***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Since 1971 , 82 patients with advanced carcinoma of the cervix have been included in a r and omised clinical trial in association with the Working Party on Radiotherapy and Hyperbaric Oxygen of the Medical Research Council . External irradiation was given in 10 fractions by an unconventional schedule , either in air or HBO , and combined with three large fractions of intracavitary irradiation using the Cathetron . The results are acceptable overall , with 69 % local control , 15 % with tumour developing outside the treated volume and 40 % survival at five years , but no improvement has been shown with HBO .  Symptoms suggestive of some degree of late damage to the small bowel were present in 13 % of patients , with a higher but not statistically significant , incidence in the HBO group . It is postulated that the schedule of radiotherapy used has allowed reoxygenation during treatment and that no further gain due to the use of HBO may be achieved . After a review of the results from other centres and taking into account the difficulties of treatment in HBO it is concluded that for advanced carcinoma of the cervix the addition of HBO to radiotherapy is not clinical ly worthwhile BACKGROUND AND PURPOSE A r and omised controlled trial of hyperbaric oxygen in the radiotherapy of Stage IIb and III carcinoma of cervix was performed between 1971 and 1980 . Apart from an abstract giving an interim report in 1977 , results have not been published . MATERIAL AND METHODS In a four arm study , 335 patients were r and omised to treatment in 10 or 28 fractions , in hyperbaric oxygen or in air . Data is available concerning 327 cases and this has been analysed . RESULTS There was no advantage in tumour control shown with the use of hyperbaric oxygen . There was evidence for an increase in late radiation morbidity when treatment was given in hyperbaric oxygen rather than in air and when , using 10 fractions , a total dose of 45 rather than 40 Gy was achieved . For late intestinal morbidity , the fractionation sensitivity ( alpha/beta ratio ) was calculated to be 4.3 Gy and the steepness of the dose response curve ( gamma50 ) to be 2.6 . CONCLUSIONS Hyperbaric oxygen gave no benefit in the treatment of patients with stage IIb and III carcinoma of the cervix treated with radiotherapy using two fractionation regimes . Important data regarding late radiation morbidity has been revealed The 15 r and omised controlled clinical trials of hyperbaric oxygen in  radiotherapy  yielded three with highly significant benefit and six with useful margins not reaching statistical significance . The increase in tumour control was partly negated by an increase in normal tissue effect . Now simple carbogen breathing in animal tumour models has shown high efficiency and there is the potential for its use in man as a simple means of hypoxic cell radiosensitization Abstract In controlled trials using the hyperbaric oxygen chamber in the radiotherapy of carcinoma of the bladder , no benefit was found in a series of 40 patients treated using 30 fractions and a total dose of 6,000 R and in a series of 27 patients treated using 15 fractions and a total dose of 4,725R . In an uncontrolled trial in advanced cases using six fractions and a maximum tissue dose of 3,600 R results seemed improved despite the selection of cases . A new trial comparing this six-fraction technique with multiple fractions in air is now being carried out . Similar trials are being performed in a number of radiotherapy centres and it is planned to pool results so as to obtain a significant result at an early time . In the work reported , doses have been quoted in R units ; the absorbed dose can be obtained by multiplying stated values by 0·97 A controlled clinical trial is in progress to assess the value of hyperbaric oxygen and radiotherapy in the management of head and neck cancer . An established dose-fractionation schedule in hyperbaric oxygen is being compared with a widely used conventional schedule in air .  Survival and local recurrence-free rates are significantly higher in the oxygen group , and the effects on normal tissue are similar in both groups . These findings suggest a genuine therapeutic advantage . There was a distinct improvement in the results of treating advanced laryngeal carcinoma , where there was a high survival rate , without resort to laryngectomy This is an interim report of a clinical trial of radiotherapy of advanced oropharyngeal cancer under hyperbaric oxygenation . Fifty-one cases are available for evaluation , 26 in the oxygen group , 12 in the Control Group I , and 13 in the Control Group II.The results are analyzed as to : ( 1 ) clearance rates of the primary tumor , in which a 23 per cent higher clearance rate for the primary tumor in the oxygen group than in the air Control Group I is noted ; ( 2 ) survival rates , in which a 13 - 15 per cent increase of the 5 year survival is revealed in the oxygen group , compared to the air Control Group I ; and ( 3 ) complication rates and incidence of distant metastases which are not higher in the oxygen group than in the control groups . Although the difference of local tumor clearance and the survival rates between the oxygen and the control groups are not statistically significant due to the small sample size , the evidence of improvement in both local tumor clearance and in survival rates from our series and from tha Twenty-seven patients with carcinoma of the bladder were treated at the Glasgow Institute of Radiotherapeutics as part of a national hyperbaric oxygen trial . These patients were treated on a 4 MeV linear accelerator either in air or in 3 atm , absolute , of oxygen , by r and om selection . Of these patients , one-third were found to have high-dose effects to an extent which necessitated surgery . No association was found between the incidence of high-dose effects and treatment in air or hyperbaric oxygen . The treatment protocol used in all cases was to give an intended modal tumour dose of 6000 rad in 24 fractions in approximately 5 weeks . As all patients had received the same modal dose , there was no apparent reason why some had developed high-dose effects . However , on the basis of a Cumulative Radiation Effect ( CRE ) analysis of the treatment regimes given , a close correlation was found between the maximum CRE achieved and the occurrence of high-dose effects . Above a threshold level of 1910 reu in the maximum CRE achieved , there was a high incidence and rapid onset of high-dose effects . The reasons for the occurrence of the exceptionally