BACKGROUND:Adrenal tumours are frequently detected by conventional imaging. However, computed tomography and magnet resonance imaging have limited specificity in classifying the most prevalent tumour type, adrenocortical adenoma (ACA), which typically does not require surgery. We proposed that combined molecular imaging with [18F]Fluorodeoxyglucose-positron emission tomography (FDG PET) and [123I]Iodometomidate-single photon emission tomography (IMTO SPECT) improves non-invasive classification of ACA. METHODS:This cross-sectional, multicentre diagnostic study included patients (≥30 years) with non-functioning indeterminate adrenal masses (>3 cm or increase >1 cm, Hounsfield units [HU] ≥10 on unenhanced computed tomography [CT]) scheduled for surgery. Using histopathology as the reference, we assessed the accuracy of FDG/IMTO imaging as an ACA-test, assuming that low FDG with high IMTO uptake is indicative of ACA, with a focus on high specificity and moderate to high sensitivity. We also investigated its accuracy in detecting or excluding adrenocortical carcinoma (ACC) and evaluated FDG and unenhanced CT in assessing malignancy. TRIAL-REGISTRATION:EudraCT 2012-003604-13; ClinicalTrials.gov-identifier NCT02010957. FINDINGS:From July 2015 to December 2020, 85 patients were enrolled, with 77 included in the final analysis (53 benign, 30 ACA, 9 ACC). FDG/IMTO-imaging classified ACA with high specificity (95·7% [95% CI 85·2%-99·47%]), high positive predictive value (87·5% [95% CI 61·7%-98·4%]) and high positive likelihood ratio (11·1 [95% CI 3·2-122]). However, sensitivity was low (48·3% [95% CI 29·4%-67·5%]) due to moderate/high FDG uptake in 14 of 30 ACA. Malignant masses were classified with high sensitivity but low-to-moderate specificity by both unenhanced CT (cut-off HU ≥20 sensitivity 100% [95% CI 85·8%-100%], specificity 26·4% [95% CI 15·3%-40·3%]) and FDG (visual analysis sensitivity 95·8% [95% CI 78·9%-99·9%], specificity 62·3% [95% CI 47·9%-75·2%]). All four study-related AEs were grade 1, the seven serious AEs were not study-related. INTERPRETATION:Combined FDG/IMTO-imaging classifies ACA with high specificity, potentially reducing unnecessary surgery. A sub-group of FDG-positive ACA lowers sensitivity. FUNDING:German Research Foundation and EU-FP7.

BackgroundPredictors for checkpoint inhibitor-related pneumonitis (cinrPneumonitis) are desperately needed. This study aimed to investigate the pretreatment standardized uptake value (SUV) on [18F]FDG-PET/CT of non-tumorous lung tissue as a predictive imaging marker for the development of cinrPneumonitis in 239 patients with lung cancer.MethodsAll patients with lung cancer receiving [18F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) prior to immune checkpoint inhibitor (ICI) therapy were included and retrospectively analyzed. Pretreatment SUVMEAN, SUVMAX, SUV95, SUV normalized by lean body mass (SULMEAN, SULMAX) and clinical variables were compared for patients with and without cinrPneumonitis. Logistic regression analyses were performed to identify the predictive value of pretreatment SUV for the development of cinrPneumonitis.ResultsA total of 239 patients were included, of whom 41 (17.2%) developed cinrPneumonitis. The pretreatment radioligand uptake (SUVMEAN, SUVMAX, SUV95, SULMEAN and SULMAX) was not significantly elevated in patients who developed cinrPneumonitis. Logistic regression using sex, age, body mass index and chronic obstructive pulmonary disease as covariables additionally showed no significant association between pretreatment radioligand uptake and the risk of cinrPneumonitis. However, an increased likelihood of developing cinrPneumonitis (relative risk = 1.979; p = 0.027) was shown in patients who received thoracic radiation during ICI therapy.ConclusionThis is the largest study on the association of pretreatment radioligand uptake of the non-tumorous lung and the risk of a cinrPneumonitis. Our results showed no significant association between elevated pretreatment radioligand uptake of non-tumorous lung tissue on FDG-PET/CT and the development of cinrPneumonitis.

