Download PET-CT with FDG - 2015 Joint Congress on Medical Imaging

Carol-Anne Davis, RT(T), AC(T), DHSA, MSc
May 28 – 30, 2015, Montréal, Québec
I do not have an affiliation, financial or otherwise, with a pharmaceutical company, medical
device or communications organization.
I have no conflicts of interest to disclose ( i.e. no industry funding received or other
commercial relationships).
I have no financial relationship or advisory role with pharmaceutical or device-making
companies, or CME provider.
I will not discuss or describe in my presentation at the meeting the investigational or
unlabeled ("off-label") use of a medical device, product, or pharmaceutical that is
classified by Health Canada as investigational for the intended use.
May 28 – 30, 2015, Montréal, Québec
PET-CT
“Over the past 20 years,
positron emission tomography
(PET) and PET/CT (computed
tomography) have revolutionized
the care of cancer patients in
developed countries and are
increasingly being adopted in
emerging economies.
PET has been, and still is,
one of the fastest growing
fields in medical imaging”*
*Permission granted from International Atomic Energy Agency:
International Atomic Energy Agency, Standard Operating Procedures for PET/CT: A Practical Approach for Use in Adult Oncology
IAEA Human Health Series 26, IAEA, Vienna (2013).
Research Question
What proportion of non-small cell carcinoma lung and
head & neck squamous cell carcinoma patients have a
significantly different CTV due to the use of PET-CT?
Target Volumes: GTV, CTV
high, low
Extent of gross tumour, i.e. what can be seen, palpated
or imaged; this is known as the gross tumour volume
(GTV).
Developments in imaging have contributed to the
definition of the GTV.
Target Volumes: GTV, CTV
high, low
 The second volume contains the GTV + a margin for
sub-clinical disease spread which therefore cannot be
fully imaged; this is known as the clinical target
volume (CTV).
 It is the most difficult because it cannot be accurately
defined for an individual patient, but future
developments in imaging, especially towards the
molecular level, should allow more specific delineation
of the CTV.
 The CTV is important because this volume must be
adequately treated to achieve cure.
Target Volumes: GTV, CTV
Target Volumes: GTV, CTV high, low
GTV primary
CTV low risk
(requires
lower dose)
GTV nodes
CTV high risk
(requires max
dose)
courtesy of G Segall (Stanford University) through the PET PROS program of the SNM PET Center of Excellence“.
http://www.snm.org/index.cfm?PageID=10044
PET-CT is a
powerful
diagnostic
imaging tool
that combines
anatomic
imaging (CT)
with physiologic data
(PET)
PET-CT is sensitive
and specific for
cancer
PET
 Stands for positron emission tomography
 Fluorine-18-deoxyglucose (18-FDG), a radionuclide
labeled glucose analogue, is injected and the pt is
imaged
 18F-fluorodeoxyglucose (FDG) is taken up by cells
proportionate to their metabolic rates
Quite simply…
 Malignant cells take inherently have a higher
metabolism than non-malignant cells. They have
a higher mitotic rate as well as more inefficient
aerobic metabolism leading to more anaerobic
metabolism
 Through these mechanisms, malignant cells will
take up the FDG at a faster rate and this will can be
seen on the scan as the FDG decays.
Imaging Protocol
Patient
- Fast 5 hrs prior to exam
- Inject tracer
- Start scan 60 min later
CT
- Topogram (scout)
- CT scan (1 min)
PET
- Brain (10 min)
- Heart (10 min)
- Body (20 min)
<130
PET/CT in oncology
PET-CT allows the clinician to better differentiate
benign vs malignant structural abnormalities seen
on CT as well as see possible malignancies where no
structural abnormalities are seen.
