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Radiation Oncology

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Open Access 01-12-2017 | Review

Diagnostic and treatment modalities for patients with cervical lymph node metastases of unknown primary site – current status and challenges

Authors: Jens Müller von der Grün, Aykut Tahtali, Shahram Ghanaati, Claus Rödel, Panagiotis Balermpas

Published in: Radiation Oncology | Issue 1/2017

Abstract

Background and Purpose

This review aims to provide a comprehensive overview of the literature and elucidate open questions for future clinical trials concerning diagnostics and treatment modalities for cervical cancer of unknown primary (CUP).

Methods

A literature search for head and neck CUP was performed with focus on diagnostics and therapies as well as molecular markers.

Results

High level evidence on CUP is limited. However, it seems that a consensus exists regarding the optimal diagnostic procedures. The correct implementation of biomarkers for patient stratification and treatment remains unclear. An even greater dispute dominates about the ideal treatment with publications ranging from sole surgery to surgery with postoperative bilateral radiotherapy with inclusion of the mucosa and concomitant chemotherapy.

Conclusions

Cervical CUP represents a very heterogeneous malignant disease. On this account many aspects concerning treatment optimization remain unclear, despite a considerable number of publications in the past. Future research in form of prospective randomized trials is needed in order to better define patient stratification criteria and enable tailored treatment.

Califano J, et al. Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin. J Natl Cancer Inst. 1999;91(7):599–604. doi:10.1093/jnci/91.7.599.PubMedCrossRef

Pavlidis N, et al. Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer. 2003;39(14):1990–2005. http://dx.doi.org/10.1016/S0959-8049(03)00547-1.PubMedCrossRef

Ries LAG, Eisner MP, Kosary CL, et al. SEER cancer statistics review. Bethesda: National Cancer Institute; 1999.

Levi F, et al. Epidemiology of unknown primary tumours. Eur J Cancer. 2002;38(13):1810–2. http://dx.doi.org/10.1016/S0959-8049(02)00135-1.PubMedCrossRef

van de Wouw AJ, et al. Epidemiology of unknown primary tumours; incidence and population-based survival of 1285 patients in Southeast Netherlands, 1984-1992. Eur J Cancer. 2002;38(3):409–13. http://dx.doi.org/10.1016/S0959-8049(01)00378-1.PubMedCrossRef

Strojan P, et al. Combined surgery and postoperative radiotherapy for cervical lymph node metastases from an unknown primary tumour. Radiother Oncol. 1998;49(1):33–40. http://dx.doi.org/10.1016/S0167-8140(98)00082-6.PubMedCrossRef

Regelink G, et al. Detection of unknown primary tumours and distant metastases in patients with cervical metastases: value of FDG-PET versus conventional modalities. Eur J Nucl Med Mol Imaging. 2002;29(8):1024–30. doi:10.1007/s00259-002-0819-0.PubMedCrossRef

Issing WJ, et al. Diagnosis and management of carcinoma of unknown primary in the head and neck. Eur Arch Otorhinolaryngol. 2003;260(8):436–43. doi:10.1007/s00405-003-0585-z.PubMedCrossRef

Bataini JP, et al. Treatment of metastatic neck nodes secondary to an occult epidermoid carcinoma of the head and neck. Laryngoscope. 1987;97(9):1080–4. doi:10.1288/00005537-198709000-00015.PubMedCrossRef

10.

Jesse RH, et al. Cervical lymph node metastasis: unknown primary cancer. Cancer. 1973;31(4):854–9. doi:10.1002/1097-0142(197304)31:4<854::AID-CNCR2820310414>3.0.CO;2-D.PubMedCrossRef

11.

Weir L, et al. Radiation treatment of cervical lymph node metastases from an unknown primary: an analysis of outcome by treatment volume and other prognostic factors. Radiother Oncol. 1995;35(3):206–11. http://dx.doi.org/10.1016/0167-8140(95)01559-Y.PubMedCrossRef

12.

Reddy SP, et al. Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation. Int J Radiat Oncol Biol Phys. 1997;37(4):797–802. http://dx.doi.org/10.1016/S0360-3016(97)00025-4.PubMedCrossRef

13.

