tbuckley/cabot-search huggingface dataset:
P01.119 TSPO imaging in High Grade Glioma - a multitracer PET, MRI and neuropathology study
Authors: E Agushi, D Lewis, R Hinz, D Coope, A Jackson
Journal: Neuro-Oncology (2018)

The translocator protein (TSPO) is an 18 kDa mitochondrial molecule (previously known as Peripheral Benzodiazepine Receptor), largely studied in neuroinflammation disorders and recently of growing interest in neuro-oncology [2,3]. The aim of our study is to investigate the uptake of [11C](R)-PK11195 (a PET radiotracer for TSPO) and [11C]Methionine and correlate with MR Imaging. Eleven patients (mean age 60 ± 16, M/F=5/6) with lesions suspicious of HGG on clinical MRI were recruited. All patients underwent contrast-enhanced structural and diffusion tensor MR imaging as well as dynamic [11C]-(R)PK11195 and [11C]Methionine PET scans before treatment. Parametric maps of [11C]-(R)PK11195 binding potential (BP) were generated using simplified reference tissue modelling with cerebellar grey matter as reference tissue. BP parametric maps were co-registered to post-contrast T1, fractional anisotropy(FA) and apparent diffusion coefficient (ADC) maps, and finally to [11C]Methionine summed image. Tumour was delineated as a T/N threshold above 1.4 on co-registered [11C]Methionine PET scans and a further regions delineating gadolinium enhancement and necrosis within the tumour were manually delineated. Co-registered MR/PET images were used to guide targeted tumour biopsies which were used to compare directly with histology. All confirmed HGG patients demonstrated a vivid uptake of [11C](R)-PK11195 (mean BP of whole tumour delineated using 1.4 [11C]Methionine threshold: 2.95 range 1.7–4.1; maximal BP: 4.12 range 2.1–6.2). [11C]Methionine uptake extended beyond gadolinium enhancement almost in all HGG cases, and regions of higher uptake did not spatially correlate to hottest [11C](R)-PK11195 areas (Figure 1). A significant correlation was found instead between increased [11C]Methionine uptake and mean diffusivity values (pairwise correlation coeficient = 0.69, p<0.01). TSPO antibody stain of hot TSPO targeted biopsies showed clearly higher values on optical density(OD) measurements, compared to cold uptake targeted areas within the tumour, confirming the correlation of [11C](R)-PK11195 PET imaging and histology (hot biopsies mean OD 4.3% vs 1.3% cold, p<0.001) (Figure 2). Further 3D histology modelling, colouring with multiple antibodies (Iba1, IDH1 and CD31) showed the localisation of TSPO in tumour hottest regions is mainly in the neoplastic cells rather than microglia or endothelium. Tumour recurrence was found to coincide with the regions of higher [11C](R)-PK11195 uptake in 2 of the patient's clinical MR scans. [11C]-(R)PK11195 has the potential to detect early recurrence and provides information complimentary to perfusion metrics in early detection of recurrence. Methionine offers a better tumour delineation which could lead to more extensive surgical resections and better chances for survival.
Early nutrition support therapy to improve the nutrition status of head and neck cancer patients accepted concurrent chemoradiotherapy (NSTIP): Interim analysis from a prospective randomized controlled clinical study.
Authors: Peng Zhang, Kang Xie, Xuemei Huang, Rong Chu Li, Yanqiong Song, Baisen Li, Wenjun Liao, Shichuan Zhang, Jinyi Lang
Journal: Journal of Clinical Oncology (2018)

TPS10127 Background: We given nutrition support treatment according to the changes by nutrition status in head and neck cancer patients at the process of definitive concurrent chemoradiotherapy(CCRT). Analyze the relationship between nutrition support therapy and CCRT side effects, quality of life score, treatment effect, prognosis and other indicators. Methods: 100 patients with head and neck cancer undergoing definitive chemoradiotherapy were enrolled. They were randomly divided into a nutritional intervention group (n= 50) and a conventional diet group (n= 50). The nutritional intervention group treated with prophylactic enteral nutrition powder formula (645.43 kcal/day; 2701.3 kJ/day) feeding before the initiation of CCRT. All patients were subjected to a standardised follow-up programme which included prospective evaluation of psychological status and HRQoL, prior to, during and after CCRT. The psychological status of those two groups were evaluated by Patient Health Questionnaire 9(PHQ-9), Generalised Anxiety Disorder Assessment 7(GAD-7) and Distress Thermometer. The primary endpoint was the nutritional indicators including body weight, white blood cells, lymphocyte, albumin etc. The secondary endpoints were the psychological status.This study is ongoing; data for this interim analysis were collected at December 30, 2017. This trial is registered with www.chictr.org.cn, number. Clinical trial information: ChiCTR-IIR-17011243.
