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Radiology Radiology Radiology Radiology
Scott Schuetze, MD, PhDScott Schuetze, MD, PhD
University of MichiganUniversity of Michigan
Scott Schuetze, MD, PhDScott Schuetze, MD, PhD
University of MichiganUniversity of Michigan
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DisclosureDisclosureDisclosureDisclosureI am not a radiologistI am not a radiologistI am not a radiologistI am not a radiologist
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Utility of imagingUtility of imagingUtility of imagingUtility of imaging
Before diagnosisBefore diagnosisDuring stagingDuring stagingDuring treatmentDuring treatment
Before diagnosisBefore diagnosisDuring stagingDuring stagingDuring treatmentDuring treatment
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Advanced imaging is Advanced imaging is overused prior to referral to overused prior to referral to
a musculoskeletal oncologista musculoskeletal oncologist
Advanced imaging is Advanced imaging is overused prior to referral to overused prior to referral to
a musculoskeletal oncologista musculoskeletal oncologist
Drs. Miller, Avedian, Cummings, BalachDrs. Miller, Avedian, Cummings, Balach
Universities of Iowa, Arizona, Stanford, Universities of Iowa, Arizona, Stanford, Connecticut, & Virginia Mason (Seattle)Connecticut, & Virginia Mason (Seattle)
Drs. Miller, Avedian, Cummings, BalachDrs. Miller, Avedian, Cummings, Balach
Universities of Iowa, Arizona, Stanford, Universities of Iowa, Arizona, Stanford, Connecticut, & Virginia Mason (Seattle)Connecticut, & Virginia Mason (Seattle)
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What should the generalist What should the generalist or primary provider know?or primary provider know?
What should the generalist What should the generalist or primary provider know?or primary provider know?
What is appropriate imaging to evaluate What is appropriate imaging to evaluate complaint?complaint? PainPain MassMass
Imaging for bone vs soft tissue lesion?Imaging for bone vs soft tissue lesion?What information is necessary for the What information is necessary for the
specialist to accept the referral?specialist to accept the referral?
What is appropriate imaging to evaluate What is appropriate imaging to evaluate complaint?complaint? PainPain MassMass
Imaging for bone vs soft tissue lesion?Imaging for bone vs soft tissue lesion?What information is necessary for the What information is necessary for the
specialist to accept the referral?specialist to accept the referral?
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Study strengthsStudy strengthsStudy strengthsStudy strengths Geographic diversity – NW, NE, Geographic diversity – NW, NE,
California, South-west, Mid-west, TxCalifornia, South-west, Mid-west, Tx Inclusion of 8 centersInclusion of 8 centers Prospective consecutive case selection Prospective consecutive case selection Relatively large number of casesRelatively large number of cases Pre-defined criteria for imaging utilityPre-defined criteria for imaging utility Statistical analysisStatistical analysis
Geographic diversity – NW, NE, Geographic diversity – NW, NE, California, South-west, Mid-west, TxCalifornia, South-west, Mid-west, Tx
Inclusion of 8 centersInclusion of 8 centers Prospective consecutive case selection Prospective consecutive case selection Relatively large number of casesRelatively large number of cases Pre-defined criteria for imaging utilityPre-defined criteria for imaging utility Statistical analysisStatistical analysis
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Study limitationsStudy limitationsStudy limitationsStudy limitations U.S. perspectiveU.S. perspective Pre-defined criteria may be subjectivePre-defined criteria may be subjective Results for bone & soft tissue combinedResults for bone & soft tissue combined Sequencing of imaging not detailedSequencing of imaging not detailed Imaging may be driven local radiologists Imaging may be driven local radiologists
interpreting radiographs and/or MRI & interpreting radiographs and/or MRI & recommending additional studiesrecommending additional studies
U.S. perspectiveU.S. perspective Pre-defined criteria may be subjectivePre-defined criteria may be subjective Results for bone & soft tissue combinedResults for bone & soft tissue combined Sequencing of imaging not detailedSequencing of imaging not detailed Imaging may be driven local radiologists Imaging may be driven local radiologists
interpreting radiographs and/or MRI & interpreting radiographs and/or MRI & recommending additional studiesrecommending additional studies
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Study findingsStudy findingsStudy findingsStudy findings MRI useful in majority of soft tissue tumors, MRI useful in majority of soft tissue tumors,
unnecessary in bone lesionsunnecessary in bone lesions Geographic differences in CT frequency Geographic differences in CT frequency
(highest in TX, OK, SC)(highest in TX, OK, SC) Bone scanning and US were infrequentBone scanning and US were infrequent PET overused in OK (12%) vs Seattle (0%)PET overused in OK (12%) vs Seattle (0%)Advanced imaging overused in benign Advanced imaging overused in benign
bone lesionsbone lesions
MRI useful in majority of soft tissue tumors, MRI useful in majority of soft tissue tumors, unnecessary in bone lesionsunnecessary in bone lesions
Geographic differences in CT frequency Geographic differences in CT frequency (highest in TX, OK, SC)(highest in TX, OK, SC)
Bone scanning and US were infrequentBone scanning and US were infrequent PET overused in OK (12%) vs Seattle (0%)PET overused in OK (12%) vs Seattle (0%)Advanced imaging overused in benign Advanced imaging overused in benign
bone lesionsbone lesions
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Lessons learnedLessons learnedLessons learnedLessons learned
Orthopaedic surgeons as guilty as primary Orthopaedic surgeons as guilty as primary carecare
CT, bone scans, PET and US are frequently CT, bone scans, PET and US are frequently unnecessary for diagnosisunnecessary for diagnosis
Opportunities for regional education?Opportunities for regional education? Opportunities for education during training?Opportunities for education during training? Target orthopaedic surgeons, primary care Target orthopaedic surgeons, primary care
and/or radiologists?and/or radiologists?
