***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: Purpose The purpose of the study was to evaluate [18F]fluoromisonidazole ( FMISO ) PET in advanced head and neck cancer during hypoxia-targeting therapy . Methods Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine ( specific cytotoxin for hypoxic cells ) in advanced ( T3/4 and /or N2/3 ) head and neck cancer underwent serial [18F]fluorodeoxyglucose ( FDG ) and FMISO PET . We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort . Results Based on blinded qualitative scoring by two readers , FMISO PET was positive in 13/15 patients at baseline : 12/15 of primary sites and 8/13 neck nodes were scored as positive . All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy , consistent with effective hypoxia-targeted therapy . With a median follow-up of 6.9 years , there have been only four locoregional failures , while three other patients have died of metachronous lung cancer . The 5-year overall survival was 50 % ( 95 % CI 27–73 % ) , the 5-year failure-free survival was 44 % ( 95 % CI 22–68 % ) and the 5-year freedom from locoregional failure was 68 % ( 95 % CI 38–88 % ) . Conclusion The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis . Evidence of the early resolution of FMISO abnormality during treatment , associated with excellent locoregional control in this patient cohort , supports further investigation of hypoxia-targeting agents in advanced head and neck cancer UNLABELLED In radiotherapy of head and neck cancer ( HNC ) and non-small cell lung cancer ( NSCLC ) , hypoxia is known to be an important prognostic factor for long-term survival and local tumor control . The PET tracer (18)F-fluoromisonidazole ( FMISO ) allows noninvasive assessment of tumor hypoxia . This study analyzed whether FMISO PET could predict tumor recurrence after radiotherapy . METHODS Forty patients with advanced HNC ( n = 26 ) or NSCLC ( n = 14 ) were studied before curative radiotherapy . Dynamic ( 0 - 15 min ) and static PET scans were acquired up to 4 h after injection of 400 MBq of FMISO .  St and ardized uptake values ( SUVs ) and ratios to reference tissues ( mediastinum or muscle ) were calculated . In addition , time-activity curves up to 14 min after injection were classified visually . PET data were correlated with clinical follow-up data ( presence or absence of local recurrence within 1 y ) , which were available for 21 patients . RESULTS For HNC , patients with local recurrence could be separated from disease-free patients by SUV 4 h after injection ( all recurrences had an SUV > 2 ) . For NSCLC , no such correlation was observed . The tumor-to-muscle ratios ( T/Mu ) and tumor-to-mediastinum ratios ( T/Me ) at 4 h after injection correlated with the risk of relapse in both tumor entities : All patients with a T/Me greater than 2.0 ( NSCLC , n = 5 ) or with a T/Mu greater than 1.6 ( HNC , n = 5 ) presented with tumor recurrence , whereas only 3 of the remaining 11 patients experienced recurrence ( 27 % ) . Qualitative analysis of time-activity curves for 37 patients revealed 3 curve types ( rapid washout , n = 9 ; intermediate [ delayed washout ] , n = 12 ; and accumulation , n = 16 ) . Eighteen patients categorized by curve type could be followed up : In 5 of 6 patients with an accumulation curve , disease recurred locally within 1 y , compared with 5 of 8 patients with a delayed-washout curve and 0 of 4 with a rapid-washout curve . CONCLUSION Our results indicate that outcome after radiotherapy can be predicted on the basis of kinetic behavior of FMISO in tumor tissue . An accumulation-type curve , high SUV , and high T/Mu and T/Me at 4 h after injection are highly suggestive of an incomplete response to treatment and might be used to select patients for intensified therapy protocol PURPOSE To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and /or N2/3 squamous cell carcinoma of the head and neck . PATIENTS AND METHODS The starting schedule was conventionally fractionated radiotherapy ( 70 Gy in 7 weeks ) with concomitant cisplatin 75 mg/m2 and tirapazamine 290 mg/m2 ( before cisplatin ) in weeks 1 , 4 , and 7 and tirapazamine alone 160 mg/m2 three times a week in weeks 2 , 3 , 5 , and 6 . Positron emission tomography scans for tumor hypoxia ( 18F misonidazole ) were performed before and during radiotherapy . RESULTS We treated 16 patients with predominantly oropharyngeal primary tumors , including 10 patients with T4 or N3 disease .  Febrile neutropenia occurred toward the end of radiotherapy in three out of six patients treated on the initial dose level . Two of these patients also developed grade 4 acute radiation reactions . Another 10 patients were treated with the same doses , but the week 5 and week 6 tirapazamine doses were omitted . This result ed in less neutropenia and only one dose-limiting toxicity ( DLT ) ( febrile neutropenia ) , and eight out of 10 patients completed treatment without any dose omissions . In these 10 patients , the acute radiation toxicities were not obviously enhanced compared with chemoradiotherapy regimens using concurrent platinum and fluorouracil . 18F misonidazole scans detected hypoxia in 14 of 15 patients at baseline , with only one patient having detectable hypoxia at the end of treatment . With a median follow-up of 2.7 years , the 3-year failure-free survival rate was 69 % ( SE , 12 % ) , the 3-year local progression-free rate was 88 % ( SE , 8 % ) , and the 3-year overall survival rate was 69 % ( SE , 12 % ) . CONCLUSION DLT was due unexpectedly to febrile neutropenia , which could be overcome by omitting tirapazamine in weeks 5 and 6 . The combination of tirapazamine , cisplatin , and radiotherapy result ed in remarkably good and durable clinical responses in patients with very advanced head and neck cancers . It warrants further investigation PURPOSE Angiogenesis is a target for the treatment of cancer and other diseases , and its complex biology suggests that establishing the appropriate dose and schedule for antiangiogenic treatment will require extensive study . We present the initial results of a dose-finding clinical trial of recombinant human endostatin ( rh-Endo ) that examined potential surrogates for response to antiangiogenic therapy . PATIENTS AND METHODS Twenty-five patients were treated with escalating doses of rh-Endo . Positron emission tomography ( PET ) was used to assess tumor blood flow ( with [15O]H2O ) and metabolism ( with [18F]fluorodeoxyglucose ) before the start of therapy and then every 4 weeks . To directly assess the effects of rh-Endo on endothelial cells within the tumors , biopsy specimens of tumor tissue were obtained before therapy and again at 8 weeks and evaluated for endothelial cell and tumor cell apoptosis . RESULTS Tumor blood flow and metabolism as measured by PET scans generally decreased with increasing doses of rh-Endo ; however , the effects were complex and in some analyses nonlinear . Tumor biopsy analysis revealed a significant increase in tumor cell apoptosis ( P = .027 ) and endothelial cell apoptosis ( P = .027 ) after 8 weeks of therapy . However , there was no statistically significant relationship between rh-Endo dose and induction of tumor cell or endothelial cell apoptosis . CONCLUSION These initial data suggest that rh-Endo has measurable effects on tumor blood flow and metabolism and induces endothelial and tumor cell apoptosis even in the absence of demonstrable anticancer effects . Further study and validation of these biomarkers in the context of antiangiogenic therapy will be required Abstract .The aim of this study was to assess the safety and biodistribution of technetium-99 m BRU 59 - 21 , a novel radioactively labelled 2-nitro-imidazole hypoxic marker , in head and neck cancer patients and to correlate uptake with pimonidazole staining . 99mTc-BRU 59 - 21 was administered intravenously ( mean dose 824 MBq , range 780–857 MBq ) to ten head and neck cancer patients scheduled for primary surgery , and whole-body images and SPET scans were then obtained . Uptake of radioactivity in the regions of interest was determined and tumour to normal tissue ratios were calculated after correlative evaluation with MRI/CT . Twelve to 16 h before surgery ( up to 2 weeks after the scan ) , patients received pimonidazole intravenously . Tumour sections were stained immunohistochemically for pimonidazole binding . No serious adverse events were reported . In five patients there were ten adverse events , which were mild in intensity and resolved completely without intervention . Uptake of 99mTc-BRU 59 - 21 was observed in eight of the ten primary tumours . Tumour to normal tissue ratios on the SPET scans for primary tumour and lymph nodes increased from 1.8 ( range 0.9–2.7 ) to 2.1 ( range 0.8–3.7 ) between 30 min and 3 h post injection . Tumour to normal tissue ratios in the primary tumour were significantly correlated with pimonidazole staining for SPET scans performed 30 min and 3 h post injection ( P=0.016 and P=0.037 , respectively ) . When primary tumour and involved lymph nodes were considered in conjunction , correlation between the tumour to normal tissue ratio and pimonidazole staining was observed for early ( P<0.001 ) but not for late SPET scans ( P=0.076 ) . However , late scans showed better tumour delineation than early scans . Administration of 99mTc-BRU 59 - 21 in head and neck cancer patients appears to be safe and feasible . Uptake and retention in tumour tissue was observed , suggestive of tumour hypoxia , and this was supported by correlations with staining for the hypoxic marker pimonidazole Abstract . Fluorine-18 fluoroerythronitroimidazole ( [18F]FETNIM ) is a nitroimidazole compound that is potentially useful as a hypoxia marker in  positron emission tomography ( PET ) studies of oncological patients . Our aim was to develop a simple protocol to quantitate uptake of [18F]FETNIM in hypoxic tumours . Dynamic imaging data from ten patients with head and neck cancer undergoing [18F]FETNIM PET was used in simulations and model fits to assess hypoxia marker uptake under different levels of blood flow . The distribution volume determined from dynamic PET study was compared with simple tumour to plasma and tumour to muscle ratios at 90–120 min . In skeletal muscle having a low but variable blood flow [ 2–6 ml/(100 g × min ) ] , differences in hypoxia-specific uptake of [18F]FETNIM remain small and may be hard to detect with PET . At higher blood flow [ > 20 ml/(100 g × min ) ] , the retention of [18F]FETNIM reflects the oxygenation status well and results in satisfactory contrast between hypoxic and well-oxygenated tissue . A good estimate of tissue hypoxia is accomplished by measuring the tissue to plasma [18F]FETNIM activity ratio using only a few late time points . The increased hypoxia-specific retention of [18F]FETNIM in tissues with high blood flow , such as malignant tumours , may facilitate application of [18F]FETNIM as a hypoxia marker in oncological patients . In the assessment of the tumour to non-target uptake ratio , plasma is the preferred reference tissue rather than muscle , which may show a more heterogeneous tracer uptake not easily controlled for Objectives : To compare blood flow measurements of tumors assessed by perfusion computed tomography ( pCT ) and the clinical gold st and ard of 15O-labeled water positron emission tomography ( 15O-PET ) . Methods : Blood flows were estimated by pCT ( 4-row multidetector , CT Perfusion 3.1 ) and 15O-PET ( Posicam , first-pass model ) in 14 patients with solid tumors , totaling 22 index tumors and 57 matched pairs of examinations . Blood flow estimates were compared using t test , Bl and -Altman , and linear mixed regression analyses . Results : There was no significant difference between the mean ( SD ) blood flow values measured by pCT and 15O-PET : 25.9 ± 15.4 and 27.8 ± 14.0 mL/min per 100 g 
    Output:
    
Conclusions A subset of radionuclide methods offers accurate quantitative scientific observations on tumour vascular physiology of relevance to angiogenesis and its treatment .