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Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma

A monocentric clinicopathologic analysis

Der Einfluss postoperativer Strahlentherapie und HER2/neu-Überexpression auf Speichelgangkarzinome

Eine monozentrische klinisch-pathologische Analyse

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Abstract

Aim

Retrospective Investigation of the prognostic relevance of clinicopathologic parameters in patients with salivary duct carcinoma (SDC).

Methods

An experienced pathologist reviewed 67 patients with de novo SDC or SDC ex pleomorphic adenoma. Paraffin-embedded tumor samples were examined by immunohistochemistry for expression of HER2/neu, androgen (AR), progesterone (PR), estrogen (ER), epidermal growth factor (EGFR) and programmed death ligand 1 (PD-L1-R) receptor. In 45 patients who had cM0 and follow-up data available, survival rates were calculated (Kaplan–Meier method) and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox-regression analysis).

Results

Overexpression of HER2/neu, AR, ER, PR, EGFR, PD-L1-R was found in 25.4%, 84%, 0%, 0%, 17.9%, 16.4% of patients. Overall (OS), disease-free (DFS), distant-metastases-free survival (DMFS) and locoregional control (LRC) were 92.3/72.4/56.9%, 78.2/58.1/58.1%, 85.4/65.2/65.2% and 89.7/81.9/81.9% after 1/3/5 years (medial follow-up 26 months). In univariate analysis a positive resection margin (p = 0.008) and no postoperative radiotherapy (p = 0.001) predict an increased locoregional recurrence rate. In multivariate analysis only postoperative radiotherapy is statistically significant (p = 0.004). Presence of lymph node metastases, a lymph node density >4 and HER2/neu overexpression predict decreased DFS and DMFS. In multivariate HER2/neu overexpression was the only significant predictor for reduced DFS (p = 0.04) and DMFS (p = 0.02).

Conclusion

Postoperative radiotherapy is the only significant predictor for LRC. HER2/neu receptor expression is an independent prognostic factor for decreased DFS and DMFS in patients with SDC. In addition to radio(chemo)therapy, intensified first-line treatment regimens should also be evaluated in the future.

Zusammenfassung

Ziel

In dieser retrospektiven Auswertung wurde der Einfluss klinisch-pathologischer Parameter auf die Prognose von Patienten mit Speichelgangkarzinomen (SDC) untersucht.

Methoden

Von einem erfahrenen Pathologen wurden 67 Patienten mit De-novo-SDC bzw. aus einem pleomorphen Adenom entstandenem SDC (SDC ex-PA) erneut befundet. Die paraffinfixierten Tumorschnitte wurden immunhistochemisch auf die Expression von HER2/neu, Androgen(AR)-, Progesteron(PR)-, Östrogen(ER)-, „epidermal growth factor“(EGFR)- und „programmed death ligand 1“(PD-L1-R)-Rezeptoren untersucht. Bei 45 Patienten ohne Fernmetastasen mit Follow-up-Daten wurden Überlebenskurven mit der Kaplan-Meier-Methode bestimmt. Der Log-rank-Test wurde für die univariate, die Cox-Regressionsanalyse für die multivariate Analyse der prognostischen Variablen eingesetzt.

Ergebnisse

HER2/neu, AR, ER, PR, EGFR, PD-L1-R waren (über)exprimiert bei 25,4 %, 84 %, 0 %, 0 %, 17,9 %, 16,4 % der Patienten. Das mediane Follow-up betrug 26 Monate. Das Gesamt- (OS), das krankheitsfreie (DFS) und das fernmetastasenfreie (DMFS) Überleben bzw. die lokoregionäre Kontrolle (LRC) betrugen 92,3/72,4/56,9 %, 78,2/58,1/58,1 %, 85,4/65,2/65,2 % und 89,7/81,9/81,9 % nach 1/3/5 Jahren. In der univariaten Analyse korrelierten positive Resektionsränder (p = 0,008) und keine postoperative Strahlentherapie (p = 0,001) mit einer erhöhten Lokalrezidivrate, in der multivariaten Analyse zeigte sich lediglich bei der postoperativen Strahlentherapie eine statistische Signifikanz (p = 0,004). Vorhandene Lymphknotenmetastasen, eine Lymphknoten-Ratio >4 und eine HER2/neu-Überexpression gingen mit einem verringerten DFS und DMFS einher. In der multivariaten Analyse ist ein positiver HER2/neu-Expressionsstatus der einzige prognostische Faktor für ein verringertes DFS (p = 0,04) und DMFS (p = 0,02).

Zusammenfassung

Die postoperative Bestrahlung ist der einzige signifikante Prädiktor für eine verbesserte LRC. Die HER2/neu-Rezeptorüberexpression ist ein unabhängiger prognostischer Faktor für ein verringertes DFS und DMFS bei SDC. Zukünftig sollte für SDC-Patienten zusätzlich zur postoperativen Radio(chemo)therapie eine intensivierte systemische First-line-Therapie evaluiert werden.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital of Erlangen, Universitätsstraße 27, 91054, Erlangen, Germany

    Marlen Haderlein, Sabine Semrau, Sebastian Lettmaier, Markus Hecht & Rainer Fietkau

  2. Department of Otorhinolaryngology, University Hospital of Erlangen, Erlangen, Germany

    Claudia Scherl & Heinrich Iro

  3. Institute of Pathology, University Hospital of Erlangen, Erlangen, Germany

    Ramona Erber & Abbas Agaimy

Authors
  1. Marlen Haderlein
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  2. Claudia Scherl
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  4. Sebastian Lettmaier
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Correspondence to Marlen Haderlein.

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Conflict of interest

M. Haderlein, C. Scherl, S. Semrau, S. Lettmaier, M. Hecht, R. Erber, H. Iro, R. Fietkau and A. Agaimy declare that they have no competing interests.

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Haderlein, M., Scherl, C., Semrau, S. et al. Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma. Strahlenther Onkol 193, 961–970 (2017). https://doi.org/10.1007/s00066-017-1196-8

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  • DOI: https://doi.org/10.1007/s00066-017-1196-8

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