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Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Research

Long term results of postoperative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of Squamous Cell Carcinoma (SCC) located in the oropharynx or oral cavity

Authors: M. Hoffmann, L. Saleh-Ebrahimi, F. Zwicker, P. Haering, A. Schwahofer, J. Debus, P.E. Huber, F. Roeder

Published in: Radiation Oncology | Issue 1/2015

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Abstract

Background

To report our long-term results with postoperative intensity-modulated radiation therapy (IMRT) in patients suffering from squamous-cell carcinoma (SCC) of the oral cavity or oropharynx.

Methods

Seventy five patients were retrospectively analyzed. Median age was 58 years and 84 % were male. 76 % of the primaries were located in the oropharynx. Surgery resulted in negative margins (R0) in 64 % of the patients while 36 % suffered from positive margins (R1). Postoperative stages were as follows: stage1:4 %, stage2:9 %, stage3:17 %, stage4a:69 % with positive nodes in 84 %. Perineural invasion (Pn+) and extracapsular extension (ECE) were present in 7 % and 29 %, respectively. All patients received IMRT using the step-and-shoot approach with a simultaneously integrated boost (SIB) in 84 %. Concurrent systemic therapy was applied to 53 patients, mainly cisplatin weekly.

Results

Median follow-up was 55 months (5–150). 13 patients showed locoregional failures (4 isolated local, 4 isolated neck, 5 combined) transferring into 5-year-LRC rates of 85 %. Number of positive lymph nodes (n > 2) and presence of ECE were significantly associated with decreased LRC in univariate analysis, but only the number of nodes remained significant in multivariate analysis. Overall treatment failures occurred in 20 patients (9 locoregional only, 7 distant only, 4 combined), transferring into 3-and 5-year-FFTF rates of 77 % and 75 %, respectively. The 3-and 5-year-OS rates were 80 % and 72 %, respectively. High clinical stage, high N stage, number of positive nodes (n > 2), ECE and Pn1 were significantly associated with worse FFTF and OS in univariate analysis, but only number of nodes remained significant for FFTF in multivariate analysis. Maximum acute toxicity was grade 3 in 64 % and grade 4 in 1 %, mainly hematological or mucositis/dysphagia. Maximum late toxicity was grade 3 in 23 % of the patients, mainly long-term tube feeding dependency.

