Positive PET Scan Research Articles

PET-Directed Therapy for Patients with Limited-Stage Diffuse Large B-Cell Lymphoma - Results of Intergroup Nctn Study S1001

PET-Directed Therapy for Patients with Limited-Stage Diffuse Large B-Cell Lymphoma - Results of Intergroup Nctn Study S1001

North American Practice Patterns for PET-2 Positive Hodgkin Lymphoma

North American Practice Patterns for PET-2 Positive Hodgkin Lymphoma

Impact of Post-Transplant Consolidative Radiotherapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma and a PET-CT Based Predictive Model for Relapse

Background Approximately half of patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) will relapse despite curative intent therapy with salvage chemotherapy (SC) and autologous stem cell transplantation (ASCT). Consolidative radiotherapy (cRT) is used to reduce the risk of local relapse in high risk patients. We aimed to examine the (i) impact of cRT on outcomes, (ii) role of positron-emission tomography computerised tomography (PET-CT) imaging in predicting outcomes, (iii) identify a subgroup most likely to benefit from cRT, (iv) assess patterns of relapse to understand the mechanisms of treatment failure and (v) propose a PET-CT based risk stratification model for relapse. Patients and Methods 104 patients with R/R cHL treated with curative intent SC and ASCT between January 2000 and May 2019 were retrospectively identified from two sites in Melbourne, Australia. Fifty-six patients (54%) received peri-transplant cRT. SC consisted of chemotherapy and/or immunotherapy of the clinician's choice followed by interim assessment by PET-CT imaging. Patients with a complete or partial metabolic response proceeded to ASCT. Disease status was routinely evaluated by physical examination and PET-CT imaging at time of disease relapse, at completion of salvage chemotherapy, and at three months following ASCT. A complete metabolic response on fluorodeoxyglucose (FDG) PET/CT was defined by Deauville Score ≤3 (uptake ≤ liver, PET negative) and compared to Deauville Score ≥4 (PET positive). Results With a median follow-up of 2.5 (range 0.2-15.2) years, the 2-year progression free survival (PFS) and overall survival (OS) rates were 68.3% and 83.6%, respectively. Inferior PFS was associated with advanced stage (III or IV) disease at relapse (AS-R) (53% vs 78%; P=0.004) and PET positivity after SC (51% vs 79%; P=0.005). Compared to PET negative patients after SC, 2-year PFS was significantly inferior in patients who were PET positive and did not receive cRT (38% vs 79%; P<0.001) which lost statistical significance with the addition of cRT (Figure 1A. 58% vs 79%; P=0.12) despite patients in each RT cohort having comparable baseline characteristics. This potential PFS benefit was statistically significant for PET positive patients after SC with limited stage disease at relapse [LS-R] (Figure 1B. 91% vs 44%; P=0.007) but not for patients with AS-R (31% vs 25%; P=0.90). Patients who achieved a negative PET scan without residual tumor mass had superior outcomes following ASCT as compared to patients who are PET negative with residual mass ≥2cm and PET positive patients (Figure 1C. 86% vs 70% vs 51%; P=0.007). Although cRT was associated with a non-significant improvement in local disease in patients with AS-R (P=0.05), 3/5 (60%) patients with LS-R and 5/12 (42%) patients with AS-R who received cRT had subsequent in-field relapse post ASCT. Conclusion One third of patients with relapsed/refractory cHL who received SC and ASCT subsequently relapsed within two years. cRT may abrogate the negative predictive value of a positive PET scan after SC, of which patients with LS-R are most likely to benefit. PET positive disease and residual mass ≥2cm after SC are associated with inferior PFS despite the use of cRT. Conversely, patients who are PET negative without residual tumor mass after SC have superior outcomes. cRT is associated with improved local disease control, yet approximately half of patients who relapse after cRT will still have in-field relapse, possibly warranting the evaluation of higher cRT doses. Therefore, we propose a PET-based model which may identify the patients at "high" risk of progressing after ASCT who are most likely to benefit from clinical trials examining different modalities of consolidative therapy (Figure 1D). Validation of this model is required in a larger independent population. Disclosures Ritchie: Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; BMS: Research Funding; Takeda: Research Funding; Beigene: Research Funding; Imago: Research Funding; Novartis: Honoraria; Sanofi: Honoraria. MacManus:National Health and Medical Research Council Australia: Research Funding. Seymour:Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria; Acerta: Consultancy, Honoraria. Dickinson:GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharpe and Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

