Volumetric and textural analysis of PET/CT in patients with diffuse large B-cell lymphoma highlights the importance of novel MTVrate feature.

OBJECTIVES: To investigate the prognostic value of clinical, volumetric, and radiomics-based textural parameters in baseline [18F]FDG-PET/CT scans of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: We retrospectively investigated baseline PET/CT scans and collected clinical data of fifty DLBCL patients. PET images were segmented semiautomatically to determine metabolic tumor volume (MTV), then the largest segmented lymphoma volume of interest (VOI) was used to extract first-, second-, and high-order textural features. A novel value, MTVrate was introduced as the quotient of the largest lesion's volume and total body MTV. Receiver operating characteristics (ROC) analyses were performed and 24-months progression-free survival (PFS) of low- and high-risk cohorts were compared by log-rank analyses. A machine learning algorithm was used to build a prognostic model from the available clinical, volumetric, and textural data based on logistic regression. RESULTS: The area-under-the-curve (AUC) on ROC analysis was the highest of MTVrate at 0.74, followed by lactate-dehydrogenase, MTV, and skewness, with AUCs of 0.68, 0.63, and 0.55, respectively which parameters were also able to differentiate the PFS. A combined survival analysis including MTV and MTVrate identified a subgroup with particularly low PFS at 38%. In the machine learning-based model had an AUC of 0.83 and the highest relative importance was attributed to three textural features and both MTV and MTVrate as important predictors of PFS. CONCLUSION: Individual evaluation of different biomarkers yielded only limited prognostic data, whereas a machine learning-based combined analysis had higher effectivity. MTVrate had the highest prognostic ability on individual analysis and, combined with MTV, it identified a patient group with particularly poor prognosis.

Radioembolization Planning With Dual-Isotope Acquisition of 166 Ho-Labeled Microparticles and 99m Tc-Mebrofenin.

ABSTRACT: A 76-year-old man with hepatocellular carcinoma was referred for liver radioembolization. Given a prior left hemihepatectomy, it was clinically important to consider potentially irradiated healthy liver at planning. Thus, at the SPECT/CT imaging of the scout dose 166 Ho-microparticles before injected superselectively in the right hepatic artery, 99m Tc-mebrofenin was injected intravenously, and functional volumetry SPECT was performed simultaneously. Based on the 2 image sets, the nonirradiated healthy liver was calculated as 1589 mL (functional liver reserve of 85.5% on 99m Tc-mebrofenin SPECT). Posttreatment dosimetry calculations showed optimal normal tissue and tumor absorbed doses, and the patient is clinically well after 3 months.

Preliminary study on individual radiation dose received by medical staff for dose constraint determination.

The staff of the Radiation Protection Service of a European clinical center measured the radiation dose by type-tested thermoluminescent dosemeter systems to which the medical staff was exposed, to assess the effectiveness of current procedures and equipment for optimalisation prompted by the requirements EU Basic Safety Standard 2013. There were three participating sites, the Site 1 was an external hospital, whereas Sites 2 and 3 are part of the same clinical center, who provided data regarding their personnel, from technologists, nurses and medical doctors. In this preliminary study, only a low number of cases were available and used to establish a new, more realistic yearly dose constraint, namely 6 (from two) mSv for whole-body effective dose, 15 (from two) mSv for eye lens dose and 300 (from 50) mSv for extremity dose. Furthermore, the state of safety culture and protection equipment was assessed. Collection of the sufficient amount of data for statistical evaluation is ongoing.

Radioligand therapies in cancer: mapping the educational landscape in Europe.

AIM: We performed a systematic survey to assess the existing gaps in Europe in multidisciplinary education for integration of radioligand therapy (RLT) into cancer care and to obtain detailed information on the current limitations and key contents relevant. METHODS: A high-quality questionnaire, with emphasis on survey scales, formulation, and validity of the different items, was designed. An expert validation process was undertaken. The survey was circulated among medical specialties involved in cancer treatment, universities, and nursing organizations. Questionnaires (156) were distributed, and 95 responses received. RESULTS: Sevety-eight percent of medical societies indicated that training in RLT was very important and 12% important. Eighty-eight percent indicated that their specialty training program included RLT. Twenty-six percent were satisfied with the existing structure of training in RLTs. Ninety-four percent indicated that the existing training is based on theory and hands-on experience. Main identified limitations were lack of centers ready to train and of personnel available for teaching. Sixty-five percent indicated that national programs could be expanded. Fifty percent of consulted universities indicated partial or scarce presence of RLT contents in their teaching programs. In 26% of the cases, the students do not have the chance to visit a RLT facility. A large majority of the universities are interested in further expansion of RLT contents in their curriculums. Nursing organizations almost never (44.4%) or occasionally (33.3%) include RLT contents in the education of nurses and technologists. Hands-on experience is almost never (38%) and sometimes (38%) offered. However, 67% of centers indicated high interest in expanding RLT contents. CONCLUSION: Centers involved recognize the importance of the training and indicate a need for inclusion of additional clinical content, imaging analysis, and interpretation as well as extended hands-on training. A concerted effort to adapt current programs and a shift towards multidisciplinary training programs is necessary for proper education in RLT in Europe.

