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 The peritoneum is the second most common site of recurrence in colorectal cancer . Early detection of peritoneal carcinomatosis ( PC ) by imaging is difficult . Patients eventually presenting with clinical ly apparent PC have a poor prognosis . Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited . Only a quarter of patients are eligible for curative treatment , consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy ( CR/HIPEC ) . However , the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate . These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases . Adjuvant hyperthermic intraperitoneal chemotherapy ( HIPEC ) seems to be suitable for this purpose . Without the need for cytoreductive surgery , adjuvant HIPEC can be performed with a low complication rate and short hospital stay . Methods / Design The aim of this study is to determine the effectiveness of  adjuvant HIPEC  in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence . This study will be performed in the nine Dutch HIPEC centres , starting in April 2015 . Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer . After resection of the primary tumour , 176 patients will be r and omized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm , or to systemic chemotherapy only in the control arm . Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection . Oxaliplatin will be used as chemotherapeutic agent , for 30 min at 42 - 43 ° C . Just before HIPEC , 5-fluorouracil and leucovorin will be administered intravenously . Primary endpoint is peritoneal disease-free survival at 18 months . Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA . Discussion Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 % . This reduction is likely to translate into a prolonged overall survival . Trial registration numberNCT02231086 ( Clinical trials.gov Background Patients with peritoneal mucinous carcinomatosis ( PMCA ) of appendiceal origin and extensive disease are commonly advised against CRS/HIPEC . We hypothesize that CRS/HIPEC is a beneficial treatment for this group . Methods Retrospective analysis of 134 patients with appendiceal cancer treated with CRS/HIPEC was performed from a prospect i ve data base . Extent of disease , measured by peritoneal cancer index ( PCI ) , was related to completeness of cytoreduction ( CC ) , lymph node ( LN ) status , and prior surgery score ( PSS ) . Overall survival ( OS ) was estimated by Kaplan-Meier curves . Test differences were calculated using log-rank test . Results A total of 77 patients ( 57 % ) had PMCA . Mean follow-up was 22 months with a median of 18 months . OS was 88 % , 56 % , and 40 % for 1 , 3 , and 5 years , respectively . 68 % had PCI ≥ 20 . LN metastasis was found in 44 % of patients in PCI ≥ 20 and PCI < 20 groups . 73 % and 60 % of patients had PSS of 2 or 3 in PCI ≥ 20 and PCI < 20 groups , respectively ( P = .196 ) . Complete cytoreduction was achieved in 65 % of PCI ≥ 20 group and 96 % of PCI < 20 group ( P = .004 ) . With complete cytoreduction , the 5-year OS was 45 % in PCI ≥ 20 group and 66 % in PCI < 20 group ( P = .139 ) . 18 of 19 patients with incomplete cytoreduction had PCI ≥ 20 , with 3- and 5-year OS of 27 % and 0 % . Hazard ratios ( by Cox regression ) were 2.8 ( 95 % confidence interval [ 95 % CI ] 0.8–10.2 ) and 3.6 ( 95 % CI 1.5–8.8 ) for PCI < 20 and complete cytoreduction , respectively . Conclusions Meaningful long-term survival could be achieved in patients with PMCA even with extensive peritoneal disease . PCI ≥ 20 should not be used as an exclusion criterion when selecting these patients for CRS/HIPEC , and every effort should be made to achieve complete cytoreduction BACKGROUND A prospect i ve r and omized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy ( complete cytoreductive surgery ( CRS ) , hyperthermic intraperitoneal chemotherapy ( HIPEC ) , and systemic chemotherapy ) on overall survival ( OS ) in patients with gastric carcinomatosis . METHODS Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum , and resectable to " no evidence of disease " were r and omized to gastrectomy , metastasectomy , HIPEC , and systemic FOLFOXIRI ( GYMS arm ) or FOLFOXIRI alone ( SA arm ) . RESULTS Seventeen patients were enrolled ( 16 evaluable ) ; 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction ( CCR0 ) . Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm . Four patients in the GYMS arm survived > 12 months , 2 patients close to 2 years at last follow-up , and 1 patient more than 4 years , with 2 of these patients still alive . No patient in the SA arm lived beyond 11 months . All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index ( PCI ) of ≤ 15 . CONCLUSION Maximal cytoreductive surgery combined with regional ( HIPEC ) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival Background The detection of intraperitoneal free cancer cells in colorectal cancer ( CRC ) patients is associated with a poorer prognosis . The aim of this study was to investigate the effects of intraperitoneal chemotherapy ( IPC ) with mitomycin C ( MMC ) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings . Methods A total of 52 CRC patients who had no clinical ly confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated . Conventional peritoneal lavage cytology was performed . Overall , 31 of the 52 patients ( 59.6 % ) were administered IPC with MMC . Before closure of the abdomen , 4 silicon catheters were inserted into peritoneal cavity . After closure , the perfusate ( diluting 20 mg MMC with 500 ml saline ) was instilled from the catheter , and all catheters were clumped . All catheters were opened 1 h later . Results The mean follow-up period was 83.1 months . According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors , patients with IPC  had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC  ( P < 0.005 ) . In multivariate analysis , IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients . Conclusions It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination , but who have positive peritoneal lavage cytology . It is necessary to verify the effectiveness of IPC with MMC in a prospect i ve trial The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies BACKGROUND St and ard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination . The Gynecologic Oncology Group conducted a r and omized , phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer . METHODS We r and omly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 ( intravenous-therapy group ) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 ( intraperitoneal-therapy group ) . Treatment was given every three weeks for six cycles . Quality of life was assessed . RESULTS Of 429 patients who underwent r and omization , 415 were eligible .  Grade 3 and 4 pain , fatigue , and hematologic , gastrointestinal , metabolic , and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group ( P < or = 0.001 ) . Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy , but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months , respectively ( P=0.05 by the log-rank test ) . The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months , respectively ( P=0.03 by the log-rank test ) . Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment . CONCLUSIONS As compared with intravenous paclitaxel plus cisplatin , intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer Adjuvant chemotherapy with fluorouracil ( FU ) and levamisole or FU/leucovorin ( LV ) has been established as effective adjuvant treatment for patients with stage III colon cancer . Among several other promising treatment strategies in resected colon cancer , intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation . To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole , the present r and omized study was initiated . A total of 241 patients with resected stage III or high-risk stage II ( T4N0M0 ) colon cancer were r and omly assigned to ' st and ard therapy ' with FU and levamisole , given for a duration of 6 months , or to an investigational arm , consisting of LV 200 mg m(-2 ) plus FU 350 mg m(-2 ) , both administered intravenously ( days 1 - 4 ) and intraperitoneally ( days 1 and 3 ) every 4 weeks for a total of six courses . In patients with stage II disease , no significant difference was noted between the two arms after a median follow-up time of 4 years ( range 2.5 - 6 years ) . Among 196 eligible 
    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 The peritoneum is the second most common site of recurrence in colorectal cancer . Early detection of peritoneal carcinomatosis ( PC ) by imaging is difficult . Patients eventually presenting with clinical ly apparent PC have a poor prognosis . Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited . Only a quarter of patients are eligible for curative treatment , consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy ( CR/HIPEC ) . However , the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate . These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases . Adjuvant hyperthermic intraperitoneal chemotherapy ( HIPEC ) seems to be suitable for this purpose . Without the need for cytoreductive surgery , adjuvant HIPEC can be performed with a low complication rate and short hospital stay . Methods / Design The aim of this study is to determine the effectiveness of  adjuvant HIPEC  in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence . This study will be performed in the nine Dutch HIPEC centres , starting in April 2015 . Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer . After resection of the primary tumour , 176 patients will be r and omized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm , or to systemic chemotherapy only in the control arm . Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection . Oxaliplatin will be used as chemotherapeutic agent , for 30 min at 42 - 43 ° C . Just before HIPEC , 5-fluorouracil and leucovorin will be administered intravenously . Primary endpoint is peritoneal disease-free survival at 18 months . Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA . Discussion Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 % . This reduction is likely to translate into a prolonged overall survival . Trial registration numberNCT02231086 ( Clinical trials.gov Background Patients with peritoneal mucinous carcinomatosis ( PMCA ) of appendiceal origin and extensive disease are commonly advised against CRS/HIPEC . We hypothesize that CRS/HIPEC is a beneficial treatment for this group . Methods Retrospective analysis of 134 patients with appendiceal cancer treated with CRS/HIPEC was performed from a prospect i ve data base . Extent of disease , measured by peritoneal cancer index ( PCI ) , was related to completeness of cytoreduction ( CC ) , lymph node ( LN ) status , and prior surgery score ( PSS ) . Overall survival ( OS ) was estimated by Kaplan-Meier curves . Test differences were calculated using log-rank test . Results A total of 77 patients ( 57 % ) had PMCA . Mean follow-up was 22 months with a median of 18 months . OS was 88 % , 56 % , and 40 % for 1 , 3 , and 5 years , respectively . 68 % had PCI ≥ 20 . LN metastasis was found in 44 % of patients in PCI ≥ 20 and PCI < 20 groups . 