Hyperbaric oxygen therapy as adjunctive strategy in treatment of glioblastoma multiforme.
Huang Lei,Boling Warren,Zhang John H
Medical gas research
Glioblastoma multiforme (GBM) is the most common type of malignant intracranial tumor in adults. Tumor tissue hypoxia, high mitotic rate, and rapid tumor spread account for its poor prognosis. Hyperbaric oxygen therapy (HBOT) may improve the sensitivity of radio-chemotherapy by increasing oxygen tension within the hypoxic regions of the neoplastic tissue. This review summarizes the research of HBOT applications within the context of experimental and clinical GBM. Limited clinical trials and preclinical studies suggest that radiotherapy immediately after HBOT enhances the effects of radiotherapy in some aspects. HBOT also is able to strengthen the anti-tumor effect of chemotherapy when applied together. Overall, HBOT is well tolerated in the GBM patients and does not significantly increase toxicity. However, HBOT applied by itself as curative strategy against GBM is controversial in preclinical studies and has not been evaluated rigorously in GBM patients. In addition to HBOT favorably managing the therapeutic resistance of GBM, future research needs to focus on the multimodal or cocktail approaches to treatment, as well as molecular strategies targeting GBM stem cells.
10.4103/2045-9912.229600
Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study.
Hartford Alan C,Davis Thomas H,Buckey Jay C,Foote Robert L,Sinesi Mark S,Williams Benjamin B,Fariss Anna K,Schaner Philip E,Claus Paul L,Okuno Scott H,Hussey James R,Clarke Richard E
International journal of radiation oncology, biology, physics
PURPOSE:To explore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS:Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy >6 months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4 atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiation therapy began within 15 minutes after HBO. Patients were followed for 2 years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+ years for local recurrence, distant metastases, disease-specific survival, and overall survival. RESULTS:Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14 weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5 minutes, with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per-protocol 5-year overall survival was 100%, local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO. CONCLUSIONS:While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation.
10.1016/j.ijrobp.2016.10.048
Partial hypoxia as a cause of radioresistance in a human tumor xenograft: its influence illustrated by the sensitizing effect of misonidazole and hyperbaric oxygen.
Reynaud-Bougnoux A,Lespinasse F,Malaise E P,Guichard M
International journal of radiation oncology, biology, physics
While previous studies with three human tumor xenografts suggest that contact-resistance plays a major role in the response of these tumors to radiation, it remains possible that partial hypoxia may provide an alternate explanation. The present study was carried out to check this possibility by investigating the influence of misonidazole (MISO) and hyperbaric oxygen (HBO) on both the initial and distal components of the survival curves of HRT18 tumor cells. The effect of a challenge dose of radiation on the initial radioresistance of this tumor was also studied. To assess the effects of MISO and HBO, tumor cell survival was determined by excision assay in two groups of tumor-bearing mice, one given MISO (1 mg/g body weight, i.p.) 45 min before irradiation and the other exposed to HBO (3.5 bars). MISO treatment caused greater sensitization than HBO. The enhancement ratios at the 5.10(-1) level were 1.7 (MISO) and 1.7 (HBO); at the 10(-1) level, they were 1.6 (MISO) and 1.4 (HBO); while at 10(-2), they were 1.6 (MISO) and 1.4 (HBO). These two sensitizing effects favor the hypothesis that solid tumors contain a compartment of partially hypoxic cells. To study the effect of a challenge radiation dose on initial radioresistance, tumors were given a challenge dose of 8 Gy, followed 24-48 hr later by doses ranging from 2-12 Gy. The challenge dose did not modify the shape of the survival curve.
10.1016/0360-3016(86)90154-9
The Leeds results for radiotherapy in HBO for carcinoma of the head and neck.
Berry G H,Dixon B,Ward A J
Clinical radiology
Follow-up data at five years are reported for 24 patients with squamous cell carcinoma of the head and neck, included in a randomised prospective MRC study of radiotherapy in hyperbaric oxygen (10 fractions) or air (15 or 20 fractions). Although few, the data show a significant gain in local control (P less than 0.001) and survival (P less than 0.05) with the use of hyperbaric oxygen but no increased tissue reactions or morbidity.
Radiotherapy after hyperbaric oxygenation for malignant gliomas: a pilot study.
Kohshi K,Kinoshita Y,Terashima H,Konda N,Yokota A,Soejima T
Journal of cancer research and clinical oncology
The results of radiotherapy combined with hyperbaric oxygen in 9 patients with malignant glioma were compared with those of radiotherapy without hyperbaric O2 in 12 patients. This is the first report of a pilot study of irradiation immediately after exposure to hyperbaric O2 in humans. All patients receiving this treatment showed more than 50% regression of the tumor, and in 4 of them, the tumors disappeared completely. Only 4 out of 12 patients without hyperbaric O2 showed decreases in tumor size, and all 12 patients died within 36 months. So far, this new regimen seems to be a useful form of radiotherapy for malignant gliomas.
Effects of hyperbaric oxygen and a perfluorooctylbromide emulsion on the radiation responses of tumors and normal tissues in rodents.
Rockwell S,Irvin C G,Kelley M,Hughes C S,Yabuki H,Porter E,Fischer J J
International journal of radiation oncology, biology, physics
Perfluorochemical emulsions are being examined in many laboratory and clinical studies as possible adjuncts to radiotherapy and chemotherapy. The studies reported here examine the clinical potential of hyperbaric oxygen (HBO) in combination with a highly concentrated perfluorochemical emulsion (Oxygent) containing 100% w/v perfluorooctylbromide (PFOB). HBO alone produced only a small improvement in the radiation response of BA1112 tumors in WAG/rij rats, while regimens combining HBO with Oxygent produced much greater radiation sensitization. A sham emulsion, formulated without the O2-carrying PFOB, did not alter the radiation response of the tumors in comparison with that seen with HBO alone. Neither HBO nor Oxygent plus HBO altered the radiosensitivity of bone marrow progenitor cells in BALB/c mice. HBO alone augmented skin reactions in BALB/c mice, but addition of Oxygent did not alter the skin reactions in comparison to those seen with HBO alone. Regimens combining Oxygent with HBO selectively increased the radiation sensitivity of tumors relative to normal tissues, thereby enhancing the therapeutic ratio. These results support the potential usefulness of perfluorochemical emulsions and HBO in clinical radiation therapy.
10.1016/0360-3016(92)90986-r
Hyperbaric oxygen as a radiotherapeutic adjuvant in advanced cancer of the uterine cervix: preliminary results of a randomized trial.
Fletcher G H,Lindberg R D,Caderao J B,Wharton J T
Cancer
From September 1968 to March 1974, a randomized clinical trial was carried out, using conventional fractionation, i.e., five treatments per week, in 233 patients with advanced cancers of the uterine cervix--Stages IIB, IIA, IIIB and IVA. The age limit was 70 years and all patients had medical clearance. Lymphangiography and, in some patients, an exploratory laparotomy with selective lymphadenectomy, were done prior to treatment to determine the extent of nodal disease. The staging has not been changed either by lymphangiogram or lymphadenectomy findings. A few patients with bulky Stage I and IIA lesions were entered into the trial because of extensive nodal disease demonstrated either by lymphangiogram and/or lymphadenectomy. First, the patients were grouped according to the clinical stage. The secondary stratification was according to the lymphangiogram and/or selective lymphadenectomy findings. The patients were then randomized to air or hyperbaric oxygen within each group. The patients were pressurized in a Vickers chamber at 3 atmosphere absolute, using a 20-minute soak time prior to the irradition. The size of the external beam portal was determined by the status of the nodes. The difference in absolute NED (no evidence of disease) survival rates for both groups as a whole and by stages is not statistically significant. There is no difference in the incidence of failures in the irradiated area between the HPO and air patients. There is no increase in distant metastases in the HP group. It does not seem that the HPO has had an effect on the major complications. However, there was an increase in the incidence of complications with extended fields. The addition of lymphadenectomy had increased the incidence of fatal complications, even with routine pelvic portals. The negative results of this trial with conventional fractioantion should not lead to the conclusion that HPO could not be useful with schemes using a few high dose fractions.
