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Low-Dose Preoperative Chemoradiation Therapy Compared with Surgery Alone with or Without Postoperative Radiotherapy in Patients with Head and Neck Carcinoma

  • Head and Neck Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Several multimodal strategies have been developed to treat patients with squamous cell carcinoma of the oral cavity (OSCC), and many have shown survival benefits. The theoretical advantages of preoperative chemoradiotherapy are downstaging of the primary tumor, an increased resectability rate, and the elimination of micrometastases. We aimed to assess whether a short low-dose preoperative radiotherapy regimen with concurrent low-dose chemotherapy with cisplatin improves outcomes for patients with OSCC undergoing surgical treatment with curative intent.

Methods

A total of 407 patients received preoperative low-dose radiotherapy of 20 Gy given in 10 fractions with concurrent low-dose chemotherapy with cisplatin (12.5 mg/m2) as part of a pre-existing protocol. This was compared with 519 patients receiving surgery alone. Endpoints were overall survival, tumor response, and toxic effects. Analysis was controlled for tumor-related and demographic factors.

Results

After controlling for age, tumor stage, nodal stage, tumor grade, recurrence, and resection margin status, which were independent and dependent predictors of survival, preoperative radiotherapy was associated with improved survival [0.79; P = 0.002; 95% confidence interval (95% CI), 0.66–0.96], in patients receiving only preoperative radiation therapy or in combination with/without postoperative radiotherapy (1.31; P = 0.041; 95% CI, 1.01–1.70 with postoperative radiotherapy; 1.40; P = 0.039; 95% CI, 1.01–1.85 without postoperative radiotherapy).

Conclusions

Low-dose preoperative radiotherapy combined with low-dose chemotherapy with cisplatin significantly improves overall survival for patients with resectable OSCC compared with surgery alone.

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References

  1. Cunningham MJ, Johnson JT, Myers EN, Schramm VL Jr, Thearle PB. Cervical lymph node metastasis after local excision of early squamous cell carcinoma of the oral cavity. Am J Surg. 1986;152:361–6.

    Article  PubMed  CAS  Google Scholar 

  2. Chang HW, Ling GS, Wei WI, Yuen AP. Smoking and drinking can induce p15 methylation in the upper aerodigestive tract of healthy individuals and patients with head and neck squamous cell carcinoma. Cancer. 2004;101:125–32.

    Article  PubMed  Google Scholar 

  3. Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med. 2001;345:1890–900.

    Article  PubMed  CAS  Google Scholar 

  4. Pignon JP, Bourhis J, Domenge C, Designé L. 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.

    PubMed  CAS  Google Scholar 

  5. Shah JP, Gil Z. Current concepts in management of oral cancer–surgery. Oral Oncol. 2009;45:394–401.

    Article  PubMed  Google Scholar 

  6. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, 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.

    Article  PubMed  Google Scholar 

  7. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091–8.

    Article  PubMed  CAS  Google Scholar 

  8. Parsons JT, Mendenhall WM, Stringer SP, Cassisi NJ, Million RR. An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity. Int J Radiat Oncol Biol Phys. 1997;39:137–48.

    PubMed  CAS  Google Scholar 

  9. Shingaki S, Takada M, Sasai K, Bibi R, Kobayashi T, Nomura T, et al. Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas. Am J Surg. 2003;185:278–84.

    Article  PubMed  Google Scholar 

  10. Mücke T, Wolff KD, Wagenpfeil S, Mitchell DA, Hölzle F. Immediate microsurgical reconstruction after tumor ablation predicts survival among patients with head and neck carcinoma. Ann Surg Oncol. 2010;17:287–95.

    Article  PubMed  Google Scholar 

  11. Kirita T, Ohgi K, Shimooka H, Yamanaka Y, Tatebayashi S, Yamamoto K, 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.

    Article  PubMed  CAS  Google Scholar 

  12. Lindholm P, Valavaara R, Aitasalo K, Kulmala J, Laine J, Elomaa L, et al. Preoperative hyperfractionated accelerated radiotherapy and radical surgery in advanced head and neck cancer: a prospective phase II study. Radiother Oncol. 2006;78:146–51.

    Article  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Wanebo HJ, Chougule P, Akerley WL III, Koness RJ, McRae R, Nigri P, et al. Preoperative chemoradiation coupled with aggressive resection as needed ensures near total control in advanced head and neck cancer. Am J Surg. 1997;174:518–22.

    Article  PubMed  CAS  Google Scholar 

  15. Wanebo HJ, Glicksman AS, Landman C, Slotman G, Doolittle C, Clark J, et al. Preoperative cisplatin and accelerated hyperfractionated radiation induces high tumor response and control rates in patients with advanced head and neck cancer. Am J Surg. 1995;170:512–6.