Somatostatin-receptor (SSTR)—targeting PET/CT is widely used for diagnosis and disease monitoring of pheochromocytoma / paraganglioma (PPGL). The aim of this study was to assess the potential of the novel SSTR-targeting tracer [18F]SiTATE in diagnosing PPGL by comparing imaging parameters to tumor marker levels and secretory activity in a small cohort of patients diagnosed with this rare tumor type. This retrospective study included 34 patients with histologically confirmed PPGL who underwent [18F]SiTATE-PET/CT at LMU University Hospital Munich between 10/2020 and 02/2024 as well as hormonal laboratory analysis within up to 100 days. Imaging parameters — standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion uptake (TLU) — were analyzed. Uptake was normalized to liver background (SUVmaxr, SUVmeanr). Radioligand uptake of biochemical subtypes and genotypes was compared with Mann-Whitney-U test. Correlation was tested using Spearman´s rank correlation test. The patient-based detection rate of [18F]SiTATE-PET was 96.6

The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. Systematic studies are required to confirm this preliminary experience and to understand underlying mechanisms.

Background: A debate persists on the prognostic value of the pre-therapeutic standardized uptake value (SUV) of non-tumorous lung tissue for the risk assessment of therapy-related pneumonitis, with most studies lacking significant correlation. However, the influence of patient comorbidities on the pre-therapeutic lung SUV has not yet been systematically evaluated. Thus, we aimed to elucidate the association between comorbidities, biological variables and lung SUVs in pre-therapeutic [18F]FDG-PET/CT. Methods: In this retrospective study, the pre-therapeutic SUV in [18F]FDG-PET/CT was measured in non-tumorous areas of both lobes of the lung. SUVMEAN, SUVMAX and SUV95 were compared to a multitude of patient characteristics and comorbidities with Spearman’s correlation analysis, followed by a Bonferroni correction and multilinear regression. Results: In total, 240 patients with lung cancer were analyzed. An elevated BMI was significantly associated with increased SUVMAX (β = 0.037, p < 0.001), SUVMEAN (β = 0.017, p < 0.001) and SUV95 (β = 0.028, p < 0.001). Patients with chronic obstructive pulmonary disease (COPD) showed a significantly decreased SUVMAX (β = −0.156, p = 0.001), SUVMEAN (β = −0.107, p < 0.001) and SUV95 (β = −0.134, p < 0.001). Multiple other comorbidities did not show a significant correlation with the SUV of the non-tumorous lung. Conclusions: Failure to consider the influence of BMI and COPD on the pre-therapeutic SUV measurements may lead to an erroneous interpretation of the pre-therapeutic SUV and subsequent treatment decisions in patients with lung cancer.

Background: Lung cancer is increasingly treated with immune-checkpoint inhibitors (ICI). Checkpoint inhibitor-associated pneumonitis (CIP) decreases the quality of life and survival of patients immediately and may limit subsequent treatment options for survivors. Aims: The aim of this research was to analyze clinical factors and biomarkers associated with pneumonitis in lung cancer patients under ICI. Methods: We analyzed data of 293 patients with lung cancer and ICI therapy. We distinguished between any pneumonitis and CIP. Using univariate logistic regression, we identified patient and clinical characteristics, and therapy significantly associated with pneumonitis. Significant factors were then included in a multivariate logistic regression analysis. Results: We found 44 patients with any pneumonitis including 12 patients with CIP. Antibiotics (OR=2.05, p=0.31), radiotherapy (OR=3.37, p=0.001), low FEV1 (OR=1.48, p=0.038), low pO2 (OR=1.36, p=0.043) and neutrophil to lymphocyte ratio (OR=0.90, p=0.037) in the univariate analysis, antibiotics (OR=2.18, p=0.035) and radiotherapy (OR=3.25, p=0.002) in the multivariate analysis were significantly associated with any pneumonitis. Age (OR=0.93, p=0.007), pericardial effusion (OR=5.52, p=0.017) and serum eosinophils (OR=1.19, p=0.004) in the univariate analysis, age (OR=0.92, p=0.003) and pericardial effusion (OR=6.86, p=0.004) in the multivariate analysis were significantly associated with CIP. Conclusion: Our results suggest differing clinical risk factors for CIP vs. other pneumonitis in ICI therapy. This highlights the need for further investigations of the pathophysiology of specific types of pneumonitis.

