Carbogen Breathing Research Articles

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: A stepwise developed treatment schedule for advanced head-and-neck cancer

Purpose: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. Methods and Materials: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m 2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m 2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. Results: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. Conclusions: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions.

Improvement of tumor oxygenation by mild hyperthermia.

There is now abundant evidence that oxygenation in rodent, canine and human tumors is improved during and for up to 1-2 days after heating at mild temperatures. An increase in tumor blood perfusion along with a decline in the oxygen consumption rate appears to account for the improvement of tumor oxygenation by mild hyperthermia. The magnitude of the increase in tumor pO(2), determined with oxygen-sensitive microelectrodes, caused by mild hyperthermia is less than that caused by carbogen breathing. However, mild hyperthermia is far more effective than carbogen breathing in increasing the radiation response of experimental tumors, probably because mild hyperthermia oxygenates both (diffusion-limited) chronically hypoxic and (perfusion-limited) acutely hypoxic cells, whereas carbogen breathing oxygenates only the chronically hypoxic cells. Mild hyperthermia is also more effective than nicotinamide, which is known to oxygenate acutely hypoxic cells, in enhancing the radiation response of experimental tumors. The combination of mild hyperthermia with carbogen or nicotinamide is highly effective in reducing the hypoxic cell fraction in tumors and increasing the radiation response of experimental tumors. A primary rationale for the use of hyperthermia in combination with radiotherapy has been that hyperthermia is equally cytotoxic toward fully oxygenated and hypoxic cells and that it directly sensitizes both fully oxygenated and hypoxic cells to radiation. Such cytotoxicity and such a radiosensitizing effect may be expected to be significant when the tumor temperature is elevated to at least 42-43 degrees C. Unfortunately, it is often impossible to uniformly raise the temperature of human tumors to this level using the hyperthermia devices currently available. However, it is relatively easy to raise the temperature of human tumors into the range of 39-42 degrees C, which is a temperature that can improve tumor oxygenation for up to 1-2 days. The potential usefulness of mild hyperthermia to enhance the response of human tumors to radiotherapy by improving tumor oxygenation merits continued investigation.

Effects of different levels of hypercapnic hyperoxia on tumour R2∗ and arterial blood gases

The hypercapnia induced by carbogen (95% O2/5% CO2) breathing, which is being re-evaluated as a clinical radiosensitiser, causes patient discomfort and hence poor compliance. Recent preclinical and clinical studies have indicated that the CO2 content might be lowered without compromising increased tumour oxygenation and radiosensitisation. This preclinical study was designed to see if lower levels of hypercapnia could evoke similar decreases in the transverse relaxation rate R2∗ of rodent tumours to those seen with carbogen breathing. The response of rat GH3 prolactinomas to 1%, 212% and 5% CO2 in oxygen, and 100% O2 breathing, was monitored by non-invasive multi-gradient echo MRI to quantify R2∗. As the oxygenation of haemoglobin is proportional to the blood paO2 and therefore in equilibrium with tissue pO2, R2∗ is a sensitive indicator of tissue oxygenation. Hyperoxia alone decreased R2∗ by 13%, whilst all three hypercapnic hyperoxic gases decreased R2∗ by 29%. Breathing 1% CO2 in oxygen evoked the same decrease in R2∗ as carbogen. The ΔR2∗ response is primarily consistent with an increase in blood oxygenation, though localised increases in tumour blood flow were also identified in response to hypercapnia. The data support the concept that levels of hypercapnia can be reduced without loss of enhanced oxygenation and hence potential radiotherapeutic benefit.

345 poster Hyperfractionated chemoradiotherapy with carbogen breathing, and with or without erythropoietin for head and neck cancer

345 poster Hyperfractionated chemoradiotherapy with carbogen breathing, and with or without erythropoietin for head and neck cancer

Fractionated irradiation combined with carbogen breathing and nicotinamide of two human glioblastomas grafted in nude mice.

