Radiation therapy in the treatment of cervical Cancer: The university of Chicago/Michael reese hospital experience

Rader, Janet S.; Haraf, Daniel J.; Halpern, Howard J.; Rotmensch, Jacob; Spelbring, D.; Sutton, Harold G.; Javaheri, Godratollah; Weichselbaum, Ralph R.

doi:10.1002/jso.2930440307

Cited by 13 publications

(3 citation statements)

References 24 publications

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“…Most of the literature concerns malignancies of the uterine cervix (Evens and Bergso, 1965;Hierlihy et al, 1969;Vigerio et al, 1973;Bush et al, 1978;Dische et al, 1983;Mendenhall et al, 1984;Bush, 1986;Girinski et al, 1989;Rader, 1990) and head and neck (Blitzer et al, 1984;Overgard et al, 1989;Dubray et al, 1996). How anaemia is causally related to poor outcome is not entirely clear but it is probably both a marker of advanced tumour and indicative of some degree of tissue hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Effect of subcutaneous recombinant human erythropoetin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial

Sweeney

Nicolae²,

Ignacio³

et al. 1998

Br J Cancer

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Summary The purpose of this study was to determine the safety, efficacy and impact on quality of life of recombinant human erythropoietin (r-HuEPO) for cancer patients undergoing radiotherapy (RT). An open-labelled randomized design was used, with patients randomized to either treatment or control arms. Patients in the treatment arm received r-HuEPO given by subcutaneous injection at a dose of 200 units kg-' day-' plus oral iron supplements (ferrous sulphate 325 mg p.o. t.i.d.). Entry was restricted to patients with carcinoma of the lung, uterine cervix, prostate or breast who presented for RT with anaemia parameters reflective of 'the anaemia of chronic disease'. Radiotherapy policies (portals, doses, fraction size, etc.) were determined by the site and stage of disease. Complete blood counts (CBCs) were obtained weekly. The target level of haemoglobin was 15 g dl-1 for men and 14 g dl-1 for women. Quality of life (QOL) was assessed weekly by using an analogue scale to judge energy, activities of daily living and overall quality of life. Forty-eight patients were entered in the study, 24 in the treatment arm and 24 in the control arm. The prerandomization demographic characteristics and mean laboratory values were comparable in both arms. The mean haemoglobin at completion was 13.6 g dl-1 for r-HuEPO-treated patients compared with 11.0 g dl-1 for control subjects (P= 0.0012). Patients who received r-HuEPO demonstrated a mean weekly haemoglobin increase of 0.41 g dl-1 compared with a decrease in mean haemoglobin level in controls for 6 of the 7 weeks of the study (mean weekly decrease of 0.073 g dl-'). Target levels of haemoglobin were achieved by 41.6% of r-HuEPO-treated patients compared with none of the control subjects. The mean platelet count declined in both arms of the study with RT but the decline from pretreatment was less rapid in r-HuEPO-treated patients (11.2% decrease) compared with controls (26.3% decrease) and was statistically significant during weeks 4-6. Toxicity was minor with only mild irritation at the injection site. Mean quality of life end points were superior in the treatment arm but not statistically significant. r-HuEPO had a beneficial effect on weekly haemoglobin levels in patients undergoing RT with response rates similar to other studies. There was also a less rapid decline in weekly platelet counts in r-HuEPO-treated patients compared with control subjects. Further studies are needed to address the optimum dose and scheduling as well as the impact of r-HuEPO on clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Effect of subcutaneous recombinant human erythropoetin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial

Sweeney

Nicolae²,

Ignacio³

et al. 1998

Br J Cancer

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“…Importantly, findings of about half of these studies suggest that the hemoglobin threshold in the radiation oncology setting should be within the range of 12-14 g/dl. Although not investigated as extensively as pretreatment hemoglobin, a decrease in hemoglobin levels during radiation therapy also appears to negatively affect postradiation outcomes of patients with head and neck or cervical cancer [107,117,122,123,126,130].…”

