Skip to main content

Advertisement

SpringerLink
Log in

Adjuvant Low Single Dose Cisplatin-based Concurrent Radiochemotherapy of Oral Cavity and Oropharynx Carcinoma

Impact of Extracapsular Nodal Spread on Distant Metastases

Adjuvante, niedrig-einzeldosierte, Cisplatin-haltige simultane Radiochemotherapie von Mundhöhlen- und Oropharynxtumoren: Der extrakapsuläre Lymphknotenbefall beeinflusst die Fernmetastasierung

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Background:

The aim of this study was to analyze the prognostic importance of extracapsular nodal spread (ECS) in patients with locally advanced squamous cell carcinoma (SCC) of the oral cavity or oropharynx, and the impact of adjuvant low single dose cisplatin-based radiochemotherapy on distant metastases-free survival (DMFS).

Patients and Methods:

The study population was selected from 195 patients with high-risk oral cavity or oropharyngeal cancer, who had either adjuvant radiotherapy (RT) or radiochemotherapy (RCT) between January 1, 1997 and December 31, 2006, at the University Clinic of Radiation Oncology of the Martin-Luther-University Halle-Wittenberg. A total of 42 matched pairs of patients with UICC stage III–IVa,b disease were analyzed. The patients were matched (one to one) according to tumor site, sex, T stage, N stage, ECS, resection margin status, and Karnofsky performance status. To analyze the correlation between the treatment modality (RT vs. RCT) and the impact of ECS on DMFS, the Cox proportional hazard model was used. Survival rates were calculated using the Kaplan–Meier method.

Results:

There was a strong correlation between the degree of nodal involvement and ECS (pN1: 33%; pN2b: 45%; pN2c: 71%). Moreover, the 5-year locoregional control rates (LC) in patients with ECS were 76% vs. 63% (n.s.) for RT and RCT, respectively. However, for patients without ECS, the LC was more favorable after RCT (RT vs. RCT: 62% vs. 88%, p < 0.05). DMFS again was better after RT, and this observation was independent of the presence or absence of ECS. Finally, in multivariate analyses, the presence of ECS significantly decreased the DMFS (p = 0.04, hazard ratio (HR) 2.64).

Conclusions:

Patients with ECS have an increased risk of distant metastases. Adjuvant low single dose cisplatin-based concurrent chemotherapy seems to have no influence on occult microscopic systemic disease.

Zusammenfassung

Hintergrund:

Ziel der Untersuchung war die Analyse der prognostischen Bedeutung der extrakapsulären Infiltration bei Lymphknotenmetastasen (extracapsular nodal spread – ECS) von Patienten mit lokal fortgeschrittenen Plattenepithelkarzinomen von Mundhöhle oder Oropharynx und des Einflusses der adjuvanten, niedrig-einzeldosierten Cisplatin-haltigen Radio-chemotherapie auf das fernmetastasenfreie Überleben (DMFS).

Patienten und Methodik:

Insgesamt wurden 195 Patienten ausgewertet, die an der Universitätsklinik für Strahlentherapie der Martin-Luther-Universität Halle-Wittenberg zwischen dem 1. Januar 1997 und dem 31. Dezember 2006 wegen eines Hochrisiko-Kopf-Hals-Karzinoms der Mundhöhle oder des Oropharynx postoperativ eine alleinige Radiotherapie (RT) oder eine simultane Radiochemotherapie (RCT) erhielten. Für die Analyse wurden dann 42 aufeinander abgestimmte Patientenpaare ausgewählt. Die Patienten der beiden Gruppen wurden eins zu eins gemäß Primärlokalisation, Geschlecht, T-Stadium, N-Stadium, ECS, Resektionsrand und Karnofsky-Performance-Status homogen verteilt. Die Analyse des Zusammenhangs zwischen der Behandlungsmodalität (RT vs. RCT) und dem Einfluss des ECS auf das Überleben erfolgte mit dem Cox-Regressions-Modell. Die Überlebenskurven wurden mit der Kaplan-Meier-Methode berechnet.

Ergebnisse:

Die Häufigkeit der extrakapsulären Weichgewebeinfiltration korrelierte mit dem Ausmaß der Lymphknoten-metastasierung (pN1: 33%; pN2b: 45%; pN2c: 71%). Die lokoregionale 5-Jahres-Kontrolle für Patienten mit ECS war nach RT vs. RCT: 76% vs. 63% (n.s.), während bei Patienten ohne ECS nach RCT bessere Ergebnisse erzielt wurden als nach RT (RT vs. RCT: 62% vs. 88%, p < 0,05). Das DMFS war ebenfalls besser nach RT im Vergleich zur RCT, unabhängig davon, ob ein ECS vorlag oder nicht. In der multivariaten Analyse war der Nachweis einer ECS mit einem signifikant schlechteren fernmetastasenfreien Überleben vergesellschaftet (p = 0.04, Hazard Ratio [HR] 2.64).

Schlussfolgerung:

Patienten mit ECS haben ein erhöhtes Risiko für Fernmetastasen. Die adjuvante, niedrig dosierte Cisplatin-basierte simultane Chemotherapie hatte keinen Einfluss auf die okkulte mikroskopische systemische Metastasierung.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bachaud JM, David JM, Boussin G et al. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 1991;20:243–246.