73 % and 60 % of patients had PSS of 2 or 3 in PCI ≥ 20 and PCI < 20 groups , respectively ( P = .196 ) . Complete cytoreduction was achieved in 65 % of PCI ≥ 20 group and 96 % of PCI < 20 group ( P = .004 ) . With complete cytoreduction , the 5-year OS was 45 % in PCI ≥ 20 group and 66 % in PCI < 20 group ( P = .139 ) . 18 of 19 patients with incomplete cytoreduction had PCI ≥ 20 , with 3- and 5-year OS of 27 % and 0 % . Hazard ratios ( by Cox regression ) were 2.8 ( 95 % confidence interval [ 95 % CI ] 0.8–10.2 ) and 3.6 ( 95 % CI 1.5–8.8 ) for PCI < 20 and complete cytoreduction , respectively . Conclusions Meaningful long-term survival could be achieved in patients with PMCA even with extensive peritoneal disease . PCI ≥ 20 should not be used as an exclusion criterion when selecting these patients for CRS/HIPEC , and every effort should be made to achieve complete cytoreduction BACKGROUND A prospect i ve r and omized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy ( complete cytoreductive surgery ( CRS ) , hyperthermic intraperitoneal chemotherapy ( HIPEC ) , and systemic chemotherapy ) on overall survival ( OS ) in patients with gastric carcinomatosis . METHODS Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum , and resectable to " no evidence of disease " were r and omized to gastrectomy , metastasectomy , HIPEC , and systemic FOLFOXIRI ( GYMS arm ) or FOLFOXIRI alone ( SA arm ) . RESULTS Seventeen patients were enrolled ( 16 evaluable ) ; 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction ( CCR0 ) . Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm . Four patients in the GYMS arm survived > 12 months , 2 patients close to 2 years at last follow-up , and 1 patient more than 4 years , with 2 of these patients still alive . No patient in the SA arm lived beyond 11 months . All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index ( PCI ) of ≤ 15 . CONCLUSION Maximal cytoreductive surgery combined with regional ( HIPEC ) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival Background The detection of intraperitoneal free cancer cells in colorectal cancer ( CRC ) patients is associated with a poorer prognosis . The aim of this study was to investigate the effects of intraperitoneal chemotherapy ( IPC ) with mitomycin C ( MMC ) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings . Methods A total of 52 CRC patients who had no clinical ly confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated . Conventional peritoneal lavage cytology was performed . Overall , 31 of the 52 patients ( 59.6 % ) were administered IPC with MMC . Before closure of the abdomen , 4 silicon catheters were inserted into peritoneal cavity . After closure , the perfusate ( diluting 20 mg MMC with 500 ml saline ) was instilled from the catheter , and all catheters were clumped . All catheters were opened 1 h later . Results The mean follow-up period was 83.1 months . According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors , patients with IPC  had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC  ( P < 0.005 ) . In multivariate analysis , IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients . Conclusions It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination , but who have positive peritoneal lavage cytology . It is necessary to verify the effectiveness of IPC with MMC in a prospect i ve trial The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies BACKGROUND St and ard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination . The Gynecologic Oncology Group conducted a r and omized , phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer . METHODS We r and omly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 ( intravenous-therapy group ) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 ( intraperitoneal-therapy group ) . Treatment was given every three weeks for six cycles . Quality of life was assessed . RESULTS Of 429 patients who underwent r and omization , 415 were eligible .  Grade 3 and 4 pain , fatigue , and hematologic , gastrointestinal , metabolic , and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group ( P < or = 0.001 ) . Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy , but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months , respectively ( P=0.05 by the log-rank test ) . The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months , respectively ( P=0.03 by the log-rank test ) . Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment . CONCLUSIONS As compared with intravenous paclitaxel plus cisplatin , intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer Adjuvant chemotherapy with fluorouracil ( FU ) and levamisole or FU/leucovorin ( LV ) has been established as effective adjuvant treatment for patients with stage III colon cancer . Among several other promising treatment strategies in resected colon cancer , intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation . To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole , the present r and omized study was initiated . A total of 241 patients with resected stage III or high-risk stage II ( T4N0M0 ) colon cancer were r and omly assigned to ' st and ard therapy ' with FU and levamisole , given for a duration of 6 months , or to an investigational arm , consisting of LV 200 mg m(-2 ) plus FU 350 mg m(-2 ) , both administered intravenously ( days 1 - 4 ) and intraperitoneally ( days 1 and 3 ) every 4 weeks for a total of six courses . In patients with stage II disease , no significant difference was noted between the two arms after a median follow-up time of 4 years ( range 2.5 - 6 years ) . Among 196 eligible 
    Output:
    