Hypoxic Modification of Radiotherapy in Squamous Cell Carcinoma of the Head and Neck - A Systematic Review and Meta-Analysis
Abstract
Background The importance of tumour hypoxia for the outcome of radiotherapy has been under investigation for decades. Numerous clinical trials modifying the hypoxic radioresistance in squamous cell carcinoma of the head and neck (HNSCC) have been conducted, but most have been inconclusive, partly due to a small number of patients in the individual trial. The present meta-analysis was, therefore, performed utilising the results from all clinical trials addressing the specific question of hypoxic modification in HNSCC undergoing curative intended primary radiotherapy alone.Methods A systematic review of published and unpublished data identified 4805 patients with HNSCC treated in 32 randomized clinical trials, applying, normobaric oxygen or carbogen breathing (5 trials); hyperbaric oxygen (HBO) (9 trials); hypoxic radiosensitizers (17 trials) and HBO and radiosensitizer (1 trial). The trials were analysed with regard to the following endpoints: loco-regional control (32 trials), disease specific survival (30 trials), overall survival (29 trials), distant metastases (12 trials) and complications to radiotherapy (23 trials).Results Overall hypoxic modification of radiotherapy in head and neck cancer did result in a significant improved therapeutic benefit. This was most dominantly observed when using the direct endpoint of loco-regional control with an odds ratio (OR) of 0.71, 95% cf.l. 0.63-0.80; p<0.001), but this was almost mirrored in the disease specific survival (OR: 0.73, 95% cf.l. 0.64-0.82; p<0.001), and to a lesser extent in the overall survival (OR: 0.87, 95% cf.l. 0.77-0.98; p=0.03). The risk of distant metastases was not significantly influenced although it appears to be less in the tumours treated with hypoxic modification (OR: 0.87, 95% cf.l. 0.69-1.09; p=0.22), whereas the radiation related late complications were not influenced by the overall use of hypoxic modifications (OR: 1.00, 95% cf.l. 0.82-1.23; p=0.96). The improvement in loco-regional control was found to be independent of the type of hypoxic modification. The trials have used different fractionation schedules, including large doses per fraction, which may result in relatively more hypoxia and greater benefit. However, analysis of HNSCC trials using conventional fractionation only, showed that the significant effect of hypoxic modification was maintained.Conclusion The meta-analysis thus demonstrates that there is level 1a evidence in favour of adding hypoxic modification to radiotherapy of squamous cell carcinomas of the head and neck.
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Hyperbaric O2 (HBO) could have some activity in squamous cancers of the head and neck in radiotherapy.
“Anti-hypoxia therapies have already been introduced in case of radiotherapy using hyperbaric O2 (HBO), which could have some activity in squamous cancers of the head and neck [91].”
From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [91]
Cites
Parmar, M. K. B., Torri, V., & Stewart, L. (1998) · Statistics in Medicine · doi:10.1002/(sici)1097-0258(19981230)17:24 · Cited by 4,519 · see citing works
Pignon, J., Maître, A. L., Maillard, E., & Bourhis, J. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.04.014 · Cited by 3,066 · see citing works
Vokes, E. E., Weichselbaum, R. R., Lippman, S. M., & Hong, W. K. (1993) · New England Journal of Medicine · doi:10.1056/nejm199301213280306 · Cited by 2,237 · see citing works
Gray, L. H., Conger, A. D., Ebert, M., Hornsey, S., & Scott, O. C. A. (1953) · The British Journal of Radiology · doi:10.1259/0007-1285-26-312-638 · Cited by 2,158 · see citing works
The hazard of accelerated tumor clonogen repopulation during radiotherapy
Withers, H. R., Taylor, J. M. G., & Maciejewski, B. (1988) · Acta Oncologica · doi:10.3109/02841868809090333 · Cited by 1,605 · see citing works
Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis
Bourhis, J., Overgaard, J., Audry, H., Ang, K. K., Saunders, M. I., Bernier, J., Horiot, J.-C., Maître, A. L., Pajak, T. F., Poulsen, M. G., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69121-6 · Cited by 1,083 · see citing works
Self-citationNordsmark, M., Bentzen, S. M., Rudat, V., Brizel, D., Lartigau, E., Stadler, P., Becker, A., Adam, M., Molls, M., Dunst, J., et al. (2005) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2005.06.038 · Cited by 953 · see citing works
Self-citationNordsmark, M., Overgaard, M., & Overgaard, J. (1996) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(96)91811-3 · Cited by 942 · see citing works
Self-citationExploring the role of cancer stem cells in radioresistance
Baumann, M. A., Krause, M., & Hill, R. P. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2419 · Cited by 817 · see citing works
Peters, L. J., O’Sullivan, B., Giralt, J., FitzGerald, T. J., Trotti, A., Bernier, J., Bourhis, J., Yuen, K., Fisher, R., & Rischin, D. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.4498 · Cited by 814 · see citing works
Overgaard, J., Hansen, H. S., Specht, L., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14361-9 · Cited by 690 · see citing works
Self-citationHypoxic Radiosensitization: Adored and Ignored
Overgaard, J. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.7878 · Cited by 619 · see citing works
Self-citationLassen, P., Eriksen, J. G., Hamilton-Dutoit, S. J., Tramm, T., Alsner, J., & Overgaard, J. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.2853 · Cited by 611 · see citing works
Self-citationOvergaard, J., Hansen, H. S., Overgaard, M., Bastholt, L., Berthelsen, A., Specht, L., Lindeløv, B., & Jørgensen, K. J. (1998) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(97)00220-x · Cited by 575 · see citing works
Self-citationBuffa, F. M., Harris, A. L., West, C., & Miller, C. J. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605450 · Cited by 558 · see citing works
The current and potential role of hyperthermia in radiotherapy
Overgaard, J. (1989) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(89)90470-7 · Cited by 507 · see citing works
Self-citationModification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers
Overgaard, J., & Horsman, M. R. (1996) · Seminars in Radiation Oncology · doi:10.1016/s1053-4296(96)80032-4 · Cited by 420 · see citing works
Self-citationRelation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers
Winter, S. C., Buffa, F. M., Silva, P., Miller, C., Valentine, H. R., Turley, H., Shah, K. A., Cox, G. J., Corbridge, R. J., Homer, J. J., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3322 · Cited by 410 · see citing works
Rischin, D., Peters, L. J., O'Sullivan, B., Giralt, J., Fisher, R., Yuen, K., Trotti, A., Bernier, J., Bourhis, J., Ringash, J., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.4449 · Cited by 380 · see citing works
Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer.
Kaanders, J. H. A. M., Wijffels, K. I. E. M., Marres, H. A. M., Ljungkvist, A. S. E., Pop, L. A. M., van den Hoogen, F. J. A., de Wilde, P. C. M., Bussink, J., Raleigh, J. A., & van der Kogel, A. J. (2002) · PubMed · Cited by 357 · see citing works
RADIOTHERAPY AND HYPERBARIC OXYGEN IN HEAD AND NECK CANCER
Henk, J. M., & Smith, C. W. (1977) · The Lancet · doi:10.1016/s0140-6736(77)90117-9 · Cited by 320 · see citing works
Valentini, V., Aristei, C., Glimelius, B. L. G., Minsky, B. D., Beets‐Tan, R. G. H., Borràs, J. M., Haustermans, K. M., Maingon, P., Overgaard, J., Påhlman, L., et al. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.06.027 · Cited by 299 · see citing works
Self-citationFreidel, D. A., Robertson, R. A., & Carr, H. S. (1986) · Southern Methodist University Press eBooks · Cited by 285 · see citing works
Nordsmark, M., & Overgaard, J. (2000) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(00)00223-1 · Cited by 282 · see citing works
