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Background: Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum. Methods: After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated. Results: After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth. Conclusion: Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH.

(18)F-FDG PET/MRI might be the diagnostic method of choice for Hodgkin lymphoma patients, as it combines significant metabolic information from PET with excellent soft-tissue contrast from MRI and avoids radiation exposure from CT. However, a major issue is longer examination times than for PET/CT, especially for younger children needing anesthesia. Thus, a targeted selection of suitable whole-body MRI sequences is important to optimize the PET/MRI workflow. Methods: The initial PET/MRI scans of 84 EuroNet-PHL-C2 study patients from 13 international PET centers were evaluated. In each available MRI sequence, 5 PET-positive lymph nodes were assessed. If extranodal involvement occurred, 2 splenic lesions, 2 skeletal lesions, and 2 lung lesions were also assessed. A detection rate was calculated dividing the number of visible, anatomically assignable, and measurable lesions in the respective MRI sequence by the total number of lesions. Results: Relaxation time–weighted (T2w) transverse sequences with fat saturation (fs) yielded the best result, with detection rates of 95% for nodal lesions, 62% for splenic lesions, 94% for skeletal lesions, and 83% for lung lesions, followed by T2w transverse sequences without fs (86%, 49%, 16%, and 59%, respectively) and longitudinal relaxation time–weighted contrast-enhanced transverse sequences with fs (74%, 35%, 57%, and 55%, respectively). Conclusion: T2w transverse sequences with fs yielded the highest detection rates and are well suited for accurate whole-body PET/MRI in lymphoma patients. There is no evidence to recommend the use of contrast agents.

Introduction Interim PET (iPET) assessment is important for response adaptation in Hodgkin lymphoma (HL). The current standard for iPET assessment is the Deauville score (DS). The aim of our study was to evaluate the causes of interobserver variability in assigning the DS for iPET in HL patients and to make suggestions for improvement. Methods All evaluable iPET scans from the RAPID study were re-read by two nuclear physicians, blinded to the results and patient outcomes in the RAPID trial. The iPET scans were assessed visually according to the DS and, thereafter, quantified using the qPET method. All discrepancies of more than one DS level were re-evaluated by both readers to find the reason for the discordant result. Results In 249/441 iPET scans (56%) a concordant visual DS result was achieved. A “minor discrepancy” of one DS level occurred in 144 scans (33%) and a “major discrepancy” of more than one DS level in 48 scans (11%). The main causes for major discrepancies were 1) different interpretation of PET-positive lymph nodes—malignant vs. inflammatory; 2) lesions missed by one reader and 3) different assessment of lesions in activated brown fat tissue. In 51% of the minor discrepancy scans with residual lymphoma uptake, additional quantification resulted in a concordant quantitative DS result. Conclusion Discordant visual DS assessment occurred in 44% of all iPET scans. The main reason for major discrepancies was the different interpretation of PET positive lymph nodes as malignant or inflammatory. Disagreements in evaluation of the hottest residual lymphoma lesion can be solved by the use of semi-quantitative assessment.

Purpose Chimeric antigen receptor (CAR)-T cells are a viable treatment option for patients with relapsed or refractory (r/r) aggressive B-cell lymphomas. The prognosis of patients who relapse after CAR-T cell treatment is dismal and factors predicting outcomes need to be identified. Our aim was to assess the value of FDG-PET/CT in terms of predicting patient outcomes. Methods Twenty-two patients with r/r B-cell lymphoma who received CAR-T cell treatment with tisagenlecleucel (n = 17) or axicabtagene ciloleucel (n = 5) underwent quantitative FDG-PET/CT before (PET-0) and 1 month after infusion of CAR-T cells (PET-1). PET-1 was classified as complete metabolic response (CMR, Deauville score 1–3) or non-CMR (Deauville score 4–5). Results At the time of PET-1, 12/22 (55%) patients showed CMR, ten (45%) patients non-CMR. 7/12 (58%) CMR patients relapsed after a median of 223 days, three of them (25%) died. 9/10 (90%) non-CMR patients developed relapse or progressive disease after a median of 91 days, eight of them (80%) died. CMR patients demonstrated a significantly lower median total metabolic tumor volume (TMTV) in PET-0 (1 ml) than non-CMR patients (225 ml). Conclusion Our results confirm the prognostic value of PET-1. 42% of all CMR patients are still in remission 1 year after CAR T-cell treatment. 90% of the non-CMR patients relapsed, indicating the need for early intervention. Higher TMTV before CAR-T cell infusion was associated with lower chances of CMR.

