COMBITEP: PET Enhanced CT Scan Performance in Cancer

• Sponsor: Institut Bergonié (Other)
• Overall Status: Completed
• CT.gov ID: NCT01881620
• Collaborator: (none)
• Enrollment: 109
• Arm: 1
• Actual Duration (Months): 63.9

Study Details

Study Description

Brief Summary

Hypothesis:

The investigators would like to demonstrate that diagnosis performance of PET/CT scan without and with contrast agent (COMBI TEP), are equivalent or better than those of PET/ non enhanced CT scan (PET scan) associated with an enhanced CT scan. This research project is a pilot study given the few available data concerning this imaging exam reproducibility.

This study is a prospective single center study.

Condition or Disease	Intervention/Treatment	Phase
Cancer Disease Progression	Device: COMBI TEP : PET / enhanced CT scan	N/A

Detailed Description

Hypothesis:

We would like to demonstrate that diagnosis performance of PET/CT scan without and with contrast agent (COMBI TEP), are equivalent or better than those of PET/ non enhanced CT scan (PET scan) associated with an enhanced CT scan. This research project is a pilot study given the few available data concerning this imaging exam reproducibility. This study allows us to assess the feasibility of such a large-scale study, but also to evaluate COMBI TEP performance. From these estimates, we can then consider a comparative study to evaluate the performance of COMBI PET.

This study is a prospective single center study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: PET / Enhanced CT Scan Performance in Cancer (Positron Emission Tomography Combined With Computed Tomography or Vascular Contrast CT Scan). COMBI TEP Study
• Actual Study Start Date: Mar 19, 2010
• Actual Primary Completion Date: Jul 19, 2012
• Actual Study Completion Date: Jul 15, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan	Device: COMBI TEP : PET / enhanced CT scan; diagnostic imaging exam; Other Names: diagnostic imaging exam

Outcome Measures

Primary Outcome Measures

1. Inter-observer (B1 and B2) Reproducibility of the PET-CT by Anatomical Regions [1 year]

   The primary endpoint was the inter-observer reproducibility of the interpretation of the combined PET / enhanced CT scan (PET-CT) by anatomical region. Reproducibility was assessed for each of the 5 anatomical regions (thorax, abdomen, pelvis, bone, nervous system). Two independant pairs (B1 and B2), each composed of one nuclear physician and one radiologist interpreted the PET-CT examination and described each of the 5 anatomical régions according to 3 modalities (Presence of suspicious lesion(s); Presence of dubious lesion(s); Absence of suspicious and dubious lesion). The inter-observer reproducibility (inter-pairs of observers) was evaluated for each anatomical region by comparing the interpretations of the two pairs, using the weighted kappa concordance coefficient [ref = Fleiss J, Levin B, Cho Paik M. Statistical methods for rates and proportions. Third ed. 2003.].Interpretation by B1 after PET-CT examination (1 month after). Interpretation by B2 at the end of the study

Secondary Outcome Measures

1. Inter-observer (B1 and B2) Reproducibility of the PET-CT at a Patient Level [1 year]

   The inter-observer reproducibility of combined PET-CT interpretations has been assessed globally for each patient. Same pairs of observer (B1 and B2) than for the primary endpoint evaluation interpreted the PET-CT examination in a global way and concluded for each patient. A weighted Kappa coefficient has been calculated from an identical methodology to that described for the primary endpoint evaluation. Interpretation by B1 was performed at least 1 month and 1 week after PET-CT examination. Interpretation by B2 was performed at the end of the study

2. Inter-observer (N1 and B2) Reproducibility of the PET-CT by Anatomical Regions [1 year]

   For each of the 5 anatomical régions (thorax, abdomen, pelvis, bone, nervous system), we evaluated the reproducibility between the interpretations of the PET-CT by the nuclear physician alone (N1) and the independent pair (B2) composed by one nuclear physician and one radiologist . The nuclear physician alone (N1) and the independent pair (B2) interpreted the PET-CT examination independently and described each anatomical region.The inter-observer reproducibility has been evaluated for each anatomical region by comparing the interpretations of the nuclear physician alone and that one of independent pair of nuclear physician and radiologist, using the weighted kappa concordance coefficient [ref = Fleiss J, Levin B, Cho Paik M. Statistical methods for rates and proportions. Third ed. 2003.].Interpretation by nuclear physician alone (N1) was performed within 1 week of PET-CT examination. Interpretation by B2 was performed at the end of the study

