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Supplemental Figure S4. Progression-free survival Kaplan-Meier curves based on PET and ctDNA parameters. A. PFS based on baseline SUV categorized into lower and higher than median. B. PFS based on baseline tumor glycolysis level lower or higher than median. C. PFS based on baseline metabolic tumor volume (MTV) lower or higher than median.

Supplemental Figure S3. A. Waterfall plot based on RECIL criteria. RECIL introduces the minimal response category which is a 10-30% reduction in the sum of longest diameters of target lesions. B. Event-free survival Kaplan-Meier curve.

Supplemental Figure S2. A. Comparison of treatment-related and -unrelated adverse events occurring in >10% of evaluable patients.

Supplemental Figure S1. Dosing of patients on study. A. MCL cohort. B. FL cohort. C. DLBCL cohort.

Purpose: Activation of Bruton tyrosine kinase (BTK) and phosphatidylinositol-3-kinase (PI3K) represent parallel, synergistic pathways in lymphoma pathogenesis. As predominant PI3Kδ inhibition is a possible mechanism of tumor escape, we proposed a clinical trial of dual BTK and pan-PI3K inhibition. Patients and Methods: We conducted a single-center phase I/Ib trial combining a BTK inhibitor (ibrutinib) and a pan-PI3K inhibitor (buparlisib) in 37 patients with relapsed/refractory (R/R) B-cell lymphoma. Buparlisib and ibrutinib were administered orally, once daily in 28-day cycles until progression or unacceptable toxicity. The clinical trial is registered with clinicaltrials.gov, NCT02756247. Results: Patients with mantle cell lymphoma (MCL) receiving the combination had a 94% overall response rate (ORR) and 33-month median progression-free survival; ORR of 31% and 20% were observed in patients with diffuse large B-cell lymphoma and follicular lymphoma, respectively. The maximum tolerated dose was ibrutinib 560 mg plus buparlisib 100 mg and the recommended phase II dose was ibrutinib 560 mg plus buparlisib 80 mg. The most common grade 3 adverse events were rash/pruritis/dermatitis (19%), diarrhea (11%), hyperglycemia (11%), and hypertension (11%). All grade mood disturbances ranging from anxiety, depression, to agitation were observed in 22% of patients. Results from serial monitoring of cell-free DNA samples corresponded to radiographic resolution of disease and tracked the emergence of mutations known to promote BTK inhibitor resistance. Conclusions: BTK and pan-PI3K inhibition in mantle cell lymphoma demonstrates a promising efficacy signal. Addition of BCL2 inhibitors to a BTK and pan-PI3K combination remain suitable for further development in mantle cell lymphoma.

Early identification of patients with diffuse large B-cell lymphoma (DLBCL) who are likely to experience disease recurrence or refractory disease after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) would be useful for improving risk-adapted treatment strategies. We aimed to assess the prognostic value of

Recent prospective clinical trial data suggest that patients with Hodgkin’s lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome.

In follicular lymphoma (FL), detection of bone marrow (BM) involvement (BMI) by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) improves the accuracy of staging vs BM biopsy (BMB) alone. Our objective was to determine the diagnostic utility of PET for BMI FL and the prognostic value of BMI by PET (positive PET result [PET+]). Records of patients (2002-2016) with PET and BMB at the time of initial treatment were reviewed. BMI was identified by positive BMB result (BMB+) and/or unifocal or multifocal BM FDG uptake on blindly reviewed PET scans with no corresponding CT abnormality (PET+). Among 261 patients, BMI was diagnosed in 78 patients (29.9%) by PET+, in 81 patients (31.0%) by BMB+, and in 113 patients (43.3%) by either PET+ or BMB+. PET+ upstaged 24 patients to stage IV, including 10 from stages I or II to stage IV. Median duration of follow-up was 6.0 years (range, 0-16.6 years). In univariate analysis, a high Follicular Lymphoma International Prognosis Index (FLIPI) score, PET+, and BMB+ correlated with shorter progression-free survival (PFS; all P ≤ .03), and high FLIPI, PET+, and combined PET+ and BMB+ with shorter overall survival (OS; all P ≤ .01). In multivariate analysis, PET+ was the only independent predictor of PFS, whereas high FLIPI score and PET+ predicted OS (P ≤ .03). Combined PET and BMB identify BMI more accurately than either BMB or PET alone, but BMB rarely adds critical information. For patients initiating treatment of FL, identification of BMI by PET is predictive of PFS and OS.

