***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: This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer OBJECTIVE Treatment options for patients with radioactive iodine ( RaI ) refractory metastases of differentiated thyroid carcinoma ( DTC ) are limited . We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression . DESIGN Open , single center , single arm 26-week prospect i ve phase II study with open-ended extension . METHODS We treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d . The primary endpoint was reinduction of RaI uptake at 26 weeks . Additional endpoints were the radiological response and the influence of bone metastases . RESULTS At 26 weeks of sorafenib therapy , no reinduction of RaI uptake at metastatic sites was observed , but 19 patients ( 59 % ) had a clinical beneficial response , eight of whom had a partial response ( 25 % ) and 11 had stable disease ( 34 % ) . Seven patients had progressive disease ( 22 % ) . Sorafenib was significantly less effective in patients with bone metastases . The estimated median progression free survival was 58 weeks ( 95 % confidence interval , CI , 47 - 68 ) . In general , thyroglobulin ( Tg ) response ( both unstimulated and TSH stimulated ) reflected radiological responses . The median time of the nadir of Tg levels was 3 months . Responses were not influenced by histological subtype , mutational status or other variables . No unusual side effects were observed . CONCLUSIONS Sorafenib has a beneficial effect on tumor progression in patients with metastatic DTC , but was less effective in patients with bone metastases . Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake Background Antivascular endothelial growth factor tyrosine kinase inhibitors have been used recently in the treatment of advanced differentiated thyroid cancer ( DTC ) and medullary thyroid cancer ( MTC ) . Off-label sorafenib is used in Turkey with special permission by the Ministry of Health for this indication . Patients and methods Patients with advanced DTC and MTC were retrospectively identified from the Turkish Ministry of Health data base . Data on these patients were prospect ively collected before permission is granted to use sorafenib . Results Thirty patients with complete data were analyzed : 14 DTC ( papillary number [ n ] = 10 ; follicular n=4 ) and 16 MTC . The median age of the patients was 57 years ( range : 28–79 years ) , and there were 18 males and 12 females . All DTC patients were iodine refractory and had received a median three doses of radioactive iodine ( range : 1–7 doses ) . Sorafenib was used for a median of 12 months ( range : 1–49 months ) . The overall response rate was 20 % , all partial responses , with no complete response . The overall response rate was 14 % in DTC and 25 % in MTC patients . The median progression-free survival ( PFS ) was 17.1 months ( 95 % confidence interval [ CI ] : 7.3–26.8 ) and overall survival ( OS ) was not reached . The 2-year PFS and OS were 39 % and 68 % , respectively . DTC and MTC patients had similar survival outcomes : median PFS of 21.3 months ( 95 % CI : 5.8–36.7 ) versus 14.5 months ( 95 % CI : 3.7–25.2 ) , respectively ( P=0.36 ) , with the median OS not reached in either group ( P=0.17 ) . Tumor marker levels did not have any prognostic or predictive role . The toxicity profile was similar to that of other sorafenib trials . Conclusion Sorafenib is an effective and well-tolerated treatment in advanced thyroid cancers PURPOSE Given the molecular pathophysiology of thyroid cancer and the spectrum of kinases inhibited by sorafenib , including Raf kinase , vascular endothelial growth factor receptors , platelet-derived growth factor receptor , and RET tyrosine kinases , we conducted an open-label phase II trial to determine the efficacy of sorafenib in patients with advanced thyroid carcinoma . PATIENTS AND METHODS Eligible patients with metastatic , iodine-refractory thyroid carcinoma received sorafenib 400 mg orally twice daily . Responses were measured radiographically every 2 to 3 months . The study end points included response rate , progression-free survival ( PFS ) , and best response by Response Evaluation Criteria in Solid Tumors . RESULTS Thirty patients were entered onto the study and treated