Opinion statement
Locoregional recurrence remains a major obstacle to achieving a cure of locally advanced head and neck cancers, despite multimodality therapy. Multiple studies report that a low hemoglobin (Hgb) before or during radiation therapy is an important risk factor for poor locoregional disease control and survival. Anemia is common in the head and neck cancer population and is suspected to contribute to intratumoral hypoxia with resultant radioresistance. Although having a low Hgb level has been shown to be detrimental, it is unclear as to exactly what the threshold should be for low Hgb (studies in this area have used thresholds ranging from 9–14.5 g/dL). Quality-of-life studies suggest that correction of moderately severe anemia may result in significant gains. Optimal Hgb levels for improving outcomes may vary across and within tumor types, and this is an area that requires further evaluation. However, the correction of anemia may be a worthwhile strategy for radiation oncologists to improve local control and survival. This article reviews the impact of anemia on outcomes after radiotherapy of head and neck cancers.
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References and Recommended Reading
Mundt AJ, Connell PP, Campbell T, et al.: Race and clinical outcome in patients with carcinoma of the uterine cervix treated with radiation therapy. Gynecol Oncol 1998, 71:151–158.
Takeshi K, Katsuyuki K, Yoshiaki T, et al.: Definitive radiotherapy combined with high-dose-rate brachytherapy for stage III carcinoma of the uterine cervix: retrospective analysis of prognostic factors concerning patient characteristics and treatment parameters. Int J Radiat Oncol Biol Phys 1998, 41:319–327.
Forastiere AA, Berkey B, Maor M, et al.: Phase III trial to preserve the larynx: induction chemotherapy and radiotherapy versus concomitant chemoradiotherapy versus radiotherapy alone. Intergroup trial R91-11. Proc Am Soc Clin Oncol 2001, 20:2a.
Teicher BA: Physiologic mechanisms of therapeutic resistance: blood flow and hypoxia. Hematol Oncol Clin North Am 1995, 9:475–506.
Harrison LB, Shasha D, Homel P: Prevalence of anemia in cancer patients undergoing radiotherapy: prognostic significance and treatment. Oncology 2002, 63(Suppl 2):11–18. This paper discusses the incidence of anemia in a wide cross-section of patients treated with radiotherapy.
Hu K, Nwokeoi E, Culliney B, et al.: Delayed accelerated hyperfractionated radiation with concurrent cis-platinum without induction chemotherapy for organ preservation therapy of stage III/IV head and neck cancer. Radiother Oncol 2002, 64(Suppl 1):S251.
Hu K, Sachoeva G, Culliney B, et al.: Accelerated fractionated radiation by concomitant boost (AFX-CB) with concurrent cis-platinum for advanced nasopharyngeal cancer. Paper presented at the 85th Annual Meeting of the American Radium Society. Chicago, IL; 2003.
Lee DJ, Cosmatos D, Marcial VA, et al.: Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas. Int J Radiat Oncol Biol Phys 1995, 32:567–576.
Fazekas JT, Scott C, Marcial V, et al.: The role of hemoglobin concentration in the outcome of misonidazole-sensitized radiotherapy of head and neck cancers: based on RTOG trial #79-15. Int J Radiat Oncol Biol Phys 1989, 17:1177–1181.
Overgaard J, Hansen HS, Overgaard M, et al.: A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma: results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. Radiother Oncol 1998, 46:135–146.
Dubray B, Mosseri V, Brunin F, et al.: Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study. Radiology 1996, 201:553–558.
Al-Sarraf M, LeBlanc M, Giri PG, et al.: Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998, 16:1310–1317.
Calais G, Alfonsi M, Bordet E, et al.: Radiation (RT) alone versus RT with concomitant chemotherapy (CT) in stages III and IV oropharynx carcinoma: final results of the 94-01 GORTEC randomized study. Int J Radiat Oncol Biol Phys 2001, 51(Suppl 1):1.
Munro AJ: An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer. Br J Cancer 1995, 71:83–91.
El-Sayed S, Nelson N: Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region: a meta-analysis of prospective and randomized trials. J Clin Oncol 1996, 14:838–847.
Bourhis J, Eschwege F: Radiotherapy-chemotherapy combinations in head and neck squamous cell carcinoma: overview of randomized trials. Anticancer Res 1996, 16:2397–2402.
Rosen FR, Haraf DJ, Kies MS, et al.: Multicenter randomized phase II study of paclitaxel (1-hour infusion), fluorouracil, hydroxyurea, and concomitant twice daily radiation with or without erythropoietin for advanced head and neck cancer. Clin Cancer Res 2003, 9:1689–1697. A randomized study evaluating whether EPO impacts QOL/ transfusion requirements in patients with head and neck cancer treated with chemoradiation.
Stadler P, Feldmann HJ, Creighton C, et al.: Changes in tumor oxygenation during combined treatment with split-course radiotherapy and chemotherapy in patients with head and neck cancer. Radiother Oncol 1998, 48:157–164.
Hockel M, et al.: Tumor oxygenation: a new predictive parameter in locally advanced cancer of the uterine cervix. Gynecol Oncol 1993, 51:141–149.