Conclusion

Postoperative IMRT achieved excellent LRC and good OS with acceptable acute and low late toxicity rates. The number of positive nodes (n > 2) was a strong prognostic factor for all endpoints in univariate and the only significant factor for LRC and FFTF in multivariate analysis. Patients with feeding tubes due to postoperative complications had an increased risk for long-term feeding tube dependency.
Literature
2.
go back to reference De Felice F, Musio D, Terenz V, Valentini V, Cassoni A, Tombolini M, et al. Treatment improvement and better patient care: which is the most important one in oral cavity cancer? Radiat Oncol. 2014;9:263.PubMedCentralCrossRefPubMed De Felice F, Musio D, Terenz V, Valentini V, Cassoni A, Tombolini M, et al. Treatment improvement and better patient care: which is the most important one in oral cavity cancer? Radiat Oncol. 2014;9:263.PubMedCentralCrossRefPubMed
3.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350:1945–52.CrossRefPubMed Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350:1945–52.CrossRefPubMed
5.
go back to reference Collan J, Lundberg M, Vaalavirta L, Bäck L, Kajanti M, Mäkitie A, et al. Patterns of relapse following surgery and postoperative intensity modulated radiotherapy for oral and oropharyngeal cancer. Acta Oncol. 2011;50:1119–25.CrossRefPubMed Collan J, Lundberg M, Vaalavirta L, Bäck L, Kajanti M, Mäkitie A, et al. Patterns of relapse following surgery and postoperative intensity modulated radiotherapy for oral and oropharyngeal cancer. Acta Oncol. 2011;50:1119–25.CrossRefPubMed
6.
go back to reference Bernier J, Cooper JS, Pajak TF, Van Glabbeke M, Bourhis J, Forastiere A, 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;27:843–50.CrossRefPubMed Bernier J, Cooper JS, Pajak TF, Van Glabbeke M, Bourhis J, Forastiere A, 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;27:843–50.CrossRefPubMed
7.
8.
go back to reference Daly ME, Le QT, Maxim PG, Loo BW, Kaplan MJ, Fischbein NJ, et al. Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. Int J Radiat Oncol Biol Phys. 2010;76:1339–46.CrossRefPubMed Daly ME, Le QT, Maxim PG, Loo BW, Kaplan MJ, Fischbein NJ, et al. Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. Int J Radiat Oncol Biol Phys. 2010;76:1339–46.CrossRefPubMed
9.
go back to reference Bastos de Souza TR, Pinto CA, Da Cunha Mercante AM, Nishimoto IN, Brasilino de Carvalho M, Kowalski LP. Long-term results of surgical treatment for advanced oropharyngeal squamous cell carcinoma. Head Neck. 2014;36:1146–54.CrossRefPubMed Bastos de Souza TR, Pinto CA, Da Cunha Mercante AM, Nishimoto IN, Brasilino de Carvalho M, Kowalski LP. Long-term results of surgical treatment for advanced oropharyngeal squamous cell carcinoma. Head Neck. 2014;36:1146–54.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference Wang ZH, Yan C, Zhang CP, Hu HS, Tu WY, Kirwan J, et al. Outcomes and xerostomia after postoperative radiotherapy for oral and oropharyngeal carcinoma. Head Neck. 2014;36:1467–73.CrossRefPubMed Wang ZH, Yan C, Zhang CP, Hu HS, Tu WY, Kirwan J, et al. Outcomes and xerostomia after postoperative radiotherapy for oral and oropharyngeal carcinoma. Head Neck. 2014;36:1467–73.CrossRefPubMed
12.
go back to reference Gupta T, Agarwal J, Jain S, Phurailatpam R, Kannan S, Ghosh-Laskar S, et al. Three-dimensional conformal radiotherapy (3D-CRT) versus intensity-modulated radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: a randomized controlled trial. Radiother Oncol. 2012;104:343–8.CrossRefPubMed Gupta T, Agarwal J, Jain S, Phurailatpam R, Kannan S, Ghosh-Laskar S, et al. Three-dimensional conformal radiotherapy (3D-CRT) versus intensity-modulated radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: a randomized controlled trial. Radiother Oncol. 2012;104:343–8.CrossRefPubMed
13.
go back to reference Nutting CM, Morden JP, Harrington KJ, Urbao TG, Bhide SA, Clark C, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011;12:127–36.PubMedCentralCrossRefPubMed Nutting CM, Morden JP, Harrington KJ, Urbao TG, Bhide SA, Clark C, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011;12:127–36.PubMedCentralCrossRefPubMed
14.
go back to reference Saleh-Ebrahimi L, Zwicker F, Muenter MW, Bischof M, Lindel K, Debus J, et al. Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer–a retrospective single center analysis. Radiat Oncol. 2013;8:20.PubMedCentralCrossRefPubMed Saleh-Ebrahimi L, Zwicker F, Muenter MW, Bischof M, Lindel K, Debus J, et al. Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer–a retrospective single center analysis. Radiat Oncol. 2013;8:20.PubMedCentralCrossRefPubMed
15.
