bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of circulating tumor cells in bone marrow or peripheral blood detected by qualitative and quantitative PCR in pediatric NPM-ALK positive anaplastic large cell lymphoma
Authors: Woessmann W. , Damm-Welk C. , Busch K. , Burkhardt B. , Viehmann S. , Oschlies I. , Klapper W. , Zimmermann M. , Harbott J. , Reiter A.
Published: March 2020

9559

Background: Clinical and histopathological characteristics have limited prognostic value for children with anaplastic large cell lymphoma (ALCL). We evaluated the presence, extent and prognostic impact of circulating tumor cells in bone marrow (BM) and peripheral blood (PB) of children and adolescents with NPM-ALK positive ALCL by real-time quantitative PCR for NPM-ALK. Methods: Qualitative and TaqMan-based quantitative PCR assays targeting NPM-ALK were developed with a sensitivity to detect 1 NPM-ALK positive cell among 105 cells. Numbers of NPM-ALK transcripts were normalized to 104 copies ABL (NCN). BM was analyzed from 80 and PB from 52 German patients registered into the subsequent protocols NHL-BFM95 and ALCL99. Results: BM was positive for NPM-ALK in 47.5% of patients, and positivity was significantly correlated with clinical stage, mediastinal or visceral involvement, microscopic BM involvement, and histological subtype, but not with skin or CNS involvement. Qualitative and quantitative PCR results in BM and PB strongly correlated. BM PCR was associated with the cumulative incidence of relapses (CI-R): CI-R was 50±10% for 38 PCR-positive and 15±7% for 42 PCR-negative patients (p10 NCN NPM-ALK in BM had a CI-R of 71±14% compared to a CI-R of 18±6% for 59 patients with =10 NCN (p10 NCN NPM-ALK in BM, clinical risk factors (skin, mediastinal or visceral involvement) and atypical histological subtype, only >10 NCN NPM-ALK remained a significant poor prognostic factor with a risk ratio of 4.74 (1.57–14.3; p<0.006). Conclusions: The detection of NPM-ALK positive cells by PCR in BM is associated with advanced stage disease, visceral involvement and atypical histology. Quantitative PCR in BM or PB allows identification of 20% of patients experiencing 60% of all relapses with an event-free survival of 20%.

No significant financial relationships to disclose.
Ectopic expression and oncogenesis of Mer tyrosine kinase in E2A-PBX1 expressing B-cell acute lymphoblastic leukemia
Authors: Sawczyn K. K. , Porter C. C. , DeGregori J. , Graham D. K.
Published: March 2020

9561

Background: Mer is a receptor tyrosine kinase that belongs to a tyrosine kinase subfamily including Axl and Tyro-3. Mer is expressed in monocytes/macrophages, dendritic cells and platelets, but not in lymphocytes or thymocytes. However, prior DNA array studies have suggested an aberrant expression of Mer in B-cell ALL (B-ALL) expressing the E2A-PBX1 fusion protein associated with t(1;19). We investigated the potential oncogenic role of Mer in E2A-PBX1 expressing B-ALL. Methods: Mer expression was evaluated in diagnostic bone marrow samples in pediatric patients with E2A-PBX1 B-ALL (EP+) and non-E2A-PBX1 B-ALL (EP-) by quantitative RT-PCR, Western blot, and flow cytometry. Using the REH B-ALL cell line with a zinc-inducible E2A-PBX1, induction of Mer expression was evaluated by Western blot. A mouse model was developed by retroviral infection of E2A-PBX1 fusion protein into Mer wild-type (WT), transgenic (TG), and knock-out (KO) mouse bone marrow cells followed by transplantation of these cells into sublethally irradiated WT recipients. Evaluation was done for E2A-PBX1 expression in peripheral blood and bone marrow cells were analyzed by flow cytometry for the development of leukemia. Results: Thirteen EP+ and 14 EP- patient samples were processed. All 13 EP+ samples had Mer protein expression by flow cytometry and/or Western blot. Conversely, 1/14 EP- samples was weakly positive for Mer protein expression by flow cytometry and Western blot. Quantitative RT-PCR was performed on 4 EP+ samples and 6 EP- samples. There was a 7–324 fold increase in Mer expression in EP+ samples when compared to the mean Mer expression of EP- samples. In our mouse transplant model, the median time to develop leukemia from Mer TG/E2A-PBX1 and Mer KO/E2A-PBX1 mice was 92 days and 117 days, respectively, with one KO mouse still surviving disease free at 140 days post-transplant. Conclusions: Mer is ectopically expressed in E2A-PBX1 expressing B-ALL. Mer TG/E2A-PBX1 mice develop leukemia sooner than Mer KO/E2A-PBX1 mice, suggesting cooperativity between the oncogenes. Mer may be an attractive therapeutic target for patients with E2A-PBX1 expressing ALL.

No significant financial relationships to disclose.
Multivariate analysis based risk grouping of ewing tumours (ET) with extra-pulmonary metastatic disease (EPMD): Final results from the Euro Ewing 99 study
Authors: Ladenstein R. , Whelan J. , Oberlin O. , Weston C. , Jürgens H.
Published: March 2020

9562

Background: To identify an effective treatment for patients with EPMD. Methods: 192 patients (pts) were registered. Median age is 15.8 years (yrs) (0.4–49.29). Primary site was extremity in 57 pts and axial/other in 135 pts (40.6% in the pelvis). Tumour volume was ≥ 200 ml in 114pts. Metastatic spread was bone marrow (BM) only in 19 pts, bone only in 93 pts and bone and BM in 79 pts. Six VIDE induction cycles were completed by 168 pts (85%). Local treatment included surgery when possible and/or radiotherapy (Rx) as indicated. Recommended HDT was busulphan (BU) 600 mg/m2 and melphalan (MEL) 140 mg/m2 with PSCR. Median follow up is 4.2 years (range: 1.9–6.6). Results: Partial remission or better was achieved after cycle 6 in 75/116 pts subjected to HDT/SCR (65%). The overall survival at 3 years for all 192 pts is 29% (95% CI=0.04). Significantly favourable univariate factors in the unselected cohort at diagnosis (Dx) were age < 14 yrs (event free survival at 3 yrs (EFS) 37%, p=0.006), BM involvement only (EFS 47%, p=0.024), single bone lesions only (EFS 35%, p=0.009), extremities (EFS 34%, p=0.007) and tumour volume of <200 ml (EFS 47%, p<0.001). For pts receiving BuMel it is noteworthy that 37 pts of <14a and EPMD achieved an EFS of 47% in comparison to older counterparts >14a (EFS 22% (p=0.026). Multivariate analysis identified two major risk factors at Dx: primary tumour volume >200 ml p<0.001 (RR 2.25) and > 5 bone metastases p=0.064 (RR 2.11). In these risk groups the 3 yr EFS was 56% for 35 pts with <200 ml and <5 bone lesions, for 17pts with <200 ml > 5 bone lesions 29%, for 67 pts >200 ml or < 5 bone lesions 19% and extremely dismal for 47 pts with >200 ml and > 5 bone lesions with 7% (p<0.001). Conclusions: Groups with differing prognoses from EPMD have been identified from this prospectively followed cohort. Aggressive treatment with HDT appears effective only for sub groups of patients with EPMD and ET.