Paraneoplastic Cushing’s syndrome (PCS) is frequently caused by neuroendocrine tumours (NETs). Approximately 20% of tumours are still occult years later. Gallium-68 somatostatin receptor-PET/CT is promising for the detection of the causal primary NET, but its role in case of recurrent PCS is rarely reported. We report our experience with DOTATOC PET/CT in localising the causal NET in cases of initial but also recurrent PCS, and its clinical impact. A retrospective review of all DOTATOC PET/CTs performed in consecutive patients referred for PCS to our centre, between January 2011 and June 2017, was done. Nineteen patients underwent 26 PET/CTs, 13 for detection of a primary NET, seven for persistent or recurrent PCS after resection, and six for surveillance after resection of NETs previously detected on a DOTATOC PET/CT in our centre. Among the 13 PET/CTs performed to search for primary NET, five were positive: four carcinoid lung tumours were confirmed after resection and one lung focus was not confirmed since surgery would have carried a high risk. Clinical impact was 23% (3/13). Among the seven PET/CTs performed for persistent or recurrent PCS, six were true-positive, with confirmation of metastatic lymph nodes after resection. Clinical impact was 57% (4/7). All PET/CTs performed for surveillance were true-negative. DOTATOC PET/CT seems to be a valuable tool for detection of the NET responsible for persistent or recurrent PCS after surgery. In this context, DOTATOC PET/CT was more effective than for the detection of the causal tumour in initial PCS.

Our purpose was to evaluate the performance of (11)C-choline PET/CT in detecting biochemically recurrent prostate cancer (PCa) in a large non-European cohort (in the context of emerging evidence for prostate-specific membrane antigen PET in this setting) and to map patterns of PCa recurrence. Methods: We retrospectively analyzed (11)C-choline PET/CT scans from 287 patients who were enrolled in an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean, 3.43 ng/mL; median, 0.94 ng/mL; range, 0.15–89.91 ng/mL) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP) (79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy, and 70 had a persistent PSA elevation after receiving initial treatment (69 after RP, 1 after radiotherapy). The level of suspicion for recurrence on (11)C-choline PET/CT was scored (0, negative; 1, equivocal; 2, positive) by 2 readers. The correlation between (11)C-choline PET/CT positivity and initial treatment, Gleason score, National Comprehensive Cancer Network stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map (11)C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the 2 readers deemed 66% of the (11)C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with a PSA of less than 0.5 ng/mL, 56% of patients with a PSA of 0.5–0.99 ng/mL, 70% of patients with a PSA of 1.0–1.99 ng/mL, and 90% of patients with a PSA of at least 2.0 ng/mL scored either 1 or 2 on (11)C-choline PET/CT scans. When considering scores of 2 only, (11)C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA < 0.5 ng/mL, 0.5–0.99 ng/mL, 1.0–1.99 ng/mL, and ≥ 2.0 ng/mL). In multivariate analysis, only PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had (11)C-choline–positive suspected recurrences outside the initial treatment field. Conclusion: (11)C-choline PET/CT can detect PCa recurrence even among patients with low PSA levels when interpretation accounts for the clinical context, providing a certain pretest probability. Until prostate-specific membrane antigen agents are fully approved for PCa, choline PET/CT may provide clinical utility.

Older patients with advanced hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplantation (allo-HCT) yet their survival outcomes remain suboptimal. We and others have previously shown that pre-HCT multi-morbidity and functional limitation and post-HCT geriatric syndromes significantly impact outcomes. Sarcopenia, an accelerated loss of muscle mass and function, has been increasingly recognized in older cancer patients. We identified 146 lymphoma patients 50 years or older who were allografted from 2008 to 2018 at our institution and found that before allo-HCT, 80 (55%) patients were sarcopenic. Pre-HCT sarcopenia was significantly associated with overall survival, progression-free survival, and non-relapse mortality independent of multi-morbidity and functional limitation. In 6-month landmark analysis, post-HCT sarcopenia remained significantly associated with survival. Our findings illustrate the high prevalence and profound impact of sarcopenia on survival. While requiring prospective confirmation, preemptive, longitudinal, and multidisciplinary interventions for sarcopenia are warranted to improve HCT outcomes for older patients.