go back to reference Roeder F, Ullrich A, Habl G, Uhl M, Saleh-Ebrahimi L, Huber PE, et al. Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis. BMC Cancer. 2014;14:617.PubMedCentralCrossRefPubMed Roeder F, Ullrich A, Habl G, Uhl M, Saleh-Ebrahimi L, Huber PE, et al. Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis. BMC Cancer. 2014;14:617.PubMedCentralCrossRefPubMed
16.
go back to reference Roeder F, Nicolay NH, Nguyen T, Saleh-Ebrahimi L, Askoxylakis V, Bostel T, et al. Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer. Radiat Oncol. 2014;9:191.PubMedCentralCrossRefPubMed Roeder F, Nicolay NH, Nguyen T, Saleh-Ebrahimi L, Askoxylakis V, Bostel T, et al. Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer. Radiat Oncol. 2014;9:191.PubMedCentralCrossRefPubMed
17.
18.
go back to reference Münter MW, Thilmann C, Hof H, Didinger B, Rhein B, Nill S, et al. Stereotactic intensity modulated radiation therapy and inverse treatment planning for tumors of the head and neck region: clinical implementation of the step and shoot approach and first clinical results. Radiother Oncol. 2003;66:313–21.CrossRefPubMed Münter MW, Thilmann C, Hof H, Didinger B, Rhein B, Nill S, et al. Stereotactic intensity modulated radiation therapy and inverse treatment planning for tumors of the head and neck region: clinical implementation of the step and shoot approach and first clinical results. Radiother Oncol. 2003;66:313–21.CrossRefPubMed
19.
go back to reference Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31:1341–6.CrossRefPubMed Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31:1341–6.CrossRefPubMed
20.
go back to reference Chen AM, Farwell DG, Luu Q, Chen LM, Vijayakumar S, Purdy JA. Marginal misses after postoperative intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2011;80:1423–9.CrossRefPubMed Chen AM, Farwell DG, Luu Q, Chen LM, Vijayakumar S, Purdy JA. Marginal misses after postoperative intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2011;80:1423–9.CrossRefPubMed
21.
go back to reference Hua YH, Hu QY, Piao YF, Tang Q, Fu ZF. Effect of number and ratio of positive lymph nodes in hypopharyngeal cancer. Head Neck. 2014;37:111–6.CrossRefPubMed Hua YH, Hu QY, Piao YF, Tang Q, Fu ZF. Effect of number and ratio of positive lymph nodes in hypopharyngeal cancer. Head Neck. 2014;37:111–6.CrossRefPubMed
22.
go back to reference Wan XC, Egloff AM, Johnson J. Histological assessment of cervical lymph node identifies patients with head and neck squamous cell carcinoma (HNSCC): Who would benefit from chemoradiation after surgery? Laryngoscope. 2012;122:2712–22.PubMedCentralCrossRefPubMed Wan XC, Egloff AM, Johnson J. Histological assessment of cervical lymph node identifies patients with head and neck squamous cell carcinoma (HNSCC): Who would benefit from chemoradiation after surgery? Laryngoscope. 2012;122:2712–22.PubMedCentralCrossRefPubMed
23.
go back to reference Geretschläger A, Bojaxhiu B, Crowe S, Arnold A, Manser P, Hallerman W, et al. Outcome and patterns of failure after postoperative intensity modulated radiotherapy for locally advanced or high-risk oral cavity squamous cell carcinoma. Radiat Oncol. 2012;7:175.PubMedCentralCrossRefPubMed Geretschläger A, Bojaxhiu B, Crowe S, Arnold A, Manser P, Hallerman W, et al. Outcome and patterns of failure after postoperative intensity modulated radiotherapy for locally advanced or high-risk oral cavity squamous cell carcinoma. Radiat Oncol. 2012;7:175.PubMedCentralCrossRefPubMed
24.
go back to reference Verma V, Liu J, Eschen L, Danieley J, Spencer C, Lewis JS, et al. Pre-radiotherapy feeding tube identifies a poor prognostic subset of postoperative p16 positive oropharyngeal carcinoma patients. Radiat Oncol. 2015;10:8.PubMedCentralCrossRefPubMed Verma V, Liu J, Eschen L, Danieley J, Spencer C, Lewis JS, et al. Pre-radiotherapy feeding tube identifies a poor prognostic subset of postoperative p16 positive oropharyngeal carcinoma patients. Radiat Oncol. 2015;10:8.PubMedCentralCrossRefPubMed
25.
go back to reference Wiggenraad RG, Flierman L, Goosens A, Brand R, Verschuur HP, Croll GA, et al. Prophylactic gastrostomy placement and early tube feeding may limit loss of weight during chemoradiotherapy for advanced head and neck cancer, a preliminary study. Clin Otolaryngol. 2007;32:384–90.CrossRefPubMed Wiggenraad RG, Flierman L, Goosens A, Brand R, Verschuur HP, Croll GA, et al. Prophylactic gastrostomy placement and early tube feeding may limit loss of weight during chemoradiotherapy for advanced head and neck cancer, a preliminary study. Clin Otolaryngol. 2007;32:384–90.CrossRefPubMed
26.