This study addressed the potential radiosensitizing effect of nicotinamide and/or carbogen on human glioblastoma xenografts in nude mice. U-87MG and LN-Z308 tumors were irradiated with either 20 fractions over 12 days or 5 fractions over 5 days in air-breathing mice, mice injected with nicotinamide, mice breathing carbogen, or mice receiving nicotinamide plus carbogen. The responses to treatment were assessed using local control and moist desquamation. In U-87MG tumors, the enhancement ratios (ERs) at the radiation dose required to produce local tumor control in 50% of the treated mice (TCD(50)) with nicotinamide and/or carbogen ranged from 1.13 to 1.24 for irradiation in 20 fractions over 12 days. In LN-Z308 tumors, the ERs at the TCD(50) with nicotinamide and/or carbogen ranged from 1.22 to 1.40 for irradiation in 5 fractions over 5 days and from 1.11 to 1.30 in 20 fractions over 12 days, respectively. Skin injury was slightly enhanced, with ERs ranged from 1.06 to 1.15 when radiation was combined with carbogen and/or nicotinamide. Thus carbogen and nicotinamide can slightly improve the radiation response of human glioblastoma xenografts.

Issues of Normal Tissue Toxicity in Patient and Animal Studies - Effect of Carbogen Breathing in Rats after 5-Fluorouracil Treatment

Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers. We report two studies of 5-FU toxicity in normal tissue?one with patients and the other an animal study. 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have no liver metastases. This is the first report of non-invasive monitoring of toxic 5-FU metabolites in normal human tissues. 2) In animals, carbogen breathing enhances tumour uptake and the efficacy of 5-FU, and the method is under trial in patients. This study demonstrates that there were no significant effects of carbogen breathing on the levels of 5-FU and its metabolites in normal rat tissues, or on the histology of the tissues assessed after treatment.

Radiosensitizing Effect of Carbogen Breathing during Pulsed Irradiation of the Rat R1H Tumor

The objective of the present study was to investigate the radiosensitizing effect of carbogen breathing during pulsed x-ray irradiation in an experimental tumor model. Rat R1H rhabdomyosarcoma tumors were irradiated with 36 Gy total dose in 1 Gy high dose rate pulses, either hourly repeated, or in an 'office hours' protocol with irradiation-free overnight intervals. With the hourly, pulsed irradiation scheme, tumor growth delay (TGD) was significantly increased from 24.4 - 0.7 days in air-breathing animals to 29.0 - 0.9 days in animals breathing carbogen during irradiation. With irradiation during office hours, the TGD was shortened, and carbogen was less effective. The data show that carbogen acts as a radiosensitizer when applied during pulsed irradiation. Translation of the experimental data to clinical practice indicates that hyperoxygenation of the tumor during pulsed dose rate (PDR) or high dose rate (HDR) brachytherapy might enhance the tumor response of patients.

Changes in tumor hypoxia measured with a double hypoxic marker technique

Purpose: Development of a double hypoxic cell marker assay, using the bioreductive nitroimidazole derivatives CCI-103F and pimonidazole, to study changes in tumor hypoxia after treatments that modify tumor oxygenation. Methods and Materials: Both hypoxic markers were visualized by immunohistochemical techniques to detect changes in hypoxic fraction induced by carbogen breathing (95% O 2 and 5% CO 2) or hydralazine injection. The protocol was tested in a human laryngeal squamous cell carcinoma xenograft line. Quantitative measurements were derived from consecutive tissue sections that were analyzed by a semiautomatic image analysis system. Qualitative analysis was obtained by double staining of the two hypoxic markers on the same tissue section. Results: A significant correlation between the hypoxic fractions for the two markers, CCI-103F and pimonidazole, was found in air breathing animals. After carbogen breathing, the hypoxic fraction decreased significantly from 0.07 to 0.03, and after hydralazine treatment, the hypoxic fraction increased significantly. Reduction of hypoxia after carbogen breathing was most pronounced close to well-perfused tumor regions. Conclusions: With this method, employing two consecutively injected bioreductive markers, changes in tumor hypoxia can be studied. A significant reduction in hypoxia after carbogen breathing and a significant increase in hypoxia after hydralazine administration was demonstrated.