The aim of this study was to investigate the value of pharmacokinetic modeling for quantifying (11)C-choline uptake in patients with recurrent prostate cancer. Methods: In total, 194 patients with clinically suspected recurrence of prostate cancer underwent (11)C-choline dynamic PET over the pelvic region (0–8 min), followed by a 6-min static acquisition at about 25 min after injection. Regions of interest were drawn over sites of disease identified by a radiologist with experience in nuclear medicine. (11)C-choline uptake and pharmacokinetics were evaluated by SUV, graphical analysis (Patlak plot; K(i)(P)), and 1- and 2-compartment pharmacokinetic models (K(1), K(1)/k(2), k(3), k(4), and the macro parameter K(i)(C)). Twenty-four local recurrences, 65 metastatic lymph nodes, 19 osseous metastases, and 60 inflammatory lymph nodes were included in the analysis, which was subsequently repeated for regions of interest placed over the gluteus maximus muscle and adipose tissue as a control. Results: SUV(mean) and K(i)(P) were 3.60 ± 2.16 and 0.28 ± 0.22 min(−1) in lesions, compared with 2.11 ± 1.33 and 0.15 ± 0.10 min(−1) in muscle and 0.26 ± 0.07 and 0.02 ± 0.01 min(−1) in adipose tissue. According to the Akaike information criterion, the 2-compartment irreversible model was most appropriate in 85% of lesions and resulted in a K(1) of 0.79 ± 0.98 min(−1) (range, 0.11–7.17 min(−1)), a K(1)/k(2) of 2.92 ± 3.52 (range, 0.31–20.00), a k(3) of 0.36 ± 0.30 min(−1) (range, 0.00–1.00 min(−1)) and a K(i)(C) of 0.28 ± 0.22 min(−1) (range, 0.00–1.33 min(−1)). The Spearman ρ between SUV and K(i)(P), between SUV and K(i)(C), and between K(i)(P) and K(i)(C) was 0.94, 0.91, and 0.97, respectively, and that between SUV and K(1), between SUV and K(1)/k(2), and between SUV and k(3) was 0.70, 0.44, and 0.33, respectively. Malignant lymph nodes exhibited a higher SUV, K(i)(P), and K(i)(C) than benign lymph nodes. Conclusion: Although (11)C-choline pharmacokinetic modeling has potential to uncouple the contributions of different processes leading to intracellular entrapment of (11)C-choline, the high correlation between SUV and both K(i)(P) and K(i)(C) supports the use of simpler SUV methods to evaluate changes in (11)C-choline uptake and metabolism for treatment monitoring.