•Detect radiographically occult lesions
•Evaluate extent of disease
•Characterize radiographic abnormalities
•Evaluate response to therapy
Abnormal PET - CT Body Scan
courtesy of G Segall (Stanford University) through the PET PROS program of the SNM PET Center of Excellence“.
http://www.snm.org/index.cfm?PageID=10044
Lesion Characterization
courtesy of G Segall (Stanford University) through the PET PROS program of the SNM PET Center of Excellence“.
http://www.snm.org/index.cfm?PageID=10044
Lesion Characterization
courtesy of G Segall (Stanford University) through the PET PROS program of the SNM PET Center of Excellence“.
http://www.snm.org/index.cfm?PageID=10044
Enhanced Detection
Enhanced Detection
courtesy of G Segall (Stanford University) through the PET PROS program of the SNM PET Center of Excellence“.
http://www.snm.org/index.cfm?PageID=10044
Background and Rationale of Research Study
What do we “know” about PET-CT with respect to RT?
PET-CT with FDG (18F-fluorodeoxyglucose) impacts:
• Target volume delineation (improves visualisation of tumour extent and
nodal involvement)
• Dose
• Treatment intent & staging.
*Alters management in 30%-70% of patients
• PET-CT is in high demand (approx 40 pts/week and is funded for 1500 NS
cases per year; 2000 including OOP)
Study Objectives
PRIMARY STUDY OBJECTIVE:
 To estimate the proportion of high-risk volumes contoured that
are impacted by the use of PET-CT.
SECONDARY OUTCOMES:
A. To investigate the dosimetric impact of PET-CT:
 estimate the proportion of CT-alone CTV volumes that differed
from the PET-CT CTV volumes
 measure and estimate changes in dose to critical structures
between PET-CT and CT-alone plans
 estimate the proportion of treatment intent changes
B. To investigate the relationship between the Concordance Index
(CI) and the approved/rejected status of RT treatment plans.
SCC Tonsil pre PET-CT: T3N2bM0 (CTV-CT in blue = 118.30 cm3)
Test tx plan generated to meet QA constraints (target volume and OARs)
Post PET-CT: T3N2cM0 (CTV-PET blue + green =125.80 cm3; 6.33% increase)
“rejected plan" status = PET-CT impact
Data Analysis
SAMPLE SIZE: 186 patients
PRIMARY ANALYSIS:
Compute a point estimate of the proportion of plans impacted by PET-CT with the
associated 95% CI.
 A full CT-alone treatment plan (based on the CT-alone target volumes) is
generated in the test database. This CT-alone Tx plan meets all QA constraints
defined by the department.
 The CT-alone Tx plan is applied to the final PET-CT target volumes (ie: the
actual volumes defined/used for Tx).
 If the CT-alone plan meets all QA parameters and dose constraints, the TEST
plan is “accepted” and it is deemed that the PET-CT had no impact on the CTV
volume delineated .
 If the CT-alone plan fails the QA parameters and dose constraints, the TEST
plan is “rejected” and the PET-CT is deemed to have impacted the CTV volume
delineated.
Data Analysis
SECONDARY ANALYSES:
Change in size of CTV volume delineated: Compare CT-alone and PET-CTV
volumes (measured in cubic centimetres) using a paired t-test, considering
statistical significance at the alpha level of 0.05.
Change in dose to critical structures: Compare doses (measured in centigray)
from CT-alone plan and PET-CT plan using a paired t-test, considering
statistical significance at the alpha level of 0.05.
Relationship between CI and Plan status (approved or rejected): Binary
partitioning will be used to determine what the critical cutpoint value of CI
that optimally partitions the patients with respect to plan status.
A
B
Concordance index =
A∩B
A∪B
A∩B
B
A
300
cc
300
cc
A
A&B
B
300
cc
300
cc
300
cc
?
CI = 0
CI = 1
Geographic
Miss
PET-CT
Impact
Identical
Volumes
No PET-CT
Impact
Results….