high CRE values found in some patients are discussed . From a review of clinical results of bladder treatments , it is apparent that at a CRE level of 1910 reu , the tumour control rate is still increasing with CRE . It is proposed that by choosing the dose given on any treatment schedule to keep the maximum value of the CRE achieved just below 1910 reu , the greatest probability of cure would be obtained with minimum complication rate Abstract An interim report is given of a r and omized controlled trial of hyperbaric oxygen in the treatment of carcinoma of the cervix . A total of 82 patients with late Stage II , Stage III and early Stage IV disease were included between January 1966 and June 1971 . A minimum tumour dose of 5,500 R was given to the pelvis , either in oxygen or in air , in 27 treatments over 37 days and was followed by a radium application . An assessment of the results in 77 cases is presented . Seventy per cent of patients treated in oxygen were alive and free from disease at one year and this compared with 50 per cent of the patients treated in air . The difference was not statistically significant and became less until the results were the same at three years . In the early years after treatment the local failure rate in oxygen cases was less than in air , but was not statistically significant . There is a significant correlation between the clinical and histological assessment of regression at the end of treatment and subsequen In a r and omized 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 result ed 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 We report the results of a prospect i ve controlled trial of the effect of hyperbaric oxygen as an adjuvant in radiotherapy of head and neck cancer . Patients were allocated r and omly 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 One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospect i ve r and omized 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 The clinical trials of the use of hyperbaric oxygen in radiotherapy conducted by the Medical Research Council 's working party have shown that local cure and survival can be improved in head and neck and cervical cancer . Evidence for benefit has been presented in carcinoma of bronchus , but none has so far been found in carcinoma of the bladder . Although hyperbaric oxygen has produced increased effect upon normal tissues as well as upon tumour , a real improvement in therapeutic ratio appears to be present . The future use of hyperbaric oxygen in radiotherapy will depend upon a comparison of effectiveness with other methods now being tested to improve radiotherapy . The trials have yielded much fundamental and clinical data of general relevance in the radiotherapy of malignant disease Abstract A prospect i ve clinical trial has been established design ed to evaluate the role of hyperbaric oxygen in the treatment of patients with Stages 2b and 3 carcinoma of the cervix . Three Cathetron fractions using a line source , plus ten fractions of high energy external irradiation either in air or hyperbaric oxygen are given to the whole of the defined tumour volume . Details concerning the method of treatment adopted are presented and discussion of the problems involved . So far , 45 patients have been included and the preliminary results lend encouragement to the continuation of the overall treatment method irrespective of any possible benefits of hyperbaric oxygen which may appear in the long term Follow-up data at five years are reported for 24 patients with squamous cell carcinoma of the head and neck , included in a r and omised prospect i ve 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 In a r and omized controlled clinical trial of hyperbaric oxygen in the radiotherapy of carcinoma of the bladder a total of 241 cases were contributed by four radiotherapy centres in the United Kingdom . In this trial where in each centre identical radiotherapy was employed for both oxygen and air cases , no benefit was shown with the use of hyperbaric oxygen Abstract A r and omized study of squamous cell carcinoma of the head and neck , with the exception of T , vocal cord lesions , compared 23 patients who were treated in air with doses of 250 rad four times a week to 6250 rad , to 21 patients who were treated at three atmospheres of hyperbaric oxygen  with 12 x 400-rad fractions in approximately 32 days . Distribution by anatomic site and age were comparable . Distribution by stage was in favor of the air group since five Stage I patients were found in the air group but none in the hyperbaric oxygen group . The sex distribution was uneven-15 males to eight females in the air group and eight males to 13 females in the oxygen group . All patients were followed for a minimum of two years ; most patients were followed more than five years , with indefinite followup . The 12 × 400-rad schedule in four and one-half weeks in the hyperbaric oxygen group proved to be well tolerated without any significant increase in complications . Radiation myelitis can be avoided by limiting the spinal cord dose to 7 × 400 rad It is now well established that most animal solid tumors contain oxygen-deficient hypoxic cells and that these cells will influence the response of those tumors to radiation . Identifying hypoxic cells in human tumors has proven more difficult , primarily because most of the direct procedures used in animals are not applicable to humans . However , substantial indirect evidence , which goes back to as early as 1909 , clearly indicates the presence of hypoxia in human tumors , although with a considerable heterogeneity among individual tumors . Experimental studies during the last 30 years have shown that this source of radiation resistance can be effectively eliminated by a variety of procedures that include high oxygen-content gas breathing , nitrometric radiation sensitizers , blood transfusions , hemoglobin-oxygen affinity modifiers , and nicotinamide . A number of these procedures have also been tested clinical ly such that by 1995 over 10,000 patients in 83 r and omized trials had undergone treatment design ed to modify tumor hypoxia before radiation therapy . Although a number of these trials showed no benefit , an overview analysis showed that modification 
    Output:
    
The effect of HBOT varied with different fractionation schemes .
Any advantage is achieved at the cost of some adverse effects .
AUTHORS ' CONCLUSIONS There is some evidence that HBOT 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 .
HBOT is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury .