Impact of Hemoglobin Levels on Tumor Oxygenation: the Higher, the Better?

Vaupel, Peter; Mayer, Arnulf; Höckel, Michael

doi:10.1007/s00066-006-1543-7

Cited by 119 publications

(81 citation statements)

References 84 publications

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“…However, the treatment programs used in the SCOPE1-trial for definitive treatment appeared not optimal. The radiation dose appeared relatively low and induction chemotherapy may have led to anemia and subsequent tumor hypoxia, which is known to impair the effect of radiotherapy (29). In contrast to the SCOPE1-trial, the preliminary results of a randomized phase II study showed a better progressionfree survival (PFS) in patients receiving cetuximab in addition to radio-chemotherapy (27).…”

Section: Definition Of Dose Limiting Toxicities (Dlts)mentioning

confidence: 99%

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

Rades

Maderer

Panzner

et al. 2017

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Section: Definition Of Dose Limiting Toxicities (Dlts)mentioning

confidence: 99%

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

Rades

Maderer

Panzner

et al. 2017

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“…Several experimental studies suggest that anemia leads to a higher degree of hypoxia (13,14) in tumor than would be expected for nonneoplastic tissues. Low levels of tissue oxygen tension (pO 2 ) induce cell signaling through the AKT-mammalian target of rapamycin, thus leading to the up-regulation of hypoxia-inducible factor 1a.…”

mentioning

confidence: 99%

Anemia Is a Significant Prognostic Factor in Local Relapse-Free Survival of Premenopausal Primary Breast Cancer Patients Receiving Adjuvant Cyclophosphamide/Methotrexate/5-Fluorouracil Chemotherapy

Dubsky

Sevelda²,

Jakesz³

et al. 2008

Clinical Cancer Research

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Purpose: To determine the effects of anemia on local relapse-free, relapse-free, and overall survival (LRFS, RFS, and OS, respectively) in premenopausal, primary breast cancer patients receiving adjuvant polychemotherapy, and to determine which conventional prognostic factors affected these outcomes. Experimental Design: Four hundred twenty-four premenopausal patients with early-stage primary breast cancer and hormone receptor^expressing tumors were treated with i.v. cyclophosphamide/methotrexate/5-fluorouracil (CMF) polychemotherapy as part of an adjuvant phase III trial (Austrian Breast and Colorectal Cancer Study GroupTrial 5).The influence of anemia (hemoglobin <12 g/dL) on LRFS, RFS, and OS was evaluated in a retrospective analysis.Results: Of 424 patients, 77 (18.2%) developed anemia on CMF chemotherapy. After a median follow-up time of 5 years, 8.9% of nonanemic patients had local relapse compared with 19.6% of anemic patients (P = 0.0006). Although mastectomy was associated with anemia (26% versus 13.7% in breast conserving surgery; P = 0.002), multivariate analysis did not show mastectomy per se to be a significant risk factor for LRFS. Age, lymph node status, and hemoglobin had an independent significant influence on LRFS (P < 0.005). Anemic patients had a relative risk of 2.96 (95% confidence interval, 1.41-6.23) for developing local relapse in comparison with nonanemic patients. Conclusion: Premenopausal breast cancer patients who developed anemia during the CMF regimen had significantly worse LRFS. In Austrian Breast and Colorectal Cancer Study Group Trial 5, anemia may have contributed to an almost doubled incidence of local recurrence in the chemotherapy arm. Molecular targets associated with tumor hypoxia and distinct from erythropoiesis should receive further attention in experimental and clinical settings.

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“…In addition, high haemoglobin levels predispose to pathologic clot formation. Haemoglobin levels must be 12-14 g/dl in women and 13-15 g/dl in men to achieve optimal tumour oxygenation and the best results from radiotherapy [5]. Th ese data have been confi rmed in a retrospective study of 108 oesophageal cancer patients, where haemoglobin levels during radiotherapy of 12-14 g/dl resulted in better 2-year loco-regional control than levels <12 g/dl or >14 g/dl (58% vs. 19% and 44%, p < 0.001) [6].…”

Section: Introductionmentioning

confidence: 99%

Challenges of anemia correction during radiotherapy and chemoradiation

Rades

Schild

2012

memo

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Th e eff ect of radiotherapy depends on optimal tumour oxygenation, as tumour hypoxia impairs the production of radiation-induced cytotoxic free radicals resulting in less tumour cell kill. Th e range of haemoglobin levels optimal for tumour oxygenation is 12-14 g/dl in women and 13-15 g/dl in men. It appears reasonable to elevate the haemoglobin level in anaemic cancer patients into this optimal range. Th is may be achieved with red blood cell transfusions (RBCT) or erythropoiesis stimulating agents (ESAs). However, RBCT have had negligible or even negative eff ect on patient outcome, possibly because RBCT induce immunosuppression or result in haemoglobin levels too high for optimal tumour oxygenation. Several randomized trials have demonstrated that patients irradiated for head-and-neck cancer had worse outcomes with ESAs than the control group. However, in the majority of these trials, over-treatment with ESAs resulted in haemoglobin levels above the optimal range. Tumour oxygenation is impaired by inappropriately high haemoglobin levels due to increased blood viscosity and decreased tumour cell perfusion. Th is concept is supported by the fi ndings of prospective studies in cervix cancer and esophageal cancer patients. In these studies the ESA administration was withheld at a haemoglobin level of 14 g/dl resulting in a positive eff ect of ESAs on treatment outcome. In summary, the eff ect of RBCT and particularly of ESAs during radiotherapy remains unclear. Further randomized trials are required. Until such trials are available, one should follow the ASCO and ESMO guidelines that are very conservative regarding the administration of ESAs during radiotherapy and chemoradiation.

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Impact of Hemoglobin Levels on Tumor Oxygenation: the Higher, the Better?

Cited by 119 publications

References 84 publications

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

Anemia Is a Significant Prognostic Factor in Local Relapse-Free Survival of Premenopausal Primary Breast Cancer Patients Receiving Adjuvant Cyclophosphamide/Methotrexate/5-Fluorouracil Chemotherapy

Challenges of anemia correction during radiotherapy and chemoradiation

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