Transcript Colorectal Cancer

Positron Emission Tomography
in Clinical Oncology
Chun Ki Kim, M.D.
Mount Sinai School of Medicine
New York, New York
Commonly used PET
Radiotracers
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[F-18] FDG
- Glucose metabolism
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[C-11] Methionine
- Amino acid transport
- Incorporation of amino acid
into protein fractions
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[O-15] Water
[N-13] Ammonia
Rb-82
- Blood flow
- Blood flow
- Blood flow
Potential PET Radiotracers
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[C-11] Thymidine
[C-11] Aminoisobutyric acid
[F-18] 5-FU
[C-11] Tyrosine
[N-13] Glutamate
Tumor cellular proliferation rate
Tumor amino acid uptake
Prediction/evaluation of ChemoTx
Tumor metabolism
Tumor metabolism
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[C-11] Acetate
[C-11] Palmitate
Myocardial oxidative metabolism
Myocardial fatty acid metabolism
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[F-18] FluoroDOPA
Many other receptor agents
Dopamine synthesis
Dopamine, serotonin, opiate etc.
PET Radiotracer approved
by FDA
• [F-18] FDG
(fluoro deoxyglucose)
 Malignancy ~  Glucose / FDG uptake
NORMAL
TUMOR
• Overexpression of Glucose transporters
• Higher levels of Hexokinase
• Down-regulation of Glucose-6-phosphatase
• Anaerobic glycolysis, less ATP per glucose molecule,
more glucose molecules needed for ATP production
• General increase in metabolism from high growth rates
 Malignancy
 Glucose/FDG uptake
Gallium
PET
Metastatic Thyroid Ca. to Lung, Mediastinum, and Skeleton
General Indications for FDG-PET Tumor Imaging
 DDx: Benign versus Malignant
 Staging & Restaging
 Metastatic work up: Rising tumor markers
 Monitoring treatment response
 Scar/necrosis/fibrosis vs. Recurrent/residual disease
 Grading/Prognosis
 Detection of unknown primary
New Medicare Coverage Policy for FDG PET
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Lung Ca (NSC):
Esophgeal Ca:
Colorectal Ca:
Lymphoma:
Melanoma:
Dx, Staging & restaging
Dx, Staging & restaging
Dx, Staging & restaging
Dx, Staging & restaging
Dx, Staging & restaging,
Non-covered for evaluating regional nodes
Head & Neck Ca: Dx, Staging & restaging
Lung Cancer
Dx: Solitary Pulmonary Nodule
Staging
Metastatic work-up
Solitary Pulmonary Nodule
• Incidence detected by CXR: 130,000/year.
50-60%: Benign
20-40%: Invasive nodule biopsy
Resection.
CT: an indeterminant
LUL nodule.
Efficacy of PET
Solitary Pulmonary Nodule
• Sensitivity = 97%
• Specificity = 78%
(Meta-analysis of >40 articles: Gould et al. JAMA 2001)
False Positives:
Active Infection/Inflammation
TB
Pneumonia
Cryptococcosis
Histoplasmosis
Aspergillosis
Inflammatory
Staging
60/M: Lung Ca.
62y/o Lung Ca. with adrenal mass
Colorectal Cancer:
Clinical Indications for PET Imaging
 Staging before primary resection?
 Detection of Lesions after Primary Resection
Staging before resection of recurrent disease.
Rising CEA in the absence of a known source.
Equivocal/residual lesion on conventional imaging.
Patient is clinically symptomatic, but CEA is normal.
 Monitoring treatment response (pre-op & post-op)
Staging before resection of recurrent disease
63 y/o woman with a H/O Colon Ca.
and liver metastases
79/M. Resection of Rectal Ca (Dukes B) 4
mos earlier,
 CEA, CT: possible local relapse.
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F/68
H/O Colon Ca.
Rising CEA
CT/MRI;
multiple cysts
T1
T2
T1 enhanced
T1 enhanced
Sagittal
Transverse
Coronal
YW: Colon Ca
• 3/00: (-) CT
• 5/00: rising CEA
• 6/00: (+) PET
• 7/00: CT
58/M - S/P Colon Ca
Rising CEA
Coronal
Coronal
Transverse
58/M - S/P Colon Ca
Rising CEA
Hemangioma
Local recurrence
• 48y/o with Colon Ca.
• S/P Primary resection.
• S/P Resection of liver
lesion
• Now with  CEA
• CT: (-) for mets
• 48y/o with Colon Ca.
• S/P Primary resection.
• S/P Resection of liver
lesion
• Now with  CEA
• CT: (-) for mets
N. G. 8/15/00
Colon cancer with a Hx of UC
Proven mesenteric carcinomatosis
1756441
Huebner et al. J Nucl Med 2000;41:1177-1189
Huebner et al. J Nucl Med 2000;41:1177-1189
Colorectal Cancer: A possible algorithm
CT evidence
of resectable
disease in
patient
suitable for
surgery
Whole
Body
PET
imaging
Colorectal Cancer: A possible algorithm
Further evaluation
of CT abnormality
All sites negative
CT evidence
of resectable
disease in
patient
suitable for
surgery
Whole
Body
PET
imaging
Colorectal Cancer: A possible algorithm
Further evaluation
of CT abnormality
All sites negative
CT evidence
of resectable
disease in
patient
suitable for
surgery
Whole
Body
PET
imaging
PET = CT and other sites negative
Surgery
Colorectal Cancer: A possible algorithm
Further evaluation
of CT abnormality
All sites negative
CT evidence
of resectable
disease in
patient
suitable for
surgery
Whole
Body
PET
imaging
PET = CT and other sites negative
+ ve at multiple
Sites
Non-surgical
management
Surgery
Staging:
44/F with Colon Ca, S/P primary resection.
CT: multiple liver mets and a lung nodule
Treated with systemic chemoTx instead of
intra-arterial chemoTx.
Colorectal Cancer:
Clinical Indications for PET Imaging
 Detection of Lesions
 Staging before resection of recurrent disease.
 Rising CEA in the absence of a known source.
 Equivocal/residual lesion on conventional imaging.
 Patient is clinically symptomatic, but CEA is normal.
 Monitoring treatment response (pre-op & post-op)
 Staging before primary resection?
S/P ChemoRx
Before
2mo after
Adjuvant chemo and radioTx
Prior to surgery for rectal Ca.
Residual FDG activity after treatment:
Not always active tumor
Uptake may be seen in inflammatory tissue / macrophages.
Optimal time to scan after treatment??
• 1 month after Chemo.
PET findings at 1 mo ~ CT findings at 3 mos
Findlay et al. J Clin Oncol 1996
• Several months after RT?
Lymphoma:
Indications for PET Imaging
 Dx
 Staging
 Monitoring treatment response
 Recurrence?
Evaluation of early therapeutic response:
Is treatment effective?
FDG uptake represents cell viability.
 FDG uptake can be markedly decreased or even
completely suppressed after 1 or 2 cycles of
chemotherapy
 Early determination is important:
To avoid the toxicity of ineffective therapy.
To allow selection of a new therapeutic regimen.
1846641
Lymphoma
Before
After
2 cylcles of
Chemo
Lymphoma
Before
After
2 cylcles of
Chemo
56y/o : Lymphoma
Before
1 month after XRT
Esophageal/Gastro-esophageal Cancer:
Clinical Indications for PET Imaging
Pre-op staging
Monitoring treatment response
Suspected recurrence
Prognostication
Esophageal/ Gastro-esophageal Cancer:
Clinical Indications for PET Imaging
Pre-op staging
CT:
Limited sensitivity
EUS: More accurate for assessing local
invasion and regional nodal mets.
