nach oben

Erschienen in:

09.08.2022 | Original Article

Long-term results of radio(chemo)therapy in metastatic carcinoma to cervical lymph nodes from an unknown primary. Adult Comorbidity Evaluation 27 score as a predictor of survival

verfasst von: MUDr. Miloslav Pala, Ph.D., MBA, Pavla Novakova, Zdena Pechacova, Lucie Vesela, Antonin Vrana, Jarmila Sukova, Petra Holeckova, Tereza Drbohlavova, Tomas Podlesak, Lubos Petruzelka

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 2/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate the effectiveness and toxicity of curative (chemo)radiotherapy in patients with metastatic carcinoma to cervical lymph nodes from an unknown primary.

Methods

Retrospective study of 90 consecutive patients, treated with curative radiotherapy from 2003 to 2018 (median age 59 years; current/former smokers 76%) was conducted. The distribution of nodal staging was as follows: N1: 12%, N2a: 21%, N2b: 43%, N2c: 10%, N3: 13%. In 62% of patients, neck dissection was performed before radiotherapy. Concomitant chemotherapy was given to 64% of patients.

Results

The median follow-up of surviving patients was 86 months. The median total radiotherapy dose achieved was 70 Gy. The 5‑ and 10-year locoregional control were 84% in both cases, while 5‑ and 10-year distant control were 90% and 89%, respectively. A primary tumor in the head and neck area was detected in only 2 patients. No patient had an initial failure in the pharyngeal axis or contralateral cervical nodes. The 5‑ and 10-year overall survival were 55% and 42%, respectively. Severe early toxicity occurred in 71%; severe late toxicity in 33% of patients. Multivariate analysis demonstrated N‑status (hazard ratio [HR] 2.424; 95% confidence interval [CI] 1.121–5.241; p = 0.024) and comorbidity scores assessed by ACE-27 (Adult Comorbidity Evaluation; HR 3.058; 95% CI 1.489–6.281; p = 0.002) as two independent prognostic factors for overall survival.

Conclusion

The results of our work study demonstrate the high effectiveness of curative (chemo)radiotherapy on the pharyngeal axis and bilateral cervical nodes with long-term locoregional and distant control in 3/4 of the treated patients. N‑status and comorbidity scores were shown as strong prognostic factors influencing overall survival.

Comess MS, Beahrs SOH, Dockerty MB (1957) Cervical metastasis from occult carcinoma. Surg Gynecol Obstet 104(5):607–617

Schmalbach CE, Miller FR (2007) Occult primary head and neck carcinoma. Curr Oncol Rep 9(2):139–146. https://doi.org/10.1007/s11912-007-0012-5CrossRef

Haas I, Hoffmann TK, Engers R, Ganzer U (2002) Diagnostic strategies in cervical carcinoma of an unknown primary (CUP). Eur Arch Otorhinolaryngol 259(6):325–333. https://doi.org/10.1007/s00405-002-0470-1CrossRef

Lu X, Hu C, Ji Q, Shen C, Feng Y (2009) Squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: the impact of radiotherapy. Tumori 95(2):185–190CrossRef

Wallace A, Richards GM, Harari PM et al (2011) Head and neck squamous cell carcinoma from an unknown primary site. Am J Otolaryngol 32(4):286–290. https://doi.org/10.1016/j.amjoto.2010.05.004CrossRef

Kirschner MJ, Fietkau R, Waldfahrer F, Iro H, Sauer R (1997) Zur Therapie von zervikalen Lymphknotenmetastasen ohne bekannten Primärtumor. Strahlenther Onkol 173(7):362–368. https://doi.org/10.1007/BF03038239CrossRef

Jereczek-Fossa BA, Jassem J, Orecchia R (2004) Cervical lymph node metastases of squamous cell carcinoma from an unknown primary. Cancer Treat Rev 30(2):153–164. https://doi.org/10.1016/j.ctrv.2003.10.001CrossRef

Pavlidis N, Pentheroudakis G (2012) Cancer of unknown primary site. Lancet 379(9824):1428–1435. https://doi.org/10.1016/S0140-6736(11)61178-1CrossRef

Grau C, Johansen LV, Jakobsen J, Geertsen P, Andersen E, Jensen BB (2000) Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish society for head and neck oncology. Radiother Oncol 55(2):121–129. https://doi.org/10.1016/s0167-8140(00)00172-9CrossRef

10.

