Good clinical practice recommendations for the use of PET/CT in oncology.

Positron emission tomography/computed tomography (PET/CT) is a nuclear medicine functional imaging technique with proven clinical value in oncology. PET/CT indications are continually evolving with fresh advances made through research. French practice on the use of PET in oncology was framed in recommendations based on Standards-Options-Recommendations methodology and coordinated by the French federation of Comprehensive Cancer Centres (FNLCC). The recommendations were originally issued in 2002 followed by an update in 2003, but since then, a huge number of scientific papers have been published and new tracers have been licenced for market release. The aim of this work is to bring the 2003 version recommendations up to date. For this purpose, a focus group was set up in collaboration with the French Society for Nuclear Medicine (SFMN) to work on developing good clinical practice recommendations. These good clinical practice recommendations have been awarded joint French National Heath Authority (HAS) and French Cancer Institute (INCa) label status-the stamp of methodological approval. The present document is the outcome of comprehensive literature review and rigorous appraisal by a panel of experts, organ specialists, clinical oncologists, surgeons and imaging specialists. These data were also used for the EANM referral guidelines.

Prognostic impact of postoperative 123I-metaiodobenzylguanidine scintigraphy: added value of SPECT/CT and semiquantification of the uptake at the surgical site.

BACKGROUND: The aim of this study was to assess the prognostic value of postoperative 123I-MIBG scintigraphy, including systematic SPECT/CT and semiquantification of the uptake at the surgical site, in a prospective series of NB patients. METHODS: Patients operated for neuroblastoma and who had benefited from postoperative 123I-MIBG scintigraphy were prospectively and consecutively included. Completeness of surgery was assessed on operative report. One month postoperative 123I-MIBG scintigraphy included planar acquisition and SPECT/CT. Semi-quantification of the 123I-MIBG SPECT/CT uptake at the surgical site was performed and ratios to reference (liver and mediastinum) areas were calculated. RESULTS: Thirty patients were included between August 2012 and July 2015. Median follow-up was 36 months (range 10-98). Surgery was considered as complete in 23 patients and incomplete in 7 patients. Eight patients (26.7%) presented progressive disease (1 progression and 7 recurrences). Seven patients died (23.3%), all from NB. Six (20%) patients had positive 123I-MIBG scintigraphy (3 on planar acquisitions and 6 on SPECT/CT) and 24 patients had negative 123I-MIBG scintigraphy. Five of the 6 patients (83%) with positive 123I-MIBG scintigraphy presented progressive disease. Ratio of the uptake at the surgical site to mediastinum was strongly and independently correlated with disease-free interval and overall survival (P=0.02 and 0.01 respectively). The amplified MYCN status was also confirmed as correlated with poorer outcomes. CONCLUSIONS: Postoperative 123I-MIBG scintigraphy including SPECT/CT and semiquantification of the uptake at the surgical site appeared to be a valuable prognostic tool in neuroblastoma.

¹8F-FDG PET/CT imaging versus dynamic contrast-enhanced CT for staging and prognosis of inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer with a poor prognosis. Locoregional staging is based on dynamic contrast-enhanced (DCE) CT or MRI. The aim of this study was to compare the performances of FDG PET/CT and DCE CT in locoregional staging of IBC and to assess their respective prognostic values. METHODS: The study group comprised 50 women (median age: 51 ± 11 years) followed in our institution for IBC who underwent FDG PET/CT and DCE CT scans (median interval 5 ± 9 days). CT enhancement parameters were net maximal enhancement, net early enhancement and perfusion. RESULTS: The PET/CT scans showed intense FDG uptake in all primary tumours. Concordance rate between PET/CT and DCE CT for breast tumour localization was 92%. No significant correlation was found between SUVmax and CT enhancement parameters in primary tumours (p > 0.6). PET/CT and DCE CT results were poorly correlated for skin infiltration (kappa = 0.19). Ipsilateral foci of increased axillary FDG uptake were found in 47 patients (median SUV: 7.9 ± 5.4), whereas enlarged axillary lymph nodes were observed on DCE CT in 43 patients. Results for axillary node involvement were fairly well correlated (kappa = 0.55). Nineteen patients (38%) were found to be metastatic on PET/CT scan with a significant shorter progression-free survival than patients without distant lesions (p = 0.01). In the primary tumour, no statistically significant difference was observed between high and moderate tumour FDG uptake on survival, using an SUVmax cut-off of 5 (p = 0.7 and 0.9), or between high and low tumour enhancement on DCE CT (p > 0.8). CONCLUSION: FDG PET/CT imaging provided additional information concerning locoregional involvement to that provided by DCE CT on and allowed detection of distant metastases in the same whole-body procedure. Tumour FDG uptake or CT enhancement parameters were not correlated and were not found to have any prognostic value.

