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Outcome and management of rare high-grade “salivary” adenocarcinoma: the important role of adjuvant (chemo)radiotherapy

Ergebnisse und Behandlung der seltenen gering differenzierten Adenokarzinome der Speicheldrüsen: wichtige Rolle der adjuvanten (Chemo)radiotherapie

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Abstract

Purpose

To determine survival and management strategies for high-grade adenocarcinoma of salivary glands (ASG).

Methods

A retrospective analysis of cases diagnosed between 1998 and 2015 from our single tertiary referral center was performed. Multivariable logistic regression was used to determine factors associated with survival.

Results

Thirty-eight cases of high-grade ASG were identified. Most patients were men (68.4%) with a median age of 65.5 years (range 23–84 years). Most tumors were T3 and T4 (65.8%). Regional metastases were common (55.2%), and 42.1% developed distant metastases. The mean follow-up was 60.5 months. All patients received surgery as primary treatment, with 84.2% of patients receiving adjuvant radiation therapy or chemoradiotherapy ([C]RT). Cumulative overall survival was 89.1%, 50.9%, and 20.7% after 1, 5, and 10 years, respectively. Disease-specific survival was 94.4%, 69.8%, and 42.8%, and distant-metastases-free survival (DMFS) was 80.5%, 50.1%, and 40.1% after 1, 5, and 10 years. On multivariable analysis, advanced T status correlated with DMFS (hazard ratio 2.75, 95% CI 0.93–8.16). Postsurgical (C)RT reduced the locoregional recurrence rate by 23.9%, and it improved the locoregional-recurrence-free survival by 39% (p = 0.094).

Conclusion

High-grade ASG is considered to have an unfavorable prognosis. Adjuvant (C)RT reduces the rate of locoregional recurrences. Distant metastases are common, and an advanced T stage has increased prognostic value for development of early distant lesions.

Zusammenfassung

Ziel

Untersuchung von Überleben und Behandlungsstrategien von gering differenzierten Adenokarzinomen der Speicheldrüsen (ASG).

Methoden

Es wurde eine retrospektive Analyse von Fällen durchgeführt, die zwischen 1998 und 2015 in unserer Universitätsklinik behandelt wurden. Faktoren, die mit dem Überleben assoziiert waren, wurden in einer multivariablen Regressionsanalyse bestimmt.

Ergebnisse

Insgesamt wurden 38 schlecht differenzierte ASG identifiziert. Die meisten Patienten waren männlich (68,4%) mit einem mittleren Alter von 65,5 Jahren (Zeitspanne: 23–84 Jahre). Die meisten Tumoren wiesen einen T3- und T4-Status auf (65,8%). Regionäre Metastasen waren häufig (55,2%); 42,1% entwickelten Fernmetastasen. Die mittlere Nachsorgezeit betrug 60,5 Monate. Bei allen Patienten wurde eine primär chirurgische Therapie durchgeführt. Insgesamt 84,2% der Patienten erhielten eine adjuvante Radiatio oder eine Radiochemotherapie ([C]RT). Das kumulative Gesamtüberleben (OS) betrug 89,1, 50,9 und 20,7% nach 1, 5 und 10 Jahren. Das krankheitsspezifische Überleben (DSS) und das fernmetastasenfreie Überleben (DMFS) waren 94,4%, 69,8%, 42,1% und 80,5%, 50,1%, 40,1% nach 1, 5 und 10 Jahren. In der multivariaten Analyse war ein fortgeschrittenes T‑Stadium mit dem DMFS korreliert (HR: 2,75; 95% KI 0,93–8,16). Eine adjuvante (C)RT reduzierte die lokoregionäre Rezidivrate um 23,9% und verbesserte das lokoregionäre rezidivfreie Überleben um 39% (p = 0,094).

Schlussfolgerung

Gering differenzierte ASG weisen eine schlechte Prognose auf. Eine adjuvante (C)RT reduziert die Rate an lokoregionären Rezidiven. Fernmetastasen sind häufig, und ein fortgeschrittener T‑Status hat einen hohen prognostischen Wert bei der Entwicklung von Fernmetastasen.

