Head & Neck, Thyroid, CNS Malignancies
Cristina Rodriguez, MD
Lakshmi Nayak, MD
A 35-year-old man of Southern Chinese descent presents with a 6-month history of left-sided middle ear effusions and a 2-month history of increasing bilateral cervical lymphadenopathy. On physical examination, he is found to have bilateral lymphadenopathy in III, IV, and V. An office endoscopic examination shows no visible mucosal abnormalities of the oral cavity; naso-, oro-, hypopharynx; or larynx.
What next step would help establish the diagnosis?
View Answer
Biopsy of palpable cervical lymph node with EBER (EBV) staining should be performed to confirm nasopharyngeal carcinoma in a patient with concerning features.
This is a patient whose demographic (Southeastern descent) and presenting signs are highly suspicious for nasopharyngeal carcinoma, and EBER testing confirms endemic disease.
Suggested Readings:
Maghami E, Ismaila N, Alvarez A, et al. Diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck: ASCO Guideline. J Clin Oncol. 2020;38(22):2570-2596. PMID: 32324430.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 35-year-old male patient of Southern Chinese descent with biopsy-proven EBER+ nasopharyngeal carcinoma is staged after diagnosis. CT of neck confirms the presence of extensive cervical lymphadenopathy and shows a mass in the left fossa of Rosenmuller. CT imaging of the chest/abdomen/pelvis shows no other evidence of metastases. He has a PS of 0 and no significant comorbidities. The treatment goal is ____, and the approach is ________.
View Answer
The treatment goal is cure, and the approach is nonsurgical/radiation based on a patient with nonmetastatic nasopharyngeal carcinoma.
Definitive radiotherapy combined with concomitant cisplatin followed by adjuvant cisplatin and 5-FU is an appropriate recommendation.
Other curative-intent options are induction chemotherapy followed by chemoradiation, or chemoradiation.
Suggested Readings:
Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16(4):1310-1317. PMID: 9552031.
Chen L, Hu CS, Chen XZ, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012;13(2):163-171. PMID: 22154591.
Zhang Y, Chen L, Hu GQ, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med. 2019;381(12):1124-1135. PMID: 31150573.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 55-year-old man from Southern China was treated with radiation and concurrent cisplatin for a locally advanced nasopharyngeal carcinoma (NPC) 2 years ago. After presenting with rib pain, he is found to have diffuse bone metastases and liver metastasis. He has an ECOG 0 and no significant comorbidities.
What is your treatment recommendation?
View Answer
Palliative systemic therapy is an appropriate recommendation for metastatic nasopharygeal carcinoma.
The combination of gemcitabine and a platinum agent is a standard of care that has been shown to have a PFS benefit compared to 5-FU and platinum regimen.
Suggested Readings:
Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016;388(10054):1883-1892.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
You evaluate a 68-year-old man after curative-intent surgery for an oral cavity squamous cell carcinoma. He is a former alcoholic and active smoker. His pathology showed negative surgical margins at the primary site, and 2 out of 37 cervical lymph nodes contained malignancy; the pathology report describes extracapsular extension in the largest lymph node measuring 2.8 cm. The patient recovered well from surgery, has no significant comorbidities, and has an ECOG 0.
What is your management recommendation?
View Answer
Adjuvant radiation therapy with concurrent cisplatin chemotherapy has been shown to improve curative outcomes in patients with high-risk head and neck cancer in the landmark trials EORTC 22931 and RTOG 9501.
High-risk factors include positive resection margin and extracapsular extension of nodal disease.
Suggested Readings:
Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27(10):843-850. PMID: 16161069.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 62-year-old, former smoker presents with hoarseness. An evaluation revealed a mass on the left vocal cord which is immobile. No evidence of laryngeal cartilage involvement was noted on CT, and no pathologic adenopathy was noted. CT of the chest shows no metastases, and biopsy reveals poorly differentiated squamous cell carcinoma. He has no significant comorbidities and has an ECOG 0.
What is the recommended management?
View Answer
This T3N0 (immobile vocal cord) larynx cancer is appropriate for larynx preservation as a curative-intent strategy. Cisplatin-based concurrent chemoradiation provides superior laryngectomy-free survival and locoregional control compared to radiation alone or induction chemotherapy followed by radiation based on the landmark trial RTOG 91-11.