Colletier PJ, et al. Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck. 1998;20(8):674–81. doi:10.1002/(SICI)1097-0347(199812)20:8<674::AID-HED3>3.0.CO;2-H.PubMedCrossRef

14.

Fernandez JA, et al. Metastatic squamous cell carcinoma in cervical lymph nodes from an unknown primary tumour: prognostic factors. Clin Otolaryngol Allied Sci. 1998;23(2):158–63. doi:10.1046/j.1365-2273.1998.00122.x.PubMedCrossRef

15.

Grau C, et al. Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology. Radiother Oncol. 2000;55(2):121–9. http://dx.doi.org/10.1016/S0167-8140(00)00172-9.PubMedCrossRef

16.

Iganej S, et al. Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse. Head Neck. 2002;24(3):236–46.PubMedCrossRef

17.

Yalin Y, et al. Management and outcome of cervical lymph node metastases of unknown primary sites: a retrospective study. Br J Oral Maxillofac Surg. 2002;40(6):484–7. http://dx.doi.org/10.1016/S0266435602002449.PubMedCrossRef

18.

Aslani M, et al. Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: Is there a need for neck dissection? Head Neck. 2007;29(6):585–90. doi:10.1002/hed.20581.PubMedCrossRef

19.

Boscolo-Rizzo P, et al. Cervical lymph node metastases from occult squamous cell carcinoma: analysis of 82 cases. ORL J Otorhinolaryngol Relat Spec. 2006;68(4):189–94. doi:10.1159/000091394.PubMedCrossRef

20.

Beldi D, et al. Role of radiotherapy in the treatment of cervical lymph node metastases from an unknown primary site: retrospective analysis of 113 patients. Int J Radiat Oncol Biol Phys. 2007;69(4):1051–8. doi:10.1016/j.ijrobp.2007.04.039.PubMedCrossRef

21.

Patel RS, et al. Squamous cell carcinoma from an unknown head and neck primary site: a “selective treatment” approach. Arch Otolaryngol Head Neck Surg. 2007;133(12):1282–7. doi:10.1001/archotol.133.12.1282.PubMedCrossRef

22.

Corry J, et al. The role of PET-CT in the management of patients with advanced cancer of the head and neck. Curr Oncol Rep. 2008;10(2):149–55. doi:10.1007/s11912-008-0023-x.PubMedCrossRef

23.

Lu X, et al. Squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: the impact of radiotherapy. Tumori. 2009;95(2):185–90. doi:10.1700/422.5007.PubMed

24.

Chen AM, et al. Radiation therapy in the management of head-and-neck cancer of unknown primary origin: how does the addition of concurrent chemotherapy affect the therapeutic ratio? Int J Radiat Oncol Biol Phys. 2011;81(2):346–52. doi:10.1016/j.ijrobp.2010.06.031.PubMedCrossRef

25.

Wallace A, et al. Head and neck squamous cell carcinoma from an unknown primary site. Am J Otolaryngol. 2011;32(4):286–90. doi:10.1016/j.amjoto.2010.05.004.PubMedCrossRef

26.

Fakhrian K, et al. Radio(chemo)therapy in the management of squamous cell carcinoma of cervical lymph nodes from an unknown primary site. A retrospective analysis. Strahlenther Onkol. 2012;188(1):56–61. doi:10.1007/s00066-011-0017-8.PubMedCrossRef

27.

Demiroz C, et al. Head and neck squamous cell carcinoma of unknown primary: neck dissection and radiotherapy or definitive radiotherapy. Head Neck. 2014;36(11):1589–95. doi:10.1002/hed.23479.PubMedCrossRef

28.

Straetmans J, et al. Management of neck metastases of unknown primary origin united in two European centers. Eur Arch Otorhinolaryngol. 2015;272(1):195–205. doi:10.1007/s00405-014-2934-5.PubMedCrossRef

29.

Ligey A, et al. Impact of target volumes and radiation technique on loco-regional control and survival for patients with unilateral cervical lymph node metastases from an unknown primary. Radiother Oncol. 2009;93(3):483–7. doi:10.1016/j.radonc.2009.08.027.PubMedCrossRef

30.