Self-citationOvergaard, J., Eriksen, J. G., Nordsmark, M., Alsner, J., & Horsman, M. R. (2005) · The Lancet Oncology · doi:10.1016/s1470-2045(05)70292-8 · Cited by 274 · see citing works
Self-citationToustrup, K., Sørensen, B. S., Nordsmark, M., Busk, M., Wiuf, C., Alsner, J., & Overgaard, J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1182 · Cited by 259 · see citing works
Self-citationARCON: a novel biology-based approach in radiotherapy
Kaanders, J. H., Bussink, J., & van der Kogel, A. J. (2002) · The Lancet Oncology · doi:10.1016/s1470-2045(02)00929-4 · Cited by 257 · see citing works
The strengths and limitations of meta-analyses based on aggregate data
Lyman, G. H., & Kuderer, N. M. (2005) · BMC Medical Research Methodology · doi:10.1186/1471-2288-5-14 · Cited by 250 · see citing works
hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer
Gee, H. E., Camps, C., Buffa, F. M., Patiar, S., Winter, S. C., Betts, G. N. J., Homer, J. J., Corbridge, R., Cox, G. J., West, C., et al. (2010) · Cancer · doi:10.1002/cncr.25009 · Cited by 245 · see citing works
Overgaard, J., Hansen, H. S., Jøsrgensen, K., et al. (1986) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(86)90058-1 · Cited by 240 · see citing works
Self-citationRADIOTHERAPY AND HYPERBARIC OXYGEN IN HEAD AND NECK CANCER
Henk, J. M., Kunkler, P. B., & Smith, C. W. (1977) · The Lancet · doi:10.1016/s0140-6736(77)90116-7 · Cited by 229 · see citing works
Clinical evaluation of nitroimidazoles as modifiers of hypoxia in solid tumors.
Overgaard, J. (1994) · PubMed · Cited by 216 · see citing works
Self-citationOvergaard, J., Hansen, H. S., Andersen, A. P., Hjelm-Hansen, M., Jørgensen, K. J., Sandberg, E., Berthelsen, A., Hammer, R., & Pedersen, M. (1989) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(89)90917-6 · Cited by 214 · see citing works
Self-citationLe, Q., Sutphin, P. D., Raychaudhuri, S., et al. (2003) · PubMed · Cited by 214 · see citing works
Kong, C. S., Narasimhan, B., Cao, H., Kwok, S., Erickson, J. P., Koong, A. C., Pourmand, N., & Le, Q. (2009) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2009.02.015 · Cited by 213 · see citing works
Lassen, P., Eriksen, J. G., Hamilton-Dutoit, S. J., Tramm, T., Alsner, J., & Overgaard, J. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.10.008 · Cited by 210 · see citing works
Self-citationLassen, P., Eriksen, J. G., Krogdahl, A., Therkildsen, M. H., Ulhøi, B. P., Overgaard, M., Specht, L., Andersen, E., Johansen, J., Andersen, L. J., et al. (2011) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2011.02.010 · Cited by 199 · see citing works
Self-citationQuality assurance in radiotherapy
Thwaites, D., Scalliet, P. G. M., Leer, J. W. H., et al. (1995) · Radiotherapy and Oncology · doi:10.1016/0167-8140(95)01549-v · Cited by 193 · see citing works
Chemical sensitizers for hypoxic cells: A decade of experience in clinical radiotherapy
Dische, S. (1985) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(85)80015-3 · Cited by 179 · see citing works
Lee, D., Cosmatos, D., Marcial, V. A., Fu, K. K., Rotman, M., Cooper, J. S., Ortiz, H. G., Beitler, J. J., Abrams, R. A., Curran, W. J., et al. (1995) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(95)00150-w · Cited by 179 · see citing works
Evidence-based radiation oncology in head and neck squamous cell carcinoma
Corvò, R. (2007) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2007.04.002 · Cited by 178 · see citing works
Carlson, D. J., Keall, P., Loo, B. W., Chen, Z. J., & Brown, J. M. (2010) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2010.10.007 · Cited by 165 · see citing works
Dynamics of Tumor Hypoxia Measured with Bioreductive Hypoxic Cell Markers
Ljungkvist, A. S. E., Bussink, J., Kaanders, J. H. A. M., & van der Kogel, A. J. (2007) · Radiation Research · doi:10.1667/rr0719.1 · Cited by 160 · see citing works
The role of Human papillomavirus in head and neck cancer and the impact on radiotherapy outcome
