***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: PURPOSE To identify prognostic clinical and treatment related factors for local control , distant metastasis-free survival , and survival by means of a multivariate analysis in patients with advanced squamous cell carcinoma of the head and neck after concomitant boost radiochemotherapy .  PATIENTS AND METHODS From 1992 to 1995 , 68 patients with squamous cell cancer of the head and neck ( 93 % stage IV disease ) were treated with a simultaneous radiochemotherapy with Carboplatin using a concomitant boost technique . The total tumor volume ( TTV ) was quantitatively determined based on computed tomography scans in 56 patients . A Cox proportional hazards regression analysis was performed for each of the above endpoints and statistical significance of the Cox models was verified using the likelihood ratio test and Bonferroni correction for multiple testing . RESULTS The survival and locoregional control rates at three years were 35 and 32 % . The multivariate analysis revealed a significant association between the TTV and survival ( P = 0.0008 ) and between the pretreatment serum hemoglobin concentration and locoregional control ( P = 0.01 ) and survival ( P = 0.05 ) . The locoregional control was significantly associated with the N-stage ( P = 0.007 ) and there was a good correlation between the N-stage and TTV in this study population . CONCLUSION Our data corroborate the prognostic relevance of the tumor volume and hemoglobin concentration . In studies comparing the survival of patients with advanced cancer of the head and neck , the use of the TTV as a covariable may improve the statistical power In trial no. 22811 on a r and omized comparison of multiple fractions per day ( MFD ) , with or without misonidazole , to conventional fractionation in advanced head and neck cancer , a large number ( 523 ) of patients was entered in a short period of time . No differences in treatment results were obtained , but the study created an important data base , allowing for detailed evaluation of the most important factors influencing prognosis . In univariate analysis , factors significantly influencing survival and locoregional control were : performance status , histological differentiation , tumor site , tumor and nodal staging , and tumoral and nodal volume . In multivariate analysis , significant factors for survival were nodal involvement , tumor stage , performance status , and tumor site . Significant factors for locoregional control were nodal involvement and total tumor burden . This analysis suggests that total tumor burden ( volume ) should be included in the interpretation of treatment results in head and neck cancer Purpose : Tumor volume after the lymph node involvement is one of the most important single prognostic factor in patients of head and neck cancers treated with radiotherapy .  We have recently demonstrated that the hypoxic subvolume is more important than the total tumor volume . We therefore propose the hypothesis that the presence of visible necrosis might be an important factor for cure by radiotherapy in squamous cell cancers of the head and neck . Methods : A total of 51 patients with locally advanced inoperable ( T3 - 4 or N2 - 3 ) squamous cell cancers of the head and neck ( mean age 57 years , range 41–75 years ) were prospect ively investigated with regard to a possible impact of tumor volume . All patients received CT examination of the  head  and  neck  according to a st and ardized protocol ( spiral CT , contrast enhancement after automatic injection ) , and the total tumor volume was calculated as the sum of volumes of all visible macroscopic tumor sites . Poorly perfused and necrotic areas ( no contrast enhancement ) within macroscopic tumor sites were also calculated . Patients were then treated with accelerated-hyperfractionated radiotherapy in about 6 weeks . Seventeen patients were treated with  only radiation . Patients without contraindications to cisplatin chemotherapy  received cisplatin chemotherapy or a combination of cisplatin and paclitaxel ( N=34 ) . The allocation of patients to certain treatment regimens was based on individual decisions in each case and not r and omized . Results : In patients treated with radiation alone , 12/17 ( 71 % ) got recurrence whereas in patients treated with radiation plus cisplatin , only 14/34 ( 41 % ) recurred ( P=0.05 ) . The 2-year overall survival was for radiation alone versus radiation plus cisplatin 0 % vs. 62 % ( P<0.0008 ) . Tumors with smaller amount of necrosis ( necrosis volume<4 cm3 ) had a good prognosis irrespective of type of treatment ( radiation alone or radiation plus cisplatin ) . However , patients with tumors with a larger amount of necrosis ( necrosis volume≥4 cm3 ) had a significantly better outcome if they were treated with radiation plus cisplatin as compared to patients treated with radiation alone . In a multi-variate analysis using a Cox-regression model the type of treatment ( radiotherapy plus versus without cisplatin ) was the only independent prognostic factor for event-free survival ( P<0.03 ) in the whole group . Conclusions : In this non-r and omized retrospective investigation with limited sample size , radiation plus cisplatin was superior to radiation alone . This result ed mainly from a higher efficacy of the radiochemotherapy regimen in patients with large and especially necrotic tumors . The prognostic and predictive impact of visible necrosis should be further evaluated PURPOSE To determine whether the immunohistochemical expression of proliferation-associated antigens ( proliferating cell nuclear antigen , MIB1 ) and the nuclear p53 reactivity in addition to total tumor volume , nodal CT density and T and N category are predictive for overall survival and locoregional tumor control in patients with squamous cell carcinoma of the head and neck region . MATERIAL S AND METHODS Between October 1989 and September 1993 , 87 patients with biopsy proven head and neck cancer were r and omly allocated to receive radiation alone or simultaneous radiation and chemotherapy as part of a multicenter trial with a total of 298 r and omized patients . There were only inoperable lesions in UICC ( 1992 ) stage III ( 8 % ) and IV ( 92 % ) . Radiotherapy was delivered with 180 cGy twice daily up to a total dose of 7020 cGy in 51 days . Three cycles of 2340 cGy each were separated by a rest period of 11 days . Chemotherapy consisted of cis-DDP , 5-fluorouracil and leucovorin and was repeated on days 22 and 44 . Routinely-processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferation-associated