The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy

Background: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. Methods: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). Results: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. Conclusions: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination

The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy

Background: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. Methods: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). Results: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5–46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. Conclusions: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination

Lymphome de Hodgkin concomitant d'une tuberculose, un challenge thérapeutique pour une prise en charge pluridisciplinaire

International audienceHodgkin lymphoma (HL) is a disease characterized by a high curability rate, and the treatment benefit-risk balance must be carefully addressed to achieve complete disease control with low risk of long-term toxicities. Most patients are treated with a combination of chemotherapy and radiotherapy, after disease staging and response to treatment evaluated by FDG PET/CT. We report the case of a 28-year-old patient concomitantly diagnosed of a Hodgkin lymphoma and active tuberculosis. Initial staging was difficult due to pulmonary and abdominal tuberculosis localization that induced FDG PET/CT hypermetabolism. Anti-tuberculosis treatment was first started, allowing secondary an early accurate Hodgkin lymphoma staging by FDG PET/CT. The patient was then treated by chemotherapy and radiotherapy. Helical TomoTherapy® was used with involved site (IS) irradiation volume was performed to decrease the high doses to organs-at-risk (OAR), especially lungs in this context of tuberculosis

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

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Can we identify "twin patients" to predict response to neoadjuvant chemotherapy in breast cancer?

International audienceObjectives: Most supervised learning approaches currently applied in radiomics consist in classifying patients in groups (eg, responder versus non-responder, short overall survival versus long overall survival). With these methods, individual information from each patient is used only to assign a patient to a group. To preserve detailed information of each patient, we are developing an alternative approach that consists in identifying a "twin patient" based on radiomic features and clinical parameters in a patient database, i.e. another patient with feature values similar to the ones observed in the tested patient. Here, we studied whether this approach could predict the response to neoadjuvant chemotherapy in breast cancer patients. Methods: 117 patients with a triple-negative breast cancer were included in this study. All patients underwent a baseline 18F-FDG PET/CT using Gemini GXL 16 (Philips, 41 patients) or Discovery 710 Elite (GE, 76 patients) with a standard imaging protocol, before a neo-adjuvant chemotherapy associating anthracycline and taxane. The pathological response was assessed on the surgical specimen after chemotherapy according to the Residual Cancer Burden (RCB score). Based on PET images, the primary lesion of each patient was segmented using a threshold set to 40% of SUVmax, and a 6 mm thick ring around the tumor region was also used to measure the peri-tumoral metabolic activity. In each resulting volume of interest, we computed 48 radiomic features using LIFEx software (intensity resampling: 128 gray-levels between 0 and 40 SUV; spatial resampling: 2x2x2 mm) [1]. Radiomic features were harmonized between the two PET devices using ComBat [2]. The profile of each patient included 96 radiomic features and 3 clinical variables (age, Ki-67 expression, body mass index), each expressed as z-score. Using a leave-one-out approach, we computed the Euclidian distance between the profile of the tested patient and the profiles of all patients of the database. The smallest distance was used to identify the twin of the tested patient. This procedure was repeated by defining profiles including only 2, 4 and 6 features using a systematic feature selection process. The performance was evaluated using the Youden Index (YI=Sensitity+Specificity-1) to predict the response to neoadjuvant chemotherapy. Results: In our cohort, 68 patients were identified as responders to therapy and 49 patients as non-responders. Without feature selection, YI was 0.13 (Se=45% ; Sp=68%). When using 2 features only, the best performance was obtained for the combination of Entropy_Tumor and LZE_Ring with YI=0.36 (Se=59% ; Sp=76%). With 4 features, the best YI (=0.50) was obtained by adding Energy_Ring and SRE_Ring to Entropy_Tumor and LZE_Ring (Se=73% ; Sp=76%). With 6 features, the best combination was obtained by adding LZE_Tumor and LZHGE_Ring, yielding a YI of 0.56 (Se=80% ; Sp=76%). When we selected features, clinical variables were never included in the best combination, and radiomic features extracted from the peri-tumoral regions (ring) improved the identification of relevant twins. Conclusion: We demonstrated that the so called "twin patients" defined as sharing a number of similar radiomic features were likely to present similar response to neo-adjuvant chemotherapy. Feature selection improved the performance by including only features relevant to the prediction task into the profile. Unlike the conventional group-based patient management, the twin approach uses the detailed individual information of each patient previously treated. Further studies involving an independent cohort and more features in the combination are underway to further explore the potential of this concept. The identification of patient similarities also acts as a discovery approach to formulate new biological hypotheses, for instance, highlighting here the association between peri-tumoral heterogeneity and response to therapy

