[en] We initially conducted a prospective study evaluating diagnostic interest of FDG PET-CT for head and neck squamous cell carcinomas subclinical recurrence. Our results showed FDG PET-CT high performance in systematic monitoring, especially for the diagnosis of recurrence in about one third of clinically asymptomatic patients 1 year after the end of treatment. Secondly, we studied the benefits of early treatment evaluation by FDG PET-CT after 2 cycles of neoadjuvant chemotherapy by DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy in a cohort of patients with locally advanced cancer (stage III-IVA). Our results showed a statistically significant correlation between metabolic tumor response and recurrence-free survival, suggesting the interest of an interim PET scan to early target patients refractory to treatment. Then, we prospectively analyzed the prognostic impact of FDG PET-CT performed at initial staging in order to select earlier this population at risk for recurrence. The results of our two studies proved that the use of volumetric or kinetic parameters of intratumoral FDG uptake was predictive of overall survival, with an independent prognostic value and a higher performance to SUV_max. Thus, this thesis opens new perspectives indications of FDG PET-CT in the management of head and neck squamous cell carcinoma, raises research issues such as the emergence of new tracers to characterize at best the tumor cell and falls within a current commitment to move towards a personalized preventive and predictive medicine. (author)

[en] 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.

[en] The objective of this study was to investigate the value of metabolic tumour volume (MTV) assessed with ¹⁸F-FDG PET/CT in predicting event-free survival (EFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC), and particularly to compare it with more conventional parameters such as maximum standardized uptake value (SUVmax). Patients referred to our department for ¹⁸F-FDG PET/CT for staging of HNSCC were prospectively included between February 2009 and March 2011. Each patient was scanned using a Philips Gemini PET/CT system at 1 h after injection. The MTV was calculated semiautomatically for the primary site using methods based on SUV with various thresholds: 3-D contour around voxels equal to or greater than 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 and 7.0 times SUV, or more than 30 %, 40 % and 50 % of SUVmax. ROC analysis was used to test the statistical significance of the differences among the calculated MTVs. EFS and OS were determined using the Kaplan-Meier method and compared with MTV in univariate and multivariate analyses, including the usual prognostic factors: age, sex, primary site, treatment, SCC histologic grade, AJCC stage, TNM classification, tumour SUVmax and SUVpeak. The study included 80 consecutive patients (70 men, 10 women; mean age 62.4 ± 9.0 years). ROC analysis revealed that pretreatment MTV using a threshold of 5.0 times SUV (MTV5.0) was the best parameter to predict recurrence and death after treatment. In univariate analysis, MTV5.0 >4.9 ml was predictive of poor EFS (p < 0.0001) and poor OS (p < 0.0001). In multivariate, MTV5.0 persisted as an independent predictive factor for EFS (p = 0.011) and OS (p = 0.010), while SUVmax became nonsignificant (p = 0.277 for EFS, p = 0.975 for OS). Our results suggest that MTV measured by ¹⁸F-FDG PET/CT has independent prognostic value of in patients with HNSCC, stronger than SUVmax. (orig.)

[en] Posttreatment follow-up for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination or conventional imaging. Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is widely validated for the diagnosis of suspected recurrence. Moreover, we have shown in a previous prospective study the high effectiveness of FDG PET/CT in the assessment of subclinical recurrence 12 months after treatment. The aim of this prospective study was to evaluate the effectiveness of an earlier FDG PET/CT, at 6 months after the end of treatment. All patients treated for histologically proven HNSCC from April 2009 to May 2012 at the University Hospital of Brest who did not show any findings suggestive of recurrence at 6 months of their usual follow-up underwent an FDG PET/CT examination. FDG PET/CT findings were correlated with histopathology or imaging follow-up. The study included 116 patients. FDG PET/CT examinations were performed within a mean period ± SD of 5.6 ± 1.8 months after treatment. FDG PET/CT examinations exhibited abnormal FDG uptake in 34 patients and found no suspected recurrence in 82 cases. Of these 82 FDG PET/CT considered as negative, only 1 had a recurrence. Among the 34 positive FDG PET/CT, 22 relapsed whereas 12 did not show evidence of recurrence. The sensitivity and specificity of FDG PET/CT in this study for the diagnosis of occult HNSCC recurrence were 96 (22/23) and 87 % (81/93), respectively. The positive predictive value was 65 % (22/34). The negative predictive value was 99 % (81/82). The overall accuracy was 89 % (103/116). Of the 116 patients, FDG PET/CT highlighted 22 (19 %) subclinical recurrences. Our study showed the high effectiveness of FDG PET/CT in the assessment of subclinical HNSCC recurrence 6 months after completion of treatment. These results confirmed that FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC, as we previously demonstrated in patients clinically asymptomatic at 12 months. (orig.)