Die Nuklearmedizin nimmt in der Diagnostik von angeborenen und erworbenen Nierenfunktionsstörungen und Nierenanomalien in der Pädiatrie eine wichtige Rolle ein. In diesem Kapitel sollen die wichtigsten Untersuchungsmethoden sowie deren Indikationen, Nutzen und Risiken erläutert werden. Während die MAG3 (Mercaptoacetyltriglycin)-Nierenfunktionsszintigraphie die seitengetrennte Nierenfunktion und eventuell vorliegende Abflussstörungen beurteilen kann, wird die DMSA-Szintigrafie zur Bewertung des funktionellen Nierenparenchyms, der Partialfunktion und der Erkennung von Narbenbildung primär herangezogen. Die direkte Radionuklid-Miktionscystogramm dient der Refluxdiagnostik. Die Strahlenexposition nuklearmedizinischer Nierenfunktionsuntersuchungen ist insgesamt sehr gering und liegt in aller Regel unter 1 mSv.

Die aktualisierte 3. Fassung der 123I-mIBG-Szintigrafie bei Kindern und Jugendlichen berücksichtigt folgende aktuelle Entwicklungen: Die Leitlinie fokussiert auf die diagnostische Anwendung von 123I-mIBG beim Neuroblastom. 131I-mIBG kommt bei der Radionuklidtherapie zum Einsatz. An wenigen Stellen wird auf Besonderheiten des 131I-mIBG bei der Befundung von Posttherapie-Szintigrammen eingegangen. Es werden aktuelle Entwicklungen in der Patientenvorbereitung bei den Medikamenteninterferenzen und Empfehlungen zur Schilddrüsenblockade berücksichtigt. Neue Empfehlungen der zu applizierenden Aktivität werden genannt und die damit assoziierten Probleme diskutiert. Die Bildakquisition unter Berücksichtigung von SPECT bzw. SPECT/CT des Körperstammes inkl. des Kopfes wird berücksichtigt. Die Befundung unter Verwendung des SIOPEN-Scores wird neu aufgenommen. Auf PET bzw. PET/CT mit 18F-DOPA bzw. 68Ga-DotaTATE wird verwiesen.

Visual Abstract 18F-FDG PET/CT quantification of whole-body tumor burden in lymphoma is not routinely performed because of the lack of fast methods. Although the semiautomatic method is fast, it is not fast enough to quantify tumor burden in daily clinical practice. Our purpose was to evaluate the performance of convolutional neural network (CNN) software in localizing neoplastic lesions in whole-body 18F-FDG PET/CT images of pediatric lymphoma patients. Methods: The retrospective image dataset, derived from the data pool of the International Atomic Energy Agency (coordinated research project E12017), included 102 baseline staging 18F-FDG PET/CT studies of pediatric lymphoma patients (mean age, 11 y). The images were quantified to determine the whole-body tumor burden (whole-body metabolic tumor volume [wbMTV] and whole-body total lesion glycolysis [wbTLG]) using semiautomatic software and CNN-based software. Both were displayed as semiautomatic wbMTV and wbTLG and as CNN wbMTV and wbTLG. The intraclass correlation coefficient (ICC) was applied to evaluate concordance between the CNN-based software and the semiautomatic software. Results: Twenty-six patients were excluded from the analysis because the software was unable to perform calculations for them. In the remaining 76 patients, CNN and semiautomatic wbMTV tumor burden metrics correlated strongly (ICC, 0.993; 95% CI, 0.989 − 0.996; P < 0.0001), as did CNN and semiautomatic wbTLG (ICC, 0.999; 95% CI, 0.998–0.999; P < 0.0001). However, the time spent calculating these metrics was significantly (<0.0001) less by CNN (mean, 19 s; range, 11–50 s) than by the semiautomatic method (mean, 21.6 min; range, 3.2–62.1 min), especially in patients with advanced disease. Conclusion: Determining whole-body tumor burden in pediatric lymphoma patients using CNN is fast and feasible in clinical practice.

