IPMN, Pancreatic Cancer, Pancreatitis
Conditions
Keywords
TOF-18F-FDG PET/CT, pancreatic lesions
Brief summary
Aim of the prospective study is a better differentiation of benign and malignant lesions in the pancreas in patients with suspected pancreatic cancer using images 30 and 90 min p.i. (post injectionen) and a diagnostic CT (computed tomography) scan of the abdomen within the Time of Flight (TOF)-18F-FDG-PET/CT and thus an improvement of the quality of PET/CT findings.
Detailed description
In the course of this the procedure follows the necessary steps of routine treatment: 1. Assignment of the patient with a suspect of pancreatic cancer. 2. Performing time of flight (TOF)-18F-FDG-PET/CT with images 30 min and 90 min p.i. 3. Performing a diagnostic CT of the abdomen with parenteral contrast medium and pancreatic protocol (in case of normal creatinine, GFR, and TSH levels) as well as oral contrast medium (in accordance with the ESUR-guidelines) as part of the PET/CT examination. 4. Routine performance of the operation /fine needle puncture/biopsy 5. Routine histopathological evaluation of the surgical specimen/biopsy For this study, a diagnostic CT of the abdomen with contrast medium (intravenous as well as oral) and with pancreatic protocol and without parenteral contrast medium in case of elevated creatinine or decreased TSH (thyroid-stimulating hormone) or GFR (glomerular filtration rate) levels is performed additionally within the routinely performed PET/CT for better differentiation of the target organ from adjacent structures. Furthermore, early (30 min p.i.) and delayed (90 min p.i.) images and a TOF-reconstruction following the PET/CT examination (without patient contact) should be performed for better differentiation between inflammatory and malignant lesions of the pancreas. The regional tracer-uptake should now be measured quantitatively by SUV (Standard Uptake Value) in the TOF-PET/CT images over the FDG-accumulating lesions in the pancreas at those two times. In case of an increased FDG-uptake in the early images, the lesion will be assessed as benign/inflammatory and with an increase of the FDG-uptake in the delayed images as malignant. No FDG-uptake in the early as well as in the delayed images will be classified as benign. As a reference standard, the histopathological diagnosis is used. Subsequently, a cut-off value of the SUV should be determined by ROC-analysis. According to current scientific evidence regarding the characterization of pancreatic masses by means of Time of Flight(TOF)-technique, there are no studies in the literature.
Interventions
DIAGNOSTIC_TESTPET/CT results with TOF/without TOF
Diagnostic CT of the abdomen or upper abdomen with parenteral contrast medium (Visipaque=Iodixanol) if creatinine, GFR, and TSH levels are within the normal range and oral (water) contrast medium within TOF-18F-FDG PET/CT. In the case of elevated creatine or decreased GFR or TSH levels a diagnostic CT of the abdomen or upper abdomen without contrast medium is performed. Biopsy or FNA or operation of the pancreas.
Sponsors
Medical University of Graz
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
All parties involved in the clinical trial have knowledge of the interventions assigned to the individual participants.
Intervention model description
Prospective study with one single group with two kinds of PET/CT imaging (with TOF-reconstruction and without TOF-reconstruction) for each patient.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients with suspected pancreatic cancer
Exclusion criteria
* persons under 18 years of age * patients with blood glucose level ≥160 mg/dl at the time of the PET/CT examination * patients who will not be operated or biopsied and in which thus there are no histopathological findings of the pancreas * pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SUVmax (Maximal Standard Uptake Value) Measurement 30 and 90 Min p.i. (Post Injection) | 2 hours | Quantitative measurement of regional tracer uptake by SUVmax in the TOF-PET/CT and standard PET/CT images over the FDG-accumulating lesions in the pancreas 30 and 90min p.i. The histopathological findings (malignant or benign) were assigned to the corresponding SUVmax values of the pancreatic lesions for the calculation of AUC values in ROC analysis. Then AUC values with and without TOF were compared with the DeLong-test to analyze if there is a significant difference in characterization of pancreatic lesions with TOF. |
| Participants With Increased Tracer Uptake Over the Pancreatic Lesion With and Without TOF | 2 hours | The number of participants with increased tracer uptake over the pancreatic lesion, i.e. the number of pancreatic lesions with increased tracer uptake with and without TOF. One pancreatic lesion per patient was measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lesion Size | 2 hours | Lesion or tumor size in cm in the pancreas measured in the diagnostic CT of the abdomen or upper abdomen. |
Participant flow
Recruitment details
Participants were recruited based on physician referral at one university hospital between February 2014 and January 2019. The first participant was enrolled on February 7, 2014, and the last participant was enrolled in January 2019.