[en] Locally advanced head and neck squamous cell carcinoma (HNSCC) has a high rate of recurrence. Induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy could lead to the best disease control of inoperable stage III/IV HNSCC but with an increased risk of acute toxicity. Early assessment of therapeutic efficacy is a key issue in considering the benefit of escalation in a poor prognosis population. Patients with stage III/IV HNSCC, in whom DCF induction chemotherapy followed by concurrent chemoradiotherapy had been validated by a multidisciplinary team, were prospectively included in the study. FDG PET/CT scans were performed in all patients before and after two of the three cycles of DCF. EORTC99 criteria were used to evaluate PET responses as follows: group 1 (metabolic responders) showing a complete response (CR) or partial response (PR), and subgroup 0 (metabolic nonresponders) showing stable disease (SD) or progressive disease (PD). The primary endpoint for monitoring patients was event-free survival (EFS). EFS probabilities between the two groups were estimated by the Kaplan-Meier method and statistically compared using the log-rank test. Fifteen consecutive patients (14 men, 1 woman; age 57.5 ± 6.2 years, mean ± SD) were analysed. Therapeutic assessment by PET/CT demonstrated CR in four patients, PR in six, SD in four and PD in one. Among the ten patients with a metabolic response (group 1), none had relapsed at the time of this report, while four of five patients with no metabolic response (group 0) showed recurrence within an average of 9.0 ± 1.6 months. Median EFS was, respectively, 18.9 months (3.8-25.3 months) and 10.2 months (7.5-12.7 months) in group 1 and group 0. The corresponding 1-year EFS rates were 100 % and 20 %, respectively. The difference in EFS between the two groups was statistically significant (p = 0.0014). Early therapeutic response demonstrated on FDG PET/CT after two cycles of induction chemotherapy with DCF in patients with inoperable stage III/IV HNSCC seems to be a predictive factor for EFS. (orig.)

[en] The aim of this management outcome study was to assess the safety of ventilation/perfusion single photon emission computed tomography (V/Q SPECT) for the diagnosis of pulmonary embolism (PE) using for interpretation the criteria proposed in the European Association of Nuclear Medicine (EANM) guidelines for V/Q scintigraphy. A total of 393 patients with clinically suspected PE referred to the Nuclear Medicine Department of Brest University Hospital from April 2011 to March 2013, with either a high clinical probability or a low or intermediate clinical probability but positive D-dimer, were retrospectively analysed. V/Q SPECT were interpreted by the attending nuclear medicine physician using a diagnostic cut-off of one segmental or two subsegmental mismatches. The final diagnostic conclusion was established by the physician responsible for patient care, based on clinical symptoms, laboratory test, V/Q SPECT and other imaging procedures performed. Patients in whom PE was deemed absent were not treated with anticoagulants and were followed up for 3 months. Of the 393 patients, the prevalence of PE was 28 %. V/Q SPECT was positive for PE in 110 patients (28 %) and negative in 283 patients (72 %). Of the 110 patients with a positive V/Q SPECT, 78 (71 %) had at least one additional imaging test (computed tomography pulmonary angiography or ultrasound) and the diagnosis of PE was eventually excluded in one patient. Of the 283 patients with a negative V/Q SPECT, 74 (26 %) patients had another test. The diagnosis of PE was finally retained in one patient and excluded in 282 patients. The 3-month thromboembolic risk in the patients not treated with anticoagulants was 1/262: 0.38 % (95 % confidence interval 0.07-2.13). A diagnostic management including V/Q SPECT interpreted with a diagnostic cut-off of ''one segmental or two subsegmental mismatches'' appears safe to exclude PE. (orig.)

[en] Cardiac positron emission tomography (PET) imaging suffers from image blurring due to the constant motion of the heart that can impact interpretation. Hybrid PET/magnetic resonance (MR) has the potential to use radiation-free MR imaging to correct for the effects of cardio-respiratory motion in the PET data, improving qualitative and quantitative PET imaging in the heart. The purpose of this study was (i) to implement a MR image-based motion-corrected PET/MR method and (ii) to perform a proof-of-concept study of quantitative myocardial PET data in patients.

The proposed method takes reconstructions of respiratory and cardiac gated PET data and applies spatial transformations to a single reference frame before averaging to form a single motion-corrected PET (MC-PET) image. Motion vector fields (MVFs) describing the transformations were derived from affine or non-rigid registration of respiratory and cardiac gated MR data.

