human
***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 Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy ( CS+HIPEC ) is associated with significant perioperative morbidity . One goal of our ongoing patient-reported health-related quality of life ( HRQoL ) program is to describe the prognostic value of HRQoL measures for predicting postoperative morbidity and mortality following CS+HIPEC . Methods A retrospective analysis of a prospect ively collected clinical data base for all patients treated for peritoneal carcinomatosis and who participated in our patient-reported HRQoL program from 2001 to 2011 was done . Patients completed the Functional Assessment of Cancer Therapy question naire plus the colon symptom subscale , in addition to the Eastern Cooperative Oncology Group ( ECOG ) performance status rating prior to CS+HIPEC . The trial outcome index ( TOI ) , a specific measure of function , symptoms , and physical well being of the patient , was analyzed . The TOI is a combination of the physical and functional well being subscales + the colon-specific subscale of the FACT-C. Results Of 855 patients , 387 ( 45.2 % ) participated in the HRQoL trials . Mean age was 53.3 years , and 213 ( 55 % ) were female versus 174 ( 45 % ) males . There were 240 patients ( 62 % ) who had a complication versus 147 ( 38 % ) who had no complication . A 30-day mortality rate of 7.7 % ( 30 ) was documented . Patients who suffered a 30-day postoperative mortality demonstrated a lower mean preoperative score in the FACT-C TOI 52.7 versus 61.7 ; P < 0.001 . Independent predictors of 30-day mortality on multivariate analysis included TOI ( 0.05 ) , age ( 0.001 ) , and smoking ( 0.001 ) . Patients with a higher TOI score were less likely to suffer a mortality ( 95 % CI 0.9–1.0 , P = 0.05 ) . Patients with a higher emotional well being ( EWB ) score were less likely to suffer a complication 0.9 ( 95 % CI 0.87–1.0 , P = 0.04 ) . Other independent predictors of postoperative morbidity included diabetic status ( P = 0.05 ) , ECOG performance status ( 0.001 ) , and gender ( 0.02 ) . Conclusions Preoperative HRQoL , as measured by FACT-C and ECOG performance status and added to traditional factors , helps predict postoperative morbidity and mortality following CS+HIPEC Background In selected patients with colorectal peritoneal carcinomatosis ( PC ) , cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemoperfusion ( HIPEC ) may improve survival . We aim ed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population . Methods Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin ( 200–460 mg/m2 ) or mitomycin C ( 35 mg/m2 ) . Postoperative outcome and long-term survival were prospect ively recorded . The impact of clinical variables on overall survival ( OS ) was assessed using univariate and Cox multivariate analysis . Results Between October 2002 and May 2012 , 166 patients were treated with CRS and HIPEC . Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients . Postoperative mortality and major morbidity were 2.4 and 35 % , respectively . Half of the patients received adjuvant chemotherapy . After a median follow-up of 18 months , OS was 27 months ( 95 % confidence interval 20.8–33.2 ) . On univariate analysis , OS was associated with extent of disease ( P < 0.001 ) , neoadjuvant chemotherapy with bevacizumab ( P = 0.021 ) , completeness of cytoreduction ( CC ) ( P < 0.001 ) , and adjuvant chemotherapy ( P = 0.04 ) , but not with primary disease site , synchronous presentation , or chemoperfusion drug . In multivariate Cox regression , independent predictors of OS were CC ( hazard ratio 0.29 , P < 0.001 ) and neoadjuvant therapy containing bevacizumab ( hazard ratio 0.31 , P = 0.019 ) . Conclusions Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab . This regimen merits prospect i ve study in patients with resectable PC of colorectal origin Background Peritoneal carcinomatosis is regarded as a common sign of advanced tumor stage , tumor progression or local recurrence of appendiceal and colorectal cancer and is generally associated with poor prognosis . Although survival of patients with advanced stage CRC has markedly improved over the last 20 years with systemic treatment , comprising combination chemotherapy + /− monoclonal antibodies , the oncological outcome —especially of the subgroup of patients with peritoneal metastases — is still unsatisfactory . In addition to systemic therapy , cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) are