Lassen, P. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.04.022 · Cited by 157 · see citing works
Sensitization of Hypoxic Tumour Cells—Clinical Experience
Overgaard, J. (1989) · International Journal of Radiation Biology · doi:10.1080/09553008914552081 · Cited by 154 · see citing works
Self-citationOvergaard, J., Mohanti, B. K., Begum, N., Ali, R., Agarwal, J. P., Kuddu, M., Bhasker, S., Tatsuzaki, H., & Grau, C. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70072-3 · Cited by 131 · see citing works
Self-citationLee, N. Y., Nehmeh, S. A., Schöder, H. M., et al. (2009) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2008.10.049 · Cited by 126 · see citing works
Le, Q., Kong, C. S., Lavori, P. W., O'Byrne, K. J., Erler, J. T., Huang, X., Chen, Y., Cao, H., Tibshirani, R. J., Denko, N., et al. (2007) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2007.01.071 · Cited by 119 · see citing works
PET-CT for response assessment and treatment adaptation in head and neck cancer
Bussink, J., van Herpen, C. M. L., Kaanders, J. H. A. M., & Oyen, W. J. G. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70353-5 · Cited by 111 · see citing works
Horsman, M. R., Chaplin, D. J., & Overgaard, J. (1990) · PubMed · Cited by 107 · see citing works
Self-citationHenk, J. M. (1986) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(86)90167-7 · Cited by 106 · see citing works
Clinical evidence on PET–CT for radiation therapy planning in head and neck tumours
Troost, E. G. C., Schinagl, D. A. X., Bussink, J., et al. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.07.017 · Cited by 92 · see citing works
Overgaard, J., Hansen, H. S., Lindeløv, B., et al. (1991) · Radiotherapy and Oncology · doi:10.1016/0167-8140(91)90202-r · Cited by 91 · see citing works
Self-citationOrlandi, E. M., Palazzi, M. F., Pignoli, E., et al. (2009) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2009.03.003 · Cited by 91 · see citing works
Carbogen breathing during radiation therapy The radiation therapy oncology group study
Rubin, P., Hanley, J. A., Keys, H. M., Marcial, V. A., & Brady, L. W. (1979) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(79)90946-5 · Cited by 90 · see citing works
Yaromina, A., Thames, H. D., Zhou, X., Hering, S., Eicheler, W., Dörfler, A., Leichtner, T., Zips, D., & Baumann, M. A. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.04.020 · Cited by 88 · see citing works
Bache, M., Kappler, M., Said, H. M., Staab, A., & Vordermark, D. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708783497391 · Cited by 87 · see citing works
Le, Q., Harris, J., Magliocco, A. M., Kong, C. S., Diaz, R., Shin, B., Cao, H., Trotti, A., Erler, J. T., Chung, C. H., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.6003 · Cited by 86 · see citing works
Implementation of hypoxia imaging into treatment planning and delivery
Thorwarth, D., & Alber, M. L. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.05.012 · Cited by 85 · see citing works
Nordsmark, M., Eriksen, J. G., Gebski, V., Alsner, J., Horsman, M. R., & Overgaard, J. (2007) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2007.04.021 · Cited by 85 · see citing works
Self-citationIdentifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro
Sørensen, B. S., Toustrup, K., Horsman, M. R., Overgaard, J., & Alsner, J. (2010) · Acta Oncologica · doi:10.3109/02841861003614343 · Cited by 82 · see citing works
Self-citationEschwège, F., Sancho-Garnier, H., Chassagne, D., Brisgand, D., Guerra, M., Malaise, E. P., Bey, P., Busutti, L., Cionini, L., Nguyen, T. D., et al. (1997) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(97)00327-1 · Cited by 81 · see citing works
Mortensen, L. S., Buus, S., Nordsmark, M., Bentzen, L., Munk, O. L., Keiding, S., & Overgaard, J. (2010) · Acta Oncologica · doi:10.3109/0284186x.2010.516274 · Cited by 79 · see citing works