FCH-PET/CT in Primary Hyperparathyroidism With Discordant/Negative MIBI Scintigraphy and Ultrasonography.

CONTEXT: The contribution of [18F]F-fluorocholine (FCH)-positron emission tomography (PET)/computed tomography (CT) in normocalcemic primary hyperparathyroidism (nPHPT) remains unknown. OBJECTIVE: To evaluate the sensitivity and specificity of FCH-PET/CT in a cohort of osteoporotic patients with nPHPT and discordant or negative [99mTc]Tc-sestamibi scintigraphy and ultrasonography who all underwent parathyroidectomy (PTX). DESIGN: Longitudinal retrospective cohort study in patients referred for osteoporosis with mild biological primary hyperparathyroidism. SETTING: Tertiary referral center with expertise in bone metabolism and surgical management of hyperparathyroidism. PATIENTS: Among 109 patients with PHPT analyzed, 3 groups were individualized according to total serum calcium (tCa) and ionized calcium (iCa): 32 patients with hypercalcemia (HtCa group), 39 patients with normal tCa and elevated iCa (NtCa group), and 38 patients with both normal tCa and iCa (NiCa). All patients had biochemical follow-up confirming or not the success of PTX. MAIN OUTCOME MEASURES: To evaluate the performance of FCH-PET/CT in terms of sensitivity and specificity, and to compare with first-line imaging procedures in the setting of nPHPT. RESULTS: The sensitivity of FCH-PET/CT was 67% in the hypercalcemic group, 48% in the NtCa group (P = .05 vs HtCa), and 33% in the NiCa group (P = .004 vs HtCa). Specificity ranged from 97% to 99%. FCH-PET/CT was positive in 64.3% of patients with negative conventional imaging, with biochemical resolution after PTX in 77.8% of patients. Triple negative imaging was observed in 20 patients, with PHPT resolution in 85% of these patients. CONCLUSION: This study highlights the contribution of FCH-PET/CT in a well-phenotyped cohort of normocalcemic patients with discordant or negative findings in [99mTc]Tc-sestamibi scintigraphy and ultrasonography. However, negative imaging in nPHPT does not rule out the possibility of surgical cure by an experienced surgeon.

18F-fluorocholine PET/CT and conventional imaging in primary hyperparathyroidism.

PURPOSE: The purpose of this study was to assess the diagnostic capabilities of preoperative conventional imaging (99mTc-MIBI scintigraphy, cervical ultrasonography [CUS]) and 18F-fluorocholine PET/CT (FCH PET/CT) in the detection of hyperfunctioning parathyroid gland in patients with primary hyperparathyroidism (PHPT) used alone or as a single imaging set. MATERIALS AND METHODS: A total of 51 consecutive patients (6 men, 45 women; mean age, 62 ± 11.6 [SD] years; age range: 28-86 years) with biochemically confirmed PHPT who underwent CUS, single-tracer dual phase 99mTc-MIBI scintigraphy and FCH PET/CT were retrospectively included. 99mTc-MIBI scintigraphy were performed immediately after CUS and interpreted by the same operators. FCH PET/CT examinations were interpreted independently by two nuclear medicine physicians. An additional reading session integrating the three imaging modalities read in consensus as a combined imaging set was performed. RESULTS: At surgery, 74 lesions were removed (32 parathyroid adenomas, 38 parathyroid hyperplasia and 4 subnormal glands). Thirty-six patients (71%) had single-gland disease and 15 patients (29%) had multiglandular disease at histopathological analysis. On a patient basis, sensitivity and accuracy of FCH PET/CT, CUS and 99mTc-MIBI scintigraphy for the detection of abnormal parathyroid glands were 76% (95% CI: 63-87%) and 76% (95% CI: 63-87%), 71% (95% CI: 56-83%) and 71% (95% CI: 56-83%), 33% (95% CI: 21-48%) and 33% (95% CI: 21-48%), respectively. The sensitivity of the combined imaging set was 94% (95% CI: 84-99%) and greater than the sensitivity of each individual imaging technique (P ≤ 0.001 for all). CONCLUSION: Our results suggest that CUS, 99mTc-MIBI scintigraphy and FCH PET/CT interpreted as a single imaging set could be the ideal practice to precisely localize parathyroid lesion in patients with PHPT before surgery.

