To determine whether radioembolization (RE) of breast cancer liver metastasis (BCLM) induces immune activation and evaluate markers of immune function for association with response to RE

We sought to understand the impact of sparing extracellular matrix at the site of irreversible electroporation (IRE) on ablation zone involution in patients treated for liver tumors, in comparison to microwave ablation (MWA), while determining the influence of functional liver status on these outcomes This retrospective study collected data from patients with successful CT/US-guided liver ablation at 1-year follow-up. Forty-four patients (17 women, 27 men, mean age 65.4 11.5 years) underwent 30 MWA (HCC:20; CRLM:10) or 14 IRE (HCC:5; CRLM:9) ablations. CECT scans were performed immediately postablation, and at 6 and 12-month follow-up. Liver function tests were collected 4 weeks prior to, 24/48 h and at follow-up after ablation. The 2 maximal diameters of the ablation zone were recorded, and surface area was calculated. The difference between ablation modalities on ablation zone involution and laboratory values were evaluated using generalized estimating equations to account for the correlation due to longitudinal measurements on the same patient. All statistical analyses were performed using SAS 9.4 or R 3.5.1. Immediate postablation zone measurement was not different between IRE (923.61 mm2) or MWA (1136.03 mm2) patients (P = 0.3586). The ablation zone area for IRE and MWA at 6 and 12-month time point differed significantly with a mean of 241.04 vs. 771.08 mm2 (P = 0.0004) and 60.47 vs. 589.43 mm2 (P = 0.0004) respectively. The rate of ablation zone involution for IRE and MWA varied significantly (Interaction P = 0.0017). The difference in the rate of ablation zone involution in IRE and MWA treated patients was significant at all assessed time points in the CRLM subgroup (P = 0.0069); but not in the HCC subgroup (P = 0.17). Transaminases values immediately after IRE were slightly higher than MWA without statistical significance. All clinical lab values returned to baseline by the 6- and 12-month follow-up in both cohorts. The rate of change in laboratory values over time did not differ significantly between IRE and MWA. IRE was associated with a faster involution of ablation on imaging when compared to MWA in both patients with healthy or cirrhotic liver.

Introduction: Histone deacetylase (HDAC) inhibitors have single agent activity in HL and FL, and may enhance antigen-specific immune recognition in cancer in addition to modulating programmed cell death (PD)-1 expression. In preclinical studies, the combination of HDAC inhibitors and anti-PD-1 antibodies acts synergistically against various tumor models in mice. Accordingly, we investigated the safety and efficacy of the novel combination of the HDAC inhibitor ENT and the PD-1-blocking antibody PEM in patients with R/R FL or HL. Methods: Patients with R/R HL or FL were eligible for this trial. Prior use of anti-PD-1 or HDAC inhibitor was allowed if there had been clinical benefit and this was not the most recent therapy. Patients received ENT 5-7 mg orally once weekly and PEM 200 mg intravenously once every three weeks. Tumor assessment was evaluated using the RECIL criteria. The primary objective is overall response rate (ORR) and 12-month progression-free survival (PFS). Results: At data cutoff on 2/7/19, 12 patients (5 HL, 7 FL) have been enrolled. Median age was 60 (26-81). Median number of prior therapies was 3 (2-11) and 3 (2-4) in HL and FL, respectively. With median duration of follow-up of 145 (33-288) days, 4 patients are currently receiving treatment on study, 3 patients have discontinued treatment due to toxicity, 3 due to disease progression, and 2 to proceed to consolidation with transplant or radiation. Out of 11 evaluable patients, there was a 64% ORR across both disease types (100% and 33% ORR in the HL and FL groups, respectively). There was one complete response (CR) in each group, including one patient with FL who had relapsed after CAR T cell therapy. A patient with HL who had previously received both PEM and ENT as monotherapy achieved a partial response (PR). Median duration of response in both groups was 172 (69-209) days. All patients experienced at least one adverse event (AE). 8/12 (67%) had grade 3 or higher adverse events (AE), which were mainly hematologic compared to non-hematologic (58% vs 8%), including neutropenia (50%), thrombocytopenia (25%), and anemia (17%). Two patients who experienced serious adverse events (SAEs) due to pericarditis and the hemophagocytic lymphohistiocytosis (HLH) syndrome and one patient with grade 3 bullous dermatitis were taken off study. ENT was dose-reduced in 5 patients and was held temporarily without dose-reduction in 4 patients. The median duration on treatment was 112 (27-288) days. Results from previously performed targeted next-generation sequencing of lymph node biopsies were available for 8 patients. All (100%) had at least one mutation in epigenetic-modulating genes and 5/8 (63%) had at least one mutation in histone acetyltransferase-encoding genes. There was no association between mutation status and response rate. Keywords: epigenetics; Hodgkin lymphoma (HL); PD-1. Disclosures: Younes, A: Honoraria: Merck.