Pre-assignment details
Of 174 enrolled participants, 120 participants met ALL inclusion criteria having TOF-18F-FDG PET/CT with diagnostic CT of the abdomen or upper abdomen AND biopsy or FNA or operation of the pancreas and were analyzed. Participants not completing the study were excluded and therefore not analyzed (54 participants).
Participants by arm
| Arm | Count |
|---|---|
| PET/CT Results With TOF/Without TOF Participants received TOF-18F-FDG PET/CT 30 and 90 min p.i. and diagnostic CT of the abdomen or upper abdomen (in case of already performed diagnostic CT of the abdomen \< 2 weeks ago) with contrast medium in case of normal creatinine, GFR, and TSH levels. In the case of elevated creatinine and decreased GFR and TSH levels a diagnostic CT without contrast medium was performed. After PET/CT examination participants received biopsy or FNA or operation of the pancreas. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 54 |
Baseline characteristics
| Characteristic | PET/CT Results With TOF/Without TOF |
|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 10.4 |
| Dignity of pancreatic lesions Benign | 35 Participants |
| Dignity of pancreatic lesions Malignant | 85 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| History of pancreatitis | 21 Participants |
| Pathological diagnoses of benign pancreatic lesions Acute pancreatitis | 3 Participants |
| Pathological diagnoses of benign pancreatic lesions Benign cyst | 1 Participants |
| Pathological diagnoses of benign pancreatic lesions Chronic pancreatitis | 11 Participants |
| Pathological diagnoses of benign pancreatic lesions Highly differentiated neuroendocrine tumor | 1 Participants |
| Pathological diagnoses of benign pancreatic lesions IPMN borderline-lesion | 2 Participants |
| Pathological diagnoses of benign pancreatic lesions Mucinous cystic neoplasm (MCN) adenoma | 2 Participants |
| Pathological diagnoses of benign pancreatic lesions No indication of malignancy | 12 Participants |
| Pathological diagnoses of benign pancreatic lesions Serous cyst adenoma | 3 Participants |
| Pathological diagnoses of malignant pancreatic lesions Acinuscellcarcinoma | 1 Participants |
| Pathological diagnoses of malignant pancreatic lesions Adenocarcinoma | 70 Participants |
| Pathological diagnoses of malignant pancreatic lesions Diffuse large cell-B-cell lymphoma | 1 Participants |
| Pathological diagnoses of malignant pancreatic lesions Follicular lymphoma | 1 Participants |
| Pathological diagnoses of malignant pancreatic lesions IPMN adenocarcinoma invasive | 1 Participants |
| Pathological diagnoses of malignant pancreatic lesions IPMN carcinoma non-invasive | 2 Participants |
| Pathological diagnoses of malignant pancreatic lesions Mesenchymal neoplasia | 1 Participants |
| Pathological diagnoses of malignant pancreatic lesions Moderately differentiated neuroendocrine tumor (G2 | 2 Participants |
| Pathological diagnoses of malignant pancreatic lesions Myeloid sarcoma | 1 Participants |
| Pathological diagnoses of malignant pancreatic lesions Neuroendocrine carcinoma | 1 Participants |
| Pathological diagnoses of malignant pancreatic lesions Pancreatic intraepithelial neoplasia III(PanINIII) | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 120 Participants |
| Region of Enrollment Austria | 120 participants |
| Sex: Female, Male Female | 43 Participants |
| Sex: Female, Male Male | 77 Participants |
| Type of pancreatic mass Cystic | 23 Participants |
| Type of pancreatic mass Solid | 86 Participants |
| Type of pancreatic mass Solid-cystic | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 101 |
| other Total, other adverse events | 0 / 101 |
| serious Total, serious adverse events | 0 / 101 |
Outcome results
Primary
Participants With Increased Tracer Uptake Over the Pancreatic Lesion With and Without TOF
The number of participants with increased tracer uptake over the pancreatic lesion, i.e. the number of pancreatic lesions with increased tracer uptake with and without TOF. One pancreatic lesion per patient was measured.