ZusammenfassungDie Nierenfunktionsszintigrafie stellt eine wichtige Säule in der Diagnostik von angeborenen oder erworbenen Niereninsuffizienzen und Nierenanomalien bei Kindern dar. Die nuklearmedizinischen Untersuchungsmodalitäten der Nieren sowie ableitenden Harnwege umfassen die MAG3-Szintigrafie, die DMSA-Szintigrafie sowie die direkte Radionuklid-Miktionszystografie. In dieser Übersichtsarbeit werden die wichtigsten Untersuchungsmethoden, deren Indikation, Nutzen und Risiko erläutert. Die MAG3-(Mercaptoacetyltriglycin)-Nierenfunktionsszintigrafie beurteilt die seitengetrennte Nierenfunktion und die Abflussverhältnisse, während die DMSA-Bildgebung hauptsächlich zur Beurteilung des funktionellen Nierenparenchyms und von Nierenparenchymdefekten verwendet wird. Zusätzlich kann die direkte Radionuklid-MCU (Urinzystografie) zur Refluxdiagnostik genutzt werden.

Abstract Following initial surgery, patients with adrenocortical carcinoma (ACC) are commonly treated with the adrenolytic substance mitotane in an adjuvant or therapeutic setting. Treatment responses, however, are variable. The objective of the study was to investigate a possible correlation between FDG-PET activity of the remaining adrenal gland and therapeutic response of mitotane treatment. This is a retrospective study enrolling patients from two German centers with operated ACC and minimal information on PET-CT scanning. Eighty-two ACC patients after adrenalectomy were included (66 treated with mitotane and 16 without medical therapy). FDG uptake of the contralateral adrenal gland, liver and mediastinum was analyzed from a total of 291 PET/CT scans (median 4 scans per patient) and correlated with clinical annotations including overall and recurrence free survival. The majority of patients (81%) displayed a temporary increase in adrenal FDG uptake within the first 18 months following surgery, which was not associated with a morphological correlate for potential malignancy. This increase was mainly present in patients treated with mitotane (51/61, 84%) but less frequent in the control group (4/7, 57%). No direct correlation with mitotane plasma levels were evident. Patients following R0 resection with high adrenal uptake showed a tendency towards better clinical outcome without reaching a significance value (HR 1.41; CI 0.42–4.75; p=0.059). FDG update of the contralateral adrenal gland may not be misinterpreted as sign of malignancy but might be rather associated with a trend towards better clinical outcome.

A 16-year-old male patient underwent 18F-FDG PET/CT staging after multiple surgical resections and radiotherapy of an uncommon metastatic pediatric sebaceous carcinoma of the parotid gland. Initial PET/CT imaging exhibited a recurrent paravertebral metastasis (C4) as well as a metabolically active tumor tissue at the primary site. Follow-up PET/CT after radiotherapy of the cervical spine (C4) and four cycles of chemotherapy with cisplatin and palbociclib revealed complete functional remission in the cervical spine and partial remission at the primary site. This case illustrates the 18F-FDG-uptake behavior and the disease course of a very rare malignant epithelial tumor of the salivary glands.

Most Non-Small-Cell lung cancer (NSCLC) patients need systemic treatment. Immunotherapy is now current standard in first- and second-line treatment. In all pivotal studies, staging was performed using conventional computer tomography (CT) scans. PET/CT-based treatment monitoring is on the contrary recommended in NSCLC guidelines. This investigation aims at describing the benefits, challenges and possible pitfalls of using PET/CT-based monitoring for lung cancer during immunotherapy. We analyzed 11 NSCLC patients treated with nivolumab at a German tertiary care lung cancer center between 2015 and 2016. All patients received at least two follow-up PET-CTs. Evaluation of response was based on both Response Evaluation Criteria in Solid Tumors (RECIST) and PET Response Criteria in Solid Tumors (PERCIST) criteria. In 7 out of 11 cases, the RECIST and PERCIST results concurred, but two patients with initial stable disease regarding RECIST were reclassified as progressive metabolic disease based on PERCIST criteria. Additionally we identified one case of pseudoprogression using PERCIST criteria in contrast to stable disease using RECIST criteria and one case showing an early and durable response to nivolumab treatment using RECIST, despite a highly hypermetabolic mediastinal lymph node metastasis. The findings indicate that the PERCIST-based evaluation could identify progressive disease earlier. Early identification of nonresponders could lead to prevention of overtreatment and to an early switch to a more effective therapy.