Haas I, et al. Diagnostic strategies in cervical carcinoma of an unknown primary (CUP). Eur Arch Otorhinolaryngol. 2002;259(6):325–33. doi:10.1007/s00405-002-0470-1.PubMed

31.

Shukla P, et al. Metastatic squamous cell carcinoma neck with occult primary: a retrospective analysis. Indian J Med Paediatr Oncol. 2009;30(4):124–30. doi:10.4103/0971-5851.65334.PubMedPubMedCentralCrossRef

32.

Mondin V, et al. A survey of metastatic central nervous system tumors to cervical lymph nodes. Eur Arch Otorhinolaryngol. 2010;267(11):1657–66. doi:10.1007/s00405-010-1357-1.PubMedCrossRef

33.

Shah JP. Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg. 1990;160(4):405–9.PubMedCrossRef

34.

Nguyen C, et al. Metastatic squamous cell carcinoma to cervical lymph nodes from unknown primary mucosal sites. Head Neck. 1994;16(1):58–63. doi:10.1002/hed.2880160112.PubMedCrossRef

35.

D’Souza G, et al. Moderate predictive value of demographic and behavioral characteristics for a diagnosis of HPV16-positive and HPV16-negative head and neck cancer. Oral Oncol. 2010;46(2):100–4. doi:10.1016/j.oraloncology.2009.11.004.PubMedCrossRef

36.

Kreimer AR, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467–75. doi:10.1158/1055-9965.EPI-04-0551.PubMedCrossRef

37.

Gillison ML, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100(6):407–20. doi:10.1093/jnci/djn025.PubMedCrossRef

38.

Fakhry C, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–9. doi:10.1093/jnci/djn011.PubMedCrossRef

39.

Coster JR, et al. Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy. Int J Radiat Oncol Biol Phys. 1992;23(4):743–9. http://dx.doi.org/10.1016/0360-3016(92)90647-Z.PubMedCrossRef

40.

Glynne-Jones RG, et al. Metastatic carcinoma in the cervical lymph nodes from an occult primary: a conservative approach to the role of radiotherapy. Int J Radiat Oncol Biol Phys. 1990;18(2):289–94. http://dx.doi.org/10.1016/0360-3016(90)90091-W.PubMedCrossRef

41.

Golfinopoulos V, et al. Comparative survival with diverse chemotherapy regimens for cancer of unknown primary site: multiple-treatments meta-analysis. Cancer Treat Rev. 2009;35(7):570–3. doi:10.1016/j.ctrv.2009.05.005.PubMedCrossRef

42.

Pentheroudakis G, et al. Cancer of unknown primary site: missing primary or missing biology? Oncologist. 2007;12(4):418–25. doi:10.1634/theoncologist.12-4-418.PubMedCrossRef

43.

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;35(1):123–32. doi:10.1002/hed.21898.PubMedCrossRef

44.

Shaha AR, Rinaldo A, Ferlito A. Metastatic squamous carcinoma in the neck from an occult primary. In: Jackler RK, Ferlito A, Silver CE, editors. Neck dissection. Management of regional disease in head and neck cancer. San Diego: Plural Publishing; 2010. p. 307–17.

45.

Lester J, et al. Random periareolar fine-needle aspiration: the new pap smear of the breast? J Adv Pract Oncol. 2012;3(6):411–4.PubMedPubMedCentral

46.

Oien KA. Pathologic evaluation of unknown primary cancer. Semin Oncol. 2009;36(1):8–37. doi:10.1053/j.seminoncol.2008.10.009.PubMedCrossRef

47.

Waltonen JD, et al. Metastatic carcinoma of the neck of unknown primary origin: evolution and efficacy of the modern workup. Arch Otolaryngol Head Neck Surg. 2009;135(10):1024–9. doi:10.1001/archoto.2009.145.PubMedCrossRef

48.

Muraki AS, et al. Metastatic cervical adenopathy from tumors of unknown origin: the role of CT. Radiology. 1984;152(3):749–53. doi:10.1148/radiology.152.3.6463256.PubMedCrossRef

49.

Freudenberg LS, et al. Dual modality of 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography in patients with cervical carcinoma of unknown primary. Med Princ Pract. 2005;14(3):155–60. doi:10.1159/000084632.PubMedCrossRef

50.