Orthopaedic surgeons as guilty as primary Orthopaedic surgeons as guilty as primary carecare
CT, bone scans, PET and US are frequently CT, bone scans, PET and US are frequently unnecessary for diagnosisunnecessary for diagnosis
Opportunities for regional education?Opportunities for regional education? Opportunities for education during training?Opportunities for education during training? Target orthopaedic surgeons, primary care Target orthopaedic surgeons, primary care
and/or radiologists?and/or radiologists?
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Pre-referral take-awayPre-referral take-awayPre-referral take-awayPre-referral take-away
High quality MRI with contrast for High quality MRI with contrast for soft tissue masssoft tissue mass
Plain x-ray for bone lesionPlain x-ray for bone lesionLet the specialists sort out the restLet the specialists sort out the rest
High quality MRI with contrast for High quality MRI with contrast for soft tissue masssoft tissue mass
Plain x-ray for bone lesionPlain x-ray for bone lesionLet the specialists sort out the restLet the specialists sort out the rest
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Pulmonary micronodules do Pulmonary micronodules do not impact survival in young not impact survival in young
patientspatients
Pulmonary micronodules do Pulmonary micronodules do not impact survival in young not impact survival in young
patientspatients
Drs. Gitelis, Cipriano & KentDrs. Gitelis, Cipriano & Kent
Rush Medical CollegeRush Medical College
Drs. Gitelis, Cipriano & KentDrs. Gitelis, Cipriano & Kent
Rush Medical CollegeRush Medical College
1212
What is the clinical significance What is the clinical significance of <1 cm lung nodules on CT?of <1 cm lung nodules on CT?
What is the clinical significance What is the clinical significance of <1 cm lung nodules on CT?of <1 cm lung nodules on CT?
Patient demographics – age, Patient demographics – age, occupation, residence, inhalational occupation, residence, inhalational substance use/abusesubstance use/abuse
Medical historyMedical historySarcoma sub-typeSarcoma sub-typeNodule number and distributionNodule number and distributionSlice thickness of scanSlice thickness of scan
Patient demographics – age, Patient demographics – age, occupation, residence, inhalational occupation, residence, inhalational substance use/abusesubstance use/abuse
Medical historyMedical historySarcoma sub-typeSarcoma sub-typeNodule number and distributionNodule number and distributionSlice thickness of scanSlice thickness of scan
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Which nodules to worry over?Which nodules to worry over?Which nodules to worry over?Which nodules to worry over?19 yo Ewings
50 yo UPS
35 yo LMS
65 yo liposarc
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Which nodules to worry over?Which nodules to worry over?Which nodules to worry over?Which nodules to worry over?19 yo Ewings
50 yo UPS
35 yo LMS
65 yo liposarc
? LMS
Histoplasma MALT
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Study designStudy designStudy designStudy design 96 pt subset of 380 pts96 pt subset of 380 pts Age <50 yrs, bone and soft tissue sarcomaAge <50 yrs, bone and soft tissue sarcoma 80% received chemotherapy80% received chemotherapy Overall survival endpointOverall survival endpoint 4 strata4 strata
No lung nodules (47%)No lung nodules (47%) Single nodule <5 mm (26%)Single nodule <5 mm (26%) >1 nodule <5 mm (13%)>1 nodule <5 mm (13%) >>1 nodule 1 nodule >>5 mm (15%)5 mm (15%)
96 pt subset of 380 pts96 pt subset of 380 pts Age <50 yrs, bone and soft tissue sarcomaAge <50 yrs, bone and soft tissue sarcoma 80% received chemotherapy80% received chemotherapy Overall survival endpointOverall survival endpoint 4 strata4 strata