Abstract 13810: Depression and Anxiety Are Associated With Sleep Quantity and Quality in Patients Hospitalized With Cardiovascular Diseases
Authors: Risa Matsuda, Takashi Kohno, Shun Kohsaka, Rikako Noda, Mikiko Ohashi, Ryoma Fukuoka, Kentaro Hayashida, Shinsuke Yuasa, Keiichi Fukuda
Journal: Circulation (2017)

Introduction: Sleep is increasingly recognized as an important lifestyle contributor to health, and sleep shortage, poor sleep quality, and sleep disordered breathing (SDB) have emerged as cardiova...
Prognostic effects of peripheral and tumor-infiltrating T-cell repertoire diversity in ovarian cancer.
Authors: Kunle Odunsi, Takemasa Tsuji, Kevin H. Eng, James Brian Szender, Junko Matsuzaki, Anthony Miliotto, Sacha Gnjatic, Wiam Bshara, Angela Omilian, Carl D Morrison, Shashikant B. Lele, Ryan O Emerson, Cindy Desmarais, Jianmin Wang, Song Liu, Harlan Robins, Amit Lugade, Richard C Koya
Journal: Journal of Clinical Oncology (2016)

5546 Background: While the prognostic value of the number of tumor-infiltrating lymphocytes (TILs) has been demonstrated in many tumor types, the significance of the clonal composition of peripheral and tumor-infiltrating T-cell repertoires is unknown due to challenges in quantifying unique clones. To delineate the impact of the T cell repertoire on anti-tumor immunity, we performed deep T-cell receptor (TCR)-sequencing on paired tumor and peripheral blood samples from 99 ovarian cancer patients. Methods: Clonotype frequencies were calculated for unique TCR-β chain sequences using the ImmunoSEQ platform in 198 total samples. Spontaneous immune responses were evaluated by measuring serum antibodies against ovarian cancer-associated antigens (NY-ESO-1, MAGE-A1, MAGE-A3, p53). The degree of CD3+ and CD8+T-cell infiltration was evaluated by immunohistochemistry. Results: We obtained 505 and 305 million TCR reads (10.3 and 1.4 million unique clones) in peripheral blood and tumors, respectively. Higher clone/CD3 TIL ratios – indicating more diverse repertoires for a given level of infiltration – were associated with poorer OS (HR = 1.7, 95% CI = 1.3-2.4) and PFS (1.7, 1.2-2.3) as were clone/CD4 TIL ratios (OS: 2.6, 1.5-4.4; PFS: 2.3, 1.4-3.7). While higher TIL clonality (scaled 0-1 from polyclonal to monoclonal) conferred a favorable prognosis in patients with spontaneous response to tumor antigens (OS per +0.1: 0.4, 0.1-1.0), it was a poor prognostic factor in patients without a response (1.6, 1.0-2.6). The fraction of peripheral T-cell repertoires that were also present in TIL is positively associated with OS (per +10%, 0.6, 0.4-0.9) and PFS (0.7, 0.5-1.0) in seropositive patients, but is negatively associated in seronegative patients (OS: 1.3, 1.0-1.6; PFS: 1.8, 1.2-2.9). Conclusions: Integration of T-cell repertoire diversity in tumor and peripheral blood with density of TILs identified clone/CD3 TIL and clone/CD4 TIL ratios; TIL clonality; and the degree of overlap of peripheral and TIL repertoire as novel prognostic biomarkers in ovarian cancer. The presence of pre-existing anti-tumor immunity shapes the correlation of TIL clonality and peripheral/TIL overlap with clinical outcome.