3. Inter-observer (N1 and B2) Reproducibility of the PET-CT at a Patient Level [1 year]

   The inter-observer reproducibility of combined PET-CT interpretations has been assessed globally for each patient. The nuclear physician alone (N1) and the independent pair (B2) interpreted the PET-CT examination independently in a global way and concluded for each patient. The inter-observer reproducibility has been evaluated at patient level by comparing the interpretations of the nuclear physician alone and that one of independent pair of nuclear physician and radiologist, using the weighted kappa concordance coefficient [ref = Fleiss J, Levin B, Cho Paik M. Statistical methods for rates and proportions. Third ed. 2003.]. Interpretation by nuclear physician alone (N1) was performed within 1 week of PET-CT examination. Interpretation by B2 was performed at the end of the study

4. Intra-observer Reproducibility of Injected CT Scan by Anatomical Regions [1 year]

   For each anatomical region, the reproducibility of the injected CT scan was evaluated. The same radiologist evaluated the two injected CT scans (CT1 and CT2) and interpreted them (Presence of suspicious lesion(s) OR presence of dubious lesion(s) OR absence of suspicious and dubious lesion). Intra-observer reproducibility was analyzed by using the individual analysis by each radiologist. A weighted Kappa concordance coefficient was calculated per anatomical region using a methodology identical to that described for the evaluation of the proncipal endpoint. Interpretation of CT1 was performed befor inclusion. Interpretation of CT2 was performed at the end of the study.

5. Intra-observer Reproducibility of Injected CT Scanat a Patient Level [1 year]

   The reproducibility of the injected CT scan was evaluated globally for each patient. The same radiologist evaluated the two injected CT scans (CT1 and CT2) and interpreted them (Presence of suspicious lesion(s) OR presence of dubious lesion(s) OR absence of suspicious and dubious lesion). Intra-observer reproducibility was analyzed by using the individual analysis by each radiologist. A weighted Kappa concordance coefficient was calculated using a methodology identical to that described for the evaluation of the proncipal endpoint. Interpretation of CT1 was performed befor inclusion. Interpretation of CT2 was performed at the end of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Any patient with a cancerous disease for which PET scan is indicated in the SOR (Standards

• Options - Recommendations) FDG PET 2003 updated in 2006 must be included in the trial, in the following locations:

1. Digestive cancers

• Colorectal cancer

• Preoperative evaluation in local and metastatic recurrence

• Location of recurrences, in case of ACE increase in a previously operated patient.

• Esophageal cancer: initial staging.

• Pancreatic cancer

• Initial staging,

• Differential diagnosis with chronic pancreatitis.

• Liver cancer: differential diagnosis of liver metastases, cholangiocarcinoma and benign tumors in the case of an isolated hepatic localization.

• Digestive Endocrine tumors: staging in case of normal pentetreotide scintigraphy.

1. Lung cancer

• Initial staging,

• Diagnosis of lung isolated lesion > 1 cm.

1. Head and neck cancer

• Initial pretreatment staging,

• Recurrence diagnosis

1. Lymphoma

• Initial staging of Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL) and aggressive follicular lymphomas,

• Diagnosis of minimal residual disease of HD and aggressive NHL,

• Early assessment of treatment response.

1. Thyroid cancer: suspicion of residual disease or relapse when conventional imaging data are insufficient.

2. Ovarian cancer recurrence

3. Age ≥ 18 years.

4. Chest-abdomen-pelvis enhanced CT scan achieved within 4 weeks before enrollment (with cuts of less than 5 mm).

5. Woman of childbearing age with negative pregnancy test and / or contraception.

6. Patient with informed consent signed.

7. Patient affiliated to social security schemes.

Exclusion Criteria:

1. Iodine known allergy.

2. Diabetes, excepted if controlled (hemoglucotest ≤ 1.6 g).

3. Known renal failure (creatinine clearance <60ml/min).

4. Indications against Xenetix ®:

• Hypersensitivity to Xenetix ® or any of the excipients,

• History of an immediate response or delayed cutaneous reaction to Xenetix ® injection.

