Evaluation of Neoadjuvant Therapy Response of Osteogenic Sarcoma Using FDG PET

Michael Schulte, Doris Brecht-Krauss, Mathias Werner, Erich Hartwig, Michael R. Sarkar, Peter Keppler, JörgKotzerke, Albrecht Guhlmann, GünterDelling and Sven N. Reske

Department ofTrauma, Hand and Reconstructive Surgery and Department ofNuclear Medicine, University of Ulm, Ulm; and Department ofOsteopathology, University ofHamburg, Hamburg, Germany

dure. Data evaluated by the Cooperative Osteosarcoma According to the current treatment protocol of the Cooperative Study (COSS) indicate that the risk of a local recurrence is OsteosarcomaStudy(COSS),monitonngpreoperativechemo linked to both the response to preoperative therapy and the therapyresponseand estimatinggradeof tumorregressionin type of surgery. Although the overall local failure rate was patientswithosteosarcomaismandatorybeforesurgicalremoval 4.8%, it rose to 14.3% in patients with poor response of the tumor,particularlyif a limb salvageprocedureis intended. (defined as less than 90% tumor destruction) when treated In addition, response to neoadjuvantchemotherapyis consid ered as an importantprognosticindicator.The aim of this by a limb salvage procedure (3). In a study by Picci et al. (4), prospective study was to assess the usefulness of 2-(18F) patients with inadequate surgical margins but excellent fluoro-2-deoxy-D-glucose (FDG) PET in the noninvasive evalua response to neoadjuvant treatment had a lower incidence of tion of neoadjuvant chemotherapy response in osteosarcoma. local relapse than patients with adequate surgical margins Methods: In 27 patientswith osteosarcoma,we determined but poor response to preoperative chemotherapy. tumor-to-backgroundratios (TBR5) of FDG uptake with PET, Because local recurrence of osteosarcoma is associated, before and after neoadjuvant chemotherapy according to COSS 86c or COSS 96 protocols, respectively. We compared changes as a rule, with synchronous or metachronous metastatic in glucosemetabolismof osteosarcomaswiththe histologicspread, even amputation does not offer a curative perspec grade of regressionin the resectedspecimen,accordingto tive. Therefore, the response to neoadjuvant chemotherapy Salzer-Kuntschik,discriminating responders (grades I—Ill;n = should be determined and considered as precisely as pos 17) and nonresponders(gradesIV—Vl;n = 10). Results:The sible before definitive operative tumor removal, particularly decreaseof FDG uptakeinosteosarcomasexpressedas a ratio if a limb salvage procedure is planned. In patients with large of posttherapeutic and pretherapeutic ThRs showed a close tumor volume and a low response, ablative surgery or correlationtotheamountoftumornecrosisinducedbypolyche motherapy(P < 0.001; Spearman).With a TBR ratiocutoff level rotation plasty should be preferred. of 0.6, all responders and 8 of 10 nonresponders could be Standard techniques for noninvasive evaluation of tumor identifiedbyPET.Inaddition,lungmetastasesofosteosarcomaregression are three-phase bone scintigraphy using @“@Tc were detectedwithFDG PET in 4 patients.Conclusion:FDG methylene diphosphonate (5) and static or dynamic gadolin PET provides a promising tool for noninvasive evaluation of ium diethylenetriamine pentaacetic acid (DTPA)-enhanced neoadjuvantchemotherapyresponsein osteosarcoma.This MRI (6—8).A new approach for this problem could be couldimplyconsequencesfor the choiceof surgicalstrategy, becausea limbsalvageprocedurecannotbe recommendedin diffusion-weighted MRI, which revealed a high sensitivity patientsnonresponsiveto preoperativechemotherapyunless in discerning viable osteosarcoma tissue and tumor necrosis widesurgicalmarginscansafelybeachieved. in an animal model (9). Key Words:osteosarcomametabolism;osteosarcomadrug Elevated uptake of 2-('8F)-fluoro-2-deoxy-D-glucose therapy; evaluation studies; osteosarcoma surgery; osteosar (FDG) determined by PET has been reported in malignant coma radionuclideimaging mesenchymal tumors in a small number of studies. FDG J NucIMed 1999;40:1637—1643 PET was proposed as a diagnostic tool for discriminating benign and malignant soft tissue and osseous lesions (10— 13), for the grading of sarcomas (12, 14, 15) and for the detection of local recurrences (16). Garcia et al. (17) found

