Case Reports in Otolaryngology

Case Reports in Otolaryngology / 2019 / Article

Case Report | Open Access

Volume 2019 |Article ID 9581259 | https://doi.org/10.1155/2019/9581259

Joseph K. Kim, Kunal Sindhu, Richard L. Bakst, "Cardiac Metastasis in a Patient with Head and Neck Cancer: A Case Report and Review of the Literature", Case Reports in Otolaryngology, vol. 2019, Article ID 9581259, 8 pages, 2019. https://doi.org/10.1155/2019/9581259

Cardiac Metastasis in a Patient with Head and Neck Cancer: A Case Report and Review of the Literature

Academic Editor: Abrão Rapoport
Received15 Nov 2018
Accepted24 Feb 2019
Published18 Apr 2019

Abstract

Cardiac metastasis from a primary head and neck cancer is a rare finding. Most patients with cardiac metastases have nonspecific symptoms that may vary depending on the severity and location of the lesion. Due to the infrequency of reported cases, there are no clear guidelines for the diagnosis or management of cardiac metastasis in head and neck cancer patients. In this report, we discuss the case of a patient with a primary diagnosis of oral tongue cancer who developed a cardiac metastasis that was detected antemortem.

1. Introduction

Cardiac metastases in patients with head and neck squamous cell carcinoma (HNSCC) are a very rare finding [1]. Most cases of cardiac metastasis are clinically silent with a majority of cases detected in the postmortem setting. If cardiac metastasis is diagnosed in a living patient, the clinical presentation is often variable with nonspecific symptoms. Here, we discuss the clinical presentation, diagnosis, and management of a patient with oral cavity cancer who developed a metastasis to the heart.

2. Case Presentation

A 46-year-old white female with a 15 pack-year smoking history initially presented 3 years ago with intense pain in the left side of the mouth that radiated to her left ear for 2 months. She was found to have a 2 cm exophytic lesion on the left lateral border of her tongue that was diffusely keratotic and extremely tender on examination. Fiberoptic laryngoscopy revealed normal findings in the nasopharynx, oropharynx, and hypopharynx. Histological biopsy of the tongue lesion confirmed well-differentiated squamous cell carcinoma of the left lateral border of the tongue. Radiographical findings on positron emission tomography (PET) scan showed hyperactivity along the left lateral aspect of the tongue and a mildly hypermetabolic left level IIa cervical lymph node with no evidence of distant metastases (Figure 1).

The patient was treated with a left hemiglossectomy and bilateral neck dissection. Pathologic evaluation revealed a 2.4 cm moderately differentiated, infiltrating squamous cell carcinoma of the left lateral tongue lesion invading into the skeletal muscle with a 0.5 cm maximal thickness. There was perineural invasion, but no lymphovascular invasion, and all margins were free of cancer. A total of 3 out of 22 lymph nodes were positive for carcinoma: 0 out of 10 in right neck level II-III, 2 out of 5 left level I with no extracapsular extension (ECE), 0 out of 1 left level II, and 1 out of 6 left level III with no ECE.

She was staged as pT2 pN2b M0 (stage IVA, AJCC 7th edition 2010) squamous cell carcinoma of the left lateral tongue. She received adjuvant treatment with concurrent afatinib and radiotherapy to a total dose of 6000 cGy in 30 fractions over 6 weeks to the oral cavity and bilateral necks, which was completed in 3 months after diagnosis.

Interval radiographical imaging did not show any evidence of disease recurrence or distant metastases until 2018. At that time, the patient had developed increasing left arm pain, left ear pain, and left throat pain. She also reported intermittent chest pressure, exertional dyspnea, and intermittent dizziness with positional changes.

In early 2018, a PET scan (Figure 2) and magnetic resonance imaging (MRI) of the chest (Figure 3) showed a new 3.4 cm left apical pleural mass encasing the left subclavian artery and abutting the left subclavian vein, both of which were patent. A computed tomography-guided fine-needle aspiration (CT-FNA) of the apical lung mass revealed squamous cell carcinoma.

