tbuckley/cabot-search huggingface dataset:
Prognostic value of PET-CT in early stage Hodgkin Lymphoma (HL) using updated 5 point scoring system.
Authors: Vishwanath Sathyanarayanan, Dai Chihara, Michelle A. Fanale, Colleen M Costelloe, Elham Ghonimi, Chan Shen, Francisco Vega, Bouthaina Shbib Dabaja, Yasuhiro Oki, Shouhao Zhou, Chuang Hubert
Journal: Journal of Clinical Oncology (2016)

e19013 Background: The Lymphoma response criteria (2007), updated in 2014, use PET-CT to evaluate response in early stage HL (Cheson et al). PET-CT is accurate in predicting responses, however there are variations. (Gallamini et al and Moskowitz et al). We evaluated for a correlation between PET-CT at end of therapy and clinical outcome (relapse/death) at 1 year as reference. Methods: In this retrospective study, we extracted stage, risk (favorable/unfavorable by German Hodgkin Study Group criteria), bulky disease (≥10cm), radiation therapy (XRT), and chemotherapy data of 133 patients with newly diagnosed early stage HL from September 2009 to October 2014. Relapse was confirmed with biopsy in all patients except for 2. NLPHL, advanced HL, and PET-CT before XRT were excluded. 2 PET-CT readers who were blinded to clinical outcome gave a consensus score based on the new criteria at the end of therapy and it was compared to clinical outcome at 1 year. Fisher’s exact test and multivariate logistic regression were used. Results: PET-CT at the end of therapy predicted clinical outcome at 1 year with asensitivity of 0.57, specificity: 0.94, positive predictive value (PPV): 0.53 and negative predictive value (NPV): 0.95. All false positive (FP) cases were scored as 4. 6 out of 8 true positive (TP) were scored as 5. Multivariate analysis showed that positive PET-CT, bulky disease and lack of XRT predicted relapse at 1 year with odds ratio (OR=14.29, p<0.001), (OR=4.25, p=0.057), and (OR=6.09, p=0.021) respectively. Conclusions: End of therapy PET-CT can predict clinical outcome of early stage HL with high specificity and NPV. However, the low sensitivity and PPV of PET-CT may result in increased FP when the cut off is 4. Patients with a score of 4 should be biopsied before initiating salvage therapy. Other factors (bulky disease and lack of XRT) should be considered as they are associated with a higher risk of relapse. Variables Relapse No relapse P value PET-CT 6 (5.08%) 112 <0.001 - 8 (53.3%) (94.9%) + 7 (46.6%) Risk 0 45 (100%) 0.003 Favorable 14 74 Unfavorable (15.91%) (84.09%) Stage 0 17 (100%) 0.21 1 14(12.07%) 102 2 (87.9%) Bulky ≥10 cm 6 (6.8%) 82 (93.1%) 0.006 No 7 (29.1%) 17 (70.8%) Yes XRT 11 (28.2%) 28 (71.7%) <0.001 No 3 (3.1%) 91 (96.8%) Yes
Modelization of the procoagulant properties of cancer cells and the alterations of the effectiveness of the anticoagulant agents.
Authors: Aurelie Rousseau, Patrick Van Dreden, Elisabeth Mbemba, Annette K. Larsen, Hayat Mokrani, Ismail Elalamy, Konstantinos N. Syrigos, Grigoris Gerotziafas
Journal: Journal of Clinical Oncology (2016)