Paraneoplastic Kelch-like protein 11 antibody-associated cerebellar and limbic encephalitis caused by metastatic "burned-out" seminoma - A scar(r)y phenomenon.

INTRODUCTION: The diagnosis of paraneoplastic neurologic syndromes is challenging when the primary tumor masquerades as scar tissue (i.e. "burned-out"). METHODS: Case report. RESULTS: A 45-year-old male patient presented with progressive cerebellar symptoms and hearing loss. Initial screening for malignancy and extensive testing of paraneoplastic and autoimmune neuronal antibodies gave negative results. Repeated whole-body FDG-PET CT revealed a single paraaortic lymphadenopathy, metastasis of a regressed testicular seminoma. Anti-Kelch-like protein-11 (KLHL11) encephalitis was finally diagnosed. CONCLUSION: Our case highlights the importance of continued efforts to find an often burned-out testicular cancer in patients with a highly unique clinical presentation of KLHL11 encephalitis.

Prognostic parameters on baseline and interim [ 18 F]FDG-PET/computed tomography in diffuse large B-cell lymphoma patients.

OBJECTIVE: 2-[ 18 F]fluoro-2-deoxy- d -glucose PET/computed tomography ([ 18 F]FDG-PET/CT) is a widely used imaging method in the management of diffuse large B-cell lymphomas (DLBCL). Our aim was to investigate the prognostic performance of different PET biomarkers in a multicenter setting. METHODS: We investigated baseline volumetric values [metabolic tumor volume (MTV) and total lesion glycolysis (TLG), also normalized for body weight] segmented with three different methods [>SUV4 (glob4); 41% isocontour (41pc), and a gradient-based lesion growing algorithm (grad)] and interim parameters [Deauville score, maximal standardized uptake value (ΔSUVmax), modified qPET, and ratio PET (rPET)] alongside clinical parameters (stage, revised International Prognostic Index), using 24-month progression-free survival as the clinical endpoint. Receiver operating characteristics analyses were performed to define optimal cutoff points for the continuous PET parameters. RESULTS: A total of 107 diffuse large B-cell lymphoma patients were included (54 women; mean age: 53.7 years). MTV and TLG calculations showed good correlation among glob4, 41pc, and grad methods; however, optimal cutoff points were markedly different.Significantly different PFS was observed between low- and high-risk groups according to baseline MTV, body weight-adjusted (bwa) MTV, TLG, bwaTLG, as well as interim parameters Deauville score, ΔSUVmax, mqPET, and rPET. Univariate Cox regression analyses showed hazard ratios (HRs) lowest for bwaMTVglob4 (HR = 2.3) and highest for rPET (HR = 9.09). In a multivariate Cox-regression model, rPET was shown to be an independent predictor of PFS ( P = 0.041; HR = 9.15). Combined analysis showed that ΔSUVmax positive patients with high MTV formed a group with distinctly poor PFS (35.3%). CONCLUSION: Baseline MTV and TLG values and optimal cutoff points achieved with different segmentation methods varied markedly and showed a limited prognostic impact. Interim PET/CT parameters provided more accurate prognostic information with semiquantitative 'Deauville-like' parameters performing best in the present study.

Potential role of MAP2K1 mutation in the trans-differentiation of interdigitating dendritic cell sarcoma: Case report and literature review.

A 5-year-old male child was diagnosed with interdigitating dendritic cell sarcoma (IDCS) during his maintenance therapy for B-cell precursor acute lymphoblastic leukemia (B-ALL). Multiplex lymph node involvements of the neck were found by positron emission tomography CT (PET-CT). Treatments, including surgical and chemotherapy, resulted in complete remission. Four years later, systemic bone infiltration was discovered. Surgical resection of the IV rib and intensive chemotherapy led to a complete morphological remission, and allogeneic bone marrow transplantation was performed. Comprehensive genomic profiling of the formalin fixed the tumor tissue, and the cryopreserved leukemic cells revealed several common alterations and divergent clonal evolution with a novel MAP2K1 mutation of the IDCS, which is responsible for the trans-differentiation of the common lymphoid-committed tumor progenitor.