No lung nodules (47%)No lung nodules (47%) Single nodule <5 mm (26%)Single nodule <5 mm (26%) >1 nodule <5 mm (13%)>1 nodule <5 mm (13%) >>1 nodule 1 nodule >>5 mm (15%)5 mm (15%)
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Study resultsStudy resultsStudy resultsStudy results75% of nodules <5 mm and 100% of 75% of nodules <5 mm and 100% of
nodules nodules >>5 mm biopsied were sarcoma5 mm biopsied were sarcomaSurvival worse for patients with nodule Survival worse for patients with nodule
>>5 mm5 mm
75% of nodules <5 mm and 100% of 75% of nodules <5 mm and 100% of nodules nodules >>5 mm biopsied were sarcoma5 mm biopsied were sarcoma
Survival worse for patients with nodule Survival worse for patients with nodule >>5 mm5 mm
80%76%68%
36%
No difference between
Groups 1-3
p < 0.05 for Groups
1 - 3 compared to Group 4
Figure 1: Influence of Pulmonary Nodules at Presentation on Survival in Sarcoma Patients Under age 50.
(N = 96, Mean Follow up 47.2 Months)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 10 20 30 40 50 60 70 80 90 100 110
Surv
ival
Time from Diagnosis (months)
Group 1: No Nodules n = 45
Group 2: 1 Nodule < 5mm n = 25
Group 4: Any number of Nodules > 5mm n = 14
Group 3: Any number of Nodules < 5mm n = 37
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Related studiesRelated studiesRelated studiesRelated studies
Indeterminate Pulmonary Nodules in Patients with Sarcoma Affect SurvivalRissing S, Rougraff B, Davis KClinical Orthopaedics & Related Research459:118-121, June 2007
71 sarcoma pts <1cm nodules# of malignant nodules
Patient group
<5 cm(n=128)
>5 - <1 cm(n=118)
>1 - <3 cm(n=123)
No cancer 13 (32%) 15 (30%) 46 (59%)
Cancer 115 (42%) 103 (69%) 77 (84%)
426 pts with nodules
Pulmonary nodules resected at VATS: etiology in 426 patientsGinsberg MS, Griff SK, Go BD, et al.Radiology 213:227-82, 1999
Nodule size at 1st CT
<5 mm >5 mm
benign 15 (60%) 7 (27%)
metastasis 10 (40%) 19 (73%)
51 pts with osteosarcoma
CT of pulmonary metastases from osteosarcoma: the less poor techniquePicci P, Vanel D, Briccoli A, et al.Ann Oncol 12:1601-04, 2001
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Informal survey results – basis Informal survey results – basis for nodules as metastatic diseasefor nodules as metastatic diseaseInformal survey results – basis Informal survey results – basis
for nodules as metastatic diseasefor nodules as metastatic disease Ewing AEWS0031: 1 nodule >1 cm or >1 Ewing AEWS0031: 1 nodule >1 cm or >1
nodules >0.5 cmnodules >0.5 cm EURAMOS-1: 1 nodule EURAMOS-1: 1 nodule >>1 cm or 1 cm or >>3 nodules 3 nodules
>>0.5 cm0.5 cm COG ARST: 1 nodule COG ARST: 1 nodule >>1 cm1 cm French trials: 1 nodule >1 cmFrench trials: 1 nodule >1 cm Italian trials: 1 nodule >0.5 cmItalian trials: 1 nodule >0.5 cm SARC012: the oncologist, radiologist and SARC012: the oncologist, radiologist and
surgeon should use best judgmentsurgeon should use best judgment
Ewing AEWS0031: 1 nodule >1 cm or >1 Ewing AEWS0031: 1 nodule >1 cm or >1 nodules >0.5 cmnodules >0.5 cm
EURAMOS-1: 1 nodule EURAMOS-1: 1 nodule >>1 cm or 1 cm or >>3 nodules 3 nodules >>0.5 cm0.5 cm
COG ARST: 1 nodule COG ARST: 1 nodule >>1 cm1 cm French trials: 1 nodule >1 cmFrench trials: 1 nodule >1 cm Italian trials: 1 nodule >0.5 cmItalian trials: 1 nodule >0.5 cm SARC012: the oncologist, radiologist and SARC012: the oncologist, radiologist and
surgeon should use best judgmentsurgeon should use best judgment
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ConclusionsConclusionsConclusionsConclusions
Metastasis (<5 mm) at diagnosis does not Metastasis (<5 mm) at diagnosis does not = poor outcome= poor outcome
Lung nodules Lung nodules >>5 mm should raise 5 mm should raise suspicionsuspicion
Many lung nodules should raise suspicionMany lung nodules should raise suspicionStandardize criteria for clinical trials?Standardize criteria for clinical trials?Treat for cure!Treat for cure!