Esthesioneuroblastoma in children, adolescents and young adults

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Role of 18F-FDG-PET/CT in the staging of metastatic rhabdomyosarcoma: a report from the European paediatric Soft tissue sarcoma Study Group

Background: Initial staging of rhabdomyosarcoma is crucial for prognosis and to tailor the treatment. The standard radiology workup (SRW) includes magnetic resonance imaging, chest computed tomography (CT) and bone scintigraphy, but 18 Fluorine-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (18F-FDG-PET/CT (PET-CT)) use is increasing. The aim of this study was to evaluate the impact of PET-CT in the initial staging of patients with metastatic rhabdomyosarcoma enrolled in the European protocol MTS2008. Methods: Two authors retrospectively reviewed the SRW and PET-CT reports comparing the number and sites of metastases detected. For bone marrow involvement, PET-CT and bone marrow aspirates/biopsies were compared. Results: Among 263 metastatic patients enrolled from October 2008 to December 2016, 121 had PET-CT performed at diagnosis, and for 118 of 121 patients, both PET-CT and radiological reports were available for review. PET-CT showed higher sensitivity than SRW in the ability to detect locoregional (96.2% versus 78.5%, P value = 0.0013) and distant lymph node involvement (94.8% versus 79.3%, P value = 0.0242), but sensitivity was lower for intrathoracic sites (lung 79.6% versus 100%, P value = 0.0025). For bone metastasis, PET-CT was more sensitive than bone scintigraphy (96.4% versus 67.9%, P value = 0.0116). The PET-CT sensitivity and specificity to detect marrow involvement were 91.8% and 93.8%, respectively. The mean number of metastatic sites was 1.94 (range 0–5) with PET-CT and 1.72 (range 0–5) with SRW. In four patients (3.4%), PET-CT changed the staging from localised to metastatic disease. Conclusion: PET can identify metastatic disease not evident on SRW in a small number of patients. This is because of its higher ability to recognise lymph node and bone involvement. Chest CT remains essential to detect lesions in intrathoracic sites, which can be performed in a one stop-shot routine examination or on a dedicated chest CT scan. PET-CT could replace bone scintigraphy to study bone involvement

18F]FDG PET/CT for predicting triple-negative breast cancer outcomes after neoadjuvant chemotherapy with or without pembrolizuma

International audiencePurpose: To determine if pretreatment [18F]FDG PET/CT could contribute to predicting complete pathological complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy with or without pembrolizumab. Methods: In this retrospective bicentric study, we included TNBC patients who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy (NAC) or chemo-immunotherapy (NACI) between March 2017 and August 2022. Clinical, biological, and pathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from the PET images. Cut-off values were determined using ROC curves and a multivariable model was developed using logistic regression to predict pCR. Results: N = 191 patients were included. pCR rates were 53 and 70% in patients treated with NAC (N = 91) and NACI (N = 100), respectively (p 12.3), and low TMTV (≤ 3.0 cm3) were predictors of pCR in the NAC cohort while tumor staging classification ( 17.2), and low TMTV (≤ 7.3 cm3) correlated with pCR in the NACI cohort. In multivariable analysis, only high tumor SUVmax (NAC: OR 8.8, p < 0.01; NACI: OR 3.7, p = 0.02) and low TMTV (NAC: OR 6.6, p < 0.01; NACI: OR 3.5, p = 0.03) were independent factors for pCR in both cohorts, albeit at different thresholds. Conclusion: High tumor metabolism (SUVmax) and low tumor burden (TMTV) could predict pCR after NAC regardless of the addition of pembrolizumab. Further studies are warranted to validate such findings and determine how these biomarkers could be used to guide neoadjuvant therapy in TNBC patients