Shortly after, the patient began systemic therapy with cisplatin and etoposide and radiation therapy to the left apical lung lesion. Following the 20th fraction of radiation therapy, a repeat computed tomography (CT) scan of the chest revealed a new 1.2 cm lesion in the inferior interventricular septum of the heart. A cardiac ultrasound was performed and demonstrated a mass in the left ventricle. The patient went on to complete radiation therapy to a total of 6000 cGy in 30 fractions. Further diagnostic imaging with a cardiac MRI was performed, which revealed a mass infiltrating the left ventricle, inferior myocardium, epicardial fat, and pericardium with associated mobile thrombus formation (Figure 4). A PET/CT scan demonstrated hypermetabolic lesions in the left neck, right thigh muscles, lung parenchyma, heart, anterior mediastinum, left scapula, and posterior right rib (Figure 2). Transthoracic echocardiogram (TTE) showed a 1.6 × 1.4 cm mobile mass in the left ventricle cavity that appeared to be attached to the base of the papillary muscle and a normal left ventricular ejection fraction of 60%. An electrocardiogram (ECG) revealed normal sinus rhythm with T-wave inversion in the inferior leads and V3–V6.

The patient initiated anticoagulation and systemic therapy with nivolumab.

3. Discussion

Cardiac metastases are a rare finding. Since patients are often clinically silent or have nonspecific symptoms, metastases to the heart are difficult to diagnose and usually detected in the postmortem setting during an autopsy. When patients present with symptoms, they can have highly variable clinical manifestations, including heart failure, arrhythmias, valvular disease, and cardiac tamponade. The most common primary cancers in patients with cardiac metastases include melanoma, mediastinal tumors, lung cancer, breast cancer, and leukemia [2]. In a large study of postmortem patients with a known malignancy, Bussani et al. reported a 9.1% overall incidence of cardiac metastases with only 5.3% (4 out of 75) secondary to oral cavity cancer compared to 48.4% secondary to mesothelioma, 27.8% to melanoma, and 21.0% to lung adenocarcinoma [2]. Four different mechanisms have been postulated by which cancer spreads to the heart, including direct extension, hematologic spread, lymphatic spread, and intracavitary diffusion via the inferior vena cava or pulmonary veins [24].

In patients with oral cavity cancer, distant metastases are seen in 4.2–23.8% of patients, with the lung, bone, and liver as the most commonly involved sites [5]. However, metastatic disease to the heart is highly unusual in patients with oral cavity cancer. The patient in this case report had an especially long duration between primary diagnosis and cardiac metastasis at almost 3 years. In a review of the literature, we found 24 cases of patients with head and neck cancer with cardiac metastases that were detected in the antemortem setting.

Due to the wide range of clinical presentations in patients with cardiac metastases, detection is often incidental. The routine use of imaging is not generally recommended in patients with head and neck cancer to detect metastatic disease unless prompted by clinical signs and symptoms or if the patient is not amenable to clinical examination. Echocardiography is the most frequent noninvasive imaging modality used to evaluate the heart. In our present literature review, echocardiography was the initial imaging modality in more than 50% of the cases of cardiac metastasis from a primary head and neck cancer (Table 1). Echocardiography allows for assessment of cardiac function, including valvular and ventricular competency, as well as identification of any intraventricular masses or structural wall abnormalities [6]. The diagnostic accuracy of echocardiography has been reported to be as high as 80%, which makes it a good initial method to evaluate suspected cardiac tumors [7]. Other imaging modalities such as CT and MRI may provide a more comprehensive assessment with additional detail, including evaluation of the pericardium and extracardiac disease [8]. Cardiac MRI offers the advantages of excellent contrast resolution and distinction of tumor from the myocardium or thrombus in comparison with CT or ultrasound [9]. MRI also allows for simultaneous assessment of the surrounding structures, including the mediastinum, lungs, and pleura [6]. Particularly in patients with primary tumor of the head and neck, PET/CT may provide additional utility in detecting metastatic disease involving the heart. In a long-term outcome study of PET/CT imaging in head and neck cancer patients treated with definitive or adjuvant radiation therapy, PET/CT had a 99% negative predictive value in the assessment of the primary site and neck, and negative findings were associated with significantly improved disease-free survival and overall survival. However, there was a high rate of false-positive results at the primary site, with a positive predictive value of 32.1% [10]. Therefore, the use of PET/CT at 3 months post-RT is generally practiced. Current National Comprehensive Cancer Network (NCCN) guidelines do not recommend the use of routine follow-up imaging unless clinically indicated and no evidence to demonstrate a benefit of surveillance imaging after 6 months [11]. However, multiple case reports have reported that the use of PET/CT may lead to improved accuracy and earlier detection of cardiac metastases in patients with head and neck cancer [4, 1215]. Some studies have suggested that routine ECG may have a diagnostic value, but findings are often nonspecific, and further confirmation with imaging would be required [1517]. Table 1 provides a literature review of patients with an antemortem diagnosis of cardiac metastasis from a primary head and neck cancer. In our present study, the patient had already developed metastatic disease in the lung prior to detection of the cardiac metastasis, which was incidentally detected on a review staging CT scan.