Background: In untreated Hodgkin lymphoma (HL), metabolic tumor volume (MTV) significantly declined following pembrolizumab monotherapy, regardless of baseline MTV, and may serve as a better measure of treatment response to PD-1 blockade than the Lugano Classification (Allen, et al. Blood 2021). Furthermore, standard PET evaluation can fail to differentiate between malignancy, pseudoprogression and physiological background in patients (pts) receiving PD-1 blockade. The predictive power and prognostic significance of MTV in patients with relapsed or refractory (RR) HL receiving PD-1 blockade is unknown. We sought to examine the role of MTV in HL pts treated with PD-1 blockade. Methods: We identified 30 pts who received pembrolizumab or nivolumab-based therapy off-study for RR HL between July 2015 and May 2021. In the PET/CT analysis, all lesions were visually identified, and all measurable lesions were selected for the analysis. Responses were assessed by Lugano Classification. Indeterminant response (IR) was defined as evidence of progression on PET without clinical deterioration as per the Lyric Criteria. MTV was obtained by summing the metabolic volumes of all measurable lesions, using the 41% SUVmax threshold to measure each lesion MTV using Beth Israel plugin. MTV was evaluated at baseline (MTV0) and at first reassessment (MTV1) after initiation of PD-1 blockade. Δ (delta) MTV was calculated as % change in MTV from MTV0 to MTV1. Receiver operating characteristic (ROC) curve was performed for ΔMTV and best overall response rate (BOR) to determine the optimal cut-off value. Overall survival (OS) was measured from PD-1 blockade initiation to death or last follow-up. We examined the association between MTV and clinical factors, PET-1 response, and overall survival using Cox proportional hazards model and Fisher exact test, respectively. Results: 25 patients had complete clinical data and PET/CT analysis (Table 1). The median age at first relapse was 39 years (range: 18-81); 64% were male. 6 pts previously received PD-1 blockade on clinical trials and discontinued treatment due to study completion or toxicity. The median time between PET0 and PET1 was 3.4 months (range 2.0-7.3). Median MTV0 and MTV1 values were 39.8 ml and 17.1 ml, respectively. With a median follow up from initiation of PD-1 blockade among survivors of 38.7 months, 5 pts (19%) died. The median OS of the entire cohort was not reached (95%CI: 76.4-NR) (Figure 1). The best response to PD-1 blockade included 15 (60%) with complete metabolic response (CMR), 5 (20%) with partial metabolic response (PMR), and 5 (20%) with progression of disease (POD). Median ΔMTV was -70% (range -100 to +909%). MTV0 was not predictive of OS, PET1 response, or BOR. However, ΔMTV predicted for PET1 response (p=0.004) and BOR (p=0.004). 18 (72%) pts had a reduction in ΔMTV (range: -100, -22), while 7 (28%) pts had an increase in ΔMTV (range: 33-909). The optimal ΔMTV threshold for prediction of BOR was 120% (Figure 1). ΔMTV Among pts with IR on PET-1, ΔMTV Conclusions: Quantitative change in MTV from baseline to first reassessment may aid in predicting treatment response and long-term outcomes in patients with RR HL receiving PD-1 blockade, particularly those initially characterized as achieving indeterminate response. Further prospective clinical trials are needed to validate the role of ΔMTV in predicting response and long-term outcomes for RR HL pts receiving PD-1 blockade. Figure 1 Figure 1. Disclosures Moskowitz: Merck & Co., Inc.: Research Funding. Matasar: Seattle Genetics: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; Juno Therapeutics: Consultancy; Merck: Consultancy; Pharmacyclics: Honoraria, Research Funding; Rocket Medical: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; GlaxoSmithKline: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding; Merck Sharp & Dohme: Current holder of individual stocks in a privately-held company; Teva: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; IGM Biosciences: Research Funding; Takeda: Consultancy, Honoraria. Zelenetz: Amgen: Honoraria; MorphoSys: Honoraria; Novartis: Honoraria; MEI Pharma: Honoraria, Research Funding; Beigene: Honoraria, Other, Research Funding; Gilead: Honoraria, Research Funding; Pharmacyclics: Honoraria; SecuraBio: Honoraria; Genentech/Roche: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Verastem: Honoraria; BMS/Celgene/JUNO: Honoraria, Other; MethylGene: Research Funding; AstraZeneca: Honoraria; Janssen: Honoraria; NCCN: Other; LFR: Other; Gilead: Honoraria. Joffe: AstraZeneca. Epizyme: Consultancy. von Keudell: Merck: Research Funding; Janssen: Research Funding; BMS: Research Funding; Incyte: Consultancy, Honoraria; AbbVie: Research Funding; Merck: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria. Batlevi: Medscape: Honoraria; Memorial Sloan Kettering Cancer Center: Current Employment; Moderna: Current holder of individual stocks in a privately-held company; Pfizer: Current holder of individual stocks in a privately-held company; ADC Therapeutics: Consultancy; Regeneron: Current holder of individual stocks in a privately-held company; TG Therapeutics: Consultancy; Kite Pharma: Consultancy; Seattle Genetics: Consultancy; TouchIME: Honoraria; BMS: Current holder of individual stocks in a privately-held company; Bayer: Research Funding; Viatris: Current holder of individual stocks in a privately-held company; Karyopharm: Consultancy; Juno/Celgene: Consultancy; Life Sciences: Consultancy; Dava Oncology: Honoraria; GLG Pharma: Consultancy; Xynomic: Research Funding; Roche/Genentech: Research Funding; Novartis: Research Funding; Epizyme: Research Funding; Janssen: Research Funding; Autolus: Research Funding. Caron: Astra-Zeneca: Current holder of individual stocks in a privately-held company; bristol myers: Current holder of individual stocks in a privately-held company; GlaxoSmithKlein: Current holder of individual stocks in a privately-held company; Johnson and Johnson: Current holder of individual stocks in a privately-held company; Novartis: Current holder of individual stocks in a privately-held company; pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company. Noy: Rafael Parhma: Research Funding; Morphosys: Consultancy; Medscape: Consultancy; Pharmacyclics: Consultancy, Research Funding; Targeted Oncology: Consultancy; Epizyme: Consultancy; Janssen: Consultancy, Honoraria. Salles: Velosbio: Consultancy; Morphosys: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Novartis: Consultancy; Epizyme: Consultancy, Honoraria; Allogene: Consultancy; Rapt: Consultancy; Genentech/Roche: Consultancy; Takeda: Consultancy; Miltneiy: Consultancy; Loxo: Consultancy; Kite/Gilead: Consultancy; Genmab: Consultancy; Incyte: Consultancy; Ipsen: Consultancy; Janssen: Consultancy; Debiopharm: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria. Moskowitz: ADC Therapeutics: Research Funding; Takeda: Consultancy; Incyte: Research Funding; Merck: Consultancy, Research Funding; Beigene: Research Funding; Seattle Genetics: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Miragen: Research Funding; Janpix Ltd.: Consultancy; Imbrium Therapeutics L.P./Purdue: Consultancy.