Nasopharyngeal carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations

AbstractNasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Main recommendations include induction chemotherapy with cisplatin and 5‐flurouracil, concomitant chemoradiotherapy in advanced disease, and to consider maintenance treatment with interferon beta (IFN‐β) for selected high‐risk patients. Dose adjustments of radiotherapy based on response to induction chemotherapy may decrease the rates of long‐term treatment‐related complications that affect most of the survivors

Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT) for the detection of bone, lung, and lymph node metastases in rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common paediatric soft‐tissue sarcoma and can emerge throughout the whole body. For patients with newly diagnosed RMS, prognosis for survival depends on multiple factors such as histology, tumour site, and extent of the disease. Patients with metastatic disease at diagnosis have impaired prognosis compared to those with localised disease. Appropriate staging at diagnosis therefore plays an important role in choosing the right treatment regimen for an individual patient. Fluorine‐18‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET) is a functional molecular imaging technique that uses the increased glycolysis of cancer cells to visualise both structural information and metabolic activity. 18F‐FDG‐PET combined with computed tomography (CT) could help to accurately stage the extent of disease in patients with newly diagnosed RMS. In this review we aimed to evaluate whether 18F‐FDG‐PET could replace other imaging modalities for the staging of distant metastases in RMS. Objectives To determine the diagnostic accuracy of 18F‐FDG‐PET/CT imaging for the detection of bone, lung, and lymph node metastases in RMS patients at first diagnosis. Search methods We searched MEDLINE in PubMed (from 1966 to 23 December 2020) and Embase in Ovid (from 1980 to 23 December 2020) for potentially relevant studies. We also checked the reference lists of relevant studies and review articles; scanned conference proceedings; and contacted the authors of included studies and other experts in the field of RMS for information about any ongoing or unpublished studies. We did not impose any language restrictions. Selection criteria We included cross‐sectional studies involving patients with newly diagnosed proven RMS, either prospective or retrospective, if they reported the diagnostic accuracy of 18F‐FDG‐PET/CT in diagnosing lymph node involvement or bone metastases or lung metastases or a combination of these metastases. We included studies that compared the results of the 18F‐FDG‐PET/CT imaging with those of histology or with evaluation by a multidisciplinary tumour board as reference standard. Data collection and analysis Two review authors independently performed study selection, data extraction, and methodological quality assessement according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2). We analysed data for the three outcomes (nodal involvement and lung and bone metastases) separately. We used data from the 2 × 2 tables (consisting of true positives, false positives, true negatives, and false negatives) to calculate sensitivity and specificity in each study and corresponding 95% confidence intervals. We did not consider a formal meta‐analysis to be relevant because of the small number of studies and substantial heterogeneity between studies. Main results Two studies met our inclusion criteria. The diagnostic accuracy of 18F‐FDG‐PET/CT was reported in both studies, which included a total of 36 participants. We considered both studies to be at high risk of bias for the domain reference standard. We considered one study to be at high risk of bias for the domain index test and flow and timing. Sensitivity and specificity of 18F‐FDG‐PET/CT for the detection of bone metastases was 100% in both studies (95% confidence interval (CI) for sensitivity was 29% to 100% in study one and 40% to 100% in study two; 95% CI for specificity was 83% to 100% in study one and 66% to 100% in study two). The reported sensitivity of 18F‐FDG‐PET/CT for the detection of lung metastases was not calculated since only two participants in study two showed lung metastases, of which one was detected by 18F‐FDG‐PET/CT. Reported specificity was 96% in study one (95% CI 78% to 100%) and 100% (95% CI 72% to 100%) in study two. The reported sensitivity for the detection of nodal involvement was 100% (95% CI 63% to 100% in study one and 40% to 100% in study two); the reported specificity was 100% (95% CI 78% to 100%) in study one and 89% (95% CI 52% to 100%) in study two