***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: OBJECTIVES to present and discuss a high-performance negative depletion method for the isolation of circulating tumor cells ( CTCs ) in the blood of patients with head and neck cancer and to determine the correlation between the presence of CTCs and early clinical outcome in these patients . DESIGN prospect i ve clinical follow-up study of patients with squamous cell carcinoma of the head and neck ( SCCHN ) undergoing surgical intervention , who had peripheral blood examined for the presence of CTCs . PATIENTS the study population comprised 48 patients diagnosed as having SCCHN and undergoing surgical intervention . INTERVENTION a negative depletion process to isolate and quantify CTCs from the blood of patients with SCCHN  using immunomagnetic separation was developed and vali date d. Immunostaining for cytokeratin was performed on the enriched sample s to determine the number of CTCs extracted from each patient 's blood sample . Correlation of the presence of CTCs , tumor stage , nodal status , clinical characteristics , and outcome was made . MAIN OUTCOME MEASURE disease-free survival . RESULTS our initial data , that have a mean follow-up of 19.0 months , suggest that patients with no detectable CTCs per milliliter of blood had a significantly higher probability of disease-free survival ( P = .01 ) . There was no correlation between the presence of CTCs with regard to age , sex , tumor site , stage , or nodal involvement . CONCLUSIONS our enrichment technology , based on the removal of normal cells , has been used on the peripheral blood of patients with head and neck cancer for which follow-up data were collected . If no CTCs were present , a statistically significant improved disease-free survival was observed in SCCHN . A blood test with such a prognostic capability could have important implication s in the treatment of patients with head and neck cancer Background The prognostic role of circulating tumor cells ( CTCs ) after induction chemotherapy using docetaxel , cisplatin and fluorouracil ( TPF ) prior to surgery and adjuvant (chemo)radiation in locally advanced oral squamous cell cancer ( OSCC ) was evaluated . Methods In this prospect i ve study , peripheral blood sample s from 40 patients of the phase II study TISOC-1 ( NCT01108042 ) with OSCC before , during , and after treatment were taken . CTCs were quantified using laser scanning cytometry of anti– epithelial cell adhesion molecule – stained epithelial cells . Their detection was correlated with clinical risk factors , recurrence-free ( RFS ) and overall survival ( OS ) . Results Before starting the treatment CTCs were detected in 32 of 40 patients ( 80 % ) . The median number at baseline was 3295 CTCs/ml . The median maximal number of CTCs during treatment was 5005 CTCs/ml . There was a significant increase of CTCs before postoperative radiotherapy compared to baseline before 1st cycle of IC ( p = 0.011 ) , 2nd cycle of IC ( p = 0.001 ) , 3rd cycle of IC ( p = 0.004 ) , and before surgery ( p = 0.002 ) , but not compared to end of therapy ( p = 0.118 ) . CTCs at baseline > median was also associated to risk of recurrence ( p = 0.014 ) . Maximal CTCs during therapy > median was more frequently observed in tumors of the oral cavity ( p=0.022 ) and related to higher risk of death during follow-up ( p = 0.028 ) . Patients with CTCs at baseline > median value had significant lower RFS than patients with CTCs at baseline < median value ( p = 0.025 ) . Patients with maximal CTCs values > median during the complete course of therapy had a significantly lower OS than patients with values < median ( p = 0.049 ) . Finally , the multivariate analysis revealed that OS was significantly lower in patients with maximal CTCs during treatment higher than the median value ( HR=6.151 ; CI : 1.244 - 30.420 ) . Conclusions Baseline CTCs and maximal CTCs during therapy both seem to be good prognostic markers for OSCC when treated by TPF induction chemotherapy , surgery , and postoperative (chemo)radiation BACKGROUND The prognostic role of persistence of circulating tumor cells ( CTC ) after upfront tumor surgery for outcome of adjuvant (chemo)radiation in locally advanced squamous cell carcinoma of the head and neck ( LASCCHN ) was evaluated . PATIENTS AND METHODS In this prospect i ve study , peripheral blood sample s from 144 patients with LASCCHN presenting after tumor resection for adjuvant treatment  were analyzed for CTC . Their detection was correlated with tumor site , clinical risk factors , disease-free ( DFS ) and overall survival ( OS ) . RESULTS  CTC  were detected in 42 of 144 patients ( 29 % ) . CTC detection was higher in cases with nodal involvement and in carcinomas located at the tonsil or base of tongue but was not influenced by age , smoking history , T stage , extracapsular lymph node extension , surgical margins or the human papillomavirus status . Overall , the presence of CTC was not predictive for OS or DFS . However , while in oropharyngeal carcinomas ( OPC , n = 63 ) , the detection of CTC was associated per trend with improved DFS [ CTC+ versus CTC- ( % of patients without evidence of disease at 2 years ) : 100 % versus 79 % ; log rank : P = 0.059 ] ; the reverse was observed for carcinomas from other sites ( non-OPC , n = 81 ; CTC+ versus CTC- : 29 % versus 75 % ; P = 0.001 ) . In multivariate analysis , CTC remained an independent prognostic marker for DFS [ hazard ratio ( HR ) 4.3 , 95 % confidence interval ( CI ) 1.7 - 10.9 , P = 0.002 ] and OS ( HR 2.7 , 95 % CI 1.2 - 6.3 , P = 0.016 ) in non-OPC . CONCLUSIONS Assessment of CTC in non-OPC should prove useful for identification of patients who benefit from treatment intensification . The basis for the good prognostic value of CTC in OPC has to be eluci date d in future studies BACKGROUND AND PURPOSE The mechanism of dissemination of locally advanced head and neck cancer ( LAHNC ) is far to be resolved . Circulating tumour cells ( CTC ) have been identified as a prognostic factor in metastatic breast and