Guidelines recommend true whole-body 18F-FDG PET/CT scans from vertex to toes in pediatric lymphoma patients, although this suggestion has not been validated in large clinical trials. The objective of the study was to evaluate the incidence and clinical impact of lesions outside the "eyes to thighs" regular field of view (R-FOV) in 18F-FDG PET/CT staging (sPET) and interim (iPET) scans in pediatric lymphoma patients. Methods: True whole-body sPET and iPET scans were prospectively obtained in pediatric lymphoma patients (11 worldwide centers). Expert panel central review of sPET and iPET scans were evaluated for lymphoma lesions outside the R-FOV and clinical relevance of these findings. Results: A total of 610 scans were obtained in 305 patients. The sPET scans did not show lesions outside the R-FOV in 91.8% of the patients, whereas in 8.2% patients the sPET scans demonstrated lesions also outside the R-FOV (soft tissue, bone, bone marrow, and skin); however, the presence of these lesions did not change the clinical stage of any patient and did not affect treatment decision. Among the 305 iPET scans, there were no new positive 18F-FDG-avid lesions outside the R-FOV, when compared with their paired sPET scans. A single lesion outside the R-FOV on iPET occurred in 1 patient (0.3%), with the primary lesion diagnosed in the femur on sPET that persisted on iPET. Conclusion: The identification of additional lesions outside the R-FOV (eyes to thighs) using 18F-FDG PET/CT has no impact in the definition of the clinical stage of disease and minimal impact in the treatment definition of patients with pediatric lymphoma. As so, R-FOV for both sPET and iPET scans could be performed.

In clinical routine, SUVmax and SUVpeak are most often used to determine the glucose metabolism in tumours by 18F-FDG PET/CT. Both metrics can be further normalised to SUVs in reference regions resulting in a SUV ratio (SUVratio). The aim of the study was to directly compare several widely used SUVs/SUVratios with regard to differentiation between common tumours in paediatric patients; a special focus was put on characteristics of reference region SUVs. The final study population consisted of 61 children and adolescents with diagnoses of non-Hodgkin lymphoma (NHL, n = 25), Hodgkin lymphoma (HL, n = 14), and sarcoma (n = 22). SUV metrics included SUVmax and SUVpeak as well as both parameters normalised to liver and mediastinal blood pool, respectively, yielding the SUVratios SUVmax/liver, SUVmax/mediastinum, SUVpeak/liver, and SUVpeak/mediastinum. The metrics SUVmax, SUVpeak, SUVmax/liver, and SUVpeak/liver all proved to be sensitive for tumour differentiation (p ≤ 0.008); in contrast, SUVmax/mediastinum and SUVpeak/mediastinum revealed to be non-sensitive approaches. Correlation analyses showed inverse associations between reference region SUVs and SUVratios (p < 0.05). Multiple regression analyses demonstrated significant effects of factors as bodyweight and uptake time on reference region SUVs (p < 0.01), and thus indirectly on the corresponding SUVratios. In the paediatric population, the ability to differentiate between common tumours remarkably varies between SUV metrics. When using SUVratios, the choice of reference region is crucial. Factors potentially influencing reference region SUVs (and thus SUVratios) should be taken into account in order to avoid erroneous conclusions. When not possible, SUVmax and SUVpeak represent less complex, more robust alternatives.