. he histologic response to neoadjuvant chemotherapy not the sensitivity of FDG PET in diagnosis of recurrent or onlyrepresentsanimportantprognosticindicatorfordisease residual musculoskeletal sarcoma to be significantly higher free survival after multimodal treatment of osteogenic compared with @mTc@methoxyisobutylisonitrile (MIBI) sarcoma (1,2), but should also influence the surgical proce SPECT. In addition, FDG PET was proposed for detection of pulmonary metastases in osteogenic sarcoma (18). ReceivedOct.25,1998;revisionacceptedApr.9, 1999. Several studies have analyzed the role of FDG PET Forcorrespondenceor reprintscontact:MichaelSchulte,MD, Musculoskel etal Tumor Unit, Departmentof Trauma, Hand and ReconstructiveSurgery, scanning in the assessment of therapeutic response in SteinhOvelstr.9,89075Ulm,Germany. patients with various carcinomas (19—26)and in malignant

THERAPY RESPONSE OF OSTEOSARCOMA •Schulte et at. 1637 lymphoma (27—29).In a recent study, Jones et al. (30) TABLE 1 presented FDG data of nine patients with soft-tissue sarco Individual Data, Histologic Subtype, Tumor Stage, mas and malignant primary bone tumors, including three Site and SurgicalProcedureof27 Patients withOsteosarcomaEligibleforthe Study osteosarcomas, who received neoadjuvant therapy. Changes of glucose metabolism could be correlated to the amount of PatientAgeno.(y) tumor necrosis induced by the preoperative treatment. Using Surgery114MChondroblasticIIBLeftSex Subtype Stage Location repeated examination with FDG PET, van Ginkel et al. (31) femurLS217MChondroblasticIIBRight found a significantly different glucose consumption in femurLS31 patients with partial and complete response after isolated fibulaLS418MOsteoblasticIIBLeft7FOsteoblasticIIBLeft limb perfusion for soft-tissue sarcoma. However, in their tibiaAM514FOsteoblasticIIIBRightfemur—@612FOsteoblasticlIBRight study, specificity of the method was compromised by an femurAM78MChondroblasticlIBRight FDG accumulation due to surrounding inflammatory reaction. femurRP81 The aim of this study was to analyze whether FDG PET femurLS923MChondroblasticIIBLeft5FOsteoblasticIIBLeft represents a more accurate tool for evaluating neoadjuvant pelvisLS1029MOsteoblasticlIBRight femurLS1117MMixedtIIBLeftfemurRP1211MOsteoblasticIIBRight chemotherapy response in osteosarcoma compared with established imaging techniques, such as contrast-enhanced femurLS1319MOsteoblasticIIBRight MRI and three-phase bone scintigraphy. humerusLS1414MChondroblasticIIBRibLS1518MOsteoblasticIIBLeft femurLS1615MChondroblasticlIBLeft MATERIALS AND METHODS femurLS1 femurAP1814FOsteoblasticIIBRight78MOsteoblasticIIBLeft PatientSelection femurRP191 In a current prospective study initiated in January 1993, 27 femurRP2022FChondroblasticIIIBRight3FOsteoblasticIIBLeft patients (17 male, 10 female; age 5—36y, median 17 y) with pelvis—@2120FOsteoblasticlIBLeft humerusLS225FTeleangiectaticIIBCervical osteogenic sarcoma were examined by FDG PET before biopsy and spineLS2322MMixedtIIBLeft again after neoadjuvant polychemotherapy. Selection criteria in femurLS2436MOsteoblasticIIIBLeft cluded first manifestation of a histologically ascertained classic femurLS2517MOsteoblasticIIBRight high-grade osteosarcoma and completion of neoadjuvant polyche femurLS2634MOsteoblasticIIBLeftfemurLS271 motherapy according to COSS-86c or COSS-96 protocol. There was no restriction regarding the age of the patients. PET was 9FChondroblasticlIBLeft femurLS performed in all patients referred to the surgical department of our institution with evidence of a malignant primary bone tumor, on the *Nosurgicaltherapybecauseof advancedtumorstage. basis of radiologic findings, including plain x-rays and contrast tOsteoblasticandchondroblasticdifferentiation. enhanced MRI. LS= limbsalvage;AM = amputation;RP= rotationplasty. All patients underwent an open biopsy, and the diagnosis of Tumorstagegradedaccordingto Enneking(45). osteosarcoma could be confirmed histologically in 32 patients. Tumor staging comprised a CT scan of the chest to exclude FDG PET pulmonary metastases; CT data were compared with the thoracic FDG PET studies were performed as described by Stolifuss et al. PET findings. Excluded from the study were 2 patients with (32) with a commercially available scanner (ECAT 931—08—12; parosteal osteosarcoma, I patient with periosteal osteosarcoma and Siemens/CT!, Knoxville, TN) that allows simultaneous acquisition I patient with central low-grade osteosarcoma, because they did of 15contiguous 6.75-mm thick sections with an axial field of view not require neoadjuvant therapy. Of 28 patients who were selected of 10.1 cm. The resolution was 7 mm (full width at half maximum) for the investigation, I patient with stage IIIB osteosarcoma at the center of the field of view. Attenuation correction was underwent rotation plasty without PET examination before defini performed with a rotating eaGeP@Gasource. Depending on tumor tive surgery; therefore data of 27 patients could be evaluated. size, transmission scans with a duration of 8 mm per bed position were obtained in at least three bed positions without overlap before Table 1 summarizes patient data, including histologic subtype, emission scans on the same day. Thus, repositioning of the patient tumor location and stage of disease. Biopsy was performed within was necessary using multiple laser-guided landmarks. Patients 5 d after the initial PET scanning,andchemotherapywas initiated fasted for at least 8 h before the study, and normal plasma glucose within 14 d thereafter. According to COSS 86c or COSS 96 levels were documented before FDG administration. According to protocol, doxorubicin, high-dose methotrexate, ifosfamide and a previous study by Ichiya et al. (23), static emission scans of the cisplatinum were administered consecutively. tumor site and the corresponding contralateral area, with two or All patients in the study were examined with a second PET scan three contiguous bed positions starting no earlier than 45 mm immediately before surgical treatment of the tumor. The minimum (range 45—60mm) after intravenous administration of a body mass interval to the last combined administration of ifosfamide/ dependent dose of 120—300MBq FDG, were used for semiquanti cisplatinum was 12d; the maximum interval was 18d. tative assessment of tumoral FDG uptake. Acquisition time was 10 All patients or their parents gave written informed consent to mm per bed position. In addition, emission scans of the chest were receive chemotherapy per COSS 86c or COSS 96 protocols and to obtained. Image reconstruction was performed with a multiplica be scanned with FDG PET twice preoperatively. tive iterative reconstruction algorithm (33).

1638 THEJOURNALOFNUCLEARMEDICINE•Vol. 40 •No. 10 •October1999 Data Analysis this evaluation: 1 patient died during a traffic accident 13 mo Qualitative and quantitative evaluation of the PET scans was after surgery,and the other patient succumbedto a septic performed by analyzing the hypermetabolic zones on transaxial, complication related to postoperative chemotherapy 9 mo coronal and sagittal sections. Regions of interest (ROIs) were aftertumorresection. individually defined for each osteosarcoma, excluding areas of Individual data on pretherapeutic and posttherapeutic lower uptake within the tumor, if present. ROIs were defined in the TBRs,the histologicgradeof regression,follow-upperiod scan expressing maximum uptake and were larger than 2.6 cm2 in and current status are listed in Table 2. Patient 5 with stage each case. The neoplasm was demarcated readily from surrounding tissue, and the boundaries of the ROl were just within the apparent ifiB osteosarcomaof thefemurshowedpulmonarymetasta hypermetabolic zone ofthe tumor. Quantitative assessment of FDG ses simultaneously; under chemotherapy both local and uptake was obtained from transaxial sections exclusively.Tumor-to pulmonaryprogresswere observed.MRI follow-up3 mo background ratios (TBRs) were calculated with an ROI of identical after biopsyrevealedan extendedtumor mass in the thigh configuration at the analogous site of the contralateral extremity, without reduction of gadolinium uptake compared with the pelvic bone or chest, respectively. In a case with a vertebral lesion initial examination. Three-phase bone scintigraphy dis (patient 22), an adjoining unaffected vertebral body was used as played an increased tracer uptake in all phases. Thus, on the reference region. The average activity within each ROl was basis of the clinical findings, this patient had to be classified corrected for radioactive decay. Ratios of TBR before and after as a “nonresponder,―and the grade of regression was neoadjuvant treatment were calculated for each patient and com estimated 5. The patient died 3 mo after confirmation of pared with the histologic extension of tumor destruction. To assess the diagnosis; her deteriorated state precluded any further the interobserver error, TBR values were obtained by two indepen dent physicians without knowledge of the clinical data and were surgery. averaged for statistical evaluation. Ratios ofpost-therapeutic and pretherapeutic ThRs showed In 25 patients, tumor regression defined as a percentage of devitalized tumor was determined histologically within the re TABLE 2 sected specimen and graded according to Salzer-Kuntschik et al. HistologicGradeofRegression,OncologicOutcome (34),discriminatingresponders(gradesI—HI)andnonresponders and Data Evaluated by FDG PET (grades IV—VI).In patient 20, who had a locally inoperable iliosacral tumor with multiple pulmonary metastases, the effect of chemotherapy was assessed by repeated biopsy. One patient with PatientGradeofFollow-upperiodCurrentno.regression(mo)status stage IIIB disease (patient 5) developed a local and pulmonary TBR1 TBR2 TBRIrBR1 progress under chemotherapy and died without further surgery. In 1 1 70 NED 17.972.270.133.262.920.906.792.270.337.795.740.7422.0020.330.928.441 this case, grade of regression was estimated with the use of 2 4 66 NED follow-up investigations with contrast-enhanced MRI and three 3 3 62 NED phase bone scan. 4 4 60 NED 5 >5* 3 DD Statistical Analysis 6 3 50 DD .930.2313.422.110.166.832.740.405.132.240.4411.487.000.6132.401 The Mann-Whitney U test was used to compare TBRs of 7 3 30 DD 8 3 47 NED responders and nonresponders. The Spearman rank correlation test 9 4 8 DD was used to compare ratios of pretherapeutic and posttherapeutic 10 4 16 DD ThRs with the grade of histologic response (34). The 95% 11 3 6 DD 7.500.545.271 confidence intervals (CIs) were calculated according to Clopper 12 1 28 NED .890.366.154.790.7810.341.990.1923.204.800.213.890.320.084.200.470.116.561 and Pearson (35). 13 4 9 14 3 25 NED 15 3 23 NED RESULTS 16 2 23 NED Interobserver deviation of TBR values ranged from 17 2 13 D 18 2 19 NED .610.2510.602.500.246.702.800.4213.108.300.633.403.100.9122.2011.100.5010.893.100.2833.207.100.2118.918.60.9817.63.100.18 2%—ll% (median 4%). ThRs before neoadjuvant chemother 19 2 13 DD apy ranged from 3.3 to 33.2 (median 10.3). No correlation of 20 3 10 ADM quantitative PET data to age, sex, tumor site, volume or 21 4 9 DD histologic subtype was apparent. Pretherapeutic median 22 6 8 NED TBR in the responder group (n = 17) was 10.34 (range 23 4 8 NED 24 3 7 ADM 3.89—33.2)and in the nonresponder group (n = 10) 9.64 25 3 6 NED (range 3.26—22.2).Post-therapeutic values differed signifi 26 5 5 NED cantly (P 0.01) for responders (median 2.27, range 27 3 5 NED 0.32—17.5) versus nonresponders (median 6.37, range 2.24— 20.33). Patients with thus far disease-free survival (n = 15) *Estimatedgradeof regression. had a pretherapeutic median TBR of 7.79 (range 3.26—33.2), TBR1= tumor-to-backgroundratiobeforebiopsy;TBR2= tumor whereas patients with metastatic disease, development of a to-backgroundratio after neoadjuvantchemotherapy;NED = no relapse or lethal course (n = 10) presented a median TBR of evidenceof disease;DD = diedof disease;D = diedof unrelated cause;ADM= alivewithmetastases. 11.19 (range 5.13—32.4).Two patients were not eligible for