e23094 Background: The pathogenesis of the prothrombotic state in cancer is complex and may alter the efficiency of the antithrombotic agents but not all mechanisms are entirely understood. In the present study we dissected the mechanisms responsible for the procoagulant activity of pancreas adenocarcinoma cells (BXPC3) and human breast carcinoma cells (MCF7) by thrombin generation assay (TG) in different relevant conditions, and we studied their influence on the antithrombotic efficiency of apixaban, fondaparinux and enoxaparin in a new experimental model. Methods: Cells were cultured and adhered in 96-well plates and normal platelet poor or rich plasma (PPP; PRP) spiked or not with apixaban, fondaparinux or enoxaparin was added. TG was done with CAT assay in different conditions of reagents, with or without any anti-tissue factor antibody (anti-TF), or corn trypsin inhibitor (CTI; inhibitor of the contact phase of coagulation). Alternatively spliced TF (asTF), TF activity (TFa) and cancer procoagulant (CP) were also assessed. Results: The TFa and asTF were found in abundant amounts in BXCP3 than MCF7 cells. The CP levels were higher in MCF7. The BXPC3 amplified TG more than MCF7 did. The anti-TF inhibited TG triggered by BXCP3 and MCF7. The CTI had more pronounced inhibitory effect on TG triggered by MCF7. TG enhancement by BXPC3 and MCF7 was mediated by FVII. Factor XII was more important for TG enhancement by MCF7. Comparison on the basis of IC50 showed that in the presence of BXPC3 or MCF7 the efficiency of apixaban was preserved or partially reversed. Fondaparinux, was more vulnerable to the presence of cancer cells as compared to apixaban. The effect of BXCP3 or MCF7 cells on the antithrombotic potency of enoxaparin was of similar magnitude as that on apixaban. Conclusions: The mechanism of activation of blood coagulation by the BXPC3 is dominated by the TF pathway, MCF7 additionally imply also FXII activation. The type of cancer cells is determinant for the antithrombotic efficiency of the specific factor Xa inhibitors. Modeling procoagulant profile of cancer cells provides an understanding of the procoagulant mechanisms and could evaluate the efficiency of antithrombotic treatment.
Abstract 17407: Modulation of N6-Methyladenosine (m6A) by the Fat Mass Obesity-Associated Gene (FTO) Regulates Cardiac Function
Authors: Prabhu Mathiyalagan, Yaxuan Liang, Yassine Sassi, Marta Adamiak, Kiyotake Ishikawa, Shihong Zhong, Erik Kohlbrenner, Xiaoke Yin, Elena Chepurko, Neha Agarwal, Jiqiu Chen, Rajvir Singh, Kenneth Fish, Manuel Mayr, Djamel Lebeche, Roger J Hajjar, Susmita Sahoo
Journal: Circulation (2017)

Introduction: Protein expression in the left ventricle of a failing human heart does not correlate with the corresponding mRNA abundance, suggesting a major role for post-transcriptional (epitransc...
Development of NKG2D chimeric antigen receptor-T cells as targeted therapy of liver cancer.
Authors: Hong-jiu Dai, Dong Yang, Bin Sun, Yu-Bo Jiang, Ru Jia, Jian-Ming Xu, Xu-dong Zhao
Journal: Journal of Clinical Oncology (2018)

e15057 Background: Liver cancer is the fifth most common cancer and the third most common cause of cancer mortality worldwide with the 5-year survival rate of ~10%. In the past decade, some studies began to choose scFv as antigen binding domain for CAR-T cell therapy to treat liver cancer, yet the clinical outcome is limited so far. We developed a chimeric antigen receptor(CAR) targeting NKG2DLs (KD-025) to leverage adoptive T cell therapy as a powerful treatment modality for liver cancer. Methods: Liver cancer SMMC7721 cell line as well as liver cancer patient samples were evaluated for NKG2DLs expression. The KD-025 CAR T cells showed antigen-specific stimulation by cytokine secretion and target cell lysis. SMMC7721 solid tumors were used to establish in vivo subcutaneous and xenograft models in NSG mice. Mice received a single treatment of 10 million KD-025 CAR-T cells intravenously. The main organs of mouse were examined by hematoxylin and eosin (HE) staining after different doses of KD-025 administration. Results: NKG2DLs were detected on SMMC7721 and most of screened liver cancer patient samples. The KD-025 expression was > 50% on the surface of T cells confirmed by flow cytometry. Co-incubation of KD-025 CAR with SMMC7721 cell specifically upregulates TNFa, IFN-γ, IL-10 and IL-2 cytokines and strongly lysis tumor cells even at low E:T ratio (40% at 1:1, 60% at 10:1). Strikingly, KD-025 CAR demonstrated very potent anti-tumor activity in vivo. All the tumor cells are gone 14 days after single treatment of KD-025 CAR T cells. Two out of 6 mice displayed tumor recurrence on day 49. The rest 4 mice were tumor free till day 77 when the mice were scarified. Regarding the CAR-T cell persistence, KD-025 CAR-T cells are barely detectable 24 days after injection, which is comparable to CD19 CAR in the same experiment as well as reported data. No obvious pathological changes were found in the tested organs. Conclusions: NKG2D ligands are highly expressed on human liver cancer samples, but not normal tissues. NKG2D based CAR T cells KD-025 potently respond to hepatic tumors and eliminate liver tumor in a xenograft mouse model with no obvious safety issue. The results support future clinical trial of KD-025 CAR in patients with liver cancer.
Implementation of the IOM 13 point care plan by Oncology Care Model (OCM) practices.
Authors: Brenton Fargnoli, Natasha Jaffe, Nick Bauer-Levey, Keith Cowing, Joanne Schneider, Rohit Parulkar, DJ Lee, Ovadia Harary, Ryan Holleran, Sen Zhang, Cindy Revol, Dan Tran, Robin Shah, Amy Pickar Abernethy, Michael A. Kolodziej
Journal: Journal of Clinical Oncology (2017)

