Raising Hemoglobin: An Opportunity for Increasing Survival?

Abstract

Although the association between low hemoglobin levels and poorer outcomes in radiation oncology has long been recognized, anemia is often overlooked and untreated. However, a growing body of clinical evidence now indicates that low hemoglobin levels during radiation treatment are associated with decreased response and survival following radiotherapy. For example, a large Canadian retrospective study in patients receiving radical radiotherapy for cervical cancer showed that the 5-year survival rate was 19% higher in those whose hemoglobin during radiation treatment was =12 g/dl compared to those with levels <12 g/dl. The data suggest that clinical trials need to be performed to determine whether increasing hemoglobin levels leads to improved local control and survival. The mechanism by which low hemoglobin levels could cause poorer outcomes is not well understood and needs further elucidation. It is postulated that lower hemoglobin levels resulting in decreased oxygen carrying capacity may lead to increased tumor hypoxia, radiation resistance and increased tumor angiogenesis. The interrelationship of low hemoglobin levels, hypoxia, tumor angiogenesis and survival is explored in this article.

VEGF signaling inhibitors: More pro-apoptotic than anti-angiogenic

“…The observation that VEGF inhibitors in fact cause chemosensitization [57] thus suggests a flaw in the conventional model of anti-angiogenic drug action. This dilemma is similar to that faced by proponents of erythropoietin therapy who predicted that erythropoietin-induced reduction of tumor hypoxia would enhance chemoresponsiveness and thus improve patient survival [70,71]-a prediction that proved directly contrary to the reality [12,14,16]. Similar evidence now indicates that the direct receptormediated effects of VEGFs on tumors-such as VEGF induction of phosphatidylinositol-3′-kinase (PI3K) and Akt, enhancing cell survival [72,73]-affect clinical outcomes more decisively than do changes in blood flow and/or oxygenation [74].…”

Synergistic Effects of Hemoglobin and Tumor Perfusion on Tumor Control and Survival in Cervical Cancer

“…The level of hemoglobin (Hgb), the body's oxygen carrier, has long been implicated as a critical factor contributing to tumor oxygenation and the radiocurability of cancer (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Cervical cancer is a classic example of the role of tumor hypoxia and the relationship between Hgb levels and tumor control.…”

“…Cervical cancer is a classic example of the role of tumor hypoxia and the relationship between Hgb levels and tumor control. Ample evidence has attested that low Hgb levels, or anemia, are associated with unfavorable local tumor control and survival in cervical cancer patients (1)(2)(3)(4)(5)(6)(7)(8)(9)(10), and the tumor oxygenation status has been well-established as a profound factor influencing radioresponsiveness and tumor control (11)(12)(13)(14).…”

“…However, the role of Hgb in cervical cancer patients treated with radiotherapy (RT) has remained controversial, with some believing Hgb is an independent prognostic factor for outcome (3)(4)(5)(6)(7)(8), and others suggesting that the adverse effect of anemia is a surrogate for advanced disease (9,10).…”

Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multicentre, randomised trial

“…Epoetin alfa therapy has been shown in both double-blind, placebo-controlled, and open-label studies to increase Hb levels in cancer patients receiving platinum-or nonplatinum-based chemotherapy, correcting anaemia, decreasing transfusion requirements, and subsequently improving patients' QOL (Abels, 1992;Leitgeb et al, 1994;Glaspy et al, 1997;Demetri et al, 1998;Dammacco et al, 2001;Gabrilove et al, 2001;Littlewood et al, 2001;Thomas, 2002;Janinis et al, 2003;Shasha et al, 2003;Savonije et al, 2004;Chang et al, 2005;Witzig et al, 2005). However, few studies to date have examined the outcome of anaemia treatment in ovarian cancer patients, and none have specifically evaluated the impact of anaemia treatment on QOL in this population (ten Bokkel Huinink et al, 1998).…”