[email protected] RESPONSEOFOsmos@co@ •Schulteet al. 1639 a close correlation to the histologic extent of tumor destruc tion (Spearman correlation coefficient 0.82, P < 0.001; Fig. 1). However, the dispersion of ThRs within the individual regression groups did not permit a precise prediction of the quantitative amount of tumor necrosis. A major reduction of glucose metabolism developed in 2 patients (9 and 23), indicating a good response to preoperative therapy, although their morphologic grade of regression was IV (nonre sponder). By using a TBR cutoff level of 0.6 for detecting responders (prevalence 63.0%), there were two false positive but no false-negative results. The sensitivity was 100% (CI 80.5%—lOO%),the specificity 80.0% (CI 44.4%— 97.5%), the accuracy92.6% (CI 75.7%—99.1%),positive predictive value 89.5% (CI 66.7%—98.7%) and negative predictive value 100% (CI 63.l%—100%). Figure 2 demon strates the findings of patient 8 (responder); Figure 3 shows patient 4 (nonresponder). PET examination of the chest revealed lung metastases in patients 5, 20, 24 and in an 8-y-old boy with osteoblastic osteosarcoma stage IIIB of the distal femur, who had to be excluded from the study because no PET scan was obtained after neoadjuvant chemotherapy. This patient underwent rotation plasty because of impending tumor exulceration and subsequent bilateral removal of pulmonary metastases. Pulmonary dissemination suspected by PET could be con firmed by CT scanning in all 4 patients, and also by histologic examination in the drop-out case previously mentioned. According to CT data, no false-negative or false-positive results concerning lung metastases were ob served in this series.

DISCUSSION Established imaging methods to assess neoadjuvant therapy response in osteosarcoma comprise three-phase bone scintig

TBR 2/1

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0,2@ S S : 2. Fifteen-y-oldgirlwithosteoblasticosteosarcoma stage II B of left femur (patient8). (A)Anteropostenorand lateral plainradiographsshowscleroticlesionof medialpartofdistal Gradeof Rgresslon femoralmetaphysis.(B) InitialcoronalFDG PET scan shows strongly hypermetabolic area in projection to distal femoral FIGURE1. TBRquotientsof 27 patientswithosteosarcomametaphysis before chemotherapy.(C) Coronal FDG PET scan after (TBR2) and before (TBR1) neoadjuvant chemotherapy, after neoadjuvantchemotherapy.Marked reduction of glucose correlated to histologic grade of regression (Spearman rank metabolicactivityis expressedwithin lesion.Histologicexamina correlationcoefficient0.82, P < 0.001). Usingcutoff level of 0.6, tionof resectedspecimenrevealedviabletumorfractionof 9%, responders could be discriminated from nonresponders in all but so patientwas classifiedas respondergrade Ill. 2 patients.

1640 THE JOURNALOF NUCLEARMEDICINE •Vol. 40 •No. 10 •October 1999 raphy and contrast-enhanced dynamic MRI. The accuracy of bone scanning for quantitative estimation of tumor necrosis A in osteogenic sarcoma was calculated at 93% by Bielack et al. (5) and 80% by Erlemann et al. (6). In a study comparing three different radioactive substances (36), 201T1-chloride and 67Ga-citrate were superior to @“@Tc-methylene-diphospho nate (MDP) in predicting bone tumor response to chemother apy; MDP bone scanning might be affected by factors other than tumor activity (e.g., osseous blood flow), giving an accurate correlation with clinical and pathologic response in only one of seven cases (36). A close correlation of 201Tl uptake changes to the grade of chemotherapy-induced tumor regression in osteosarcomas was confirmed by Ohtomo et al. (37) and by Imbriaco et al. (38). An 86% accuracy of dynamic MRI in predicting tumor response was reported by Erlemann et al. (6). In our series, FDG PET attained a similar level of accuracy. It might be considered an advan tage that PET directly assesses glucose metabolism, which is maintained in viable tumor cells only, whereas MRI and bone scanning are restricted to an indirect estimation of B tumor necrosis by monitoring blood perfusion. Our study attempts to evaluate preoperative monitoring of osteosarcoma using FDG PET with emphasis on prediction of tumor response to neoadjuvant chemotherapy, because surgical strategy must consider response behavior. Param eters for quantification of FDG uptake are represented by standardized uptake values (SUVs) and ThRs. For reasons of practicality and independence of transmission scanning, we have used TBR instead of SUV. Because SUV is the more conventional method of quantification, it will have to be shown that the validity of TBR matches that of SUV for such purposes. Because TBR is dependent on metabolic background activity, it does not reflect absolute glucose uptake, but only changes relative to some ill-defined “nor mal―tissue. if that tissue is muscle, it is known that muscle C FDG uptake varies with activity and rest. For evaluation of tumor response to fluorouracil in colorectal cancer liver metastases, it has been shown that semiquantitative analysis by FDG SUV is not as reliable as the tumor-to-liver ratio (21). This is indicative of the problems of introducing extra measurement variables when trying to establish a semiquantitative method. Inadequate injection with extravasation of some of the FDG at the time of intravenous administration most likely led to an underes timate of the tumor SUV. This problem did not affect the TBR, because it is purely a ratio of the observed radioactiv ity in the two ROIs, therefore injected activity is irrelevant. As a further potential confounding factor for SUV calcula tion, a competing organ such as the myocardium could take FIGURE3. Eighteen-y-oldmanwithosteoblasticosteosar up a greater proportion of the injected FDG dose, leaving coma stage lIB of left proximaltibia (patient4). (A) TI-weighted less for the tumor. If this is present only on the pretreatment unenhancedcoronalspinechoMR imageshowsextensionof or post-treatment scan, it may result in a misinterpretation of lesion.(B)CoronalFDG PETscanbeforeincisionbiopsyshows tumor response. highly elevated glucose metabolismof tibial head. (C) Coronal FDG PET scan after neoadjuvant chemotherapy.Hypermeta From studies concerning potential confounding factors bolicarea appearsunchanged.With viabletumorfractionof for SUV calculation, it appeared that the time to scanning 22%, patienthadto be classifiedas nonrespondergrade IV. did not have any impact on the SUV. When planning the

THERAPYRESPONSEOF Osmos@coMA •Schulte et al. 1641 timing of the scans, it was initially considered that 45—60 post-therapeutic FDG accumulation not exclusively caused mm from the time of FDG injection was an appropriate by viable tumor cells. In this series we did not observe a period for tumor FDG levels to plateau. This was based on false-positive result caused by inflammatory processes or data from normal brain studies and colorectal liver metasta nonspecific postoperative hypermetabolism. None of our sis studies. A subsequent study of 68 scans in 47 patients patients had inflammatory complications, and because the suggested a good correlation between the fractional rate of second PET scan was obtained at least 10 wk after the tracer uptake from Patlak plots and SUVs at 60 mm for a biopsy, relevant reparative activity could not be expected. range of tumor types (39). Furthermore, in most of the studies concerning therapy monitoring of malignant tumors, CONCLUSION semiquantitative analysis of tumor FDG uptake for evalua Because FDG PET depicts metabolic activity rather than tion of therapy response was performed on static emission scans from 45—60mm (19—30).Hamberg et al. (40) reported topographic information, it has been shown to be especially valuable for monitoring therapy response in patients with the results of a study examining this issue. In eight patients advanced tumor disease. Likewise, data from our ongoing with non-small cell lung cancer, they found that FDG SUV study suggest that FDG PET provides a promising nomnva (or dose-uptake ratio) plateau in these tumors was not sive tool to identify responders after neoadjuvant treatment reached by 90 mm in the majority of scans, both before and in osteogenic sarcoma. This could imply consequences for after treatment. The average time to reach 95% ofthe plateau the choice of surgical strategy, because a limb salvage SUV in pretreatment scans was about 300 mm (range procedure cannot be recommended in patients nonrespon 130-500 mm) and in post-treatment scans was about 150 sive to preoperative chemotherapy unless wide surgical mm (range 65—400mm). They calculated that because the margins can be achieved safely. Another advantage of FDG time-activity curve is increased more steeply in the pretreat PET scanning compared with current imaging modalities, ment scans, probably because of a treatment-induced reduc such as bone scintigraphy and dynamic MRI, is the possibil tion in glycolytic rates, there will be an underestimation of ity of simultaneous whole-body tumor staging, which en the change with treatment when based on 60 mm data. In this ables the detection of occult skeletal, lung and visceral study, however, FDG PET correctly identified all respond metastases. cr5, whereas 2 patients with tumor necrosis rates below 90% after preoperative chemotherapy showed a decrease of glucose metabolism similar to the responders and, therefore, ACKNOWLEDGMENTS were falsely classified as responders with FDG PET. The The authors thank Irene Staudle and Drs. Alexandra von timing of scans in relation to the EDO injection needs further Baer and Gerhard Glatting, University of Ulm, for clinical investigation to determine the impact or the utility of the and editorial assistance. This study was presented in part at clinical method, although it did not appear to be a major the Congress of the European Association of Nuclear factor in this study. Medicine in Düsseldorf, Germany, August 1994; at the In this study, the exclusive use ofTBR values resulted in a second European Congress of Orthopaedics and Traumatol high accuracy concerning the evaluation of chemotherapy ogy in Munich, Germany, July 1995; at the Congress of the response in osteogenic sarcomas. However, assessment of European Association of Nuclear Medicine in Copenhagen, relative decrease of TBR values before and after chemother Denmark, September 1996; at the second Osteosarcoma apy did not permit a precise quantification of tumor necrosis, Research Conference in Bologna, Italy, November 1996; but enabled a discrimination of responders and nonre and at the 44th Annual Meeting of the Society of Nuclear sponders, except for 2 patients (9 and 23) with a pelvic and a Medicine in San Antonio, TX, June 1997. femoral lesion, respectively. 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