***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Background Preoperative diffusion-weighted MRI ( DW-MRI ) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients . A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy . Objective To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma , more specifically at mid-course of treatment . Material s and methods This study was carried out on a prospect i ve series of adolescents treated for long-bone osteosarcoma .  MR examinations were performed at diagnosis ( MRI-1 ) , at mid-course of chemotherapy ( MRI-2 ) , and immediately before surgery ( MRI-3 ) . A DW sequence was performed using diffusion gradients of b0 and b900 . The apparent diffusion coefficients ( ADC1 , ADC2 , ADC3 , respectively ) , their differentials ( ADC2 − ADC1 and ADC3 − ADC1 ) , and their variation ( ADC2 − ADC1/ADC1 and ADC3 − ADC1/ADC1 ) were calculated for each of these three time points . Results Fifteen patients were included . Patients with no increase in ADC showed a poor response to chemotherapy on their histology results . At mid-course , the three calculated values were significantly different between good and poor responders . ADC2 − ADC1 enabled us to detect , with 100 % specificity , four out of seven of the poor responders . There was no significant difference in the values at MRI-3 between the two groups . Conclusion DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma . This method could be used as an early prognostic factor to monitor preoperative chemotherapy The objective of this study was to prospect ively evaluate dynamic contrast‐enhanced magnetic resonance imaging ( DCE‐MRI ) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event‐free survival ( EFS ) and overall survival in pediatric patients with newly diagnosed , nonmetastatic osteosarcoma who were treated on a single , multi‐institutional phase 2 trial BACKGROUND Previous r and omized controlled trials that used the two-drug chemotherapy regimen of cisplatin and doxorubicin as the conventional arm showed no evidence of benefit from an increase in the number of agents or the length of treatment . It was then proposed that survival could be improved by increasing the planned dose intensity of cisplatin and doxorubicin . METHODS Previously untreated patients with nonmetastatic , high- grade , central osteosarcoma of an extremity were r and omly assigned to Regimen-C ( conventional treatment with six 3-week cycles of cisplatin [ 100 mg/m2 by 24-hour infusion ] and doxorubicin [ 25 mg/m2/day by 4-hour infusion for 3 days ] ) or to Regimen-DI ( intensified treatment with identical total doses of cisplatin and doxorubicin , planned as six 2-week cycles supported by granulocyte colony stimulating factor ( G-CSF ) . Surgery was scheduled for week 6 in both arms . Primary and secondary outcome measures were overall and progression-free survival , respectively . Intention-to-treat analyses were performed using st and ard survival analysis methods . L and mark analyses were performed in patients with known surgical details and central ly review ed histologic response . All statistical tests were two-sided . RESULTS Between May 1993 and September 2002 , treatment was r and omly allocated to 497 eligible patients . Six cycles of chemotherapy were completed by 78 % of patients in Regimen-C and 80 % of patients in Regimen-DI . The delivered preoperative median dose intensity of cisplatin was 86 % in Regimen-C and 111 % in Regimen-DI ( as the percentage of that planned for the conventional regimen ) . Postoperative median dose intensity of cisplatin was 82 % in Regimen-C and 110 % in Regimen-DI ( the corresponding figures for doxorubicin dose intensity were similar ) . Regimen-DI was associated with lower risks of severe leucopenia and neutropenia and higher risks of thrombocytopenia and mucositis . Good histologic response ( > 90 % tumor necrosis ) was observed in 36 % of Regimen-C patients and 50 % of Regimen-DI patients ( P = .003 , chi2 test ) . There was no evidence of a difference in overall survival ( hazard ratio [ HR ] = 0.94 , 95 % CI = 0.71 to 1.24 ; P = .64 ) or progression-free survival ( HR = 0.98 , 95 % CI = 0.77 to 1.24 ; P = .83 ) . L and mark analyses showed similar results . CONCLUSIONS Planned intensification of chemotherapy with cisplatin and doxorubicin increased received dose intensity and result ed in a statistically significant increase in favorable histologic response rate , but not in increased progression-free or overall survival . Our results call into question the use of histologic response as a surrogate outcome measure in trials of this disease PURPOSE To prospect ively assess whether there is a relationship between the apparent diffusion coefficient ( ADC ) and the histopathologic cell count and whether the ADC can enable differentiation of benign and malignant extracranial mass lesions in children . MATERIAL S AND METHODS Institutional ethics approval and parent or guardian consent were obtained . Eleven malignant and eight benign lesions in 19 children ( 11 girls , eight boys ; median age , 3.9 years ; age range , 11 days to 15.5 years ) who underwent magnetic resonance ( MR ) imaging of extracranial mass lesions-including a diffusion-weighted sequence ( with b values 0 , 500 , and 1000 sec/mm(2))- and histopathologic analysis to prove findings were studied . The median ADC within each mass lesion was compared with the median cell count for 10 high-power microscopic fields in the specimen . The inverse regression between cell count and ADC was calculated . The difference in ADC between benign and malignant lesions was assessed by using the Mann-Whitney U test . RESULTS There was an inverse relationship between ADC and cell count , expressed as ADC ( in x10(-3 ) mm(2)/sec ) = 0.56 + ( 66.2/cell count ) , with a relatively good fit to the observed data ( analysis of variance R(2 ) = 0.541 , F = 20.0 , P < .001 ) . The ADCs of benign lesions ranged from ( 0.84 - 2.83 ) x 10(-3 ) mm(2)/sec ( median , 1.35 x 10(-3 ) mm(2)/sec ; st and ard deviation , 0.68 ) . The ADCs of malignant lesions ranged from ( 0.73 - 1.53 ) x 10(-3 ) mm(2)/sec ( median , 1.00 x 10(-3 ) mm(2)/sec ; st and ard deviation , 0.29 ) . There was no significant difference in ADC between benign and malignant lesions ( Mann-Whitney U = 22 , P = .069 ) . All highly cellular ( > 150 cells per high-power field ) lesions had an ADC lower than 1.5 x 10(-3 ) mm(2)/sec . CONCLUSION Although there is a significant relationship between cellularity and ADC , cell count probably is not the sole determinant of the ADC . Use of the ADC can not enable accurate differentiation of malignant and benign lesions We evaluated the potential of 18F-FDG PET/CT and diffusion-weighted imaging ( DWI ) to monitor the histologic response in patients with extremity osteosarcoma receiving neoadjuvant chemotherapy , using sequential PET/CT and MR imaging . Methods : We prospect ively registered 28 patients with high- grade osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy and surgery .  All patients underwent sequential 18F-FDG PET/CT and MR imaging before ( PET/MR1 ) and after neoadjuvant chemotherapy ( PET/MR2 ) . Maximum st and ardized uptake value ( SUV ) , tumor volume based on MR imaging ( MRV ) , and the mean apparent diffusion coefficient ( ADC ) values were measured on PET/MR1 ( SUV1 , MRV1 , and ADC1 ) and PET/MR2 ( SUV2 , MRV2 , and ADC2 ) . The percentage changes in maximum SUV ( ΔSUV ) , MRV ( ΔMRV ) , and ADC ( ΔADC ) were calculated , and the correlations among these parameters were evaluated . After surgery , the effects of neoadjuvant chemotherapy were grade d histopathologically : grade s III and IV ( necrosis of ≥ 90 % ) indicated a good response , and grade s I and II ( necrosis of < 90 % ) indicated a poor response . The optimum cutoff values of ΔSUV , ΔMRV , ΔADC , and their combination for predicting histologic response were assessed by single- and multi-receiver-operating-characteristic curve analysis . Results : Twenty-seven patients were enrolled in the present study after 1 patient with inadequate acquisition of MR imaging was excluded . ΔSUV and ΔADC negatively correlated with each other ( ρ = −0.593 , P = 0.001 ) , and ΔMRV did not correlate with ΔSUV or ΔADC . The cutoff value , sensitivity , specificity , and accuracy for predicting good histologic response were ≤ −52 % , 67 % , 87 % , and 78 % , respectively , for ΔSUV and > 13 % , 83 % , 73 % , and 78 % , respectively , for ΔADC . However , ΔMRV did not predict histologic response . Sensitivity , specificity , and accuracy were 83 % , 87 % , and 85 % , respectively , using the combined criterion of ΔSUV ≤ −31 % and ΔADC > 13 % . Conclusion : In the current preliminary study , both PET/CT and DWI are useful for predicting histologic response after neoadjuvant chemotherapy in osteosarcoma . Combining PET/CT and DWI may be an effective method to predict the histologic  response  of patients to neoadjuvant chemotherapy From January 1993 to March 1995 , 162 patients with osteosarcoma of extremities were treated according to the IOR/OS-4 protocol . 133 patients had localised disease , while 29 had metastases at diagnosis . These last patients were simultaneously operated upon for their primary and metastatic lesions . Chemotherapy consisted preoperatively of two cycles of high dose methotrexate ( HDMTX ) and one cycle each of cisplatin (CDP)-doxorubicin ( ADM ) , CDP/ifosfamide ( IFO ) and IFO/ADM . After surgery , patients were treated with the aforementioned drugs used as single agents . The mean follow-up of all patients was 6.5 years ( 5.5 - 8 years ) . Surgery was a limb salvage in 94 % of cases , and the 5-year event-free survival ( EFS ) and overall survival ( OS ) rates were 56 and 71 % for patients with localised disease , and 17 and 24 % for patients with metastases at diagnosis . These results did not differ from those achieved in our previous study ( IOR/OS-3 ) in which IFO was used only postoperatively in poor responders PURPOSE It has been observed previously in osteosarcoma ( OS ) that the degree of necrosis of the resected primary tumor following a period of preoperative chemotherapy is predictive of subsequent event-free survival ( EFS ) . The aim of this study was to determine if more intensive preoperative chemotherapy would increase the proportion of patients with a good histologic response and improve EFS . PATIENTS AND METHODS Seventy-three patients with OS were treated at Memorial-Sloan Kettering Cancer Center ( MSKCC ) on the T12 protocol between 1986 and 1993 . Patients were r and omized between therapy based on the T10 protocol and therapy with more intensive preoperative chemotherapy . The more intensive preoperative regimen consisted of two courses of cisplatin ( CDDP ) and doxorubicin ( DOX ) in addition to the usual preoperative regimen of high-dose methotrexate ( HD MTX ) and bleomycin , cyclophosphamide , and dactinomycin ( BCD ) . RESULTS The regimen with more intensive preoperative chemotherapy achieved a modest increase in the proportion of patients with a good histologic response ( 44 % with a grade III or IV histologic response v 37 % in the control arm , 33 % with grade IV histologic response v 13 % in the control arm ) . EFS continued to correlate with histologic response . The actuarial 5-year EFS in patients with localized disease was 78 % for the regimen with more intensive preoperative chemotherapy and 73 % for the control arm . CONCLUSION Despite modest increases in the proportion of patients with good histologic response with intensified preoperative chemotherapy , no improvement in EFS was observed Objective The objective of this study was to evaluate whether the average apparent diffusion coefficient ( ADC ) or the minimum ADC is more useful for evaluating the chemotherapeutic response of osteosarcoma . Material s and methods Twenty-two patients with o 
    Output:
    
DWI performed with ADC values was useful for predicting the chemotherapeutic response of osteosarcoma .
This method may have promising potential as a preoperative non-invasive modality