***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: Previous studies have shown that activating mutations of c-KIT/PDGFRA , potential therapeutic targets for imatinib mesylate , are implicated in the pathophysiology of gastrointestinal stromal tumours ( GISTs ) . In this study , GISTs from 37 patients enrolled in an European Organisation for Research and Treatment of Cancer ( EORTC ) phase I/II clinical study of imatinib  were examined for mutations of c-KIT/PDGFRA in order to explore whether the mutational status of the tumour predicts the clinical response to therapy . Mutations were screened by denaturing high-pressure liquid chromatography ( DHPLC ) and characterised by bi-directional DNA sequencing . Activating mutations of c-KIT or PDGFRA were found in 29 ( 78 % ) and 2 ( 6 % ) GISTs , respectively . Most c-KIT mutations involved exon 11 ( n=24 ; 83 % ) , all but one being an in-frame deletion ; no isolated point mutations were found . The other c-KIT mutations included exon 9 AY 502 - 503 duplication ( n=4 ; 14 % ) and exon 13 Lys-->Glu(642 ) missense mutation ( n=1 ; 3 % ) . Two tumours with no detectable c-KIT mutations demonstrated PDGFRA Asp-->Glu(842 ) amino acid substitutions .  Patients with GISTs harbouring exon 11 mutations were more likely to achieve a partial response ( PR ) on imatinib therapy ( 83 % ) than all of the others ( 23 % ) . The overall survival and progression-free survival rates for the entire group at 106 weeks were 78.3 % and 46.9 % , respectively . Based on a Kaplan-Meier analysis , patients with GISTs harbouring c-KIT mutations had longer median survival times and were less likely to progress than the other patients . These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P<0.001 ) . In a multivariate Cox model , the recurrence score provided significant predictive power that was independent of age and tumor size ( P<0.001 ) . The recurrence score was also predictive of overall survival ( P<0.001 ) and could be used as a continuous function to predict distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer Current accepted prognostic indicators in ovarian cancer include performance status , surgical ( FIGO ) staging , and residual disease after operation . Here we present data from a  prospect i ve analysis of patients with ovarian cancer treated at the Christie Hospital . We confirm the independent prognostic effects of FIGO staging , performance status , and residual disease in our group of patients and furthermore show that CA125 levels at presentation to the oncology service are of independent prognostic significance ( P= 0.02 ) . We present survival data and show that the 3-year , cancer-specific survival for stage I disease is 90 % . We postulate that this good survival may in part be due to the use of computed tomography scanning at presentation to allow accurate staging . Further clinical trials are needed to test whether combinations of surgical , histologic , biochemical , and radiologic parameters can be used to identify a population with such a good prognosis that adjuvant therapy is not required BACKGROUND Most patients with lymph node-negative breast cancer are cured by locoregional treatment ; however , about 30 % relapse . Because traditional histomorphologic and clinical factors fail to identify the high-risk patients who may benefit from adjuvant chemotherapy , other prognostic factors are needed . In a unicenter study , we have found that levels of  urokinase-type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI-1 ) in the primary tumor are predictive of disease recurrence . Thus , we design ed the Chemo N(0 ) prospect i ve r and omized multicenter therapy trial to investigate further whether uPA and PAI-1 are such prognostic factors and whether high-risk patients identified by these factors benefit from adjuvant chemotherapy . After 4.5 years , we present results of the first interim analysis . METHODS We studied 556 patients with lymph node-negative breast cancer . The median follow-up was 32 months . All patients with low tumor levels of uPA ( < or = 3 ng/mg of protein ) and of PAI-1 ( < or = 14 ng/mg of protein ) were observed . Patients with high tumor levels of uPA ( > 3 ng/mg of protein ) and /or of PAI-1 ( > 14 ng/mg of protein ) were r and omly assigned to combination chemotherapy or subjected to observation only . All statistical tests were two-sided . RESULTS A total of 241 patients had low levels of uPA and PAI-1 , and 315 had elevated levels of uPA and /or PAI-1 . The estimated 3-year recurrence rate for patients with low tumor levels of uPA and PAI-1 ( low-risk group ) was 6.7 % ( 95 % confidence interval [ CI ] = 2.5 % to 10.8 % ) . This rate for patients with high tumor levels of uPA and /or PAI-1 ( high-risk group ) was 14.7 % ( 95 % CI = 8.5 % to 20.9 % ) ( P = 0.006 ) . First interim analysis suggests that high-risk patients in the chemotherapy group benefit , with a 43.8 % lower estimated probability of disease recurrence at 3 years than high-risk patients in the observation group ( intention-to-treat analysis : relative risk = 0.56 ; 95 % CI = 0.25 to 1.28 ) , but further follow-up is needed for confirmation . CONCLUSIONS Using uPA and PAI-1 , we have been able to classify about half of the patients with lymph node-negative breast cancer as low risk , for whom adjuvant chemotherapy may be avoided , and half as high risk , who appear to benefit from adjuvant chemotherapy BACKGROUND Issues