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Erschienen in: Strahlentherapie und Onkologie 8/2018

17.05.2018 | Original Article

Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy

verfasst von: Timo Carpén, MD, Kauko Saarilahti, Caj Haglund, Antti Markkola, Jussi Tarkkanen, Jaana Hagström, Petri Mattila, Antti Mäkitie

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 8/2018

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Abstract

Purpose

To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients.

Methods

The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC).

Results

pGTV was a significant independent prognostic factor for overall survival (OS; p = 0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III–IVc) p16-negative tumors were only associated with significantly poorer OS (p = 0.046) but not with poorer LRC or DFS when compared with the low-stage (I–II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p = 0.005) and LRC (p = 0.007) in multivariate analyses.

Conclusion

pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.
Literatur
3.
Zurück zum Zitat Lok BH, Setton J, Caria N, Romanyshyn J, Wolden SL, Zelefsky MJ, Park J, Rowan N, Sherman EJ, Fury MG, Ho A, Pfister DG, Wong RJ, Shah JP, Kraus DH, Zhang Z, Schupak KD, Gelblum DY, Rao SD, Lee NY (2012) Intensity-modulated radiation therapy in oropharyngeal carcinoma: effect of tumor volume on clinical outcomes. Int J Radiat Oncol Biol Phys 82(5):1851–1857. https://doi.org/10.1016/j.ijrobp.2011.03.029 CrossRefPubMed Lok BH, Setton J, Caria N, Romanyshyn J, Wolden SL, Zelefsky MJ, Park J, Rowan N, Sherman EJ, Fury MG, Ho A, Pfister DG, Wong RJ, Shah JP, Kraus DH, Zhang Z, Schupak KD, Gelblum DY, Rao SD, Lee NY (2012) Intensity-modulated radiation therapy in oropharyngeal carcinoma: effect of tumor volume on clinical outcomes. Int J Radiat Oncol Biol Phys 82(5):1851–1857. https://​doi.​org/​10.​1016/​j.​ijrobp.​2011.​03.​029 CrossRefPubMed
5.
Zurück zum Zitat Linge A, Lohaus F, Lock S, Nowak A, Gudziol V, Valentini C, von Neubeck C, Jutz M, Tinhofer I, Budach V, Sak A, Stuschke M, Balermpas P, Rodel C, Grosu AL, Abdollahi A, Debus J, Ganswindt U, Belka C, Pigorsch S, Combs SE, Monnich D, Zips D, Buchholz F, Aust DE, Baretton GB, Thames HD, Dubrovska A, Alsner J, Overgaard J, Krause M, Baumann M, DKTK-ROG (2016) HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Radiother Oncol 121(3):364–373. https://doi.org/10.1016/j.radonc.2016.11.008 CrossRefPubMed Linge A, Lohaus F, Lock S, Nowak A, Gudziol V, Valentini C, von Neubeck C, Jutz M, Tinhofer I, Budach V, Sak A, Stuschke M, Balermpas P, Rodel C, Grosu AL, Abdollahi A, Debus J, Ganswindt U, Belka C, Pigorsch S, Combs SE, Monnich D, Zips D, Buchholz F, Aust DE, Baretton GB, Thames HD, Dubrovska A, Alsner J, Overgaard J, Krause M, Baumann M, DKTK-ROG (2016) HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Radiother Oncol 121(3):364–373. https://​doi.​org/​10.​1016/​j.​radonc.​2016.​11.​008 CrossRefPubMed
9.
Zurück zum Zitat Strongin A, Yovino S, Taylor R, Wolf J, Cullen K, Zimrin A, Strome S, Regine W, Suntharalingam M (2012) Primary tumor volume is an important predictor of clinical outcomes among patients with locally advanced squamous cell cancer of the head and neck treated with definitive chemoradiotherapy. Int J Radiat Oncol Biol Phys 82(5):1823–1830. https://doi.org/10.1016/j.ijrobp.2010.10.053 CrossRefPubMed Strongin A, Yovino S, Taylor R, Wolf J, Cullen K, Zimrin A, Strome S, Regine W, Suntharalingam M (2012) Primary tumor volume is an important predictor of clinical outcomes among patients with locally advanced squamous cell cancer of the head and neck treated with definitive chemoradiotherapy. Int J Radiat Oncol Biol Phys 82(5):1823–1830. https://​doi.​org/​10.​1016/​j.​ijrobp.​2010.​10.​053 CrossRefPubMed
10.
Zurück zum Zitat Knegjens JL, Hauptmann M, Pameijer FA, Balm AJ, Hoebers FJ, de Bois JA, Kaanders JH, van Herpen CM, Verhoef CG, Wijers OB, Wiggenraad RG, Buter J, Rasch CR (2011) Tumor volume as prognostic factor in chemoradiation for advanced head and neck cancer. Head Neck 33(3):375–382. https://doi.org/10.1002/hed.21459 PubMedCrossRef Knegjens JL, Hauptmann M, Pameijer FA, Balm AJ, Hoebers FJ, de Bois JA, Kaanders JH, van Herpen CM, Verhoef CG, Wijers OB, Wiggenraad RG, Buter J, Rasch CR (2011) Tumor volume as prognostic factor in chemoradiation for advanced head and neck cancer. Head Neck 33(3):375–382. https://​doi.​org/​10.​1002/​hed.​21459 PubMedCrossRef
11.
