***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: OBJECTIVE Serial circulating tumor cell ( CTC ) counts have demonstrated predictive and prognostic value in patients with metastatic breast , colorectal , and prostate cancer . In a phase III study of pegylated liposomal doxorubicin ( PLD ) with trabectedin vs. PLD for relapsed ovarian cancer , we evaluated the correlation , if any , between numbers of CTCs and progression free survival , ( PFS ) and overall survival ( OS ) . METHODS CTCs were isolated from peripheral blood ( 10 mL ) using the Cell Search system and reagents ( Veridex ) . A CTC is defined as EpCAM+ , cytokeratin+ , CD45- , and is positive for the nuclear stain DAPI . The normal reference range for Cell Search is < 2 CTC/7.5 mL of blood . Hazard ratios adjusted for known prognostic factors were estimated by Cox regression . RESULTS Two-hundred sixteen patients had baseline CTC measurements of which 111 ( 51.4 % ) were r and omized to the trabectedin+PLD arm ; 143/216 patients ( 66.2 % ) were platinum-sensitive . Thirty-one of 216 patients ( 14.4 % ) had 2 or more CTCs detected prior to the start of therapy ( range 2 - 566 ) . Univariate Cox regression analyses indicated that patients with ≥2 CTCs prior to therapy had 1.89- ( p=0.003 ) and 2.06-fold ( p=0.003 ) higher risk for progression and death respectively . Multivariate analyses that include baseline CA-125 , platinum sensitivity status , largest diameter lesion , number of tumor lesions , ECOG PS , and tumor grade show that patients with elevated baseline CTC had 1.58- ( p=0.058 ) and 1.54-fold ( p=0.096 ) higher risk for progression and death respectively . CONCLUSIONS Results from this study indicate that elevated numbers of CTCs impart an unfavorable prognosis for ovarian cancer patients OBJECTIVE Serum CA-125 values have been advocated in the monitoring of ovarian cancer patients receiving intravenous ( IV ) chemotherapy .  This evaluation sought to determine if the CA-125 test can be used to monitor treatment effect among patients receiving intraperitoneal chemotherapy ( IP ) .  METHODS Patient charts from a phase III clinical trial ( GOG 172 ) were retrospectively review ed . Serum CA-125 levels prior to each cycle of therapy were collected and compared between the IV and IP chemotherapy delivery . The association between CA-125 and progression-free survival ( PFS ) or overall survival ( OS ) was estimated and the homogeneity of the results between IP and IV chemotherapy was assessed . RESULTS A total of 177 patients were treated with IV chemotherapy and 165 patients with IP chemotherapy with CA-125 data available were included in this analysis . The observed difference was not statistically significant in median CA-125 levels between the IV and IP arms at any time point ( P>0.05 for all ) . Following surgery and adjuvant chemotherapy , patients with an abnormal CA-125 > 35 U/ml were 2.45 times more likely to have disease progression ( 95 % CI : 1.52 - 3.95 , P<0.001 ) and 2.78 times more likely to die of disease ( 95 % CI : 1.66 - 4.65 , P<0.001 ) , compared to those with a CA-125 < 35 U/ml . These results were consistent with IP and IV chemotherapy . CONCLUSION Serum CA-125 levels decrease in a similar manner during IP chemotherapy when compared to IV chemotherapy . Serum CA-125 algorithms for monitoring treatment effect that have been established for IV chemotherapy may also be applied for patients receiving IP chemotherapy OBJECTIVE Patients with persistent/recurrent epithelial ovarian cancer/ primary peritoneal cancer ( EOC/PPC ) have limited treatment options . AKT and PI3 K pathway activation is common in EOC/PPC , result ing in constitutive activation of downstream mTOR . The GOG conducted a phase II evaluation of efficacy and safety for the mTOR inhibitor , temsirolimus in EOC/PPC and explored circulating tumor cells ( CTC ) and AKT/mTOR/downstream tumor markers . METHODS Eligible women with measurable , persistent/recurrent EOC/PPC who had received 1 - 3 prior regimens were treated with 25 mg weekly IV temsirolimus until progression or intolerable toxicity . Primary endpoints were progression-free survival ( PFS ) ≥6-months , tumor response , and toxicity . Cell Search ® system was used to examine CTC , and AKT/mTOR/downstream markers were evaluated by archival tumor immunohistochemistry . Kendall 's tau-b correlation coefficient ( r ) and Cox regression modeling were used to explore marker