Cianchetti M, et al. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Laryngoscope. 2009;119(12):2348–54. doi:10.1002/lary.20638.PubMedCrossRef

51.

Zhuang SM, et al. Management of lymph node metastases from an unknown primary site to the head and neck (Review). Mol Clin Oncol. 2014;2(6):917–22. doi:10.3892/mco.2014.361.PubMedPubMedCentral

52.

Johansen J, et al. Prospective study of 18FDG-PET in the detection and management of patients with lymph node metastases to the neck from an unknown primary tumor. Results from the DAHANCA-13 study. Head Neck. 2008;30(4):471–8. doi:10.1002/hed.20734.PubMedCrossRef

53.

Seve P, et al. The role of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography in disseminated carcinoma of unknown primary site. Cancer. 2007;109(2):292–9. doi:10.1002/cncr.22410.PubMedCrossRef

54.

Rusthoven KE, et al. The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer. 2004;101(11):2641–9. doi:10.1002/cncr.20687.PubMedCrossRef

55.

Al-Ibraheem A, et al. Clinical applications of FDG PET and PET/CT in head and neck cancer. J Oncol. 2009;2009:208725. doi:10.1155/2009/208725.PubMedPubMedCentralCrossRef

56.

Kwee TC, et al. Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol. 2009;19(3):731–44. doi:10.1007/s00330-008-1194-4.PubMedCrossRef

57.

de Bree R. The real additional value of FDG-PET in detecting the occult primary tumour in patients with cervical lymph node metastases of unknown primary tumour. Eur Arch Otorhinolaryngol. 2010;267(11):1653–5. doi:10.1007/s00405-010-1372-2.PubMedPubMedCentralCrossRef

58.

Jones AS, et al. Squamous carcinoma presenting as an enlarged cervical lymph node. Cancer. 1993;72(5):1756–61. doi:10.1002/1097-0142(19930901)72:5<1756::AID-CNCR2820720540>3.0.CO;2-5.PubMedCrossRef

59.

Ang KK, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35. doi:10.1056/NEJMoa0912217.PubMedPubMedCentralCrossRef

60.

Rischin D, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28(27):4142–8. doi:10.1200/JCO.2010.29.2904.PubMedPubMedCentralCrossRef

61.

Lingen MW, et al. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol. 2013;49(1):1–8. doi:10.1016/j.oraloncology.2012.07.002.PubMedCrossRef

62.

Shi W, et al. Comparative prognostic value of HPV16 E6 mRNA compared with in situ hybridization for human oropharyngeal squamous carcinoma. J Clin Oncol. 2009;27(36):6213–21. doi:10.1200/JCO.2009.23.1670.PubMedCrossRef

63.

Jordan RC, et al. Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol. 2012;36(7):945–54. doi:10.1097/PAS.0b013e318253a2d1.PubMedCrossRef

64.

Rietbergen MM, et al. Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment De-escalation trials. Ann Oncol. 2013;24(11):2740–5. doi:10.1093/annonc/mdt319.PubMedCrossRef

65.

Chung CH, et al. p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clin Oncol. 2014;32(35):3930–8. doi:10.1200/JCO.2013.54.5228.PubMedPubMedCentralCrossRef

66.

Dixon PR, et al. Impact of p16 expression, nodal status, and smoking on oncologic outcomes of patients with head and neck unknown primary squamous cell carcinoma. Head Neck. 2016;38(9):1347–53. doi:10.1002/hed.24441.PubMedCrossRef

67.

Tribius S, et al. HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome. Oral Oncol. 2012;48(11):1178–84. doi:10.1016/j.oraloncology.2012.05.022.PubMedCrossRef

68.

Ragin CC, et al. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer. 2007;121(8):1813–20. doi:10.1002/ijc.22851.PubMedCrossRef

69.

Vent J, et al. p16 expression in carcinoma of unknown primary: diagnostic indicator and prognostic marker. Head Neck. 2013;35(11):1521–6. doi:10.1002/hed.23190.PubMedCrossRef

70.

Keller LM, et al. p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary. Head Neck. 2014;36(12):1677–84. doi:10.1002/hed.23514.PubMedPubMedCentralCrossRef

71.