PatientStudyYear of publicationPrimary sitePrimary treatmentLocation of metastasisSigns/symptomsECG findingsBiopsy proven cardiac metastasisTreatment for cardiac metastasisInitial imaging modality to detect cardiac metastasisPET scan used?

1Werbel et al. [18]1985Base of tongueHemiglossectomyMediastinal mass compressing right ventricular outflow tract and encasing the ascending aorta, right atrium massIntermittent positional chest pain, dysphagia, weight lossNew ST depression with T-wave inversions anteriorlyYesSurgical exploration via modified right-sided Chamberlain procedure, but deemed unresectable. Planned to proceed with radiotherapy, but patient expired before initiation2D EchocardiogramNo

2Rivkin et al. [19]1999Right base of tongueLocal excision and adjuvant radiotherapy to primary site and bilateral neckRight ventricleChest pain, lower extremity edemaMild ST elevation in V4 and V5, atrial fibrillation with ST elevation in V2 to V6 and Q waves in V2 and IIIYesChemotherapy with cisplatin, 5-FU, bleomycin, and methotrexateChest X-ray and EchocardiogramNo

3Schwender et al. [20]2002Right buccal mucosaChemotherapy with cisplatin and radiotherapyPericardial effusionWeakness, lightheadedness, dyspneaAtrial fibrillation with rapid ventricular responseYesNoneChest X-ray, CT ChestNo

4Zemann et al. [13]2007Oral cavityRight mandibulectomy, right hemiglossectomy, right radical neck dissection, and left supraomohyoid dissection with immediate microvascular flap reconstruction followed by adjuvant radiotherapy to right lower jaw and right neck to 60 Gy/50GyRight ventricleRespiratory distressNormal findingsNoNoneCT ChestNo

5Hans et al. [21]2008Base of tongueInduction chemotherapy (5-FU/cisplatin), glossectomy and left radical neck dissection and adjuvant radiotherapy to primary site and neck to 60 Gy/46 GyRight ventricle extending into the pulmonary infundibulumDyspnea, lower extremity edema, hemoptysisRight bundle branch blockNoNoneCT ChestNo

6Tsai et al. [22]2010Left retromolar trigoneSegmental mandibulectomy and ipsilateral modified radical neck dissection followed by adjuvant radiotherapy to primary site and whole neck to 64 GyPericardial effusion, mediastinal massProgressive dyspnea, tachycardia, pulsus paradoxusLow QRS voltageYesChest tube insertion and drainage, emergency thoracotomy, palliative chemotherapy with cisplatin and cetuximab2D EchocardiogramYes

7Nagata et al. [1]2012Right lingualPreoperative concurrent chemoradiation therapy to 30 Gy followed by partial glossectomy and right radical neck dissection and rectus abdominis musculocutaneous flap reconstruction followed by adjuvant chemotherapyLeft atrium to the left pulmonary vein, Pericardial effusionFeverYesResection of cardiac massChest CT and EchocardiogramYes
8Left soft palatePreoperative concurrent chemoradiation therapy to 40 Gy followed by partial maxillectomy and radical neck dissection followed by adjuvant chemotherapyRight atrium and right ventricle, pericardial effusionRight bundle branch block and borderline Q waveNoNoneChest CTYes

9Onwuchekwa and Banchs [23]2012Right oral tongueRight partial glossectomy and extensive neck dissectionRight ventricle invading interventricular septum and left ventricleSyncope, mild dyspneaSinus rhythmNoNoneCT angiogram and 2D echocardiogramNo
10Left oral tongueConcurrent chemoradiotherapy, left partial glossectomy, left neck dissectionAnteroseptal wall of the left ventricle extending toward the right ventricular outflow tract, pericardial effusionPalpitations, dyspneaSinus rhythm with ST elevation in the anterolateral leadsNoRadiotherapy and chemotherapyChest X-Ray and 2D echocardiogramNo