10.1002/1097-0142(197702)39:2<617::aid-cncr2820390237>3.0.co;2-2
The treatment of locally advanced head and neck cancer with misonidazole, hyperbaric oxygen and irradiation: an interim report.
Sealy R,Cridland S
International journal of radiation oncology, biology, physics
Thirty-one patients with advanced inoperable squamous carcinoma of the mouth were treated in a pilot study with misonidazole (2.0 gm/m2) with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The one and two year disease free survival was 48 and 26%, respectively. A prospective randomized trial is now being conducted comparing this regimen with 63.0 Gy in 30 fractions in 38 days in air. One hundred-fourteen patients have been entered; 91 are available for analysis at six months or more. The preliminary results at 6 and 12 months favor the combination of sensitizers. There is no added toxicity.
10.1016/0360-3016(84)90536-4
Increase in radiosensitivity of lung micrometastases by hyperbaric oxygen.
Milas L,Hunter N M,Ito H,Brock W A,Peters L J
Clinical & experimental metastasis
Four-day-old artificial pulmonary micrometastases of two murine fibrosarcomas, designated FSA and NFSA, showed increased sensitivity to ionizing radiation by a factor of 1.13 when animals were exposed to hyperbaric oxygen breathing before and during irradiation, implying the presence of hypoxia in the micrometastases. At the time of irradiation the diameter of FSA and NFSA metastases was smaller than 200 and 100 microns, respectively, which, on the basis of oxygen diffusion, could not be responsible for hypoxia. It is assumed that hypoxia of micrometastases is passive, reflecting the radiobiological hypoxia of lung tissue that could exist under normal breathing conditions.
10.1007/bf01758951
Effect of anemia on tumor radiosensitivity under normo and hyperbaric conditions.
Rojas A,Stewart F A,Smith K A,Soranson J A,Randhawa V S,Stratford M R,Denekamp J
International journal of radiation oncology, biology, physics
The effect of chronic anemia on tumor radiosensitivity in a murine tumor has been investigated. Anemia was induced by bilateral kidney irradiation given several months before tumor implantation. Anemic, anemic transfused, and normal non-anemic age-matched tumor bearing animals were irradiated with X rays (2 F/24 hr) either in air, air plus misonidazole, or under hyperbaric oxygen. The most resistant response was that of tumors grown in normal mice treated in air. Anemia produced an increase in radiosensitivity which was further enhanced by red blood cell replacement. The most sensitive overall response was seen in the anemic-transfused group treated with HBO.
10.1016/0360-3016(87)90165-9
Radiotherapy of bronchogenic carcinoma. Analysis of a treatment schedule designed for use with hyperbaric oxygen.
Sause W T,Sweeney R A,Plenk H P,Thomson J W
Radiology
All cases of bronchogenic carcinoma treated with curative intent over an eight-year period were reviewed. Most were treated with 12 X 400 rad in 32 days using 60Co, a schedule designed to optimize the radiation-sensitizing properties of hyperbaric oxygen. While O2 gave no obvious benefit, overall four-year survival was 10.6% and that of patients with good prognostic indicators was 18%. No radiation myelitis was observed. This protocol delivers an adequate tumor dose and appears to be tolerated well by most patients.
10.1148/radiology.140.1.7244227
Irradiation with misonidazole and hyperbaric oxygen: final report on a randomized trial in advanced head and neck cancer.
Sealy R,Cridland S,Barry L,Norris R
International journal of radiation oncology, biology, physics
One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease.
10.1016/0360-3016(86)90168-9
[Treatment of rhabdomyosarcoma in mice C3H/He by Co 60 and hyperbaric oxygen (author's transl)].
Agnius-Delord C,Couderc P,Laval P,Mourret A,Rinaldi R,Rinaldi C
Bulletin du cancer
UNLABELLED:Experimental study of rhabdomyosarcoma with successive transplantation upon C3H/He mice, treated by irradiation (Co 60) and combined irradiation-hyperbaric oxygen (HBO), dating from 3, 14 and 15 days after transplantation. The data (tumor volume evolution, histological modifications, pulmonary metastases) are compared with controls. CONCLUSIONS:curative radiotherapy depends on starting treatment as soon as possible with or without HBO. After the 14th day, sensitisation to combined HBO and C60 is seen. The extension of pulmonary metastases is a function of tumor growth. Paradoxically metastases were less frequent after HBO only and more frequent after HBO-Co 60.
[Radiotherapy under conditions of hyperbaric oxygen tension in a case of stage IV carcinoma of the cervix (author's transl)].
Kärcher K H
Wiener klinische Wochenschrift
A case report is given of bilateral renal obstruction, uraemia and anaemia in a patient with carcinoma of the uterine cervix treated by Wertheim hysterectomy with bilateral tumour recurrence in the true pelvis. Combined therapeutic management - medical, urological and radiotherapeutic - brought about complete symptomatic improvement and clinical recovery of renal function. The significance of radiotherapy with ultra-hard photons under conditions of hyperbaric oxygen tension is stressed.
Glottic cancer: results of treatment with radiotherapy in air and hyperbaric oxygen.
Whittle R J,Fuller A P,Foley R R
Clinical oncology (Royal College of Radiologists (Great Britain))
This paper is a retrospective analysis of 397 patients with glottic cancer, in which 240 patients were treated in air, and 157 patients in a hyperbaric oxygen chamber (HBO). The three principal dose/time schedules in air and HBO are contrasted, and shown to be iso-effective. The local tumour control rates show a significant improvement in favor of HBO: Stage I, 10%; Stage II, 37%; Stage III, 73%. Morbidity rates are explored, and suggest that the increased local control rate is not attained at the cost of an increased morbidity rate. The planning of the treatment, the preparation of the patient, and any subsequent complications are described. Treatment in the HBO chamber in a busy department has been shown to be a safe and routine procedure.
Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix.
Watson E R,Halnan K E,Dische S,Saunders M I,Cade I S,McEwen J B,Wiernik G,Perrins D J,Sutherland I
The British journal of radiology
In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of advanced carcinoma of the uterine cervix a total of 320 cases were contributed by four radiotherapy centres in the United Kingdom. The use of hyperbaric oxygen resulted in improved local control and survival. The benefit was greatest in patients under the age of 55 who presented with stage III disease. There was a slight increase in radiation morbidity but it seemed that the benefit of hyperbaric oxygen outweighed this increase in morbidity and that there was a true improvement in the therapeutic ratio.
10.1259/0007-1285-51-611-879
Clinical experience with radiation enhancement by hyperbaric oxygen in children with recurrent neuroblastoma stage IV.