go back to reference Silander E, Nyman J, Bove M, Johansson L, Larrson S, Hammerlid E. Impact of prophylactic percutaneous endoscopic gastrostomy on malnutrition and quality of life in patients with head and neck cancer: a randomized study. Head Neck. 2012;34:1–9.CrossRefPubMed Silander E, Nyman J, Bove M, Johansson L, Larrson S, Hammerlid E. Impact of prophylactic percutaneous endoscopic gastrostomy on malnutrition and quality of life in patients with head and neck cancer: a randomized study. Head Neck. 2012;34:1–9.CrossRefPubMed
27.
go back to reference Cady J. Nutritional support during radiotherapy for head and neck cancer: the role of prophylactic feeding tube placement. Clin J Oncol Nurs. 2007;11:875–80.CrossRefPubMed Cady J. Nutritional support during radiotherapy for head and neck cancer: the role of prophylactic feeding tube placement. Clin J Oncol Nurs. 2007;11:875–80.CrossRefPubMed
28.
go back to reference Madhoun MF, Blankenship MM, Blankenship DM, Krempl GA, Tierney WM. Prophylactic PEG placement in head and neck cancer: how many feeding tubes are unused (and unnecessary)? World J Gastroenterol. 2011;17:1004–8.PubMedCentralCrossRefPubMed Madhoun MF, Blankenship MM, Blankenship DM, Krempl GA, Tierney WM. Prophylactic PEG placement in head and neck cancer: how many feeding tubes are unused (and unnecessary)? World J Gastroenterol. 2011;17:1004–8.PubMedCentralCrossRefPubMed
29.
go back to reference Mclaughlin BT, Gokhale AS, Shuai Y, Diacopulos J, Carrau R, Heron DE, et al. Management of patients treated with chemoradiotherapy for head and neck cancer without prophylactic feeding tubes: the university of Pittsburgh experience. Laryngoscope. 2010;120:71–5.CrossRefPubMed Mclaughlin BT, Gokhale AS, Shuai Y, Diacopulos J, Carrau R, Heron DE, et al. Management of patients treated with chemoradiotherapy for head and neck cancer without prophylactic feeding tubes: the university of Pittsburgh experience. Laryngoscope. 2010;120:71–5.CrossRefPubMed
30.
go back to reference Chen AM, Li BQ, Jenelle RL, Lau DH, Yang CC, Courquin J, et al. Late esophageal toxicity after radiation therapy for head and neck cancer. Head Neck. 2010;32:178–83.CrossRefPubMed Chen AM, Li BQ, Jenelle RL, Lau DH, Yang CC, Courquin J, et al. Late esophageal toxicity after radiation therapy for head and neck cancer. Head Neck. 2010;32:178–83.CrossRefPubMed
31.
go back to reference Shaw SM, Flowers H, O’Sullivan B, Hope A, Liu LW, Martino R. The effect of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement on swallowing and swallow-related outcomes in patients undergoing radiotherapy for head and neck cancer: a systematic review. Dysphagia. 2015;30:152–75.CrossRefPubMed Shaw SM, Flowers H, O’Sullivan B, Hope A, Liu LW, Martino R. The effect of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement on swallowing and swallow-related outcomes in patients undergoing radiotherapy for head and neck cancer: a systematic review. Dysphagia. 2015;30:152–75.CrossRefPubMed
32.
go back to reference Münter MW, Karger CP, Hoffner G, Hof H, Thilmann C, Rudat V, et al. Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys. 2004;58:175–84.CrossRefPubMed Münter MW, Karger CP, Hoffner G, Hof H, Thilmann C, Rudat V, et al. Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys. 2004;58:175–84.CrossRefPubMed
33.
go back to reference Münter MW, Hoffner S, Hof H, Herfarth KK, Haberkorn U, Rudat V, et al. Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without amifostine. Int J Radiat Oncol Biol Phys. 2007;67:651–9.CrossRefPubMed Münter MW, Hoffner S, Hof H, Herfarth KK, Haberkorn U, Rudat V, et al. Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without amifostine. Int J Radiat Oncol Biol Phys. 2007;67:651–9.CrossRefPubMed
34.
go back to reference Spiotto M, Weichselbaum RR. Comparison of 3D conformal radiotherapy and intensity modulated radiotherapy with or without simultaneous integrated boost during concurrent chemoradiation for locally advanced head and neck cancers. Plos one. 2014;9, e94456.PubMedCentralCrossRefPubMed Spiotto M, Weichselbaum RR. Comparison of 3D conformal radiotherapy and intensity modulated radiotherapy with or without simultaneous integrated boost during concurrent chemoradiation for locally advanced head and neck cancers. Plos one. 2014;9, e94456.PubMedCentralCrossRefPubMed
Metadata
Title
Long term results of postoperative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of Squamous Cell Carcinoma (SCC) located in the oropharynx or oral cavity
Authors
M. Hoffmann
L. Saleh-Ebrahimi
F. Zwicker
P. Haering
A. Schwahofer
J. Debus
P.E. Huber
F. Roeder
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0561-y

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