Gastric cancer; Metastasectomy; Oligometastasis Cáncer gástrico; Metastasectomía; Oligometástasis Càncer gàstric; Metastasectomia; Oligometàstasi Background Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. Methods In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). Conclusion The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.

Oesophageal neoplasm; Oligometastasis; Radiosurgery Neoplàsia esofàgica; Oligometàstasi; Radiocirurgia Neoplasia esofágica; Oligometástasis; Radiocirugía Background Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking. Objective To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe. Material and methods European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (

In first-line treatment of Hodgkin lymphoma (HL), Deauville scores 1-3 define complete metabolic remission. Interim 18F-FDG PET is also used for relapse-treatment adaptation; however, PET response criteria are not validated for relapse treatment. Methods: We performed a pairwise comparative analysis of early response to first- and second-line treatments in 127 patients with classic HL who experienced relapse. The patients participated in the prospective, multicenter EuroNet-PHL-C1 study. Residual uptake was measured retrospectively using the qPET method, a validated semiautomatic quantitative extension of the Deauville score. Empiric cumulative distribution functions of the qPET values were used to systematically analyze the response to first- and second-line treatments. Results: Individual patients responded variably to first- and second-line treatments. However, the empiric cumulative distribution functions of the qPET values from all patients were nearly superimposable. Conclusion: The findings support that first- and second-line treatments in HL do not require different response criteria.

Purpose Although participation in multidisciplinary tumor boards (MTBs) is an obligatory quality criterion for certification, there is scarce evidence, whether MTB recommendations are consistent with consensus guidelines and whether they are followed in clinical practice. Reasons of guideline and tumor board deviations are poorly understood so far. Methods MTB’s recommendations from the weekly MTB for gastrointestinal cancers at the University Cancer Center Leipzig/Germany (UCCL) in 2020 were analyzed for their adherence to therapy recommendations as stated in National German guidelines and implementation within an observation period of 3 months. To assess adherence, an objective classification system was developed assigning a degree of guideline and tumor board adherence to each MTB case. For cases with deviations, underlying causes and influencing factors were investigated and categorized. Results 76% of MTBs were fully adherent to guidelines, with 16% showing deviations, mainly due to study inclusions and patient comorbidities. Guideline adherence in 8% of case discussions could not be determined, especially because there was no underlying guideline recommendation for the specific topic. Full implementation of the MTBs treatment recommendation occurred in 64% of all cases, while 21% showed deviations with primarily reasons of comorbidities and differing patient wishes. Significantly lower guideline and tumor board adherences were demonstrated in patients with reduced performance status (ECOG-PS ≥ 2) and for palliative intended therapy (p = 0.002/0.007). Conclusions The assessment of guideline deviations and adherence to MTB decisions by a systematic and objective quality assessment tool could become a meaningful quality criterion for cancer centers in Germany.

ZusammenfassungStudierende der Humanmedizin müssen sich im Rahmen ihrer universitären Ausbildung ein umfangreiches Wissen zunächst aus den Grundlagenwissenschaften und später aus den verschiedensten medizinischen Fachgebieten aneignen. Für Vertiefungen, insbesondere in kleinere, aber dennoch hochinteressante Fachbereiche − etwa der Nuklearmedizin – bleibt dabei oft wenig Zeit. Eine Option, Vertiefungen über den in Seminaren und Vorlesungen vermittelten, vorwiegend klinisch orientierten Stoff zu ermöglichen, bieten Wahlfächer. Die Klinik und Poliklinik für Nuklearmedizin des Universitätsklinikums Leipzig hat in diesem Jahr ein zusätzliches Wahlfach etabliert („Nuklearmedizin universal“), welches v. a. auf die Vermittlung des interdisziplinären Zusammenwirkens von Ärzten, Radiochemikern, Medizinphysikern/-technikern und Medizinisch-technischen Assistenten innerhalb der Nuklearmedizin abzielt. Das entsprechende Curriculum sowie die ersten Erfahrungen werden beschrieben und reflektiert.

ZusammenfassungIm Oktober 2020 vermeldeten die Laienpresse, aber auch einige medizinische Journale und Internetseiten, die angebliche Entdeckung einer neuen Speicheldrüse im Nasenrachen ausgehend von Positronen-Emissions-Tomografie-Computertomografie-Untersuchungen mit Liganden für das Prostata-spezifische Membranantigen (PSMA-PET/CT). Als interdisziplinäre Gruppe aus den Fachbereichen Anatomie, Pathologie, Nuklearmedizin und HNO-Heilkunde kommen wir zu der Ansicht, dass hier eine Anhäufung von kleinen Speicheldrüsen beschrieben wird. Kleine Speicheldrüsen im Nasenrachen und peritubar sind mindestens seit 1866 bekannt und immer wieder in der Literatur und in Lehrbüchern beschrieben. Das PSMA-PET/CT könnte aber geeignet sein, bei einer Bestrahlungsplanung funktionell relevante Anhäufungen von Schleimhautspeicheldrüsen, wie beispielsweise im Bereich des Nasenrachens, besser darzustellen und zu schonen. Dies sollte in klinischen Studien geprüft werden.

Aim In 2015, the revised International Pediatric Non-Hodgkin Lymphoma Staging System was published. It mentions [18F]-FDG-PET/MRI as the latest method to perform whole-body imaging. However, supporting data are pending. Our aim was to investigate the performance of whole-body [18F]-FDG-PET/MRI in pediatric non-Hodgkin lymphoma patients by using a limited number of MRI sequences. Materials and methods Ten pediatric patients with histologically proven non-Hodgkin lymphoma underwent whole-body [18F]-FDG-PET/MRI at staging. The retrospective analysis included three steps: First, [18F]-FDG-PET and MR scans were evaluated separately by a nuclear medicine physician and a pediatric radiologist. Nineteen nodal and two extranodal regions as well as six organs were checked for involvement. Second, discrepant findings were reviewed together in order to reach consensus. Third, [18F]-FDG-PET/MRI findings were correlated with the results of other clinical investigations. Results Of the 190 lymph node regions evaluated, four were rated controversial. Consensus was reached by considering metabolic, functional and morphologic information combined. Concordantly, [18F]-FDG-PET and MRI detected Waldeyer’s ring involvement in two patients whose Waldeyer’s ring was negative on clinical assessment. In four patients MRI showed pleural effusion. However, in only two of them an increased glucose metabolism as a reliable sign of pleural involvement was detectable. In six patients [18F]-FDG-PET and MRI detected skeletal lesions although bone marrow biopsy was positive in only one of them. Conclusion Despite the small number of cases evaluated, whole-body [18F]-FDG-PET turned out to be a valuable tool for staging of pediatric non-Hodgkin lymphoma.

The enzyme O6-methylguanine-DNA methyltransferase (MGMT) is an important component of the DNA repair machinery. MGMT removes O6-methylguanine from the DNA by transferring the methyl group to a cysteine residue in its active site. Recently, we detected the single nucleotide polymorphism (SNP) rs12917 (C/T) in the MGMT sequence adjacent to the active site in Hodgkin lymphoma (HL) cell line KM-H2. We now investigated whether this SNP is also present in other HL cell lines and patient samples. Furthermore, we asked whether this SNP might have an impact on metabolic response in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET), and on overall treatment outcome based on follow-up intervals of at least 34 months. We determined the frequency of this MGMT polymorphism in 5 HL cell lines and in 29 pediatric HL (PHL) patients. The patient cohort included 17 female and 12 male patients aged between 4 and 18 years. After characterization of the sequence, we tested a possible association between rs12917 and age, gender, Ann Arbor stage, treatment group, metabolic response following two courses of OEPA (vincristine, etoposide, prednisone, and doxorubicin) chemotherapy, radiotherapy indication, and relapse status. We detected the minor T allele in four of five HL cell lines. 11/29 patients carried the minor T allele whereas 18/29 patients showed homozygosity for the major C allele. Interestingly, we observed significantly better metabolic response in PHL patients carrying the rs12917 C allele resulting in a lower frequency of radiotherapy indication. MGMT polymorphism rs12917 seems to affect chemotherapy response in PHL. The prognostic value of this polymorphism should be investigated in a larger patient cohort.

BACKGROUND: In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging. PATIENTS, MATERIALS, AND METHODS: The EuroNet-PHL-C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross-sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re-assessed by applying an imaging-based algorithm considering information from 18 F-fluorodeoxyglucose positron emission tomography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging-based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment. RESULTS: The imaging-based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging-based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient. CONCLUSIONS: The imaging-based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future. ispartof: PEDIATRIC BLOOD & CANCER vol:68 issue:4 ispartof: location:United States status: published

Background: Children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma achieve an event-free survival at 5 years of about 90% after treatment with vincristine, etoposide, prednisone, and doxorubicin (OEPA) followed by cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) and radiotherapy, but long-term treatment effects affect survival and quality of life. We aimed to investigate whether radiotherapy can be omitted in patients with morphological and metabolic adequate response to OEPA and whether modified consolidation chemotherapy reduces gonadotoxicity. Methods: Our study was designed as a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial, and was carried out at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed intermediate-stage (treatment group 2) and advanced-stage (treatment group 3) classical Hodgkin lymphoma who were younger than 18 years and stratified according to risk using Ann Arbor disease stages IIAE, IIB, IIBE, IIIA, IIIAE, IIIB, IIIBE, and all stages IV (A, B, AE, and BE) were included in the study. Patients with early disease (treatment group 1) were excluded from this analysis. All patients were treated with two cycles of OEPA (1·5 mg/m2 vincristine taken intravenously capped at 2 mg, on days 1, 8, and 15; 125 mg/m2 etoposide taken intravenously on days 1–5; 60 mg/m2 prednisone taken orally on days 1–15; and 40 mg/m2 doxorubicin taken intravenously on days 1 and 15). Patients were randomly assigned to two (treatment group 2) or four (treatment group 3) cycles of COPP (500 mg/m2 cyclophosphamide taken intravenously on days 1 and 8; 1·5 mg/m2 vincristine taken intravenously capped at 2 mg, on days 1 and 8; 40 mg/m2 prednisone taken orally on days 1 to 15; and 100 mg/m2 procarbazine taken orally on days 1 to 15) or COPDAC, which was identical to COPP except that 250 mg/m2 dacarbazine administered intravenously on days 1 to 3 replaced procarbazine. The method of randomisation (1:1) was minimisation with stochastic component and was centrally stratified by treatment group, country, trial sites, and sex. The primary endpoint was event-free survival, defined as time from treatment start until the first of the following events: death from any cause, progression or relapse of classical Hodgkin lymphoma, or occurrence of secondary malignancy. The primary objectives were maintaining 90% event-free survival at 5 years in patients with adequate response to OEPA treated without radiotherapy and to exclude a decrease of 8% in event-free survival at 5 years in the embedded COPDAC versus COPP randomisation to show non-inferiority of COPDAC. Efficacy analyses are reported per protocol and safety in the intention-to-treat population. The trial is registered with ClinicalTrials.gov (trial number NCT00433459) and EUDRACT (trial number 2006-000995-33), and is closed to recruitment. Findings: Between Jan 31, 2007, and Jan 30, 2013, 2102 patients were recruited. 737 (35%) of the 2102 recruited patients were in treatment group 1 (early-stage disease) and were not included in our analysis. 1365 (65%) of the 2102 patients were in treatment group 2 (intermediate-stage disease; n=455) and treatment group 3 (advanced-stage disease; n=910). Of these 1365, 1287 (94%) patients (435 [34%] of 1287 in treatment group 2 and 852 [66%] of 1287 in treatment group 3) were included in the titration trial per-protocol analysis. 937 (69%) of 1365 patients were randomly assigned to COPP (n=471) or COPDAC (n=466) in the embedded trial. Median follow-up was 66·5 months (IQR 62·7–71·7). Of 1287 patients in the per-protocol group, 514 (40%) had an adequate response to treatment and were not treated with radiotherapy (215 [49%] of 435 in treatment group 2 and 299 [35%] of 852 in treatment group 3). 773 (60%) of 1287 patients with inadequate response were scheduled for radiotherapy (220 [51%] of 435 in the treatment group 2 and 553 [65%] of 852 in treatment group 3. In patients who responded adequately, event-free survival rates at 5 years were 90·1% (95% CI 87·5–92·7). event-free survival rates at 5 years in 892 patients who were randomly assigned to treatment and analysed per protocol were 89·9% (95% CI 87·1–92·8) for COPP (n=444) versus 86·1% (82·9–89·4) for COPDAC (n=448). The COPDAC minus COPP difference in event-free survival at 5 years was −3·7% (−8·0 to 0·6). The most common grade 3–4 adverse events (intention-to-treat population) were decreased haemoglobin (205 [15%] of 1365 patients during OEPA vs 37 [7%] of 528 treated with COPP vs 20 [2%] of 819 treated with COPDAC), decreased white blood cells (815 [60%] vs 231 [44%] vs 84 [10%]), and decreased neutrophils (1160 [85%] vs 223 [42%] vs 174 [21%]). One patient in treatment group 2 died of sepsis after the first cycle of OEPA; no other treatment-related deaths occurred. Interpretation: Our results show that radiotherapy can be omitted in patients who adequately respond to treatment, when consolidated with COPP or COPDAC. COPDAC might be less effective, but is substantially less gonadotoxic than COPP. A high proportion of patients could therefore be spared radiotherapy, eventually reducing the late effects of treatment. With more refined criteria for response assessment, the number of patients who receive radiotherapy will be further decreased. Funding: Deutsche Krebshilfe, Elternverein für Krebs-und leukämiekranke Kinder Gießen, Kinderkrebsstiftung Mainz, Tour der Hoffnung, Menschen für Kinder, Programme Hospitalier de Recherche Clinique, and Cancer Research UK.