* Authors contributed equally to this work. Introduction: CD19-specific second generation chimeric antigen receptor (CAR) T cell therapy with either CD28 or 41BB co-stimulatory domain demonstrate complete remission (CR) rates of 30-50% in relapsed/refractory (R/R) NHL and 20-30% in CLL. Concurrent expression of 4-1BBL in a CD19 CAR T cell enhances T cell proliferation, IL-2 secretion, and cytolytic activity of CAR T cells in the inhibitory tumor microenvironment (Zhao Z et al. Cancer Cell 2015). We report the outcomes of adult patients (pts) with NHL and CLL treated with escalating doses of autologous 19-28z/4-1BBL+ CAR T cells (NCT03085173). Methods: Pts with R/R NHL (DLBCL, follicular lymphoma (FL), transformed FL (tFL), Waldenström's macroglobulinemia (WM)) and CLL including Richter's transformation were eligible. Pts received conditioning chemotherapy with cyclophosphamide (Cy) alone or combined with fludarabine (Flu) followed by escalating doses of CAR T cells. For DLBCL pts, R-GemOx was the preferred bridging chemotherapy. CAR T cells were administered at dose level (DL) 1 (1x105 cells/kg), DL2 (3x105 cells/kg), DL3 (1x106 cells/kg), and DL4 (3x106 cells/kg). The primary and secondary objectives of the study was to evaluate safety of autologous 19-28z/4-1BBL CAR T cells and assess overall response rate. Results: 28 pts were enrolled with R/R CLL (n=9), de novo R/R DLBCL (n=6), tFL (n=3), FL and WM (n=5), Richter's transformation (n=4), and B-ALL (n=1). Median age of the pts was 70 (range, 53-81), and median number of prior treatments was 5 (range, 2-17). No dose-limiting toxicity (DLT) was observed. All 28 pts are at least 2 weeks from T cell infusion and evaluable for toxicity. Cytokine release syndrome (CRS) was observed in 11 pt (39.3%), one patient with a grade 3 event. Neurotoxicity was observed in 11 pts (39.3%), grade 1-2 in 8 pts and grade 3 in 3 pts. Twenty-seven patients were evaluable for response; one patient was not evaluable because of progressive multifocal leukoencephalopathy attributed to prior therapy, which developed within 1 month after CAR T cell therapy. Responses were observed at all DL. Three patients received multiple infusion of CAR T cells with response from first infusion considered evaluable. Sixteen of 27 pts (59%) achieved a CR, including 7/9 (78%) pts with DLBCL, 3/4 (75%) pts with FL, 3/9 (33%) pts with CLL, 2/3 (67%) pts with Richter's transformation, and one pt with B-ALL. The pt with WM achieved a VGPR. With a median follow-up of 169 days (24-534 days), 8 pts (29%) remain in CR. Peak CAR T cell expansion occurred at a median of 9 days after CAR T cell infusion (range, 2-82). CAR T cell detection beyond 160 days noted. Keywords: CD19; non-Hodgkin lymphoma (NHL); T-cells. Disclosures: Batlevi, C: Consultant Advisory Role: GLG, Lifesci Consulting; Honoraria: Dava Oncology; Research Funding: Janssen, Novartis, Epizyme, Xynomics, Mediimune. Palomba, M: Research Funding: Juno. Park, J: Research Funding: Juno. Brentjens, R: Stock Ownership: Juno; Research Funding: Juno.

