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Carcinoma of Unknown Primary: The Role of Transoral Robotic Surgery Christine M. Kim, MS4 Georgetown University School of Medicine
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CC: Right neck swelling HPI: JD is a 63M initially presented to PCP with a painful R neck mass after URI, thought to be neck abscess Saw outside HNS and received antibiotics and needle aspiration showing frank pus Sent to WHC ED and admitted to HNS ROS: Negative
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CC: Right neck swelling PMH: HTN PSH: Lithotripsy for left renal calculus, arthroscopy R knee Meds: Atenolol-Chlorthalidone, Aspirin FamHx: Denies Social Hx: Employed as mailman. Never smoked. Occasional EtOH
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Physical Exam Gen: NAD, AAOx3 Eyes: EOMI, PERRLA Ant nares: Clear Ears: Clear, TM intact OC/OP: Tonsils symmetric 1+ b/l, tongue mobile, no palpable masses, no erythema Neck: Rightlevels II and III LAD. Salivary glands soft and symmetric b/l.Thyroid normal to palpation. Trachea midline, no masses or tenderness.
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Flexible laryngoscopy Nasal mucosa: no signs of inflammation Turbinates: normal morphology Polyps: No polyps or masses Septum: No performations Nasopharynx: No significant adenoid enlargement, eustachian tube orifices clear Oropharynx: Pharyngeal walls normal Hypopharynx: No pooling of secretions; no lesions or erythema Larynx: Vocal cord motion is normal; no lesions Vocal Folds: No vocal fold lesions
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CT
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Evaluation FNA: no signs of malignancy Taken to OR for LN biopsy and I&D of neck abscess: 2 large nodes  Frozen (+) for metastatic SCCa DL completed PET/CT
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PET/CT
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Evaluation FNA: no signs of malignancy Taken to OR for LN bx and I&D of neck abscess: 2 large nodes. Frozen positive for metastatic SCCa. DL completed PET/CT: Concordant FDG-PET and CT images with necrotic LAD R neck R MRND: 2/44 R level III nodes with metastatic SCCa Diagnosis: TxN2bM0 SCCa, primary site unknown
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Carcinoma of unknown primary Definition Presentation Evaluation Management Emerging diagnostic modalities - TORS Outcomes
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Carcinoma of unknown primary WHO definition: histologicdx of malignant neoplasm metastatic to cervical LN without identifiable 1o tumor following comprehensive evaluation SCC: 53-77% of CUP histologies1 Constitutes 2-4% of head and neck SCCa2 Presentation3 Neck mass 94-100% Pain 9% Weight loss 7% Dysphagia 4% M:F = 75% : 25% Mean age 55 1. Strojan P et al. Contemporary management of lymph node metastases from an unknown primary to the neck, I: a review of diagnostic approaches. Head Neck, 2013. 2. Nieder et al. Curr Treat Options Oncol, 2000; Karni et al; Laryngoscope, 2011 3. Issing et al; Eur Arch ORL, 2003, Grau et al; RadiotherOncol, 2000. Photo: http://www.aafp.org/afp/2002/0901/p831.html
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Evaluation H&N exam, FFL, CT, FNA, panendoscopy, PET/CT Directed biopsies Only 17 – 63% of primary tumors identified1,2 Failure to find primary3: Small size Cryptic location Tumor regression Most common primary sites identified in workup of CUP are palatine tonsils and BOT4 1. Mehta et al. “A new paradigm for diagnosis and management of unknown primary tumors of the head and neck: a role for transoral robotic surgery.” Laryngoscope, 2009 2. Haas I et al. “Diagnostic strategies in cervical carcinoma of an unknown primary.” Eur Arch Otorhinolaryngol 2002 3. Eisele, D. “Squamous cell carcinoma of the neck with unknown primary.” Auto-Digest Otolaryn 2013. 4. Cianchetti M et al. “Diagnostic evaluation of SCC metastatic from an unknown primary to neck: II. A review of therapeutic options.” Head Neck 2013.