No significant financial relationships to disclose.
Decitabine (DAC) in combination with doxorubicin (DOX) and cyclophosphamide (CTX) in relapsed neuroblastoma (NBL): A Children's Oncology Group Study
Authors: George R. , Lahti J. , Ingle M. , Krailo M. , Blaney S. , Adamson P. , Murgo A. , Kidd V. , Diller L.
Published: March 2020

9565

Background: Loss of caspase-8 expression causes resistance to apoptosis-inducing agents and potentiates metastasis in NBL. In vitro treatment of NBL cell lines with DAC results in increased caspase-8 expression and enhanced apoptosis following exposure to DOX. As a component of a pediatric phase 1 study, we evaluated low-dose DAC with DOX and CTX in a cohort of children with relapsed NBL. Promoter specific DNA methylation in peripheral blood mononuclear cells (PBMC) was studied. Methods: Patients received a 1-hour infusion of DAC, 5 mg/m2, daily on days 0–6, followed on day 7 by 45 mg/m2 of DOX (with dexrazoxane) and 1 g/m2 of CTX. All patients received G-CSF. Cycles were repeated every 28 days. Methylation-specific and quantitative PCR were used to measure promoter-specific DNA methylation in PBMC prior to and after DAC (day 7 and day 28). Results: Twelve patients with recurrent NBL (median age 9 years, 10 males) were enrolled. DAC/DOX/CTX was well tolerated with grade 4 myelosuppression being the predominant toxicity. Grade 4 neutropenia, median 11 days duration, occurred in 10 pts and grade 4 thrombocytopenia, median 10 days, in 7 patients. Eight patients had progressive disease after = 2 courses of therapy. The remaining 4 patients had stable disease with 5 to 8 courses. Methylation and subsequent demethylation (40–90% decreased methylation) of the MAGE-1 promoter was detected before and after DAC respectively, in PBMC from 6 of 9 patients analyzed to date. Re-expression of MAGE-1 mRNA was also demonstrated in post treatment samples. Caspase-8 demethylation was not detected in PBMC; nor was hypermethylation of caspase-8 detected in pre-treatment PBMC, possibly due to low tumor burden in blood. Conclusions: DAC in combination with cytotoxic chemotherapy was relatively well tolerated in heavily pre-treated children with relapsed NBL. Low-dose DAC induces demethylation and re-expression of MAGE-1 in PBMC, and may be a potential surrogate marker of demethylation within tumor cells. The use of low dose DAC in combination with other agents warrants further study in NBL.

No significant financial relationships to disclose.
Phase I study of oral irinotecan and temozolomide in children with relapsed high-risk neuroblastoma: A New Approach to Neuroblastoma Therapy (NANT) Consortium study
Authors: Wagner L. M. , Villablanca J. G. , Stewart C. F. , Crews K. R. , O'Shaughnessy M. A. , Groshen S. , Reynolds C. P. , Park J. R. , Maris J. M. , Matthay K. K.
Published: March 2020

9567

Background: Irinotecan (IRN) and temozolomide (TEM) have single-agent activity and schedule-dependent synergy against neuroblastoma. Because intravenous IRN is costly and inconvenient, especially with protracted scheduling common in pediatric trials, we sought to determine the maximum tolerated dose (MTD) of oral IRN combined with TEM in children with recurrent/resistant high-risk neuroblastoma, using the antibiotic cefixime to reduce IRN-associated diarrhea. Methods: Patients received oral TEM on days 1–5 and oral IRN on days 1–5 and 8–12, with courses repeated every 21 days. Oral cefixime 8 mg/kg (max 400 mg/day) was started on day -5 and continued daily. Results: Fifteen patients (median age 7 years, range 2–22) with a median of 3.5 previous treatment regimens were evaluable for toxicity and have to date received 71 courses (median 2, range 1–19+). Neutropenia and thrombocytopenia were dose-limiting in the first 6 patients, and TEM was reduced from 100 to 75 mg/m2/day for all subsequent patients. IRN was then escalated from 30 to 60 mg/m2/day. First-course grade 3 diarrhea was dose-limiting in 1 of 6 patients treated at the IRN MTD of 60 mg/m2/day. Other toxicities were mild and reversible. No grade 4 therapy-related toxicity occurred in 27 courses administered at the MTD. The median SN-38 lactone AUC at this dose was 72 ng*hr/ml, similar to that reported with protracted intravenous IRN at the single-agent MTD. Of 14 patients evaluable for response, one with measurable nodal disease had a very good partial response through 6 courses. Six additional patients had stable disease for a median of 7.5 courses (range 6–19+). Two patients remain on study after 10 and 19 courses. Conclusions: This combination was well tolerated in heavily-pretreated children with resistant neuroblastoma, and 7 (50%) of 14 evaluable patients had response/stable disease for 6 or more courses in this Phase I trial. This all-oral regimen was feasible and resulted in favorable SN-38-lactone exposures. The dose recommended for further study in this patient population is TEM 75 mg/m2/day plus IRN 60 mg/m2/day when given with cefixime.