Oncologic patient with COVID-19 discovered incidentally by PET/CT examination: (A COVID­19-pandémia orvosszakmai kérdései) / Onkológiai beteg tervezett PET/CT vizsgálata során véletlenszeruen felfedezett COVID-19-betegség

The scientific literature of coronavirus-disease 2019 (COVID-19) is rapidly expanding. There is a growing evidence on the discrepancy between clinical symptoms and radiologic findings in many patients. This case report gives details about a patient with only mild symptoms but relatively severe radiological findings. The 75-year-old patient suffering from oncologic disease had a planned a F18-fluoro-deoxy-glucose positron-emission tomography/computer tomography scan with a routine oncological indication where incidental radiomorphologic findings of pneumonia suspect for COVID-19 were detected. After immediate isolation, the patient was transferred to the corresponding medical department, where further investigations verified the diagnosis of COVID-19. With this case, our aim is to raise the awareness for the importance of the instant evaluation of chest computer tomography series when performing planned imaging examination, especially in frail patients. With this practice, potential radiomorphologic findings of pneumonia suspect for COVID-19 could be identified in time, which fundamentally determines further patient management steps. Orv Hetil. 2020; 161(23): 971-976.

Combined Visual and Semiquantitative Evaluation Improves Outcome Prediction by Early Midtreatment 18F-FDG PET in Diffuse Large B-Cell Lymphoma.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immunochemotherapy after 2 cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying 2 different methods of interpretation: the Deauville visual 5-point scale (5-PS) and a change in SUV (ΔSUV) by semiquantitative evaluation. Methods: In total, 145 patients with newly diagnosed DLBCL underwent pretreatment PET and PET-2 assessment. PET-2 was classified according to both 5-PS and percentage ΔSUV. Receiver-operating-characteristic analysis was performed to compare the accuracy of the 2 methods for predicting progression-free survival. Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET-) groups and compared. Results: Both with 5-PS and with ΔSUV-based evaluations, significant differences were found between the progression-free survival of iPET- and iPET+ patient groups (P < 0.001). Visually, the best negative predictive value (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if the Deauville score was 4-5 (89% and 59%, respectively). Using the 66% ΔSUV cutoff reported previously, NPV and PPV were 80% and 76%, respectively. ΔSUV at the 48.9% cutoff, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). The 5-PS and a semiquantitative ΔSUV of less than 48.9% for each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100%, respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL patients, iPET had good prognostic value interpreted either visually or semiquantitatively. We determined that the most effective ΔSUV cutoff was 48.9% and that when combined with 5-PS assessment, a positive PET-2 result was highly predictive of treatment failure.

Predictive and prognostic value of FDG-PET/CT imaging and different response evaluation criteria after primary systemic therapy of breast cancer.

OBJECTIVES: (1) To predict pathological complete remission (pCR) and survival after primary systemic therapy (PST) in patients diagnosed with breast cancer by using two different PET/CT based scores: a simplified PERCIST-based PET/CT score (Method 1) and a combined PET/CT score supplemented with the morphological results of the RECIST system (Method 2) and (2) to assess the effect of different breast carcinoma subtypes on tumor response and its evaluation. METHODS: Eighty-eight patients were enrolled in the study who underwent PET/CT imaging before and after PST. PET/CTs were evaluated by changes in maximum Standardized Uptake Value (SUVmax) and tumor size. Method 1 and 2 were applied to predict pathological complete remission (pCR). Kaplan-Meier analyses for survival were performed. Classification into biological subtypes was performed based on the pre-therapeutic tumor characteristics. RESULTS: A total of 30/88 patients showed pCR (34.1 %). Comparing pCR/non-pCR patient groups, significant differences were detected by changes in SUVmax (p < 0.001) and tumor size (p < 0.001) regarding the primary breast lesions. To predict pCR, Method 2 had higher sensitivity (72.4 % vs. 44.8 %) and negative predictive value (57.9 % vs. 45.8 %) with lower false negativity rate (16 vs. 32) than Method 1. pCR rate was higher in Her2-positive and triple negative tumors. Despite the significant differences detected between the biological subtypes regarding changes in primary tumor SUVmax (p = 0.007) and size (p = 0.015), the subtypes only had significant impact on response evaluation with Method 2 and not with Method 1. In our study, neither clinical nor pathological CR were predictors of longer progression-free survival. CONCLUSIONS: Our results suggest that combined PET/CT criteria are more predictive of pCR. The effect of biological subtypes is significant on pCR rate as well as on the changes in FDG-uptake and morphological tumor response. Response evaluation with combined criteria was also able to reflect the differences between the biological behavior of breast tumor subtypes.

