Strahlentherapie und Onkologie

, Volume 185, Issue 5, pp 296–302

Outcome and Histopathologic Regression in Oral Squamous Cell Carcinoma after Preoperative Radiochemotherapy

  • Oliver Driemel
  • Tobias Ettl
  • Oliver Kölbl
  • Torsten E. Reichert
  • Bernd V. Dresp
  • Jürgen Reuther
  • Hans Pistner
Original Article

Background and Purpose:

Preoperative radiochemotherapy has been reported to enhance tumor response and to improve long-term survival in advanced squamous cell carcinoma of the head and neck. This retrospective study evaluates regression rate and long-term survival in 228 patients with primary oral squamous cell carcinoma treated by neoadjuvant radiochemotherapy and radical surgery.

Patients and Methods:

All patients with biopsy-proven, resectable oral squamous cell carcinoma – TNM stages II–IV without distant metastasis – received preoperative treatment consisting of fractioned irradiation of the primary and the regional lymph nodes with a total dose of 40 Gy and additional cisplatin (n = 160) or carboplatin (n = 68) during the 1st week of treatment. Radical surgery and neck dissection followed after a delay of 10–14 days. The study only included cases with histologically negative resection margins.

Results:

After a median follow-up of 5.2 years, 53 patients (23.2%) had experienced local-regional recurrence. The median 2-year disease-specific survival (DSS) rate was 86.2%. 5-year DSS and 10-year DSS were 76.3% and 66.7%, respectively. Complete histological local tumor regression after surgery (ypT0) was observed in 50 patients (21.9%) and was independent of pretreatment tumor classification. Uni- and multivariate survival analysis revealed that ypT- and ypN-stage were the most decisive predictors for DSS.

Conclusion:

Preoperative radiochemotherapy with cisplatin/carboplatin followed by radical surgery attains favorable long-term survival rates. This applies especially to cases with complete histological tumor regression after radiochemotherapy, which can be assumed for one of five patients.

Key Words:

Oral squamous cell carcinoma Preoperative radiochemotherapy Cis-/carboplatin Histological regression Survival 

Behandlungsergebnisse und histopathologische Regression bei oralen Plattenepithelkarzinomen nach neoadjuvanter Radiochemotherapie

Hintergrund und Ziel:

Die präoperative simultane Radiochemotherapie soll die lokale Tumorkontrolle erhöhen und das Gesamtüberleben beim Plattenepithelkarzinom des Kopf-Hals-Bereichs verbessern. Hierzu wurden retrospektiv die Regressionrate und das Langzeitüberleben bei 228 Patienten mit primären oralen Plattenepithelkarzinomen, die durch neoadjuvante Radiochemotherapie und radikale Tumorresektion behandelt wurden, untersucht.

Patienten und Methodik:

Bei 228 Patienten mit bioptisch-histologisch gesicherten, operablen oralen Plattenepithelkarzinomen – TNM-Stadien II–IV ohne Fernmetastasen (Tabelle 1) – wurde eine präoperative Bestrahlung des Primärbefunds und der regionalen Lymphknoten mit einer Gesamtdosis von 40 Gy bei zusätzlicher Gabe von Cisplatin (n = 160) oder Carboplatin (n = 68) in der 1. Woche durchgeführt. Im Anschluss folgten die radikale Tumor- und Lymphknotenresektion. In die Analyse wurden lediglich Fälle mit histologisch negativen Resektionsrändern eingeschlossen.

Ergebnisse:

Nach einer medianen Beobachtungszeit von 5,2 Jahren war es bei 53 Patienten (23,2%) zu einem Lokalrezidiv gekommen. Die mittlere tumorspezifische 2-Jahres-Überlebensrate lag bei 86,2%, das 5- und 10-Jahres-Überleben bei 76,3% bzw. 66,7% (Abbildung 1). Eine histologisch komplette lokale Tumorregression im Resektionspräparat (ypT0) konnte bei 50 Patienten (21,9%) festgestellt werden, unabhängig von der präoperativen Tumorgröße (Tabellen 2 und 3). In der uni- und multivariaten Analyse erwiesen sich ypT und ypN als wichtigste prognostische Parameter (Abbildung 2, Tabelle 4).