Voûte P A,van der Kleij A J,De Kraker J,Hoefnagel C A,Tiel-van Buul M M,Van Gennip H
European journal of cancer (Oxford, England : 1990)
The high risk group of patients with neuroblastoma are children over 1 year with stage IV disease. Most series report a maximum of 20% survival at 5 years. For recurrent neuroblastoma stage IV, cure rates are not reported in the literature, but they are nil. Any treatment for recurrent neuroblastoma stage IV remains a therapeutic dilemma. The outcome of radiation therapy is variable. A very important factor in tumour treatment remains tumour hypoxia, and others, such as metabolic factors, also play a role. Combined application of radiation modifiers may influence the final survival rate. In an attempt to improve the survival of recurrent neuroblastoma stage IV, hyperbaric oxygen and radioionated meta-Iodobenzylguanidine (MIBG) was used in a clinical setting. Although survival may not be used as a determinant of the usefulness of a treatment for stage IV neuroblastoma disease, a better one is not available. In this study, at 28 months, a cumulative probability of survival of 32% was recorded for patients treated with [131I]MIBG and hyperbaric oxygen compared to 12% for [131I]MIBG treatment alone. These preliminary results are promising but further studies are needed to reveal substantial therapeutic gain.
10.1016/0959-8049(95)00073-r
Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas.
Kohshi K,Kinoshita Y,Imada H,Kunugita N,Abe H,Terashima H,Tokui N,Uemura S
British journal of cancer
The purpose of this non-randomized trial was to evaluate the efficacy of radiotherapy combined with hyperbaric oxygen (HBO) in patients with malignant glioma. Between 1987 and 1997, 29 patients in whom computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed post-operative residual tumours were locally irradiated with nitrosourea-based chemotherapy. Treatments were consecutively combined with HBO at two institutions since 1991 and 1993. Fifteen patients were irradiated daily after HBO, and the periods of time from decompression to irradiation were within 15 and 30 min in 11 and four patients respectively. Fourteen other patients were treated without HBO. Tumour responses were assessed by CT or MRI scans and survival times were compared between the treated groups. In the HBO group, 11 of 15 patients (73%) showed > or = 50% tumour regression. All responders were irradiated within 15 min after decompression. In the non-HBO group, four of 14 patients (29%) showed tumour regression. The median survivals in patients with and without HBO were 24 and 12 months, respectively, and were significantly different (P < 0.05). No serious side-effects were observed in the HBO patients. In conclusion, irradiation after HBO seems to be a useful form of treatment for malignant gliomas, but irradiation should be administered immediately after decompression.
10.1038/sj.bjc.6690345
Hyperbaric oxygen in the radiation treatment of head and neck cancers.
Sealy R
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Published reports on the use of hyperbaric oxygen in the radiation therapy of head and neck cancer are reviewed. The weight of evidence, from randomised trials, is that it is of clinical value in the control of medium sized head and neck tumours. It is also of value in the treatment of lymph node disease. Four attempts to improve the results of the treatment, by various physiological measures, are reviewed. It is concluded that hyperbaric oxygen may be of use when combined with nitroimidazoles as a radiation sensitiser and warrants further study when combined with induced anaemia, aimed to reduce the tumour cord and prevent repopulation between fractions.
Hyperbaric oxygen and radiobiology of a C3H mouse mammary carcinoma.
Suit H D,Maeda M
Journal of the National Cancer Institute
A series of radiation dose-tumor control response assays was performed on the first-to-fourth generation isotransplants of a C3H/J mouse mammary carcinoma for radiation administered under four different conditions: hypoxia, a clamp across the root of the tumor-bearing part for 1 minute before treatment; air, animal respiring air at one atmosphere of pressure; O2 30 or 44 psi, animal respiring pure oxygen at 30 or 44 psi for 15 minutes before and during local tumor irradiation. When radiation was administered as a single dose (v = 1) to 250 mm3 tumors, high pressure oxygen was only modestly effective in reducing the tumor control dose (TCD50); TCD50 hypoxia/O2 30 psi and TCD50 hypoxia/O2 44 psi were only 1.2 and 1.3, respectively. However, for similar treatment of 0.6 mm3 tumors and of even smaller "microcolonies," the ratios TCD50 hypoxia/O2 44 psi were 2.5 and 3.2, respectively. These results are discussed with respect to simple tumor models so as to estimate the proportion of hypoxic cells present in tumors under normal conditions and the influence of oxygen breathed at increased pressure on that proportion. High pressure oxygen was found much more effective when combined with fractionated irradiation (v = 10) than with single-dose therapy. Thus TCD50 hypoxia/O2 30 psi was 2.2 (v = 10) instead of 1.2 (v = 1). Finally, the ratio TCD50 hypoxia = 10/v = 1 was 2.15. These results are reviewed and inferences drawn as to the extent of tumor cell proliferation between treatments, repair of sublethal radiation injury by hypoxic cells, and the movement of cells from the hypoxic compartment to the aerobic compartment during fractionated irradiation (v = 10) under normal conditions.
Carcinoma of the cervix--anaemia, radiotherapy and hyperbaric oxygen.
Dische S,Anderson P J,Sealy R,Watson E R
The British journal of radiology
Further analyses of the material contained in trials of the hyperbaric oxygen chamber in the radiotherapy of carcinoma of the cervix have shown that patients who were severely anaemic prior to radiotherapy, and who required blood transfusion, showed very poor local tumour control when conventionally treated after transfusion, but very good local tumour control when treated in hyperbaric oxygen. The finding of a special sub-group where hypoxia would seem to be an important cause of radiation failure, and where hyperbaric oxygen was successful in overcoming it, may have importance in the evaluation of other methods for overcoming the hypoxia, including the use of chemical sensitising agents.
10.1259/0007-1285-56-664-251
Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial.
Henk J M,Kunkler P B,Smith C W
Lancet (London, England)
We report the results of a prospective controlled trial of the effect of hyperbaric oxygen as an adjuvant in radiotherapy of head and neck cancer. Patients were allocated randomly to treatment in oxygen or air. The radiotherapy in both groups was identical in planning, dose, and fractionation--i.e., 3500 rads in 10 fractions in 3 weeks. There was no difference in the survival rate between the two groups. However, significantly better local tumour control was seen in the hyperbaric-oxygen group, particularly in smaller lesions; there was significantly greater need for salvage surgery in the air group. Radiation effects on normal tissue appeared somewhat greater in the oxygen series, especially on laryngeal cartilage.
10.1016/s0140-6736(77)90116-7
Hyperbaric oxygen in radiation therapy.
Glassburn J R,Brady L W,Plenk H P
Cancer
The importance of oxygen with low LET radiations has been established beyond any doubt in many different systems, both plant and animal. While some studies, especially head and neck tumors, are impressive, it has not been demonstrated unequivocally that radiation under hyperbaric conditions is superior to well fractionated, well conceived, conventional radiotherapy. Any resulting gain in survival from the addition of hyperbaric oxygen will be limited, especially with more advanced stages of disease. Well controlled studies, especially with earlier stage disease, are still necessary. It would be worthwhile to undertake such trials, especially with tumors of the head and neck constituting the most promising site of study, as others have noted, since even a 5% to 10% improvement in survival would mean many lives saved. Continued trials with hyperbaric oxygen, oxygen in other forms, neutrons and other particles, and radiation sensitizing drugs are all justified in an attempt to overcome the oxygen effect on human tumors.
10.1002/1097-0142(197702)39:2+<751::aid-cncr2820390710>3.0.co;2-o
Radiation therapy with hyperbaric oxygen at 4 atmospheres pressure in the management of squamous cell carcinoma of the head and neck: results of a randomized clinical trial.