Prognostic Value of FDG-PET/CT Parameters in Patients with Relapse/Refractory Multiple Myeloma before Anti-CD38 Based Therapy.

Although anti-CD38 monoclonal antibodies have improved the prognosis of relapsed/refractory multiple myeloma (RRMM), some patients still experience early relapses with poor outcomes. This present study evaluated the predictive value of FDG PET/CT parameters for RRMM prior to initiating anti-CD38 treatment. We included 38 consecutive RRMM patients who underwent a PET/CT scan treated at our institution at relapse. The median PFS was 12.5 months and the median OS was not reached. 42% of the patients had an initial ISS score of 1, 37% of 2, and 21% of 3. The presence of >3 focal lesions (FLs, n = 19) and the ISS score were associated with inferior PFS (p = 0.0036 and p = 0.0026) and OS (p = 0.025 and p = 0.0098). Patients with >3 FLs had a higher initial ISS score (p = 0.028). In multivariable analysis, the ISS score and >3 FLs were independent prognostic factors for PFS (p = 0.010 and p = 0.025 respectively), and combined they individualized a high-risk group with a median PFS and OS of 3.1 months and 8.5 months respectively vs. not reached for the other patients. The presence of >3 FLs on PET was predictive of survival outcomes in patients with RRMM treated using CD38 targeted therapy. Combined with the initial ISS, an ultra-high-risk RRMM population can thus be identified.

[Update of the recommendations of good clinical practice for the use of PET in oncology]. / Actualisation des recommandations de bonne pratique clinique pour l'utilisation de la TEP en cancérologie.

Positron Emission Tomography (PET) is a functional nuclear medicine imaging technique which clinical value in oncology has been demonstrated. PET indications are constantly evolving, thanks to the contribution of research. The use of PET in oncology has been the subject of recommendations according to the Standard-Options-Recommendations methodology from the Fédération Nationale des Centres de Lutte Contre le Cancer in 2002, updated in 2003. However, many scientific works have been published since 2003 and new tracers have also obtained a marketing authorization in France. The objective of this work was therefore to update the recommendations established in 2003. In this context, in collaboration with the Société française de médecine nucléaire, a working group was set up for the development of good clinical practice recommendations under the HAS-INCA methodological label. The present document is issued from a comprehensive review of the literature and rigorous appraisal by a panel of national experts, organ specialists, clinical oncologists, surgeons, and imaging specialists. It is intended to be used as a guide to decision-making for those oncology teams that are able to manage patients in various situations in which the AMM label is not sufficiently precise.

High and typical 18F-FDG bowel uptake in patients treated with metformin.