REACTIONS TO AMYLOID PET SCAN RESULTS AND LEVELS OF ANXIETY AND DEPRESSION AMONG CARE PARTNERS: CARE IDEAS STUDY

Few studies have examined caregiver reactions to their loved ones receiving the results of an Amyloid PET scan which can be indicative of Alzheimer’s disease. Therefore, we examine: 1) What are care partner’s reactions to their loved one receiving negative or positive amyloid PET scan results?, and 2) To what extent are scan results and diagnostic category (dementia vs. mild cognitive impairment) associated with care partner depressive symptoms (PHQ-2) and anxiety (STAI-6)? Using data from 1,799 care partners in the CARE IDEAS study, we applied a sequential mixed-methods design and explored the reactions of 192 care partners who answered open-ended interview questions after learning about the Amyloid PET scan results. We first conducted qualitative content analysis of transcripts from open-ended questions to explore caregivers’ emotional responses after their loved one received an Amyloid PET scan result. The qualitative data suggest that when the scan results fit care partner’s expectations, i.e. positive scan when the patient has dementia and negative scan when the patient has mild impairment, care partners report satisfaction with this information and relief, rather than shock and frustration. Adjusted logistic regression models of survey responses support this finding; having dementia and a positive scan both increased the likelihood of care partners having high levels of anxiety, and a significant interaction indicated that a positive scan was associated with high anxiety among care partners of patients with mild cognitive impairment but not dementia. Only lower education and higher impairment in everyday cognitive function were associated with high depressive symptoms.

Positron Emission Tomography Can Support the Diagnosis of Dialysis-Related Amyloidosis

Background: The improvements in dialysis have not eliminated long-term problems, including dialysis-related amyloidosis (DRA), caused by Beta-2 microglobulin deposition. Several types of scintigraphy have been tested to detect DRA, none entered the clinical practice. Aim of the study was to assess the potential of PET-FDG scan in the diagnosis of DRA. Methods: Forty-six dialysis patients with at least one PET scan (72 scans) were selected out 162 patients treated in 2016–2018. Subjective global assessment (SGA), malnutrition inflammation score (A), Charlson Comorbidity Index (CCI), were assessed at time of scan; 218 age-matched cases with normal kidney function were selected as controls. PET scans were read in duplicate. Carpal tunnel syndrome was considered a proxy for DRA. A composite “amyloid score” score considered each dialysis year = 1 point; carpal tunnel-DRA = 5 points per site. Logistic regression, ROC curves and a prediction model were built. Results: The prevalence of positive PET was 43.5% in dialysis, 5% in controls (p < 0.0001). PET was positive in 14/15 (93.3%) scans in patients with carpal tunnel. PET sensitivity for detecting DRA was 95% (specificity 64%). Carpal tunnel was related to dialysis vintage and MIS. A positive PET scan was significantly associated with dialysis vintage, MIS and amyloid score. A prediction model to explain PET positivity combined clinical score and MIS, allowing for an AUC of 0.906 (CI: 0.813–0.962; p < 0.001). Conclusions: PET-FDG may identify DRA, and may be useful in detecting cases in which inflammation favours B2M deposition. This finding, needing large-scale confirmation, could open new perspectives in the study of DRA.

Outcome predictors of autologous hematopoietic stem cell transplantation in children with relapsed and refractory Hodgkin lymphoma: Single-center experience in a lower-middle-income country.

Children and adolescents with HL have excellent long-term survival exceeding 95% after combined modality treatment. However, about 20% will either relapse or have PRF. Salvage HDCT followed by AHSCT is considered to be the preferential treatment. To describe the outcome (OS and EFS) and prognostic factors in pediatric patients with relapsed or refractory HL (r/rHL) who underwent AHSCT. We retrospectively included 43 pediatric patients with r/rHL who underwent AHSCT from July 1, 2007, till December 31, 2016, at the Children's Cancer Hospital of Egypt. MAC regimen given was CMV. Of the whole cohort, 88.4% of patients achieved CR, while 11.6% had a positive PET scan prior to transplantation. The 3-year OS and EFS were 85% and 70.6%, respectively. The 3-year OS for patients>10years was 94% versus 65.5% for patients 10years of age or younger (P=0.046). There is strong tendency toward better 3-year OS for patients with negative PET scan as compared to those with positive PET scan before AHSCT, 89.4% vs 60%, respectively (P=0.059). This tendency is also applicable when looking at the 3-year EFS for the two groups, 78.3% vs 40%, respectively (P=0.069). Poor predictors of OS were younger age and positive PET scan before AHSCT. The latter, along with single modality treatment before AHSCT, were poor predictors of EFS.

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant

PurposeTo apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation. Material and methodsThe study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy. ResultsThe median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1–7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12–40Gy). At a median follow-up of 35 months (range, 1–132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis. ConclusionThe adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.