Effects of nicotinamide and carbogen on oxygenation in human tumor xenografts measured with luminescense based fiber-optic probes

Background and purpose: In head and neck cancer, addition of both carbogen breathing and nicotinamide to accelerated fractionated radiotherapy showed increased loco-regional control rates. An assay based on the measurement of changes in tumor pO 2 in response to oxygenation modification could be helpful for selecting patients for these new treatment approaches. Materials and methods: The fiber-optic oxygen-sensing device, OxyLite™, was used to measure changes in pO 2, at a single position in tumors, after treatment with nicotinamide and carbogen in three human xenograft tumor lines with different vascular architecture and hypoxic patterns. Pimonidazole was used as a marker of hypoxia and was analyzed with a digital image processing system. Results: At the position of pO 2 measurement, half of the tumors showed a local increase in pO 2 after nicotinamide administration. Steep increases in pO 2 were measured in most tumors during carbogen breathing although the increase was less pronounced in tumor areas with a low pre-treatment pO 2. A trend towards a faster local response to carbogen breathing for nicotinamide pre-treated tumors was found in all three lines. There were significant differences in hypoxic fractions, based on pimonidazole binding, between the three tumor lines. There was no correlation between hypoxic marker binding and the response to carbogen breathing. Conclusion: Temporal changes in local pO 2 can be measured with the OxyLite™. This system was used to quantitate the effects of oxygen modifying treatments. Rapid increases in pO 2 during carbogen breathing were observed in most tumor areas. The locally measured response to nicotinamide was smaller and more variable. Bio-reductive hypoxic cell marker binding in combination with OxyLite™ pO 2 determination gives spatial information about the distribution patterns of tumor hypoxia at the microscopic level together with the possibility to continuously measure changes in pO 2 in specific tumor areas.

Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI

Purpose: In an effort to improve radiotherapy treatments, methods aimed at increasing the quantity of oxygen delivered to tumors were investigated. The aim of this study was to evaluate the effect of one nitric oxide (NO) donor (isosorbide dinitrate) on pO 2 and blood flow in a murine tumor model. The effect was compared to carbogen, used as a reference treatment. Methods and Materials: Thirty-six liver tumors implanted in mouse thighs were imaged using magnetic resonance imaging (MRI) at 4.7 Tesla with dynamic Gd-DTPA and blood oxygen level-dependent (BOLD) contrast-enhanced imaging after administration of isosorbide dinitrate or carbogen. The effect on the pO 2 was also tested by EPR oximetry (1.1 GHz) on 52 mice. Results: A significant increase in MRI intensity was observed for both treatments in comparison with the control group. EPR oximetry showed a dose-dependant increase in tumor pO 2 for isosorbide dinitrate (by 5.9 mmHg at 0.2 mg/kg) and a substantially greater change for carbogen breathing (by 23 mmHg). Conclusion: Both tumor blood flow and pO 2 were increased by isosorbide dinitrate and carbogen. Carbogen is more efficient than isosorbide dinitrate in increasing the BOLD image intensity, as well as the tumor pO 2, but as efficient as isosorbide dinitrate in the Gd-DTPA contrast-enhanced imaging. We conclude that the effects of carbogen on improving tumor pO 2 involve both improved blood flow and improved hemoglobin oxygenation, whereas the effects of isosorbide dinitrate are predominantly mediated by improved blood flow alone.