Becker A, Hansgen G, Richter C, Dunst J: Oxygenation status of squamous cell carcinoma of the head and neck: comparison of primary tumors, their neck node metastases and normal tissue. Strahlenther Onkol 1998, 174:484–486.
Brizel DM, Dodge RK, Clough RW, Dewhirst MW: Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol 1999, 53:113–117.
Nordsmark M, Overgaard J: A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. Radiother Oncol 2000, 57:39–43.
Hirst DG: What is the importance of anaemia in radiotherapy? The value of animal studies. Radiother Oncol 1991, 20(Suppl 1):29–33.
Warde P, O’Sullivan B, Bristow RG, et al.: T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control. Int J Radiat Oncol Biol Phys 1998, 41:347–353.
Hirst DG: Anemia: a problem or an opportunity in radiotherapy? Int J Radiat Oncol Biol Phys 1986, 12:2009–2017.
Rockwell S, Keyes SR, Sartorelli AC: Modulation of the antineoplastic efficacy of mitomycin C by dicoumarol in vivo. Cancer Chemother Pharmacol 1989, 24:349–353.
Overgaard J, Horsman MR: Modification of hypoxiainduced radioresistance in tumors by the use of oxygen and sensitizers. Semin Radiat Oncol 1996, 6:10–21.
Stadler P, Becker A, Feldmann HJ, et al.: Influence of the hypoxic subvolume on the survival of patients with head and neck cancer. Int J Radiat Oncol Biol Phys 1999, 44:749–754.
Overgaard J: Sensitization of hypoxic tumour cells: clinical experience. Int J Radiat Biol 1989, 56:801–811.
Bush RS, Jenkin RD, Allt WE, et al.: Definitive evidence for hypoxic cells influencing cure in cancer therapy. Br J Cancer Suppl 1978, 37:302–306.
Bush RS: The significance of anemia in clinical radiation therapy. Int J Radiat Oncol Biol Phys 1986, 12:2047–2050.
Harrison LB, Chadha M, Hill RJ, et al.: Impact of tumor hypoxia and anemia on radiation therapy outcomes. Oncologist 2002, 7:492–508.
Fein DA, Lee WR, Hanlon AL, et al.: Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 1995, 13:2077–2083.
van Acht MJ, Hermans J, Boks DE, Leer JW: The prognostic value of hemoglobin and a decrease in hemoglobin during radiotherapy in laryngeal carcinoma. Radiother Oncol 1992, 23:229–235.
Grant DG, Hussain A, Hurman D: Pre-treatment anaemia alters outcome in early squamous cell carcinoma of the larynx treated by radical radiotherapy. J Laryngol Otol 1999, 113:829–833.
Blitzer P, Wang C, Suit H: Blood pressure and hemoglobin concentration: multivariate analysis of local control after irradiation for head and neck cancer. Int J Radiat Oncol Biol Phys 1984, 10(Suppl 2):98.
Haddad R, Suntharalingam M, Chen T, et al.: Pretreatment hemoglobin is associated with response to chemoradiation therapy (CRT) in patients with advanced unresectable squamous cell carcinoma of the head and neck. Proc Am Soc Clin Oncol 2001, 19:417a.
Overgaard J, Hansen HS, Andersen AP, et al.: Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx: report from the DAHANCA 2 study. Int J Radiat Oncol Biol Phys 1989, 16:1065–1068.
Skladowski K, Tarnawski R, Maciejewski B, et al.: Clinical radiobiology of glottic T1 squamous cell carcinoma. Int J Radiat Oncol Biol Phys 1999, 43:101–106.
Tarnawski R, Skladowski K, Maciejewski B: Prognostic value of hemoglobin concentration in radiotherapy for cancer of supraglottic larynx. Int J Radiat Oncol Biol Phys 1997, 38:1007–1011.
Canaday DJ, Regine WF, Mohiuddin, et al.: Significance of pretreatment hemoglobin level in patients with T1 glottic cancer. Radiat Oncol Investig 1999, 7:42–48.
Tucker J, Hixson W, Kim R: Pretreatment hemoglobin in early stage glottic cancer: red flag or red herring? Int J Oncol Biol Phys Proc 1996, 36:336.
Sakata K, Aoki Y, Karasawa K, et al.: Radiation therapy in early glottic carcinoma: uni-and multivariate analysis of prognostic factors affecting local control. Int J Radiat Oncol Biol Phys 1994, 30:1059–1064.
Lutterbach J, Guttenberger R: Anemia is associated with decreased local control of surgically treated squamous cell carcinomas of the glottic larynx. Int J Radiat Oncol Biol Phys 2000, 48:1345–1350.
Degner FL, Sutherland RM: Mathematical modelling of oxygen supply and oxygenation in tumor tissues: prognostic, therapeutic, and experimental implications. Int J Radiat Oncol Biol Phys 1988, 15:391–397.
Evans SM, Jenkins WT, Shapiro M, Koch CJ: Evaluation of the concept of “hypoxic fraction” as a descriptor of tumor oxygenation status. Adv Exp Med Biol 1997, 411:215–225.