To compare the effect of autologous blood patch injection (ABPI) versus BioSentry hydrogel tract plug (BioSentry) on the rate of pneumothorax in image-guided percutaneous lung biopsy. Our Institutional Review Board approved this randomized prospective clinical trial. A non-inferiority design for ABPI with a 10% margin was set with a target patient population of 552 (276 in each arm). From October 2014 all patients referred for image-guided percutaneous lung biopsy (N = 2052) were assessed for enrollment. A total of 1598 patients were excluded. In February 2017 the study was closed to accrual after an interim analysis. The study group consisted of 454 patients randomized into ABPI (n = 226) versus BioSentry (n = 228) arms. Analyses were performed on a modified intent-to-treat basis on 407 randomized patients who received lung biopsy using a z-test. Pneumothorax rates within 2 hours of biopsy were 21% (42/199) and 29% (60/208) for ABPI and BioSentry arms, respectively. Chest tube rates for ABPI and BioSentry arms were 9% (n = 18) and 13% (n = 27), respectively. Delayed pneumothorax rates within 2 weeks of biopsy were 2% (n = 3) and 1% (n = 3) for ABPI and BioSentry arms, respectively. The difference in the proportions of pneumothorax within 2 hours between ABPI versus BioSentry (-7.7%) along with the corresponding 95% confidence interval of the difference (-16.1%, 0.6%) and the tests of non-inferiority (p<.0001) exceeded the stopping boundary for noninferiority of ABPI arm and the study was closed to accrual prior to reaching the target total patient population of 552. Autologous blood patch injection is not inferior to BioSentry regarding iatrogenic pneumothorax in image-guided percutaneous lung biopsy.•Patient refused (396)•Coaxial 19 G technique not used (27)•Needle through non-aerated lung (258)•Needle through fissure or bulla (88)•More than 1 biopsy on same side (11)•Target - visceral pleura <1.5 cm (467)•Skin - visceral pleura >7 cm (7)•Needle length >15 cm (2)•Prior ipsilateral lung interventions:•Surgery (247)•Radiation (63)•Chest tube (17)•Pleurodesis (8)•Same target biopsy (7)•Excluded subjects (n)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Rhabdomyosarcoma, the most common soft tissue sarcoma of childhood. makes up less than 1% of solid malignancies in adults with around 400 new cases each year in the United States. They have not previously been reported concurrently.Case presentation: A 37 year old woman presented with painful enlarging leg mass. Biopsy of the mass was consistent with embryonal rhabdomyosarcoma. Staging imaging revealed a PET avid anterior mediastinal lymph node. Excisional biopsy of this mass was consistent with diffuse large B-cell lymphoma. Hybridization capture-based next-generation DNA sequencing did not reveal shared somatic tumor mutations. Germline analysis did not show identifiable aberrations of TP53 or other heritable cancer susceptibility genes. She was treated with a personalized chemotherapy regimen combining features of R-CHOP and Children's Oncology Group ARST 0331.Conclusions: This case illustrates a unique clinical entity successfully treated with a personalized chemotherapeutic regimen.