PURPOSE: This prospective and bi-centric study was conducted in order to determine the impact of antidiabetic treatments (AD) on (18)F-FDG bowel uptake in type 2 diabetic patients. METHODS: Fifty-five patients with previously diagnosed and treated type 2 diabetes mellitus (group 1) were divided in two subgroups: AD treatment including metformin (n=32; group 1a) and AD treatment excluding metformin (n=23; group 1b). The 95 patients without diabetes mellitus made up controls (group 2). (18)F-FDG uptake in small intestine and colon was visually graded and semi-quantitatively measured using the maximum standardized uptake value. RESULTS: (18)F-FDG bowel uptake was significantly increased in AD patients (group 1) as compared to controls (group 2) (p<0.001). Bowel uptake was significantly higher in AD patients including metformin (group 1a) as compared to AD patients excluding metformin (group 1b) (p<0.01), whose bowel uptake was not significantly different from controls (group 2). A metformin treatment was predictive of an increased bowel uptake in the small intestine (odds ratio OR=16.9, p<0.0001) and in the colon (OR=95.3, p<0.0001), independently of the other factors considered in the multivariate analysis. Bowel uptake pattern in the patients treated with metformin was typically intense, diffuse and continuous along the bowel, strongly predominant in the colon, in both the digestive wall and lumen. CONCLUSION: This study emphasizes that metformin significantly increases (18)F-FDG uptake in colon and, to a lesser extent, in small intestine. It raises the question of stopping metformin treatment before an (18)F-FDG PET/CT scan is performed for intra-abdominal neoplasic lesion assessment.

Impact of FDG PET-CT imaging on the decision making in the biologic suspicion of ovarian carcinoma recurrence.

OBJECTIVES: The aim of this prospective study was to evaluate the impact of integrated PET-CT on treatment management in ovarian carcinoma recurrence suspicion because of increased CA-125. METHODS: Twenty-nine patients (mean age=61 years), initially treated for ovarian carcinoma (FIGO stage I n=2, stage II n=3, stage III n=21 and stage IV n=3), presenting with increased CA-125 (mean=160 IU/ml, range 33-1930), underwent subsequently a CT and a PET-CT scans. The recurrence was acknowledged by the referring physicians for all patients. The impact of PET-CT on patient's management was evaluated by comparing the therapeutic decision mentioned respectively on the pre and post PET-CT questionnaires filled in by the oncologists. RESULTS: The CT scan was positive in 22/29 patients (76%) and negative in 7/29 patients (24%). The PET-CT scan was positive in 27/29 patients (93%) and negative in 2/29 (7%) patients. Five out of the seven patients with a negative CT scan had a positive PET-CT scan. In comparison to CT scan alone, the PET-CT scan modified the disease distribution for 16 patients (55%; p<0.001) in the following ways: more advanced disease (n=11), more limited disease (n=4), and different localizations (n=1). The assessment of pre and post PET-CT questionnaires showed a statistically significant change in the decision making for 10 patients (34%, p<0.0001). CONCLUSION: This questionnaire-based study showed that PET-CT imaging allows a better restaging than CT and induces a change in clinical management in over one third of patients with suspected ovarian carcinoma recurrence on increased CA-125.

Diagnosis and localization of renal cyst infection by 18F-fluorodeoxyglucose PET/CT in polycystic kidney disease.

Renal cyst infection in polycystic kidney disease is a serious complication. Early diagnosis and localization of infected cyst are crucial and usually require conventional imaging modalities, including ultrasound and computed tomography (CT). However, their contribution is limited because of nonspecific results. We report on a patient with suspected renal cyst infection for which 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan allowed the exact localization of the infected cyst and guided a drainage procedure. FDG-PET/CT imaging could be a valuable tool for early identification of infected renal cyst infection, and may contribute to better patient management.

In search of an unknown primary tumour presenting with cervical metastases: performance of hybrid FDG-PET-CT.

OBJECTIVES: In patients with cervical lymph node metastases from unknown primary tumour (UPT), the primary tumour is frequently localized in the head and neck area. Because the detection of the primary tumour is of importance to optimize the patient's management and allows a targeted therapy, the performances of hybrid positron emission tomography-computed tomography (PET-CT) using fluorodeoxyglucose (FDG) were evaluated in a retrospective study. METHODS: Thirty-eight consecutive patients with cervical lymph node metastases, and in whom the primary was not detected by the comprehensive diagnostic work-up including endoscopy and conventional imaging methods, were referred for a PET-CT scan. RESULTS: PET-CT was positive with an increased FDG focal uptake suggesting the potential primary site in 68% of patients (26/38), which guided the biopsies during a second rigid panendoscopy in 17 of these 26 patients: 13 primary tumours were then histologically proven. PET-CT showed distant lesions in three patients. It had treatment-related implications in 23/38 patients (60%), consisting of modification of radiation planning, surgery or abstention from surgery. CONCLUSION: Hybrid FDG-PET-CT is helpful for the detection of a potential head and neck primary tumour. Furthermore, hybrid FDG-PET-CT has the ability to diagnose occult or distant second tumour and metastatic disease and modify patient management.