PB1998 PROGNOSTIC VALUE OF PRETRANSPLANT PET/CT IN HODGKIN LYMPHOMA

Background:Autologous stem cell transplant (ASCT) is the standard of treatment in patients with refractory/relapsed Hodgkin lymphoma (HL). Several adverse prognostic factors at relapse are known (stage, anaemia, B signs, Karnofsky score, early relapse etc.) to predict the outcome after ASCT.Aims:We analyzed the prognostic value of pre‐ transplant PET/CT and number of salvage therapy retrospectively.Methods:Between January 1, 2007 and December 31, 2018 pre‐transplantation 18FDG‐PET/CT scans of Hodgkin‐lymphoma patients were performed. Deauville criteria were used for evaluation of PET/CT scans. Positive PET scans were defined, if Deauville score was 4 or 5. We analyzed the effect of PET/CT results for survival (overall‐, relapse‐ and event free), and investigated differences between PET positive and PET negative groups. Statistical analysis was performed using IBM SPSS 25 programme.Results:Sixty‐two Hodgkin‐lymphoma patients (33 men and 29 women) had PET/CT scan before AHSCT. Median age at the time of AHSCT was 35 (19‐65) years. Median follow up time was 55.4 (0‐175) months. There were 49 (79%) PET negative and 13 (21%) PET positive patients. Five‐year overall survival rate was 80% in PET‐ group, and 46.2 % in PET+ group (p &lt; 0.042). Five‐year relapse‐free and event‐free survival rate for negative and positive groups were 85.5% and 43.5% (p &lt; 0.012), and 70.3% and 30.8% (p &lt; 0.006). There were 6 relapse and 9 deaths (3 due to HL) in PET‐ group, and 5 relapse and 6 deaths (due to HL) in PET+ group. Twenty‐five of 49 patients in the PET‐ group got only one type of salvage treatment (DHAP) before AHSCT, against 2 of 13 patients in PET+ group (p = 0.046). Patients who acquired PET negative status after DHAP therapy only, had no relapse. Patients who were treated with 2 or more lines of salvage therapy and acquired PET negative status after these treatments, has no significantly better relapse‐free survival, than patients who remained PET positive.Summary/Conclusion:Clinical routine use of PET/CT before AHSCT is highly suggested based on our investigation. PET‐ patients have significantly better OS, PFS and EFS. PET negative status attends better prognosis, if it is reached with first salvage treatment.

ASSOCIATION BETWEEN ODOR IDENTIFICATION AND REGIONAL GRAY MATTER IN EARLY PRECLINICAL ALZHEIMER'S DISEASE

Introduction Poor performance on odor identification tests has been associated with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD-dementia) in older individuals (Mesholam RI et al., 1998). In addition, longitudinal studies have indicated that the University of Pennsylvania Smell Identification Test (UPSIT) is a sensitive measure that predicts conversion from MCI to AD-dementia (Devanand DP et al., 2015) However, precise biological correlates between smell identification and neurodegeneration remain to be identified. Autopsy studies and PET imaging studies indicate amyloid bplaques and neurofibrillary tangle deposition in the olfactory network, suggesting the olfactory bulb as a possible contributor (Kovacs T et al., 1999). Regardless of the etiology, deficits in smell identification measured by the UPSIT may be a useful biomarker for early presymptomatic AD. In a recent study by Risacher et al., (2017), lower UPSIT scores were inversely associated with tau burden in the temporal lobe of cognitively normal (CN) older individuals (mean age 68.5). However, no association was found between UPSIT score and amyloid deposition or neuro-degeneration as measured by gray matter (GM) volume in CN individuals. In a previous study, we reported that in middle-aged preclinical participants with varying genetic risk for AD, amyloid burden correlated inversely with the GM fraction but not with UPSIT scores. In this study, we aim to investigate the correlations between smell identification scores and regional GM fraction among CN middle-aged individuals at varying genetic risk for AD. Methods Sample consisted of 45 cognitively normal participants aged 50-66 with a first-degree family history for AD divided among three groups: APOE genotype e4e4 (n=15), e3e4 (n=15), and e3e3 (n=15), who underwent [11C]PiB PET, MRI, and neuropsychological testing. The UPSIT was administered to all participants. To quantify GM within 9 regions (ROIs), we applied inverse transformations of the AAL from MNI to subject space and calculated GM fraction as the number of voxels segmenting as GM divided by the total number of voxels in a region. The ROIs were basal ganglia, posterior cingulate, frontal cortex, lateral parietal cortex, lateral temporal cortex, medial temporal lobe, occipital cortex, precuneus and composite cortex. GM fractions which account for intersubject variability in brain size were thus generated for each ROI using the AAL atlas after the structural MRI of each participant was normalized to the MNI template. Statistical analysis was performed using SPSS version 24.0 (IBM Corp). Pearson's r was calculated to assess bivariate correlations. p-values Results Mean age of the participants was 59.1 years (SD=4.71). The mean UPSIT score was 34.58 (SD=4.09). 22 subjects (out of 45) met quantitative criteria for a positive amyloid PET scan using the [11C]PiB BPNDcut-off of 0.08 in this cognitively normal sample (Villeneuve et al., 2015). No statistically significant correlations were found between the UPSIT and GM fraction in any ROI. (Table 1). Additional analyses were performed on groups stratified by genetic risk. After excluding individuals with lower genetic risk (APOE e3e3) from the sample, no statistically significant correlation was found between UPSIT scores and GM fraction (Table 2). Similarly, no correlation was found between UPSIT score and GM fraction in participants with APOE e4e4 genotype or APOE e3e3 genotype. Conclusions In middle aged preclinical AD participants, olfactory identification performance did not correlate with gray matter fraction. Our findings appear consistent with previously reported studies and indicate that olfactory identification may not be a sensitive biomarker for early preclinical disease. Further studies to assess associations between olfactory identification deficits and pathological tau accumulation in a similar early preclinical sample may be warranted. This research was funded by This research was supported by the Alzheimer's Association IIRG-07-60026 (CHvD) and National Institute on Aging (P50-AG047270). APM was supported in part by the NIH/NIA K23-AG057794. RSO was supported in part by the NIMH R25 IMPORT grant (R25MH071584).