Schlussfolgerung:

Die präoperative Radiochemotherapie mit Cisplatin/Carboplatin und nachfolgender Tumorresektion erzielt hohe Langzeitüberlebensraten (Tabelle 5). Dies gilt insbesondere in Fällen kompletter histologischer Tumorregression nach Radiochemotherapie, welche bei einem von fünf Patienten zu beobachten ist.

Schlüsselwörter:

Orales Plattenepithelkarzinom Neoadjuvante Radiochemotherapie Cis-/Carboplatin Histologische Regression Überleben 

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References

  1. 1.
    Adelstein DJ, Li Y, Adams GL, et al. An Intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21:92–8.PubMedCrossRefGoogle Scholar
  2. 2.
    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;350:1945–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Bolke E, Gerber PA, Lammering G, et al. Development and management of severe cutaneous side effects in head-and-neck cancer patients during concurrent radiotherapy and cetuximab. Strahlenther Onkol 2008;184:105–10.PubMedCrossRefGoogle Scholar
  4. 4.
    Bottke D, Bathe K, Wiegel T, et al. Phase I trial of radiochemotherapy with bendamustine in patients with recurrent squamous cell carcinoma of the head and neck. Strahlenther Onkol 2007;183:128–32.PubMedCrossRefGoogle Scholar
  5. 5.
    Braun OM, Neumeister B, Popp W, et al. Histologic tumor regression grades in squamous cell carcinoma of the head and neck after preoperative radiochemotherapy. Cancer 1989;63:1097–100.PubMedCrossRefGoogle Scholar
  6. 6.
    Chougule PB, Suk S, Chu QD, et al. Cisplatin as a radiation sensitizer in the treatment of advanced head and neck cancers. Results of a phase II study. Cancer 1994; 74:1927–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Cohen EE, Lingen MW, Vokes EE. The expanding role of systemic therapy in head and neck cancer. J Clin Oncol 2004;22:1743–52.PubMedCrossRefGoogle Scholar
  8. 8.
    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;350:1937–44.PubMedCrossRefGoogle Scholar
  9. 9.
    Eckardt A, Rades D, Rudat V, et al. [Prospective phase II study of neoadjuvant radiochemotherapy in advanced operable carcinoma of the mouth cavity. 3-year outcome.] Mund Kiefer Gesichtschir 2002;6:117–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Eckardt A, Sinikovic B, Hofele C, et al. Preoperative paclitaxel/carboplatin radiochemotherapy for stage III/IV resectable oral and oropharyngeal cancer: seven-year follow-up of a phase II trial. Oncology 2007;73:198–203.PubMedCrossRefGoogle Scholar
  11. 11.
    Eckardt A, Wegener G, Karstens JH. [Preoperative radiochemotherapy of advanced resectable cancer of the oral cavity with cisplatin vs paclitaxel/carboplatin. Analysis of two multimodality treatment concepts.] Mund Kiefer Gesichtschir 2006;10:30–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Eich HT, Loschcke M, Scheer M, et al. Neoadjuvant radiochemotherapy and radical resection for advanced squamous cell carcinoma of the oral cavity. Outcome of 134 patients. Strahlenther Onkol 2008;184:23–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Ernst-Stecken A, Grabenbauer G, Iro H, et al. Phase II trial of hyperfractionated accelerated split-course radiochemotherapy with 5-FU and Cis-DDP in advanced head and neck cancer: results and toxicity. Strahlenther Onkol 2004;180:805–10.PubMedCrossRefGoogle Scholar
  14. 14.
    Fietkau R, Iro H, Grabenbauer GG, et al. [Simultaneous radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in advanced head and neck tumors.] Strahlenther Onkol 1991;167:693–700.PubMedGoogle Scholar
  15. 15.