    Article  PubMed  CAS  Google Scholar 

  2. Bernier J, Cooper JS, Pajak TF et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:843–850.

    Article  PubMed  Google Scholar 

  3. Bernier J, Domenge C, Ozsahin M et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945–1952.

    Article  PubMed  CAS  Google Scholar 

  4. Carvalho AL, Nishimoto IN, Califano JA et al. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 2005;114:806–816.

    Article  PubMed  CAS  Google Scholar 

  5. Cooper JS, Pajak TF, Forastiere AA et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937–1944.

    Article  PubMed  Google Scholar 

  6. Cooper JS, Pajak TF, Forastiere AA et al. Precisely defining high-risk operable head and neck tumors based on RTOG #85-03 and #88-24: targets for postoperative radiochemotherapy? Head Neck 1998;20:588–594.

    Article  PubMed  CAS  Google Scholar 

  7. De Carvalho MB. Quantitative analysis of the extent of extracapsular invasion and its prognostic significance: a prospective study of 170 cases of carcinoma of the larynx and hypopharynx. Head Neck 1998;20:16–21.

    Article  Google Scholar 

  8. Devinemi VR, Simpson JR, Sessions D et al. Supraglottic carcinoma: impact of radiation therapy on outcome of patients with positive margins and extracapsular nodal disease. Laryngoscope 1991;101:767–770.

    Google Scholar 

  9. Fietkau R, Lautenschläger C, Sauer R et al. Postoperative concurrent radio-chemotherapy versus radiotherapy in high-risk SCCA of the head and neck: Results of the German phase III trial ARO 96-3. J Clin Oncol 2006;24:5507.

    Google Scholar 

  10. Forastiere AA, Koch W, Trotti A et al. Head and neck cancer. N Engl J Med 2001;345:1890–1900.

    Article  PubMed  CAS  Google Scholar 

  11. Gillison ML, Koch WM, Capone RB et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000;92:709–720.

    Article  PubMed  CAS  Google Scholar 

  12. Hermanek P, Hutter RVP, Sobin LH et al. TNM atlas: illustrated guide to the TNM/pTNM-classification of malignant tumours, 4th ed. Springer Verlag, Berlin, 1998.

    Google Scholar 

  13. Hinerman RW, Mendenhall WM, Morris CG et al. Postoperative irradiation for squamous cell carcinoma of the oral cavity: 35-year experience. Head Neck 2004;26:984–994.

    Article  PubMed  Google Scholar 

  14. Hirabayashi H, Koshii K, Uno A et al. Extracapsular spread of squamous cell carcinoma in neck lymph nodes: prognostic factor of laryngeal cancer. Laryngoscope 1991;101:502–506.

    Article  PubMed  CAS  Google Scholar 

  15. Huang DT, Johnson CR, Schmidt-Ullrich R et al. Postoperative radiotherapy in head and neck carcinoma with extracapsular lymph node extension and/or positive resection margins: a comparative study. Int J Radiat Oncol Biol Phys 1992;23:737–742.

    Article  PubMed  CAS  Google Scholar 

  16. Kaplan EL, Meier P. Nonparametric estimation for incomplete observation. J Am Stat Assoc 1958;53:457–481.

    Article  Google Scholar 

  17. Kuhnt T, Janich M, Götz U et al. Presentation of a 3D conformal radiotherapy technique for head-and-neck tumors resulting in substantial protection of the parotid glands. Strahlenther Onkol 2006;182:325–330.

    Article  PubMed  Google Scholar 

  18. Laramore GE, Scott CB, Al-Sarraf M et al. Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034. Int J Radiat Oncol Biol Phys 1992;23:706–713.

    Google Scholar 

  19. Rades D, Stoehr M, Meyners T et al. Evaluation of prognostic factors and two radiation techniques in patients treated with surgery followed by radio(chemo)therapy or definitive radio(chemo)therapy for locally advanced head-and-neck cancer. Strahlenther Onkol 2008;184:198–205.

    Article  PubMed  Google Scholar 

  20. Steinmann D, Cerny B, Karstens JH et al. Chemoradiotherapy with weekly cisplatin 40 mg/m(2) in 103 head-and-neck cancer patients: a cumulative dose-effect analysis. Strahlenther Onkol 2009;185:682–688.

    Article  PubMed  Google Scholar 

  21. Studer G, Seifert B, Glanzmann C. Prediction of distant metastasis in head neck cancer patients: implications for induction chemotherapy and pre-treatment staging? Strahlenther Onkol 2008;184:580–585.

    Article  PubMed  Google Scholar 

  22. Tribius S, Kronemann S, Kilic Y et al. Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck. Strahlenther Onkol 2009;185:675–681.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital of Rostock, Rostock, Germany

    Thomas Kuhnt MD, Ulf Klockenbrink & Guido Hildebrandt

  2. Department of Otorhinolaryngology, Head and Neck Surgery, Städtisches Klinikum Dessau, Dessau, Germany

    Stephan Knipping

  3. Department of Otorhinolaryngology, Head and Neck Surgery, Hospital Martha-Maria, Halle-Doelau, Germany

    Juergen Lautermann

  4. Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

    Karen Kriese & Steffen Hauptmann

  5. Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

    Andreas Wienke

  6. Department of Radiation Oncology, University Rostock, Suedring 75, 18059, Rostock, Germany

    Thomas Kuhnt MD

Authors
  1. Thomas Kuhnt MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ulf Klockenbrink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephan Knipping
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juergen Lautermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karen Kriese
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andreas Wienke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guido Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Steffen Hauptmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Kuhnt MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuhnt, T., Klockenbrink, U., Knipping, S. et al. Adjuvant Low Single Dose Cisplatin-based Concurrent Radiochemotherapy of Oral Cavity and Oropharynx Carcinoma. Strahlenther Onkol 187, 292–299 (2011). https://doi.org/10.1007/s00066-011-2186-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-011-2186-x

Key Words

Schlüsselwörter

Search

Navigation