• Thyrotoxicosis.

1. Pregnant or lactating women.

2. Unable to undergo medical follow up for geographical, social or psychological reasons,

3. Private of freedom patient and adult under a legal guardianship or unable to consent.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Institut Bergonié

Investigators

• Study Chair: CAZEAU Anne Laure, MD, Institut Bergonié

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Site internet du promoteur, l'Institut Bergonié

Publications

None provided.

• Responsible Party: Institut Bergonié
• ClinicalTrials.gov Identifier: NCT01881620
• Other Study ID Numbers: IB2009-70
• First Posted: Jun 19, 2013
• Last Update Posted: Oct 1, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Institut Bergonié: PET scan; CT scan; Diagnostic performance
• Additional relevant MeSH terms: Disease Progression

Study Results

Participant Flow

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan : diagnostic imaging exam First, realisation of CT scan without injection followed by a PET scan (TEPSCAN) on the same Phillips GEMINI TF PET/CT camera. A few minutes after the TEPSCAN, injection CT is performed (XenetiX, iodinated contrast agent 350 mg l/mL). The COMBI TEP exam includes the TEP and the 2 series of scans (not injected low dose and injected full dose).
Period Title: Overall Study
STARTED	109
COMPLETED	105
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
Overall Participants	109
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.6 (14.2)
Sex: Female, Male (Count of Participants)
Female	46 42.2%
Male	63 57.8%
Region of Enrollment (participants) [Number]
France	109 100%
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	69.1 (15)
height (centimetre) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimetre]	168.4 (9.7)
Tumor localisation (Count of Participants)
Not available	1 0.9%
Digestive	66 60.6%
Lung	17 15.6%
Ear Nose and Throat	2 1.8%
Lymphoma	21 19.3%
Thyroid	1 0.9%
ovarian	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Inter-observer (B1 and B2) Reproducibility of the PET-CT by Anatomical Regions
Description	The primary endpoint was the inter-observer reproducibility of the interpretation of the combined PET / enhanced CT scan (PET-CT) by anatomical region. Reproducibility was assessed for each of the 5 anatomical regions (thorax, abdomen, pelvis, bone, nervous system). Two independant pairs (B1 and B2), each composed of one nuclear physician and one radiologist interpreted the PET-CT examination and described each of the 5 anatomical régions according to 3 modalities (Presence of suspicious lesion(s); Presence of dubious lesion(s); Absence of suspicious and dubious lesion). The inter-observer reproducibility (inter-pairs of observers) was evaluated for each anatomical region by comparing the interpretations of the two pairs, using the weighted kappa concordance coefficient [ref = Fleiss J, Levin B, Cho Paik M. Statistical methods for rates and proportions. Third ed. 2003.].Interpretation by B1 after PET-CT examination (1 month after). Interpretation by B2 at the end of the study
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Eligible patients with PET-CT scanner performed AND interpretation of 2 pairs of observors available.

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
Measure Participants	105
Thorax region	0.7254
Abdomen region	0.7854
Pelvis region	0.7597
Bone region	0.6711
Nervous system region	1

2. Secondary Outcome

Title	Inter-observer (B1 and B2) Reproducibility of the PET-CT at a Patient Level
Description	The inter-observer reproducibility of combined PET-CT interpretations has been assessed globally for each patient. Same pairs of observer (B1 and B2) than for the primary endpoint evaluation interpreted the PET-CT examination in a global way and concluded for each patient. A weighted Kappa coefficient has been calculated from an identical methodology to that described for the primary endpoint evaluation. Interpretation by B1 was performed at least 1 month and 1 week after PET-CT examination. Interpretation by B2 was performed at the end of the study
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Reproducibility was not calculated for 1 patient because 9 area from thorax region were not assessed by the pair of observer B2.

