***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND The concentration of osteopontin ( SPP1 ) in plasma is associated with tumour hypoxia . The DAHANCA 5 trial found that the hypoxia radiosensitiser nimorazole significantly improved the outcome of radiotherapy for patients with head and neck cancer compared with placebo . However , whether all patients benefit from such modification of hypoxia is unclear . We aim ed to assess whether the concentration of plasma osteopontin could predict response to the hypoxia radiosensitiser . METHODS Plasma concentrations of osteopontin  were measured by use of ELISA from stored sample s of 320 patients r and omised in the DAHANCA 5 trial . Sample s were grouped into tertiles according to high ( 167 - 1382 microg/L ) , intermediate ( 69 - 166 microg/L ) , or low ( 0 - 68 microg/L ) concentrations of plasma osteopontin , and analysed for locoregional tumour control and disease-specific survival at 5 years . FINDINGS Overall , locoregional tumour failure and disease-specific mortality were more frequent in patients assigned placebo than in those assigned nimorazole ( relative risk [ RR ] 0.51 [ 95 % CI 0.32 - 0.79 ] and 0.54 [ 0.35 - 0.85 ] , respectively ) . Locoregional tumour failure was more frequent in patients with high concentrations of osteopontin assigned placebo than in those with high concentrations assigned nimorazole ( 0.19 [ 0.08 - 0.44 ] ) , as was disease-specific mortality ( 0.25 [ 0.11 - 0.59 ] ) . However , neither locoregional tumour failure nor disease-specific mortality differed between groups for patients with low concentrations of plasma osteopontin ( 0.79 [ 0.26 - 1.70 ] ) and ( 0.69 [ 0.31 - 1.51 ] ) or for those with intermediate concentrations ( 0.90 [ 0.41 - 1.98 ] and 0.89 [ 0.41 - 1.96 ] , respectively ) . INTERPRETATION High plasma concentrations of osteopontin are associated with a poor outlook after radiotherapy for patients with head and neck cancer , but can be improved by use of nimorazole . High concentrations of osteopontin can predict clinical ly relevant hypoxia , and might identify patients who will benefit from modification of hypoxia during radiotherapy 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 PURPOSE To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma ( SCC ) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial . PATIENTS AND METHODS One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were r and omized to receive definitive radiotherapy ( 70 Gy in 7 weeks ) concurrently with either cisplatin ( 75 mg/m(2 ) ) plus tirapazamine ( 290 mg/m(2)/d ) on day 2 of weeks 1 , 4 , and 7 , and tirapazamine alone ( 160 mg/m(2)/d ) on days 1 , 3 , and 5 of weeks 2 and 3 ( TPZ/CIS ) , or cisplatin ( 50 mg/m(2 ) ) on day 1 and infusional fluorouracil ( 360 mg/m(2)/d ) on days 1 through 5 of weeks 6 and 7 ( chemoboost ) . RESULTS Three-year failure-free survival rates were 55 % with TPZ/CIS ( 95 % CI , 39 % to 70 % ) and 44 % with chemoboost ( 95 % CI , 30 % to 60 % ; log-rank P = .16 ) . Three-year locoregional failure-free rates were 84 % in the TPZ/CIS arm ( 95 % CI , 71 % to 92 % ) and 66 % in the chemoboost arm ( 95 % CI , 51 % to 79 % ; P = .069 ) . More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS , while acute skin radiation reaction was more severe and prolonged with chemoboost . Compliance with protocol treatment was satisfactory on both arms . CONCLUSION Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting . Based on the promising efficacy seen in this trial , TPZ/CIS is being evaluated in a large phase III trial Sensitizing and neurotoxic effect of ornidazole , was tested in a double-blind r and omized study in patients with carcinoma of the cervix and larynx .  Ornidazole or placebo were given orally , two times weekly , for 3 weeks . Dose was 2.5 g/m2 for each administration . Total dose given was 15 g/m2 . Radiation therapy was given 3 h after the drug administration . Ornidazole was well tolerated in the majority of the patients . No neurotoxic side effects , such as peripheral neuropathy or convulsion , were observed with a total dose of up to 30 g. Dizziness , somnolence and nausea were the prominent acute side effects , seen mostly ( 70 % ) in women . In the  placebo group this rate was 17 % ( p less than 0.01 ) . No important side effect was observed in men receiving ornidazole .  Serum concentration of ornidazole  reached the maximum level in 2 - 4 h after oral administration and ranged ( 23 patients ) from 65.1 to 139.8 micrograms/ml . Mean half-life was 15.6 + /- 2.8 h. Peak concentration in tumour tissue was achieved 1 - 3 h after the administration , ranging from 13.0 to 78.0 micrograms/g . Tumour concentration of ornidazole  ranged from 14 to 93 % of the serum concentration at the time of irradiation Hypoxia is associated with tumor aggressiveness and is an important cause of resistance to radiation treatment . Assays of tumor hypoxia could provide selection tools for hypoxia-modifying treatments . This study correlated the exogenous 2-nitroimidazole hypoxia marker 1-[(2-hydroxy-3-piperidinyl)propyl]-2-nitroimidazole hydrochloride ( pimonidazole ) with the endogenous hypoxia-related marker carbonic anhydrase 9 ( CA9 ) and with vascular parameters using immunohistochemical techniques and a computerized image analysis system . Tumor biopsies were obtained from patients with head and neck carcinomas that were potential c and i date s for a Phase II trial with accelerated radiotherapy combined with carbogen and nicotinamide ( ARCON ) .  