Zurück zum Zitat Brenner DJ (1993) Dose, volume, and tumor-control predictions in radiotherapy. Int J Radiat Oncol Biol Phys 26(1):171–179CrossRefPubMed Brenner DJ (1993) Dose, volume, and tumor-control predictions in radiotherapy. Int J Radiat Oncol Biol Phys 26(1):171–179CrossRefPubMed
12.
Zurück zum Zitat Dubben HH, Thames HD, Beck-Bornholdt HP (1998) Tumor volume: a basic and specific response predictor in radiotherapy. Radiother Oncol 47(2):167–174CrossRefPubMed Dubben HH, Thames HD, Beck-Bornholdt HP (1998) Tumor volume: a basic and specific response predictor in radiotherapy. Radiother Oncol 47(2):167–174CrossRefPubMed
13.
Zurück zum Zitat Johnson CR, Thames HD, Huang DT, Schmidt-Ullrich RK (1995) The tumor volume and clonogen number relationship: tumor control predictions based upon tumor volume estimates derived from computed tomography. Int J Radiat Oncol Biol Phys 33(2):281–287CrossRefPubMed Johnson CR, Thames HD, Huang DT, Schmidt-Ullrich RK (1995) The tumor volume and clonogen number relationship: tumor control predictions based upon tumor volume estimates derived from computed tomography. Int J Radiat Oncol Biol Phys 33(2):281–287CrossRefPubMed
15.
Zurück zum Zitat Edge SBBD, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New York Edge SBBD, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New York
18.
Zurück zum Zitat Hermans R, Op de beeck K, Van den Bogaert W, Rijnders A, Staelens L, Feron M, Bellon E (2001) The relation of CT-determined tumor parameters and local and regional outcome of tonsillar cancer after definitive radiation treatment. Int J Radiat Oncol Biol Phys 50(1):37–45CrossRefPubMed Hermans R, Op de beeck K, Van den Bogaert W, Rijnders A, Staelens L, Feron M, Bellon E (2001) The relation of CT-determined tumor parameters and local and regional outcome of tonsillar cancer after definitive radiation treatment. Int J Radiat Oncol Biol Phys 50(1):37–45CrossRefPubMed
19.
20.
Zurück zum Zitat Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR (2017) AJCC cancer staging manual, 8th edn. Springer, New YorkCrossRef Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR (2017) AJCC cancer staging manual, 8th edn. Springer, New YorkCrossRef
22.
23.
Zurück zum Zitat Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, Roberts S (2013) Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer—systematic review and meta-analysis of trends by time and region. Head Neck 35(5):747–755. https://doi.org/10.1002/hed.22015 CrossRefPubMed Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, Roberts S (2013) Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer—systematic review and meta-analysis of trends by time and region. Head Neck 35(5):747–755. https://​doi.​org/​10.​1002/​hed.​22015 CrossRefPubMed
25.
Zurück zum Zitat Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100(4):261–269. https://doi.org/10.1093/jnci/djn011 CrossRefPubMed Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100(4):261–269. https://​doi.​org/​10.​1093/​jnci/​djn011 CrossRefPubMed
31.
Zurück zum Zitat Martinez I, Wang J, Hobson KF, Ferris RL, Khan SA (2007) Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer 43(2):415–432. https://doi.org/10.1016/j.ejca .2006.09.001CrossRefPubMed Martinez I, Wang J, Hobson KF, Ferris RL, Khan SA (2007) Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer 43(2):415–432. https://​doi.​org/​10.​1016/​j.​ejca .2006.09.001CrossRefPubMed
33.
Zurück zum Zitat van den Broek GB, Rasch CR, Pameijer FA, Peter E, van den Brekel MW, Tan IB, Schornagel JH, de Bois JA, Zijp LJ, Balm AJ (2004) Pretreatment probability model for predicting outcome after intraarterial chemoradiation for advanced head and neck carcinoma. Cancer 101(8):1809–1817. https://doi.org/10.1002/cncr.20556 CrossRefPubMed van den Broek GB, Rasch CR, Pameijer FA, Peter E, van den Brekel MW, Tan IB, Schornagel JH, de Bois JA, Zijp LJ, Balm AJ (2004) Pretreatment probability model for predicting outcome after intraarterial chemoradiation for advanced head and neck carcinoma. Cancer 101(8):1809–1817. https://​doi.​org/​10.​1002/​cncr.​20556 CrossRefPubMed
Metadaten
Titel
Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy
verfasst von
Timo Carpén, MD
Kauko Saarilahti
Caj Haglund
Antti Markkola
Jussi Tarkkanen
Jaana Hagström
Petri Mattila
Antti Mäkitie
Publikationsdatum
17.05.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 8/2018
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-018-1309-z

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