11Yadav et al. [16]2014Right piriform sinusChemotherapy with cisplatin and radiotherapyRight and left ventricular apex and distal interventricular septumNoneInferior and anterolateral ST elevationYesPemetrexed and gemcitabinePET/CTYes
12Oral tonguePartial glossectomyLeft and right ventricle with extension to chordae tendinaePresented with pneumoniaNew anterolateral myocardial infarction (ST elevation)NoNoneChest X-Ray and EchocardiogramNo

13Puranik et al. [4]2014Left buccal mucosaConcurrent chemoradiotherapyLeft ventricular myocardiumWeight lossNoPalliative chemotherapyPET/CTYes
14Right lateral oral tongueWide excision and right lateral neck dissectionLeft ventricular myocardiumSwelling over ala of noseNoPalliative chemotherapyPET/CTYes
15Right ValleculaChemoradiotherapyRight ventricular myocardiumPalliative chemotherapyPET/CTYes

16Pattni et al. [5]2015Left retromolar trigoneBegan radiotherapy, but then elected to pursue surgery with curative intent-Cardiac metastasis was detected and surgery was cancelledApex of right ventricle extending to the tricuspid valveCentral chest “heaviness,” tachycardia, irregularly irregular pulseST-segment elevationNoNoneTransthoracic echocardiogramNo

17Browning et al. [14]2015Base of tongueRadiotherapyAnterior wall of right ventricleNoNonePET/CTYes

18Martell et al. [24]2016Right retromolar trigonePharyngotomy and segmental mandibular resection, right selective neck dissection, free fibular flap reconstruction followed by adjuvant concurrent chemoradiotherapy to 60 Gy with cisplatinRight ventricle, prevascular lymph node, pericardial effusionAcute dyspnea, palpitationsRapid atrial fibrillationYesPlanned for palliative radiotherapy to 20 Gy in 5 fractions, but patient expired prior to treatmentEchocardiogram and CT ChestNo

19Vaduganathan et al. [25]2016LarynxUnknownLeft ventricleArrhythmiaStable ventricular tachycardiaNoPermanent pacemaker placement and systemic chemotherapyTransthoracic echocardiogramNo

20Malekzadeh et al. [3]2017Oral tongueRight hemiglossectomy and adjuvant radiotherapyRight ventricleAcute chest painSlight ST elevation inV3 and V4NoPalliative chemotherapy with cetuximab, carboplatin, and 5-FUCT ChestYes

21Chua et al. [26]2017TongueResection and reconstructionRight ventricle, minor pericardial effusionProgressive dyspneaConcurrent chemoradiotherapyTransthoracic echocardiogramNo

22Cho et al. [15]2018Oral CavityInduction chemotherapy (doxetaxel/cisplatin/5-FU) followed by concurrent chemoradiotherapy to 66 Gy with cisplatin followed by complete surgical excisionInterventricular septum protruding into right ventricleDizzinessComplete AV blockNoPermanent pacemaker placement and palliative chemotherapyCT Chest and EchocardiogramYes

23Present Study2018Left lateral tongueT-wave inversion in the inferior and V3-V6 leads.Left ventricleChest pressure, dizziness, dyspneaT-wave inversionNoNivolumabCT ChestYes

There is no standard of care in the treatment of cardiac metastases. Many patients are not surgical candidates due to the location of disease and are treated with palliative chemotherapy and supportive care, but prognosis is often poor. In our present study, the patient initially had presented with metastatic disease to the lung and began treatment with cisplatin-based chemotherapy and radiotherapy, but developed progression of disease and a new cardiac metastasis. In the current era, novel immunotherapeutic drugs, such as pembrolizumab or nivolumab (anti-PDL-1 antibodies), may have a significant impact on the survival outcomes of these patients [2729]. Upon detection of the cardiac metastasis, the patient began treatment with nivolumab, which is approved for patients with recurrent and metastatic head and neck cancer that is refractory to cisplatin chemotherapy.