Resumen Introduccion Es necesaria una toma de imagenes precisa y fiable para mejorar el manejo del cancer de prostata. Durante los ultimos anos la PET/TC colina ha cambiado el manejo del cancer de prostata en Europa, y se utiliza comunmente para la estadificacion inicial o para diagnostico de la recurrencia bioquimica, aunque no carece de limitaciones. Otros marcadores estan a prueba, incluyendo el ligando del antigeno prostatico especifico de membrana (PSMA), que parece ofrecer perspectivas alentadoras. El objetivo de este trabajo fue revisar criticamente la actuacion de la colina y PSMA PET/TC en el cancer de prostata. Adquisicion de la evidencia Se realizo una revision sistematica de la literatura en la base de datos PUBMED/MEDLINE y EMBASE mediante la busqueda de articulos de texto completo en ingles publicados en el marcador PET en el cancer de prostata en la aplicacion clinica. Sintesis de la evidencia y Discusion Parece que 68Ga-PSMA PET/TC es mejor que PET/TC en el cancer de prostata para la deteccion de lesiones de prostata primarias, la deteccion inicial de metastasis en los ganglios linfaticos y la recurrencia. Sin embargo, se necesitan mas estudios para obtener pruebas de alto nivel. Ademas, en esta revision se analizan futuros otros marcadores de PET. Por otra parte, la aparicion de una nueva camara PET/RM puede cambiar el rendimiento de la toma de imagenes mediante PET.

e20017 Background: FDG avidity above liver on interim PET (PET2) during frontline ABVD is considered a marker of impending treatment failure and an indication to switch to an intensified regimen. However, in clinical practice the utility of PET2 for treatment decisions is less clear. We describe outcomes of patients with positive PET2 who continued treatment with ABVD in the clinical setting. Methods: A retrospective study of all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at Memorial Sloan Kettering Cancer Center between 2008-2017. Eligibility criteria were set to correspond with the RATHL inclusion criteria (stage IIB - IV, or IIA bulky or ≥ 3 involved sites). We identified all PET2 reports indicating suspected residual uptake. All positive PET2 images were then reviewed by a single study radiologist. To increase reproducibility and avoid selection of borderline cases, we defined as PET2 positive only those cases with a lesion-to-liver (mean) SUV ratio ≥ 1.3. We also used a recently published stringent criterion of lesion-to-liver (max) ratio ≥ 1.4 (mPET2+). Progression-free and overall survival (PFS, OS) were calculated from the date of initial treatment until progression or death of any cause. Consolidative radiation was not considered a PFS event, and all progressions were verified by biopsy. Results: We identified 227 patients fitting RATHL inclusion criteria treated with ABVD. Median age was 34, with 25% (58) ≥ 45 years, 12% (26) had an IPS ≥ 4; 28% (64) stage II (5% II-X) and 38% (87) with extranodal involvement. 57 (25%) patients had a PET2 report indicating suspected residual lymphoma (PET2+), however, only 32 (14%) met the more stringent mPET2+ criterion. Most patients with PET2+ continued ABVD (84%, 48), and 9 switched to escBEACOPP (this subset of patients had substantially worse disease and are not the focus of this analysis). 21 (9%) patients received consolidative radiation. With a median follow-up of 47 months (42-54m), PET2+ patients who continued ABVD had a 3yPFS of 70% (58-85%, n = 48); mPET+ had a 3yPFS of 71% (55-92%, n = 24). Overall survival was excellent regardless of PET2 status (5yOS 97%). Conclusions: The outcome of PET2+ patients in this analysis was better than previously reported and the continuation of ABVD was appropriate for most patients. Use of a confirmatory biopsy is important for identifying true progressions. Patients with PET2+ had an excellent OS. Evaluation of the superiority of alternative regimens in PET2+ patients requires an ABVD comparator arm.