Haffty B G,Hurley R,Peters L J
The cancer journal from Scientific American
PURPOSE:The purpose of this study was to present the results of a randomized trial evaluating HBO-4 in combination with hypofractionated radiation therapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS:Between April 1974 and December 1975, 48 patients with locally advanced unresected SCCHN, referred for primary radiation therapy, were randomized to radiation delivered in air in two fractions of 12.65 Gy over 21 days to a total of 25.30 Gy (air, n = 25); or radiation under HBO-4 in two fractions of 11.50 Gy over 21 days to at total of 23.00 Gy (HBO-4, n = 23). The HBO-4 was administered under general anesthesia to minimize patient discomfort and potential problems with seizures associated with rapid compression to 4 atmospheres. Patients were monitored regularly by the radiation oncologists for toxicity, response, local control, and survival. The original hospital records, radiation records, and hyperbaric treatment logs were recently reviewed, and all data were entered onto a computerized database for the current analysis. The results of this trial have not previously been published. RESULTS:The air and HBO-4 arms were evenly matched with respect to age, sex, performance status, hemoglobin level, primary site, and stage of disease. Acute toxicities were acceptable with no significant differences between the two treatment arms. A trend toward excess severe late complications were noted in the hyperbaric arm (12 vs 7). There was a highly significant difference in complete clinical responses between the two arms, with 21/25 in complete dinical responses in the HBO-4 arm compared with 13/25 in complete clinical responses in the air arm, and a statistically insignificant trend toward improved 5-year local control in the HBO-4 arm (29% vs 16%). There were no significant differences between the two arms with respect to 5-year survival, distant metastasis, or second primary tumors. CONCLUSIONS:Long-term outcome from this historical randomized trial demonstrate substantial improvements in response rate with the use of HBO-4. The hypofractionation scheme used in the trial resulted in relatively low local control and high complication rates in this group of patients with very advanced SCCHN. However, these results support the theory that radioresistant hypoxic cells limit the radiocurability of SCCHN. Further investigations addressing the hypoxic cell problem with hypoxic cytotoxins or hypoxic cell sensitizers in combination with radiation therapy using more conventional fractionation schemes are warranted.
Hyperbaric oxygen and radiation therapy in the management of glioblastoma.
Chang C H
National Cancer Institute monograph
A pilot clinical trial on radiotherapy of glioblastoma with and without hyperbaric oxygen was performed at the Columbia-Presbyterian Medical Center. Eighty previously untreated patients with histologically proved glioblastoma were evaluated; 38 were irradiated under hyperbaric oxygen and 42 (controls) in atmospheric air. The survival rates were calculated according to the actuarial analysis method. At the end of 18 months, the survival rate appeared considerably higher in the oxygen group (28%) than in the controls (10%). At the end of 36 months, no patients in the control group survived, whereas 2 patients in the oxygen group were alive beyond 45 and 48 months, respectively. The median survival time was 38 weeks for those treated under oxygen and 31 weeks for the air control group. Owing to the small population samples and the pilot nature of this study, the difference in survival rates between the two groups was not statistically significant. The toxicity of hyperbaric oxygen was well tolerated by most patients, and the quality of survival in the hyperbaric oxygen group was equal to or slightly better than that of the control group. This pilot clinical study paved the way for further controlled clinical trials of hyperbaric oxygen and oxygen-mimicking drugs, including the electron-affinic compounds that could have differentially sensitized the hypoxic tumor cells.
A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas.
Beppu Takaaki,Kamada Katsura,Nakamura Ryuji,Oikawa Hiroshi,Takeda Masaru,Fukuda Takeshi,Arai Hiroshi,Ogasawara Kuniaki,Ogawa Akira
Journal of neuro-oncology
Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15 min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68 +/- 14 days. The response rates (CR + PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.
Chronic anaemia, hyperbaric oxygen and tumour radiosensitivity.
McCormack M,Nias A H,Smith E
The British journal of radiology
Anaemia is an important factor in the response of some human tumours to radiotherapy. The outcome is also influenced by whether the treatment is given in air or high pressure oxygen (HPO). The present study examined the relationship between anaemia and tumour response to radiation given in air or HPO in C3H mice transplanted with a mammary adenocarcinoma using a growth delay assay to assess the radiation response. Chronic anaemia was induced by the use of a low iron diet and was characterized by a significant reduction in host haematocrit and whole blood viscosity. In addition, anaemia was associated with a right shift in the oxyhaemoglobin dissociation curve and an increase in the volume doubling time of the tumour; but there was no change in the concentration of 2,3-diphosphoglycerate in the red cells. Radiation studies with these anaemic mice demonstrated that the tumour radiosensitivity was decreased when treatment was given in air. HPO was successful in overcoming the increased radioresistance associated with anaemia. This result suggested that tumours grown in anaemic mice have a higher hypoxic fraction than those grown in control mice. Changes in host physiology with chronic anaemia may contribute to the benefit seen with HPO but such alterations per se may be inadequate to maintain tumour oxygenation when treatment is given in air.
10.1259/0007-1285-63-754-752
Radiotherapy and hyperbaric oxygen. Report of a Medical Research Council Working Party.
Lancet (London, England)
The M.R.C. Working Party has coordinated randomised clinical trials to assess hyperbaric oxygen as a sensitiser in radiotherapy. 1669 patients were registered in these studies between 1963 and 1976. Hyperbaric oxygen significantly improved both survival and local tumour control after radiotherapy for head-and-neck tumours and for advanced carcinoma of the cervix. In carcinoma of the bronchus there seemed to be some improvement in survival but this was not statistically singificant. In carcinoma of the bladder hyperbaric oxygen has shown no benefit. Centres already equipped with hyperbaric chambers should continue to use them for those types of tumour shown to benefit. Since hyperbaric oxygen treatment makes great demands on medical and other staff, extension of its use must await comparison with other methods for improving radiotherapy which are now being evaluated.
Radiotherapy after hyperbaric oxygenation improves radioresponse in experimental tumor models.
Kunugita N,Kohshi K,Kinoshita Y,Katoh T,Abe H,Tosaki T,Kawamoto T,Norimura T
Cancer letters
We examined the effect of radiotherapy after hyperbaric oxygen (HBO) breathing in experimental tumors using a tumor growth delay assay. Tumor models used were SCCVII (radiobiological hypoxic fraction: approximately 10%) and 9L tumors (containing less hypoxic cells) subcutaneously transplanted into C3H/He mice and Fisher 344 rats, respectively. Irradiation using X-rays was locally administered to the tumors immediately after decompression. HBO breathing enhanced the radiation response in SCCVII tumors but not in 9L ones. In the next experiment using SCCVII tumors, irradiation was administered 5, 15, 30, and 90 min after decompression. A significant growth delay was seen in the treated animals within 30 min after HBO breathing, and the tumor growth delay time was prolonged 1.61 times as long as that in radiotherapy alone. We concluded that: (1) radiotherapy after HBO breathing is effective for tumors with hypoxic cells; and (2) the time lapse from decompression to irradiation is an important factor in improving radiosensitivity. Radiotherapy after HBO breathing can be used to enhance the efficacy of clinical treatments.
10.1016/s0304-3835(00)00721-7
[131I meta-iodobenzylguanidine in combination with hyperbaric oxygen therapy in the treatment of prognostically high-risk forms of neuroblastoma].