    Fountzilas G, Tolis C, Kalogera-Fountzila A, et al. Induction chemotherapy with cisplatin, epirubicin, and paclitaxel (CEP), followed by concomitant radiotherapy and weekly paclitaxel for the management of locally advanced nasopharyngeal carcinoma. A Hellenic Cooperative Oncology Group phase II study. Strahlenther Onkol 2005;181:223–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Garden AS, Harris J, Vokes EE, et al. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol 2004;22:2856–64.PubMedCrossRefGoogle Scholar
  17. 17.
    Glicksman AS, Wanebo HJ, Slotman G, et al. Concurrent platinum-based chemotherapy and hyperfractionated radiotherapy with late intensification in advanced head and neck cancer. Int J Radiat Oncol Biol Phys 1997;39:721–9.PubMedGoogle Scholar
  18. 18.
    Hermann RM, Krech R, Hartlapp J, et al. [The value of qualitative regression grading as a prognostic factor for survival after preoperative radiochemotherapy in patients with advanced head and neck cancer.] Strahlenther Onkol 2001;177:277–82.PubMedCrossRefGoogle Scholar
  19. 19.
    Hoeller U, Biertz I, Flinzberg S, et al. Hyperfractionated-accelerated radiotherapy followed by radical surgery in locally advanced tumors of the oral cavity. Strahlenther Onkol 2006;182:157–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Kessler P, Grabenbauer G, Leher A, et al. [Five year survival of patients with primary oral squamous cell carcinoma. Comparison of two treatment protocols in a prospective study.] Strahlenther Onkol 2007;183:184–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Kirita T, Ohgi K, Shimooka H, et al. Preoperative concurrent chemoradiotherapy plus radical surgery for advanced squamous cell carcinoma of the oral cavity: an analysis of long-term results. Oral Oncol 1999;35:597–606.PubMedCrossRefGoogle Scholar
  22. 22.
    Klug C, Berzaczy D, Voracek M, et al. Preoperative chemoradiotherapy in the management of oral cancer: a review. J Craniomaxillofac Surg 2008;36:75–88.PubMedGoogle Scholar
  23. 23.
    Klug C, Keszthelyi D, Ploder O, et al. Neoadjuvant radiochemotherapy of oral cavity and oropharyngeal cancer: evaluation of tumor response by CT differs from histopathologic response assessment in a significant fraction of patients. Head Neck 2004;26:224–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Klug C, Wutzl A, Kermer C, et al. Preoperative radiochemotherapy and radical resection for stages II to IV oral and oropharyngeal cancer: grade of regression as crucial prognostic factor. Int J Oral Maxillofac Surg 2005;34: 262–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Koelbl O, Rosenwald A, Haberl M, et al. p53 and Ki-67 as predictive markers for radiosensitivity in squamous cell carcinoma of the oral cavity? An immunohistochemical and clinicopathologic study. Int J Radiat Oncol Biol Phys 2001;49:147–54.PubMedGoogle Scholar
  26. 26.
    Kovacs AF, Mose S, Bottcher HD, et al. Multimodality treatment including postoperative radiation and concurrent chemotherapy with weekly docetaxel is feasible and effective in patients with oral and oropharyngeal cancer. Strahlenther Onkol 2005;181:26–34.PubMedCrossRefGoogle Scholar
  27. 27.
    Kuhnt T, Becker A, Pigorsch S, et al. Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I–II trial. Strahlenther Onkol 2003;179:673–81.PubMedCrossRefGoogle Scholar
  28. 28.
    Kunkel M, Forster GJ, Reichert TE, et al. Radiation response non-invasively imaged by [18F]FDG-PET predicts local tumor control and survival in advanced oral squamous cell carcinoma. Oral Oncol 2003;39:170–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Lavertu P, Adelstein DJ, Saxton JP, et al. Management of the neck in a randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer. Head Neck 1997;19:559–66.PubMedCrossRefGoogle Scholar
  30. 30.
    Lavertu P, Adelstein DJ, Saxton JP, et al. Aggressive concurrent chemoradiotherapy for squamous cell head and neck cancer: an 8-year single-institution experience. Arch Otolaryngol Head Neck Surg 1999;125:142–8.PubMedGoogle Scholar
  31. 31.