In conclusion, metastatic disease to the heart in oral cavity cancer is an uncommon finding, lacking optimal guidelines in terms of diagnosis and management. Diagnosis is quite challenging since cardiac metastases are often clinically silent, and there is no clear beneficial role of routine surveillance imaging. In symptomatic patients, a multimodality approach using imaging such as PET/CT, cardiac MRI, echocardiogram, and ECG findings should be used to confirm the location and extent of disease, which may help to guide treatment options.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

References

  1. S. Nagata, K. Ota, M. Nagata, and M. Shinohara, “Cardiac metastasis of head and neck squamous cell carcinoma,” International Journal of Oral and Maxillofacial Surgery, vol. 41, no. 12, pp. 1458–1462, 2012. View at: Publisher Site | Google Scholar
  2. R. Bussani, F. De-Giorgio, A. Abbate, and F. Silvestri, “Cardiac metastases,” Journal of Clinical Pathology, vol. 60, no. 1, pp. 27–34, 2007. View at: Publisher Site | Google Scholar
  3. S. Malekzadeh, A. Platon, and P. A. Poletti, “Cardiac metastasis of tongue squamous cell carcinoma complicated by pulmonary embolism: a case report,” Medicine, vol. 96, no. 28, Article ID e7462, 2017. View at: Publisher Site | Google Scholar
  4. A. D. Puranik, N. C. Purandare, S. Sawant et al., “Asymptomatic myocardial metastasis from cancers of upper aero-digestive tract detected on FDG PET/CT: a series of 4 cases,” Cancer Imaging, vol. 14, p. 16, 2014. View at: Publisher Site | Google Scholar
  5. N. Pattni, A. Rennie, T. Hall, and A. Norman, “Cardiac metastasis of oral squamous cell carcinoma,” BMJ Case Report, vol. 2015, Article ID bcr2015211275, 2015. View at: Publisher Site | Google Scholar
  6. C. Chiles, P. K. Woodard, F. R. Gutierrez, and K. M. Link, “Metastatic involvement of the heart and pericardium: CT and MR imaging,” Radiographics, vol. 21, no. 2, pp. 439–449, 2001. View at: Publisher Site | Google Scholar
  7. N. Nomoto, T. Tani, T. Konda et al., “Primary and metastatic cardiac tumors: echocardiographic diagnosis, treatment and prognosis in a 15-years single center study,” Journal of Cardiothoracic Surgery, vol. 12, no. 1, p. 103, 2017. View at: Publisher Site | Google Scholar
  8. T. Strecker, J. Rosch, M. Weyand, and A. Agaimy, “Primary and metastatic cardiac tumors: imaging characteristics, surgical treatment, and histopathological spectrum: a 10-year-experience at a German heart center,” Cardiovascular Pathology, vol. 21, no. 5, pp. 436–443, 2012. View at: Publisher Site | Google Scholar
  9. S. Neragi-Miandoab, J. Kim, and G. J. Vlahakes, “Malignant tumours of the heart: a review of tumour type, diagnosis and therapy,” Clinical Oncology, vol. 19, no. 10, pp. 748–756, 2007. View at: Publisher Site | Google Scholar
  10. C. F. Chen, O. Tsutsumi, T. Fujiwara, N. Mitsuhashi, and M. Mizuno, “Human chorionic gonadotropin levels in the follicular fluid in relation to oocyte maturity in in vitro fertilization,” Nihon Sanka Fujinka Gakkai Zasshi, vol. 43, no. 7, pp. 789-790, 1991. View at: Google Scholar
  11. Network NCC, “Head and neck cancers,” 2018, https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. View at: Google Scholar
  12. R. Rodel, H. J. Straehler-Pohl, H. Palmedo et al., “PET/CT imaging in head and neck tumors,” Radiologe, vol. 44, no. 11, pp. 1055–1059, 2004. View at: Publisher Site | Google Scholar
  13. W. Zemann, M. Feichtinger, E. Kowatsch, M. Schanbacher, and H. Karcher, “Cardiac metastasis after squamous cell carcinoma of the oral cavity: case report,” British Journal of Oral and Maxillofacial Surgery, vol. 45, no. 5, pp. 425-426, 2007. View at: Publisher Site | Google Scholar
  14. C. M. Browning, J. F. Craft, M. Renker, U. J. Schoepf, and S. Baumann, “Squamous cell carcinoma of the tongue with metastasis to the right ventricle,” American Journal of the Medical Sciences, vol. 349, no. 5, pp. 461-462, 2015. View at: Publisher Site | Google Scholar
