***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 report the short-term clinical outcomes and acute and late treatment-related genitourinary ( GU ) and gastrointestinal ( GI ) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy ( SBRT ) .  METHODS AND MATERIAL S Between 2011 and 2014 , 24 patients with prostate cancer were treated with SBRT to the prostate gl and and proximal seminal vesicles . A high-dose avoidance zone ( HDAZ ) was created by a 3-mm expansion around the rectum , urethra , and bladder . Patients were treated to a minimum dose of 36.25 Gy in 5 fractions , with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ . Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale , version 4 . RESULTS The median follow-up was 25 months ( range , 18 - 45 months ) . Nine patients ( 38 % ) experienced an acute grade 2 GU toxicity , which was medically managed , and no patients experienced an acute grade 2 GI toxicity . Two patients ( 8 % ) experienced late grade 2 GU toxicity , and 2 patients ( 8 % ) experienced late grade 2 GI toxicity . No acute or late grade ≥3 GU or GI toxicities were observed . The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8 % ( 95 % confidence interval 75.6%-99.4 % ) , and both biochemical failures occurred in patients with high-risk disease . All patients are currently alive at the time of this analysis and continue to be followed . CONCLUSIONS A heterogeneous prostate SBRT planning technique with differential treatment volumes ( low dose : 36.25 Gy ; and high dose : 50 Gy ) with an HDAZ provides a safe method of dose escalation . Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated  with SBRT Objectives To evaluate the feasibility of intensity-modulated radiotherapy with simultaneous integrated boost to the dominant intraprostatic lesion for definitive treatment of prostate cancer . Material s and Methods Patients were deemed eligible for the study if they had histologically proven stage cT2-T3 N0M0 prostate adenocarcinoma . In addition < 20 % risk of lymph nodal involvement according to Roach formula , was required for enrollment . Patients were treated with intensity-modulated radiotherapy with simultaneous integrated boost technique to the dominant intraprostatic lesion defined by magnetic resonance imaging . The prescribed dose to the prostate and seminal vesicles was 72 Gy ( 1.8 Gy per fraction ) . The dose delivered to the intraprostatic lesion received was 80 Gy ( 2 Gy per fraction ) . Acute gastrointestinal ( GI ) and genitourinary ( GU ) toxicity was evaluated weekly during treatment , and at 1 and 3 months thereafter . Late GI and GU toxicity was evaluated by Kaplan Meier method . Results Forty patients were deemed evaluable .  Acute and late GI and GU toxicity were evaluated in all patients . Two patients ( 5 % ) developed acute grade 3 GI toxicity and 1 patient ( 2.5 % ) developed acute grade 3 GU toxicity . No grade 4 acute GI or GU toxicity occurred . With a median follow-up of 19 months ( interquartile range , 15 to 26 mo ) , the 2-year actuarial cumulative incidence of grade ≥2 rectal toxicity was 9.5 % . The 2-year actuarial cumulative incidence of grade ≥2 urinary toxicity was 13.3 % . Conclusions Treatment related acute toxicity was low in our cohort . Prolonged observation with a larger series of patients is necessary to evaluate late toxicity and local control PURPOSE To report the primary endpoint of biochemical progression-free survival ( b-PFS ) and secondary survival endpoints from ASCENDE-RT , a r and omized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer . METHODS AND MATERIAL S ASCENDE-RT enrolled 398 men , with a median age of 68 years ; 69 % ( n=276 ) had high-risk disease . After stratification by risk group , the subjects were r and omized to a st and ard arm with 12 months of and rogen deprivation therapy , pelvic irradiation to 46 Gy , followed by a dose-escalated external beam radiation therapy ( DE-EBRT ) boost to 78 Gy , or an experimental arm that substituted a low-dose-rate prostate brachytherapy ( LDR-PB ) boost . Of the 398 trial subjects , 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost . The median follow-up was 6.5 years . RESULTS In an intent-to-treat analysis , men r and omized to DE-EBRT were twice as likely to experience biochemical failure ( multivariable analysis [ MVA ] hazard ratio [ HR ] 2.04 ; P=.004 ) . The 5- , 7- , and 9-year Kaplan-Meier b-PFS estimates were 89 % , 86 % , and 83 % for the LDR-PB boost versus 84 % , 75 % , and 62 % for the DE-EBRT boost ( log-rank P<.001 ) . The LDR-PB boost benefited both intermediate- and high-risk patients . Because the b-PFS curves for the treatment arms diverge sharply after 4 years , the relative advantage of the LDR-PB should increase with longer follow-up . On MVA , the only variables correlated with reduced overall survival were age ( MVA HR 1.06/y ; P=.004 ) and biochemical failure ( MVA HR 6.30 ; P<.001 ) . Although biochemical failure was associated with increased mortality and r and omization to DE-EBRT doubled the rate of biochemical failure , no significant overall survival difference was observed between the treatment arms ( MVA HR 1.13 ; P=.62 ) . CONCLUSIONS Compared with 78 Gy EBRT , men r and omized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years Background : In prior retrospective studies , we assessed a number of prostate tumor tissue biomarkers that were associated independently with the clinical outcome of men treated with radiotherapy ( RT ) ± and rogen deprivation therapy ( ADT ) .  