In diffuse large B-cell lymphoma, early assessment of treatment response by 18F-FDG PET may trigger treatment modification. Reliable identification of good and poor responders is important. We compared 3 competing methods of interim PET evaluation. Methods: Images from 449 patients participating in the "PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas" trial were reanalyzed by applying the visual Deauville score and the SUV-based qPET (q = quantitative) and ΔSUVmax scales to interim PET scans performed after 2 cycles of chemotherapy. qPET relates residual lymphoma 18F-FDG uptake to physiologic liver uptake, converting the ordinal Deauville scale into a continuous scale and permitting a direct comparison with the continuous ΔSUVmax scale, which is based on SUVmax changes between baseline and interim scans. Positive and negative predictive values were calculated for progression-free survival. Results: When established thresholds were used to distinguish between good and poor responders (visual Deauville score 1-3 vs. 4-5; ΔSUVmax > 66% vs. ≤ 66%), the positive predictive value was significantly lower with Deauville than ΔSUVmax (38.4% vs. 56.6%; P = 0.03). qPET and ΔSUVmax were strongly correlated on the log scale (Pearson r = 0.75). When plotted along corresponding percentiles, the positive predictive value curves for qPET and ΔSUVmax were superimposable, with low values up to the 85th percentile and a steep rise thereafter. The recommended threshold of 66% SUVmax reduction for the identification of poor responders was equivalent to qPET = 2.26, corresponding to score 5 on the visual Deauville scale. The negative predictive value curves were also superimposable but remained flat between 80% and 70%. Conclusion: Continuous scales are better suited for interim PET-based outcome prediction than the ordinal Deauville scale. qPET and ΔSUVmax essentially carry the same information. The proportion of poor-risk patients identified is less than 15%.

Background Interim [18F]fluoro-deoxyglucose-positron emission tomography predicts outcome in peripheral T-cell lymphoma (PTCL). We compared two quantitative evaluation methods. Methods Interim scans from 43 patients with anaplastic lymphoma kinase-negative PTCL from the ‘Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas’ trial were re-analyzed by qPET (relating residual lymphoma-related uptake to liver uptake) and ∆SUVmax (relating interim scan to baseline scan). The endpoint was progression-free survival. Results qPET and ∆SUVmax were closely correlated (Pearson’s r = 0.627). Up to the 60th percentile of values ranked by increasing residual activity, the positive predictive value for progression or death increased from 60 to 95%, with stable negative predictive values (NPV) of 60%. Beyond the 60th percentile, the NPV decreased to 40%. qPET ≥ 2 and ∆SUVmax Conclusions qPET and ∆SUVmax identify large fractions of PTCL patients destined to experience treatment failure. qPET may be preferred because it requires a single PET scan, halving the diagnostic effort.

In October 2020, the lay press, but also some medical journals and websites reported the putative discovery of a new salivary gland in the nasopharynx based on prostate-specific membrane antigen positron emission tomography computed tomography (PSMA-PET/CT) examinations. As an interdisciplinary group from the fields of anatomy, pathology, nuclear medicine and otorhinolaryngology, we come to the view that an accumulation of minor salivary glands has been described here. Minor salivary glands in the nasopharynx and in the peritubar region have been described at least since 1866. The current description in PSMA-PET/CT does not justify the definition of a new, independent salivary gland. The PSMA-PET/CT could, however, be suitable to better protect salivary glands in the nasopharynx when planning radiation therapy. This should be evaluated in clinical trials.Im Oktober 2020 vermeldeten die Laienpresse, aber auch einige medizinische Journale und Internetseiten, die angebliche Entdeckung einer neuen Speicheldrüse im Nasenrachen ausgehend von Positronen-Emissions-Tomografie-Computertomografie-Untersuchungen mit Liganden für das Prostata-spezifische Membranantigen (PSMA-PET/CT). Als interdisziplinäre Gruppe aus den Fachbereichen Anatomie, Pathologie, Nuklearmedizin und HNO-Heilkunde kommen wir zu der Ansicht, dass hier eine Anhäufung von kleinen Speicheldrüsen beschrieben wird. Kleine Speicheldrüsen im Nasenrachen und peritubar sind mindestens seit 1866 bekannt und immer wieder in der Literatur und in Lehrbüchern beschrieben. Das PSMA-PET/CT könnte aber geeignet sein, bei einer Bestrahlungsplanung funktionell relevante Anhäufungen von Schleimhautspeicheldrüsen, wie beispielsweise im Bereich des Nasenrachens, besser darzustellen und zu schonen. Dies sollte in klinischen Studien geprüft werden.