    Article  PubMed  CAS  Google Scholar 

  16. Mücke T, Wagenpfeil S, Kesting MR, Hölzle F, Wolff KD. Recurrence interval affects survival after local relapse of oral cancer. Oral Oncol. 2009;45:687–91.

    Article  PubMed  Google Scholar 

  17. Poulsen MG, Denham JW, Peters LJ, Lamb DS, Spry NA, Hindley A, et al. A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study. Radiother Oncol. 2001;60:113–22.

    Article  PubMed  CAS  Google Scholar 

  18. Dische S. The uniform reporting of treatment-related morbidity. Semin Radiat Oncol. 1994;4:112–8.

    Article  PubMed  Google Scholar 

  19. Eich HT, Loschcke M, Scheer M, Kocher M, Bongartz R, Wacker S, 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.

    Article  PubMed  Google Scholar 

  20. Chen YK, Huang HC, Lin LM, Lin CC. Primary oral squamous cell carcinoma: an analysis of 703 cases in southern Taiwan. Oral Oncol. 1999;35:173–9.

    Article  PubMed  CAS  Google Scholar 

  21. Gonzalez-Moles MA, Esteban F, Rodriguez-Archilla A, Ruiz-Avila I, Gonzalez-Moles S. Importance of tumour thickness measurement in prognosis of tongue cancer. Oral Oncol. 2002;38:394–7.

    Article  PubMed  Google Scholar 

  22. Hibbert J, Marks NJ, Winter PJ, Shaheen OH. Prognostic factors in oral squamous carcinoma and their relation to clinical staging. Clin Otolaryngol Allied Sci. 1983;8:197–203.

    Article  PubMed  CAS  Google Scholar 

  23. Koo BS, Lim YC, Lee JS, Choi EC. Recurrence and salvage treatment of squamous cell carcinoma of the oral cavity. Oral Oncol. 2006;42:789–94.

    Article  PubMed  Google Scholar 

  24. Levy R, Segal K, Hadar T, Shvero J, Abraham A. Squamous cell carcinoma of the oral tongue. Eur J Surg Oncol. 1991;17:330–4.

    PubMed  CAS  Google Scholar 

  25. Rogers SN, Brown JS, Woolgar JA, Lowe D, Magennis P, Shaw RJ, et al. Survival following primary surgery for oral cancer. Oral Oncol. 2008;45:201–11.

    Article  PubMed  Google Scholar 

  26. Mücke T, Loeffelbein DJ, Hohlweg-Majert B, Kesting MR, Wolff KD, Hölzle F. Reconstruction of the maxilla and midface—surgical management, outcome, and prognostic factors. Oral Oncol. 2009;45:1073–8.

    Article  PubMed  Google Scholar 

  27. Dobrowsky W, Dobrowsky E, Strassl H, Braun O, Scheiber V. Response to preoperative concomitant radiochemotherapy with mitomycin C and 5-fluorouracil in advanced head and neck cancer. Eur J Cancer Clin Oncol. 1989;25:845–9.

    Article  PubMed  CAS  Google Scholar 

  28. Kessler P, Grabenbauer G, Leher A, Bloch-Birkholz A, Vairaktaris E, Neukam FW, 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.

    Article  PubMed  Google Scholar 

  29. Klug C, Wutzl A, Kermer C, Voracek M, Kornek G, Selzer E, et al. Preoperative radiochemotherapy and radical resection for stages II–IV oral and oropharyngeal cancer: outcome of 222 patients. Int J Oral Maxillofac Surg. 2005;34:143–8.

    Article  PubMed  CAS  Google Scholar 

  30. Mohr C, Bohndorf W, Carstens J, Härle F, Hausamen JE, Hirche H, et al. Preoperative radiochemotherapy and radical surgery in comparison with radical surgery alone. A prospective, multicentric, randomized DOSAK 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.

    Article  PubMed  CAS  Google Scholar 

  31. Wanebo H, Chougule P, Ready N, Safran H, Ackerley W, Koness RJ, 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.

    Article  PubMed  CAS  Google Scholar 

  32. Klug C, Wutzl A, Kermer C, Ploder O, Sulzbacher I, Selzer E, 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.

    Article  PubMed  CAS  Google Scholar 

  33. Schultze J, Schillmoller H, Roldan JC, Wiltfang J, Kimmig B. Preoperative radiochemotherapy for advanced oral cavity tumours: the Kiel DOSAK experience regarding curability and quality of life. Mund Kiefer Gesichtschir. 2006;10:249–57.

    Article  PubMed  Google Scholar 

  34. Muller RP, Staar S, Samek M, Pape HD. Simultaneous preoperative radiochemotherapy with cisplatin in advanced oral cavity carcinomas: acute response and follow-up. Recent Results Cancer Res. 1994;134:165–72.