Accrual and initial findings to date:
Head and Neck Patient Characteristics:
# of Pts
Mean Age
(years)
53
60.8
(range 45-80)
Gender
45 male
8 female
ECOG
(Modal)
1
(range 0-3)
Disease Site
Oropharynx: 33
Oral cavity: 2
Larynx: 8
Nasopharynx: 5
Primary unknown: 5
Accrual and initial findings to date:
NSCLC Patient Characteristics:
# of Pts
Mean Age
(years)
36
68.2
(range 44-88)
Gender
22 male
14 female
ECOG
(Modal)
2
(range 0-3)
Pathology
SCC: 21
Adenocarcinoma: 10
Not specified: 5
HNSCC n=49
n =46 test plan
evaluated
n= 3 test plan
not evaluated
n=3 study steps
not followed
n=1 CT-alone
contours failed
peer review
n=28
no impact
n= 18
impact
n=2 change
from radical to
palliative
n=1 change in
dose (increase)
n= 28
n=21
no impact
(57.1%)
impact
(42.9%)
n=4 not
assessed
NSCLC n=31
n =27 test plan
evaluated
n= 4 test plan
not evaluated
n=4 study steps
not followed
n=1 PET-CT
deemed not
useable by RO
n=17
no impact
n= 10
impact
n=2 change from
radical to palliative
n=2 RT cancelled
completely
n= 17
n=14
no impact
(54.8%)
impact
(45.2%)
n=5 not
assessed
Volume Size Change: H&N
CTV-CT
(cm3)
CTV-PET
(cm3)
%
Change
149.84
160.42
+11.83
Minimum
17.64
17.64
n/a
Maximum
624.98
619.58
n/a
Max Increase
n/a
n/a
+123.78
Max decrease
n/a
n/a
-17.53
Mean
41.3% (n=19) no change, 50% (n=23) increased CTVs; 8.7% (n=4) decreased CTVs
Mean absolute difference =10.58 cm3 with 95% CI (5.02, 16.13) (p<0.01)
Mean relative volume change = 11.83% with 95% CI (4.29, 19.35) (p<0.01)
Volume Size Change: NSCLC
CTV-CT
(cm3)
CTV-PET
(cm3)
%
Change
159.35
166.78
+3.08
Minimum
3.32
3.80
n/a
Maximum
415.45
453.33
n/a
Max Increase
n/a
n/a
+43.44
Max decrease
n/a
n/a
-37.33
Mean
11.1% (n=3) no change, 51.8% (n=14) increased CTV; 37.1% (n=10) decreased CTVs
Mean absolute volume = 7.42 cm3 with 95% CI (-6.86, 27.72) (p=0.29)
Mean relative volume = 3.08% with 95% CI (-4.24, 10.41) (p= 0.39)
Organs-at-risk (OARs)
 For all OARs assessed, no statistically significant
differences were noted with the exception of mean
parotid dose.
 Mean parotid dose for the right and left parotids were
significantly different (p<0.01 and p<0.03 respectively)
although the dose differences were considered
clinically insignificant.
Conclusion
 Interim analysis of data found that the use of PET-CT
in the RT planning process impacted CTV selection,
resulting in a major change in RT plans in 44% of
patients
 The CI may provide a means to predict the impact of
PET-CT on CTV delineation.
 Continuation of study to full accrual: 186 patients.