Section: Correction Of Anemiamentioning

confidence: 99%

Impact of Tumor Hypoxia and Anemia on Radiation Therapy Outcomes

et al. 2002

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Local recurrence remains a major obstacle to achieving cure of many locally advanced solid tumors treated with definitive radiation therapy. The microen-vironment of solid tumors is hypoxic compared with normal tissue, and this hypoxia is associated with decreased radiosensitivity. Recent preclinical data also suggest that intratumoral hypoxia, particularly in conjunction with an acid microenvironment, may be directly or indirectly mutagenic. Investigations of the prognostic significance of the pretreatment oxygenation status of tumors in patients with head and neck or cer-vical cancer have demonstrated that increased hypoxia, typically designated in these studies as pO 2 levels below 2.5-10 mm Hg, is associated with decreased local tumor control and lower rates of disease-free and overall survival. Hypoxia-directed therapies in the radiation oncology setting include treatment using hyperbaric oxygen, fluosol infusion, carbogen breathing, and electron-affinic and hypoxic-cell sensitizers. These interventions have shown the potential to increase the effectiveness of curative-intent radiation therapy, demonstrating that the strategy of overcoming hypoxia may be a viable and important approach. Anemia is common in the cancer population and is suspected to contribute to intratu-moral hypoxia. A review of the literature reveals that a low hemoglobin level before or during radiation therapy is an important risk factor for poor locoregional disease control and survival, implying that a strong correlation could exist between anemia and hypoxia (ulti-mately predicting for a poor outcome). While having a low hemoglobin level has been shown to be detrimental, it is unclear as to exactly what the threshold for "low" should be (studies in this area have used thresholds ranging from 9-14.5 g/dl). Optimal hemoglobin and pO 2 thresholds for improving outcomes may vary across and within tumor types, and this is an area that clearly The Oncologist 2002;7:492-508 www.TheOncologist.com The Oncologist ® LEARNING OBJECTIVES After completing this course, the reader will be able to: 1. Discuss the prognostic significance of intratumoral hypoxia and low hemoglobin levels in patients receiving curative-intent radiation for head and neck or cervical cancer. 2. Describe the potential relationship between anemia and intratumoral hypoxia in patients with solid tumors. 3. List possible interventions for improving intratumoral oxygenation and radiosensitivity in the radiation oncology setting. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

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“…For all patients, the differences in disease-free survival were statistically significant (p<0.01). This strongly suggests that anemia is a poor prognostic indi cator [52]. Evans and Bergsjo's report [53] from Norwegian Radiam Hos pital studied two groups of patients: the first group of 895 pa tients was treated from 1940 to 1945, and a second group of 490 patients was treated between 1956 and 1958.…”

Section: Carcinoma O F Cervixmentioning

confidence: 99%

Blood Transfusion in Patients Receiving Radical Radiotherapy: A Reappraisal

Levine

Vijayakumar

1993

Oncol Res Treat

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Blood transfusion has been widely touted as a useful adjunct to radiation therapy. This is based on the premise that higher hemoglobin levels will increase tissue oxygenation thereby improving the efficacy of therapeutic radiation. Consequently, it has become common clinical practice to transfuse patients undergoing radiotherapy to arbitrary hemoglobin levels. There has been extensive research evaluating the use of transfusion with radiotherapy. Animal data are divided regarding the radiobiologic benefits of transfusion. Clinical experience has established that anemia is a poor prognostic indicator in patients receiving radiotherapy. However, clinical trials have not clearly shown that correction of anemia by transfusion improves the outcomes. This may be explained by adverse effects of transfusion on tumor immunobiology. In addition to the well-known risks of infectious disease, alloimmunization, and allergic reactions, homologous blood has been shown to be immunosuppressive. This immunosuppression has been associated with decreased survival as well as increased rates of recurrence in the treatment of a variety of malignancies, thus making homologous transfusion particularly hazardous for the tumor-bearing patient. This suggests that routine use of transfusion to support patients receiving radiotherapy must be reappraised, and alternative methods of increasing hemoglobin, such as recombinant human erythropoietin (r-HuEPO), need to be considered. r-HuEPO represents a unique opportunity to assess the value of increasing hemoglobin mass without the confounding variable of immunosuppression. Consequently, a prospective clinical trial utilizing r-HuEPO in patients undergoing radiotherapy seems warranted.

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Radiation therapy in the treatment of cervical Cancer: The university of Chicago/Michael reese hospital experience

Cited by 13 publications

References 24 publications

Effect of subcutaneous recombinant human erythropoetin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial

Effect of subcutaneous recombinant human erythropoetin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial

Impact of Tumor Hypoxia and Anemia on Radiation Therapy Outcomes

Blood Transfusion in Patients Receiving Radical Radiotherapy: A Reappraisal

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