e18279 Background: The completion of the IOM 13 point care plan is mandatory for all patients enrolled in the OCM. We built an integrated care plan into the electronic medical record, with 9 points being auto-populated by data documented elsewhere in the EMR and 4 points requiring completion by the caregiver. We report on preliminary experience with care plan completion. Methods: Of the 190 practices selected by CMMI for the OCM, 32 practices utilized the embedded care plan. Patient eligibility for the OCM was determined by identification of a qualifying episode by an electronic algorithm. Initiation of a care plan was determined by physician completion of any field in the care plan field. Completion of the care plan was defined by the act of printing and distributing the care plan to the patient. Correlations between number of eligible patients and completion rates were calculated using Pearson’s product moment correlation coefficient (r). P-values were calculated using a t-distribution and null hypothesis of 0. Results: Over the first 6 months, 15,705 patients were identified as eligible for the OCM. At these practices, 69% (10,851) of patients had care plans initiated (range 0-100%) and 34% (5,290) had a care plan printed (range 0-100%). Within the care plans initiated, 53% (5,711) had the advance directive field completed (range 0-87%). There was no correlation between percent of care plans initiated or percent of care plans printed and number of eligible patients in the practice (r = -0.16, p = 0.51 and r = -0.13, p = 0.44); likewise, advance directive field completion percent was not correlated with the number of eligible patients (r = -0.16, p = 0.37). Conclusions: Completion of the IOM care plan has proven challenging for practices in the OCM irrespective of practice size. This suggests technological solutions represent only one component needed for success in this component of the OCM.
Phase I/II trial of glasdegib in patients with primary or secondary myelofibrosis.
Authors: Aaron Thomas Gerds, Tetsuzo Tauchi, Ellen K. Ritchie, Michael W.N. Deininger, Catriona HM Jamieson, Ruben A. Mesa, Mark L. Heaney, Norio Komatsu, Hironobu Minami, Yun Su, Mohammed Naveed Shaik, Xiaoxi Zhang, Christine DiRienzo, Mirjana Zeremski, Adrian Woolfson, Geoffrey Chan, Moshe Talpaz
Journal: Journal of Clinical Oncology (2017)