antigens ( MIB1 and PCNA ) and p53 oncoprotein to determine the labeling index ( LI ) . In addition , the total tumor volume and the percentage of necrosis were measured using CT data . The median follow-up was 3.9 years ( range 1.9 - 5.0 years ) . RESULTS The overall survival and locoregional control for all 87 patients were 34 and 39 % at 3 years , respectively . The addition of chemotherapy result ed in a better overall survival ( 27 versus 47 % , P = 0.03 ) but did not influence locoregional control ( 31 versus 47 % , P = 0.08 ) . In univariate analysis , nodal CT density ( P < 0.0001 ) , total tumor volume ( P < 0.0001 ) , age ( P = 0.001 ) and the MIB1-LI ( P = 0.04 ) had a significant impact on overall survival . However , in the final Cox model only the nodal CT density ( P = 0.0003 ) and age ( P = 0.05 ) were independent prognostic factors for survival and only the nodal CT density ( P = 0.0006 ) was an independent prognostic factor for locoregional control . The expression of the p53 oncoprotein was not found to have a clear predictive value . CONCLUSION Nodal CT density , total tumor volume and age will remain the relevant prognostic factors in stage III/IV head and neck cancer The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging ( MRI ) as a method of screening for breast cancer in women at genetic risk is described . The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography .  Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years , with annual MRI and x-ray mammography continuing for up to 5 years . A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres . The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment , followed by a high-specificity contrast-enhanced study in equivocal cases . Multiparametric analysis will encompass morphological assessment , the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters . Retrospective analysis will identify the most specific indicators of malignancy . Sensitivity and specificity , together with diagnostic performance , diagnostic impact and therapeutic impact will be assessed with reference to pathology , follow-up and changes in diagnostic certainty and therapeutic decisions . Mammography , lesion localisation , pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance st and ards . Similar st and ards of quality assurance will be applied for MR measurements and evaluation PURPOSE To investigate the value of CT-derived tumor parameters as predictor of local and regional outcome of tonsillar squamous cell carcinoma treated by definitive radiation therapy . METHODS AND MATERIAL S The pretreatment CT studies of 112 patients with tonsillar squamous cell carcinoma were review ed . After redigitizing the films , primary and nodal tumor volume was calculated with the summation-of- areas technique . The nodal CT aspect was grade d using a 3-point scale ( homogenous , inhomogeneous , and necrotic ) . Mean follow-up time was 33 months . Actuarial statistical analysis of local and regional outcome was done for each of the covariates ; multivariate analysis was performed using Cox 's proportional hazards model . RESULTS In the actuarial analysis , CT-determined primary tumor volume was significantly correlated with local recurrence rate ( p < 0.05 ) when all patients were considered , but primary tumor volume did not predict local control within the T2 , T3 , and T4 category . CT-determined nodal volume was significantly related to regional outcome ( p < 0.01 ) , but nodal density was not . Total tumor volume was not significantly related to locoregional outcome ( p = 0.1 ) . In the multivariate analysis , the T and N categories were the independent predictors of local and regional outcomes , respectively . CONCLUSION Compared to other head- and -neck sites , primary and nodal tumor volume have only marginal predictive value regarding local and regional outcome after radiation therapy in tonsillar cancer PURPOSE Tumor volume ( TV ) is one of the main reported factors determining the outcome of treatment in head- and -neck carcinomas . In this study , the prognostic impact of TV was explored in the context of a r and omized trial with the patients assigned to receive st and ard radiotherapy ( RT ) alone or RT plus platinum compounds ( RT alone , RT plus cisplatin , or RT plus carboplatin ) . METHODS AND MATERIAL S The tumor outlines were traced and digitized on each pretreatment CT slice for each of the 101 patients studied . Taking into account the magnification factor of the scan and CT slice thickness , a computer with specifically design ed software calculated the TV in cubic centimeters . RESULTS The median overall survival for the whole group of patients was 21.6 months ( 95 % confidence interval , 13.0 - 30.2 ) and the 3-year survival rate was 40 % . The addition of platinum compounds to RT ( Groups 2 and 3 ) significantly improved the survival rate  ( RT alone vs. RT plus cisplatin , hazard ratio 0.36 , p = 0.002 ; RT alone vs. RT plus carboplatin , hazard ratio 0.53 , p = 0.029 ) . In univariate analysis , the most significant parameters for survival were treatment group , total gross tumor volume ( TGTV ) , complete response , nodal GTV , primary GTV , and performance status . In multivariate analysis , treatment group , TGTV , gender , and primary site were independent prognostic factors for survival . A prognostic threshold of 22.8 cm(3 ) was detected for TGTV . Patients with a TGTV of < 22.8 cm(3 ) were more likely to achieve a complete response and had a median survival of 45.3 months , and those with a TGTV > 22.8 cm(3 ) had a median survival of 12.3 months ( log-rank test , p = 0.0102 ) . CONCLUSION The prognostic significance of the TGTV was confirmed and a cutoff value of 22.8 cm(3 ) derived . Our data indicated that locally advanced head- and -neck carcinomas should not be treated by st and ard ( once-daily ) RT alone . Tumor size and disease subsite should be taken into account in future r and omized trials to increase their statistical power OBJECTIVES /HYPOTHESIS Just as tumor volume is a prognostic indicator for local disease control among patients with head and neck cancer of intermediate size treated with radiation therapy  , we hypothesized a similar association for patients with advanced disease treated with chemoradiation therapy .  STUDY DESIGN Retrospective analysis of primary and nodal tumor volume was correlated with prospect ively 
    Output:
    
Until now , there 's no clear statistical evidence for the use of either TTV or nodal volume versus primary tumor volume to predict the individual loco-regional control or survival after treatment .