No significant financial relationships to disclose.
A phase I trial of vorinostat in children with refractory solid tumors: A Children's Oncology Group Study
Authors: Fouladi M. , Park J. , Sun J. , Fraga C. , Ames M. M. , Stewart C. F. , Gilbertson R. J. , Zweibel J. , Adamson P. C. , Blaney S. M.
Published: March 2020

9569

Background: Vorinostat, an orally administered histone deacetylase inhibitor, has potent antitumor activity against human cell lines in vitro (IC50 0.5 to 5 μM) and in xenograft models. A phase I trial of vorinostat was conducted in children with recurrent or refractory solid tumors to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), pharmacokinetics (PK) of vorinostat, and to assess accumulation of histone acetylation in peripheral blood mononuclear cells (PBMCs). Methods: Vorinostat was administered once daily at dose levels of 180, 230, and 300 mg/m2/d. Courses were 28 days in duration, without interruption. PK analysis was performed during the 1st course. Vorinostat's ability to induce acetyl-histone (H3) accumulation in vivo was studied by western blot analysis. Results: 30 patients, 17 males, median age 15 years (range 4–21), were enrolled; 24 patients were fully evaluable for toxicity. At 180 mg/m2/d, 1/6 pts developed DLT (deep vein thrombosis) and at 230 mg/m2/d 1/6 pts developed DLT (hypokalemia). At 300 mg/m2/d, DLTs consisted of reversible hypokalemia (n=1), neutropenia (n=1) and thrombocytopenia (n=2), defining the MTD as 230 mg/m2/d. Other non-dose limiting grade 3 or 4 toxicities included elevated ALT/AST, hyperbilirubinemia, leucopenia, and lymphopenia. Western blot analysis of PBMC protein isolates found clear evidence of dose- dependent accumulation of acetylated H3 histones. 1 patient with a spindle cell sarcoma received 8 courses and 1 patient with a low-grade astrocytoma had an unconfirmed minor response. Conclusions: Vorinostat is well tolerated in children with recurrent or refractory solid tumors and inhibits histone deacetylase activity in PBMC. The recommended phase II dose for children with solid tumors is 230 mg/m2/d.

No significant financial relationships to disclose.
Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine (PCG) and gemcitabine/cisplatin (GC) in patients with locally advanced (LA) or metastatic (M) urothelial cancer without prior systemic therapy; EORTC30987/Intergroup Study
Authors: Bellmunt J. , von der Maase H. , Mead G. M. , Heyer J. , Houede N. , Paz-Ares L. G. , Winquist E. , Laufman L. R. , de Wit R. , Sylvester R.
Published: March 2020

LBA5030

Background: GC is a standard alternative to M-VAC for LA/M urothelial cancer (UC) based on comparable efficacy and a more favorable toxicity profile. Based on a phaseII trial, it has been suggested that the PCG triplet might provide improved response and survival. To evaluate the role of paclitaxel when added to GC, a randomized, international study (EORTC30987/Intergroup Study) comparing GC with PCG in LA/M UC was initiated in 2001, with the main endpoint being overall survival (OS). Methods: Chemo naive patients with histologic evidence of LA or M transitional UC, with GFR>60ml/min were eligible. After stratification for institution, PS(WHO 0–1) and presence/absence of metastatic disease, patients were randomized to receive PCG(armA) or GC(armB). PCG treatment included: paclitaxel(P) 80mg/m2 d1&8, cisplatin(C) 70mg/m2 d1 and gemcitabine(G) 1000mg/m2 d1&8, every 21d. GC: C70mg/m2 d1 or 2, G1000mg/m2 d1,8,15 every 28d. To detect an increase in median survival from 14 to 18m(HR=0.778) based on a two sided logrank test at error rates a=0.05 and β=0.20, 498 deaths were required. The planned sample size was of 610 pts. Results: From June 01 to May 04, 627pts (82% primary bladder) were included, (312 PCG, 315 GC). Median age was 61y with 81% males and similar baseline prognostic characteristics on both arms. PS 1 in 47%PCG and 46%GC pts. On PCG 47% had visceral and 83% M; on CG 49%-83% respectively. Overall response rate (RR): 57,1% for PCG (CR15%) and 46,4% for GC (CR10%), p=0.02. Median PFS: 8.4m and 7.7m for PCG and GC, p=0.10. 478 pts have died; the EORTC IDMC has released the study because the required number of events will occur prior to presentation. Median survival is 15.7m for PCG and 12.8m for CG, with no significant difference in OS (p=0.10, HR0.86, CI95% 0.72–1.03, p=0.12 adjusted for risk factors). Both treatments were overall well tolerated, with more thrombopenia and bleeding on GC (12%vs7%) and more febrile neutropenia on PCG (13%vs4%). Conclusions: This large, multicenter, Phase III study shows that PCG provided a better RR when compared with GC in LA/M UC; however the predefined endpoint for PFS and OS improvement was not reached.

[Table: see text]
Hypofractionation for early breast cancer: First results of the UK standardization of breast radiotherapy (START) trials
Authors: Dewar J. A. , Haviland J. S. , Agrawal R. K. , Bliss J. M. , Hopwood P. , Magee B. , Owen J. R. , Sydenham M. A. , Venables K. , Yarnold J. R.
Published: March 2020

LBA518

Background: The START Trials (ST-A and ST-B) test the hypothesis that breast cancer is as sensitive to fraction (Fr) size as late reacting normal tissues, with an a/β value of about 4Gy. Methods: The phase III randomised START Trials tested hypofractionated post-operative RT in women with completely excised invasive breast cancer (T1–3, N0–1, M0). Centres opted for either ST-A or ST-B. ST-A tested 50Gy in 25Fr (5 wks) vs 41.6Gy vs 39Gy, both in 13Fr (5 wks). ST-B tested 50Gy in 25Fr (5 wks) vs 40Gy in 15Fr (3 wks). Stratification was by centre, surgery and boost. The primary endpoint was local-regional (LR) relapse. Late normal tissue effects (NTE) were assessed by breast photographs, clinical examination and quality of life (QL) questionnaires. Survival analysis methods were used to estimate rates of relapse and NTEs, and hazard ratios (HR) (with 95%CI). Smoothed estimates of absolute differences in relapse rates were obtained from the rates in the 50Gy control arms and the HR. Results: 2236 (ST-A) and 2215 (ST-B) patients were recruited from 35 UK centres during 1999–2002. Median follow-up is 5.1 years (ST-A) and 6.0 years (ST-B). There were 93 LR relapses in ST-A (4.1% at 5 years, 3.2- 5.0%), with absolute differences in LR relapse rates at 5 years compared with 50Gy of 0.2% (−1.3%−2.6%) for 41.6Gy and 0.9% (−0.8%−3.7%) for 39Gy. The a/β estimate for tumour control was 5.0Gy (−2.7–12.7). In ST-B, there were 65 LR relapses (2.8% at 5 years, 2.1–3.5%), with an absolute difference in LR relapse rates at 5 years of −0.6% (−1.7%−0.9%) for 40Gy vs 50Gy. In ST-A the rate of mild/marked change in photographic breast appearance was lower in 39Gy vs 50Gy (HR 0.69, 0.52–0.91), and similarly for 40Gy vs 50Gy in ST-B (HR 0.83, 0.66–1.04). The a/β estimate for change in breast appearance was 3.1Gy (1.6–4.6). Rates of induration, telangiectasia and breast oedema were lower in 39Gy (ST-A) and 40Gy (ST-B) compared with the 50Gy arms. QL results were consistent with the clinical findings. Conclusions: The fractionation sensitivity of breast cancer is comparable to that of late reacting normal tissues, confirming the results of a recent pilot trial. These results support the use of hypofractionated RT schedules for early breast cancer.