Metastasis (<5 mm) at diagnosis does not Metastasis (<5 mm) at diagnosis does not = poor outcome= poor outcome
Lung nodules Lung nodules >>5 mm should raise 5 mm should raise suspicionsuspicion
Many lung nodules should raise suspicionMany lung nodules should raise suspicionStandardize criteria for clinical trials?Standardize criteria for clinical trials?Treat for cure!Treat for cure!
2020
Total lesion glycolysis by Total lesion glycolysis by FDG-PET is of predictive FDG-PET is of predictive
value in soft tissue sarcomavalue in soft tissue sarcoma
Total lesion glycolysis by Total lesion glycolysis by FDG-PET is of predictive FDG-PET is of predictive
value in soft tissue sarcomavalue in soft tissue sarcoma
Drs. Choi, Ha, Cho, Kang, Kim, Drs. Choi, Ha, Cho, Kang, Kim, Pang & HanPang & Han
Seoul National University HospitalSeoul National University Hospital
Drs. Choi, Ha, Cho, Kang, Kim, Drs. Choi, Ha, Cho, Kang, Kim, Pang & HanPang & Han
Seoul National University HospitalSeoul National University Hospital
2121
Potential value of dynamic Potential value of dynamic imaging in sarcomaimaging in sarcoma
Potential value of dynamic Potential value of dynamic imaging in sarcomaimaging in sarcoma
Prognostic information: natural Prognostic information: natural course of diseasecourse of disease
Predictive information: disease Predictive information: disease response to interventionresponse to intervention
Prognostic information: natural Prognostic information: natural course of diseasecourse of disease
Predictive information: disease Predictive information: disease response to interventionresponse to intervention
2222
FDG PET semi-quantitative FDG PET semi-quantitative measurementsmeasurements
FDG PET semi-quantitative FDG PET semi-quantitative measurementsmeasurements
SUVSUVmaxmax: maximum pixel value w/i slice with highest FDG : maximum pixel value w/i slice with highest FDG uptakeuptake
SUVSUVpeakpeak: average pixel value w/i fixed ROI in area with : average pixel value w/i fixed ROI in area with highest FDG uptakehighest FDG uptake
SUVSUVaveave: average pixel value w/i tumor ROI: average pixel value w/i tumor ROI TBR: average value w/i tumor ROI / average value w/i TBR: average value w/i tumor ROI / average value w/i
blood poolblood pool TLG: SUVTLG: SUVaveave of uptake above minimum threshold x TV of uptake above minimum threshold x TV MTV: volume of tumor within ROI in which FDG uptake is MTV: volume of tumor within ROI in which FDG uptake is
>40% of SUV>40% of SUVmaxmax
SUVSUVmaxmax: maximum pixel value w/i slice with highest FDG : maximum pixel value w/i slice with highest FDG uptakeuptake
SUVSUVpeakpeak: average pixel value w/i fixed ROI in area with : average pixel value w/i fixed ROI in area with highest FDG uptakehighest FDG uptake
SUVSUVaveave: average pixel value w/i tumor ROI: average pixel value w/i tumor ROI TBR: average value w/i tumor ROI / average value w/i TBR: average value w/i tumor ROI / average value w/i
blood poolblood pool TLG: SUVTLG: SUVaveave of uptake above minimum threshold x TV of uptake above minimum threshold x TV MTV: volume of tumor within ROI in which FDG uptake is MTV: volume of tumor within ROI in which FDG uptake is
>40% of SUV>40% of SUVmaxmax
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Challenges in Challenges in standardizationstandardizationChallenges in Challenges in
standardizationstandardization
Dynamic versus static measurementsDynamic versus static measurementsFDG administration protocolFDG administration protocolHardware calibrationHardware calibrationObserver dependent ROIObserver dependent ROIDefinitionsDefinitions
Dynamic versus static measurementsDynamic versus static measurementsFDG administration protocolFDG administration protocolHardware calibrationHardware calibrationObserver dependent ROIObserver dependent ROIDefinitionsDefinitions
2424
FDG PET and sarcoma FDG PET and sarcoma prognosisprognosis
FDG PET and sarcoma FDG PET and sarcoma prognosisprognosis
Recurrence-free survival
Factor Disease HR 95% CI P value
SUVmax >6 STS 3.2 1.3-8.2 0.015
SUVmax >6 EWS 0.47
SUVmax >6 OS 0.41
SUVmax >15 OS 4.5 1.3-15.3 0.015
SUVmax does not account for tumor heterogeneitySUVmax does not account for tumor heterogeneity Do other parameters improve prognostic information?Do other parameters improve prognostic information?