Self-citationDittfeld, C., Dietrich, A., Peickert, S., Hering, S., Baumann, M. A., Grade, M., Ried, T., & Kunz‐Schughart, L. A. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.06.034 · Cited by 76 · see citing works
Horsman, M. R., Khalil, A. A., Siemann, D. W., et al. (1994) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(94)90434-0 · Cited by 74 · see citing works
den Bogaert, W. V., van der Schueren, E., Horiot, J.-C., et al. (1986) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(86)90067-2 · Cited by 74 · see citing works
Mechanism of action of the selective tumor radiosensitizer nicotinamide
Horsman, M. R., Brown, J. M., Phil, D., et al. (1988) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(88)90312-4 · Cited by 71 · see citing works
Saunders, M. I., & Dische, S. (1996) · PubMed · Cited by 70 · see citing works
Choi, W., Lee, S.-W., Park, S. H., et al. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.04.012 · Cited by 70 · see citing works
Grau, C., Agarwal, J. P., Jabeen, K., et al. (2003) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(03)00020-3 · Cited by 69 · see citing works
Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer
Lambin, P., Ramaekers, B. L. T., van Mastrigt, G. A. P. G., et al. (2009) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006158.pub2 · Cited by 68 · see citing works
Hoff, C. M., Hansen, H. S., Overgaard, M., Grau, C., Johansen, J., Bentzen, J., & Overgaard, J. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.09.024 · Cited by 63 · see citing works
Self-citationFazekas, J. T., Pajak, T. F., Wasserman, T. H., et al. (1987) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(87)90188-x · Cited by 58 · see citing works
The limitation of PET imaging for biological adaptive-IMRT assessed in animal models
Christian, N., Lee, J. A., Bol, A., et al. (2008) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2008.11.014 · Cited by 54 · see citing works
den Bogaert, W. V., van der Schueren, E., Horiot, J. C., et al. (1995) · Radiotherapy and Oncology · doi:10.1016/0167-8140(95)01538-r · Cited by 52 · see citing works
Busk, M., Horsman, M. R., Jakobsen, S., et al. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.08.026 · Cited by 52 · see citing works
Fraction size in radiobiology and radiotherapy
菅原, 努., Révész, L., & Scott, O. C. A. (1973) · Medical Entomology and Zoology · Cited by 51 · see citing works
van den Brenk, H. A. S. (1968) · PubMed · Cited by 49 · see citing works
HYPERBARIC OXYGEN IN RADIATION THERAPY
van den Brenk, H. A. S. (1968) · American Journal of Roentgenology · doi:10.2214/ajr.102.1.8 · Cited by 48 · see citing works
Moule, R. N., Kayani, I. A., Moinuddin, S. A., et al. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.04.025 · Cited by 45 · see citing works
Individual Patient- versus Literature-Based Meta-analysis of Survival Data
Duchateau, L., Pignon, J., Bijnens, L., Bertin, S., Bourhis, J., & Sylvester, R. J. (2001) · Controlled Clinical Trials · doi:10.1016/s0197-2456(01)00152-0 · Cited by 44 · see citing works
Lee, N. Y., & Le, Q. (2008) · Seminars in Oncology · doi:10.1053/j.seminoncol.2008.03.003 · Cited by 42 · see citing works
Lee, D.-J., Pajak, T. F., Stetz, J., Order, S. E., Weissberg, J. B., & Fischer, J. J. (1989) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(89)90343-x · Cited by 41 · see citing works
Molecular radiation biology: Perspectives for radiation oncology
Rodemann, H. P. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.08.023 · Cited by 40 · see citing works
Sørensen, B. S., Horsman, M. R., Vorum, H., Honoré, B., Overgaard, J., & Alsner, J. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.05.019 · Cited by 38 · see citing works
Self-citationHæmangiomatous Lesions of the Colon
Hollingsworth, G. (1951) · British Journal of Radiology · doi:10.1259/0007-1285-24-280-220 · Cited by 38 · see citing works
Bennett, M. R., Feldmeier, J., Smee, R., & Milross, C. G. (2008) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2008.01.001 · Cited by 36 · see citing works