of reported study quality have not been addressed empirically with large-scale data in the cancer prognostic literature . METHODS Eight quality measures pertaining to study design and assay methods ( i.e. , blinding , prospect i ve versus retrospective design , power calculations , outcomes ' definitions , time of enrollment , reporting of variables , assay description , and assay reference ) were evaluated in cancer prognostic marker studies included in meta-analyses identified in Medline and EMBASE . To be eligible , meta-analyses had to include at least six studies and to examine binary outcomes . We estimated the ratios of relative risks , which compared the overall prognostic effects ( summary relative risks ) between poor- quality and good- quality studies for each quality item . Between- study heterogeneity was tested with the Q statistic ( statistically significant at P<.10 ) . All statistical tests were two-sided . RESULTS We identified 20 meta-analyses that included 331 cancer prognostic marker studies published between 1987 and 2005 . Only three ( 0.9 % ) of the 331 studies presented power calculations , 129 ( 39.0 % ) studies stated that analyses were blinded , and 73 ( 21.5 % ) stated that they were prospect i ve . Time of enrollment was defined in 232 ( 70.0 % ) , 234 ( 70.7 % ) gave lists of c and i date variables , and 254 ( 76.7 % ) defined outcomes . The assay used was described in 317 ( 95.8 % ) , but only 177 ( 53.5 % ) provided the assay reference . Estimates of prognostic effects from poor- quality studies varied considerably and could be larger or smaller than summary estimates derived from meta-analyses . Summary ratios of relative risks of poor- versus good- quality studies for the seven quality measures ranged from 0.95 to but 1.26 , but none was statistically significantly . There was statistically significant heterogeneity ( P<.10 ) between the ratios of relative risk estimates across meta-analyses for blinding , defining endpoints , and stating variables and assay references . CONCLUSIONS Among cancer prognostic marker studies , reporting quality of design and assay information often appears suboptimal , indicating that this literature may be largely unreliable . Given the potential clinical importance of prognostic marker information , improved design and reporting of these studies are warranted The 70-gene profile is a new prognostic tool that has the potential to greatly improve risk assessment and treatment decision making for early breast cancer . Its prospect i ve validation is currently ongoing through the MINDACT ( Microarray in Node-Negative Disease May Avoid  Chemotherapy ) trial , a 6,000-patient r and omized , multicentric trial . This article review s the several steps in the development of the profile from its discovery to its clinical validation PURPOSE The 21-gene recurrence score ( RS ) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive , lymph node-negative breast cancer treated with adjuvant tamoxifen .  The relationship between the RS and chemotherapy benefit is not known . METHODS The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B20 trial . Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS . RESULTS A total of 651 patients were assessable ( 227 r and omly assigned to tamoxifen and 424 r and omly assigned to tamoxifen plus chemotherapy ) . The test for interaction between chemotherapy treatment and RS was statistically significant ( P = .038 ) . Patients with high-RS ( > or = 31 ) tumors ( ie , high risk of recurrence ) had a large benefit from  chemotherapy  ( relative risk , 0.26 ; 95 % CI , 0.13 to 0.53 ; absolute decrease in 10-year distant recurrence rate : mean , 27.6 % ; SE , 8.0 % ) . Patients with low-RS ( < 18 ) tumors derived minimal , if any , benefit from chemotherapy treatment ( relative risk , 1.31 ; 95 % CI , 0.46 to 3.78 ; absolute decrease in distant recurrence rate at 10 years : mean , -1.1 % ; SE , 2.2 % ) . Patients with intermediate-RS tumors did not appear to have a large benefit , but the uncertainty in the estimate can not exclude a clinical ly important benefit . CONCLUSION The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative , estrogen receptor-positive breast cancer , but also predicts the magnitude of  chemotherapy benefit PURPOSE This phase II study evaluated the efficacy and safety of a 7-day on/7-day off regimen of temozolomide before radiotherapy ( RT ) in patients with inoperable newly diagnosed glioblastoma . PATIENTS AND METHODS Patients received temozolomide ( 150 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days ; 7 days on/7 days off ) for up to four cycles before conventional RT ( 2-Gy fractions to a total of 60 Gy ) and for four cycles thereafter or until disease progression . The primary end point was tumor response . Tumor tissue from 25 patients was analyzed for O6-methylguanine-DNA methyltransferase ( MGMT ) expression . RESULTS Twenty-nine patients with a median age of 60 years were treated , and 28 were assessable for response . Seven ( 24 % ) of 29 patients had a partial response , nine patients ( 31 % ) had stable disease , 
    Output:
    
Markers available for identifying drug-induced adverse reactions include thiopurine methyltransferase ( TPMT ) to predict toxicity from thiopurines in the treatment of acute lymphoblastic leukemia and uridine diphosphate glucuronyltransferase to predict toxicity from irinotecan in the treatment of colorectal cancer .