FDG PET scan (PET) positive residual lesions after chemotherapy (chemo) for metastatic seminoma: Results of an International Global Germ Cell Cancer Group (G3) registry.
Authors: Richard Cathomas, Dirk Klingbiel, Brandon David Bernard, Anja Lorch, Xavier Garcia del Muro, Franco Morelli, Ugo De Giorgi, Mikhail Fedyanin, Christoph Oing, Hege Sagstuen Haugnes, Marcus Hentrich, Christian Daniel Fankhauser, Margarida Brito Goncalves, Gabriella Elisabeth Cohn-Cedermark, Gedske Daugaard, Giuseppe Fornarini, Gaetano Aurilio, Frank Mayer, Katharina Huss, Joerg Beyer
Journal: Journal of Clinical Oncology (2017)

4521 Background: Residual disease is a frequent finding after chemo for metastatic seminoma. Watchful waiting is recommended for residual lesions &lt; 3 cm or lesions ≥3 cm with negative PET. Data on the optimal management of PET positive residual lesions is lacking. Methods: A retrospective analysis within the G3 Group identified 91 patients (pts) from 9 countries with metastatic seminoma and residual PET positive lesions after chemo. Pts with elevated AFP ( &gt; 2xULN) or non-seminomatous components at diagnosis were excluded. We analyzed the post PET management chosen and its impact on relapse and survival. Results: Median follow-up was 29 (IQR 10 – 64) months. Median age at diagnosis was 41 (range 19 – 69) years. The primary tumor was gonadal in 68 pts (76%), retroperitoneal in 12 pts (13%) and mediastinal in 10 pts (11%). Prior to chemo the median size of the largest metastasis was 10 (range 1.4 – 23) cm, 67 pts (74%) had elevated LDH and 51 pts (57%) elevated HCG. Median diameter of the largest residual mass was 4.8 (range 1.1 – 14) cm mainly located in the retroperitoneum (77%), pelvis (15%), mediastinum (16%) or lung (4%). Median time from last day of chemo to PET was 7 (IQR 4 – 10) weeks. Post PET management was repeated imaging in 46 pts (51%), resection in 32 pts (35%), biopsy in 9 pts (10%) and radiotherapy in 4 pts (4%). Histology of the resected specimen was necrosis only in 25 (78%) and vital seminoma in 7 cases (22%). No biopsy revealed vital seminoma. Relapses occurred after a median of 3.7 (IQR 2.5 – 4.9) months in 16 pts (18%): 2/9 (22%) after biopsy, 12/46 (26%) on repeated imaging and 2/32 (6%) after resection (one necrosis, one &lt; 10% vital seminoma). Site of relapse was the area of residual disease in 14 pts (88%) and additional distant relapse (one bone, one lung) in 2 pts (12%). All relapsed pts received successful salvage chemo apart from one who died from treatment and two pts who are alive with ongoing treatment. Conclusions: PET positive post chemo residual lesions in seminoma pts are false positive in about 75%. Relapses in PET positive pts occur early and can be salvaged with chemo. Further analysis is needed to identify risk factors for relapse.
Virtual metastatic breast multidisciplinary meeting: The next step in personalised medicine.