Sinnathamby K, Peters LJ, Laidlaw C, Hughes PG (1997) The occult head and neck primary: to treat or not to treat? Clin Oncol (R Coll Radiol) 9(5):322–329. https://doi.org/10.1016/s0936-6555(05)80066-4CrossRef

11.

Erkal HS, Mendenhall WM, Amdur RJ, Villaret DB, Stringer SP (2001) Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection. Int J Radiat Oncol Biol Phys 50(1):55–63. https://doi.org/10.1016/s0360-3016(00)01554-6CrossRef

12.

Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 31(5):1341–1346. https://doi.org/10.1016/0360-3016(95)00060-CCrossRef

13.

Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL Jr. (2004) Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 291(20):2441–2447. https://doi.org/10.1001/jama.291.20.2441CrossRef

14.

Bugat R, Bataillard A, Lesimple T et al (2002) Standards, options et recommandations 2002 pur la prise en charge des patients atteints de carcinomes de site primitif inconnu (rapport abrégé) [standards, options and recommendations for the management of patient with carcinoma of unknown primary site. Bull Cancer 89(10):869–875

15.

Nguyen C, Shenouda G, Black MJ, Vuong T, Donath D, Yassa M (1994) Metastatic squamous cell carcinoma to cervical lymph nodes from unknown primary mucosal sites. Head Neck 16(1):58–63. https://doi.org/10.1002/hed.2880160112CrossRef

16.

Colletier PJ, Garden AS, Morrison WH, Goepfert H, Geara F, Ang KK (1998) Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck 20(8):674–681. https://doi.org/10.1002/(sici)1097-0347(199812)20:8〈674::aid-hed3〉3.0.co;2‑hCrossRef

17.

Tong CC, Luk MY, Chow SM, Ngan KC, Lau WH (2002) Cervical nodal metastases from occult primary: undifferentiated carcinoma versus squamous cell carcinoma. Head Neck 24(4):361–369. https://doi.org/10.1002/hed.10054CrossRef

18.

Aslani M, Sultanem K, Voung T, Hier M, Niazi T, Shenouda G (2007) Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: is there a need for neck dissection? Head Neck 29(6):585–590. https://doi.org/10.1002/hed.20581CrossRef

19.

Cuaron J, Rao S, Wolden S et al (2016) Patterns of failure in patients with head and neck carcinoma of unknown primary treated with radiation therapy. Head Neck 38(1):E426–E431. https://doi.org/10.1002/hed.24013CrossRef

20.

Demiroz C, Vainshtein JM, Koukourakis GV, Gutfeld O, Prince ME, Bradford CR, Wolf GT, McLean S, Worden FP, Chepeha DB, Schipper MJ, McHugh JB (2014) Head and neck squamous cell carcinoma of unknown primary: neck dissection and radiotherapy or definitive radiotherapy. Head Neck 36(11):1589–1595. https://doi.org/10.1002/hed.23479CrossRef

21.

Dragan AD, Nixon IJ, Guerrero-Urbano MT, Oakley R, Jeannon JP, Simo R (2014) Selective neck dissection as a therapeutic option in management of squamous cell carcinoma of unknown primary. Eur Arch Otorhinolaryngol 271(5):1249–1256. https://doi.org/10.1007/s00405-013-2643-5CrossRef

22.

Tribius S, Hoffmann AS, Bastrop S et al (2012) HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome. Oral Oncol 48(11):1178–1184. https://doi.org/10.1016/j.oraloncology.2012.05.022CrossRef

23.