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Waldeyer’s Ring
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What if 1o site is not found? Remaining true CUP cases are treated with either primary wide-field radiation or chemoradiation therapy with or without neck dissection 5-year actuarial survival1: 69% for N1 58% for N2 30% for N3 1. Grau C, Johansen LV, Jakobsen J, Geertsen P, Andersen E, Jensen BB. "Cervical lymph node metastases from unknown primary tumors.” RadiotherOncol 2005.
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Toxicity of chemoradiation 25% with grade 2 xerostomia 32% grade 3 radiation dermatitis 72% grade 1-2 dysphagia  95% had G tube for median of 6 mo 50% grade 3 mucositis 46% esophageal stricture 40% skin fibrosis Madani I, Vakaet L, Bonte K, Boterberg T, De Neve W. Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J RadiatOncolBiolPhys 2008. Top photo: http://www.headandneckcancerpatient.com/uploads/1/3/8/1/1381721/1368688.jpg?922. Bottom photo: http://ida.cdeworld.com/courses/4587-Oral_Pretreatment_of_the_Cancer_Patient
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N=44 CUP patients from the University of Pittsburgh Match-paired analyses Improved overall, disease-free, and cause-specific survival
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5-year overall survival: 95.7% (1o found) vs. 52% (1o not found)
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TORS daVinci robot system with 3D magnified view Improved visualization Freedom of motion Access to OP subsites Useful for both ablative purposes and potentially as diagnostic modality Top: http://www.uphs.upenn.edu/pennorl/education/images/daVinci_ Machine2.jpg Bottom: http://www.medicalgrapevineasia.com/mg/2013/03/17/ minimally-invasive-head-and-neck-surgery/
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N = 10 CUP patients from the University of Pittsburgh All patients underwent cervical bx, PET/CT, formal endoscopy, bilateral tonsillectomy, random bx BOT When 1o site not found  TORS lingual tonsillectomy 9/10 (90%) with pathologic exam revealing invasive SCCa Mean diameter = 0.9 cm
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Multi-institutional study: University of Washington, MD Anderson, University of Alabama-Birmingham, UT-Houston, Johns Hopkins, Oregon Health Sciences N = 47 patients with CUP Tumor siteidentified by TORS in 34 of 47 (72.3%) 18 with no suspicious findings  72.2% identified Suggests that regardless of the preoperative findings, TORS had a consistently high diagnostic rate JAMA Otolaryngol Head Neck Surg. 2013
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Primary identified Management appropriate for size and extent of disease Allows options for surgical resection Better definition of primary tumor target volume Focused radiation field Assists in post-treatment surveillance Eisele, D. “Squamous cell carcinoma of the neck with unknown primary.” Auto-Digest Otolaryngology 2013.
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N = 22 at Ohio State University Long-term QOL scores collected at baseline, 3 weeks, 3 months, 6 months, 12 months post-op Four domains: speech, eating, aesthetics, social disruptions
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Patient JD Palatine tonsillectomy and TORS lingual tonsillectomy Path: Infiltrating SCC, moderately differentiated, left BOT Chemoradiation for definitive treatment
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Conclusions CUP is a devastating diagnosis with previously poor treatment options and prognoses Wide-field radiation therapy causes significant morbidity Finding primary site leads to much better survival outcomes TORS has potential to improve both discovery of primary tumor sites and overall survival in these pts Analysis of quality-of-life studies after TORS has shown minimal disruptions in day-to-day functions
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Thank you
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TORS Quality-of-Life study SCC detected in palatine tonsil in 12 pts (54.5%) and BOT in four pts (18.2%) No primary tumor identified in six patients (27.3%) Complete tumor resection with negative margins achieved in 12 of 16 pts (75%)
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SCC detected in palatine tonsil in 12 pts (54.5%) and BOT in four pts (18.2%) No primary tumor identified in six patients (27.3%) Complete tumor resection with negative margins achieved in 12 of 16 pts (75%)
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Grau et al; RadiotherOncol, 2000
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