Hepatic involvement in Hodgkin lymphoma (HL) is uncommon (∼5% of patients) but always implies stage IV disease. Accurate staging is mandatory for making the appropriate risk assignment and treatment decisions. The Staging Evaluation and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) international working group conducted a systematic literature review of liver involvement in HL patients with the aim to propose a universally acceptable definition for liver involvement in pediatric HL. Thirty-three articles describing 6985 pediatric and adult HL patients were reviewed, of which 539 (7.7%) mentioned liver involvement. The literature did not provide a uniform definition of hepatic involvement and we propose consensus criteria derived from the EuroNet and Children's Oncology Group protocols, where liver involvement is defined as any hepatic lesion on computed tomography scan that correlates with 18 F-FDG uptake greater than background liver. A clear definition of liver lesions is necessary to consistently identify liver involvement and compare its impact on outcomes among protocols worldwide.

We used hybrid capture-targeted next-generation sequencing of circulating cell-free DNA (ccfDNA) of pediatric Hodgkin lymphoma (PHL) patients to determine pathogenic mechanisms and assess the clinical utility of this method. Hodgkin-Reed/Sternberg (HRS) cell-derived single nucleotide variants, insertions/deletions, translocations and VH-DH-JH rearrangements were detected in pretherapy ccfDNA of 72 of 96 patients. Number of variants per patient ranged from 1 to 21 with allele frequencies from 0.6 to 42%. Nine translocation breakpoints were detected. Genes involved in JAK/STAT, NFkB and PI3K signaling and antigen presentation were most frequently affected. SOCS1 variants, mainly deletions, were found in most circulating tumor (ct) DNAs, and seven of the nine translocation breakpoints involved SOCS1. Analysis of VH-DH-JH rearrangements revealed an origin of PHL HRS cells from partially selected germinal center B cells. Amounts of pretherapy ctDNA were correlated with metabolic tumor volumes. Furthermore, in all ccfDNA samples of 43 patients with early response assessment quantitative qPET 3, indicative of a favorable clinical course, ctDNA was not detectable. In contrast, in five of six patients with qPET 3, indicative of an unfavorable clinical course, ctDNA remained detectable. ccfDNA analysis of PHL is thus a suitable approach to determine pathogenic mechanisms and monitor therapy response.

Background The International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH) seeks to provide a universally acceptable definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma. Procedure A comprehensive literature search was performed using PubMed and Google Scholar with the search terms "Hodgkin lymphoma," "osseous lesions," "bony involvement," and "pediatric." Publications reviewed included case reports, retrospective analyses, and literature reviews. Each was evaluated for study design, number of participants, median age and age range at diagnosis, percentage of pediatric patients, criteria of interest definition, diagnostic tools, study objectives, and level of evidence. The final definition was based on the available data and consensus of the SEARCH working group. Results Twenty-five papers specifically addressing cortical bone involvement in Hodgkin lymphoma met the inclusion criteria. Eighteen papers were case reports with literature reviews; the remainder were observational cohort studies. Of these, 14 included pediatric patients (aged 0-21 years). The criteria for cortical bone involvement were not clearly defined in any paper, often varied within a study, and were inconsistent between publications. Conclusions The SEARCH group for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (CAYAHL) proposes the following criteria as defining cortical bone involvement: any cortical bone biopsy-proven lesion; a positive bony window lesion on computer tomography (CT), with an FDG-PET positive correlate in a patient with biopsy-proven Hodgkin lymphoma, if there is no other typical skeletal pathology; auspicious skeletal lesions on FDG-PET or magnetic resonance imaging should be confirmed by CT or Tc-99m scan to distinguish cortical lesions from bone marrow involvement. Nodal masses that extend into bone with bony destruction are considered extranodal extension or "E" lesions and do not represent metastatic or stage IV disease.

PET using 18F-FDG for treatment monitoring in patients with lymphoma is one of the most well-developed clinical applications. PET/CT is nowadays used during treatment to assess chemosensitivity, with response-adapted therapy given according to ‘interim’ PET in clinical practice to adults and children with Hodgkin lymphoma. PET is also used to assess remission from disease and to predict prognosis in the pretransplant setting. Mature data have been reported for the common subtypes of aggressive B-cell lymphomas, with more recent data also supporting the use of PET for response assessment in T-cell lymphomas. The Deauville five-point scale incorporating the Deauville criteria (DC) is recommended for response assessment in international guidelines. FDG uptake is graded in relation to the reference regions of normal mediastinum and liver. The DC have been validated in most lymphoma subtypes. The DC permit the threshold for adequate or inadequate response to be adapted according to the clinical context or research question. It is important for PET readers to understand how the DC have been applied in response-adapted trials for correct interpretation and discussion with the multidisciplinary team. Quantitative methods to perform PET in standardized ways have also been developed which may further improve response assessment including a quantitative extension to the DC (qPET). This may have advantages in providing a continuous scale to refine the threshold for adequate/inadequate response in specific clinical situations or treatment optimization in trials. qPET is also less observer-dependent and limits the problem of optical misinterpretation due to the influence of background activity.