[The role of PET scan in gastrointestinal stromal tumors]. / Place de l'imagerie par Tomographie par Emission de Positons pour les tumeurs stromales gastro-intestinales.

Abdominal CT is considered the imaging method of choice for the staging and treatment monitoring of Gastrointestinal Stromal Tumors (GIST). The role of Whole-body FDG-PET seems limited for staging because of the low rate of extra-abdominal tumoral involvement and lower sensitivity than CT. However, PET provides assessment of therapeutic response to imatinib as early as 8 days after treatment is begun. The decrease in the metabolic tumor activity is often marked and intense and it is easier to evaluate than changes in tumor shrinkage and density measured on CT. PET may also be useful when morphological findings are unclear, treatment efficacy uncertain or when progression is identified on CT scan, especially when these findings do not agree with clinical data. PET and CT are complementary and hybrid PET/CT systems have been shown to be useful in GIST. PET may be proposed for the assessment of treatment response in prospective studies with imatinib or other molecules. In patients with GIST, FDG-PET should be performed based on a pluridisciplinary decision.

Rate of Distant Metastases on 18F-FDG PET/CT at Initial Staging of Breast Cancer: Comparison of Women Younger and Older Than 40 Years.

Women who have breast cancer and are younger than 40 y have a poorer outcome than older women. A higher rate of undetected metastases at the time of diagnosis in younger women has been proposed to account for this difference. Our main objective was to test this hypothesis by comparing the distant metastasis rate (DMR) on initial 18F-FDG PET/CT in a group of breast cancer patients younger than 40 y (<40 y group) with that in a group of breast cancer patients older than 40 y (≥40 y group). An assessment of associations between distant metastases and tumor characteristics was a second objective of the present study. METHODS: A retrospective single-institution study was performed on women who had breast cancer and no prior malignancy, who were asymptomatic for metastatic lesions on initial clinical examination, and who had initial 18F-FDG PET/CT within 3 mo after pathologic breast cancer diagnosis and before initial treatment. On the basis of these criteria, data for 2 groups of women differing only in age (<40 y and ≥40 y) were extracted from the hospital information system of Curie Institute-Paris. 18F-FDG PET/CT examinations were reviewed, and the DMR was recorded for each clinical stage subgroup (stages I-III). RESULTS: For each group (<40 y and ≥40 y), 107 patients were included, with the same number of patients in each clinical stage subgroup (12 stage I patients, 32 stage IIA patients, 30 stage IIB patients, and 33 stage III patients). The ages of the patients (mean ± SD) were 34.5 ± 4.0 y (<40 y group) and 56.0 ± 10.7 y (≥40 y group). No significant difference in DMRs was observed between the <40 y group and the ≥40 y group (DMRs, 21% and 22%, respectively; P = 1). The DMRs in patients not selected for age were 8% for stage I, 11% for stage IIA, 15% for stage IIB, and 44% for stage III. CONCLUSION: The DMR was not significantly higher in younger breast cancer patients (<40 y) than in older breast cancer patients (≥40 y), ruling out the assumption that undetected metastases at diagnosis explain the poorer outcome of younger women. However, our results highlight the high yield of 18F-FDG PET/CT for initial breast cancer staging, even in stage II patients, whatever their age.

[Positron emission tomography (PET) in gastro-intestinal cancer]. / La tomographie par émission de positons (TEP) en oncologie digestive.

The existing recommendations for fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) use in digestive cancers (excluding neuroendocrine tumours) are summarized in the present article. FDG-PET/CT is nowadays a routine imaging modality for digestive malignancies and its use is currently increasing. FDG-PET/CT is considered to be a crucial tool in pretherapeutic assessment of esophageal, localized pancreatic and anal cancer. It represents a key exam in suspicion of recurrence of colorectal cancer in case of elevated serum tumor markers. New data are emerging regarding FDG-PET/CT in therapeutic efficacy assessment, radiotherapy treatment planning and detection of recurrence in many digestive cancers. Incidental focal colonic FDG uptake has to be explored by colonoscopy, as often associated with premalignant or malignant lesions.