  15. J. Y. Cho, K. H. Kim, H. Park, H. J. Yoon, and J. C. Park, “Complete atrioventricular block as an initial manifestation of recurred oral cavity cancer: a case report,” BMC Cardiovascular Disorders, vol. 18, no. 1, p. 142, 2018. View at: Publisher Site | Google Scholar
  16. N. U. Yadav, D. Gupta, M. S. Baum, N. Roistacher, and R. M. Steingart, “Cardiac metastases from head and neck cancer mimicking a myocardial infarction,” Journal of Oral and Maxillofacial Surgery, vol. 72, no. 8, pp. 1627–1635, 2014. View at: Publisher Site | Google Scholar
  17. S. Gullulu, B. Ozdemir, T. Senturk, I. Baran, J. Cordan, and G. Filiz, “Cardiac metastasis in a laryngeal carcinoma and associated electrocardiographic changes,” Otolaryngology–Head and Neck Surgery, vol. 135, no. 4, pp. 645–647, 2006. View at: Publisher Site | Google Scholar
  18. G. B. Werbel, J. H. Skom, D. Mehlman, and L. L. Michaelis, “Metastatic squamous cell carcinoma to the heart. Unusual cause of angina decubitus and cardiac murmur,” Chest, vol. 88, no. 3, pp. 468-469, 1985. View at: Google Scholar
  19. A. Rivkin, J. G. Meara, K. K. Li, C. Potter, and R. Wenokur, “Squamous cell metastasis from the tongue to the myocardium presenting as pericardial effusion,” Otolaryngology–Head and Neck Surgery, vol. 120, no. 4, pp. 593–595, 1999. View at: Publisher Site | Google Scholar
  20. F. T. Schwender, I. Wollner, L. P. Kunju, R. E. Nakhleh, and K. M. Chan, “Squamous cell carcinoma of the buccal mucosa with metastases to the pericardial cavity, lung and thyroid,” Oral Oncology, vol. 38, no. 1, pp. 114–116, 2002. View at: Publisher Site | Google Scholar
  21. S. Hans, D. Chauvet, B. Sadoughi, and D. F. Brasnu, “Cardiac metastasis after squamous cell carcinoma of the base of tongue,” American Journal of Otolaryngology, vol. 30, no. 3, pp. 206–208, 2009. View at: Publisher Site | Google Scholar
  22. Y. T. Tsai, S. W. Kuo, and S. P. Hao, “Cardiac tamponade: a rare presentation from a rare metastatic site in oral squamous cell carcinoma,” European Archives of Oto-Rhino-Laryngology, vol. 267, no. 9, pp. 1483–1485, 2010. View at: Publisher Site | Google Scholar
  23. J. Onwuchekwa and J. Banchs, “Early cardiac metastasis from squamous cell carcinoma of the tongue in 2 patients,” Texas Heart Institute Journal, vol. 39, no. 4, pp. 565–567, 2012. View at: Google Scholar
  24. K. Martell, R. Simpson, and D. Skarsgard, “Solitary myocardial metastasis from locoregionally controlled squamous cell carcinoma of the oral cavity,” Cureus, vol. 8, no. 6, p. e650, 2016. View at: Publisher Site | Google Scholar
  25. M. Vaduganathan, N. K. Patel, S. A. Lubitz, T. G. Neilan, and D. M. Dudzinski, “A “Malignant” Arrhythmia: Cardiac Metastasis and Ventricular Tachycardia,” Texas Heart Institute Journal, vol. 43, no. 6, pp. 558-559, 2016. View at: Publisher Site | Google Scholar
  26. S. Chua, W. H. Liu, and W. C. Lee, “Isolated huge right ventricular tumor: cardiac metastasis of tongue cancer,” Korean Journal of Internal Medicine, vol. 32, no. 6, pp. 1119-1120, 2017. View at: Publisher Site | Google Scholar
  27. R. L. Ferris, G. Blumenschein Jr., J. Fayette et al., “Nivolumab for recurrent squamous-cell carcinoma of the head and neck,” New England Journal of Medicine, vol. 375, no. 19, pp. 1856–1867, 2016. View at: Publisher Site | Google Scholar
  28. T. Y. Seiwert, B. Burtness, R. Mehra et al., “Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial,” Lancet Oncology, vol. 17, no. 7, pp. 956–965, 2016. View at: Publisher Site | Google Scholar
  29. J. Bauml, T. Y. Seiwert, D. G. Pfister et al., “Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study,” Journal of Clinical Oncology, vol. 35, no. 14, pp. 1542–1549, 2017. View at: Publisher Site | Google Scholar

Copyright © 2019 Joseph K. Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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