Coster JR, Foote RL, Olsen KD, Jack SM, Schaid DJ, DeSanto LW (1992) Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy. Int J Radiat Oncol Biol Phys 23(4):743–749. https://doi.org/10.1016/0360-3016(92)90647-zCrossRef

24.

Strojan P, Anicin A (1998) Combined surgery and postoperative radiotherapy for cervical lymph node metastases from an unknown primary tumour. Radiother Oncol 49(1):33–40. https://doi.org/10.1016/s0167-8140(98)00082-6CrossRef

25.

Reddy SP, Marks JE (1997) 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 37(4):797–802. https://doi.org/10.1016/s0360-3016(97)00025-4CrossRef

26.

Nieder C, Gregoire V, Ang KK (2001) Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple? Int J Radiat Oncol Biol Phys 50(3):727–733. https://doi.org/10.1016/s0360-3016(01)01462-6CrossRef

27.

Beldì D, Jereczek-Fossa BA, D’Onofrio A et al (2007) 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 69(4):1051–1058. https://doi.org/10.1016/j.ijrobp.2007.04.039CrossRef

28.

Shukla P, Gupta D, Bisht SS et al (2009) Metastatic squamous cell carcinoma neck with occult primary: a retrospective analysis. Indian J Med Paediatr Oncol 30(4):124–130. https://doi.org/10.4103/0971-5851.65334CrossRef

29.

Harper CS, Mendenhall WM, Parsons JT, Stringer SP, Cassisi NJ, Million RR (1990) Cancer in neck nodes with unknown primary site: role of mucosal radiotherapy. Head Neck 12(6):463–469. https://doi.org/10.1002/hed.2880120603CrossRef

30.

Maulard C, Housset M, Brunel P et al (1992) Postoperative radiation therapy for cervical lymph node metastases from an occult squamous cell carcinoma. Laryngoscope 102(8):884–890. https://doi.org/10.1288/00005537-199208000-00007CrossRef

31.

Rödel RM, Matthias C, Blomeyer BD, Wolff HA, Jung K, Christiansen H (2009) Impact of distant metastasis in patients with cervical lymph node metastases from cancer of an unknown primary site. Ann Otol Rhinol Laryngol 118(9):662–669. https://doi.org/10.1177/000348940911800911CrossRef

32.

Iganej S, Kagan R, Anderson P et al (2002) Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse. Head Neck 24(3):236–246. https://doi.org/10.1002/hed.10017CrossRef

33.

Bataini RP, Rodriguez J, Jaulerry C, Brugere J, Ghossein NA (1987) Treatment of metastatic neck nodes secondary to an occult epidermoid carcinoma of the head and neck. Laryngoscope 97:1080–1084CrossRef

34.

Ligey A, Gentil J, Créhange G et al (2009) 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 93(3):483–487. https://doi.org/10.1016/j.radonc.2009.08.027CrossRef

35.

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

36.

Al Kadah B, Papaspyrou G, Linxweiler M et al (2017) Cancer of unknown primary (CUP) of the head and neck: retrospective analysis of 81 patients. Eur Arch Otorhinolaryngol 274(6):2557–2566. https://doi.org/10.1007/s00405-017-4525-8CrossRef

37.

Liu X, Li D, Li N, Zhu X (2016) Optimization of radiotherapy for neck carcinoma metastasis from unknown primary sites: a meta-analysis. Oncotarget 7(48):78736–78746. https://doi.org/10.18632/oncotarget.12852CrossRef

38.

Eisbruch A, Schwartz M, Rasch C et al (2004) Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys 60(5):1425–1439. https://doi.org/10.1016/j.ijrobp.2004.05.050CrossRef

39.

Braam PM, Terhaard CH, Roesink JM, Raaijmakers CP (2006) Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy. Int J Radiat Oncol Biol Phys 66(4):975–980. https://doi.org/10.1016/j.ijrobp.2006.06.045CrossRef

40.

Yao M, Karnell LH, Funk GF, Lu H, Dornfeld K, Buatti JM (2007) Health-related quality-of-life outcomes following IMRT versus conventional radiotherapy for oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys 69(5):1354–1360. https://doi.org/10.1016/j.ijrobp.2007.05.003CrossRef

41.