    Mohr C, Bohndorf W, Carstens J, et al. Preoperative radiochemotherapy and radical surgery in comparison with radical surgery alone. A prospective, multicentric, randomized DÖSAK study of advanced squamous cell carcinoma of the oral cavity and the oropharynx (a 3-year follow-up). Int J Oral Maxillofac Surg 1994;23:140–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Mucke R, Blynow M, Ziegler PG, et al. [Simultaneous radiochemotherapy with carboplatin in patients with inoperable advanced stage III and IV head and neck tumors.] Strahlenther Onkol 1999;175:213–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Onizawa K, Yoshida H, Ohara K, et al. Predictive factors for the histologic response to preoperative radiotherapy in advanced oral cancer. J Oral Maxillofac Surg 2006;64:81–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Pignon JP, Bourhis J, Domenge C, et al. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000;355:949–55.PubMedGoogle Scholar
  35. 35.
    Reuther T, Posselt NK, Rabbels J, et al. [Oral squamous cell carcinoma. Retrospective analysis of therapy results and prognosis by neoadjuvant, preoperative radiochemotherapy.] Mund Kiefer Gesichtschir 2006;10:18–29.PubMedCrossRefGoogle Scholar
  36. 36.
    Schultze J, Schillmoller H, Roldan JC, et al. [Preoperative radiochemotherapy for advanced oral cavity tumours: the Kiel DÖSAK experience regarding curability and quality of life.] Mund Kiefer Gesichtschir 2006;10:249–57.PubMedCrossRefGoogle Scholar
  37. 37.
    Schutze C, Dorfler A, Eicheler W, et al. Combination of EGFR/HER2 tyrosine kinase inhibition by BIBW 2992 and BIBW 2669 with irradiation in FaDu human squamous cell carcinoma. Strahlenther Onkol 2007;183:256–64.PubMedCrossRefGoogle Scholar
  38. 38.
    Slotman GJ, Doolittle CH, Glicksman AS. Preoperative combined chemotherapy and radiation therapy plus radical surgery in advanced head and neck cancer. Five-year results with impressive complete response rates and high survival. Cancer 1992;69:2736–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Soulieres D, Senzer NN, Vokes EE, et al. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol 2004;22:77–85.PubMedCrossRefGoogle Scholar
  40. 40.
    Suntharalingam M, Haas ML, Van Echo DA, et al. Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck. Cancer 2001;91:548–54.PubMedCrossRefGoogle Scholar
  41. 41.
    Wanebo H, Chougule P, Ready N, et al. Surgical resection is necessary to maximize tumor control in function-preserving, aggressive chemoradiation protocols for advanced squamous cancer of the head and neck (stage III and IV). Ann Surg Oncol 2001;8:644–50.PubMedCrossRefGoogle Scholar
  42. 42.
    Wendt TG, Grabenbauer GG, Rodel CM, et al. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol 1998;16:1318–24.PubMedGoogle Scholar
  43. 43.
    Zamboglou N, Pape H, Schnabel T, et al. [Combined radiotherapy with cis- or carboplatin in advanced head and neck tumors.] Strahlenther Onkol 1989;165:647–51.PubMedGoogle Scholar

Copyright information

© Urban & Vogel, Muenchen 2009

Authors and Affiliations

  • Oliver Driemel
    • 1
    • 5
  • Tobias Ettl
    • 1
  • Oliver Kölbl
    • 2
  • Torsten E. Reichert
    • 1
  • Bernd V. Dresp
    • 3
  • Jürgen Reuther
    • 3
  • Hans Pistner
    • 4
  1. 1.Department of Oral and Maxillofacial SurgeryUniversity Hospital RegensburgRegensburgGermany
  2. 2.Department of RadiotherapyUniversity Hospital RegensburgRegensburgGermany
  3. 3.Department of Oral and Maxillofacial SurgeryUniversity Hospital WürzburgWürzburgGermany
  4. 4.Department of Oral and Maxillofacial SurgeryHelios Hospital ErfurtErfurtGermany
  5. 5.Klinik und Poliklinik für Mund-, Kiefer- und GesichtschirurgieKlinikum der Universität RegensburgRegensburgGermany

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