Para-aortic Lymph Node Invasion in High-risk Endometrial Cancer: Performance of 18FDG PET-CT.

18F-Fluorodeoxyglucose positron-emission tomography integrated with computed tomography (18FDG PET-CT) is a non-invasive examination that could be helpful for the management of endometrial cancer. This study investigated the performance of 18FDG PET-CT in assessing para-aortic (PA) lymph-node involvement in high-risk endometrial cancer. This was a retrospective, single-center study carried out between 2009 and 2018. The inclusion criteria were high-risk and locally advanced type 1 or 2 endometrial cancer with 18FDG PET-CT before PA lymphadenectomy. During the study period, among 142 patients with high-risk endometrial cancer, 35 patients (24.6%) underwent 18FDG PET-CT followed by PA lymphadenectomy. In 25% of cases, PA lymphadenectomy was not performed due to the discovery of metastasis. 18FDG PET-CT had a sensitivity of 50%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 75%, accuracy of 80% and an area under the curve of 0.75 for the evaluation of PA involvement. According to its high specificity in PA lymph-node evaluation, a positive PET scan might allow PA lymphadenectomy to be avoided.

Management of Residual Mass in Germ Cell Tumors After Chemotherapy.

The purpose of this review is to educate medical oncologists on the management of patients with residual germ cell tumors and the role of surgical resection after platinum-based chemotherapy. Patients with non-seminomatous testicular cancer and residual enlarged retroperitoneal lymph nodes > 1cm following induction chemotherapy with normal tumor markers should undergo a post-chemotherapy retroperitoneal lymph node dissection. All patients with primary mediastinal non-seminoma should undergo surgical resection of the mediastinal mass post-chemotherapy. These are complex surgeries and require expert surgeons in high-volume centers. Patients with advanced testicular seminoma who have residual masses less than 3cm after chemotherapy can be observed without further intervention. Patients with a residual mass > 3cm should be evaluated with PET scan after 6weeks of chemotherapy. Residual mass with negative PET scan can be followed by surveillance while a positive PET scan requires further work up to rule out active disease.

Clinical value of 18F-FDG-PET/CT in suspected serious disease with special emphasis on occult cancer.

Suspected serious disease (SSD) is a disease designation often given to patients with one or more non-specific symptoms of severe disease that could be due to cancer; the optimal diagnostic strategy is largely left to the clinician's discretion. Being a sensitive non-invasive whole-body imaging modality 18F-FDG-PET/CT may have a potential role in this cancer-prevalent group of patients to confirm or refute suspected malignancy. We aimed to investigate the diagnostic value of 18F-FDG-PET/CT in SSD using long-term follow-up as reference. We retrospectively studied results obtained in all SSD patients referred for 18F-FDG-PET/CT at a single institution in 2010-2011 retrieving the following clinical data in all patients: journal entries, examinations, and evaluations made from 6 months before the scan and until the latest recorded entry. A true positive PET scan was a positive scan with a subsequently biopsy-confirmed diagnosis of cancer in the same target organ, whereas a false positive scan had no subsequent cancer diagnosis. A true negative PET scan was a negative scan without a cancer diagnosis during follow-up, whereas a false negative PET scan was one with a subsequently confirmed cancer diagnosis. Ninety-three patients, aged 67years (range 25-89) were included and followed for up to 7.3years (median 6). Of these, 21 [22.6% (95% CI 15.3-32.1)] turned out to have cancer. With 18F-FDG-PET/CT, the sensitivity was 81.0% (95% CI 60.0-92.3), specificity 76.4% (95% CI 65.4-84.7), positive predictive value 50% (95% CI 34.1-65.9), and negative predictive value 93.2% (95% CI 83.8-97.3). Five patients with negative scans were subsequently diagnosed with cancer. Cancer prevalence is substantial among patients with SSD. 18F-FDG-PET/CT is a promising option in this setting, in particular because a high negative predictive value equals a low incidence of cancer during follow-up. Further studies are needed to establish the role of 18F-FDG-PET/CT in SSD.