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References

  1. Xiao CC, Zhan KY, White-Gilbertson SJ, Day TA (2016) Predictors of nodal metastasis in Parotid malignancies: a national cancer data base study of 22,653 patients. Otolaryngol Head Neck Surg 154:121–130

    Article  Google Scholar 

  2. Wang YL, Zhu YX, Chen TZ, Wang Y, Sun GH, Zhang L et al (2012) Clinicopathologic study of 1176 salivary gland tumors in a Chinese population: experience of one cancer center 1997–2007. Acta Otolaryngol 132:879–886

    Article  Google Scholar 

  3. Wahlberg P, Anderson H, Biorklund A, Moller T, Perfekt R (2002) Carcinoma of the parotid and submandibular glands—a study of survival in 2465 patients. Oral Oncol 38:706–713

    Article  Google Scholar 

  4. Boukheris H, Curtis RE, Land CE, Dores GM (2009) Incidence of carcinoma of the major salivary glands according to the WHO classification, 1992 to 2006: a population-based study in the United States. cancer Epidemiol Biomarkers Prev 18:2899–2906

    Article  Google Scholar 

  5. Seifert G (1996) Histological typing of salivary gland tumors, 2nd edn. Springer, Berlin

    Google Scholar 

  6. Renehan A, Gleave EN, Hancock BD, Smith P, McGurk M (1996) Long-term follow-up of over 1000 patients with salivary gland tumours treated in a single centre. Br J Surg 83:1750–1754

    Article  CAS  Google Scholar 

  7. Vander Poorten V, Bradley PJ, Takes RP, Rinaldo A, Woolgar JA, Ferlito A (2012) Diagnosis and management of parotid carcinoma with a special focus on recent advances in molecular biology. Head Neck 34:429–440

    Article  Google Scholar 

  8. Bjørndal K, Krogdahl A, Therkildsen MH, Overgaard J, Johansen J, Kristensen CA et al (2011) Salivary gland carcinoma in Denmark 1990–2005: a national study of incidence, site and histology. Oral Oncol 47:677–682

    Article  Google Scholar 

  9. Bhattacharyya N, Fried MP (2002) Nodal metastasis in major salivary gland cancer: predictive factors and effects on survival. Arch Otolaryngol Head Neck Surg 128(8):904–908

    Article  Google Scholar 

  10. Huang MW, Zheng L, Liu SM, Shi Y, Zhang J, Yu GY, Zhang JG (2013) 125I brachytherapy alone for recurrent or locally advanced adenoid cystic carcinoma of the oral and maxillofacial region. Strahlenther Onkol 189(6):502–507

    Article  Google Scholar 

  11. Mao MH, Zhang JG, Zhang J, Zheng L, Liu SM, Huang MW, Shi Y (2014) Postoperative [125I] seed brachytherapy in the treatment of acinic cell carcinoma of the parotid gland: with associated risk factors. Strahlenther Onkol 190(11):1008–1014

    Article  Google Scholar 

  12. Mao MH, Zhang JG, Zheng L, Gao H, Zhang J, Liu SM, Huang MW, Shi Y (2015) The incidence of radioepidermitis and the dose-response relationship in parotid gland cancer patients treated with 125I seed brachytherapy: incidence of radioepidermitis and the dose-response relationship. Strahlenther Onkol 191(1):26–33

    Article  Google Scholar 

  13. Armstrong JG, Harrison LB, Spiro RH, Fass DB, Strong EW, Fuks ZY (1990) Malignant tumors of major salivary gland origin. A matched-pair analysis of the role of combined surgery and postoperative radiotherapy. Arch Otolaryngol Head Neck Surg 116(3):290–293

    Article  CAS  Google Scholar 

  14. Terhaard CH, Lubsen H, Rasch CR, Levendag PC, Kaanders HH, Tjho-Heslinga RE, van Den Ende PL, Burlage F, Dutch Head and Neck Oncology Cooperative Group (2005) The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiat Oncol Biol Phys 61(1):103–111