Authors: Helen Winter, Steve Rumbles, Bernie Hughes, Marcella O'Brien, Sharmin Rahman, Carmen Murias, John Conibear, Mark Harries, Peter George Harper, Paul Chandler, Sofia Naureen, Naiome Carter, Steve Dixon, Susan Cleator, Peter Schmid, Tim Crook, Paul Anthony Ellis, Hendrik-Tobias Arkenau, Alison Jones
Journal: Journal of Clinical Oncology (2018)

e18794 Background: Face to face MDT discussion underpins the delivery of high quality management in early breast cancer. A virtual electronic MDT (vMDT) in metastatic disease offers broader oncological input with expertise in supportive care, clinical trials, decisions to re-biopsy and molecular profiling. Methods: Terms of reference and governance were established by a working party with representation from Oncology, Clinical Nurse Specialists, Pharmacy, SCRI trials team, Supportive Care and Psychology. An IT solution was developed within the existing electronic patient record (EPR) in-house team. Once an MDT EPR request initiated, email alerts were generated to oncologists. On completion of a quorate number of replies an automatic MDT recommendation was generated and integrated into EPR. Lead clinician acted as chair and arbitrator. MDT discussion was mandated in third line and beyond in the pilot vMDT. Sixty percent concordance was required for treatment approval. Results: Thirty patients were discussed in this vMDT pilot and key outcomes are shown in table 1. Three patients have enrolled in clinical trials as a direct result of discussion at the vMDT, however more potential trials patients were identified. Seven other patients had changes in their proposed treatment. Conclusions: Virtual MDT decision-making was feasible and offered high quality, time -efficient enhancement of complex care and management. Offering opportunities for tailoring treatment to the individual with access to suitable trials, broader oncological input the vMDT is enhancing care in a time efficient, asynchronous virtual forum. Number of patients with metastatic breast cancer 30 Median number of oncologists responding/ patient (range) 5 (3-7) Concordance with requesting oncologist proposed plan 20 (67%) Discordance leading to change from planned treatment (excluding trials) 7 (23%) Patients considered potentially suitable for clinical trials 23 (77%) Patients enrolled in clinical trials 3 (10%)
Analysis of molecular and protein signatures on farletuzumab pharmacokinetics from a phase 3 ovarian cancer study.
Authors: Daniel John O'Shannessy, Charles Schweizer, Wenquan Wang, Elizabeth Brooke Somers, Susan Weil, Carole Antinori, Rhonda Meredith, Mark Andrew Landers, Nicholas Nicolaides
Journal: Journal of Clinical Oncology (2016)

e14508 Background: Farletuzumab (FAR) is a humanized monoclonal antibody that binds to folate receptor alpha which is highly expressed in epithelial ovarian cancer (EOC). An 1100 subject Phase 3 EOC trial of carboplatin/taxane plus either FAR or placebo did not meet the primary PFS endpoint. Prespecified subgroup analysis demonstrated subjects with CA125 ≤ 3×ULN and higher FAR exposure showed superior PFS and OS compared to placebo. As serum proteins and associated gene products related to the neonatal Fc receptor (FcRn) pathway have been reported to influence antibody pharmacokinetics (PK), biomarker analysis was conducted to determine the impact of molecular and protein signatures on FAR steady state serum levels. Methods: Nucleic acids isolated from PBMCs for genotyping and serum samples for protein biomarker analyses were obtained at patient screening from 468 consenting patients. Candidate serum proteins and gene products, including FcRN were analyzed for coding changes and promoter variable nucleotide tandem repeats (VNTR) to determine if a correlation exists with FAR PK. Results: FcRn coding region sequence analysis identified 63 patients (13.5%) with 9 distinct heterozygous single nucleotide polymorphisms (SNP), 5 of which resulted in amino acid changes. A similar frequency of promoter VNTRs were found as previously reported. SNP nor promoter genotypes had a correlation with steady state FAR, serum albumin or IgG levels. When compared to the lowest quartile, subjects at the highest quartile of FAR steady state Cmin had a statistically significant difference of higher serum albumin (p = < .0001) and lower endogenous IgG levels (p = 0.0066). Higher albumin and lower IgG had a similar effect on FAR Cmin1 and AUC. Conclusions: FcRn genotype did not influence serum FAR, albumin or IgG levels. However, subjects with highest FAR levels had higher serum albumin and lower IgG. As therapeutic effects of antibodies such as FAR could potentially be enhanced with improved serum exposure, these proteins warrant further study to determine if their relative values can predetermine patients who may accumulate higher steady state exposure levels of therapeutic antibodies.
Effectiveness of bendamustine in relapse or refractory lymphoma cases: A report from Turkey—The Turkish Oncology Group (TOG) study.