Utility of Amyloid PET Scans in the Evaluation of Patients Presenting with Diverse Cognitive Complaints.

The impact of amyloid positron emission tomography (Aβ-PET) in a "real-world" memory disorders clinic remains poorly studied. We studied the impact of Aβ-PET in diagnosis and management in the memory clinic and factors making the most impact in diagnosis and management. We studied 102 patients who had presented at a memory disorders clinic (the Wien Center for Alzheimer's Disease and Memory Disorders, Miami Beach, FL) and had a diagnostic work-up for cognitive complaints, including Aβ-PET scans. Following Aβ-PET, changes were made in diagnosis (37.3%), in specific treatments for Alzheimer's disease (26.5%) and in psychiatric treatments (25.5%). The agreement between diagnosis pre-Aβ-PET versus post-Aβ-PET diagnosis was only fair, with a Cohen's kappa of 0.23 (95% CI 0-0.42). Patients with MRI findings suggestive of AD (medial temporal and/or parietal atrophy) were more frequently amyloid positive than amyloid negative (66.2% versus 33.8%, p = 0.04). Among patients with atypical clinical features for AD, but with MRI findings suggestive of AD, an amyloid negative PET scan had a greater impact than an amyloid positive PET scan on diagnosis (84.2% versus 17.1%, p < 0.001), management (84.2% versus 40%, p < 0.01) and discussion of results and advice on lifestyle (73.7% versus 22.9%, p < 0.001). We conclude that MRI features suggestive of AD predict a positive amyloid PET scan. However, among those with MRI features suggestive of AD but with atypical clinical features of AD, the clinical impact on diagnosis and management is greater for an amyloid negative than an amyloid positive Aβ-PET scans.

Influence of the Intensity of the Conditioning Regimens on the Risks of Gvhd in Patients Receiving Rituximab Prophylaxis during Allogeneic Stem Cell Transplantation (alloSCT)

Purpose: Rituximab (R) use can attenuate the risks of graft-versus-host disease (GVHD) after non-myeloablative allogeneic (NMA) alloSCT. There is a paucity of information on the impact of this strategy in patients receiving myeloablative (MA) conditioning.Experimental design: We compared the risk of GVHD after an NMA regimen of BFR (bendamustine, fludarabine, rituximab) (Khouri et al. Blood 20014;124:2306-12.) to the MA regimen of bortezomib-R-BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Patients were treated on 2 prospective trials at our center between 2009-2013 and 2007-2011, respectively. Patients were considered for NMA if they were not eligible for myeloablative chemotherapy. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. All patients received rituximab (375 mg/m2 intravenously on day -13 and 1000 mg/m2 on days -6, +1, and +8) as described previously. Patients in both groups also received thymoglobulin 1 mg/kg on days -2 and -1 if the transplant was from matched unrelated donor (MUD). In addition, the MA group received bortezomib (1 mg/m2 per dose) on days -13, -6, -1, and +2. Because the treatment groups were not randomized, we performed inverse probability weighting (Robins JM. Epidemiol. 2000; 11:550-60) to correct for potential bias in patients' selection for the comparison of GVHD.Results: The analysis included 95 patients (MA=39 and NMA=56). The majority of the patients were male (68%) with a median age of 58 years (range: 22-71). The most common histology was diffuse large B-cell lymphoma (26%), followed by chronic lymphocytic leukemia (23%), mantle cell lymphoma (19%), and follicular lymphoma (18%). Transplant characteristics included MUDs in 43 (45%) patients, 23 (24%) female-to-male donors, and 49 (52%) ABO-mismatched. In addition, CMV was reactive in 80% of patients/ and or donors. Most patients (95%) had alloSCT from peripheral blood. Significant differences between treatment groups were observed for patient age, histology, PET scan status, LDH, disease status, and prior number of chemotherapies. On average, patients receiving MA conditioning were younger (p=0.008) and had higher LDH (p=0.026) pre-transplant, compared with NMA group. In addition, a higher percentage of MA patients were diagnosed with diffuse large B-cell lymphoma (41% vs. 16%, p=0.003), had a positive PET scan (p<0.001), had refractory disease (p=0.001), and received > 3 prior number of chemotherapies (p=0.007) compared with the NMA patients. The median follow-up duration for surviving patients was 64.8 and 62.1 months for the MA and NMA groups, respectively. The groups' weighted (adjusting for patient age, donor age, donor type, disease status, sex mismatch status, histology, PET scan status, LDH, and prior number of chemotherapies) cumulative incidences of grade II-IV acute GVHD was 63% and 10%, respectively (p<0.0001) (Fig 1), grade III- IV acute GVHD 34% vs. 8% (p < 0.0001), and chronic GVHD (80% vs. 35%, p<0.0001; Fig 2), for MA and NMA groups, respectively. Among the patients who developed chronic GVHD, a significantly higher percentage of patients in the NMA group experienced de novo subtype of chronic GVHD compared with the MA group (71% vs. 32%; p=0.025) resulting in a significant difference of 5-year survival in patients who developed chronic GVHD (90% vs. 62%, respectively; p=0.047) between NMA and MA groups.Conclusions: This is the first study to analyze the impact of the conditioning regimen intensity on the risk of GVHD in patients receiving rituximab prophylaxis with their transplants. Our results indicate that the intensity of the conditioning regimen remains a strong predictor of acute and chronic GVHD despite the use of rituximab. [Display omitted] DisclosuresJabbour:Pfizer: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Research Funding; Takeda: Consultancy, Research Funding; Abbvie: Research Funding. Oran:Celgene: Consultancy, Research Funding; ASTEX: Research Funding; AROG pharmaceuticals: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

