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: Purpose : To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis ( PC ) . Patients and Methods : From 1999 to 2009 , 41 patients without any sign of recurrence on imaging studies underwent second-look surgery  aim ed at treating limited PC earlier and more easily . They were selected based on 3 primary tumor-associated criteria : resected minimal synchronous macroscopic PC ( n = 25 ) , synchronous ovarian metastases ( n = 8) , and perforation ( n = 8) . Results : PC was found and treated with complete surgery plus HIPEC in 23 of the 41 ( 56 % ) patients . The other patients underwent complete abdominal exploration plus systematic HIPEC . Median follow-up was 30 ( 9–109 ) months . One patient died postoperatively at day 69 . Grade 3 - 4 morbidity was low ( 9.7 % ) . The 5-year overall survival rate was 90 % and the 5-year disease-free survival rate was 44 % . Peritoneal recurrences occurred in 7 patients ( 17 % ) , 6 of whom had macroscopic PC discovered during the second-look ( 26 % ) , and one patient had no macroscopic PC ( 6 % ) . In the univariate analysis , the presence of PC at second-look surgery was a significant risk factor for recurrence ( P = 0.006 ) . Conclusion : Selection criteria for high-risk patients appear to be accurate . In these patients , the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage , yielding promising results . This study has allowed us to design a multicentric r and omized trial ( comparing the second-look + HIPEC approach versus st and ard follow-up alone ) , which is beginning 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 This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery ( CRS ) plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis ( PC ) from gastrointestinal and gynecological cancers . Methods Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m2 and docetaxel 60 mg/m2 in 6000 mL of normal saline at 43 ± 0.5 ° C for 60 min . Vital signs were recorded for 6 days after CRS + HIPEC  procedures . Perioperative serious adverse events ( SAE ) , hematological , hepatic , renal , and electrolytes parameters , the changes in serum tumor markers ( TM ) before and after operation , patient recovery , and overall survival ( OS ) were analyzed . Results One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy .  The median CRS + HIPEC duration was 463 ( range , 245–820 ) min , and the highest temperature and heart rate during six postoperative days were 38.6 ° C ( median 37.5 ° C ) and 124 bpm ( median 100 bpm ) , respectively . The 30-day perioperative SAE occurred in 16 ( 15.2 % ) and mortality occurred in 2 ( 1.9 % ) patients . Most routine blood laboratory tests at 1 week after surgery turned normal . Among 82 cases with increased preoperative TM CEA , CA125 , and CA199 , 71 cases had TM levels reduced or turned normal . Median time to nasogastric tube removal was 5 ( range , 3–23 ) days , to liquid food intake 6 ( range , 4–24 ) days , and to abdominal suture removal 15 ( range , 10–30 ) days . At the median follow-up of 19.7 ( range , 7.5–89.2 ) months , the median OS was 24.2 ( 95 % CI , 15.0–33.4 ) months , and the 1- , 3- , and 5-year OS rates were 77.5 , 32.5 , and 19.8 % , respectively . Univariate analysis identified five independent prognostic factors on OS : the origin of PC , peritoneal cancer index , completeness of CRS , cycles of adjuvant chemotherapy , and SAE . Conclusions CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC.Trial registration Clinical Trials.gov , Introduction The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy . In 2003 , a r and omized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy . This trial showed a positive result favoring the studied treatment . This trial has now been up date d to a minimal follow-up of 6 years to show long-term results . Patients and Methods For all patients still alive , the follow-up was up date d until 2007 . In the original study , four patients were excluded — two because of no eligible histology/pathology and two because of major protocol violations . After r and omization , four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy , one patient because of withdrawal , one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment . During the follow-up , one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease , after the assigned treatment was completed . The data from these patients were censored at the moment of the cross-over . Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method . The long-term results were studied in more detail to evaluate efficacy and toxicity . Results At the time of this up date , the median follow-up was almost 8 years ( range 72–115 months ) . In the st and ard arm , 4 patients were still alive , 2 with and 2 without disease ; in the “ HIPEC ’ arm , 5 patients were still alive , 2 with and 3 without disease . The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm ( P = 0.020 ) . The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm ( P = 0.028 ) . The 5-year survival was 45 % for those patients in whom a R1 resection was achieved . Conclusion With 90 % of all events having taken place up to this time , this r and omized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin . For a selected group , there is a possibility of long-term survival 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 - PURPOSE Complete resection of macroscopic colorectal peritoneal carcinomatosis ( PC ) , followed by intraoperative intraperitoneal chemohyperthermia ( IPCH ) to treat residual microscopic disease achieves cure in some patients . We report long-term results concerning survival of a phase II study using oxaliplatin ( LOHP ) . PATIENTS AND METHODS From June 1998 to December 2003 , thirty patients with macroscopic colorectal PC underwent complete resection of PC followed by IPCH with LOHP performed in an open abdominal cavity . The dose of LOHP was 460 mg/m2 in 2 L/m2 of iso-osmotic 5 % dextrose , over 30 min at an intraperitoneally homogenous temperature of 43 degrees C and at a flow rate of 2 L/min in the continuous closed circuit . During the hour preceding IPCH , patients received 5-fluorouracil ( 400 mg/m2 ) and leucovorin ( 20 mg/m2 ) intravenously . All patients received neoadjuvant and adjuvant systemic chemotherapy . RESULTS Mean peritoneal tumor extension ( Sugarbaker 's Score ) was 14.3 + /- 3.8 , median operative duration , 450 min , and median blood loss , 940 mL. Eleven ( 37 % ) patients had associated extra-peritoneal lesions which were resected during the same procedure . There were no postoperative deaths and grade 2 - 3 morbidity ( requiring specific treatment ) was 40 % . Median follow-up was 55 months ( range : 31 - 84 ) . Twenty-two patients ( 73 % ) relapsed after a median interval of 14 months , but 7 of them ( 32 % ) were amenable to curative repeat surgery . At 3 and 5 years , overall survival rates ( 95 % confidence interval ) were 53 % ( 9 - 72 ) , and 48.5 % ( 31 - 66 ) respectively . At 3 and 5 years , disease-free survival rates were 41.5 % ( 27 - 59 ) , and 34 % ( 19 - 52 ) respectively . Median survival was 60. 
    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: Purpose : To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis ( PC ) . Patients and Methods : From 1999 to 2009 , 41 patients without any sign of recurrence on imaging studies underwent second-look surgery  aim ed at treating limited PC earlier and more easily . They were selected based on 3 primary tumor-associated criteria : resected minimal synchronous macroscopic PC ( n = 25 ) , synchronous ovarian metastases ( n = 8) , and perforation ( n = 8) . Results : PC was found and treated with complete surgery plus HIPEC in 23 of the 41 ( 56 % ) patients . The other patients underwent complete abdominal exploration plus systematic HIPEC . Median follow-up was 30 ( 9–109 ) months . One patient died postoperatively at day 69 . Grade 3 - 4 morbidity was low ( 9.7 % ) . The 5-year overall survival rate was 90 % and the 5-year disease-free survival rate was 44 % . Peritoneal recurrences occurred in 7 patients ( 17 % ) , 6 of whom had macroscopic PC discovered during the second-look ( 26 % ) , and one patient had no macroscopic PC ( 6 % ) . In the univariate analysis , the presence of PC at second-look surgery was a significant risk factor for recurrence ( P = 0.006 ) . Conclusion : Selection criteria for high-risk patients appear to be accurate . In these patients , the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage , yielding promising results . This study has allowed us to design a multicentric r and omized trial ( comparing the second-look + HIPEC approach versus st and ard follow-up alone ) , which is beginning 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 This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery ( CRS ) plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis ( PC ) from gastrointestinal and gynecological cancers . Methods Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m2 and docetaxel 60 mg/m2 in 6000 mL of normal saline at 43 ± 0.5 ° C for 60 min . Vital signs were recorded for 6 days after CRS + HIPEC  procedures . Perioperative serious adverse events ( SAE ) , hematological , hepatic , renal , and electrolytes parameters , the changes in serum tumor markers ( TM ) before and after operation , patient recovery , and overall survival ( OS ) were analyzed . Results One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy .  The median CRS + HIPEC duration was 463 ( range , 245–820 ) min , and the highest temperature and heart rate during six postoperative days were 38.6 ° C ( median 37.5 ° C ) and 124 bpm ( median 100 bpm ) , respectively . The 30-day perioperative SAE occurred in 16 ( 15.2 % ) and mortality occurred in 2 ( 1.9 % ) patients . Most routine blood laboratory tests at 1 week after surgery turned normal . Among 82 cases with increased preoperative TM CEA , CA125 , and CA199 , 71 cases had TM levels reduced or turned normal . Median time to nasogastric tube removal was 5 ( range , 3–23 ) days , to liquid food intake 6 ( range , 4–24 ) days , and to abdominal suture removal 15 ( range , 10–30 ) days . At the median follow-up of 19.7 ( range , 7.5–89.2 ) months , the median OS was 24.2 ( 95 % CI , 15.0–33.4 ) months , and the 1- , 3- , and 5-year OS rates were 77.5 , 32.5 , and 19.8 % , respectively . Univariate analysis identified five independent prognostic factors on OS : the origin of PC , peritoneal cancer index , completeness of CRS , cycles of adjuvant chemotherapy , and SAE . Conclusions CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC.Trial registration Clinical Trials.gov , Introduction The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy . In 2003 , a r and omized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy . This trial showed a positive result favoring the studied treatment . This trial has now been up date d to a minimal follow-up of 6 years to show long-term results . Patients and Methods For all patients still alive , the follow-up was up date d until 2007 . In the original study , four patients were excluded — two because of no eligible histology/pathology and two because of major protocol violations . After r and omization , four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy , one patient because of withdrawal , one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment . During the follow-up , one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease , after the assigned treatment was completed . The data from these patients were censored at the moment of the cross-over . Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method . The long-term results were studied in more detail to evaluate efficacy and toxicity . Results At the time of this up date , the median follow-up was almost 8 years ( range 72–115 months ) . In the st and ard arm , 4 patients were still alive , 2 with and 2 without disease ; in the “ HIPEC ’ arm , 5 patients were still alive , 2 with and 3 without disease . The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm ( P = 0.020 ) . The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm ( P = 0.028 ) . The 5-year survival was 45 % for those patients in whom a R1 resection was achieved . Conclusion With 90 % of all events having taken place up to this time , this r and omized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin . For a selected group , there is a possibility of long-term survival 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 - PURPOSE Complete resection of macroscopic colorectal peritoneal carcinomatosis ( PC ) , followed by intraoperative intraperitoneal chemohyperthermia ( IPCH ) to treat residual microscopic disease achieves cure in some patients . We report long-term results concerning survival of a phase II study using oxaliplatin ( LOHP ) . PATIENTS AND METHODS From June 1998 to December 2003 , thirty patients with macroscopic colorectal PC underwent complete resection of PC followed by IPCH with LOHP performed in an open abdominal cavity . The dose of LOHP was 460 mg/m2 in 2 L/m2 of iso-osmotic 5 % dextrose , over 30 min at an intraperitoneally homogenous temperature of 43 degrees C and at a flow rate of 2 L/min in the continuous closed circuit . During the hour preceding IPCH , patients received 5-fluorouracil ( 400 mg/m2 ) and leucovorin ( 20 mg/m2 ) intravenously . All patients received neoadjuvant and adjuvant systemic chemotherapy . RESULTS Mean peritoneal tumor extension ( Sugarbaker 's Score ) was 14.3 + /- 3.8 , median operative duration , 450 min , and median blood loss , 940 mL. Eleven ( 37 % ) patients had associated extra-peritoneal lesions which were resected during the same procedure . There were no postoperative deaths and grade 2 - 3 morbidity ( requiring specific treatment ) was 40 % . Median follow-up was 55 months ( range : 31 - 84 ) . Twenty-two patients ( 73 % ) relapsed after a median interval of 14 months , but 7 of them ( 32 % ) were amenable to curative repeat surgery . At 3 and 5 years , overall survival rates ( 95 % confidence interval ) were 53 % ( 9 - 72 ) , and 48.5 % ( 31 - 66 ) respectively . At 3 and 5 years , disease-free survival rates were 41.5 % ( 27 - 59 ) , and 34 % ( 19 - 52 ) respectively . Median survival was 60. 
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