No significant financial relationships to disclose.
Phase 3 Study: Canfosfamide (C, TLK286) plus carboplatin (P) vs liposomal doxorubicin (D) as 2nd line therapy of platinum (P) resistant ovarian cancer (OC)
Authors: Rose P. , Edwards R. , Finkler N. , Seiden M. , Duska L. , Krasner C. , Cappuccini F. , Kolevska T. , Brand E. , Brown G. , Runowicz C.
Published: March 2020

LBA5529

Background: Canfosfamide (C) is a novel glutathione analog prodrug activated by glutathione S-transferase P1–1. C has single agent activity in P resistant OC and is synergistic with P. Methods: Pts with P resistant OC following ≤ 2 P regimens, measurable disease (RECIST) were eligible. Pts received C (750 mg/m2) and P (AUC 5) or D (50 mg/m2) IV q4wks until progression. Randomization was stratified by ECOG PS, best prior P response and bulky disease (≥ 5cm). Results: All 247 P refractory or resistant pts received 505/494 cycles median 3 (range 1–17), CP/D respectively. Most common toxicities for CP were hematologic and as expected for each drug alone. By independent radiologic review (IRR), 25% of pts discontinued treatment without documented progression. Overall ORR varied between clinician and IRR assessments. Overall median PFS was 3.5 mos for both CP and D. Overall median survival (MS) has not been reached. Planned analysis of the effect of time from last P dose to study treatment (TFP; not from time of recurrence) identified a P resistant subgroup for TFP ≥ 6 mos (med 7.1) [ Table ]. Subgroup ORR for CP was 31.6% vs 10.5% for D. Subgroup median PFS for CP has not been reached vs 3.5 mos for D (p=0.0099). Subgroup MS for CP has not been reached vs 11.1 mos for D(p=0.0014). Subgroup CP had superior QOL outcomes per FACIT-FACT-O. Conclusions: Primary endpoint of overall PFS was comparable. Subgroup TFP ≥ 6 mos reported large differences in ORR and QOL and statistical significance in PFS and survival for CP. OC trials with C in combination with other standard agents are in progress.

[Table: see text] [Table: see text]
Retrospective analysis of outcomes among more than 1,000 patients with newly diagnosed anaplastic oligodendroglial tumors
Authors: Lassman A. B.
Published: March 2020

2014

Background: Treatment of anaplastic oligodendroglial tumors is controversial. Early results of randomized trials suggest chemotherapy (CT) with procarbazine-lomustine-vincristine (PCV) before or after radiotherapy (RT) improves progression-free but not overall survival (OS) versus RT alone. It is unknown if CT alone affects outcome versus CT&RT, or if temozolomide (TMZ) compares favorably with PCV. Methods: We retrospectively identified adults with newly diagnosed anaplastic oligodendroglioma (AO) or oligo-astrocytoma (AOA) seen at 17 medical centers from 1981–2007 exclusive of phase III or bone marrow transplant trials. Data were updated January 1, 2009. Survivals were estimated by Kaplan-Meier method and compared with log-rank. Results: There were 1054 patients: 594 men, 460 women; median age 42 (18–88); 661 with AO, 443 with AOA. Treatment was: observation (82, 8%), RT alone (n = 210, 20%), RT then chemotherapy (283, 27%), RT + CT concurrently (118, 11%), CT alone (205, 19%), CT then RT (137, 13%), or other (19, 2%). Median time to progression (TTP) and OS were 2.8 and 6.5 years, respectively, with median follow up of 4.1 years (0.03–20.8) on surviving patients (n = 560, 53%). 1p19q co-deletion was observed in 292 (48%) and no deletion in 232 (38%) of 606 tested tumors. Co-deletion predicted longer median TTP (4.2 vs. 1.8 years for no deletion, p = 0.0002) and OS (8.4 vs. 3.3 years, p < 0.0001). Median TTP was longer following CT&RT (sequential or concurrent) than CT alone (3.7 vs. 2.6 years, p = 0.0007), but median OS did not differ (6.6 vs. 7.1 years, p = 0.8); co-deletion was more common with CT alone than CT&RT (p < 0.0001, χ2), although restricting analysis of CT&RT versus CT to the co-deletion cohort yielded analogous results (median TTP 7.2 vs. 3.8 years, p = 0.011; OS 7.9 vs. 10.4 years, p = 0.26). Median TTP was longer following PCV alone (7.6 years, n = 17) than TMZ alone (3.3 years, n = 65) with co-deletion (p < 0.02); median OS was also longer (not reached, vs. 7.1 years), but did not reach statistical significance (p = 0.07 log-rank). Conclusions: 1p19q co-deletion predicted improved outcome. Treatment strategies varied widely. CT alone did not appear to shorten OS versus CT&RT. PCV may be superior in efficacy to TMZ. Multivariate analyses and additional 1p19q testing are in progress.