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
Measure Participants	104
Number (95% Confidence Interval) [weighted Kappa coefficient]	0.6528

3. Secondary Outcome

Title	Inter-observer (N1 and B2) Reproducibility of the PET-CT by Anatomical Regions
Description	For each of the 5 anatomical régions (thorax, abdomen, pelvis, bone, nervous system), we evaluated the reproducibility between the interpretations of the PET-CT by the nuclear physician alone (N1) and the independent pair (B2) composed by one nuclear physician and one radiologist . The nuclear physician alone (N1) and the independent pair (B2) interpreted the PET-CT examination independently and described each anatomical region.The inter-observer reproducibility has been evaluated for each anatomical region by comparing the interpretations of the nuclear physician alone and that one of independent pair of nuclear physician and radiologist, using the weighted kappa concordance coefficient [ref = Fleiss J, Levin B, Cho Paik M. Statistical methods for rates and proportions. Third ed. 2003.].Interpretation by nuclear physician alone (N1) was performed within 1 week of PET-CT examination. Interpretation by B2 was performed at the end of the study
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Interpretation by nuclear physician alone was not performed for 1 patient

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
Measure Participants	104
Thorax region	0.8526
Abdomen region	0.8153
Pelvis region	0.7452
Bone region	0.8722
Nervous system region	1

4. Secondary Outcome

Title	Inter-observer (N1 and B2) Reproducibility of the PET-CT at a Patient Level
Description	The inter-observer reproducibility of combined PET-CT interpretations has been assessed globally for each patient. The nuclear physician alone (N1) and the independent pair (B2) interpreted the PET-CT examination independently in a global way and concluded for each patient. The inter-observer reproducibility has been evaluated at patient level by comparing the interpretations of the nuclear physician alone and that one of independent pair of nuclear physician and radiologist, using the weighted kappa concordance coefficient [ref = Fleiss J, Levin B, Cho Paik M. Statistical methods for rates and proportions. Third ed. 2003.]. Interpretation by nuclear physician alone (N1) was performed within 1 week of PET-CT examination. Interpretation by B2 was performed at the end of the study
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Interpretation by nuclear physician alone was not performed for 1 patient. Interpretation by the pair of observor B2 was incomplete for 1 patient because 9 area from thorax region were not assessed.

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
Measure Participants	103
Number (95% Confidence Interval) [Weighted kappa concordance coefficient]	0.7859

5. Secondary Outcome

Title	Intra-observer Reproducibility of Injected CT Scan by Anatomical Regions
Description	For each anatomical region, the reproducibility of the injected CT scan was evaluated. The same radiologist evaluated the two injected CT scans (CT1 and CT2) and interpreted them (Presence of suspicious lesion(s) OR presence of dubious lesion(s) OR absence of suspicious and dubious lesion). Intra-observer reproducibility was analyzed by using the individual analysis by each radiologist. A weighted Kappa concordance coefficient was calculated per anatomical region using a methodology identical to that described for the evaluation of the proncipal endpoint. Interpretation of CT1 was performed befor inclusion. Interpretation of CT2 was performed at the end of the study.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
Measure Participants	105
Thorax region	0.8141
Abdomen region	0.7991
Pelvis region	0.7947
Bone region	-0.0095
Nervous system region	1

6. Secondary Outcome

Title	Intra-observer Reproducibility of Injected CT Scanat a Patient Level
Description	The reproducibility of the injected CT scan was evaluated globally for each patient. The same radiologist evaluated the two injected CT scans (CT1 and CT2) and interpreted them (Presence of suspicious lesion(s) OR presence of dubious lesion(s) OR absence of suspicious and dubious lesion). Intra-observer reproducibility was analyzed by using the individual analysis by each radiologist. A weighted Kappa concordance coefficient was calculated using a methodology identical to that described for the evaluation of the proncipal endpoint. Interpretation of CT1 was performed befor inclusion. Interpretation of CT2 was performed at the end of the study.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
Measure Participants	105
Number (95% Confidence Interval) [Weighted Kappa concordance coefficient]	0.7984

Adverse Events

Arm/Group Title	COMBI TEP : PET / Enhanced CT Scan
Arm/Group Description	COMBI TEP : PET / enhanced CT scan COMBI TEP : PET / enhanced CT scan: diagnostic imaging exam
All Cause Mortality
	COMBI TEP : PET / Enhanced CT Scan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	COMBI TEP : PET / Enhanced CT Scan
	Affected / at Risk (%)	# Events
Total	0/109 (0%)
Other (Not Including Serious) Adverse Events
	COMBI TEP : PET / Enhanced CT Scan
	Affected / at Risk (%)	# Events
Total	0/109 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.