Eight patients with suspected cardiac sarcoidosis underwent cardiac PET/MR imaging after injection of 5 MBq kg⁻¹ of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Myocardial regions affected by motion were identified by expert readers within which target-to-background ratios (TBR) and contrast-to-noise ratios (CNR) were measured on non-MC-non-gated, MC-PET, and double respiratory and cardiac gated PET images. Paired t-tests were used to determine statistical differences in quantitative uptake-measures between the different types of PET images.

MC-PET images showed less blurring compared to non-MC-non-gated PET and tracer activity qualitatively aligned better with the underlying myocardial anatomy when fused with MR. TBR and CNR were significantly greater for MC-PET (2.8  ±  0.9; 21  ±  22) compared to non-MC-non-gated PET (2.4  ±  0.9, p  =  0.0001; 15  ±  13, p  =  0.02), while TBR was lower and CNR greater compared to double-gated PET (3.2  ±  0.9, p  =  0.04; 6  ±  3, p  =  0.004).

This study demonstrated in a patient cohort that motion-corrected (MC) cardiac PET/MR is feasible using a retrospective MR image-based method and that improvement in TBR and CNR are achievable. MC PET/MR holds promise for improving interpretation and quantification in cardiac PET imaging. (paper)

[en] 

Background

: The standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant K_i expected from ¹⁸F-Sodium Fluoride (¹⁸F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for ¹⁸F-NaF and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) PET/MR cardiovascular imaging.

Methods

: We introduce 5-class K_i/MR-AC for (i) ¹⁸F-NaF studies where the bones are segmented from Patlak K_i images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class K_i/MR-AC for (ii) ¹⁸F-FDG-only data, with a streamlined simultaneous administration of ¹⁸F-FDG and ¹⁸F-NaF at 4:1 ratio (R4:1), or (iii) for ¹⁸F-FDG-only or both ¹⁸F-FDG and ¹⁸F-NaF dual-tracer data, by administering ¹⁸F-NaF 90 minutes after an equal ¹⁸F-FDG dosage (R1:1). The K_i-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD).

Results

: In rabbits, we observed similar (< 1.2% mean difference) vertebral bone ¹⁸F-NaF SUV_mean scores when applying 5-class AC with K_i-segmented bone (5-class K_i/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUV_mean bias was reduced by 17.6% (¹⁸F-NaF) and 15.4% (R4:1) with 5-class K_i/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher ¹⁸F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean ¹⁸F-FDG:¹⁸F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (¹⁸F-FDG) and 15.5% (¹⁸F-NaF) at carotid bifurcations and 21.6% (¹⁸F-FDG) and 22.5% (¹⁸F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication.

Conclusions

: K_i-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance ¹⁸F-NaF and ¹⁸F-FDG contrast and quantification in bone tissues and carotid walls.

[en] To develop machine learning models to predict para-aortic lymph node (PALN) involvement in patients with locally advanced cervical cancer (LACC) before chemoradiotherapy (CRT) using ${}^{18}$F-FDG PET/CT and MRI radiomics combined with clinical parameters. We retrospectively collected 178 patients (60% for training and 40% for testing) in 2 centers and 61 patients corresponding to 2 further external testing cohorts with LACC between 2010 to 2022 and who had undergone pretreatment analog or digital ${}^{18}$F-FDG PET/CT, pelvic MRI and surgical PALN staging. Only primary tumor volumes were delineated. Radiomics features were extracted using the Radiomics toolbox${}^{\mathrm{\circledR <!--\; ??\; -->}}$. The ComBat harmonization method was applied to reduce the batch effect between centers. Different prediction models were trained using a neural network approach with either clinical, radiomics or combined models. They were then evaluated on the testing and external validation sets and compared. In the training set (n = 102), the clinical model achieved a good prediction of the risk of PALN involvement with a C-statistic of 0.80 (95% CI 0.71, 0.87). However, it performed in the testing (n = 76) and external testing sets (n = 30 and n = 31) with C-statistics of only 0.57 to 0.67 (95% CI 0.36, 0.83). The ComBat-radiomic (GLDZM_HISDE_PET_FBN64 and Shape_maxDiameter2D3_PET_FBW0.25) and ComBat-combined (FIGO 2018 and same radiomics features) models achieved very high predictive ability in the training set and both models kept the same performance in the testing sets, with C-statistics from 0.88 to 0.96 (95% CI 0.76, 1.00) and 0.85 to 0.92 (95% CI 0.75, 0.99), respectively. Radiomic features extracted from pre-CRT analog and digital ${}^{18}$F-FDG PET/CT outperform clinical parameters in the decision to perform a para-aortic node staging or an extended field irradiation to PALN. Prospective validation of our models should now be carried out.

[en] 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 Federation 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 Societe francaise de medecine nucleaire, 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. (authors)