[Table: see text]
Pilot study of NKTR214 and nivolumab in patients with sarcomas.
Authors: D'Angelo Sandra P. , Conley Anthony Paul , Kelly Ciara Marie , Dickson Mark Andrew , Gounder Mrinal M. , Chi Ping , Keohan Mary Louise , Livingston J. Andrew , Patel Shreyaskumar , Adamson Travis , Kiesler Hannah , Biniakewitz Matthew , Phelan Haley , Condy Mercedes M. , Agaram Narasimhan P , Qin Li-Xuan , Erinjeri Joseph Patrick , Hwang Sinchun , Tap William D.
Published: March 2020

11010

Background: Monotherapy checkpoint inhibitors have minimal efficacy in most patients with metastatic sarcoma. NKTR-214 is a CD122-preferential IL-2 pathway agonist that activates and expands natural killer and CD8+ T cells. Phase I/II data demonstrated the safety and efficacy of nivolumab plus NKTR-214 in multiple tumor types. A trial of NKTR-214 plus nivolumab was initiated in patients with selected sarcomas. Methods: This is a multi-center pilot study enrolling patients (pts) failing prior regimens within 9 cohorts: leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), chondrosarcoma (CS), osteosarcoma (OS), angiosarcoma (AS), alveolar soft part sarcoma (ASPS), synovial sarcoma/small blue round cell and other. Pts received NKTR 0.006mg/kg with nivolumab 360 mg every 3 weeks. Primary endpoint was objective response rate (ORR), secondary endpoints were adverse events (AEs), progression-free, overall survival (PFS,OS) and clinical benefit rate (CBR.) Pre/on treatment biopsies performed on patients for correlative studies including PD-L1 expression and TIL characterization by immunohistochemistry, whole exome sequencing and RNAseq. Results: Enrollment completed with 10 patients in cohorts below. 50 pts enrolled (median age 58, range 14-80), 54% female. Median follow-up time is 13m. 50% of patients were refractory ≥3 lines of therapy. Grade 3/4 treatment related adverse events occurred in 26% of patients. 2% of patients stopped due to AEs. Median time to response was 3.6m. Responses seen in LMS, UPS, dedifferentiated CS; on-going in UPS/CS. Prolonged disease stability in DDLPS. 6 patients remain on treatment. Conclusions: Nivolumab plus NKTR-214 was safe and tolerable in heavily pre-treated and refractory sarcoma patients. Responses were protracted overtime; on-going in UPS and dedifferentiated CS. Prolonged disease stability seen in DDLPS in patients. All correlative analyses are in progress and will be presented. Enrollment continues with plans to add a treatment naïve cohort. Clinical trial information: NCT03282344. [Table: see text]
Temporal trends among survivors of rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Hingorani Pooja , Wang Mingjuan , Srivastava Deokumar , Nathan Paul C. , Oeffinger Kevin C. , Yasui Yutaka , Leisenring Wendy M. , Howell Rebecca M. , Mueller Emily L. , Gibson Todd M. , Wolden Suzanne L. , Bjornard Kari L. , Meyer William H. , Arndt Carola A. S. , Robison Leslie L. , Green Daniel M. , Armstrong Gregory T. , Ness Kirsten K.
Published: March 2020

11570

Background: Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols included treatment modifications, which may have ameliorated late health outcomes for rhabdomyosarcoma (RMS) survivors treated in more recent era. Methods: We evaluated chronic health conditions (CHCs) and late mortality ( > 5 years from diagnosis) among survivors treated 1970-1990 (IRSG I-III) and 1991-1999 (IRSG IV), and associations with specific treatments to identify treatment-related factors for adverse outcomes. Associations between treatments and CHCs and mortality were evaluated using Fine and Gray’s proportional hazards method accounting for competing risks. Results: 856 survivors treated 1970-90 (median diagnosis age 5.4 years [0- 20]) and 306 treated 1991-99 (median diagnosis age 5.5 years [0-20]) were included. Significant exposure differences between eras included higher percentage (53% vs. 17%, p < 0.01) receiving ≥ 20gm/m2 cumulative alkylators in 1991-99, but more receiving platinums (13% vs 5%, p < 0.01) and abdomen/ pelvis radiation (29% vs. 23%, p = 0.04) in 1970-90. 20-year cumulative incidence for any (40% vs. 28%, p < 0.01), ≥2 (16% vs. 7%, p < 0.01), and endocrine (8% vs. 2.5%, p < 0.01) grade 3-5 CHCs was higher in 1970-90 compared to 1991-99. The hazard ratio (HR) for any (HR 0.7, 95% Confidence Interval [CI] 0.55-0.9), ≥2 (HR 0.38, 95% CI 0.22-0.66) and endocrine (HR 0.25, 95% CI 0.09-0.67) grade 3-5 CHC was lower for 1991-99 survivors than 1970-90. The effect of era (1991-99 vs 1970-90, HR 0.73; 95% CI 0.59-0.91) on CHC was not attenuated when treatment variables were added to multivariable model. Exposures with increased risk of grade 3-5 CHC included platinums (hearing, HR 2, 95% CI 1.07-3.8), anthracycline ≥250mg/m2 (cardiovascular, HR 2.7, 95% CI 1.2-6) and abdomen/ pelvis radiation (second malignant neoplasms, HR 2.1, 95% CI 1.1-4, gastrointestinal, HR 7.4, 95% CI 3.5-16 and endocrine, HR 2.5, 95% CI 1.4-4.4). Gonadal dysfunction was the most common endocrine CHC. There was no difference in all cause or cause-specific mortality between the two cohorts. Conclusions: RMS survivors from the IRSG IV era are at reduced risk for late onset chronic health conditions compared to previous era.
Ixazomib and dexamethasone in high risk smoldering multiple myeloma: A clinical and correlative pilot study.
Authors: Mailankody Sham , Salcedo Meghan , Tavitian Elizabet , Korde Neha , Lendvai Nikoletta , Hassoun Hani , Lesokhin Alexander M. , Lahoud Oscar Boutros , Smith Eric L. , Hultcrantz Malin , Devlin Sean M. , Landgren Ola
Published: March 2020