    PubMed  CAS  Google Scholar 

  35. Freier K, Engel M, Lindel K, Flechtenmacher C, Mühling J, Hassfeld S, et al. Neoadjuvant concurrent radiochemotherapy followed by surgery in advanced oral squamous cell carcinoma (OSCC): a retrospective analysis of 207 patients. Oral Oncol. 2008;44:116–23.

    Article  PubMed  CAS  Google Scholar 

  36. Giralt JL, Gonzalez J, del Campo JM, Maldonado J, Sanz X, Pamias J, et al. Preoperative induction chemotherapy followed by concurrent chemoradiotherapy in advanced carcinoma of the oral cavity and oropharynx. Cancer. 2000;89:939–45.

    Article  PubMed  CAS  Google Scholar 

  37. Henry LR, Goldberg M, Scott W, Konski A, Meropol NJ, Freedman G, et al. Induction cisplatin and paclitaxel followed by combination chemoradiotherapy with 5-fluorouracil, cisplatin, and paclitaxel before resection in localized esophageal cancer: a phase II report. Ann Surg Oncol. 2006;13:214–20.

    Article  PubMed  Google Scholar 

  38. Willett CG, Warland G, Hagan MP, Daly WJ, Coen J, Shellito PC, et al. Tumor proliferation in rectal cancer following preoperative irradiation. J Clin Oncol. 1995;13:1417–24.

    PubMed  CAS  Google Scholar 

  39. Jellema AP, Doornaert P, Slotman BJ, Leemans CR, Langendijk JA. Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy? Radiother Oncol. 2005;77:164–71.

    Article  PubMed  Google Scholar 

  40. Jen YM, Lin YC, Wang YB, Wu DM. Dramatic and prolonged decrease of whole salivary secretion in nasopharyngeal carcinoma patients treated with radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:322–7.

    Article  PubMed  Google Scholar 

  41. Nguyen LN, Ang KK. Radiotherapy for cancer of the head and neck: altered fractionation regimens. Lancet Oncol. 2002;3:693–701.

    Article  PubMed  Google Scholar 

  42. Schultze-Mosgau S, Grabenbauer GG, Radespiel-Troger M, Wiltfang J, Ries J, Neukam FW, et al. Vascularization in the transition area between free grafted soft tissues and pre-irradiated graft bed tissues following preoperative radiotherapy in the head and neck region. Head Neck. 2002;24:42–51.

    Article  PubMed  Google Scholar 

  43. Schultze-Mosgau S, Grabenbauer GG, Wehrhan F, Radespiel-Tröger M, Wiltfang J, Sauer R, et al. Histomorphological structural changes of head and neck blood vessels after pre- or postoperative radiotherapy. Strahlenther Onkol. 2002;178:299–306.

    Article  PubMed  Google Scholar 

  44. Tsao AS, Garden AS, Kies MS, Morrison W, Feng L, Lee JJ, et al. Phase I/II study of docetaxel, cisplatin, and concomitant boost radiation for locally advanced squamous cell cancer of the head and neck. J Clin Oncol. 2006;24:4163–9.

    Article  PubMed  CAS  Google Scholar 

  45. Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortés-Funes H, Hitt R, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005;23:5568–77.

    Article  PubMed  CAS  Google Scholar 

  46. Schena M, Barone C, Birocco N, Dongiovanni D, Numico G, Colantonio I, et al. Weekly cisplatin paclitaxel and continuous infusion fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma: a phase II study. Cancer Chemother Pharmacol. 2005;55:271–6.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Technische Universität München, Klinikum Rechts der Isar, München, Germany

    Thomas Mücke MD, Mario Konen MD, Marco R. Kesting MD, DDS, PhD, Klaus-Dietrich Wolff MD, DDS, PhD & Frank Hölzle MD, DDS, PhD

  2. Institute for Medical Statistics and Epidemiology, Technische Universität München, München, Germany

    Stefan Wagenpfeil MSc, PhD

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  1. Thomas Mücke MD
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  2. Mario Konen MD
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  3. Stefan Wagenpfeil MSc, PhD
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  4. Marco R. Kesting MD, DDS, PhD
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  6. Frank Hölzle MD, DDS, PhD
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Correspondence to Thomas Mücke MD.

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Mücke, T., Konen, M., Wagenpfeil, S. et al. Low-Dose Preoperative Chemoradiation Therapy Compared with Surgery Alone with or Without Postoperative Radiotherapy in Patients with Head and Neck Carcinoma. Ann Surg Oncol 18, 2739–2747 (2011). https://doi.org/10.1245/s10434-011-1643-1

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