Stanková J,Kavan P,Krízová H,Hermanská E,Dosel P,Sázel M
Casopis lekaru ceskych
BACKGROUND:Despite of improving diagnostics, development of new drugs and treatment strategies, patients with biologically unfavourable, advanced or relapsed neuroblastoma remain practically incurable. Treatment related toxicity, requirement for personnel and financial costs have became limiting. Tumor specific therapy represented by 131I-meta-iodobenzylguanidine (MIBG) administration could become an alternative improving the overall survival. In comparison with standard external radiotherapy the targeted therapy enables to achieve radiation 5 to 10 times higher with lower organ toxicity. Data published by European and American colleagues brought evidence of high efficacy of this method. It motivated us to set and develop the method at our department. TYPE OF STUDY:Retrospective analysis of therapeutic results and side effects of the administration of 131I-meta-iodobenzylguanidine in high-risk neuroblastoma patients cured at the Department of Pediatric Oncology in Prague since 1997 till 2000. METHOD AND RESULTS:131I-meta-iodobenzylguanidine was fourteen times therapeutically administered in seven high-risk relapsed neuroblastoma patients. Four children received a single dose of 131I-meta-iodobenzylguanidine, three patients were treated repeatedly. The first dose represented 5.5 GBq, repeated dose 3.7 GBq, irrespective to the body weight. Each MIBG administration was followed by four days hyperbaric oxygen therapy. The treatment was well tolerated, acute and late side effects were not serious and only rarely reached grade 3 or 4 according to the International North American Children's Cancer Group Classification. Three of the seven children have survived with no evidence of the disease. Four children died of the disease progress. CONCLUSIONS:131I-meta-iodobenzylguanidine treatment combined with hyperbaric oxygen therapy becomes a well-tolerated therapy for high-risk neuroblastoma patients non-responding to the conventional treatment. Though the 131I-meta-iodobenzylguanidine administration probably cannot cure these patients, the repeated administration can bring long lasting remission.
Clinical results of hypoxic cell radiosensitisation from hyperbaric oxygen to accelerated radiotherapy, carbogen and nicotinamide.
Saunders M,Dische S
The British journal of cancer. Supplement
The 40-year history of hypoxic cell sensitisation can be traced from hyperbaric oxygen to the present clinical studies with carbogen, nicotinamide and accelerated radiotherapy. A meta-analysis by Overgaard (1995) included 10703 cases entered into 83 randomised controlled trials and showed an overall improvement in local tumour control of 4.6% (P = 0.00001) and in survival of 2.8% (P = 0.005). Hyperbaric oxygen gave a 6.6% (P = 0.003) improvement in local control and hypoxic cell sensitisers 3.9% (P = 0.04). Despite this, the only hypoxic cell-sensitising method in routine clinical use is the giving of nimorazole in supraglottic and pharyngeal carcinomas. Acute, as well as chronic hypoxia has been recognised and nicotinamide, the amide derivative of B3 is believed to prevent the former. Thus ARCON (accelerated radiotherapy, carbogen and nicotinamide) has been introduced in the clinic in an effort to overcome tumour proliferation, chronic and acute hypoxia, respectively. The success of future randomised controlled trials would be improved greatly if methods were available to measure the concentration of hypoxic cells in tumours before treatment and thus select those where benefit may be gained. The use of ARCON recognises that tumour cell proliferation is an important cause of failure in addition to hypoxia. However, intrinsic radiosensitivity may also need to be taken into account in the future. Clinical trials aim to improve the therapeutic ratio and thus the study of morbidity is as important as local tumour control. International collaboration is essential if randomised controlled trials are to be carried out within reasonable periods of time.
Carcinoma of the larynx treated with hypofractionated radiation and hyperbaric oxygen: long-term tumor control and complications.
Haffty B G,Hurley R A,Peters L G
International journal of radiation oncology, biology, physics
PURPOSE:To evaluate the long-term outcome with respect to local control, survival, and complications in a cohort of patients with locally advanced laryngeal carcinoma treated with hypofractionated radiation and hyperbaric oxygen at 4 atmospheres of pressure (HBO-4). METHODS AND MATERIALS:Between January 1970 and August 1982, 45 patients with locally advanced carcinoma of the larynx were treated with primary radiation using a unique hypofractionated schedule of 2 fractions of 11 Gy separated by 21 days, with concomitant HBO-4 during each radiotherapy session. To avoid seizures, discomfort and other complications of HBO-4, each session was performed under general anesthesia. All patients had pathologically confirmed squamous cell carcinoma of the glottic (23) or supraglottic larynx (22) and were staged as follows: T2-5, T3-24, T-4-16; N0-26, N1-4, N2-13, N3-1. Patients were treated with opposed lateral wedged fields of 4-6 MV photons, with a median field size of 5.5 x 9.75 to a total median dose of 22.5 Gy. RESULTS:As of February 1998, follow-up was complete on all but one patient, who relocated to another country after 8 years. Complete clinical responses were observed in 39 (87%) of the cases. The 10-year local control rate for all 45 patients was 58%, and local control for the complete responders was 69%. Three patients underwent laryngectomy for complications and were found to have no pathological evidence of disease in the laryngectomy specimen. The 10-year survival of the overall population was 27%. The 10-year voice preservation rate for the the 39 complete responders was 55%. Acute mucosal and skin reactions were modest and acceptable. Significant late complications occurred in 14 patients consisting of severe fibrosis, necrosis, pharyngeal fistula, with 3 patients requiring laryngectomy for complications. The actuarial rate of severe complications at 5 years was 42%. CONCLUSIONS:The response rate and long-term tumor control rate obtained with this treatment program were comparable to more protracted radiation schedules with or without systemic chemotherapy. The complication rate was high resulting in an adverse therapeutic ratio. The radiobiologic interpretation of this clinical data, and implications for hypoxia directed therapy, are discussed.
10.1016/s0360-3016(99)00126-1
Hyperbaric oxygen improves tumor radiation response significantly more than carbogen/nicotinamide.
Brizel D M,Hage W D,Dodge R K,Munley M T,Piantadosi C A,Dewhirst M W
Radiation research
This laboratory previously demonstrated that hyperbaric oxygen and hyperbaric carbogen improved oxygenation in the R3230Ac tumor, but normobaric 100% O2 and carbogen did not. The current study assessed tumor growth after exposure to radiation plus either hyperbaric oxygen, carbogen or carbogen/nicotinamide and the relationship between pretreatment tumor oxygenation and growth time. R3230Ac carcinomas were grown in the flanks of F344 rats. Animals were randomized to one of seven radiation treatment groups: sham irradiation or irradiation plus room air, hyperbaric oxygen (100% O2/3 atmospheres), nicotinamide (0.3 mg/g intraperitoneally 20 min before irradiation), carbogen, carbogen/nicotinamide or hyperbaric oxygen/nicotinamide. Tumors received 20 Gy in a single dose. Median growth times were 6, 18, 18, 20, 22, 28 and 27 days for controls and irradiation plus room air, carbogen, nicotinamide, carbogen/nicotinamide, hyperbaric oxygen and hyperbaric oxygen/nicotinamide, respectively. Irradiation with hyperbaric oxygen, hyperbaric oxygen/ nicotinamide and carbogen/nicotinamide increased growth time (P < 0.001, P < 0.001 and P = 0.003, respectively) relative to room air. Hyperbaric oxygen was significantly more effective than carbogen/nicotinamide (P = 0.001). Growth times for all tumors exposed to hyperbaric oxygen were longer than those of the most fully oxygenated tumors (no baseline pO2 values < 10 mm Hg) not exposed to hyperbaric oxygen (P < 0.001). These results suggest that hyperbaric oxygen may improve radiation response by additional mechanisms separate from overcoming the oxygen effect.
Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases.
Ohguri Takayuki,Imada Hajime,Kohshi Kiyotaka,Kakeda Shingo,Ohnari Norihiro,Morioka Tomoaki,Nakano Keita,Konda Nobuhide,Korogi Yukunori
International journal of radiation oncology, biology, physics
PURPOSE:The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS:The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). The radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. RESULTS:The radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). CONCLUSIONS:The present study showed a potential value of prophylactic HBO for the radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit.