(*Final accrual of 189 patients was reached January 2014)
Next steps
 Investigate the impact of PET-CT on outcomes:
 Overall survival
 Disease free survival
 Local control
 Distant metastases
 Investigate the ability of ‘size’ vs ‘spatial’ volume
differences as means of predicting impact of a
technology
Case Studies
T2 N2a M0 SCC LT Tonsil before PET: CTV70 (red): 93.53 cm3
New RT tonsil primary found: CTV70 after PET (blue): 101.70 cm3 (8.74% increase)
T2N2bM0 SCC Lt Tonsil before PET: CTV70 (pink) = 93.29 cm3
T2N2bM0 after PET: CTV70 (pink & orange) 96.85 cm3 (3.81% increase)
T3N0M0 SCC BoT before PET: CTV70 (blue) = 173.24 cm3
T4N2cM0 after PET: CTV70 (blue & red) = 210.47 cm3 (21.49% increase)
NSCLC: Stage III before PET-CT CTV-CT (green) = 204.01 cm3
CTV-PET (blue) vol= 166.25 cm3; 18.51% decrease
(PET-CT reduced V5 from 64.0% to 46.5% and V20 from 29.8% to 22.5 %)
NSCLC: T1bN1M0 before PET-CT CTV-CT (green) = 32.84 cm3
CTV-PET (pink) vol= 25.78 cm3; 21.49% decrease
Patient restaged to T1bN0M0
NSCLC: T2N0M0 before PET-CT CTV-CT (green) = 163.24 cm3
CTV-PET (pink) vol= 225.08 cm3; 37.9% increase
Patient restaged to T2N1M0
NSCLC: before PET-CT CTV-CT (blue) = 217.28 cm3
CTV-PET (pink) vol= 174.63 cm3; 19.6% decrease
References
Gregoire V, Dainse JF, Bauvois C, et al. Selection and delineation of lymph node target volumes in head and neck neoplasms.
Cancer Radiother. 2001;5:614-628.
Messa C, Ceresoli G, Rizzo G, et al. Feasibility of 18F FDG-PET and coregistered CT on clinical target volume definition of
advanced non-small lung cancer. Q J Nucl Med Mol Imaging. 2005;49(3): 259-266.
Vorwerk H, Hess CF. Guidelines for delineation of lymphatic clinical target volumes for high conformal radiotherapy: head and
neck region. Radiat Oncol. 2011; 6:97.
Peters L, O’Sullivan B, Giralt J, et al. Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced
head and neck cancer: results from TROG 02.02. J Clin Oncol. 2010;28: 2996-3001.
Rasch C, Steenbakkers R, Fitton I, et al. Decreased 3D observer variation with matched CT-MRI, for target delineation in
nasopharynx cancer. Radiat Oncol. 2010; 5:21.
Bradley J, Bae K, Choi N, et al. A phase II comparative study of gross tumor volume definition with or without PET/CT fusion in
dosimetric planning for non-small-cell lung cancer (NSCLC): primary analysis of Radiation Therapy Oncology Group (RTOG)
0515. Int J Radiat Oncol Biol Phys. 2012;82(1):435-41.
Gupta T, Beriwal S. PET/CT-guided radiation therapy planning: From present to the future. Indian J Cancer. 2010;47(2):126-33.
Gardner M, Halimi P, Valinta D, et al. Use of single MRI and 18F-FDG PET-CT scans in both diagnosis and radiotherapy treatment
planning patients with head and neck cancer: advantage on target volume and critical organ delineation. Head and Neck.
2009;31(4):461-7.
Wasif M, Ifigenia S, Nektaria T, et al. Role and Cost Effectiveness of PET/CT in Management of Patients with Cancer. Yale J Biol
Med. Jun 2010; 83(2): 53–65. Published online Jun 2010.
Geets X, Daisne JF, Tomsej M, et al. Impact of the type of imaging modality on target volumes delineation and dose distribution in
pharyngo-laryngeal squamous cell carcinoma : a comparison between pre- and per- treatment studies. Radiother Oncol.
2006;78:291-297.
MacManus M, Hicks R. The use of positron emission tomography (PET) in the staging/evaluation, treatment, and follow-up of
patients with lung cancer: a critical review. . Int J Radiat Oncol Biol Phys. 2008;72(5):1298-1306.
Paulino A, Koshy M, Howell R, Schuster D, Davis LW. 2005. Comparison of CT- and FDG-PET-defined gross tumor volume in
intensity-modulated radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2005;61(5):1385-1392.