specific treatment options for a selected group of these patients and may provide an additional therapeutic benefit in the framework of an interdisciplinary treatment concept . Methods / design The COMBATAC trial is a prospect i ve , multicenter , open-label , single-arm , single-stage phase II trial investigating perioperative systemic polychemotherapy including cetuximab in combination with CRS and HIPEC patients with histologically proven wild-type KRAS colorectal or appendiceal adenocarcinoma and synchronous or metachronous peritoneal carcinomatosis . The planned total number of patients to be recruited is 60 . The primary endpoint is progression-free survival ( PFS ) . Secondary endpoints include overall survival ( OS ) , perioperative morbidity and treatment-associated toxicity , feasibility of the combined treatment regimen , quality of life ( QoL ) and histopathological regression after preoperative chemotherapy . Discussion The COMBATAC trial is design ed to evaluate the feasibility and efficacy of the combined multidisciplinary treatment regimen consisting of perioperative systemic combination chemotherapy plus cetuximab and CRS plus bidirectional HIPEC with intraperitoneal oxaliplatin . Trial registration Clinical Trials.gov Identifier : NCT01540344 , EudraCT number : 2009 - 014040 - The effects of vascular endothelial growth factor ( VEGF ) blockade on the vascular biology of human tumors are not known . Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion , vascular volume , microvascular density , interstitial fluid pressure and the number of viable , circulating endothelial and progenitor cells , and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients . These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors PURPOSE Three-year disease-free survival ( DFS ) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin ( LV5FU2 ) with the addition of oxaliplatin ( FOLFOX4 ) . Final results of the study , including 6-year overall survival ( OS ) and 5-year up date d DFS , are reported . PATIENTS AND METHODS A total of 2,246 patients were r and omly assigned to receive LV5FU2 or FOLFOX4 for 6 months . The primary end point was DFS . Secondary end points were OS and safety . Results Five-year DFS rates were 73.3 % and 67.4 % in the FOLFOX4 and LV5FU2 groups , respectively ( hazard ratio [ HR ] = 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .003 ) . Six-year OS rates were 78.5 % and 76.0 % in the FOLFOX4 and LV5FU2 groups , respectively ( HR = 0.84 ; 95 % CI , 0.71 to 1.00 ; P = .046 ) ; corresponding 6-year OS rates for patients with stage III disease were 72.9 % and 68.7 % , respectively ( HR = 0.80 ; 95 % CI , 0.65 to 0.97 ; P = .023 ) . No difference in OS was seen in the stage II population . The incidence of second noncolorectal cancers was 5.5 % and 6.1 % in the FOLFOX4 and LV5FU2 groups , respectively . Among patients receiving oxaliplatin , the frequency of grade 3 peripheral sensory neuropathy was 1.3 % 12 months after treatment and 0.7 % at 48 months . CONCLUSION Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease BACKGROUND Cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) are increasingly used to treat peritoneal carcinomatosis from colorectal cancer . It is still relatively unknown which poor prognostic factors to avoid in order to optimize patient selection for CRS + HIPEC . METHODS Between February 2003 and October 2011 , 68 consecutive colorectal cancer patients who underwent CRS + HIPEC with a complete cytoreduction were identified from a prospect i ve data base .  Survival analysis was performed using the Kaplan-Meier method , with log rank testing of differences between groups . Multivariate analysis was conducted using Cox proportional hazard regression . RESULTS Median follow-up was 30.3 ( range , 2 - 88 ) months amongst survivors . Patients with a peritoneal cancer index ( PCI ) of 10 or less showed improved survival over those with a PCI of 11 or higher ( P = 0.03 ) . No difference in survival was seen for the other potentially poor prognostic variables including lymph node status , synchronous peritoneal disease , peri-operative systemic chemotherapy , and rectal cancer primary . CONCLUSIONS A low PCI was associated with improved survival .  