10.1016/j.ijrobp.2006.08.009
Effects of hyperbaric oxygen and normobaric carbogen on the radiation response of the rat rhabdomyosarcoma R1H.
Hartmann K A,van der Kleij A J,Carl U M,Hulshof M C,Willers R,Sminia P
International journal of radiation oncology, biology, physics
PURPOSE:Hypoxic tumor cells are an important factor of radioresistance. Hyperbaric oxygen (HBO) and normobaric carbogen (95% oxygen, 5% carbon dioxide) increase the oxygen delivery to tumors. This study was performed to explore changes of tumor oxygenation during a course of fractionated irradiation and to determine the effectiveness of normobaric carbogen and HBO during the final phase of the radiation treatment. METHODS AND MATERIALS:Experiments were performed on the rhabdomyosarcoma R1H growing on WAG/Rij rats. After 20 X-ray fractions of 2 Gy within 4 weeks, oxygen partial pressure (pO2) was measured using the Eppendorf oxygen electrode under ambient conditions, with normobaric carbogen or HBO at a pressure of 240 kPa. Following the 4-week radiation course, a top-up dose of 10-50 Gy was applied in 2-10 fractions of 5 Gy with or without hyperoxygenation. RESULTS:HBO but not carbogen significantly increased the median pO2 in irradiated tumors. The radiation doses to control 50% of tumors were 38.0 Gy, 29.5 Gy, and 25.0 Gy for air, carbogen, and HBO, respectively. Both high oxygen content gas inspirations led to significantly improved tumor responses with oxygen enhancement ratios (OERs) of 1.3 for normobaric carbogen and 1.5 for HBO (air vs. carbogen: p = 0.044; air vs. HBO: p = 0.02; carbogen vs. HBO: p = 0.048). CONCLUSION:Both normobaric carbogen and HBO significantly improved the radiation response of R1H tumors. HBO appeared to be more effective than normobaric carbogen, both with regard to tumor oxygenation and response to irradiation.
10.1016/s0360-3016(01)01712-6
The effect of hyperbaric oxygen therapy on quality of life in oral and oropharyngeal cancer patients treated with radiotherapy.
Gerlach N L,Barkhuysen R,Kaanders J H A M,Janssens G O R J,Sterk W,Merkx M A W
International journal of oral and maxillofacial surgery
Radiotherapy is used in the setting of curative treatment for head and neck cancer. Xerostomia and related problems occur when major salivary glands are included in the irradiation fields. This reduces quality of life (QOL). Hyperbaric oxygen therapy (HBOT) is a well accepted treatment or prevention modality for osteoradionecrosis of the jawbones and soft-tissue necrosis. It is unknown if and to what extent HBOT influences xerostomia and xerostomia-related QOL. To address this, a prospective study was conducted. Twenty-one patients who underwent radiotherapy for an oral or oropharyngeal carcinoma completed a European Organization for Research and Treatment of Cancer QOL questionnaire before HBOT, as part of the treatment/prevention of osteoradionecrosis, and 1 and 2 years after HBOT. Swallowing-related problems significantly decreased in time, and there was a reported subjective increase in saliva quantity and an improvement in sense of taste. The results suggest that HBOT may positively influence these long-term radiotherapy sequelae.
10.1016/j.ijom.2007.11.013
Hyperbaric oxygen therapy for late radiation-associated tissue necroses: is it safe in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers?
Lin Hon-Yi,Ku Chih-Hung,Liu Dai-Wei,Chao Hsing-Lung,Lin Chun-Shu,Jen Yee-Min
International journal of radiation oncology, biology, physics
PURPOSE:To test, in a retrospective matched-pair study, whether necrosis-rescuing hyperbaric oxygen therapy (HBOT) increases the risk of cancer re-recurrence in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. METHODS AND MATERIALS:Between January 1995 and July 2004, we retrospectively identified 22 patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. We defined two groups: the HBOT group, 11 patients with HBOT for rescuing late radiation-associated tissue necroses; and the non-HBOT group, the other 11 matched-pair patients without HBOT. Between the two groups, the following four factors were matched for case pairing: primary cancer subsite, initial cancer stage, age, and gender. RESULTS:Three findings indicate that HBOT increases the risk of cancer re-recurrence. First, we observed more cancer re-recurrences in the HBOT group than in the non-HBOT group: 9 of 11 vs. 4 of 11, with 5-year disease-free survival rates after salvage of 32.7% vs. 70.0% (hazard ratio 3.2; 95% confidence interval 1.03-10.7; p = 0.048). Second, re-recurrences developed rapidly after HBOT in 6 patients. Third, 3 patients had unusual cancer re-recurrences after HBOT. Remarkably, of 9 patients with cancer re-recurrences in the HBOT group, 4 patients had cancer disease-free intervals of 9 months or less before HBOT. CONCLUSIONS:Necrosis-rescuing HBOT should be given with caution in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers; if it cannot be omitted entirely, deferring HBOT 9 months or longer after cancer re-treatment may be prudent.
10.1016/j.ijrobp.2008.08.076
Hyperbaric oxygen therapy for radiation-induced brain necrosis in a patient with primary central nervous system lymphoma.
Cihan Yasemin Benderli,Uzun Günalp,Yildiz Senol,Dönmez Halil
Journal of surgical oncology
A 45-year-old man who developed brain radionecrosis in the right frontal and left temporoparietal lobes after receiving whole brain radiotherapy and stereotactic radiosurgery for primary central nervous system lymphoma. Since high dose steroid treatment failed and he declined to undergo surgery, he was referred to hyperbaric oxygen (HBO) therapy. Both clinical and radiological findings improved after HBO therapy. Steroid requirements were also reduced. HBO therapy may have a potential value in treatment of brain radionecrosis.
10.1002/jso.21387
Hyperbaric oxygen and radiotherapy.
Mayer Ramona,Hamilton-Farrell Martin R,van der Kleij Adrian J,Schmutz Jörg,Granström Gösta,Sicko Zdzislaw,Melamed Yehuda,Carl Ulrich M,Hartmann K Axel,Jansen Erik C,Ditri Luciano,Sminia Peter
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]
BACKGROUND:Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure of at least 1.5 atmospheres absolute (150 kPa). It uses oxygen as a drug by dissolving it in the plasma and delivering it to the tissues independent of hemoglobin. For a variety of organ systems, HBO is known to promote new vessel growth into areas with reduced oxygen tension due to poor vascularity, and therewith promotes wound healing and recovery of radiation-injured tissue. Furthermore, tumors may be sensitized to irradiation by raising intratumoral oxygen tensions. METHOD:A network of hyperbaric facilities exists in Europe, and a number of clinical studies are ongoing. The intergovernmental framework COST B14 action "Hyperbaric Oxygen Therapy" started in 1999. The main goal of the Working Group Oncology is preparation and actual implementation of prospective study protocols in the field of HBO and radiation oncology in Europe. RESULTS:In this paper a short overview on HBO is given and the following randomized clinical studies are presented: a) reirradiation of recurrent squamous cell carcinoma of the head and neck after HBO sensitization; b) role of HBO in enhancing radiosensitivity on glioblastoma multiforme; c) osseointegration in irradiated patients; adjunctive HBO to prevent implant failures; d) the role of HBO in the treatment of late irradiation sequelae in the pelvic region. The two radiosensitization protocols (a, b) allow a time interval between HBO and subsequent irradiation of 10-20 min. CONCLUSION:Recruitment of centers and patients is being strongly encouraged, detailed information is given on www.oxynet.org.
10.1007/s00066-005-1277-y
Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer.