Authors: Nuri Karadurmus, Semra Paydas, Ramazan Ocal, Birol Yildiz, Erdinc Nayir, Mutlu Dogan, Ahmet Taner Sumbul, Zeki Surmeli, Ibrahim Barısta, Burhan Ferhanoglu, Gokhan Ozgur, Ismail Erturk, Sukru Ozaydin, Halil Ibrahim Petekkaya, Necdet Uskent
Journal: Journal of Clinical Oncology (2017)

e19027 Background: Bendamustine is an old conventional agent which is used in the treatment of hodgkin's lymphoma (HL), non-hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL) patients despite they are relapsed or refractory cases. In our study we wanted to reveal retrospectively the efficacy and side effects of bendamustine in relapse/refractory patients from Turkey. Methods: We included in the study relapse/refractory HL and NHL patients who underwent multiple line chemotherapy. Bendamustine was administered at 90 mg/m² on days 1 and 2, every 3 weeks by 60 minutes infusion. The primary endpoint of the study was to determine the objective response and toxicity. Results: Seventy-five patients (31 female) with a median age of 62.8 years (range 16-89 years) were included in the study. 58 of the patients were NHL (follicular lymphoma:8, diffuse large B-cell lymphoma: 17, mantle cell lymphoma: 11, marginal zone lymphoma: 4, Small lymphocytic lymphoma:11, Others:7) and 17 of them were HL patients. The patients were underwent median three lines chemotherapy (range 1-8) accept autologous stem cell transplantation, 20 patients (HL: 12, NHL:8) were underwent autologous stem cell transplantation. Bendamustine was performed an average of 6 cycles (range 1-38). The objective response rate was 73.3%, complete response rate was 44% (n = 33), partial response rate was 29.3% (n = 22), respectively. The response rate was 65% (11/17) in HL cases, 79% (30/38) in indolent NHL cases and 70% (14/20) in aggressive NHL cases. For median follow-up of 20.7 months, the median overall survival (OS) was 64.9 months, OS rate was 75.5% for 1 year, 67.6% for 2 years and 63.1% for 3 years. The most common side effects associated with treatment were lymphopenia, neutropenia, thrombocytopenia, abdominal pain, fatigue and diarrhea. Side effects which were seen as grade 3 and higher levels: 9.6% lymphopenia, thrombocytopenia 8% and 12% fatigue. Conclusions: Objective response rate of bendamustine with tolerable side effect profile was found to be 73.3% in relapsed / refractory HL and NHL patients as a rescue agent. It appears to be an ideal agent for rescue treatment which had previously received intensive treatment.
Persistent prevention of CIPN using calmangafodipir (PledOx): Results from a placebo-controlled randomized phase II study (PLIANT) in patients with metastatic colorectal cancer (mCRC).
Authors: Bengt Glimelius, Nebojsa Manojlovic, Per Pfeiffer, Baadur Mosidze, Galina Petrova Kurteva, Mia Karlberg, Devalingam Mahalingam, Marie Helene Bengtson, Jacques Nasstrom
Journal: Journal of Clinical Oncology (2016)

10018 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major problem after oxaliplatin treatment. Calmangafodipir (CaM) has shown promising activities in model systems in preventing oxaliplatin-induced adverse effects. In a dose-escalating phase I study including 11 patients, doses up to 10 µmol/kg were well tolerated and had promising preventive effects on CIPN (Glimelius, MASCC 2015). A randomized placebo-controlled multicenter phase II study (NCT 01619423) assessed safety and efficacy of CaM in ameliorating CIPN. Methods: The PLIANT study included 173 mCRC patients treated with the FOLFOX-6 regimen (oxaliplatin 85 mg/m2, calciumfolinate 200 mg/m2, 5FU bolus 400 mg/m2, 5FU infusion 2400 mg/m2) every fortnight either in first or second-line. Ten minutes prior to each chemotherapy cycle CaM 2 and 5 (initially 10) µmol/kg or placebo was given intravenously during 5 minutes. The primary endpoint