In this report , the associations of selected biomarkers with biochemical or clinical disease failure ( BCDF ) were prospect ively evaluated in men with T1‐T3 prostate cancer on a r and omized hypofractionation trial . Methods : Biomarkers were analyzed in 263 of 303 men r and omly assigned to st and ard vs moderate hypofractionation .  Median follow‐up was 65.9 months . Archival tissue was analyzed for Ki‐67 ( n = 231 ) , MDM2 ( n = 209 ) , p16 ( n = 195 ) , Cox‐2 ( n = 126 ) , p53 ( n = 206 ) , bcl2 ( n = 223 ) , bax ( n = 210 ) , and PKA ( n = 160 ) . The base model for multivariable Fine‐Gray regression analysis included treatment assignment and risk groups . All statistical tests were two‐sided . Results : Each biomarker was tested one at a time relative to the base model and selected for inclusion in multivariable analysis . Ki‐67 ( hazard ratio [ HR ] = 2.31 , 95 % confidence interval [ CI ] = 1.19 to 4.48 , P = .01 ) and bcl2&bax ( HR = 2.19 , 95 % CI = 1.08 to 4.46 , P = .03 ) were statistically significantly related to higher BCDF and were independently statistically significant when considered jointly ( Ki‐67 : HR = 2.26 , 95 % CI = 1.12 to 4.58 , P = .02 ; bcl2&bax : HR = 2.14 , 95 % CI = 1.03 to 4.41 , P = .04 ) . At 2.5 years postradiotherapy , the C‐index of Ki‐67 was 73.2 % , while for the base model was only 46.2 % ; Ki‐67 was the most statistically significant when tested without bcl2&bax . Conclusions : In this prospect i ve multiple biomarker analysis in men with prostate cancer treated with RT±ADT  , both Ki‐67 and bcl2&bax were independently related to early BCDF ; however , Ki‐67 alone is indicated to be the most clinical ly meaningful by C‐index analysis and is universally available PURPOSE To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy ( RT ) on a phase 3 dose-escalation trial . METHODS AND MATERIAL S The trial was initiated with 3-dimensional conformal RT ( 3D-CRT ) and amended after 1 year to allow intensity modulated RT ( IMRT ) . Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles , then 23.4 Gy to prostate only . The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy . Common Toxicity Criteria , version 2.0 , and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects . RESULTS Of 763 patients r and omized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol , 748 were eligible and evaluable : 491 and 257 were treated with 3D-CRT and IMRT , respectively . For both bladder and rectum , the volumes receiving 65 , 70 , and 75 Gy were significantly lower with IMRT ( all P<.0001 ) . For grade ( G ) 2 + acute gastrointestinal/genitourinary ( GI/GU ) toxicity , both univariate and multivariate analyses showed a statistically significant decrease in G2 + acute collective GI/GU toxicity for IMRT . There were no significant differences with 3D-CRT or IMRT for acute or late G2 + or 3 + GU toxicities . Univariate analysis showed a statistically significant decrease in late G2 + GI toxicity for IMRT ( P=.039 ) . On multivariate analysis , IMRT showed a 26 % reduction in G2 + late GI toxicity ( P=.099 ) . Acute G2 + toxicity was associated with late G3 + toxicity ( P=.005 ) . With dose-volume histogram data in the multivariate analysis , RT modality was not significant , whereas white race ( P=.001 ) and rectal V70 ≥15 % were associated with G2 + rectal toxicity ( P=.034 ) . CONCLUSIONS Intensity modulated RT is associated with a significant reduction in acute G2 + GI/GU toxicity . There is a trend for a clinical ly meaningful reduction in late G2 + GI toxicity  with IMRT . The occurrence of acute GI toxicity and large ( > 15 % ) volumes of rectum > 70 Gy are associated with late rectal toxicity PURPOSE Perirectal spacing , whereby bio material s are placed between the prostate and rectum , shows promise in reducing rectal dose during prostate cancer radiation therapy . A prospect i ve multicenter r and omized controlled pivotal trial was performed to assess outcomes following absorbable spacer ( SpaceOAR system ) implantation . METHODS AND MATERIAL S Overall , 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography ( CT ) and magnetic resonance imaging ( MRI ) scans for treatment planning , followed with fiducial marker placement , and were r and omized to receive spacer injection or no injection ( control ) . Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy ( 79.2 Gy in 1.8-Gy fractions ) . Spacer safety and impact on rectal irradiation , toxicity , and quality of life were assessed throughout 15 months . RESULTS Spacer application was rated as " easy " or " very easy " 98.7 % of the time , with a 99 % hydrogel placement success rate . Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups , respectively . There were no device-related adverse events , rectal perforations , serious bleeding , or infections within either group . Pre-to postspacer plans had a significant reduction in mean rectal V70 ( 12.4 % to 3.3 % , P<.0001 ) . Overall acute rectal adverse event rates were similar between groups , with fewer spacer patients experiencing rectal pain ( P=.02 ) . A significant reduction in late ( 3 - 15 months ) rectal toxicity severity in the spacer group was observed ( P=.04 ) , with a  
    Output:
    
This review shows encouraging results for focal dose escalation to the IDN with acceptable short- to medium-term side effects and biochemical disease control rates .