    Article  Google Scholar 

  15. Jones AS, Beasley NJP, Houghton DJ, Helliwell TR, Husband DJ (1998) Tumors of the minor salivary glands. Clin Otolaryngol Allied Sci 23(1):27–33

    Article  CAS  Google Scholar 

  16. Le QT, Birdwell S, Terris DJ, Gabalski EC, Varghese A, Fee WE Jr, Goffinet DR (1999) Postoperative irradiation of minor salivary gland malignancies of the head and neck. Radiother Oncol 52(2):165–171

    Article  CAS  Google Scholar 

  17. Cros J, Sbidian E, Hans S, Roussel H, Scotte F, Tartour E, Brasnu D, Laurent-Puig P, Bruneval P, Blons H, Badoual C (2013) Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours. Ann Oncol 24(10):2624–2629

    Article  CAS  Google Scholar 

  18. Luk PP, Weston JD, Yu B, Selinger CI, Ekmejian R, Eviston TJ, Lum T, Gao K, Boyer M, O’Toole SA, Clark JR, Gupta R (2016) Salivary duct carcinoma: clinicopathologic features, morphologic spectrum, and somatic mutations. Head Neck 38(Suppl 1):E1838–47

    Article  Google Scholar 

  19. Masubuchi T, Tada Y, Maruya S, Osamura Y, Kamata SE, Miura K, Fushimi C, Takahashi H, Kawakita D, Kishimoto S, Nagao T (2015) Clinicopathological significance of androgen receptor, HER2, Ki-67 and EGFR expressions in salivary duct carcinoma. Int J Clin Oncol 20(1):35–44

    Article  CAS  Google Scholar 

  20. Haderlein M, Scherl C, Semrau S, Lettmaier S, Hecht M, Erber R, Iro H, Fietkau R, Agaimy A (2017) Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma: a monocentric clinicopathologic analysis. Strahlenther Onkol 193(11):961–970

    Article  Google Scholar 

  21. Locati LD, Perrone F, Cortelazzi B, Imbimbo M, Bossi P, Potepan P, Civelli E, Rinaldi G, Quattrone P, Licitra L, Pilotti S (2014) Activity of abiraterone in rechallenging two AR-expressing salivary gland adenocarcinomas, resistant to androgen-deprivation therapy. Cancer Biol Ther 15(6):678–682

    Article  Google Scholar 

  22. Ferrell JK, Mace JC, Clayburgh D (2019) Contemporary treatment patterns and outcomes of salivary gland carcinoma: a National Cancer Database review. Eur Arch Otorhinolaryngol 276(4):1135–1146

    Article  Google Scholar 

  23. Zhan KY, Huang AT, Khaja SF, Bell D, Day TA (2016) Predictors of survival in parotid adenocarcinoma not otherwise specified: a National Cancer Database study of 3155 patients. Head Neck 38(8):1208–1212

    Article  Google Scholar 

  24. Erovic BM, Shah MD, Bruch G, Johnston M, Kim J, O’Sullivan B, Perez-Ordonez B, Weinreb I, Atenafu EG, de Almeida JR, Gullane PJ, Brown D, Gilbert RW, Irish JC, Goldstein DP (2015) Outcome analysis of 215 patients with parotid gland tumors: a retrospective cohort analysis. J Otolaryngol Head Neck Surg 29(44):43.

    Article  Google Scholar 

  25. Xiao CC, Zhan KY, White-Gilbertson SJ, Day TA (2016) Predictors of nodal metastasis in Parotid malignancies: a national cancer data base study of 22,653 patients. Otolaryngol Head Neck Surg 154(1):121–130

    Article  Google Scholar 

  26. Huang AT, Tang C, Bell D, Yener M, Izquierdo L, Frank SJ, El-Naggar AK, Hanna EY, Weber RS, Kupferman ME (2015) Prognostic factors in adenocarcinoma of the salivary glands. Oral Oncol 51(6):610–615

    Article  Google Scholar 

  27. Wahlberg P, Anderson H, Biörklund A, Möller T, Perfekt R (2002) Carcinoma of the parotid and submandibular glands—a study of survival in 2465 patients. Oral Oncol 38(7):706–713