Time frame: 2 hours
Population: 120 participants meeting ALL inclusion criteria, i.e. completed TOF-18F-FDG PET/CT AND biopsy or FNA or operation were analyzed. 54 participants had TOF-18F-FDG PET/CT but no biopsy or FNA or operation or the tumor was not in the pancreas and were therefore excluded from the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SUVmax TOF 30min p.i. | Participants With Increased Tracer Uptake Over the Pancreatic Lesion With and Without TOF | 116 Participants |
| SUVmax Without TOF 30min p.i. | Participants With Increased Tracer Uptake Over the Pancreatic Lesion With and Without TOF | 101 Participants |
Primary
SUVmax (Maximal Standard Uptake Value) Measurement 30 and 90 Min p.i. (Post Injection)
Quantitative measurement of regional tracer uptake by SUVmax in the TOF-PET/CT and standard PET/CT images over the FDG-accumulating lesions in the pancreas 30 and 90min p.i. The histopathological findings (malignant or benign) were assigned to the corresponding SUVmax values of the pancreatic lesions for the calculation of AUC values in ROC analysis. Then AUC values with and without TOF were compared with the DeLong-test to analyze if there is a significant difference in characterization of pancreatic lesions with TOF.
Time frame: 2 hours
Population: 120 participants meeting ALL inclusion criteria, i.e. completed TOF-18F-FDG PET/CT AND biopsy or FNA or operation were analyzed. 54 participants had TOF-18F-FDG PET/CT but no biopsy or FNA or operation or the tumor was not in the pancreas and were therefore excluded from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SUVmax TOF 30min p.i. | SUVmax (Maximal Standard Uptake Value) Measurement 30 and 90 Min p.i. (Post Injection) | 0.77 SUVmax |
| SUVmax Without TOF 30min p.i. | SUVmax (Maximal Standard Uptake Value) Measurement 30 and 90 Min p.i. (Post Injection) | 0.78 SUVmax |
| SUVmax TOF 90min p.i. | SUVmax (Maximal Standard Uptake Value) Measurement 30 and 90 Min p.i. (Post Injection) | 0.81 SUVmax |
| SUVmax Without TOF 90min p.i. | SUVmax (Maximal Standard Uptake Value) Measurement 30 and 90 Min p.i. (Post Injection) | 0.8 SUVmax |
Comparison: It was calculated that 118 participants would have at least 90% power to demonstrate an improvement in specificity of 25% (to 70%) with the new method assuming a specificity of the current method of 45% at a prevalence of malignant lesions of 70% (corresponding to 30% benign lesions). Assumptions included a discontinuation rate of 25%.p-value: 0.78DeLong-test
p-value: 0.95DeLong-test
Secondary
Lesion Size
Lesion or tumor size in cm in the pancreas measured in the diagnostic CT of the abdomen or upper abdomen.
Time frame: 2 hours
Population: 120 participants meeting ALL inclusion criteria, i.e. completed TOF-18F-FDG PET/CT AND biopsy or FNA or operation were analyzed. 54 participants had TOF-18F-FDG PET/CT but no biopsy or FNA or operation or the tumor was not in the pancreas and were therefore excluded from the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SUVmax TOF 30min p.i. | Lesion Size | 3.0 cm | Standard Deviation 1.67 |