Marta G, Hanna S, Etchebehere E, et al. The value of positron-emission tomography/computed tomography for radiotherapy
treatment planning: a single institutional series. Nuc Med Comm. 2011;32(10): 903-907.
Hanna G, Hounsell M, O’Sullivan. Geometric analysis of radiotherapy target volume delineation: a systematic review or reported
comparison methods. J Clin Oncol. 2010;22:515-525.
Kouwenhoven E, Giezen Mm Struikmans H. Measuring the similarity of target volume delineations independent of the number of
observers. Phys in Med and Biol. 2009;54:2863-2873.
Abdolell M, LeBlanc M, Stephens D, Harrison RV. Binary partitioning for continuous longitudinal data: categorizing a prognostic
variable. Stat Med. 2002;21(22); 3395-409.
Nie Y, Li Q, Pu Y, et al. Integrating PET and CT information to improve diagnostic accuracy for lung nodules. J Nuc Med.
2006;47(7):1075-1080.
Gardner M, Halimi P, Valinta D, et al. Use of single MRI and 18F-FDG PET-CT scans in both diagnosis and radiotherapy treatment
planning in patients with head and neck cancer: advantage on target volume and critical organ delineation. Head and Neck.
2009;31(6):461-467.
Townsend D, Carney J, Yap J, Hall N. PET/CT today and tomorrow. J Nucl Med. 2004;45:4S–14S.
Schwartz D, Ford E, Rajendran J, et al. FDG-PET/CT guided intensity modulated head and neck radiotherapy: a pilot investigation.
Head and Neck. 2005;27(6):478-487
Somer E, Pike L, Marsden P. Recommendations for the use of PET and PET-CT for radiotherapy planning in research projects. Br J
Radiol. 2012 ;85:e544-e548.
Kruser T, Bradley K, Bentzen S, et al. The impact of hybrid PET-CT scan on overall oncologic management, with a focus on
radiotherapy planning: A prospective, blinded study. Technol Cancer Res Treat. 2009;8(2):149-158.
Bradley J, Dehdashti F, Mintun M, et al. Positron emission tomography in limited stage small cell lung cancer: a prospective study. J
Clin Oncol. 2004; 22:3248-3254.
Igdem S, Alco G, Ercan T, et al. The application of positron emission tomography/computed tomography in radiation treatment
planning: effect on gross target volume definition and treatment management. Clin Oncol. 2010 Apr;22(3):173-8
Scarfone C, Lavely W, Cmelak A, et al. Prospective feasibility trial of radiotherapy target definition for head and neck cancer using
3-dimensional PET and CT imaging. J Nucl Med. 2004; 45:543-52.
Nestle U, Kremp S, Grosu AL. Practical integration of [18F]-FDG-PET and PET-CT in the planning of radiotherapy for non-small
cell lung cancer (NSCLC): the technical basis, ICRU-target volumes, problems, perspectives. Radiother and Oncol. 2006;81;
209-225.
Newbold K, Partridge M, Cook G, et al. Evaluation of the role of 18-FDG-PET-CT in radiotherapy target definition in patients with
head and neck cancer. Acta Oncol. 2008;47:1229-1236.
de Figueiredo B, Barrett O, Demeaux H, et al. Comparison between CT and FDG-PET-CT-defined target volumes for radiotherapy
planning in head-and-neck cancers. Radiother and Oncol. 2009;93; 479-482.
McNulty, S. radiology.med.sc.edu/presentations/Presentation%20Sam.ppt accessed on 2013.09.25
Acknowledgements
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Dr. Derek Wilke
Prof. Mohamed Abdolell
Dr. Chris Thomas
Mr. Allan Day
Dr. Helmut Hollenhorst
Dr. Murali Rajaraman
Dr. Liam Mulroy
Dr. Dorianne Rheaume
Dr. Slawa Cwajna
Dr. Nikhilesh Patil
Dr. David Bowes
Dr. Steven Burrell