Effect of carbogen breathing on the pharmacodynamics of 5-fluorouracil in a murine colon carcinoma

To determine whether carbogen breathing has an effect on 5-fluorouracil (5-FU) uptake, retention and metabolism in C38 murine colon tumours grown in C57Bl/6 mice, we used in vivo 19F nuclear magnetic resonance (NMR) spectroscopy. Eleven tumour-bearing mice were treated with 150 mg/kg of 5-FU given intraperitoneally (i.p.). Five mice received carbogen gas (95% O 2 and 5% CO 2) for 9.5 min, starting 1 min before 5-FU administration. We found increased levels of 5-FU and its anabolites and catabolites by sequential [ 19F] NMR spectroscopy in the group treated with 5-FU in combination with carbogen compared with the group treated with 5-FU alone. The maximum of normalised values of 5-FU and its metabolites, reached after carbogen breathing, was almost 2-fold higher than after treatment with 5-FU alone. Despite these increased concentrations no significant effect of carbogen on growth inhibition of the tumour by 5-FU was observed, which may be related to the size as well as the well vascularised and perfused conditions of the tumours studied.

Effects of nicotinamide and carbogen on tumour oxygenation, blood flow, energetics and blood glucose levels.

Both host carbogen (95% oxygen/5% carbon dioxide) breathing and nicotinamide administration enhance tumour radiotherapeutic response and are being re-evaluated in the clinic. Non-invasive magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) methods have been used to give information on the effects of nicotinamide alone and in combination with host carbogen breathing on transplanted rat GH3 prolactinomas. Gradient recalled echo (GRE) MRI, sensitive to blood oxygenation changes, and spin echo (SE) MRI, sensitive to perfusion/flow, showed large signal intensity increases with carbogen breathing. Nicotinamide, thought to act by suppressing the transient closure of small blood vessels that cause intermittent tumour hypoxia, induced a small increase in blood oxygenation but no detectable change in perfusion/flow. Carbogen combined with nicotinamide was no more effective than carbogen alone. Both carbogen and nicotinamide caused significant increases in the nucleoside triphosphate/inorganic phosphate (βNTP/P i) ratio, implying that the tumour cells normally receive sub-optimal substrate supply, and is consistent with either increased glycolysis and/or a switch to more oxidative metabolism. The most striking observation was the marked increase in blood glucose (twofold) induced by both nicotinamide and carbogen. Whether this may play a role in tumour radiosensitivity has yet to be determined. Copyright 2000 Cancer Research Campaign© 2000 Cancer Research Campaign

ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Co-operative Group of Radiotherapy of the European Organization for Research and Treatment of Cancer (EORTC)

Background: Since there is increasing evidence that both acute (perfusion-limited) and chronic (diffusion-limited) hypoxia, and tumor repopulation may prejudice the outcome of radiotherapy, the combination of carbogen (95% oxygen–5% carbon dioxide) and nicotinamide with accelerated radiotherapy (ARCON) should reduce the impact of these factors of radioresistance.Aim: This clinical study was aimed at determining the feasibility, as well as the qualitative and quantitative toxic effects of a therapeutic approach based on ARCON, and assessing the tumor response rates that can be achieved with this regime in patients with locally advanced tumors of the head and neck.Methods: A phase I/II study conducted between 1993 and 1996 by the Co-operative Group of Radiotherapy of the EORTC included three consecutive steps: accelerated fractionation (AF) combined with carbogen (11 analyzable patients), AF combined with the daily administration of nicotinamide (n=10), and AF with both carbogen and nicotinamide (n=17). Radiotherapy was based on an accelerated regime (72 Gy in 5.5 weeks). Nicotinamide was delivered 90 min before the first irradiation session, at a daily dose of 6 g. Carbogen breathing started 5 min before irradiation and lasted throughout the entire radiotherapy sessions.Results: No significant difference in loco-regional toxicity was found among the three study steps, when carbogen and nicotinamide, either alone or in combination, were combined with AF. The feasibility of the ARCON protocol, as proposed in the present EORTC study, appears to be significantly impaired when nicotinamide is added, at a daily dose of 6 g, to AF and carbogen, in an unselected group of patients. More than 20% of patients experienced grade 2 or 3 emesis. It also demonstrates, in unselected groups of patients, no significant difference in tumor response and local control when carbogen and nicotinamide, either alone or in combination, are added to accelerated radiotherapy. The percentages of objective response at 2 months were 81, 70 and 87%, respectively.Conclusion: Future ARCON trials should target selected head and neck tumor localizations and stages, and a lower nicotinamide dose is needed to reduce severe upper gastro-intestinal toxicity.