Girinski T, Pejovic-Lenfant MH, Bourhis J, et al.: Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: results of a retrospective study of 386 patients. Int J Radiat Oncol Biol Phys 1989, 16:37–42.
Surgenor DM, Wallace EL, Hao SH, Chapman RH: Collection and transfusion of blood in the United States, 1982–1988. N Engl J Med 1990, 322:1646–1651.
Lavey RS, Dempsey WH: Erythropoietin increases hemoglobin in cancer patients during radiation therapy. Int J Radiat Oncol Biol Phys 1993, 27:1147–1152.
Pedersen D, Sogaard H, Overgaard J: Prognostic value of pretreatment factors in patients with locally advanced carcinoma of the uterine cervix treated by radiotherapy alone. Acta Oncol 1995, 34:787–795.
Henry DH: Changing patterns of care in the management of anemia. Semin Oncol 1992, 19(Suppl 8):3–7.
Littlewood TJ, Bajetta E, Nortier JW, et al.: Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001, 19:2865–2874. This paper demonstrates that EPO can improve QOL in patients treated with chemotherapy. It showed a trend toward improved survival in patients receiving EPO.
Quirt I, Robeson C, Lau CY, et al.: Epoetin alpha therapy increases hemoglobin levels and improves quality of life in patients with cancer-related anemia who are not receiving chemotherapy and patients with anemia who are receiving chemotherapy. J Clin Oncol 2001, 19:4126–4134.
Gabrilove J, Cleeland CS, Livingston RB, et al.: Clinical evaluation of once-weekly dosing of epoetin alpha in chemotherapy patients: improvements in hemoglobin and quality of life are similar to three-times-weekly dosing. J Clin Oncol 2001, 19:2875–2882.
Cleeland C, Demetti G, Glaspy J, et al.: Identifying hemoglobin level for optimal quality of life: results of an incremental analysis. Proc Am Soc Clin Oncol 1999, 18:574a.
Cella D, Dobrez D, Glaspy J: Control of cancer-related anemia with erythropoietic agents: a review of evidence for improved quality of life and clinical outcomes. Ann Oncol 2003, 14:511–519.
Henke M, Guttenberger R, Barke A, et al.: Erythropoietin for patients undergoing radiotherapy: a pilot study. Radiother Oncol 1999, 50:185–190.
Thews O, Koenig R, Kelleher DK, et al.: Enhanced radiosensitivity in experimental tumours following erythropoietin treatment of chemotherapy-induced anaemia. Br J Cancer 1998, 78:752–756.
Stuben G, Pottgen C, Knuhmann K, et al.: Erythropoietin restores the anemia-induced reduction in radiosensitivity of experimental human tumors in nude mice. Int J Radiat Oncol Biol Phys 2003, 55:1358–1362.
Sweeney PJ, Nicolae D, Ignacio L, et al.: Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial. Br J Cancer 1998, 77:1996–2002.
Dusenbery K, McGuire WA, Holt PJ, et al.: Erythropoietin increases hemoglobin during radiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys 1994, 29:1079–1084.
Shasha D, George MJ, Harrison LB: Once-weekly dosing of epoetin-alpha increases hemoglobin and improves quality of life in anemic cancer patients receiving radiation therapy either concomitantly or sequentially with chemotherapy. Cancer 2003, 98:1072–1079.
Lavey RS: Clinical trial experience using erythropoietin during radiation therapy. Strahlenther Onkol 1998, 174(Suppl 4):24–30.
Glaser C, Millesi W, Gossweiner S, et al.: rHuEPO supply increases efficacy of neoadjuvant radiochemotherapy in patients with oral squamous cell carcinoma. Proc Am Soc Clin Oncol 1998, 17:397a.
Glaser C, Millesi W, Wanschitz F, et al.: rHuEPO treatment increases efficacy of neoadjuvant radiochemotherapy and improves cancer free survival of patients with oral squamous cell carcinoma: a 17-month follow-up. Proc Am Soc Clin Oncol 1999, 18:399a.
Glaser CM, Millesi W, Kornek GV, et al.: Impact of hemoglobin level and use of recombinant erythropoietin on efficacy of preoperative chemoradiation therapy for squamous cell carcinoma of the oral cavity and oropharynx. Int J Radiat Oncol Biol Phys 2001, 50:705–715. An important paper that shows that the use of EPO to correct anemia in patients with head and neck cancer treated with multimodality therapy appears to improve locoregional control and survival outcomes.
Machtay M: A randomized phase III trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiotherapy for carcinoma of the head and neck. RTOG 99-03. Radiat Ther Oncol Group 2000.
Henke M, Laszig R, Rube C, et al.: Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003, 362:1255–1260.
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Hu, K., Harrison, L.B. Impact of anemia in patients with head and neck cancer treated with radiation therapy. Curr. Treat. Options in Oncol. 6, 31–45 (2005). https://doi.org/10.1007/s11864-005-0011-4
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DOI: https://doi.org/10.1007/s11864-005-0011-4