Limitations: stenosis,
celiac,
right hepatic lobe,
peritoneum
Evaluation of N stage of patients with Esophageal Cancer:
48 patients underwent esohagectomy and lymph node
dissection (2 field=35pts, 3 field=13pts)
(Choi et al: J Nucl Med 2000)
Evaluation of metastases in Esophageal Cancer:
CT versus PET
CT
PET
Kole 1998
Lymph nodes
Resectability
62%
65%
90%
88%
Choi 2000
Lymph nodes
N staging
78%
60%
86%
83%
Luketich 1999
Distant mets
63%
84%
Rt. Paratracheal
Rt. Paratracheal
Subcarinal
Subcarinal
Lt. Gastric
Lt. Gastric
Common hepatic
&
Celiac
Common hepatic
&
Celiac
62F: Gastric Ca. S/P Resection
CT: Recurrence
PET performed to exclude other sites of tumor
Ultrasound: confirmed a liver mets
Surgery cancelled and the patient treated with Chemo
Gastro-esophageal Cancer:
Clinical Indications for PET Imaging
Pre-op staging
Monitoring treatment response
Suspected recurrence
Prognostication
49M: large squamous esophageal Ca.
Echo-endoscopy – an enlarged node
Before
sagittal
After
Radiochemo
coronal
Gastro-esophageal Cancer:
Clinical Indications for PET Imaging
Pre-op staging
Monitoring treatment response
Suspected recurrence
Prognostication
45M: S/P esophagectomy,
Patient is clinically asymptomatic
 alkaline phosphatase
Gastro-esophageal Cancer:
Clinical Indications for PET Imaging
Pre-op staging
Monitoring treatment response
Suspected recurrence
Prognostication
Surviavl based on initial PET scan identification of
distant versus local disease only:
(Luketich et al: Ann Thorac Surg 1999;68)
Pancreatic Cancer:
Potential Indications for PET Imaging
 DDx: Chronic pancreatic mass vs. Cancer
 Staging: Nodal mets and liver mets.
 Monitoring treatment response
 Prognostication
53/F:
Pancreatic mass
51F: CT:
(1) Mass forming pancreatitis vs Cancer
(2) Hepatic Hemangioma vs Metastasis
Coronal
Sagittal
Pancreatic Cancer:
DDx: Chronic pancreatic mass vs. Cancer
Delbeke et al: J Nucl Med 1999
Brain Tumor
 Grading
 Prognosis/Survival.
Necrosis or Residual disease after
radiation therapy?
High Grade
Low Grade
Kim CK et al. J Neuro-Oncol 1991
Thyroid Cancer
Thyroglobulin (+)
Iodine-131 scan (-)
FDG PET scan is useful.
FDG-PET
L
I-131
M
M
I
2 Coronal slices
V
Anterior
Posterior
62 y/o male
S/P Resection of transglottic right laryngeal cancer
R/O Recurrence
FDG PET Imaging
Determination of the site of
unknown primary tumor
20~30%
Prediction of tumor response to treatment:
Will the tumor respond to treatment?
 Labeled Estrogen
 [F-18] 5-Fluorouracil (5-FU)
FDG-PET Tumor Imaging
 DDx: Is the lesion benign or malignant?
 Staging:
Re-staging:
 Evaluation of early therapeutic response:
 Scar/Necrosis vs recurrent/residual disease after surgery.
Scar/Necrosis vs recurrent/residual disease after XRT.
 Histologic grading / Prognosis.
 Detection of unknown primary.
Summary: PET
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Safe.
Shows all the organ systems of the body with one image.
Decreases the number of diagnostic (imaging) procedures.
Diagnoses disease often before it shows up on other tests.
Shows the progress of disease and how the body responds
to treatment.
Reduces or eliminates ineffective or unnecessary surgical
or medical treatments and hospitalization.
Significantly reduces multiple medical costs and avoids
needless pain to the patient.
The influence of blood glucose levels
on 18FDG uptake in cancer
(Crippa et al. Tumori 1997:83:748-752)
8 patients - 20 liver metastases on CT
• PET 1: Fasting (92.4±10.2)
All 20 were (+) on PET.
• PET 2: Glucose infusion (158±13.8)
6/20 undetected, and 10 lesions localized
less clearly.
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70-years-old female smoker
CT showed Rt mid lung mass and inhomogeneity
throughout the liver
Coronal
Sagittal
55 y/o woman
Dx’ed with colon ca.
S/P resection 2 yrs
ago
CEA level is rising
No evidence of
recurrence.
CT: normal.