Suggested Readings:
Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31(7):845-852. PMID: 23182993.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 56-year-old male, active smoker presents with hoarseness, dysphagia, and aspiration. An evaluation revealed a large tumor originating from the left supraglottic larynx, with radiographic evidence of cricoid and thyroid cartilage invasion. A biopsy of this tumor revealed a moderately differentiated squamous cell carcinoma. A full staging evaluation revealed the laryngeal mass, as well as bilateral necrotic cervical lymph nodes. There was no evidence of distant metastases. He has no significant comorbidities and has an ECOG 1.
What considerations preclude larynx preservation among those with laryngeal cancer and what is the most appropriate management for this patient?
View Answer
Considerations for Larynx Preservation: Larynx preservation through chemoradiation is not recommended for patients with laryngeal destruction/dysfunction and were excluded from landmark clinical trials.
Management: Upfront laryngectomy and bilateral neck dissection with postoperative therapy directed by pathologic features of the resected specimen in this patient with invasive laryngeal cancer.
Radiation is a reasonable option for patients with early-stage laryngeal cancer.
Risk factors for laryngeal cancer includes smoking and gastroesophageal reflux disease.
Suggested Readings:
Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31(7):845-852. PMID: 23182993.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 45-year-old woman undergoes larynx preservation for a T3N2bM0 squamous cell carcinoma of the glottis with concomitant chemoradiation. A reevaluation of her disease at 12 weeks after completion of therapy reveals biopsy-proven persistent disease in the larynx and residual pathologically enlarged neck lymph nodes. The patient has an ECOG 0 and is interested in additional therapy, if one is available.
What is the most appropriate management?
View Answer
Surgical referral for consideration of salvage laryngeal resection for residual disease. Salvage laryngectomy is a curative-intent procedure in the setting of failure of concurrent chemoradiation.
Suggested Readings:
Weber RS, Berkey BA, Forastiere A, et al. Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group Trial 91-11. Arch Otolaryngol Head Neck Surg. 2003;129(1):44-49. PMID: 12525193.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 55-year-old patient successfully completes curative-intent concurrent chemoradiation for a T2N3M0 squamous cell carcinoma of the oropharynx. You order a PET 12 weeks after completion of therapy and a residual PET-avid 2.2 cm level 3 cervical lymph node is noted.
What is your recommendation?
View Answer
Surgical referral for posttreatment neck dissection is appropriate in patients with residual PET-avid adenopathy after concurrent chemoradiation.
Patients with residual adenopathy after concurrent chemoradiation have ˜20% chance of pathologically confirmed viable tumor. PET-CT can aid in identification of patients appropriate for neck dissection.
Suggested Readings:
Mehanna H, Wong WL, McConkey CC, et al. PET-CT surveillance versus neck dissection in advanced head and neck cancer. N Engl J Med. 2016;374(15):1444-1454. PMID: 27007578.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
You treated a 58-year-old man with a T3N2cM0 p16+ oropharynx squamous cell carcinoma with chemoradiation. He develops biopsy-proven evidence of lung metastases 6 months after completion of curative-intent therapy. He has an ECOG 0 and has no other comorbidities.
What FDA-approved therapy do you recommend?
View Answer
Single-agent immune checkpoint inhibitor should be considered in this patient with recurrent oropharyngeal carcinoma. Both nivolumab and pembrolizumab were compared to methotrexate or cetuximab or docetaxel in the relapsed setting. Both studies showed overall survival advantage with the use of the immune checkpoint inhibitor, and both are FDA approved for patients previously treated with a platinum agent independent of PDL1 status.
Suggested Readings:
Cohen EEW, Soulières D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167. PMID: 30509740.
Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. PMID: 27718784.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 70-year-old man treated with prior surgical resection and adjuvant radiation for a T1N2a oral cavity squamous cell carcinoma develops multiple lung nodules 1 year after curative-intent treatment. A biopsy reveal squamous cell carcinoma. He has an ECOG of 0 and has no other comorbidities.
What biomarker testing on tissue would assist in management of metastatic setting?
View Answer
Obtain CPS (combined proportion score) testing of tissue in metastatic head and neck cancer to identify patients who may benefit from single-agent pembrolizumab.
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