Complete CRS + HIPEC appears to result in similar survival outcomes regardless of delivery of peri-operative systemic chemotherapy . Rectal origin , lymph node status , and synchronous peritoneal disease should not be used as an absolute exclusion criteria for CRS + HIPEC based on current data The purpose of this prospect i ve Phase II study was to analyze morbidity and mortality of cytoreductive surgery ( CRS ) and intraperitoneal hyperthermic perfusion ( IPHP ) in the treatment of peritoneal surface malignancies Background Selected patients with peritoneal carcinomatosis ( PC ) from colorectal cancer ( CRC ) benefit from cytoreductive surgery ( CRS ) combined with intraperitoneal chemoperfusion ( IPC ) . However , even after optimal cytoreduction , systemic and locoregional recurrence are common . Perioperative chemotherapy with bevacizumab ( BEV ) may improve the outcome of these patients . Methods / Design The BEV-IP study is a phase II , single-arm , open-label study aim ed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC . This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality ( primary composite endpoint ) . Secondary endpoints are treatment completion rate , chemotherapy-related toxicity , pathological response , progression free survival , and overall survival . Discussion The BEV-IP trial is the first prospect i ve assessment of the safety and efficacy of perioperative chemotherapy combined with anti-angiogenic treatment in patients undergoing CRS and  IPC for colorectal peritoneal metastases . Trial registration Clinical Trials.gov Identifier : NCT02399410 EudraCT number : 2015 - 001187 - 19 ( registered March 9 , 2015 ) Background Cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemoperfusion ( HIPEC ) for peritoneal carcinomatosis ( PC ) of colorectal origin increases survival ( OS ) compared to systemic chemotherapy alone . Signet ring histology demonstrates aggressive behavior with poor survival . We sought to determine whether CRS/HIPEC increases survival in this subset of patients . Methods We review ed 67 patients with PC of appendiceal ( AP , n = 37 ) or colorectal origin ( CRC , n = 30 ) with signet cell histology from a prospect i ve data base between May 2001 and August 2011 .  Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival . Results Complete CRS ( CC-0/1 ) was achieved in 77 % ( CRC ) and 73 % ( AP ) of patients . Progression-free survival 
    Output:
    
agent
***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 Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy ( CS+HIPEC ) is associated with significant perioperative morbidity . One goal of our ongoing patient-reported health-related quality of life ( HRQoL ) program is to describe the prognostic value of HRQoL measures for predicting postoperative morbidity and mortality following CS+HIPEC . Methods A retrospective analysis of a prospect ively collected clinical data base for all patients treated for peritoneal carcinomatosis and who participated in our patient-reported HRQoL program from 2001 to 2011 was done . Patients completed the Functional Assessment of Cancer Therapy question naire plus the colon symptom subscale , in addition to the Eastern Cooperative Oncology Group ( ECOG ) performance status rating prior to CS+HIPEC . The trial outcome index ( TOI ) , a specific measure of function , symptoms , and physical well being of the patient , was analyzed . The TOI is a combination of the physical and functional well being subscales + the colon-specific subscale of the FACT-C. Results Of 855 patients , 387 ( 45.2 % ) participated in the HRQoL trials . Mean age was 53.3 years , and 213 ( 55 % ) were female versus 174 ( 45 % ) males . There were 240 patients ( 62 % ) who had a complication versus 147 ( 38 % ) who had no complication . A 30-day mortality rate of 7.7 % ( 30 ) was documented . Patients who suffered a 30-day postoperative mortality demonstrated a lower mean preoperative score in the FACT-C TOI 52.7 versus 61.7 ; P < 0.001 . Independent predictors of 30-day mortality on multivariate analysis included TOI ( 0.05 ) , age ( 0.001 ) , and smoking ( 0.001 ) . Patients with a higher TOI score were less likely to suffer a mortality ( 95 % CI 0.9–1.0 , P = 0.05 ) . Patients with a higher emotional well being ( EWB ) score were less likely to suffer a complication 0.9 ( 95 % CI 0.87–1.0 , P = 0.04 ) . Other independent predictors of postoperative morbidity included diabetic status ( P = 0.05 ) , ECOG performance status ( 0.001 ) , and gender ( 0.02 ) . Conclusions Preoperative HRQoL , as measured by FACT-C and ECOG performance status and added to traditional factors , helps predict postoperative