8051

Background: Patients with high risk smoldering multiple myeloma (HR-SMM) have an increased risk of progression to multiple myeloma (MM)- median time < 2 years. The standard management of these patients currently is close clinical monitoring; however, randomized trials show longer progression-free and overall survival in in HR-SMM patients treated with the oral immunomodulatory drug lenalidomide. We report the use ixazomib, the first oral proteasome inhibitor, in combination with dexamethasone in the setting of HR-SMM. Because proteasome inhibitors can provide deep clinical responses in patients with MM, we set the pre-specified threshold for efficacy high (overall response rate of ≥75%). Methods: In this single arm pilot trial of ixazomib/dexamethasone, patients received 12 4-week cycles of ixazomib/dexamethasone followed by ixazomib maintenance for 24 cycles. The primary endpoint is best overall response after 12 cycles and second objectives include duration of response, safety, and progression free survival. Results: 14 patients with HR-SMM were enrolled between 06/2016 and 03/2018. The median age is 65 years and 10 (71%) of patients were male. 11 (79%) patients were high-risk by the PETHEMA criteria, 2 (14%) by the Mayo Clinic criteria and 1 (7%) by both. At data cut-off (02/07/2019), patients completed a median of 17 cycles and 10 (71%) are continuing treatment. 4 patients have stopped treatment (2 patients for raise in serum markers without progression to MM, and 1 each for toxicities, and co-morbidities unrelated to treatment). 9 (64%) achieved an objective response (8 PR, and 1 VGPR) and no patient has progressed to MM. Non-heme adverse events included 3 grade 1 GI events, 2 grade 3 lung infection, 1 grade 2 acute kidney injury, and 1 had grade 1 fatigue that was possibly related to treatment. Conclusions: Ixazomib/dexamethasone appears well tolerated with high overall response (9/14; 64%) in patients with HR-SMM. Although the trial does not meet our pre-specified threshold for efficacy (i.e. best overall response rate of 75%), with a median follow-up of 17 months, no patient progressed to MM and only 2 patients had serologic progression. These results support further evaluation of ixazomib/dexamethasone alone and in combination with other agents as treatment for patients with HR-SMM. Clinical trial information: NCT02697383.
Association of BAP1 alterations with malignant pleural mesothelioma treated with trimodality therapy.
Authors: Zauderer Marjorie Glass , Rizvi Hira , DuBoff Mariel A. , Adusumilli Prasad S. , Rusch Valerie W. , Sauter Jennifer L. , Ladanyi Marc , Rimner Andreas
Published: March 2020

8552

Background: Trimodality therapy with pleurectomy/decortication, cytotoxic chemotherapy, and adjuvant pleural intensity modulated radiation therapy (IMPRINT) is an emerging standard of care for locally advanced epithelioid mesothelioma (Rimner, Zauderer et al. JCO 2016). Some patients, however, progress rapidly and we therefore sought to identify potential predictive markers of response to this treatment. Given the putative role of BAP1 in DNA damage repair, we hypothesized that alteration in BAP1 would be associated with improved local control after radiation therapy. Methods: We identified patients previously treated at our institution with IMPRINT to a median dose of 4680cGy in 26 fractions. Targeted next generation sequencing was performed with MSK-IMPACT on archival tissue samples. Chart review was undertaken for clinicopathologic features and outcome data. Results: MSK-IMPACT testing was successfully performed on 58 patients who completed IMPRINT. The majority were male with a median age of 70 years. Ninety-seven percent had epithelioid subtype while 3% were biphasic with predominantly epithelioid histology. Median overall survival was 30.2 months with a median follow-up of 45.3 months, consistent with prior reports. Somatic BAP1 mutations were identified in 34% of the specimens. Those with BAP1 mutant tumors had a median time to local failure of 22.4 months (IQR 10.9 – 36.9 months) while those with BAP1 wild type tumors only had a median of 12.1 months (IQR 8.7-15.85 months) to local failure (p = 0.057). We identified a trend towards improved overall survival among those with BAP1 altered tumors compared to those with BAP1 wild type (HR = 0.61, p = 0.14). Conclusions: BAP1 alteration may be associated with improved duration of local control and improved overall survival after IMPRINT therapy. Further analysis and validation in a large data set is needed and a platform for identifying and validating predictive biomarkers should be included in the planned NRG randomized trial of IMPRINT.
Antitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertions.
Authors: Janne Pasi A. , Neal Joel W. , Camidge D. Ross , Spira Alexander I. , Piotrowska Zofia , Horn Leora , Costa Daniel Botelho , Tsao Anne S. , Patel Jyoti D. , Gadgeel Shirish M. , Bazhenova Lyudmila , Zhu Viola Weijia , West Howard , Vincent Sylvie , Zhu Jian , Li Shuanglian , Riely Gregory J.
Published: March 2020

9007

Background: TAK-788 is an oral investigational EGFR/HER2 inhibitor under evaluation in NSCLC patients (pts) with EGFR exon 20 insertions. We report results of a phase 1/2 open-label, multicenter study (NCT02716116). Methods: Pts with advanced, previously treated NSCLC received daily TAK-788 in dose escalation and expansion cohorts based on tumor genotype. Antitumor activity was determined for pts with EGFR exon 20 insertions who received TAK-788 at the RP2D. Safety is reported for all pts across all doses and at 160 mg. Results: As of 14 Sep 2018, 101 pts (median age, 61 y; female, 70%; ≥2 prior anticancer therapies, 76%; brain metastases, 53%) were treated with TAK-788 at 5–180 mg qd. RP2D was determined to be 160 mg. 28 pts with EGFR exon 20 insertions were treated with 160 mg qd during dose escalation or in expansion cohort 1 (median 3.6 mo on treatment; median 3.8 treatment cycles); 24 pts remain on treatment. Antitumor activity in pts with EGFR exon 20 insertions is shown in Table. At data cutoff, 7/14 responses were confirmed with 6 awaiting confirmation and 1 unconfirmed PR at 160 mg qd; median time to response in these 14 pts was 56 days. 23/24 evaluable pts with EGFR exon 20 insertions treated at 160 mg qd had decreased target lesion measurements (median best percent change, -32.6% [-79.1%, 3.8%]). Rate of treatment discontinuation due to AEs was 10.7% in pts treated at 160 mg. Most common TEAEs (≥20%) in pts treated with 160 mg qd: diarrhea (85%), rash (43%), nausea (41%), vomiting (30%), decreased appetite (28%), and stomatitis (22%); gr ≥3 TEAEs (≥5%) were diarrhea (26%) and hypokalemia, nausea, and stomatitis (7% each). Median dose intensity for pts treated with 160 mg qd was 93%. There is no clear trend that response to TAK-788 is enriched in particular EGFR exon 20 insertion variants. Conclusions: In NSCLC pts with EGFR exon 20 insertions, TAK-788 demonstrated antitumor activity and an AE profile consistent with other EGFR TKIs. Clinical trial information: NCT02716116. [Table: see text]
Safety and preliminary antitumor activity of U3-1402: A HER3-targeted antibody drug conjugate in EGFR TKI-resistant, EGFRm NSCLC.
Authors: Janne Pasi A. , Yu Helena Alexandra , Johnson Melissa Lynne , Steuer Conor Ernst , Vigliotti Michele , Iacobucci Corinne , Chen Shuquan , Yu Channing , Sellami Dalila B.
Published: March 2020