for a minimum of 16 weeks . Seven patients ( 23 % ; 95 % CI , 0.10 to 0.42 ) had a partial response lasting 18 + to 84 weeks . Sixteen patients ( 53 % ; 95 % CI , 0.34 to 0.72 ) had stable disease lasting 14 to 89 + weeks . Seventeen ( 95 % ) of 19 patients for whom serial thyroglobulin levels were available showed a marked and rapid response in thyroglobulin levels with a mean decrease of 70 % . The median PFS was 79 weeks . Toxicity was consistent with other sorafenib trials , although a single patient died of liver failure that was likely treatment related . CONCLUSION Sorafenib has clinical ly relevant antitumor activity in patients with metastatic , iodine-refractory thyroid carcinoma , with an overall clinical benefit rate ( partial response + stable disease ) of 77 % , median PFS of 79 weeks , and an overall acceptable safety profile . These results represent a significant advance over chemotherapy in both response rate and PFS and support further investigation of this agent in these patients BACKGROUND The use of preoperative chemotherapy for breast cancer has been demonstrated to result in similar disease-free survival ( DFS ) and overall survival ( OS ) as postoperative adjuvant chemotherapy . Additionally , the rate of pathologic complete response ( pCR ) in the breast after preoperative chemotherapy has been shown to correlate with survival . The objective of this study was to determine the pCR rate in patients with stage III breast cancer treated with 4 cycles of TAC ( docetaxel 75 mg/m2 , doxorubicin 50 mg/m2 , cyclophosphamide 500 mg/m2 ) on day 1 before surgery . PATIENTS AND METHODS From November 1998 through August 2001 , we treated 40 patients ( mean age , 47 years ) with stage III breast cancer with TAC administered every 3 weeks for 4 cycles . RESULTS We now report follow-up at 24 months . Responses were seen in 83 % of patients , with 25 % experiencing a clinical complete response , of which 4 patients ( 10 % ) had pCRs . At a follow-up of 2 years , data on DFS and OS are available on 37 patients : 12 patients ( 38 % ) had disease progression , and 7 patients ( 21 % ) had died . Despite the use of prophylactic ciprofloxacin , some degree of myelosuppression was seen in all patients , with 24 patients ( 63 % ) experiencing grade 3/4 neutropenia . CONCLUSION Based on the pCR rate seen in this trial , docetaxel given concomitantly with AC ( doxorubicin/cyclophosphamide ) for 4 cycles does not appear to be superior to 4 cycles of AC as preoperative treatment for stage III breast cancer . Based on other trials , longer duration s of therapy and /or sequencing of AC and docetaxel may result in a higher pCR rate AIM To evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma . METHODS Patients with progressive locally advanced/metastatic medullary thyroid carcinoma ( MTC ) , or differentiated thyroid carcinoma ( DTC ) with non-radioiodine-avid disease , were treated with sorafenib 400 mg twice daily until disease progression . The primary endpoint was the radiological response rate ( RR ) at 6 months . Secondary endpoints were RR at 3 , 9 and 12 months , biochemical responses , toxicity , biomarker analyses and progression free and overall survival ( OS ) . RESULTS A total of 34 patients were recruited to the study ( 15 medullary and 19 differentiated ) . After 6 months , the RR rate was 15 % and a further 74 % of patients achieved stable disease in the first 6 months . After 12 months of treatment , the RR was 21 % . In the MTC patients , the RR at 12 months was 25 % and OS was 100 % . In DTC patients corresponding rates were 18 and 79 % respectively . Median overall and progression-free survival points were not reached at 19 months . Commonest adverse events included h and -foot syndrome , other skin toxicities , diarrhoea and alopecia . Dose reduction was required in 79 % patients . Median time on treatment was 16.5 months . CONCLUSION This study demonstrates that sorafenib is tolerable at reduced doses over prolonged periods of time in patients with thyroid cancer . Sorafenib leads to radiological and biochemical stabilisation of disease in the majority of these patients despite dose reductions 
    Output:
    
Sorafenib could improve PFS in patients with progressive RR-DTC , comparing with placebo .