    Article  Google Scholar 

  28. Deng R, Tang E, Yang X, Huang X, Hu Q (2102) Salivary adenocarcinoma, not otherwise specified: a clinicopathological study of 28 cases. Oral Surg Oral Med Oral Pathol Oral Radiol 113(5):655

    Article  Google Scholar 

  29. Li LJ, Li Y, Wen YM, Liu H, Zhao HW (2011) Clinical analysis of salivary gland tumor cases in West China in past 50 years. Oral Oncol 44(2):187–192

    Article  Google Scholar 

  30. Bhattacharyya N, Fried MP (2005) Determinants of survival in parotid gland carcinoma: a population-based study. Am J Otolaryngol 26(1):39–44

    Article  Google Scholar 

  31. Yamada SI, Kurita H, Kamata T, Kirita T, Ueda M, Yamashita T, Ota Y, Otsuru M, Yamakawa N, Okura M, Aikawa T, Umeda M (2018) Significant prognostic factors affecting treatment outcomes of salivary gland carcinoma: a multicenter retrospective analysis. Odontology 106(1):96–102

    Article  CAS  Google Scholar 

  32. Haderlein M, Scherl C, Semrau S, Lettmaier S, Uter W, Neukam FW, Iro H, Agaimy A, Fietkau R (2016) High-grade histology as predictor of early distant metastases and decreased disease-free survival in salivary gland cancer irrespective of tumor subtype. Head Neck 38(Suppl 1):E2041–E2048

    Article  Google Scholar 

  33. Bradley PJ (2001) Distant metastasis from salivary glands cancer. ORL J Otorhinolaryngol Relat Spec 63:233–242

    Article  CAS  Google Scholar 

  34. Gallo O, Franchi A, Bottai GV, Fini-Storchi I, Tesi G, Boddi V (1997) Risk factors for distant metastases from carcinoma of the parotid gland. Cancer 80:844–851

    Article  CAS  Google Scholar 

  35. Ali S, Bryant R, Palmer FL, DiLorenzo M, Shah JP, Patel SG, Ganly I (2015) Distant metastases in patients with carcinoma of the major salivary glands. Ann Surg Oncol 22:4014–4019

    Article  Google Scholar 

  36. Mücke T, Robitzky LK, Kesting MR, Wagenpfeil S, Holhweg-Majert B, Wolff KD, Hölzle F (2009) Advanced malignant minor salivary glands tumors of the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108(1):81–89

    Article  Google Scholar 

  37. Jones AV, Craig GT, Speight PM, Franklin CD (2008) The range and demographics of salivary gland tumours diagnosed in a UK population. Oral Oncol 44(4):407–417

    Article  CAS  Google Scholar 

  38. Vander Poorten VL, Balm AJ, Hilgers FJ, Tan IB, Keus RB, Hart AA (2000) Stage as major long term outcome predictor in minor salivary gland carcinoma. Cancer 89(6):1195–1204

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Friedrich-Alexander-University (FAU), Waldstraße 1, 91054, Erlangen, Germany

    Claudia Scherl, Konstantinos Mantsopoulos, Michael Koch, Maximilian Traxdorf, Philipp Grundtner & Heinrich Iro

  2. Department of Radiation Oncology, Friedrich-Alexander-University (FAU), Universitätsstraße 27, 91054, Erlangen, Germany

    Marlen Haderlein & Rainer Fietkau

  3. Department of Pathology, Friedrich-Alexander-University (FAU), Krankenhausstraße 8–10, 91054, Erlangen, Germany

    Abbas Agaimy

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  1. Claudia Scherl
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Correspondence to Claudia Scherl.

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C. Scherl, M. Haderlein, A. Agaimy, K. Mantsopoulos, M. Koch, M. Traxdorf, R. Fietkau, P. Grundtner, and H. Iro declare that they have no competing interests.

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Scherl, C., Haderlein, M., Agaimy, A. et al. Outcome and management of rare high-grade “salivary” adenocarcinoma: the important role of adjuvant (chemo)radiotherapy. Strahlenther Onkol 195, 1050–1059 (2019). https://doi.org/10.1007/s00066-019-01499-6

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