Jabbari S, Kim HM, Feng M, Lin A, Tsien C, Elshaikh M et al (2005) Matched case–control study of quality of life and xerostomia after intensity-modulated radiotherapy or standard radiotherapy for head-and-neck cancer: initial report. Int J Radiat Oncol Biol Phys 63:725–731CrossRef

42.

Saarilahti K, Kouri M, Collan J et al (2005) Intensity modulated radiotherapy for head and neck cancer: evidence for preserved salivary gland function. Radiother Oncol 74(3):251–258. https://doi.org/10.1016/j.radonc.2004.11.004CrossRef

43.

Klem ML, Mechalakos JG, Wolden SL, Zelefsky MJ, Singh B, Kraus D et al (2006) Intensity-modulated radiotherapy for head and neck cancer of unknown primary. J Clin Oncol 24(18S):5565 (2006 ASCO Annual Meeting Proceedings Part I)CrossRef

44.

Frank SJ, Rosenthal DI, Petsuksiri J et al (2010) 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 78(4):1005–1010. https://doi.org/10.1016/j.ijrobp.2009.09.006CrossRef

45.

Shoushtari A, Saylor D, Kerr KL et al (2011) Outcomes of patients with head-and-neck cancer of unknown primary origin treated with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 81(3):e83–e91. https://doi.org/10.1016/j.ijrobp.2011.01.014CrossRef

46.

Sher DJ, Balboni TA, Haddad RI et al (2011) Efficacy and toxicity of chemoradiotherapy using intensity-modulated radiotherapy for unknown primary of head and neck. Int J Radiat Oncol Biol Phys 80(5):1405–1411. https://doi.org/10.1016/j.ijrobp.2010.04.029CrossRef

47.

Frank SJ, Petsuksiri J, Ang KK, Morrison WH, Chao K, Rosenthal DI et al (2007) Intensity modulated radiation therapy for squamous cell carcinoma metastatic to cervical lymph nodes from unknown primary site: outcomes and pattern of failure. Int J Radiat Oncol Biol Phys 69:S425CrossRef

48.

Madani I, Vakaet L, Bonte K, Boterberg T, De Neve W (2008) Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J Radiat Oncol Biol Phys 71(4):1158–1166. https://doi.org/10.1016/j.ijrobp.2007.11.059CrossRef

49.

Lu H, Yao M, Tan H (2009) Unknown primary head and neck cancer treated with intensity-modulated radiation therapy: to what extent the volume should be irradiated. Oral Oncol 45(6):474–479. https://doi.org/10.1016/j.oraloncology.2008.06.006CrossRef

50.

Villeneuve H, Després P, Fortin B et al (2012) Cervical lymph node metastases from unknown primary cancer: a single-institution experience with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 82(5):1866–1871. https://doi.org/10.1016/j.ijrobp.2011.02.031CrossRef

51.

Chen AM, Farwell DG, Lau DH, Li BQ, Luu Q, Donald PJ (2011) 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 81(2):346–352. https://doi.org/10.1016/j.ijrobp.2010.06.031CrossRef

52.

Huang CC, Tseng FY, Yeh TH et al (2008) Prognostic factors of unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 139(3):429–435. https://doi.org/10.1016/j.otohns.2008.05.015CrossRef

53.

Koivunen P, Laranne J, Virtaniemi J et al (2002) Cervical metastasis of unknown origin: a series of 72 patients. Acta Otolaryngol 122(5):569–574. https://doi.org/10.1080/00016480260092435CrossRef

54.

Hauswald H, Lindel K, Rochet N, Debus J, Harms W (2008) Surgery with complete resection improves survival in radiooncologically treated patients with cervical lymph node metastases from cancer of unknown primary. Strahlenther Onkol 184(3):150–156. https://doi.org/10.1007/s00066-008-1765-yCrossRef

55.