Durable Remissions Achieved with R-CHOP Chemotherapy without Radiotherapy in Patients with Primary Mediastinal B-Cell Lymphoma - the Royal Marsden Experience

Introduction: Primary mediastinal B Cell Lymphoma (PMBL) is a high-grade non-hodgkin lymphoma with distinct clinical and biological features. Optimal chemotherapy for this lymphoma is not established but some centres favour more intensive regimes such as DA EPOCH-R over R-CHOP. The role of consolidation radiotherapy is yet to be clarified and whether it can be omitted in those patients with a negative end-of-treatment PET scan (EOT PET) regardless of induction chemotherapy. Furthermore, the occurrence of false positive EOT PET scans may lead to overtreatment. The aim of this study was to establish the outcomes of patients (pts) with PMBL who had been treated in a single centre.Methods: Pts diagnosed with PMBL between 2003 and 2015 in Royal Marsden Hospital were included. Data was collected from electronic patient records and PET CT images review. Survival was defined from date of diagnosis until date of death or date of last follow up.Results: Thirty-four pts were identified with characteristics as shown in the table. Median diameter of the mediastinal mass was 12cm (range 5.5 - 24cm); 25 (74%) pts had a mass of ≥ 10cm. The majority of pts received R-CHOP chemotherapy (2 had 14 day cycles, 30 had 21 day cycles), 1 R-GCVP and another R-PACEBOM. Median number of cycles of chemotherapy was 6 (range 1-8). Seven out of 32 (22%) pts received involved field radiotherapy (IFRT).EOT PET was available for 30 pts. Median time to obtaining EOT PET from completion of chemotherapy was 31 days (20-81). Twenty-three out of 30 pts had EOT PET negative disease with a Deauville score (DS) of 1-3. Twenty-one of these 23 pts did not receive IFRT. Two of these 21 pts relapsed in the mediastinum and were treated with salvage chemotherapy followed by autologous stem cell transplant (ASCT) of whom 1 died due to their lymphoma. The 2 patients who received consolidation radiotherapy remain in remission.Seven out of 30 pts had a positive EOT PET (DS 4-5); of whom 5 received IFRT. Two out of 5 patients relapsed and proceeded with further chemotherapy of whom 1 died due to treatment-related causes while the other 4 patients were alive at time of last follow-up. Two pts with a positive EOT PET did not have IFRT, 1 proceeded with salvage chemotherapy but died due to lymphoma and the other patient was followed up with serial PET scans and ultimately the residual avidity was considered to be due to thymic hyperplasia.Conclusion: Our analysis demonstrates that for the 23 patients who achieved a complete metabolic response on EOT PET the risk of relapse was low (9%) (despite that only 2 patients received consolidation radiotherapy) and only one patient (4%) died of lymphoma. Thus the majority of patients with a negative EOT PET scan following R-CHOP chemotherapy may not need consolidation radiotherapy. This finding should be taken into account when considering the risk/benefit of adding radiotherapy treatment to patients who are already in metabolic CR after chemotherapy. Consolidation radiotherapy is currently being investigated in a prospective IELSG37 trial, NCT01599559. [Display omitted] DisclosuresChau:Eli-Lilly: Honoraria, Other: Advisory Board, Research Funding; Bristol Meyers Squibb: Other: Advisory Board; MSD: Other: Advisory Board; Bayer: Other: Advisory Board; Roche: Other: Advisory Board; Merck Serono: Other: Advisory Board, Research Funding; Five Prime Therapeutics: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Janssen-Cilag: Research Funding; Sanofi Oncology: Research Funding. Cunningham:Roche pharmaceuticals: Research Funding.

Evaluation of 11C-Methionine PET and Anatomic MRI Associations in Diffuse Intrinsic Pontine Glioma.