Haffty, B., Hurley, R. A., & Peters, L. J. (1999) · PubMed · Cited by 35 · see citing works
RADIOTHERAPY OF ADVANCED CARCINOMA OF THE OROPHARYNGEAL REGION UNDER HYPERBARIC OXYGENATION
Chang, C. H., Conley, J., & Herbert, C. (1973) · American Journal of Roentgenology · doi:10.2214/ajr.117.3.509 · Cited by 35 · see citing works
Hyperbaric oxygen in radiation therapy
Glassburn, J. R., Brady, L. W., & Plenk, H. P. (1977) · Cancer · doi:10.1002/1097-0142(197702)39:2+ · Cited by 32 · see citing works
Mendenhall, W. M., Morris, C. G., Amdur, R. J., Mendenhall, N. P., & Siemann, D. W. (2005) · Cancer · doi:10.1002/cncr.21146 · Cited by 31 · see citing works
Sealy, R., Cridland, S., Barry, L., et al. (1986) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(86)90168-9 · Cited by 31 · see citing works
Arcangeli, G., Overgaard, J., González, D., et al. (1988) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(88)90171-x · Cited by 28 · see citing works
Self-citationHuilgol, N., Chatterjee, N., & Mehta, A. R. (1996) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(95)02181-7 · Cited by 27 · see citing works
Zips, D., Le, K., Yaromina, A., et al. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.04.006 · Cited by 24 · see citing works
The leeds results for radiotherapy in HBO for carcinoma of the head and neck
Berry, G., Dixon, B., & Ward, A. (1979) · Clinical Radiology · doi:10.1016/s0009-9260(79)80207-x · Cited by 23 · see citing works
Fazekas, J. T., Scott, C., Marcial, V. A., et al. (1989) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(89)90523-3 · Cited by 23 · see citing works
Starmans, M. H. W., Zips, D., Wouters, B. G., Baumann, M. A., & Lambin, P. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.06.016 · Cited by 19 · see citing works
A report on misonidazole in a randomized trial in locally advanced head and neck cancer
Sealy, R., Williams, A., Cridland, S., et al. (1982) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(82)90635-6 · Cited by 19 · see citing works
Sause, W. T., & Plenk, H. P. (1979) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(79)90567-4 · Cited by 19 · see citing works
Janssens, G. O. R. J., Terhaard, C. H. J., Doornaert, P., Bijl, H. P., van den Ende, P. L. A., Chin, A., Pop, L. A. M., & Kaanders, J. H. A. M. (2011) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2010.11.045 · Cited by 19 · see citing works
Panis, X., Nguyen, T. D., Froissart, D., et al. (1984) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(84)90260-8 · Cited by 18 · see citing works
Targeting Hypoxia in Head and Neck Cancer
Peters, L. J. (2001) · Acta Oncologica · doi:10.1080/02841860152708215 · Cited by 18 · see citing works
Tobin, D. A., & Vermund, H. (1971) · American Journal of Roentgenology · doi:10.2214/ajr.111.3.613 · Cited by 17 · see citing works
Hyperbaric oxygen in the radiation treatment of head and neck cancers
Sealy, R. (1991) · Radiotherapy and Oncology · doi:10.1016/0167-8140(91)90192-j · Cited by 15 · see citing works
International Clinical Trials in Radiation Oncology. Hyperthermia trials.
Arcangeli, G., Overgaard, J., Gonzalez Gonzalez, D., et al. (1988) · PubMed · Cited by 12 · see citing works
Self-citationRadiotherapy in Developing Countries
Yazıcı, Z. (1987) · Cited by 12 · see citing works
Ullal, S., Kr, S., Pai, M., Chowta, M. N., Adiga, S., Dinesh, M. G., Kamath, A., Kotian, M., & Pai, D. (2006) · Indian Journal of Cancer · doi:10.4103/0019-509x.29419 · Cited by 9 · see citing works
Okkan, S., Yazıcı, Z., Uzel, R., Akçasu, A., Türkan, S., Hacibekirolu, M., Olgun, P., & Egehan, Î. (1986) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(86)80178-5 · Cited by 8 · see citing works
EXPLOSIVE DECOMPRESSION IN A HYPERBARIC OXYGEN CHAMBER
Tobin, D. A. (1971) · American Journal of Roentgenology · doi:10.2214/ajr.111.3.622 · Cited by 8 · see citing works
Clinical trial of atmospheric oxygen breathing during radiotherapy for cancer of the oropharynx.
