***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: Background The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35 % . Several r and omized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival . However , further dose escalation to the whole gl and is limited due to an unacceptable high risk of acute and late toxicity . Moreover , local recurrences often originate at the location of the macroscopic tumor , so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control . A reduction of distant metastases and improved survival can be expected by reducing local failure . The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer . Methods / Design The FLAME-trial ( F ocal L esion A blative M icroboost in prostatE cancer ) is a single blind r and omized controlled phase III trial . We aim to include 566 patients ( 283 per treatment arm ) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification . With this number of patients , the expected increase in five-year freedom from biochemical failure rate of 10 % can be detected with a power of 80 % . Patients allocated to the st and ard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions . The secondary outcome measures include treatment-related toxicity , quality of life and disease-specific survival . Furthermore , by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose , we can obtain accurate dose-effect information for both the macroscopic tumor and sub clinical disease in prostate cancer . The rationale , study design and the first 50 patients included are described . Trial registration This study is registered at Clinical Trials.gov : Purpose To assess whether an exp and ed ( five level ) risk stratification system can be used to identify the sub-group of intermediate risk patients with prostate cancer who benefit from combining and rogen deprivation therapy ( ADT ) with external beam radiotherapy ( EBRT ) .  Material s and methods Using a previously vali date d 5-risk group schema , a prospect i ve non-r and omized data set of 1423 men treated at the British Columbia Cancer Agency was assessed for the primary end point of biochemical control ( bNED ) with the RTOG-ASTRO " Phoenix " definition ( lowest PSA to date + 2 ng/mL ) , both with and without adjuvant ADT . The median follow-up was 5 years . Results There was no bNED benefit for ADT in the low or low intermediate groups but there was a statistically significant bNED benefit in the high intermediate , high and extreme risk groups . The 5-year bNED rates with and without ADT were 70 % and 73 % respectively for the low intermediate group ( p = non-significant ) and 72 % and 58 % respectively for the high intermediate group ( p = 0.002 ) . Conclusion There appears to be no advantage to ADT where the Gleason score is 6 or less and PSA is 15 or less . ADT is beneficial in patients treated to st and ard dose radiation with Gleason 6 disease and a PSA greater than 15 or where the Gleason score is 7 or higher When analysis of results of radiotherapy for nearly 500 patients with oropharyngeal cancer showed evidence for rapid tumor regrowth during extensions of treatment from about 5 weeks to about 8 weeks , we search ed the literature on radiotherapy for head and neck cancer to determine whether it revealed similar evidence of accelerated tumor regrowth . Estimates of doses to achieve local control in 50 % of cases ( TCD50 ) were made from published local control rates , and the dependence of these doses on overall treatment duration was evaluated . In parallel , published scattergrams were analyzed to estimate the rate of tumor regrowth over the period of 4 - 10 weeks from initiation of therapy . Both analyses suggested that , on average , clonogen re population in squamous cell carcinomas of the head and neck accelerates only after a lag period of the order of 4 + /- 1 weeks after initiation of radiotherapy and that a dose increment of about 0.6 Gy per day is required to compensate for this re population . Such a dose increment is consistent with a 4-day clonogen doubling rate , compared with a median of about 60 days in published reports of unperturbed tumor growth rates . The values presented here are average values for a large number of patients : it is necessary , not only to verify the results of these retrospective analyses in prospect i ve studies , but also to develop methods to predict the time of onset and rate of accelerated tumor clonogen re population in the individual patient OBJECTIVES To investigate whether low partial pressure of oxygen ( PO2 ) in prostate cancer ( CaP ) predicts for biochemical outcome after  radiotherapy .  We previously reported that hypoxic regions exist in human CaP. METHODS Custom-made Eppendorf PO2 microelectrodes were used to obtain approximately 100 PO2 readings from both pathologically involved regions of the prostate ( as determined by sextant biopsies ) and normal muscle ( as an internal control ) . Fifty-seven patients with localized disease were prospect ively studied ; all received brachytherapy implants ( 48 low dose rate and 9 high dose rate ) under spinal anesthesia .  Nine patients had received prior hormonal therapy .  Biochemical failure was defined as two consecutive rises in prostate-specific antigen level , without a return to baseline . Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control , while adjusting for prostate-specific antigen , Gleason score , stage , implant type ( low dose rate versus high dose rate ) , perineural invasion , hemoglobin level , use of hormonal therapy , average ( mean ) of the median prostate PO2 , average median muscle PO2 , and prostate/muscle PO2 ( P/M ) ratio . RESULTS With a median follow-up of 19 months ( range 4 to 31 ) , 9 patients developed biochemical failure . A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater ( 31 % versus 92 % , P < 0.0001 ) . However , the classic prognosticators were similar in these two groups . On multivariate analysis , the P/M ratio was the only predictor of biochemical control ( P = 0.0002 ) . CONCLUSIONS To our knowledge , this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy . The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis . Longer follow up with more patients is planned to confirm this result BACKGROUND AND PURPOSE Heavy ion radiotherapy is a promising modality because of its excellent dose localization and high biological effect on tumors . Using carbon beams , a dose escalation study was conducted for the treatment of stage I non-small cell lung cancer ( NSCLC ) to determine the optimal dose . MATERIAL S AND METHODS The first stage phase I/II trial using 18 fractions over 6 weeks for 47 patients and the second one using nine fractions over 3 weeks for 34 patients were conducted by the dose escalation method from 59.4 to 95.4 Gray equivalents ( GyE ) in incremental steps of 10 % and from 68.4 to 79.2 GyE in 5 % increments , respectively . The local control and survival rates were obtained using the Kaplan-Meier method . RESULTS Radiation pneumonitis at grade III occurred in three of 81 patients , but they fully recovered . This was not a dose-limiting factor . The local control rates in the first and second trials were 64 % and 84 % , respectively . The total recurrence rate in both trials was 23.2 % . The infield local recurrence in the first trial was significantly dependent on carbon dose . The doses greater than 86.4 GyE at 18 fractions and 72 GyE at nine fractions achieved a local control of 90 % and 95 % , respectively . The 5 year overall and cause-specific survivals in 81 patients were 42 % and 60 % , respectively . CONCLUSIONS With our dose escalation study , the optimum safety and efficacy dose of carbon beams was determined . Carbon beam therapy attained almost the same results as surgery for stage I NSCLC although this was a I/II study PURPOSE Analysis of the results of hypofractionated conformal carbon ion radiotherapy for localized prostate cancer was performed , with special regard to normal tissue morbidity and biochemical relapse-free rate ( bNED ) . METHODS AND MATERIAL S Analysis was performed for 201 patients treated with the dose fractionation regimen established during three clinical trials performed between June 1995 and February 2004 . Outcomes were measured in terms of toxicity , survival , freedom from local recurrence , and bNED . RESULTS No Grade 3 or higher toxicities were observed in either the rectum or genitourinary system , and the incidences of Grade 2 rectum or genitourinary morbidity were only 1.0 % and 6.0 % , respectively . The overall 5-year biochemical relapse-free survival was 83.2 % without any local recurrence . Gleason score , initial PSA , and T stage were all significant prognostic factors for bNED , which was 97.1 % in patients with Gleason score < or = 7 and initial PSA < 20 ng/mL. CONCLUSION Hypofractionated carbon ion radiotherapy with the established dose fractionation regimen yielded satisfactory bNED without local recurrence and with minimal morbidity . Long-term results are necessary to confirm the utility of carbon ion radiotherapy in the treatment of localized prostate cancer BACKGROUND AND PURPOSE The objectives of the current study were to compare genito-urinary ( GU ) and gastro-intestinal ( GI ) toxicities as well as biochemical control ( bRFS ) in prostate cancer , utilizing conventional ( 2.0 Gy daily ) ( STD ) or hyperfractionated ( HFX ) conformal irradiation ( CRT ) . HFX ( 1.2 Gy BID ) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control . PATIENTS AND METHODS Three-hundred- and -seventy consecutive patients ( pts ) entered this prospect i ve , non-r and omized trial in the period January 1993-January 2003 ; 209 were treated with STD and 161 with HFX CRT .  All were evaluable for acute toxicity analysis , 179 ( STD ) and 151 pts ( HFX ) being evaluable for late sequelae and bRFS analyses . Pt characteristics were not statistically different in the two groups . CRT consisted of a 4-field technique for prostate and /or pelvic nodes and a 5-field boost with rectal shielding . Median doses were 74 and 79.2 Gy for STD and HFX patients respectively , the latter dose being isoeffective for tumour control assuming alpha/beta=10 ( EQD(2)=73.9 Gy ) . Median follow-up was 29.4 months ( 25.2 mos for STD ; 37.7 mos for HFX ; P<0.01 ) . The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses . RESULTS Acute grade > or = 2 GU toxicity was higher in the STD group ( 48.6 % versus 37.3 % in HFX , P=0.03 ) , while no significant difference was found for acute GI toxicity . Late grade > or = 2 GU and GI toxicities were lower in the HFX group ( 5-year actuarial rate : GU : 10.1 % versus 20.3 % , P=0.05 ; GI : 6.0 % versus 10.6 % , P=0.18 ) . Five-year bRFS were 70 % ( + /-13.8 % , 95 % CI ) and 82.6 % ( + /-7.2 % ) for STD and HFX , respectively ( P=0.44 ) ; a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy ( 5-year bRFS : 85.9%+/-12.4 % versus 63.9%+/-23.8 % , P=0.15 ) . Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation regimen . Using the Nahum-Chapman TLCP model and prostate parameter set , which includes hypoxia , the TLCPs are approximately equal for the two regimens , whereas assuming alpha/beta=1.5 and no hypoxia we obtain 73 % for the STD group but only 36 % for the HFX group . CONCLUSIONS As expected from radiobiological considerations , HFX reduces GI and GU late toxicities . Concerning early bRFS , our clinical findings suggest that HFX is no less effective than STD when delivering an isoeffective ( alpha/beta=10 ) dose . Despite the relatively short follow-up , this result appears to be inconsistent with a low alpha/beta ratio for prostate cancer Gamma knife treatments are usually planned manually , requiring much expertise and time . We describe a new , fully automatic method of treatment planning . The treatment volume to be planned is first compared with a data base of past treatments to find volumes closely matching 
    Output:
    
This TCP model fitted and vali date d to clinical outcome data , appears to be an appropriate model for the inclusion of all clinical prostate cancer risk categories , and allows evaluation of current EBRT modalities with regard to tumor control prediction