Keller LM, Galloway TJ, Holdbrook T et al (2014) p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary. Head Neck 36(12):1677–1684. https://doi.org/10.1002/hed.23514CrossRef

56.

Guntinas-Lichius O, Peter Klussmann J, Dinh S et al (2006) Diagnostic work-up and outcome of cervical metastases from an unknown primary. Acta Otolaryngol 126(5):536–544. https://doi.org/10.1080/00016480500417304CrossRef

57.

Christiansen H, Hermann RM, Martin A, Nitsche M, Schmidberger H, Pradier O (2005) Neck lymph node metastases from an unknown primary tumor retrospective study and review of literature. Strahlenther Onkol 181(6):355–362. https://doi.org/10.1007/s00066-005-1338-2CrossRef

58.

Horowitz G, Hosni A, Yu E et al (2018) Prevalence, prognosis, and treatment implications of retropharyngeal nodes in unknown primary head and neck carcinoma. Oral Oncol 82:162–167. https://doi.org/10.1016/j.oraloncology.2018.05.023CrossRef

59.

Bøje CR, Dalton SO, Primdahl H et al (2014) Evaluation of comorbidity in 9388 head and neck cancer patients: a national cohort study from the DAHANCA database. Radiother Oncol 110(1):91–97. https://doi.org/10.1016/j.radonc.2013.11.009CrossRef

60.

Rietbergen MM, Brakenhoff RH, Bloemena E et al (2013) Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment de-escalation trials. Ann Oncol 24(11):2740–2745. https://doi.org/10.1093/annonc/mdt319CrossRef

61.

Yung KC, Piccirillo JF (2008) The incidence and impact of comorbidity diagnosed after the onset of head and neck cancer. Arch Otolaryngol Head Neck Surg 134(10):1045–1049. https://doi.org/10.1001/archotol.134.10.1045CrossRef

62.

Monteiro AR, Garcia AR, Pereira TC et al (2021) ACE-27 as a prognostic tool of severe acute toxicities in patients with head and neck cancer treated with chemoradiotherapy: a real-world, prospective, observational study. Support Care Cancer 29(4):1863–1871. https://doi.org/10.1007/s00520-020-05679-4CrossRef

63.

Dornfeld K, Simmons JR, Karnell L et al (2007) Radiation doses to structures within and adjacent to the larynx are correlated with long-term diet- and speech-related quality of life. Int J Radiat Oncol Biol Phys 68(3):750–757. https://doi.org/10.1016/j.ijrobp.2007.01.047CrossRef

64.

Barker CA, Morris CG, Mendenhall WM (2005) Larynx-sparing radiotherapy for squamous cell carcinoma from an unknown head and neck primary site. Am J Clin Oncol 28(5):445–448. https://doi.org/10.1097/01.coc.0000162963.69302.12CrossRef

65.

Mendenhall WM, Mancuso AA, Amdur RJ, Stringer SP, Villaret DB, Cassisi NJ (2001) Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site. Am J Otolaryngol 22(4):261–267. https://doi.org/10.1053/ajot.2001.24820CrossRef

66.

Maghami E, Ismaila N, Alvarez A et al (2020) Diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck: aSCO guideline. J Clin Oncol 38(22):2570–2596. https://doi.org/10.1200/JCO.20.00275CrossRef

Titel: Long-term results of radio(chemo)therapy in metastatic carcinoma to cervical lymph nodes from an unknown primary. Adult Comorbidity Evaluation 27 score as a predictor of survival
verfasst von: MUDr. Miloslav Pala, Ph.D., MBA
Pavla Novakova
Zdena Pechacova
Lucie Vesela
Antonin Vrana
Jarmila Sukova
Petra Holeckova
Tereza Drbohlavova
Tomas Podlesak
Lubos Petruzelka
Publikationsdatum: 09.08.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 2/2023
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-022-01983-6

Springer Medizin

Long-term results of radio(chemo)therapy in metastatic carcinoma to cervical lymph nodes from an unknown primary. Adult Comorbidity Evaluation 27 score as a predictor of survival