SUVmax does not account for tumor heterogeneitySUVmax does not account for tumor heterogeneity Do other parameters improve prognostic information?Do other parameters improve prognostic information?
Schuetze S et al. 2005, Cancer 103:339Hawkins D et al. 2009, Cancer 115:3519Hawkins D et al. 2005, JCO 23:8828.Costelloe C et al, 2009, J Nuc Med 50:340.
2525
Study dataStudy dataStudy dataStudy data 66 pts with STS66 pts with STS RetrospectiveRetrospective AJCC stageAJCC stage
I: 16%I: 16% II: 24%II: 24% III: 46%III: 46% IV: 14%IV: 14%
Adjuvant txAdjuvant tx Radiotherapy: 47%Radiotherapy: 47% Chemotherapy: 29%Chemotherapy: 29%
66 pts with STS66 pts with STS RetrospectiveRetrospective AJCC stageAJCC stage
I: 16%I: 16% II: 24%II: 24% III: 46%III: 46% IV: 14%IV: 14%
Adjuvant txAdjuvant tx Radiotherapy: 47%Radiotherapy: 47% Chemotherapy: 29%Chemotherapy: 29% SUVmax: 6
TLG: 250MTV: 40 cm3
Receiver operating characteristics
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K-M analysis of sarcoma K-M analysis of sarcoma FDG metabolismFDG metabolism
K-M analysis of sarcoma K-M analysis of sarcoma FDG metabolismFDG metabolism
Choi E-S et al. 2013, Eur J Nucl Med Mol Imaging DOI 10.1007/s00259-013-2511-y
P<0.001 P=0.022 P=0.031
2727
Multivariate analysis factors Multivariate analysis factors affecting PFSaffecting PFS
Multivariate analysis factors Multivariate analysis factors affecting PFSaffecting PFS
Factor Value Univariate Multivariate
P value RR 95% CI P value
AJCC stage III or IV 0.035 3.36 1.01-11.02 0.047
Metastases Present <0.001 5.99 1.81-19.8 0.003
TLG 250 0.001 4.79 1.51-15.23 0.008
SUVmax 6 0.031 0.203
MTV 40 cm3 0.022 0.736
2828
Multivariate analysis factors Multivariate analysis factors affecting PFSaffecting PFS
Multivariate analysis factors Multivariate analysis factors affecting PFSaffecting PFS
Factor Value Univariate Multivariate
P value RR 95% CI P value
AJCC stage III or IV 0.035 3.36 1.01-11.02 0.047
Metastases Present <0.001 5.99 1.81-19.8 0.003
TLG 250 0.001 4.79 1.51-15.23 0.008
SUVmax 6 0.031 0.203
MTV 40 cm3 0.022 0.736
Is TLG predictive of response to therapy ina uniformly treated high-risk population?
2929
FDG PET in sarcomaFDG PET in sarcomaFDG PET in sarcomaFDG PET in sarcoma Potential roles in sarcoma managementPotential roles in sarcoma management
Prognostic information / risk of relapsePrognostic information / risk of relapse Predict response to adjuvant therapyPredict response to adjuvant therapy Early marker of response to drug therapyEarly marker of response to drug therapy
Foundation of single-institutional experience Foundation of single-institutional experience (variability minimized)(variability minimized)
Need more experience in multi-site trials Need more experience in multi-site trials (more variability)(more variability)
Potential roles in sarcoma managementPotential roles in sarcoma management Prognostic information / risk of relapsePrognostic information / risk of relapse Predict response to adjuvant therapyPredict response to adjuvant therapy Early marker of response to drug therapyEarly marker of response to drug therapy
Foundation of single-institutional experience Foundation of single-institutional experience (variability minimized)(variability minimized)
Need more experience in multi-site trials Need more experience in multi-site trials (more variability)(more variability)
3030
Thanks to the presenters & Thanks to the presenters & session chairssession chairs
Thanks to the presenters & Thanks to the presenters & session chairssession chairs