Purpose The aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection. Methods Twenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI. Results 18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5 ± 2.3), while 11C-Methionine’s tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0 ± 2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p

To compare the impact of 18F-sodium-fluoride (NaF) PET/CT, 18F-fluorocholine (FCH) PET/CT and diffusion-weighted whole-body MRI (DW-MRI) on the management of patients with prostate cancer (PCa) suspicious for distant metastasis.Prostate cancer patients were prospectively included between December 2011 and August 2014 and benefited from these three whole-body imaging (WBI) modalities within 1 month in addition to the standard PCa workup. Management was prospectively decided by clinicians during two multidisciplinary meetings, before and after the whole-body imaging workup. Rates of induced changes of whole-body imaging modalities were compared by Cochran's Q test.One-hundred-one patients (27 at staging, 59 at first biochemical recurrence (BCR) and 15 at first episode of rising serum level of prostate-specific antigen during androgen-deprivation therapy) were included. The overall rate of management changes was 52%: 29% as a consequence of WBI, higher for FCH-PET/CT than for NaF-PET/CT or DW-MRI (p 0.0001) and highest (41%) for FCH-PET/CT at BCR. Actual management was adequate in all patients but two.Whole-body imaging induced a change in management in approximately a third of PCa patients suspicious for metastasis. The impact rate was determined to be greatest at first BCR using FCH-PET/CT. NaF-PET/CT and DW-MRI seemed less useful in this context.

Background Current imaging techniques may not detect all prostate cancer (PCa) lesions. Objective To evaluate positron emission tomography (PET)/computed tomography (CT) using the radiolabeled GRPR antagonist probe BAY86-7548 (68Ga-RM2) for localization of newly diagnosed PCa in comparison with multiparametric magnetic resonance imaging (mpMRI), histopathology, and immunohistochemistry (IHC). Design, setting, and participants This was a prospective study of 16 men with biopsy-proven PCa (2 low, 8 intermediate, and 6 high risk). 68Ga-RM2 PET/CT was performed within 4 wk after mpMRI and within 2 wk before radical prostatectomy and extended bilateral pelvic lymph node dissection. Outcome measurements and statistical analysis The presence of cancer was evaluated by blinded specialists using a 5-point Likert scale, with lesions scoring 4 or 5 considered positive, on 68Ga-RM2 PET/CT, mpMRI, and 68Ga-RM2 PET/CT-mpMRI fused images for each of 12 anatomic areas of the prostate. Whole-mount, step-section pathology served as the reference standard. Expression of GRPR and prostate-specific membrane antigen (PSMA) was analyzed via IHC of tumor paraffin sections. Results and limitations Of 192 areas analyzed, 128 contained cancer. The sensitivity, specificity, and accuracy of 68Ga-RM2 PET/CT imaging and mpMRI did not differ significantly; fusing the images maximized the sensitivity and accuracy (85.2% and 83.9%, respectively) and averaged the specificity (81.3%). The area under the receiver operating characteristic curve was 0.76 for PET visual analysis, 0.72 for PET quantitative analysis, 0.76 for mpMRI, and 0.85 for combined PET/CT and mpMRI analysis. 68Ga-RM2 uptake did not correlate with Gleason score. IHC analysis revealed weaker staining for GRPR than for PSMA, and the expression of these markers was not correlated (r = 0.3882). The major limitation is the small sample size. Conclusions 68Ga-RM2 PET/CT is promising for detection and localization of primary PCa, and complements mpMRI. GRPR expression appears to be independent from PSMA expression, suggesting that GRPR- and PSMA-targeted PET imaging may be complementary. Patient summary This pilot prospective study shows that a positron emission tomography probe that binds to a marker of prostate cancer, GRPR, improves the ability of magnetic resonance imaging to detect prostate cancer.