The role of metabolic imaging in the diagnosis, treatment, and response assessment of diffuse intrinsic pontine glioma (DIPG) is poorly defined. We investigated the uptake of 11C-methionine in pediatric patients with newly diagnosed DIPG and evaluated the associations of 11C-methionine PET metrics with conventional MRI indices and survival outcomes. Methods: Twenty-two patients with newly diagnosed DIPG were prospectively enrolled on an institutional review board-approved investigational study of 11C-methionine PET. All patients underwent baseline 11C-methionine PET/CT, and initial treatment-response scans after chemotherapy or radiation therapy were obtained for 17 patients. Typical and atypical DIPGs were assessed clinically and radiographically and defined by multidisciplinary consensus. Three-dimensional regions of interest, reviewed by consensus between a nuclear medicine physician and a radiation oncologist, were delineated after coregistration of PET and MR images. Associations of 11C-methionine uptake intensity and uniformity with survival, along with associations between 11C-methionine uptake and conventional MRI tumor indices over time, were evaluated. 11C-methionine PET voxel values within regions of interest were assessed as threshold values across proportions of the study population, and 11C-methionine uptake at baseline was assessed relative to MRI-defined tumor progression. Results:11C-methionine uptake above that of uninvolved brain tissue was observed in 18 of 22 baseline scans (82%) and 15 of 17 initial response scans (88%). 11C-methionine avidity within MRI-defined tumor was limited in extent, with 11 of 18 positive baseline 11C-methionine PET scans (61%) showing less than 25% 11C-methionine-avid tumor. The increase in total tumor volume with 11C-methionine PET was relatively limited (17.2%; interquartile range, 6.53%-38.90%), as was the extent of 11C-methionine uptake beyond the MRI-defined tumor (2.2%; interquartile range, 0.55%-10.88%). Although baseline 11C-methionine PET intensity and uniformity metrics did not correlate with survival outcomes, initial 11C-methionine avidity overlapped with recurrent tumor in 100% of cases. A clinical diagnosis of atypical DIPG was associated with borderline significantly prolonged progression-free survival (P = 0.07), yet 11C-methionine PET indices at diagnosis did not differ significantly between atypical and typical DIPGs. Conclusion: Most newly diagnosed DIPGs are successfully visualized by 11C-methionine PET. Baseline 11C-methionine uptake delineates regions at increased risk for recurrence, yet intensity and uniformity metrics did not correlate with treatment outcomes in children with DIPG in this study.

Increased overall survival after introduction of structured bedside consultation in Staphylococcus aureus bacteraemia

Staphylococcus aureus bacteraemia (SAB) is a common and severe disease. In 2012, a structured bedside consultation (SBC) was introduced at Rijnstate Hospital. We analysed the effect of this SBC on the overall survival of patients with SAB and the effect on the diagnostic workup. We performed a retrospective cohort study, including all patients over 18years with SAB from 2009 until 2017. The cases preceding versus those after implementation of SBC in 2012 were compared. In total, 613 episodes of SAB were analysed: 234 cases before and 379 cases since SBC. In 484 patients at risk for a complicated course, there was no significant difference in the 30-day survival (77 versus 82%, p = 0.18); however, an increase in 365-day survival was seen (56 versus 64%, p = 0.05). Overall, more patients received adequate therapy, both in the first 2weeks (67.8 versus 86.7%, p < 0.001), as in complicated SAB (70.5 versus 93.2%, p < 0.001). In 21% of patients with transoesophageal echocardiogram (TEE) following a negative or inconclusive TTE, endocarditis was diagnosed. In patients at risk for complicated SAB, the PET scan revealed a metastatic infection which was not clinically suspected in 65% of positive PET scans. Structured bedside consultation is associated with a better 365-day survival in patients at risk for complicated SAB. Moreover, the additional value of TEE and the PET scan was shown. We strongly advise compliance to SBC in all patients at risk for complicated SAB and the use of both TEE and PET scans in these patients. Even in uncomplicated SAB, TEE or PET scan can reveal metastatic infections.

Odor Identification Ability Predicts PET Amyloid Status and Memory Decline inOlder Adults.