PURPOSE In 2014, we published the qPET method to quantify fluorodeoxyglucose positron emission tomography (FDG-PET) responses. Analysis of the distribution of the quantified signals suggested that a clearly abnormal FDG-PET response corresponds to a visual Deauville score (vDS) of 5 and high qPET values ≥ 2. Evaluation in long-term outcome data is still pending. Therefore, we analyzed progression-free survival (PFS) by early FDG-PET response in a subset of the GPOH-HD2002 trial for pediatric Hodgkin lymphoma (PHL). PATIENTS/METHODS Pairwise FDG-PET scans for initial staging and early response assessment after two cycles of chemotherapy were available in 93 PHL patients. vDS and qPET measurement were performed and related to PFS. RESULTS Patients with a qPET value ≥ 2.0 or vDS of 5 had 5-year PFS rates of 44%, respectively 50%. Those with qPET values

Zusammenfassung Hintergrund: Die Diagnose einer Krebserkrankung in der Schwangerschaft ist selten, aufgrund einer Verschiebung des Alters der Erstgebärenden hin zum letzten Drittel des reproduzierfähigen Alters aber auch für Kopf-Hals-Tumorpatientinnen möglicherweise zunehmend relevant. Dabei besteht eine große Unsicherheit bezüglich des Nutzens und Risikos von diagnostischen oder therapeutischen Tumortherapiemodalitäten für das Ungeborene, sodass eine fundierte Empfehlung in diesen Fällen besonders schwer fällt. Nach neuen Literaturdaten scheint aber sogar eine multimodale Tumortherapie (Operation, Bestrahlung, Chemotherapie) trotz Schwangerschaft möglich und sollte streng gegen das Risiko einer Frühgeburtlichkeit abgewogen werden. Material und Methoden: Die Arbeit gibt eine Literaturübersicht über aktuelle Erkenntnisse zu diagnostischen Verfahren in der Schwangerschaft und zu dem Risiko von tumortherapeutischen Maßnahmen wie Bestrahlung und Chemotherapie für das Ungeborene. Die Erkenntnisse werden anhand eines konkreten Falls einer Schwangeren mit einem ausgedehnten Gehörgangskarzinom diskutiert und es werden Empfehlungen formuliert. Ergebnisse: Suffizient durchgeführte diagnostische Modalitäten erreichen die gefährdenden Uterusdosen praktisch nicht. Eine Reihe von Fallberichten und Beobachtungsstudien zeigen auch keinen Entwicklungsnachteil für die Kinder pränatal exponierter tumorkranker Mütter durch Bestrahlung oder Chemotherapie, wohingegen der langfristige Entwicklungsnachteil durch die Frühgeburtlichkeit nachgewiesen ist. Schlussfolgerung: Wenn während einer Schwangerschaft eine Tumorneuerkrankung im Kopf-Hals-Bereich festgestellt wird, erscheint auch die Durchführung einer etablierten Therapie mittels Operation und/oder Cisplatin-basierter Radiochemotherapie mit vertretbarem Risiko für das ungeborene Kind möglich.

To determine whether the current 18F-FDG PET response criterion for skeletal involvement in Hodgkin lymphoma (HL) is suitable, we performed a systematic evaluation of the different types of skeletal involvement and their response on PET after 2 cycles of chemotherapy (PET-2). A secondary objective was to observe the influence of the initial uptake intensity (measured as qPET) and initial metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: The initial PET scans of 1,068 pediatric HL patients from the EuroNet- PHL-C1 trial were evaluated for skeletal involvement by central review. Three types of skeletal lesions were distinguished: PET-only lesions (those detected on PET only), bone marrow (BM) lesions (as confirmed by MRI or BM biopsy), and bone lesions. qPET and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response for skeletal and nodal involvement on PET-2 were compared. Results: Of the 1,068 patients, 139 (13%) showed skeletal involvement (44 PET-only, 32 BM, and 63 bone). Of the 139 patients with skeletal involvement, 101 (73%) became PET-2–negative in the skeleton and 94 (68%) became PET-2–negative in the lymph nodes. The highest number of PET-2–negative scans in the skeleton was 42 (95%) in the 44 PET-only patients, followed by 22 skeletal lesions (69%) in the 32 BM patients and 37 (59%) in the 63 bone patients. Lesions that became PET-2–negative showed a lower initial median qPET (2.74) and MTV (2 cm3) than lesions that remained PET-2– positive (3.84 and 7 cm3, respectively). Conclusion: In this study with pediatric HL patients, the complete response rate for skeletal involvement on PET-2 was similar to that for nodal involvement. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion—comparison with the local skeletal background—is well suited. The initial qPET and MTV of skeletal lesions were predictive of the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response.