9010

Background: Treatment options are limited for EGFRm NSCLC resistant to EGFR TKIs. HER3 is expressed in a majority of NSCLC tumors. U3-1402 is a HER3-targeted antibody drug conjugate with a fully human HER3-targeted antibody, novel cleavable peptide-based linker, and topoisomerase I inhibitor payload. Methods: An ongoing multicenter phase 1 dose escalation and expansion study is assessing U3-1402 safety/tolerability and preliminary activity in metastatic or unresectable EGFRm NSCLC patients (pts) who are T790M negative after disease progression while on erlotinib, gefitinib or afatinib; or develop disease progression while on osimertinib regardless of T790M status. Dose escalation is based on dose-limiting toxicities (DLTs) and guided by the modified Continuous Reassessment Method. U3-1402 is administered via intravenous infusion in 21-day cycles. Pretreatment tumor tissue is required. Results: As of 11 Nov 2018, 15 pts (6 M; 9 F) were enrolled across 3 dose levels (3.2, 4.8, 6.4 mg/kg). Median age was 63 y; 10 pts had EGFR exon 19 deletion and 5 EGFR L858R mutation. Median sum of longest diameters (SLD) at baseline was 69 (range 22–143) mm. All pts had prior EGFR TKIs; 14 had 2nd line or later osimertinib. Six had prior chemotherapy. All 11 evaluable tumors demonstrated HER3 expression (median HER3 membrane H-score 188, range 150–290). Five pts discontinued treatment: 4 due to progressive disease, 1 due to adverse event (AE). All Grade (Gr) treatment-emergent AEs (TEAEs) in ≥20% of pts were nausea (60%), vomiting (40%), fatigue (33%), decreased appetite (27%), and alopecia (20%). Gr≥3 TEAEs were nausea (1/15; Gr3; related), hypoxia (1/15; Gr3; unrelated), and platelet count decreased (2/15; both Gr4 at 6.4 mg/kg and considered DLTs). In 13 evaluable pts, all but 1 had a decrease in SLD (median best change −29%, range +10% to −67%), 2 had confirmed partial response per RECIST v1.1 (best changes −44%, −67%). Conclusions: U3-1402 showed a manageable safety profile and preliminary antitumor activity in EGFR TKI-resistant EGFRm NSCLC. Evaluation of candidate biomarkers, including HER3 expression, which correlate with U3-1402 response is ongoing. Clinical trial information: NCT03260491.
Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1 fusion-positive non-small cell lung cancer (TRIDENT-1 study).
Authors: Cho Byoung Chul , Drilon Alexander E. , Doebele Robert Charles , Kim Dong-Wan , Lin Jessica Jiyeong , Lee Jeeyun , Ahn Myung-Ju , Zhu Viola Weijia , Ejadi Samuel , Camidge D. Ross , Liu Yuwei Juliet , Stopatschinskaja Shanna , Cui Jingrong Jean , Hyman David Michael , Ou Sai-Hong Ignatius , Shaw Alice Tsang
Published: March 2020

9011

Background: Repotrectinib is a next-generation ROS1/TRK/ALK TKI inhibiting ROS1 with > 90-fold greater potency than crizotinib. Preclinical studies showed robust kinase inhibitory activity of repotrectinib against all known ROS1 fusion positive resistance mutations, including the most common ROS1 solvent-front mutation (SFM) G2032R. Methods: In this ongoing phase 1 study (NCT03093116), TKI-naïve and TKI-refractory (≥1 TKI) patients (pts) with advanced ROS1/TRK/ALK+ solid tumors received repotrectinib treatment. Endpoints include safety, PK, and confirmed overall response (cORR). Safety analysis for all pts (n = 75) and efficacy analysis for ROS1+ NSCLC pts (n = 28) enrolled on the study was conducted. Results: As of 31-Oct-2018, 75 pts were treated with repotrectinib at dose levels from 40 mg QD to 200 mg BID. Most AEs were manageable and grade (Gr) 1-2. Common ( > 20%) treatment-related AEs were dizziness (49%), dysgeusia (48%), paresthesia (28%), and constipation (20%). Four DLTs (Gr3 dyspnea/hypoxia (n = 1); Gr2 (n = 1) and Gr3 (n = 1) dizziness at 160 mg BID, and Gr3 dizziness (n = 1) at 240 mg QD) occurred and were managed with dose modifications. The MTD has not been reached. Median number of prior TKI treatment was 1 (0-3) with all of TKI naïve and 83% of TKI pre-treated pts received prior chemotherapy. Among 10 evaluable TKI-naïve ROS1+ NSCLC pts, confirmed ORR by Blinded Central Review (BCR) was 90% (95% CI 56 - 100) with median duration of response (DOR) not reached ((range 5.5+ – 14.9+ months (mos)). Among 18 TKI-pretreated pts, confirmed ORR by BCR was 28% (95% CI 10 – 54) with DOR of 10.2 mos. Subgroup analysis showed cORR 44% (95% CI 14 - 79) in 9 prior TKI pts and treated at dose levels of 160 mg QD or above. In 7 pts with measurable target CNS lesions at baseline, the intracranial ORR was 3/3 (100%) with DOR (5.5+; 7.2+; 14.85+ mo) in TKI-naïve pts and 2/4 (50%) with DOR (5.5+;14.8+, mo) in TKI-pretreated pts, respectively. Conclusions: Repotrectinib was well tolerated and demonstrated encouraging overall and intracranial clinical activity in pts with ROS1 fusion-positive NSCLC. Enrollment in phase 1 continues until the RP2D is determined. A global phase 2 study is planned. Clinical trial information: NCT03093116.
Clinical haematological biomarkers: Derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) and their relationship to survival outcomes in non small cell lung cancer (NSCLC) treated with immunotherapy: A multicenter review.
Authors: Dennehy Colum , McMahon Eileen , Power Derek Gerard , O'Reilly Seamus , Collins Dearbhaile Catherine , O'Mahony Deirdre , Horgan Anne M. , O'Connor Miriam , Jordan Emmet , Calvert Paula , Bambury Richard Martin
Published: March 2020

