UCSF A. Dimitrios Colevas MD • Alain Algazi MD. Associate Professor of Medicine, UCSF Professor of Medicine (Oncology) and, by courtesy, of • Otolaryngology ‐ Head and Neck Surgery, Stanford Jed Katzel MD. Medical Oncologist, The Permanente Medical Group 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1 / Question 1: How important is the completeness of resection for Case 1: 65 year old woman with papillary thyroid cancer differentiated thyroid cancers? • Presented in Taiwan with large right thyroid mass (cancer suspected) A. Not important if radioactive iodine (RAI) ablation is planned • Clinically staged T3N0M0 anyway • June 2011: total thyroidectomy, right neck dissection B. Not important if radiation is planned anyway • Solitary tumor in right lobe, tracheal deviation, tight fixation to trachea, infiltration of strap muscles C. An important factor, significantly influencing risk of • Residual tumor on trachea (R2 resection) recurrence • Pathology: 8.5cm papillary thyroid cancer in right lobe, extensive capsule invasion, margins D. Important for papillary but not follicular thyroid cancers extensively positive, 0/5 LN positive. • AJCC T3N0M0 | Stage III 1
3/8/2018 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Incomplete tumor resection portends high risk for recurrence in DTCs Case 1: 65 year old woman with papillary thyroid cancer • Incomplete resection is considered high Patient received postoperative RAI therapy with 200 mCi risk for recurrence by both ATA and ETA • Adjuvant radiotherapy recommended, but patient declined • R0 Started on levothyroxine 100 mcg daily R1 • Lost to follow‐up R2 5‐year DSS R0 – 94.4% • Moved to the United States R1 – 87.6% R2 – 67.9% p = 0.030 n = 153 MSKCC Operative Series Wang et al., Surgery (2016) ATA Guidelines 2015 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1 / Question 2: What is the appropriate follow‐up of patients with locally Case 1: 65 year old woman with papillary thyroid cancer advanced differentiated thyroid cancers after initial therapy? A. Periodic thyroglobulin (Tg), anti‐Tg antibody, thyroid Question for the radiotherapists: stimulating hormone (TSH) and radioiodine scan What do medical oncologists need to know about 131 I dosing? B. Periodic Tg, anti‐Tg antibody, TSH and neck ultrasound C. Periodic Tg, anti‐Tg antibody, TSH and PET/CT (Our patient received 200 mCi) D. Clinical follow‐up only; no benefit to Tg measurements or surveillance scans 2
3/8/2018 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Follow‐up depends on estimation of recurrence risk Case 1: 65 year old woman with papillary thyroid cancer High risk patients: • April 2017: Patient presents with recurrent large right neck mass, difficulty swallowing, • Serum Tg, anti‐Tg antibody, TSH every 3‐6 months inspiratory and expiratory sounds, and diffuse neck pain • Periodic neck ultrasound • Consider TSH‐stimulated 131 I imaging • Referred to a surgeon, who performs a fine needle aspiration (FNA) of the neck mass and • Additional imaging (CT, MRI, PET, extended orders a neck MRI ultrasounds) as clinically indicated • FNA results: papillary thyroid carcinoma 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) ATA Guidelines 2015 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1: 65 year old woman with recurrent papillary thyroid cancer Case 1: 65 year old woman with papillary thyroid cancer • 10 cm mass • Traversing midline Question for the surgeons: • Completely encasing right common carotid What defines a resectable vs. an unresectable tumor? artery • Extending along C2 through C7 vertebrae • Infiltrating bilateral cricoarytenoid complex • Narrowing airway to a 3 mm slit 3
3/8/2018 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1 / Question 3: What is the appropriate next step in management? Case 1: 65 year old woman with recurrent papillary thyroid cancer PET/CT June 2017 A. Evaluate for resection or debulking to facilitate retreatment • with radioactive iodine Large right neck mass • Extensive right neck B. 68 Ga‐DOTATATE PET/CT to complete staging adenopathy • Many pulmonary nodules, 18 FDG PET/CT to complete staging C. largest 1.7cm D. Blood thyroglobulin level, anti‐Tg antibodies, TSH • Tg = 9432 ng/mL • E. Tracheostomy TSH = 0.070 μIU/mL 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1 / Question 4: 18 FDG‐PET‐avid differentiated thyroid cancer… FDG PET‐avid DTCs are generally resistant to radioiodine treatment Retrospective study of 25 PET(+) and Retrospective study of 32 PET(+) and 13 A. …is typically resistant to radioactive iodine therapy 22 PET(‐) patients with metastatic PET(‐) patients with treated DTC but now DTC given 131 I therapy rising Tg, who were then given 131 I 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 Wang et al., Thyroid (2001) Salvatore et al., Q J Nucl Med Mol Imaging (2008) 4
3/8/2018 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach FDG PET avidity is associated with worse prognosis in DTC BRAF V600E ‐mutant DTCs are more likely to be FDG PET‐avid and have higher SUVs Likelihood of PET positivity Mean SUV difference 4 studies 7 studies 338 patients 1144 patients 268 BRAF V600E (+) 843 BRAF V600E (+) • • 301 BRAF V600E (‐) 70 BRAF V600E (‐) • • Pooled odds ratio of Pooled mean difference in SUV MAX on FDG PET = having a positive FDG PET = 2.12 5.1 • 125 patients with thyroid cancer • 76 patients with positive Tg and negative 131 I scan • Volume of PET‐avid disease was single strongest predictor • 5‐year survival: • 10 patients with PET(‐) distant metastatic disease • 100% in PET‐negative group remained alive and well • 63% in PET‐positive group Santhanam et al., Endoc Pract (2017) A review and metanalysis of PET‐avidity and BRAF Wang et al., J Endocrinol Metab (2000) mutation status in PTCs 18 th Multidisciplinary Management of Cancers: A Case‐based Approach 18 th Multidisciplinary Management of Cancers: A Case‐based Approach Case 1: 65 year old woman with recurrent papillary thyroid cancer Lenvatinib improves PFS in RAI‐refractory thyroid cancer • RAI re‐challenge deferred given large tumor that could not be debulked (and given PET • Lenvatinib inhibits VEGF receptors, FGF avidity, less likely to respond to RAI therapy) receptors, PDGFRα, RET, and KIT • Molecular testing and trial of targeted therapy recommended • Lenvatinib significantly improved PFS over • If no response, recommended to consider radiation therapy placebo (18 months vs 4 months) • No overall survival difference, but many • Started on lenvatinib 20mg daily (unclear if molecular testing ultimately performed) patients crossed over Schlumberger et al., NEJM (2015) 5
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