Feasibility of Detecting Hypoxia in Experimental Mouse Tumours with 18F-fluorinated Tracers and Positron Emission Tomography: A Study Evaluating [18F]Fluoromisonidazole and [18F]Fluoro-2-deoxy-D-glucose

The study was designed to investigate the binding of [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluoro-2-deoxy-D-glucose ([18F]FDG) in a C3H mouse mammary carcinoma. Non-anaesthetized tumour-bearing animals breathing either normal air or carbogen (to reduce tumour hypoxia) were examined by PET after tracer injection. Tumours were identified by radioactive labelling and methods of defining regions of interest (ROI) in the tumours were investigated. Reference tissue was selected elsewhere in the mice and the ratio between mean radioactivity in tumour and reference tissue was compared. The results showed a correlation between the methods of identifying ROIs and a significantly lower tumour to reference tissue ratio for carbogen-treated mice compared with controls when using [18F]FMISO. Only one of the methods showed a significant difference in the tumour labelling between treatment groups using [18F]FDG. The study supports the contention that [18F]FMISO may be able to identify hypoxia in tumours, whereas a similar role for [18F]FDG is more doubtful.

Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing

The effects of hyperoxia (induced by host carbogen 95% oxygen/5% carbon dioxide breathing. and hypoxia (induced by host carbon monoxide CO at 660 ppm. breathing) were compared by using noninvasive magnetic resonance (MR) methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD) MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb), which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen breathing, or carboxyhemoglobin with CO breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO breathing. There was no change in nucleoside triphosphates (NTP)/PI in either tumor or liver after CO breathing, whereas NTP/Pl increased twofold in the hepatoma (but not in the liver) after carbogen breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO breathing and more acid after carbogen breathing, respectively. This tumor type and the liver are unaffected by CO breathing at 660 ppm, which implies an adequate oxygen supply.

Formula omitted]w and [formula omitted]xygenation [formula omitted]ependent (FLOOD) contrast MR imaging to monitor the response of rat tumors to carbogen breathing

Gradient recalled echo (GRE) images are sensitive to both paramagnetic deoxyhaemoglobin concentration (via T ∗ 2) and flow (via T ∗ 1). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbogen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect flow and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and flow contribute to image intensity contrast changes. T 1-weighted images, with and without outer slice suppression, and calculated T 2, T ∗ 2 and “flow” maps, were obtained for subcutaneous GH3 prolactinomas in rats during air and carbogen breathing. T 1-weighted images showed bright features that increased in size, intensity and number with carbogen breathing. H&E stained histological sections confirmed them to be large blood vessels. Apparent T 1 and T 2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T 1 and 11% for T 2 during carbogen breathing. The apparent T ∗ 2 over all tumors was very heterogeneous, with values between 9 and 23 ms and localized increases of up to 75% during carbogen breathing. Synthesised “flow” maps also showed heterogeneity, and regions of maximum increase in flow did not always coincide with maximum increases in T ∗ 2. Carbogen breathing caused a threefold increase in arterial rat blood p aO 2, and typically a 50% increase in tumor blood volume as measured by 51Cr-labelled RBC uptake. The T ∗ 2 increase is therefore due to a decrease in blood deoxyhaemoglobin concentration with the magnitude of the FLOOD response being determined by the vascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of response of individual tumors to blood flow modifiers for both chemotherapy, anti-angiogenesis therapy in particular, and radiotherapy.