If , after completion of the diagnostic workup , the eligibility criteria were met and informed consent was obtained , patients were treated with ARCON . Those patients that were not eligible or refused ARCON were treated with radiotherapy , surgery , or a combined modality .  Forty-three biopsies were analyzed , and the results were related with treatment outcome . The distribution patterns of pimonidazole and CA9 were similar , although the CA9 signal was generally observed already at shorter distances from blood vessels . There was a weak but significant correlation between the relative tumor areas positive for pimonidazole binding and areas with CA9 expression . Locoregional tumor control was significantly lower for patients who had hypoxic tumors or tumors with low vascular density . The 2-year control rates were 48 versus 87 % for tumors with high and low pimonidazole binding levels ( stratified by median , P = 0.01 ) and 48 and 88 % for tumors with low and high vascular density ( stratified by median , P = 0.01 ) . These associations disappeared in the subgroup of patients treated with ARCON . There was no relationship between the level of CA9 expression and treatment outcome . It is concluded that pimonidazole binding and vascular density can predict treatment outcome in head and neck cancer and may be useful as selection tools for hypoxia-modifying treatments . Pimonidazole and CA9 demonstrate concordant staining patterns , but the latter is a less specific marker for hypoxia A r and omized clinical trial of atmospheric oxygen breathing during radiotherapy of advanced cancer of the tonsillar region has been conducted . In order to achieve a high level of inspired oxygen , a closed system with a " head tent " was used . Over 2 years after treatment , 30 percent of the oxygen patients  survived without evidence of disease compared to 17 percent in the control group BACKGROUND AND PURPOSE Hypoxia adversely affects treatment outcome in human uterine cervical cancer . Here , we present the results of a prospect i ve international multi-centre study evaluating the prognostic value of pre-treatment tumour oxygen partial pressure  ( pO(2 ) ) and the hypoxia marker pimonidazole ( pimo ) . MATERIAL S AND METHODS One hundred and twenty-seven patients with primary cervix cancer were entered . Pre-treatment tumour pO(2 ) measurements were obtained , and reported by the median tumour pO(2 ) , the fraction of pO(2 ) values < or=10 mmHg ( HP(10 ) ) , < or=5 mmHg ( HP(5 ) ) and < or=2.5 mmHg ( HP(2.5 ) ) . Following intravenous pimonidazole administration , biopsies were taken , stained for pimonidazole adducts , and scored for the area of labelled tumour cells on a scale from 0 to 4 . Treatment modalities were surgery ( 11 % ) , radiotherapy ( 98 % ) , chemotherapy ( 33 % ) and carbogen ( 14 % ) . RESULTS None of the hypoxia descriptors were statistically significant prognostic factors for loco-regional tumour control or overall survival when analyzed as continuous variables or divided by the sample median . By univariate analysis only tumour size and nodal status were significant prognostic factors for local control . Tumour size and FIGO stage were significant for overall survival . In a multivariate analysis stratified by centre , only tumour size above 5 cm and lower pre-treatment haemoglobin predicted poorer overall survival among FIGO stage , nodal involvement , tumour size , pre-treatment haemoglobin dichotomized at 12 g/dl and pimo 1 , pimo 4 and HP(5 ) as continuous variables . CONCLUSION Neither Eppendorf nor pimonidazole should be dismissed based on the current results . However , further investigations are needed to readdress the hypotheses of the current study having optimized statistical design s , and a population of sufficient size treated more homogenously following rigorous protocol In animal models carbogen ( normobaric 95 % oxygen , 5 % carbon dioxide ) provides significant enhancement of local tumor control with fractionated radiotherapy . This approach to radiosensitization has been evaluated in the treatment of patients with bladder carcinoma using radical radiotherapy UNLABELLED Oropharynx is an important site of cancer in India . Global comparison indicates higher incidences in India . Radiotherapy remains an important treatment modality . Efforts to improve loco-regional treatment and prolong survival are areas of focus . Radiosensitizers in hypoxic tumors have shown promise . AIM To study the safety and radiosensitizing efficacy of sanazole in oropharyngeal squamous cell carcinoma ( stage T2 - 4 , N0 - 3 , M0 ) as phase-II double blind controlled trial in patients treated with conventional radiotherapy . SETTING S AND DESIGN Single institutional , r and omized , double-blind , placebo-controlled trial . MATERIAL S AND METHODS Group 1 ( control ; n = 23 ) received normal saline infusion , group 2 ( test ; n = 23 ) received sanazole biweekly 1.25 g intravenous infusion 15 minutes before radiotherapy . Surrogate end points of efficacy were tumor and nodal size ; safety parameters were mucositis , salivary and skin reactions , dysphagia , vomiting , dysgeusia and neurological deficit . Investigators blinded to the trial evaluated patients , weekly during treatment for six weeks and thereafter monthly for three months . STATISTICAL M 
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No significant influence was found on the incidence of distant metastases or on the risk of radiation-related complications .
Ample data exist to support a high level of evidence for the benefit of hypoxic modification .
However , hypoxic modification still has no impact on general clinical practice