Zusammenfassung Klinischer Hintergrund Bei der laborchemischen Diagnose des Phäochromozytoms (PC) bzw. Paraganglioms (PGL) ist die Lokalisationsdiagnostik für das weitere Management entscheidend. Das PC/PGL kann neben pathognomonischen hormonellen Befunden auch typische Merkmale in der Bildgebung zeigen. Morphologisch lässt es sich jedoch häufig nicht sicher von anderen Pathologien differenzieren. Radiologische Standardverfahren Die primäre Modalität für die Abklärung eines PC ist die Computertomographie (CT). Bei extraadrenaler Lage ist die Magnetresonanztomographie (MRT) der CT überlegen. Darüber hinaus beinhaltet die PET-CT (Positronen-Emissions-Tomographie/Computertomographie) komplementäre Informationen zur Diagnose von PC/PGL und ist die Methode der Wahl für maligne PC/PGL. Das 68 Ga-DOTATATE(bzw. 68 Ga-DOTATOC‑/ 68 Ga-DOTANOC-PET-CT)-PET-CT hat hohe Sensitivität für SDHx-mutierte PC/PGL und dient insbesondere zur Planung einer Radiorezeptortherapie mit Somatostatinanaloga. Die 123 Iod-Metajodbenzylguanidin(MIBG)-Szintigraphie findet heutzutage ihren Stellenwert in der Planung einer Radiorezeptortherapie mit MIBG. Methodische Details Das CT-Protokoll für die Abklärung des PC sollte eine native, arterielle und portalvenöse Phase sowie eine Spätphase zur Beurteilung des Wash-outs enthalten; nach neueren Studien ist ein Protokoll mit rein nativer CT auch eine gute Option zur Ausschlussdiagnostik. Bei der MRT muss zu den Kontrastmittelphasen eine native In- und Opposed-phase-Sequenz akquiriert werden. Empfehlung für die Praxis Ein relevanter und zunehmender Anteil der PC sind inzidentelle Befunde. Der Bildgebung kommt daher eine immer größere Bedeutung zu. Neueste Studien zeigen bessere Stabilisierungsraten von PC/PGL unter Radiorezeptortherapie mit Somatostatinanaloga ( 177 Lu-DOTATATE) als mit MIBG. Daher kommt neuerdings dem 68 Ga-DOTATATE-PET-CT ein hoher Stellenwert zu – sowohl in der Diagnostik als auch in der Therapie.

Background: PET/CT is well established as method for prognostic stratification in adult Hodgkin (HL) and Non-Hodgkin lymphoma (NHL). In pediatric lymphoma, there is no uniform system of prognostic stratification. This study evaluates the prognosis of interim FDG-PET/CT in HL and NHL pediatric patients in a large multicenter population from low-middle, upper-middle and high income countries. Methods: Eleven worldwide centers prospectively performed FDG-PET/CT studies on pediatric patients for staging and interim response evaluation. Clinical and PET/CT findings, events, and mortality data were collected. Expert panel performed central review of baseline and interim FDG-PET/CT examinations visually with Lugano classification (LC) and semi-quantitatively (including SUVmax and Delta SUVmax). LC scores of 1, 2, 3 and X were considered negative (LC-); LC scores 4 and 5 were considered positive (LC ). Prognostic analysis compared the 2-y event-free survival (EFS) rate to the PET2 results, and clinical data. Findings: Whole-body FDG-PET/CT acquisitions were performed in 250 patients (183 males; mean age = 10 ± 4 years; 70% with Hodgkin lymphoma) with clinical stage I-IV represented. There were 9 deaths and 46 events during follow-up and 194 (78%) patients with LC- interim studies. LC studies were significantly and independently associated with increased overall mortality (HR=8.96; p 0.002) and more events (HR 5.80; p<0.001). At multivariate analysis neither Delta SUV nor SUVmax were predictor of events. LC studies were associated with more events in children with HL (HR=9.77; p<0.001) than in NHL (HR 2.41; p=0.10). Interpretation: LC FDG-PET/CT scan at interim evaluation is an independent predictor of OS and EFS in pediatric lymphoma patients. LC studies are able to independently predict decreased EFS in patients with HL but not patients with NHL. Funding Statement: IAEA provided funding to investigator institutions from developing countries (Brazil, South Africa, India, Israel, Uruguay, Bangladesh, Pakistan, Philippines) for support of study data management. This research/study/project was funded by IAEA and supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre.Declaration of Interests: No potential conflicts of interest relevant to this article exist.Ethics Approval Statement: Each center obtained research ethics approval for the study protocol and patient information from local Ethics Review Board. Full informed consent was obtained for all patients with the signed consent forms kept by each institution. To ensure confidentiality while sharing data internationally, all cases were anonymized.