Complexity of Response Evaluation During Primary Systemic Therapy of Breast Cancer: Scoring Systems and Beyond-Preliminary Results.

BACKGROUND: Precise and standardized response evaluation enables clinicians to tailor primary systemic therapy (PST). PATIENTS AND METHODS: Breast cancer patients underwent (18)F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) before and after PST. Response was assessed by maximal Standardized Uptake Value (SUVmax); morphological changes and Ki-67 labeling index (LI). In parallel response assessment was performed by European Organization for Research and Treatment of Cancer (EORTC); PET Response Criteria in Solid Tumors (PERCIST); World Health Organization (WHO); Response Evaluation Criteria in Solid Tumors (RECIST); Chevallier and Sataloff classifications, and by a novel Ki-67 score. Accuracy of different scoring systems was evaluated. RESULTS: In the 42 enrolled patients, SUVmax, size, and Ki-67 LI decreased significantly on PST. Significant differences between patients with versus those without pathological complete response were observed for pre-treatment Ki-67 LI and SUVmax and for post-treatment Ki-67 LI, SUVmax and size. Change in Ki-67 LI was the best predictor of pathological complete response. Correlation patterns of the directly measured metabolic, morphological, and proliferation responses differed from those determined by scoring methods. CONCLUSION: During PST, FDG-PET/CT enables for robust assessment of treatment efficacy, but more reliable scoring systems are still needed for more precise response evaluation.

Response evaluation after primary systemic therapy of Her2 positive breast cancer ­ an observational cross-sectional study.

AIM: To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring. METHODS: 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Ten patients (38.5%) in Group 1 and eight (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1: (P=0.043) and Group 2: (P=0.029). PET/CT evaluated by the breast cancer specific criteria (Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens=77.8%, spec=%, PPV=100%, NPV=71.4%; Group 2: sens=87.5%, spec=62.5%, PPV=70%, NPV=83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens=22.2% spec=100% PPV=100% NPV=41.7%; in Group 2: sens=37.5%, spec=87.5%, PPV=75% NPV=58.3%) or breast ultrasound (Group 1, sens=83.3% spec=25% PPV=62.5% NPV=50%; Group 2, sens=100% spec=12.5% PPV=41.6% NPV=100%). CONCLUSION: The benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.

Prospective international cohort study demonstrates inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma.

UNLABELLED: The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). METHODS: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. RESULTS: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. CONCLUSION: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.

Combined PET and biopsy evidence of marrow involvement improves prognostic prediction in diffuse large B-cell lymphoma.

UNLABELLED: Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. METHODS: The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. RESULTS: Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (n = 231) were 81% (95% confidence interval [CI], 76%-86%) for event-free survival (EFS) and 88% (83%-91%) for overall survival (OS); cases identified only on PET (n = 61), 81% (69%-89%) for EFS and 88% (77%-94%) for OS; cases indentified only on biopsy (n = 10), 80% (41%-95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (n = 25), 45% (25%-64%) for EFS and 55% (32%-73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/biopsy-positive cases were 2.67 (95% CI, 1.48-4.79) for EFS and 3.94 (1.93-8.06) for OS. CONCLUSION: This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow (18)F-FDG uptake identified on the staging PET scan. Abnormal (18)F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.

Diffusion weighted magnetic resonance imaging demonstrates tumor response following palliative embolization of a recurrent shoulder plasmacytoma.

We report the palliative embolization and functional imaging follow-up of a recurrent shoulder plasmacytoma. The multiple myeloma patient complained of severe pain and discomfort, while he could not tolerate further chemotherapy. The left shoulder lesion had earlier received a high dose of irradiation. Thus, the well-vascularized lesion was embolized via feeding arteries branching off from the left subclavian artery in two sessions. The patient's symptoms rapidly improved post-embolization and the serum free light chain ratio stabilized at a lower level. The follow-up magnetic resonance image showed increased diffusivity in previously restricted tumor foci. This has negatively correlated with the decreased fludeoxyglucose uptake on PET, suggesting post-embolization necrosis.