e20704

Background: Efficient use of immunotherapy in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. Recently considerable efforts have been invested to develop biomarkers to predict which patients should receive immune checkpoint inhibitors. This retrospective cohort study aimed to determine whether clinical factors and inflammation-based biological markers such as pre-treatment derived neutrophils to lymphocytes (dNLR) ratio, platelets to lymphocytes (PLR) ratio and prognostic nutritional index (PNI) were associated with outcomes in NSCLC patients treated with immunotherapy. Methods: This study was a multicentered, retrospective systematic review. Clinical and electronic records were retrospectively examined from metastatic NSCLC patients treated with immunotherapy from August of 2015 to September 2018 in 2 regional cancer centers and a total of 69 patients were enrolled. NLR ≥5 and PLR ≥260 were defined as elevated and PNI ≤35 was defined as reduced. Results: Approximately, 57% of patients had NLR ≤ 5 and 51% had PLR ≤260. We found utilising univariant analysis, that pretreatment NLR ≤ 5 was independently associated with superior OS (median 12.4 vs. 6.8 months; HR 2.13, 95% CI 1.66-2.6; p = 0.007) and PFS (median 3.55 vs. 2.6 months; HR 1.75, 95% CI 1.18-2.32; p = 0.024). Results were similar when examining PLR ≤260 median OS 13.64 vs. 7.36 months; HR 1.92, 95% CI 1.1-3.5; p = 0.028) The optimal cutoff for PNI was designated to be 35. The majority (87%) had PNI > 35. NSCLC patients with PNI > 35 were found to have significantly higher median OS compared to patients with PNI ≤35 (11.11 vs. 2.4 months; HR 5.36, 95% CI ; p = 0.001). Conclusions: Immunotherapy is considered as an effective new method to treat advanced NSCLC. In this cohort of patients pretreatment NLR < 5,PLR < 260 and PNI > 35 were associated with superior outcomes. It is unclear whether these markers are predictive or prognostic or both.
Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma
Authors: Hori Atsushi , Ohira Ryosuke , Nakamura Tomoyuki , Kimura Yasushi , Ueda Shota , Torii Masahiro , Kennoki Norifumi , Hori Shinichi
Published: March 2020

Objective:

To evaluate the feasibility, efficacy and safety of transcatheter arterial chemoembolization (TACE) with HepaSphere for patients with pulmonary or mediastinal metastases from hepatocellular carcinoma (HCC).

Methods:

Between June 2009 and January 2018, 14 patients with pulmonary or mediastinal metastases from HCC were treated with TACE with a combination of 1–3 chemotherapeutic drugs followed by HepaSphere embolization. As first end point, local tumor response and adverse events were evaluated after the first session of TACE, with Response Evaluation Criteria In Solid Tumors v. 1.1 and Common Terminology Criteria for Adverse Events v. 4 criteria, respectively. Overall survival was evaluated as secondary end point. TACE was repeated on-demand.

Results:

TACE with HepaSphere was well tolerated with acceptable safety profile and no 30 day mortality. 1 month objective response and disease control rate were calculated to be 7.1 and 100%, respectively. Mean tumor size reduction rate was 15.6±9.5% at the first month. Two Grade 3 cytopenia events were seen (14.3 %), however none of the Grade 2 or more post-embolization syndrome was observed. The median overall survival time was 15.0 months and the 1 year, 3 year and 5 year survival rate were, 57.1%, 28.6%, 19.1%, respectively.

Conclusion:

Early experience showed that the transarterial treatment with HepaSphere is safe and effective treatment for patients with pulmonary or mediastinal metastases from HCC.

Advances in knowledge:

Currently, the effects of molecular targeted drugs on HCC metastases are limited and side-effects are relatively frequent. In the present study, transarterial treatment might be a promising treatment for HCC metastasis.
Measurement of total and visceral fat mass in young adult women: a comparison of MRI with anthropometric measurements with and without bioelectrical impedance analysis
Authors: Froelich Matthias F. , Fugmann Marina , Daldrup Charlotte Lütke , Hetterich Holger , Coppenrath Eva , Saam Tobias , Ferrari Uta , Seissler Jochen , Popp Daniel , Lechner Andreas , Sommer Nora Narvina
Published: March 2020

Objective:

MRI is established for measurement of body fat mass (FM) and abdominal visceral adipose tissue (VAT). Anthropometric measurements and bioelectrical impedance analysis (BIA) have been proposed as surrogates to estimation by MRI. Aim of this work is to assess the predictive value of these methods for FM and VAT measured by MRI.

Methods:

Patients were selected from cohort study PPS-Diab (prediction, prevention and subclassification of Type 2 diabetes). Total FM and VAT were quantified by MRI and BIA together with clinical variables like age, waist and hip circumference and height. Least-angle regressions were utilized to select anthropometric and BIA parameters for their use in multivariable linear regression models to predict total FM and VAT. Bland–Altman plots, Pearson correlation coefficients, Wilcoxon signed-rank tests and univariate linear regression models were applied.

Results:

116 females with 35 ± 3 years and a body mass index of 25.1 ± 5.3 kg/m2 were included into the analysis. A multivariable model revealed weight (β = 0.516, p < 0.001), height (β = −0.223, p < 0.001) and hip circumference (β = 0.156, p = 0.003) as significantly associated with total FM measured by MRI. A additional multivariable model also showed a significant predictive value of FMBIA (β = 0.583, p < 0.001) for FM. In addition, waist circumference (β = 0.054, p < 0.001), weight (β = 0.016, p = 0.031) in one model and FMBIA (β = 0.026, p = 0.018) in another model were significantly associated with VAT quantified by MRI. However, deviations reached more than 5 kg for total FM and more than 1 kg for VAT.

Conclusion:

Anthropometric measurements and BIA show significant association with total FM and VAT.

Advances in knowledge:

As these measurements show significant deviations from the absolute measured values determined by MRI, MRI should be considered the gold-standard for quantification.