was neurotoxicity according to the Oxaliplatin Sanofi Specific Scale (OSSS) each cycle up to cycle 8. Secondary endpoints included the patient reported outcomes Cold Allodynia Test (CAT) and the Leonard Scale (LS) at end-of-treatment (EOT) and during follow-up (FU) every 3 month (mo), tumor evaluations after 4 and 8 cycles and overall survival (OS). Results: CaM was well tolerated. CIPN according to OSSS was clearly less in patients treated with 5 µmol/kg after the 3rd up to the 8th cycle (OR (90%CI) 0.57(1.13), p=0.15). CaM had a dose-dependent and significant effect on persistent CIPN measured as mean sensory score on the LS at 3 and 6 mo FU. See table for further details († p<0.1, * p<0.05, **p=0.01 vs. placebo). Conclusions: The activity of the chemoprotector CaM is promising in preventing acute and persistent CIPN without any detectable negative influence on the antitumor activity of an oxaliplatin-5FU combination in patients with mCRC. A phase III trial using the 5 µmol/kg dose will be initiated. Clinical trial information: NCT 01619423.Placebo (n=60) PledOx 2 µmol (n=57) 5 µmol (n=45) 5+10 µmol (n=56) OSSS ≥2 (OR) 1.00 0.84 0.57 0.55 CAT (EOT) 2.4 1.3† 1.5† 1.6 LS (3 mo) 5.8 2.8 1.9** 1.6** LS (6 mo) 5.0 2.6 1.4* 1.2** ORR (%) 27 40* 27 30 OS (mo) >16 >16 >17 >17
Real-world utilization and patient outcomes associated with pembrolizumab in advanced melanoma in US academic centers and affiliated satellite clinics.
Authors: Richard Wayne Joseph, Frank Xiaoqing Liu, Cynthia Macahilig, Scott J. Diede, Vaidehi Dave, Qing Harshaw, Alicia Shillington
Journal: Journal of Clinical Oncology (2018)

e21500 Background: Pembrolizumab (PEMBRO) is the first US FDA approved PD-1 antibody for the treatment of patients with advanced (metastatic/unresectable) melanoma. Clinical trials such as KEYNOTE-006, have demonstrated efficacy and safety in controlled settings. However, patients in trials often differ from non-trial populations. Very limited information exists for real-world utilization and outcomes associated with PEMBRO in US academic centers and affiliated satellite clinics. Methods: A retrospective, chart-review study was conducted in the US; 12 oncologists from 12 US academic centers and affiliated satellite clinics were recruited to contribute patients ≥18 years of age with advanced (unresectable/metastatic) melanoma treated with PEMBRO in any line between Jan 1, 2016 – Jun 30, 2017 with a minimum of 6 months follow-up. Baseline demographics, disease characteristics and real-world response rate (rwRR) were examined in an observational (OBS) cohort and compared to findings from KEYNOTE-006 using X2tests. 12-month survival was estimated using Kaplan Meier analysis. Results: A total of 148 real-world PEMBRO patients were included in the OBS cohort. Compared to KEYNOTE-006, the OBS cohort had a similar median age, 63, more females (52.7% vs 39.7, p < 0.001), higher proportion of front-line PEMBRO utilization (85.1% vs. 66.2%, p = .005), and elevated LDH at treatment initiation (47.3% vs 32.2%, p < 0.001). PD-L1 expression testing was available in 66.2% of the OBS cohort, and of those tested there was a lower percentage of PD-L1 positive patients (72.4% vs. 81.2%, p = .045). While KEYNOTE-006 did not include patients with Eastern Cooperative Group (ECOG) > 1, the OBS cohort had 35.8% with ECOG 2 or higher. rwRR (complete or partial) was 70.0% in the OBS cohort vs 36.5% in trial data (p < 0.001), and 12-month survival was 84.6% compared with 71.3%. Conclusions: PEMBRO has been used in a wider melanoma patient population than trials. Findings of this study support its effectiveness in the real world with higher rwRR and longer OS than in the Keynote-006 clinical trial. However, real world response to therapy may be overestimated by treating clinicians in the real-world.