morbidity and mortality following CS+HIPEC Background In selected patients with colorectal peritoneal carcinomatosis ( PC ) , cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemoperfusion ( HIPEC ) may improve survival . We aim ed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population . Methods Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin ( 200–460 mg/m2 ) or mitomycin C ( 35 mg/m2 ) . Postoperative outcome and long-term survival were prospect ively recorded . The impact of clinical variables on overall survival ( OS ) was assessed using univariate and Cox multivariate analysis . Results Between October 2002 and May 2012 , 166 patients were treated with CRS and HIPEC . Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients . Postoperative mortality and major morbidity were 2.4 and 35 % , respectively . Half of the patients received adjuvant chemotherapy . After a median follow-up of 18 months , OS was 27 months ( 95 % confidence interval 20.8–33.2 ) . On univariate analysis , OS was associated with extent of disease ( P < 0.001 ) , neoadjuvant chemotherapy with bevacizumab ( P = 0.021 ) , completeness of cytoreduction ( CC ) ( P < 0.001 ) , and adjuvant chemotherapy ( P = 0.04 ) , but not with primary disease site , synchronous presentation , or chemoperfusion drug . In multivariate Cox regression , independent predictors of OS were CC ( hazard ratio 0.29 , P < 0.001 ) and neoadjuvant therapy containing bevacizumab ( hazard ratio 0.31 , P = 0.019 ) . Conclusions Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab . This regimen merits prospect i ve study in patients with resectable PC of colorectal origin Background Peritoneal carcinomatosis is regarded as a common sign of advanced tumor stage , tumor progression or local recurrence of appendiceal and colorectal cancer and is generally associated with poor prognosis . Although survival of patients with advanced stage CRC has markedly improved over the last 20 years with systemic treatment , comprising combination chemotherapy + /− monoclonal antibodies , the oncological outcome —especially of the subgroup of patients with peritoneal metastases — is still unsatisfactory . In addition to systemic therapy , cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) are specific treatment options for a selected group of these patients and may provide an additional therapeutic benefit in the framework of an interdisciplinary treatment concept . Methods / design The COMBATAC trial is a prospect i ve , multicenter , open-label , single-arm , single-stage phase II trial investigating perioperative systemic polychemotherapy including cetuximab in combination with CRS and HIPEC patients with histologically proven wild-type KRAS colorectal or appendiceal adenocarcinoma and synchronous or metachronous peritoneal carcinomatosis . The planned total number of patients to be recruited is 60 . The primary endpoint is progression-free survival ( PFS ) . Secondary endpoints include overall survival ( OS ) , perioperative morbidity and treatment-associated toxicity , feasibility of the combined treatment regimen , quality of life ( QoL ) and histopathological regression after preoperative chemotherapy . Discussion The COMBATAC trial is design ed to evaluate the feasibility and efficacy of the combined multidisciplinary treatment regimen consisting of perioperative systemic combination chemotherapy plus cetuximab and CRS plus bidirectional HIPEC with intraperitoneal oxaliplatin . Trial registration Clinical Trials.gov Identifier : NCT01540344 , EudraCT number : 2009 - 014040 - The effects of vascular endothelial growth factor ( VEGF ) blockade on the vascular biology of human tumors are not known . Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion , vascular volume , microvascular density , interstitial fluid pressure and the number of viable , circulating endothelial and progenitor cells , and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients . These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors PURPOSE Three-year disease-free survival ( DFS ) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin ( LV5FU2 ) with the addition of oxaliplatin ( FOLFOX4 ) . Final results of the study , including 6-year overall survival ( OS ) and 5-year up date d DFS , are reported . PATIENTS AND METHODS A total of 2,246 patients were r and omly assigned to receive LV5FU2 or FOLFOX4 for 6 months . The primary end point was DFS . Secondary end points were OS and