Jc, E., & Pj, C. (1975) · PubMed · Cited by 4 · see citing works
Oxygen tension of oral cavity carcinoma.
Jc, E., & Lj, S. (1970) · PubMed · Cited by 4 · see citing works
COMORBIDITY AMONG 13,651 HEAD AND NECK CANCER PATIENTS FROM THE DAHANCA-DATABASE
Boeje, C. R., Dalton, S. O., Kristensen, C. A., et al. (2011) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(11)70004-4 · Cited by 3 · see citing works
Gałecki, J., Dukowicz, A., Hliniak, A., Mierzwińska, J., Mykowiecka, A., Osiadacz, W., Prejbisz, J., & Hipsz, K. (1989) · PubMed · Cited by 3 · see citing works
[Controlled clinical studies].
Merte, K. (1980) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Tumour Microenvironment after Radiotherapy: Mechanisms of Resistance and Recurrence
Barker, H. E., Paget, J. T. E., Khan, A. A., & Harrington, K. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3958 · Cited by 2,144 · see citing works
Imaging hypoxia to improve radiotherapy outcome
Horsman, M. R., Mortensen, L. S., Petersen, J. B., Busk, M., & Overgaard, J. (2012) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2012.171 · Cited by 614 · see citing works
Self-citationEustace, A., Mani, N., Span, P. N., Irlam, J. J., Taylor, J., Betts, G. N. J., Denley, H., Miller, C. J., Homer, J. J., Rojas, A. M., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0542 · Cited by 240 · see citing works
Hypoxia Signaling in Cancer: From Basics to Clinical Practice
Sebestyén, A., Kopper, L., Dankó, T., & Tímár, J. (2021) · Pathology and Oncology Research · doi:10.3389/pore.2021.1609802 · Cited by 110 · see citing works
Keulers, T. G., Koch, A., van Gisbergen, M. W., Barbeau, L. M. O., Zonneveld, M. I., de Jong, M. C., Savelkouls, K. G. M., Wanders, R. G., Bussink, J., Melotte, V., et al. (2022) · Autophagy · doi:10.1080/15548627.2021.2008690 · Cited by 30 · see citing works
- Authors
- Overgaard, J.
- Affiliations
- Aarhus University Hospital (DK)
- Corresponding author
- Overgaard, Jens
- ORCID
- Overgaard, Jens
- Venue
- Radiotherapy and Oncology
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 100
- Issue
- 1
- Pages
- 22-32
- ISSN
- 0167-8140 (ISSN-L)
- OpenAlex
- W2053662954
- Cited by
- 456
- References
- 115
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 20 · 2023: 25 · 2022: 25 · 2021: 39 · 2020: 32 · 2019: 30 · 2018: 20 · 2017: 38 · 2016: 44 · 2015: 42 · 2014: 26 · 2013: 37 · 2012: 29
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Radiotherapy and Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CIRRO – The Lundbeck Foundation Center for Interventional Research in Radiation Oncology
- Danish Research Council
- Danish Cancer Society
- Topics
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Keywords
- tumor hypoxia, head and neck squamous cell carcinoma, hypoxic radiosensitizer, hyperbaric oxygen therapy, normobaric oxygen, carbogen, locoregional control, disease-specific survival, overall survival, distant metastasis, primary radiotherapy, radioresistance (biology)
- MeSH terms
- Squamous Cell Carcinoma of Head and Neck, Hypoxia, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Humans, Neoplasm Metastasis, Radiotherapy, Radiotherapy Dosage
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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