Bedeutung des sekundär auftretenden Primärtumors bei einem zervikalen CUP-Syndrom

Zusammenfassung

Fragestellung: Ziel der vorgestellten retrospektiven Analyse ist es, die Bedeutung des Primärtumors bei Patienten mit einem zervikalen CUP-Syndrom nach Abschluss von Diagnostik und Therapie zu ermitteln.

Patienten/Methoden: In die Untersuchung wurden 36 Patienten eingeschlossen, die wir zwischen 2001 und 2009 diagnostizierten. Die Primärtumorsuche umfasste eine Panendoskopie mit Mapping und Tonsillektomie, Sonografie und CT oder MRT. Es erfolgte eine multimodale, primär chirurgische Therapie der Metastasen und eine limitierte Bestrahlung der Schleimhäute des oberen Aerodigestivtraktes (IMRT, GHD 50 Gy). Die Daten zur Tumorkontrolle und die Therapie-assoziierte Toxizität wurden ermittelt.

Ergebnisse: Ein sekundärer Primärtumor der zervikalen Metastasen wurde bei keinem Patienten nachgewiesen. 6 Patienten verstarben an Fernmetastasen, ein Patient infolge der Chemotherapie, 4 an einem infraklavikulären Zweitkarzinom und 2 interkurrent. Eine Grad-4-Spättoxizität trat nicht auf, in 8% bestand eine Grad-3-Dysphagie.

Diskussion: Für die Frequenz sekundär auftretender Primärtumore bei einem CUP-Syndrom sind die Effektivität von Diagnostik und Therapie entscheidend. Unser Ergebnis zeigt, dass der Verzicht auf eine PET-Diagnostik sich nicht nachteilig auf die Manifestationsrate auswirkte bzw. durch die durchgeführte intensive Therapie kompensiert wurde. Die Prognose-entscheidenden Ereignisse (Fernmetastasen, infraklavikuläre Zweitkarzinome) traten unabhängig von sekundären Primärtumoren auf. Die elektive Therapie des mutmaßlichen Primärtumors sollte unter Berücksichtigung von Effektivität und Toxizität in ein individualisiertes Therapiekonzept einbezogen werden.

Abstract

Background: We discuss the significance of an occult primary in the prognosis of cervical carcinoma with unknown primary (CUP) after completion of diagnostic and treatment.

Patients/Methods: A series of 36 patients diagnosed between 2001 and 2009 underwent staging including panendoscopy, mapping and tonsillectomy, ultrasound and CT/MRI of the neck, thorax and abdomen. The patients recieved neck surgery followed by adjuvant radio-(chemo-)therapy of cervical fields as well as limited mucosal irradiation (IMRT, GHD 50 Gy). The results of tumor control and therapy-related toxicity were ascertained.

Results: A secondary primary of the cervical metastases was not detected during follow-up. 6 patients died from distant metastases and 1 from chemotherapy; 4 patients died from a different secondary tumour, 2 patients died intercurrently. We did not observe late toxicity but 8% of patients had Grade 3 dysphagia.

Discussion: Efficacy of diagnostic procedure and therapy are important in treating occult primary tumours in CUP. Our results show that omitting PET-CT, which was not available in diagnostic workup of the study-patients, did not impact negatively on the manifestation rate of mucosal primaries and/or was compensated for by intensive therapy. Distant metastases and infraclavicular secondary primaries had a negative impact for the survival. Elective therapy of a presumed occult primary tumour in CUP should be included into the therapeutic discussion considering its efficacy and toxicity.

Schlüsselwörter

Karzinommetastasen - Kopf- und Halskarzinome - unbekannte Primärtumore - Diagnostik - Therapie

Key words

neoplasm metastasis - head and neck cancer - unknown primary neoplasm - diagnostics - therapy - outcome assessment