[FDG (18 fluorodeoxyglucose) positron emission tomography and breast cancer]. / Tomographie par emission de positons (TEP) au FDG et cancer du sein.

Positron emission tomography (PET) is a metabolic radionuclide imaging method in which a tracer labeled with a positron emitter is detected with a dedicated system. 18F-fluorodeoxyglucose (FDG) accumulates in tumor cells because of their increased glycolytic activity, and is thus widely used as a tracer in oncology. This increased metabolic activity precedes morphologic modifications, making FDG-PET a very useful tool for detecting and staging cancer. It can also be used to characterize morphologic changes, differentiating not only between benign and malignant lesions, but also between viable tumor cells and areas of necrosis and/or fibrosis induced by treatments. Being a whole-body examination, it allows malignancies to be staged in a single procedure. Systems combining PET and CT (computed tomography) offer improved performance, providing both metabolic and anatomical data. This technique appears to be useful for initial breast cancer staging, especially of locally advanced forms and suspected recurrences (increase of isolated tumor marker). Early studies of PET evaluation of responses to hormonal and/or cytotoxic therapies have also given very promising results. However, this technique does not seem sufficiently sensitive to be included in the initial screening or diagnosis of primary tumors, owing to its limited resolution (about 5 mm) and its restricted availability. This approach is poorly sensitive when used for axillary assessment, but offers good specificity.

Weak uptake of 123I-MIBG and 18F-FDOPA contrasting with high 18F-FDG uptake in stage I neuroblastoma.

Hypertension in a 6-year-old girl was the presenting sign of a stage I neuroblastoma. This tumor corresponded to a left adrenal gland mass. Hypertension resolved immediately after complete surgical resection of the tumor with an uneventful follow-up (24 months at the present time). Preoperative assessment by nuclear medicine techniques showed weak uptake of I-MIBG and F-FDOPA contrasting with high F-FDG uptake by the tumor.

18F-FDG PET/CT to Predict Response to Neoadjuvant Chemotherapy and Prognosis in Inflammatory Breast Cancer.

UNLABELLED: The aim of this prospective study was to assess the predictive value of (18)F-FDG PET/CT imaging for pathologic response to neoadjuvant chemotherapy (NACT) and outcome in inflammatory breast cancer (IBC) patients. METHODS: Twenty-three consecutive patients (51 y ± 12.7) with newly diagnosed IBC, assessed by PET/CT at baseline (PET1), after the third course of NACT (PET2), and before surgery (PET3), were included. The patients were divided into 2 groups according to pathologic response as assessed by the Sataloff classification: pathologic complete response for complete responders (stage TA and NA or NB) and non-pathologic complete response for noncomplete responders (not stage A for tumor or not stage NA or NB for lymph nodes). In addition to maximum standardized uptake value (SUVmax) measurements, a global breast metabolic tumor volume (MTV) was delineated using a semiautomatic segmentation method. Changes in SUVmax and MTV between PET1 and PET2 (ΔSUV1-2; ΔMTV1-2) and PET1 and PET3 (ΔSUV1-3; ΔMTV1-3) were measured. RESULTS: Mean SUVmax on PET1, PET2, and PET3 did not statistically differ between the 2 pathologic response groups. On receiver-operating-characteristic analysis, a 72% cutoff for ΔSUV1-3 provided the best performance to predict residual disease, with sensitivity, specificity, and accuracy of 61%, 80%, and 65%, respectively. On univariate analysis, the 72% cutoff for ΔSUV1-3 was the best predictor of distant metastasis-free survival (P = 0.05). On multivariate analysis, the 72% cutoff for ΔSUV1-3 was an independent predictor of distant metastasis-free survival (P = 0.01). CONCLUSION: Our results emphasize the good predictive value of change in SUVmax between baseline and before surgery to assess pathologic response and survival in IBC patients undergoing NACT.