Duffy MJ, et al. p53 as a target for the treatment of cancer. Cancer Treat Rev. 2014;40(10):1153–60. doi:10.1016/j.ctrv.2014.10.004.PubMedCrossRef

72.

Poeta ML, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 2007;357(25):2552–61. doi:10.1056/NEJMoa073770.PubMedPubMedCentralCrossRef

73.

Sivars L, et al. Human papillomavirus and p53 expression in cancer of unknown primary in the head and neck region in relation to clinical outcome. Cancer Med. 2014;3(2):376–84. doi:10.1002/cam4.199.PubMedPubMedCentralCrossRef

74.

Pezzuto F, et al. Update on head and neck cancer: current knowledge on epidemiology, risk factors, molecular features and novel therapies. Oncology. 2015;89(3):125–36. doi:10.1159/000381717.PubMedCrossRef

75.

Yoshizaki T, et al. Pathogenic role of Epstein-Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma. Cancer Lett. 2013;337(1):1–7. doi:10.1016/j.canlet.2013.05.018.PubMedCrossRef

76.

Raab-Traub N. Epstein-Barr virus in the pathogenesis of NPC. Semin Cancer Biol. 2002;12(6):431–41. http://dx.doi.org/10.1016/S1044579X0200086X.PubMedCrossRef

77.

Yoshizaki T. Promotion of metastasis in nasopharyngeal carcinoma by Epstein-Barr virus latent membrane protein-1. Histol Histopathol. 2002;17(3):845–50.PubMed

78.

Yoshizaki T, et al. Current understanding and management of nasopharyngeal carcinoma. Auris Nasus Larynx. 2012;39(2):137–44. doi:10.1016/j.anl.2011.02.012.PubMedCrossRef

79.

Macdonald MR, et al. Role of Epstein-Barr virus in fine-needle aspirates of metastatic neck nodes in the diagnosis of nasopharyngeal carcinoma. Head Neck. 1995;17(6):487–93.PubMedCrossRef

80.

Lei ZX, et al. Detection of Epstein-Barr virus DNA in fine needle aspiration specimen from cervical lymphnodes with polymerase chain reaction. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2000;14(10):454–5.PubMed

81.

Yap YY, et al. Epstein-Barr virus DNA detection in the diagnosis of nasopharyngeal carcinoma. Otolaryngol Head Neck Surg. 2007;136(6):986–91. doi:10.1016/j.otohns.2006.11.027.PubMedCrossRef

82.

Plaza G, et al. Neck lymph node metastases of unknown origin: nasopharyngeal origin and EBV (Epstein-Barr virus). Acta Otorrinolaringol Esp. 1999;50(8):623–9.PubMed

83.

Strojan P, et al. Contemporary management of lymph node metastases from an unknown primary to the neck: II. a review of therapeutic options. Head Neck. 2013;35(2):286–93. doi:10.1002/hed.21899.PubMedCrossRef

84.

Galloway TJ, et al. Management of squamous cancer metastatic to cervical nodes with an unknown primary site. J Clin Oncol. 2015;33(29):3328–37. doi:10.1200/JCO.2015.61.0063.PubMedCrossRef

85.

Suarez C, et al. Neck dissection with or without postoperative radiotherapy in supraglottic carcinomas. Otolaryngol Head Neck Surg. 1993;109(1):3–9.PubMedCrossRef

86.

Rodrigo JP, et al. Efficacy of postoperative radiation therapy for squamous cell carcinoma of the head and neck: results of a prospective randomised clinical trial. Acta Otorrinolaringol Esp. 2004;55(9):415–9. doi:10.1016/S0001-6519(04)78546-5.PubMedCrossRef

87.

Wang RC, et al. Unknown primary squamous cell carcinoma metastatic to the neck. Arch Otolaryngol Head Neck Surg. 1990;116(12):1388–93. doi:10.1001/archotol.1990.01870120034004.PubMedCrossRef

88.

Fletcher GH, Jesse Jr RH, Lindberg RD, Westbrook KC. Neck nodes. In: Fletcher GH, editor. Textbook of radiotherapy. 3rd ed. Philadelphia: Lea & Febiger; 1980. p. 249–71.