Pharmacological modifications of the partial pressure of oxygen in murine tumors: evaluation using in vivo EPR oximetry.

EPR oximetry using an implantable paramagnetic probe was used to quantify the partial pressure of oxygen (pO(2)) in tissues in a transplantable mouse tumor model (TLT) after administration of 34 different vasodilators belonging to one of the following classes: angiotensin-converting enzyme inhibitors, calcium antagonists, alpha antagonists, potassium channel openers, beta-blockers, NO donors, and peripheral vasoactive agents. Twenty-four compounds were efficient in significantly increasing the local pO(2) in a majority of tumors. The increase of local pO(2) using pharmacological treatments was lower than that achieved by using oxygen or carbogen breathing. This technique offers an unprecedented tool for rapidly and accurately measuring treatment-induced modifications of pO(2) in tumors. Magn Reson Med 42:627-630, 1999.

Effect of carbogen breathing on the physiological profile of human glioma xenografts

Effect of carbogen breathing on the physiological profile of human glioma xenografts

Effect of carbogen breathing on the physiological profile of human glioma xenografts.

The aim of this study was to evaluate the effect of carbogen breathing on the physiological profile of human glioma xenografts. Near infrared spectroscopy was used to investigate changes in oxy- and deoxyhemoglobin concentrations in tumor blood. Oxygen tension changes in tumor tissue were evaluated by (19)F-MR relaxometry, using perfluoro-15-crown-5-ether, and modifications of tumor blood perfusion (TBP) were analyzed by fast dynamic (1)H-MR imaging of Gd-DTPA uptake. Finally, changes of the bioenergetic status and pH of tumor cells were analyzed by (31)P-MRS. After 5 to 8 min of carbogen breathing, the average oxygen tension increase in tumor tissue was 4.6 +/- 1.3 mm Hg, which is in agreement with an increase of the oxyhemoglobin concentration in tumor blood (Delta[O(2)Hb] = 9. 2 +/- 3 microM). However, simultaneously the TBP was reduced, the bioenergetic status was diminished, and pH was decreased. As 100% O(2) breathing alone did not result in a detectable increase of oxyhemoglobin in tumor blood, the increase of the tumor oxygenation by carbogen appears to be mediated by its CO(2) content. This component may cause a nutrient-limited decrease of oxidative energy metabolism, indirectly via a steal-effect and/or by inhibition of the glycolytic rate resulting from tissue acidification. Magn Reson Med 42:490-499, 1999.

Carbogen Inhalation in Cervical Cancer: Assessment of Oxygenation Change

Objective. Our objectives were (1) to examine tumor oxygenation measured with an Eppendorf pO2 histograph, prior to and during carbogen (95% oxygen, 5% carbon dioxide) breathing in patients with primary cervical cancer; and (2) to assess the feasibility of delivering external beam radiation therapy and concurrent carbogen to patients treated for cervical cancer.Methods. Pretreatment tumoral pO2 measurements were obtained using an Eppendorf pO2 histograph in patients with primary cervical cancers while breathing room air and after 4 min of carbogen breathing. Patients able to tolerate the carbogen inhalation were asked to inhale it for 4 min prior to and during all external beam radiation therapy.Results. Two sets of pO2 measurements were obtained from 25 patients. The average median pO2 increased from 8 mm Hg when breathing room air to 96 mm Hg after carbogen breathing. Twenty-four of 25 patients tolerated the carbogen; they inhaled carbogen during their daily external beam radiation therapy. All 24 patients completed their planned course of external beam radiation therapy and daily concurrent carbogen without significant difficulty.Conclusion. (1) Carbogen inhalation increased the average median pO2 value 10-fold and decreased the percentage of values ≤2.5 and 5 mm Hg. (2) Carbogen inhalation is feasible during external beam pelvic radiation.