Gothard Lone,Haviland Joanne,Bryson Phil,Laden Gerard,Glover Mark,Harrison Steven,Woods Mary,Cook Gary,Peckitt Clare,Pearson Ann,Somaiah Navita,Stanton Anthony,Mortimer Peter,Yarnold John
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
BACKGROUND:A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial. METHODS:Fifty-eight patients with ≥ 15% increase in arm volume after supraclavicular ± axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO (n=38) or to best standard care (n=20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire. FINDINGS:Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7-151.5%) in the control group and 133.5% (IQR 122.3-144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups. INTERPRETATION:No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer.
10.1016/j.radonc.2010.04.026
Hyperbaric oxygenation for tumour sensitisation to radiotherapy.
Bennett M,Feldmeier J,Smee R,Milross C
The Cochrane database of systematic reviews
BACKGROUND:Cancer is common and radiotherapy is one well-established treatment for some solid tumours. HBO may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing HBO may result in a reduction in mortality and tumour recurrence. OBJECTIVES:To assess the benefits and harms of radiotherapy while breathing HBO. SEARCH STRATEGY:In November 2004 we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library Issue 3), MEDLINE, EMBASE , CINAHL, DORCTHIM and reference lists of articles. Relevant journals were handsearched. SELECTION CRITERIA:Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air (with or without sham therapy). DATA COLLECTION AND ANALYSIS:Three reviewers independently evaluated the quality of the relevant trials using the method of Schulz (Schulz 1995) and extracted the data from the included trials. MAIN RESULTS:Nineteen trials contributed to this review (2286 patients: 1103 allocated to HBO and 1153 control). With HBO, there was a reduction in mortality for head and neck cancers at both one year and five years after therapy (Relative risk (RR) 0.83, P = 0.03, number needed to treat (NNT) = 11 and RR 0.82, P = 0.03, NNT = 5 respectively), as well as improved local tumour control at three months (RR with HBOT 0.58, P = 0.006, NNT = 7). The effect of HBO varied with different fractionation schemes. Local tumour recurrence was less likely with HBO at one year (head and neck, RR 0.66, P < 0.0001, NNT = 5), two years (uterine cervix RR 0.60, P = 0.04, NNT = 5) and five years (head and neck (RR 0.77, P = 0.01). Any advantage is achieved at the cost of some adverse effects. There was a significant increase in the rate of both severe radiation tissue injury (RR 2.35, P < 0.0001, (number needed to harm (NNH) = 8) and the chance of seizures during therapy (RR 6.76, P = 0.03, NNH 22) with HBO. AUTHORS' CONCLUSIONS:There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the head and neck, and uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury. The methodological and reporting inadequacies of the primary studies included in this review demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other anatomical sites on which to base a recommendation.
10.1002/14651858.CD005007.pub2
Hyperbaric oxygenation for tumour sensitisation to radiotherapy: a systematic review of randomised controlled trials.
Bennett M,Feldmeier J,Smee R,Milross C
Cancer treatment reviews
BACKGROUND:Radiotherapy is a well-established treatment for some solid tumours. Hyperbaric oxygenation (HBO) may improve radiotherapeutic killing of hypoxic cancer cells, so the simultaneous administration of radiotherapy and HBO may reduce mortality and tumour recurrence. METHODS:We performed a systematic search of the literature in September 2007 for randomised controlled trials, and made pooled analyses of pre-determined clinical outcomes. RESULTS:Nineteen trials contributed to this review (2286 patients). There was a reduction in mortality for head and neck cancers at one and five years after therapy (at five years RR 0.82, P=0.03, NNT=5), and improved local tumour control at three months (RR 0.58, P=0.006, NNT=7). Any advantage is achieved at the cost of an increased rate of both severe radiation tissue injury (RR 2.35, P<0.0001, NNH=8) and the chance of seizures during therapy (RR 6.76, P=0.03, NNH=22). CONCLUSIONS:There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe radiation tissue injury. The methodological and reporting inadequacies of the studies included in this review demand a cautious interpretation. More research is needed for head, neck and uterine cervical cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other sites.
10.1016/j.ctrv.2008.01.001
Successful hyperbaric oxygen therapy for laryngeal radionecrosis after chemoradiotherapy for mesopharyngeal cancer: case report and literature review.
Abe Madoka,Shioyama Yoshiyuki,Terashima Kotaro,Matsuo Mioko,Hara Iwao,Uehara Satoru
Japanese journal of radiology
Laryngeal radionecrosis is one of the most troublesome late complications of radiotherapy, because it is frequently resistant to treatment and laryngectomy is required in the worst case. Here, we report a case of laryngeal radionecrosis, successfully treated by use of hyperbaric oxygen (HBO) therapy, in which laryngectomy was avoided. A 67-year-old male received radical chemoradiotherapy (CRT) for mesopharyngeal cancer, which included radiotherapy with a total dose of 71.4 Gy/38 Fr and chemotherapy with CDDP + S-1. He developed dyspnea and throat pain 9 months after completion of CRT. Laryngoscopy revealed vocal cord impairment because of severe laryngeal edema. He was diagnosed as having laryngeal radionecrosis and initially received conservative therapy combined with antibiotics, steroids, and prostaglandins. Because his dyspnea was persistent despite this treatment, HBO therapy was administered 20 times, and resulted in complete remission of the dyspnea. HBO therapy, therefore, is regarded as an effective conservative therapeutic option for laryngeal radionecrosis.
10.1007/s11604-011-0046-3
Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study.
Forner Lone,Hyldegaard Ole,von Brockdorff Annet Schack,Specht Lena,Andersen Elo,Jansen Erik C,Hillerup Søren,Nauntofte Birgitte,Jensen Siri Beier
Oral oncology
Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO in irradiated head and neck cancer patients. Eighty patients eligible for HBO treatment on the indication of prevention/treatment of osteoradionecrosis or soft tissue radiation injury were consecutively sampled, of whom 45 had hyposalivation (i.e. unstimulated whole saliva (UWS) flow rate <0.1ml/min), and 69 complained of xerostomia. UWS and stimulated whole saliva (SWS) were collected prior to and after 30 sessions of hyperbaric oxygen treatment over 6weeks. Xerostomia was assessed using the visual analogue scale (VAS). Each HBO session involved compression to 243kPa (2.4 ATA) for 90min while breathing 100% oxygen from a facemask or hood. There was a significant decrease in xerostomia (p<0.001) and slight increase in UWS (p<0.001) and SWS (p<0.001) flow rate, from before HBO as compared to after. Twenty-five of 45 patients with hyposalivation achieved an increased UWS flow rate after HBO. In 12 of these, the flow rates increased to levels not associated with hyposalivation. Patient-assessed improvement of xerostomia and slightly increased UWS and SWS secretion after HBO treatment suggest that HBO may have a beneficial effect on radiation-induced salivary gland damage.
10.1016/j.oraloncology.2011.03.021
Hyperbaric oxygen therapy for late radiation tissue injury.
Bennett Michael H,Feldmeier John,Hampson Neil,Smee Robert,Milross Christopher
The Cochrane database of systematic reviews
BACKGROUND:Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of patients having radiotherapy with be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery. OBJECTIVES:To assess the benefits and harms of HBOT for treating or preventing LRTI. SEARCH METHODS:In March 2011 we updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 1), MEDLINE, EMBASE, DORCTIHM and reference lists of articles. SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS:Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials. MAIN RESULTS:Eleven trials contributed to this review (669 participants). For pooled analyses, investigation of heterogeneity suggested important variability between trials but there was some evidence that HBOT is more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P = 0.0002, NNTB = 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse effects. AUTHORS' CONCLUSIONS:These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected patients and tissues may be justified. Further research is required to establish the optimum patient selection and timing of any therapy. An economic evaluation should be undertaken.