89.

Liu X, et al. Optimization of radiotherapy for neck carcinoma metastasis from unknown primary sites: a meta-analysis. Oncotarget. 2016. doi:10.18632/oncotarget.12852.

90.

Nieder C, et al. Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple? Int J Radiat Oncol Biol Phys. 2001;50(3):727–33. http://dx.doi.org/10.1016/S0360-3016(01)01462-6.PubMedCrossRef

91.

NCCN: National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf Accessed 28 Nov 2016.

92.

Gani C, et al. Cervical squamous cell lymph node metastases from an unknown primary site: survival and patterns of recurrence after radiotherapy. Clin Med Insights Oncol. 2013;7:173–80. doi:10.4137/CMO.S12169.PubMedPubMedCentralCrossRef

93.

Rodel RM, et al. Impact of distant metastasis in patients with cervical lymph node metastases from cancer of an unknown primary site. Ann Otol Rhinol Laryngol. 2009;118(9):662–9. doi:10.1177/000348940911800911.PubMedCrossRef

94.

Million RR CN, Mancuso AAL. The unknown primary. In: Cassisi N, Million RR, editors. Management of head and neck cancer: a multidisciplinary approach. 2nd ed. Philadelphia: PA, Lippincott; 1994. p. 311–20.

95.

Frank SJ, et al. Intensity-modulated radiotherapy for cervical node squamous cell carcinoma metastases from unknown head-and-neck primary site: M. D. Anderson Cancer Center outcomes and patterns of failure. Int J Radiat Oncol Biol Phys. 2010;78(4):1005–10. doi:10.1016/j.ijrobp.2009.09.006.PubMedCrossRef

96.

Mourad WF, et al. Initial experience with oropharynx-targeted radiation therapy for metastatic squamous cell carcinoma of unknown primary of the head and neck. Anticancer Res. 2014;34(1):243–8.PubMed

97.

Shehadeh NJ, et al. Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck. Head Neck. 2006;28(12):1090–8. doi:10.1002/hed.20470.PubMedCrossRef

98.

Perkins SM, et al. Radiotherapeutic management of cervical lymph node metastases from an unknown primary site. Arch Otolaryngol Head Neck Surg. 2012;138(7):656–61. doi:10.1001/archoto.2012.1110.PubMedCrossRef

99.

Klem ML, et al. Intensity-modulated radiotherapy for head and neck cancer of unknown primary: toxicity and preliminary efficacy. Int J Radiat Oncol Biol Phys. 2008;70(4):1100–7. doi:10.1016/j.ijrobp.2007.07.2351.PubMedCrossRef

100.

Garden AS, et al. Is concurrent chemoradiation the treatment of choice for all patients with Stage III or IV head and neck carcinoma? Cancer. 2004;100(6):1171–8. doi:10.1002/cncr.20069.PubMedCrossRef

101.

Hosni A, et al. Radiotherapy characteristics and outcomes for head and neck carcinoma of unknown primary vs T1 base-of-tongue carcinoma. JAMA Otolaryngol Head Neck Surg. 2016. doi:10.1001/jamaoto.2016.3083.PubMed

102.

Masterson L, et al. De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials. Eur J Cancer. 2014;50(15):2636–48. doi:10.1016/j.ejca.2014.07.001.PubMedCrossRef

103.

O’Sullivan B, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17(4):440–51. doi:10.1016/S1470-2045(15)00560-4.PubMedCrossRef

104.

Cooper JS, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937–44. doi:10.1056/NEJMoa032646.PubMedCrossRef

105.

Bernier J, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–52. doi:10.1056/NEJMoa032641.PubMedCrossRef

Title: Diagnostic and treatment modalities for patients with cervical lymph node metastases of unknown primary site – current status and challenges
Authors: Jens Müller von der Grün
Aykut Tahtali
Shahram Ghanaati
Claus Rödel
Panagiotis Balermpas
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2017
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/s13014-017-0817-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Diagnostic and treatment modalities for patients with cervical lymph node metastases of unknown primary site – current status and challenges

Abstract

Background and Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background and Purpose

Methods

Results

Conclusions

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