Introduction: Based on preclinical studies that demonstrated synergism between BTK and PI3K inhibitors in B-cell non-Hodgkin lymphoma, we conducted a phase I/Ib investigator-initiated study of ibrutinib (BTK inhibitor) and buparlisib (pan-PI3K inhibitor) combination in patients (pts) with relapsed or refractory B cell lymphoma. Methods: Patients (pts) were eligible if they had relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL), ECOG ≤2, and adequate organ function. Ibrutinib and buparlisib were given daily by mouth on a 28-day cycle with dose reductions permitted after cycle 1. Tumor response was based on a modified Lugano Classification; with CRs requiring both FDG-PET resolution and ≥ PR by CT. Results: To-date, 25 pts enrolled (DLBCL 10, FL 5, MCL 10) with median prior systemic therapies being 4 for DLBCL (range 1-7), 2 for FL (all had 2 prior regimens), and 1 for MCL (range 1-2). 23 pts completed at least one cycle and were evaluable for toxicity. Pts received escalating doses of once daily ibrutinib and buparlisib in 3 dose levels (ibrutinib 420-560 mg; buparlisib 80-100 mg). Dose level 3 (Ibrutinib 560 mg, buparlisib 100 mg) was selected for dose expansion based on 1/6 pt with DLT. Nine patients enrolled on the dose expansion. Four of the first 7 patients enrolled on the dose expansion developed grade 2-3 toxicities requiring dose reductions and/or interruptions, most notably rash and diarrhea. Dose expansions then proceeded at reduced dose level 2 (ibrutinib 560 mg, buparlisib 80 mg) and all patients on buparlisib 100 mg were dose reduced to 80 mg. Adverse events of all grades ≥20% related to therapy include diarrhea (65%), fatigue (57%), hyperglycemia (52%), thrombocytopenia (48%), anorexia (43%), nausea (43%), hyperbilirubinemia (35%), rash (35%), depression (26%), mucositis (26%), mood swings (22%) (Figure 1A). Of 23 pt, dose reduction/interruption required for ibrutinib in 11(48%) pt, buparlisib in 14 (61%) pt. All 14 pt treated beyond cycle 3 were able to tolerate subsequent cycles with dose modification as needed for toxicities. Serious adverse events (SAE) related to therapy include: colitis, orthostatic hypotension, cerebrovascular ischemia, rash, diarrhea, fall. One unexpected death from unknown cause occurred in pt on protocol. 20 pts were evaluable for response. The overall response rate (ORR) as follows: DLBCL 14%, FL 25%, MCL 100% (Figure 1B). Targeted sequencing and cell-free DNA analysis is on-going. Keywords: ibrutinib; non-Hodgkin lymphoma (NHL); PI3K/AKT/mTOR.

Zu untersuchen, ob quantitative multi-parametrische MR- Bildgebung die Differenzierung zwischen klarzelligen Nierenzellkarzinomen und anderen Nierentumoren ermöglicht.

Ermittlung des Wertes der multi-parametrischen MR- Bildgebung in der Beurteilung des Therapieansprechens des Prostatakarzinoms unter Androgendeprivationstherapie.

Die Untersuchung von Zusammenhängen zwischen CT Tumorcharakteristika von klarzelligen Nierenzellkarzinomen und Patientenüberleben.

Prädiktion der Aggressivität von Prostatakarzinomen mittels apparent diffusion coefficient (ADC)- Werten des diffusions-gewichteten MRTs alleine und in Kombination mit der der Transferkonstante Ktrans des kontrastmittelgestützten MRTs.

OBJECTIVES:The objective of this study was to determine whether, in patients with prostate cancer (PCa) bone metastases receiving chemotherapy, early post-treatment changes on CT are reproducible and associated with clinical outcomes.METHODS:Blinded to outcomes, two radiologists with 1 year and 5 years of experience independently reviewed CTs obtained before and 3 months after chemotherapy initiation in 38 patients with bone metastases from castration-resistant PCa, recording the size, matrix and attenuation of ≤5 lesions; presence of new lesions, extraosseous components, periosteal reactions and cortical thickening; and overall CT assessment (improved, no change or worse). Kappa statistics were used to assess inter-reader agreement; the Kruskal-Wallis test and Cox regression model were used to evaluate associations.RESULTS:Inter-reader agreement was low/fair for size change (concordance correlation coefficient=0.013), overall assessment and extraosseous involvement (κ=0.3), moderate for periosteal reaction and cortical thickening (κ=0.4-0.5), and substantial for CT attenuation (κ=0.7). Most metastases were blastic (Reader 1, 58%; Reader 2, 67%) or mixed lytic-blastic (Reader 1, 42%; Reader 2, 34%). No individual CT features correlated with survival. Readers 1 and 2 called the disease improved in 26% and 5% of patients, unchanged in 11% and 21%, and worse in 63% and 74%, respectively, with 64% interreader agreement. Overall CT assessment did not correlate with percentage change in prostate-specific antigen level. For the more experienced reader (Reader 2), patients with improved or unchanged disease had significantly longer median survival (p=0.036).CONCLUSIONS:In PCa bone metastases, interreader agreement is low in overall CT post-treatment assessment and varies widely for individual CT features. Improved or stable disease identified by an experienced reader is statistically associated with longer survival.