safety . Results Five-year DFS rates were 73.3 % and 67.4 % in the FOLFOX4 and LV5FU2 groups , respectively ( hazard ratio [ HR ] = 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .003 ) . Six-year OS rates were 78.5 % and 76.0 % in the FOLFOX4 and LV5FU2 groups , respectively ( HR = 0.84 ; 95 % CI , 0.71 to 1.00 ; P = .046 ) ; corresponding 6-year OS rates for patients with stage III disease were 72.9 % and 68.7 % , respectively ( HR = 0.80 ; 95 % CI , 0.65 to 0.97 ; P = .023 ) . No difference in OS was seen in the stage II population . The incidence of second noncolorectal cancers was 5.5 % and 6.1 % in the FOLFOX4 and LV5FU2 groups , respectively . Among patients receiving oxaliplatin , the frequency of grade 3 peripheral sensory neuropathy was 1.3 % 12 months after treatment and 0.7 % at 48 months . CONCLUSION Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease BACKGROUND Cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) are increasingly used to treat peritoneal carcinomatosis from colorectal cancer . It is still relatively unknown which poor prognostic factors to avoid in order to optimize patient selection for CRS + HIPEC . METHODS Between February 2003 and October 2011 , 68 consecutive colorectal cancer patients who underwent CRS + HIPEC with a complete cytoreduction were identified from a prospect i ve data base .  Survival analysis was performed using the Kaplan-Meier method , with log rank testing of differences between groups . Multivariate analysis was conducted using Cox proportional hazard regression . RESULTS Median follow-up was 30.3 ( range , 2 - 88 ) months amongst survivors . Patients with a peritoneal cancer index ( PCI ) of 10 or less showed improved survival over those with a PCI of 11 or higher ( P = 0.03 ) . No difference in survival was seen for the other potentially poor prognostic variables including lymph node status , synchronous peritoneal disease , peri-operative systemic chemotherapy , and rectal cancer primary . CONCLUSIONS A low PCI was associated with improved survival .  Complete CRS + HIPEC appears to result in similar survival outcomes regardless of delivery of peri-operative systemic chemotherapy . Rectal origin , lymph node status , and synchronous peritoneal disease should not be used as an absolute exclusion criteria for CRS + HIPEC based on current data The purpose of this prospect i ve Phase II study was to analyze morbidity and mortality of cytoreductive surgery ( CRS ) and intraperitoneal hyperthermic perfusion ( IPHP ) in the treatment of peritoneal surface malignancies Background Selected patients with peritoneal carcinomatosis ( PC ) from colorectal cancer ( CRC ) benefit from cytoreductive surgery ( CRS ) combined with intraperitoneal chemoperfusion ( IPC ) . However , even after optimal cytoreduction , systemic and locoregional recurrence are common . Perioperative chemotherapy with bevacizumab ( BEV ) may improve the outcome of these patients . Methods / Design The BEV-IP study is a phase II , single-arm , open-label study aim ed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC . This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality ( primary composite endpoint ) . Secondary endpoints are treatment completion rate , chemotherapy-related toxicity , pathological response , progression free survival , and overall survival . Discussion The BEV-IP trial is the first prospect i ve assessment of the safety and efficacy of perioperative chemotherapy combined with anti-angiogenic treatment in patients undergoing CRS and  IPC for colorectal peritoneal metastases . Trial registration Clinical Trials.gov Identifier : NCT02399410 EudraCT number : 2015 - 001187 - 19 ( registered March 9 , 2015 ) Background Cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemoperfusion ( HIPEC ) for peritoneal carcinomatosis ( PC ) of colorectal origin increases survival ( OS ) compared to systemic chemotherapy alone . Signet ring histology demonstrates aggressive behavior with poor survival . We sought to determine whether CRS/HIPEC increases survival in this subset of patients . Methods We review ed 67 patients with PC of appendiceal ( AP , n = 37 ) or colorectal origin ( CRC , n = 30 ) with signet cell histology from a prospect i ve data base between May 2001 and August 2011 .  Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival . Results Complete CRS ( CC-0/1 ) was achieved in 77 % ( CRC ) and 73 % ( AP ) of patients . Progression-free survival 
    Output:
    