Odor identification deficits occur in Alzheimer's disease (AD), as measured by the 40-item University of Pennsylvania Smell Identification Test (UPSIT). To determine if UPSIT scores predict amyloid-β (Aβ) status, determined by 11C-Pittsburgh Compound B PET. We also compared UPSIT scores to Aβ status in predicting future memory decline. Subjects were recruited into a longitudinal clinical prediction study. We analyzed data from those who had UPSIT, cognitive testing, PIB PET, and at least 12 months' clinical follow-up. Forty-six amnestic mild cognitive impairment patients and 25 cognitively normal controls were included. Amyloid-positivity was defined as composite PIB standardized uptake value ratio >1.5. Logistic regression and Receiver Operating Characteristic Curve analyses tested the predictive utility of impaired olfaction (defined as UPSIT score <35) and amyloid-positivity for memory decline. High UPSIT scores predicted absence of amyloidosis on PET, with negative predictive value of 100%. Positive predictive value of low UPSIT scores on positive Aβ status was only 41%. Both low UPSIT score (OR = 4.301, 95% CI = 1.248, 14.821, p = 0.021) and positive PET scan (OR = 20.898, 95% CI = 2.222, 196.581, p = 0.008) predicted memory decline. Individuals with high UPSIT scores are less likely to have cerebral amyloidosis or experience memory decline. Therefore, UPSIT has potential as a screening tool to determine utility of Aβ PET in clinical practice or enrollment in clinical trials. Low UPSIT score is a non-specific marker of neurodegeneration that could indicate further workup in patients with memory complaints.

Biological tumour volumes of gliomas in early and standard 20-40min 18F-FET PET images differ according to IDH mutation status.

For the clinical evaluation of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET images, the use of standard summation imagesobtained 20-40min after injection is recommended. However, early summation imagesobtained 5-15min after injection have been reported to allow better differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) by capturing the early 18F-FET uptake peak specific for HGG. We compared early and standard summation images with regard to delineation of the PET-derived biological tumour volume (BTV) in correlation with the molecular genetic profile according the updated 2016 WHO classification. The analysis included 245 patients with newly diagnosed, histologically verified glioma and a positive 18F-FET PET scan prior to any further treatment. BTVs were delineated during the early 5-15min and standard 20-40min time frames using a threshold of 1.6 × background activity and were compared intraindividually. Volume differences between early and late summation images of >20% were considered significant and were correlated with WHO grade and the molecular genetic profile (IDH mutation and 1p/19q codeletion status). In 52.2% of the patients (128/245), a significant difference in BTV of >20% between early and standard summation images was found. While 44.3% of WHO grade II gliomas (31 of 70) showed a significantly smaller BTV in the early summation images, 35.0% of WHO grade III gliomas (28/80) and 37.9% of WHO grade IV gliomas (36/95) had a significantly larger BTVs. Among IDH-wildtype gliomas, an even higher portion (44.4%, 67/151) showed significantly larger BTVs in the early summation images, which was observed in 5.3% (5/94) of IDH-mutant gliomas only: most of the latter had significantly smaller BTVs in the early summation images, i.e. 51.2% of IDH-mutant gliomas without 1p/19q codeletion (21/41) and 39.6% with 1p/19q codeletion (21/53). BTVs delineated in early and standard summation images differed significantly in more than half of gliomas. While the standard summation images seem appropriate for delineation of LGG as well as IDH-mutant gliomas, a remarkably high percentage of HGG and, particularly, IDH-wildtype gliomas were depicted with significantly larger volumes in early summation images. This finding might be of interest for optimization of treatment planning (e.g. radiotherapy) in accordance with the individual IDH mutation status.

Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment.

Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as 'fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called 'fixels') to assess potential axonal loss in subjects with Alzheimer's disease and mild cognitive impairment. We hypothesized that patients with Alzheimer's disease would exhibit extensive degeneration across key fibre pathways connecting default network nodes, while patients with mild cognitive impairment would exhibit selective degeneration within fibre pathways connecting regions previously identified as functionally implicated early in Alzheimer's disease. Diffusion MRI data from Alzheimer's disease (n = 49), mild cognitive impairment (n = 33), and healthy elderly control subjects (n = 95) were obtained from the Australian Imaging, Biomarkers and Lifestyle study of ageing. We assessed microstructural differences in fibre density, and macrostructural differences in fibre bundle morphology using fixel-based analysis. Whole-brain analysis was performed to compare groups across all white matter fixels. Subsequently, we performed a tract of interest analysis comparing fibre density and cross-section across 11 selected white matter tracts, to investigate potentially subtle degeneration within fibre pathways in mild cognitive impairment, initially by clinical diagnosis alone, and then by including amyloid status (i.e. a positive or negative amyloid PET scan). Our whole-brain analysis revealed significant white matter loss manifesting both microstructurally and macrostructurally in Alzheimer's disease patients, evident in specific fibre pathways associated with default mode network nodes. Reductions in fibre density and cross-section in mild cognitive impairment patients were only exhibited within the posterior cingulum when statistical analyses were limited to tracts of interest. Interestingly, these degenerative changes did not appear to be associated with high amyloid accumulation, given that amyloid-negative, but not positive, mild cognitive impairment subjects exhibited subtle focal left posterior cingulum deficits. The findings of this study demonstrated a stereotypical distribution of white matter degeneration in patients with Alzheimer's disease, which was in line with canonical findings from other imaging modalities, and with a network-based conceptualization of the disease.awx355media15726254535001.