PURPOSE: To compare the impact of 18F-sodium-fluoride (NaF) PET/CT, 18F-fluorocholine (FCH) PET/CT and diffusion-weighted whole-body MRI (DW-MRI) on the management of patients with prostate cancer (PCa) suspicious for distant metastasis. METHODS: Prostate cancer patients were prospectively included between December 2011 and August 2014 and benefited from these three whole-body imaging (WBI) modalities within 1 month in addition to the standard PCa workup. Management was prospectively decided by clinicians during two multidisciplinary meetings, before and after the whole-body imaging workup. Rates of induced changes of whole-body imaging modalities were compared by Cochran's Q test. RESULTS: One-hundred-one patients (27 at staging, 59 at first biochemical recurrence (BCR) and 15 at first episode of rising serum level of prostate-specific antigen during androgen-deprivation therapy) were included. The overall rate of management changes was 52%: 29% as a consequence of WBI, higher for FCH-PET/CT than for NaF-PET/CT or DW-MRI (p

Older patients with advanced hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplantation (allo-HCT). However, survival outcomes, especially non-relapse mortality (NRM) in these patients remain suboptimal due to multi-morbidity and geriatric vulnerabilities. We and others have shown previously that pre-transplant multi-morbidity, and functional limitation and post-HCT geriatric syndromes of delirium and fall significantly impact allo-HCT outcomes. Sarcopenia, an accelerated loss of muscle mass and function, has been increasingly recognized to affect HCT outcomes. However, it remains unknown whether sarcopenia is a simple surrogate of multi-morbidity or functional impairment and whether post-transplant sarcopenia also impacts outcomes. From our institutional database and the electronic medical record, we identified 146 lymphoma patients 50 years or older who were transplanted at our institution from 2008 to 2018 using reduced-intensity/nonmyeloablative conditioning and a matched related or unrelated, mismatched unrelated, or haploidentical donor, and who had either a PETCT or CT within 60 days of HCT. Two adjacent axial images within the same series at the third lumbar vertebra were selected for the analysis of total muscle cross-sectional area (cm2) and of total fat (subcutaneous and visceral adipose tissues) cross-sectional area (cm2) using MIM software. Skeletal muscle cross-sectional area was normalized for stature and reported as skeletal muscle index in cm2/m2. Sarcopenia was defined as a skeletal muscle index Before allo-HCT, 80 (55%) patients were sarcopenic. Baseline demographic, transplant, and geriatric characteristics were well matched among the two groups except for slightly more females in the sarcopenic group (38% versus 21%, p=0.046). In multivariable analysis (Table 1), pre-HCT sarcopenia was significantly associated with overall survival (OS) with hazard ratio (HR) of 2.12 (95% CI 1.18 - 3.80, p=0.01); progression-free survival (HR 1.78, 95% CI 1.07 - 2.98, p=0.03); and NRM (HR 2.06, 95% CI 1.02 - 4.19, p=0.044). Multi-morbidity (HCT-CI ≥3) was independently associated with OS, PFS, and NRM, while functional impairment as measured by prior fall was significantly associated with PFS (Table 1). One hundred twenty-eight patients had CT images within 3-6 months post-HCT. Comparing to pre-transplant values, there were median decrease in total lean body mass of -2.86 kg (range -16.68 -9.87, p While limited by the retrospective design, single diagnosis of lymphoma, and inability to establish causal relationships among GVHD, steroid use, and post-HCT sarcopenia, our findings nevertheless illustrated the high prevalence of sarcopenia in older allo-HCT recipients. Importantly, we demonstrated significant negative impact of both pre- and post-HCT sarcopenia on survival which were independent of geriatric multi-morbidity, functional impairment, and acute GVHD. While requiring prospective confirmation, the temporal pattern and adverse survival impact of sarcopenia warrants preemptive, targeted, longitudinal, and multidisciplinary interventions to improve HCT outcomes for older patients. Disclosures Sauter: Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; GSK: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy; Kite/Gilead: Consultancy; Celgene: Consultancy; Sanofi-Genzyme: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding. Perales:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Medigene: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MolMed: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Kyte/Gilead: Research Funding; Miltenyi: Research Funding. Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Giralt:Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Actinium: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Kite: Consultancy; Jazz Pharmaceuticals: Consultancy; Amgen: Consultancy, Research Funding; Miltenyi: Research Funding; Takeda: Consultancy, Research Funding.

In this article, we estimate the structure of costs of hiring, terminating, and retiring employees in France. We use a representative panel data set of French establishments that contains direct measures of these various costs as well as measures of entries and exits for the years 1992 and 1996. First, we show that our panel data source is able to reproduce results obtained by Abowd and Kramarz (2003) when we use the cross-section dimension. Our estimates show that collective terminations are much more expensive than individual terminations: legislation, namely the requirement to set up a “social plan” in case of collective terminations, magnifies firing costs. Collective terminations entail very large fixed costs. Termination costs are essentially linear in the number of terminated workers, with collective terminations being much more expensive. The costs of retirement are concave in the number of retired workers with a fixed cost component which is smaller than the one estimated for terminations, and quite smaller than that obtained by Abowd and Kramarz (2003). Finally, we find that hiring costs are small and seem only present when hiring on CDI; costs of hiring on short-term contracts are almost zero. Finally, the fixed (firm-specific) component of hiring costs is very small.

Over the last two decades, EU institutions have been increasingly concerned with the issues of unemployment reduction and job creation. The EU has recommended that member states develop welfare systems that moderate the negative effects of market relationships on the one hand, and enhance the efficiency of market performance on the other. This paper provides an overview of labour market policies to protect individuals from unemployment. It shows that in the context of EMU and EU enlargement, policies such as unemployment insurance could improve welfare, to the extent that it encourages labour mobility, but has negative effects on individuals’ job search efforts. To counter welfare and inactivity traps, member state governments are asked to reform benefit and tax systems towards more employment-friendly policies. Further, the effect of population ageing on the labour force is considered, along with options to sustain labour force supply and state pension provision. The paper concludes that measures to expand the range and quality of employment opportunities available to older workers will become increasingly important and that governments will have an important educational and coordinating role to play in facilitating these adjustments.

In this article, we estimate the structure of costs of hiring, terminating, and retiring employees in France using a representative sample of French establishments. The estimates are estimated using a panel data set for two years (1992 and 1996) that matches two sources: the Wage Structure Survey (Enquête sur la Structure des Salaires) and the Workforce Questionnaire (Déclarations des Mouvements de Main-d'Oeuvre). We show that separation costs are significantly larger than hiring costs. The cost of hiring into Permanent Contracts is larger than the cost of hiring into Fixed Term Contracts and collective termination (dismissal of at least ten workers during a 30 days period) are much more expensive than individual terminations. Hiring and separations are similar in one aspect: they entail no firm-specific fixed cost. Furthermore, the termination and hiring costs are concave, and induce firms to group their hirings (into Permanent Contracts) and separations. Retirement costs are linear. Finally, legislation appears to be a major component of these costs.

A 72-year-old man was admitted with acute kidney failure. His previous medical history included clear-cell renal cell carcinoma of the right kidney treated with an enlarged nephrectomy 1 year ago. An adenocarcinoma of the right colon had been recently diagnosed and treated with a right colectomy and chemotherapy (folinic acid, fluorouracil, and oxaliplatin: cumulative dose 85 mg/m2). Anuria had developed over the previous 3 weeks. Renal ultrasound ruled out obstruction of the left urinary tract, and a Doppler excluded vascular thrombosis. Hemodialysis was started, and a transjugular renal biopsy was performed to determine the cause of kidney injury (Figure 1). Several lymphatic capillaries were dilated by clusters of atypical cells with a high nuclear/cytoplasm ratio, coarse chromatin, and prominent nucleoli. Immunochemistry revealed a nuclear expression of CDX2, a marker for colonic carcinoma (Figure 2). An 18F-fluorodeoxyglucose positron emission tomography/computed tomography examination confirmed the diagnosis of massive, hypermetabolic, carcinomatous lymphangitis in both lungs and kidney. As far as we are aware, this is the first report of a carcinomatous lymphangitis of non-renal origin spreading into the kidney. Whether the carcinomatous lymphangitis per se caused the kidney failure here is uncertain.