associations with baseline characteristics and outcome . RESULTS Sixty patients were enrolled in a two-stage sequential design . Of 54 eligible and evaluable patients , 24.1 % ( 90 % CI 14.9%-38.6 % ) had PFS ≥6 months ( median 3.1 months ) , 9.3 % ( 90 % CI 3.7%-23.4 % ) experienced a partial response . Grade 3/4 adverse events included metabolic ( 8) , gastrointestinal ( 8) , pain ( 6 ) , constitutional ( 5 ) and pulmonary ( 4 ) . Suggested associations were between cyclin D1 and PFS ≥6 months , PFS or survival ; positive CTC pre-treatment and lack of response ; and high CTC expression of M30 and PFS ≥6 months/longer PFS . CONCLUSIONS Temsirolimus appears to have modest activity in persistent/recurrent EOC/PPC ; however , PFS is just below that required to warrant inclusion in phase III studies in unselected patients . Cyclin D1 as a selection marker and CTC measures merit further study BACKGROUND Our group evaluated the risk of recurrence for optimally treated advanced epithelial ovarian cancer ( adEOC ) in patients with a low-level rising serum CA-125 concentration within the normal range ( 0 - 35 kU/l ) . In addition , we tested the new proposed early CA-125 signal of progressive disease ( EPD ) criterion in the same study population . PATIENTS AND METHODS Patients treated from 1998 to 2006 for adEOC were identified at our institution . Inclusion criteria were as follows : CA-125 at time of diagnosis ( > 35 kU/l ) ; International Federation of Gynecology and Obstetrics stages III-IV treated with optimal primary treatment ; and complete response ( CR ) to primary treatment with normalization of CA-125 . RESULTS Median progression-free survival and overall survival for the recurrence group ( n = 60 ) were 17.7 and 38.2 months , respectively . The median follow-up time from CR to last contact was 40.2 months for patients in the nonrecurrence group ( n = 36 ) . An absolute increase in serum CA-125 levels of > or=5 kU/l compared with baseline CA-125 nadir values was significantly predictive of recurrence ( odds ratio for recurrence = 402.98 , P < 0.0001 ) . The progression date was pre date d by the EPD criterion in 77 % of patients with known progressive disease ( median , 58 days early ) with a sensitivity of 90 % , a positive predictive value of 96.4 % , and a false-positive rate of 5.6 % . CONCLUSIONS Among patients with optimally treated adEOC in complete remission , a low-level increase in serum CA-125 concentration within the normal range is a strong independent predictive factor for disease recurrence . In this patient population , future prospect i ve r and omized trials should consider the evaluation of the EPD criterion OBJECTIVE To determine whether circulating tumor cells ( CTCs ) , as detected and enumerated by the Veridex Cell Search system , could predict for clinical outcomes in women with newly diagnosed or recurrent epithelial ovarian cancer . METHODS Serial measurements of CTC s and paired serum CA125 were collected in a series of 78 women with newly diagnosed or recurrent ovarian cancer seen at our institution over a period of 15 months . Clinical data were abstract ed from patient medical records . CTCs were detected and enumerated by the Cell Search protocol , and patients were divided into CTC negative ( < 2 CTCs ) or positive ( ≥2 CTCs ) groups . CTC groups were correlated with clinical characteristics and outcomes . A longitudinal analysis of CTC change and CA125 trends was also performed . RESULTS At least one CTC was isolated from the peripheral blood of over 80 % of the women participating in this study , with a range from 0 to 8 . No correlations were observed between CTC numbers and clinical characteristics or outcomes . Although both serum CA125 and CTC number exhibited an overall significant decreasing trend over time , there was no correlation observed between change in CTCs and CA125 . CONCLUSION Using the FDA -approved Cell Search system , CTCs can be isolated from women with newly diagnosed or recurrent ovarian cancer . However , CTC numbers do not significantly correlate with clinical characteristics or patient outcomes . Future studies should focus on phenotypic characterization of CTCs and whether different isolation protocol s yield a higher number of CTCs or add prognostic value 
    Output:
    
The presence of CTCs and DTCs is associated with adverse clinicopathological characteristics and poor clinical outcomes in ovarian cancer patients .