10.1002/14651858.CD005005.pub3
Radiotherapy after hyperbaric oxygenation in malignant gliomas.
Chen Jun-rui,Xu Hong-zhi,Ding Jian-bo,Qin Zhi-yong
Current medical research and opinion
OBJECTIVE:This review was to evaluate the efficacy and toxicity of radiation therapy (RT) administered immediately after hyperbaric oxygen (HBO) therapy in patients with high grade gliomas. RESEARCH DESIGN AND METHODS:PubMed, Embase, ISI Web of Knowledge, and Cochrane databases were searched using combinations of the following search terms: radiotherapy, hyperbaric oxygenation, chemotherapy, glioma, brain tumor. Selection was limited to prospective studies involving patients given HBO followed by RT for high-grade gliomas. Data extracted from studies included the clinical research phase of the study, number of study arms, number of patients, patient age and gender, glioma type and grade, pressure and length of HBO, protocol of radiation therapy, duration of follow-up, and the outcomes. MAIN OUTCOME MEASURES:Overall survival, time to progression, response rate, tumor regression, and toxic effects associated with HBO plus RT treatment. RESULTS:Literature search/screening yielded eight studies for analysis. Six of the studies were single-arm in design and enrolled a total of 203 patients, of whom 142 had grade IV gliomas and 61 had grade III gliomas. In these six studies, all patients received HBO then RT. Two studies were double-arm in design, with 24 patients treated with HBO followed by RT and 26 patients treated with RT alone. The findings from both the single- and double-arm studies indicated improved outcomes (survival rate, progression free survival, time to progression, response rate) with HBO and RT therapy. Reported toxicity included leucopenia, anemia, thrombocytopenia, fever, loss of appetite, constipation, nausea, vomiting, and liver dysfunction. The addition of HBO had minimal effect on toxicity or side effects; across the eight studies, only one patient with severe middle ear barotrauma had a complication directly related to HBO exposure. CONCLUSION:This systematic reviews suggests that the addition of HBO to RT is tolerated and may be beneficial in patients with high-grade gliomas.
10.1185/03007995.2015.1082988
Old but new methods in radiation oncology: hyperbaric oxygen therapy.
Ogawa Kazuhiko,Kohshi Kiyotaka,Ishiuchi Syogo,Matsushita Masayuki,Yoshimi Naoki,Murayama Sadayuki
International journal of clinical oncology
The presence of hypoxic tumor cells is widely regarded as one of the main reasons behind the failure to control malignant tumors with radiotherapy treatments. Since hyperbaric oxygenation (HBO) improves the oxygen supply to the hypoxic tumor cells, HBO therapy has previously been used in combination with simultaneous radiotherapy to treat malignant tumors. In some clinical trials, significant improvements in local control and survival have been seen in cancers of the head and neck and the uterine cervix. However, the delivery of simultaneous HBO therapy and radiotherapy is both complex and time-consuming, with some trials reporting increased side effects. As a result, the regimen of HBO therapy in combination with simultaneous radiotherapy has yet to be used as a standard treatment for malignant tumors. In recent years, however, radiotherapy immediately after HBO therapy has been emerging as an attractive approach for overcoming hypoxia in cancer treatment. Several studies have reported that radiotherapy immediately after HBO therapy was safe and seemed to be effective in patients with high-grade gliomas. Also, this approach may protect normal tissues from radiation injury. To accurately estimate whether the delivery of radiotherapy immediately after HBO therapy can be beneficial in patients with high-grade gliomas and other cancers, further prospective studies are warranted.
10.1007/s10147-013-0537-6
Hyperbaric Oxygen Therapy and Radiation-Induced Injuries.
Kirby John P
Missouri medicine
Initial clinical uses of hyperbaric oxygen (HBO) capitalized upon physical effects to drive offending gases back into solution and deliver more oxygen to tissues in early treatments of decompression sickness. HBO has a myriad of other effects, including stimulating angiogenesis and new cellular in growth for healing.
Successful treatment of brain radiation necrosis resulting from triple-negative breast cancer with Endostar and short-term hyperbaric oxygen therapy: a case report.
Xing Shiyun,Fan Zhenhai,Shi Lei,Yang Ze,Bai Yuju
OncoTargets and therapy
Radiation necrosis (RN) is one of the complications of radiotherapy. Angiogenesis is a key factor underlying the development of RN, and Endostar, a safe and well-tolerated recombinant human endostatin, has been used to treat a variety of tumors. Thus far, however, no definitive reports on the use of Endostar for RN treatment have been reported. Here, we report the successful treatment of one patient with symptomatic brain radiation necrosis (BRN) using Endostar in combination with short-term hyperbaric oxygen therapy (HBO). One triple-negative breast cancer patient with recurrent brain metastatic lesions after standard chemoradiotherapy was referred to a specialty center outside our hospital for stereotaxic radiotherapy. Two months later, the patient showed deteriorating clinical symptoms, and magnetic resonance imaging (MRI) showed radiation necrosis with significant surrounding edema. The patient had a poor response to mannitol and steroids. After diagnosing this patient with BRN, we began short-term HBO therapy and intravenously administered Endostar for 4 cycles. The patient responded well to this strategy, showing rapidly and dramatically improved MRI findings and clinical symptoms. No tumor progression was observed at 10 months after treatment. Endostar in combination with short-term HBO therapy had marked effects on symptomatic BRN. However, additional large-scale, double-blinded, controlled trials are necessary to confirm the clinical effect of Endostar in combination with a short-term HBO therapy regimen on BRN.
10.2147/OTT.S190409
Vitexin, an inhibitor of hypoxia-inducible factor-1α, enhances the radiotherapy sensitization of hyperbaric oxygen on glioma.
Xie T,Wang J-R,Dai C-G,Fu X-A,Dong J,Huang Q
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
PURPOSE:Vitexin, an inhibitor of hypoxia-inducible factor (HIF)-1α, has anti-tumor effect. However, whether it can enhance the radiotherapy sensitization of hyperbaric oxygen (HBO) on glioma is unclear. This study aimed to investigate the effect of vitexin. METHODS:The nude mice with paw-transplanted glioma were divided into four groups: control group, HBO + radiation group, HBO + vitexin group, and HBO + vitexin + radiation group. The mice of last two groups were daily given vitexin 75 mg/kg by intraperitoneal injection. 30 min after administration of vitexin, the HBO-treated mice were daily placed in HBO chamber for 60 min. The radiation-treated mice were given local tumor irradiation once every week during the HBO treatment, and the dose of irradiation was 10 Gy/time. The experimental treatment lasted for 21 days. RESULTS:Compared with the HBO + radiation group, the tumor volume, tumor weight, and tumor weight coefficient in the HBO + vitexin + radiation group were lower (p < 0.05). Importantly, the contents of reduced glutathione and glutathione peroxidase as well as expressions of HIF-1α, vascular endothelial growth factor, glucose transporter (GLUT)-1, and GLUT-3 proteins in tumor tissues were also lower in the HBO + vitexin + radiation group than in the HBO + radiation group (p < 0.01). CONCLUSIONS:Vitexin can cooperate with HBO to sensitize the glioma radiotherapy, and its mechanisms may be correlated to the inhibition of HIF-1α protein expression and subsequent decrements of its downstream protein expressions, which finally cause the reduction of antioxidant capacity.
10.1007/s12094-019-02234-4