Hodgkin lymphoma (HL) is one of the most curable pediatric and adult cancers, with long-term survival rates now exceeding 90% after treatment with chemotherapy alone or combined with radiotherapy (RT). Of note, global collaboration in clinical trials within cooperative pediatric HL study groups has resulted in continued progress; however, survivors of pediatric HL are at high risk of potentially life-limiting second cancers and treatment-associated cardiovascular disease. Over the last three decades, all major pediatric and several adult HL study groups have followed the paradigm of response-based treatment adaptation and toxicity sparing through the reduction or elimination of RT and tailoring of chemotherapy. High treatment efficacy is achieved using dose-dense chemotherapy. Refinement and reduction of RT have been implemented on the basis of results from collaborative group studies, such that radiation has been completely eliminated for certain subgroups of patients. Because pediatric staging and response criteria are not uniform, comparing the results of trial series among different pediatric and adult study groups remains difficult; thus, initiatives to harmonize criteria are desperately needed. A dynamic harmonization process is of utmost importance to standardize therapeutic risk stratification and response definitions as well as improve the care of children with HL in resource-restricted environments.

Nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is a very rare disease in childhood and adolescence. In Germany, about 15 newly diagnosed patients present with this disease annually; this number comprises less than 10% of all pediatric Hodgkin lymphoma cases. Since the EuroNet-PHL-LP1 trial for early stage nLPHL patients stopped recruiting in Germany in October 2014, the GPOH-HD writing committee reviewed the literature and decided to deliver treatment recommendations for childhood and adolescent nLPHL patients. These guidelines shall be applicable to young nLPHL patients in European countries that will no longer be able to participate in nLPHL trials for young patients. Therefore, the EuroNet-PHL-nLPHL-registry will be installed to provide quality assured central review of staging and response assessment for registered patients by the Central Review Board of EuroNet-PHL in Halle/Leipzig, Germany.

Knocheneigene maligne Tumoren, Tumoren mit sekundarer Knochenbeteiligung sowie benigne Knochenerkrankungen im Kindes- und Jugendalter stellen den behandelnden Arzt oftmals vor grose Herausforderungen hinsichtlich des weiteren Vorgehens. Dieser Artikel adressiert die Knochenszintigrafie als integralen Bestandteil der Diagnostik o.g. Erkrankungen. Neben Indikationen werden altersspezifisch vorbereitende Masnahmen und angepasste Untersuchungsdurchfuhrungen, Befundinterpretation sowie die Strahlenexposition dargestellt. Hierbei wird sowohl auf die planare Szintigrafie als auch auf raumlich aufgeloste Verfahren wie die SPECT bzw. SPECT/CT eingegangen.

Die PET/MRT ist die neueste und innovativste Entwicklung auf dem Gebiet der bildgebenden Diagnostik. Die wesentlich geringere Strahlenexposition im Vergleich zur PET/CT stellt gerade fur kinderonkologische Fragestellungen einen ganz entscheidenden Vorteil dar. Die gleichzeitige Abbildung von Metabolismus, verschiedenen funktionellen Parametern und hochaufgeloster Anatomie ermoglicht zudem eine noch genauere Diagnostik und verspricht neue Erkenntnisse zur Pathophysiologie padiatrischer Tumoren. So ist zu erwarten, dass mit der PET/MRT neue Wege hinsichtlich weiterer Individualisierung von kinderonkologischen Therapien beschritten werden konnen. Der vorliegende Artikel beschreibt zunachst allgemeine Vorteile dieser Kombinationsbildgebung, geht auf praktische Aspekte der Untersuchungsdurchfuhrung ein und erlautert die Anwendbarkeit von PET/MRT-Protokollen einmal zur Beurteilung eines Lokalgeschehens am Beispiel von kindlichen Hirntumoren und zum anderen zur Ausbreitungsdiagnostik am Beispiel des Neuroblastoms.