prostate cancer . This prospect i ve multi-centric analysis studied the possible role of CTC identification in LAHNC . MATERIAL S AND METHODS CTC were search ed in 73 patients with LAHNC ( oropharynx , n=39 ; nasopharynx , n=10 ; larynx , n=10 ; paranasal sinuses , n=6 , of whom 3 with sinonasal undifferentiated carcinoma , SNUC ; hypopharynx , n=5 ; oral cavity , n=3 ) . All of them ( apart from SNUC ) had squamous cell cancers . The relationship between CTC positivity and other clinical prognostic factors has been investigated . Response to treatment and survival has been related with changes in CTC number during the treatment . RESULTS CTC were frequently identified in oro- and hypopharyngeal cancer and in SNUC . They were more frequent in stage IV than in stages I-III disease ( 18 % versus 6 % , p = NS ( not significant ) ) . Partial or complete response ( CR ) was related with the absence or disappearance of CTC during treatment ( p=0.017 ) . A decrease in the CTC number or their absence throughout the treatment seems also related with non-progressive disease , after both complete or incomplete remission and with the proportion of patients alive and NED ( no evidence of disease ) ( p=0.009 ) . CONCLUSIONS These preliminary data suggest a possible role of CTC determination in head and neck cancer . Additional and longer follow up data need to be collected to confirm these findings PURPOSE The numbers of circulating tumor cells ( CTCs ) and their expression/activation of epidermal growth factor receptor ( EGFR ) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck ( SCCHN ) were determined . METHODS AND MATERIAL S Peripheral blood sample s from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab  were included in this study . Using flow cytometry , the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form ( pEGFR ) during the course of treatment were assessed . RESULTS Before treatment , we detected ≥1 CTC per 3.75 mL blood in 9 of 31 patients ( 29 % ) . Basal expression of EGFR was detected in 100 % and pEGFR in 55 % of the CTC+ cases . The frequency of CTC detection was not influenced by induction chemotherapy . However , the number of CTC+ sample s significantly increased after radiotherapy . This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil . The former treatment regimen was also more effective in reducing pEGFR expression in CTCs . CONCLUSIONS Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells . Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases CD133 has been associated with cell properties such as self renewal , migration and vasculogenic mimicry , potentially involved in generation of circulating tumor cells ( CTCs ) . We characterized CD133 expression in CTCs of 98 nometastatic breast cancer ( BC ) patients .  CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody ( CK3 - 11D5 ) and CTCs and CD133 detection through immunocytochemical methods .  CK(+ ) /CD133(+ ) CTCs were identified in 65 % of patients at baseline and 47.8 % after systemic therapy ( p = 0.53 ) . Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed . Her2 not amplified and low Ki-67 index were positively correlated with presence of CK(+ ) /CD133(+ ) CTCs . Before any treatment , CK(+ ) /CD133(+ ) CTCs were more frequently isolated in patients with luminal BC subtype . No statistically significant differences were found between proportion of CK(+ ) /CD133(+ ) CTCs and BC subtypes after systemic therapy , implying a relative enrichment of CK(+ ) /CD133(+ ) CTCs in triple negative and HER2-amplified tumors . While CK(+ ) /CTCs decreases after chemotherapy when analyzing the whole population , CK(+ ) /CD133(+ ) CTCs were enriched in post-treatment sample s in nonluminal BC subtypes . These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients . Further prospect i ve studies and extensive pre clinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy , and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature Studies in circulating tumor cells ( CTCs ) have proceeded to be accepted as prognostic markers in several types of cancers . But they are still limited because many are mainly from enumeration of CTCs . Here , we tried to evaluate the tumorigenicity of CTCs from advanced gastric cancer patients ( n = 42 ) . Peripheral blood mononuclear cells ( P BMC ) from the patients were separated into CD45 negative and positive fractions and both were subcutaneously injected into immunodeficient mice . Within 5 months nine tumor-like-structures from six patients but not from healthy volunteers were established . They were durable for passages and all had been confirmed human origin . Eight of the nine tumor-like-structures were from nonauthorized CTC containing cells expressing CD45 and B-cell markers . On the contrary , one of them was developed from CD45(- ) P BMC fraction of a patient with bone marrow metastasis reflecting authorized CTCs . Histopathology showed common features with that of original gastric tumor . The cells isolated from the tumor-like-structure expressed EpCAM and CEA further supporting they were from the original tumor . Moreover the cells were CD44 positive to varying degree and a limiting dilution study showed that the CD44(+/high ) fraction had tumorigenicity . The CD44 was dominantly in the form of CD44 variant 8 - 10 . The CD44(+/high ) cells had higher expression of the glutamate/cysteine transporter xCT compared with the CD44(-/low ) cells . Our results showed the existence of tumor-initiating cells in blood of advanced gastric cancer patients and they could be a therapeutic target and prospect i ve tool for further investigations Background Successful application of programmed death 1 ( PD1 ) checkpoint inhibitors in the clinic may ultimately benefit from appropriate patient selection based upon predictive biomarkers . Molecular characterization of circulating tumor cells ( CTC ) is crucial for the investigation of molecular-target 
    Output:
    
Our meta- analysis results indicated that CTCs are significant associated with prognosis of patients with HNSCC .