• Literatur

• 1 Fischer DS. Management of cancer of unknown primary. Conn Med 1975; 39: 205-208
• 2 Strojan P, Ferlito A, Langendijk JA, Corry J, Woolgar JA, Rinaldo A 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: 286-293
• 3 Strojan P, Ferlito A, Medina JE, Woolgar JA, Rinaldo A, Robbins KT 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: 123-132
• 4 Doty JM, Gossman D, Kudrimoti M, Valentino J, Arnold S, Spring PM. Analysis of unknown primary carcinomas metastatic to the neck: diagnosis, treatment, and outcomes. J Ky Med Assoc 2006; 104: 57-64
• 5 Werner J, Duenne AA. Halslymphknotenmetastasen bei unbekanntem Primärtumor. Lymphknotenerkrankungen im Kopf-Hals-Bereich Onkologie und Differenzialdiagnostik. Springer; 2002. p 273-285
• 6 Neben K, Hübner G, Folprecht G, Jäger D, Krämer A. Metastases in the Absence of a Primary Tumor: Advances in the Diagnosis and Treatment of CUP Syndrome. Dtsch Arztebl Int 2008; 105: 733-740
• 7 Califano J, Westra WH, Koch W, Meininger G, Reed A, Yip L et al. Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin. J Natl Cancer Inst 1999; 91: 599-604
• 8 Huang C-C, Tseng F-Y, Yeh T-H, Wen Y-H, Hsu C-J, Ko J-Y et al. Prognostic factors of unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2008; 139: 429-435
• 9 Hauswald H, Lindel K, Rochet N, Debus J, Harms W. Surgery with complete resection improves survival in radiooncologically treated patients with cervical lymph node metastases from cancer of unknown primary. Strahlenther Onkol 2008; 184: 150-156
• 10 Beldì D, Jereczek-Fossa BA, D’Onofrio A, Gambaro G, Fiore MR, Pia F 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: 1051-1058
• 11 Ligey A, Gentil J, Créhange G, Montbarbon X, Pommier P, Peignaux K 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: 483-487
• 12 Wallace A, Richards GM, Harari PM, Kirwan JM, Morris CG, Katakam H et al. Head and neck squamous cell carcinoma from an unknown primary site. Am J Otolaryngol 2011; 32: 286-290
• 13 Johansen J, Buus S, Loft A, Keiding S, Overgaard M, Hansen HS 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: 471-478
• 14 Haas I, Hoffmann TK, Engers R, Ganzer U. Diagnostic strategies in cervical carcinoma of an unknown primary (CUP). Eur Arch Otorhinolaryngol 2002; 259: 325-333
• 15 Yabuki K, Tsukuda M, Horiuchi C, Taguchi T, Nishimura G. Role of 18F-FDG PET in detecting primary site in the patient with primary unknown carcinoma. Eur Arch Otorhinolaryngol 2010; 267: 1785-1792
• 16 Wong WL, Sonoda LI, Gharpurhy A, Gollub F, Wellsted D, Goodchild K et al. 18F-fluorodeoxyglucose positron emission tom ography/computed tomography in the assessment of occult primary head and neck cancers – an audit and review of published studies. Clin Oncol (R Coll Radiol) 2012; 24: 190-195
• 17 O’Hara J, Ferlito A, Takes RP, Rinaldo A, Strojan P, Shaha AR et al. Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland–a review of current recommendations. Head Neck 2011; 33: 1789-1795
• 18 Nair S, Mohan S, Nilakantan A, Gupta A, Malik A, Gupta A. Impact of (18)f-fluorodeoxyglucose positron emission tomography/computed tomography scan on initial evaluation of head and neck squamous cell carcinoma: our experience at a tertiary care center in India. World J Nucl Med 2015; 14: 19-24
• 19 Cacicedo J, Fernandez I, Del Hoyo O, Dolado A, Gómez-Suarez J, Hortelano E et al. Should PET/CT be implemented in the routine imaging work-up of locally advanced head and neck squamous cell carcinoma? A prospective analysis. Eur J Nucl Med Mol Imaging 2015; [EPub ahead of print]
• 20 Keller LM, Galloway TJ, Holdbrook T, Ruth K, Yang D, Dubyk C 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: 1677-1684
• 21 Harper CS, Mendenhall WM, Parsons JT, Stringer SP, Cassisi NJ, Million RR. Cancer in neck nodes with unknown primary site: role of mucosal radiotherapy. Head Neck 1990; 12: 463-469
• 22 Koscielny Gudziol H, Kretschmar J. Cervical lymph nodes of unknown primary. Laryngo-Rhino-Otol 2000; 79: 483-489
• 23 Sinnathamby K, Peters LJ, Laidlaw C, Hughes PG. The occult head and neck primary: to treat or not to treat?. Clin Oncol (R Coll Radiol) 1997; 9: 322-329
• 24 Issing WJ, Taleban B, Tauber S. Diagnosis and management of carcinoma of unknown primary in the head and neck. Eur Arch Otorhinolaryngol 2003; 260: 436-443
• 25 Chen AM, Li B-Q, Farwell DG, Marsano J, Vijayakumar S, Purdy JA. Improved dosimetric and clinical outcomes with intensity-modulated radiotherapy for head-and-neck cancer of unknown primary origin. Int J Radiat Oncol Biol Phys 2011; 79: 756-762
• 26 Frank SJ, Rosenthal DI, Petsuksiri J, Ang KK, Morrison WH, Weber RS 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 2010; 78: 1005-1010
• 27 Reddy SP, Marks JE. 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: 797-802
• 28 Christiansen H, Hermann RM, Martin A, Nitsche M, Schmidberger H, Pradier O. Neck lymph node metastases from an unknown primary tumor retrospective study and review of literature. Strahlenther Onkol 2005; 181: 355-362
• 29 Lu X, Hu C, Ji Q, Shen C, Feng Y. Squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: the impact of radiotherapy. Tumori 2009; 95: 185-190
• 30 Rödel RMW, Matthias C, Blomeyer BD, Wolff HA, Jung K, Christiansen H. Impact of distant metastasis in patients with cervical lymph node metastases from cancer of an unknown primary site. Ann Otol Rhinol Laryngol 2009; 118: 662-669
• 31 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 Radiat Oncol Biol Phys 2008; 71: 1158-1166