7061 Background: Glasdegib is a small molecule inhibitor of the Sonic Hedgehog pathway, and data from the single arm, lead-in cohort of a phase 1b/2 trial in myelofibrosis (MF) are shown. Methods: Patients (age ≥18 yrs) with primary/secondary MF previously-treated with ≥1 Janus Kinase inhibitor (JAKi) were enrolled and received glasdegib 100 mg QD orally in 28 day cycles. AEs and laboratory abnormalities were assessed. Key efficacy endpoints were proportion of patients with spleen volume reduction (SVR) ≥35% and ≥50% reduction in total symptom score (TSS) measured by the MPN Symptom Assessment Diary (MPN-SAD) at Week 24. Results: 21 patients were enrolled between Oct '14-Oct '15 in this ongoing study. Mean age was 69.3 yrs (range 58-83). Median duration of treatment was 85 days (22-343). 52% were refractory patients with inadequate response to prior JAKi. Baseline symptoms were mostly mild (1-4), except fatigue (&gt;4). No patients achieved SVR ≥35%, 5 patients had some SVR (maximum 2.3-21.4% reduction from baseline), and no progressive disease prior to Day 71. At week 24, 1 patient had ≥50% reduction in TSS, but 3/21 and 4/21, respectively showed 30% and 20% TSS reduction. Of 14 patients with severe baseline symptoms (1 with ≥5, or ≥2 with ≥3), 1, 1, and 2 achieved 50%, 30%, and 20% TSS reduction, respectively at week 24. TSS, spleen-related, and constitutional symptom scores showed a trend of reduction over 24 weeks with spleen-related symptoms, inactivity, and fatigue showing greatest improvement (52%, 58%, and 36%, respectively). Dysgeusia (N=13), muscle spasms (N=12), alopecia (N=8), decreased appetite (N=7), fatigue (N=7), lipase increase (N=5), and weight decrease (N=5) occurred in ≥20% patients. None, except 1 episode of fatigue, were considered serious AEs. Glasdegib steady state PK was consistent with previous single agent data. Conclusions: Glasdegib has an acceptable toxicity profile in patients with primary/secondary MF previously treated with JAKi. Symptom responder definition for refractory patients may not be the same as for JAKi naïve patients. Patient reported symptom improvement may be a more sensitive indicator of treatment benefit vs SVR. Further study of glasdegib may be warranted. Clinical Trial Information: NCT02226172.
Applicability of the concept of ‘platinum sensitivity’ to recurrent cervical cancer: A JGOG Net Work study.
Authors: Munetaka Takekuma, Keita Mori, Tetsuji Iida, Kazuko Kurihara, Motoaki Saitou, Hideki Tokunaga, Kei Kawana, Masae Ikeda, Toyomi Satoh, Toshiaki Saito, Etsuko Miyagi, Yutaka Nagai, Akiko Furusawa, Yoshiaki Kawano, Shin Nishio, Tsutomu Tabata, Yukinobu Ota, Ryoji Hayase, Mikio Mikami, Toru Sugiyama
Journal: Journal of Clinical Oncology (2016)

e17003 Background: The aim of this study was to evaluate a hypotheses regarding the validity of the concept of platinum sensitivity in recurrent cervical cancer. Methods: In this multicenter retrospective cohort study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving first-line platinum-based chemotherapy (including concurrent chemoradiotherapy with cisplatin) and who received second-line platinum-based chemotherapy at the time of recurrence between January 2008 and December 2012 were reviewed. The relationship between the survival and a platinum free interval (PFI), which is defined as the period between the completion of platinum based primary chemotherapy and the disease recurrence, was analyzed. Results: A total of 723 patients from 71 centers were enrolled. The median age was 54 years (range, 26 to 82 years). 519 squamous cell carcinoma (71.8%), 162 adenocarcinoma (22.4%) and 42 adenosquamous cell carcinoma (5.8%) were enrolled. The median progression-free survival (PFS) for patients with PFI of < 6 months, ≥6 months and < 12 months, ≥ 12 months and < 18 months and ≥ 18 months was 3.0 (95% CI = 2.4-4.2) months, 4.0 (95% CI = 3.7-4.5) months, 5.2 (95% CI = 4.4-5.9) months and 6.9 (95% CI = 6.0-7.4) months, respectively (log-rank, p < 0.0001). The median overall survival (OS) for patients with PFI of < 6 months, ≥ 6 months and < 12 months, ≥ 12 months and < 18 months and ≥ 18 months was 7.6 (95% CI = 5.2-9.6) months, 14.0 (95% CI = 12.3-15.5) months, 19.4 (95% CI = 16.6-21.2) months and 29.6 (95% CI = 25.6-31.7) months, respectively (log-rank, p < 0.0001). The threshold of PFI which affected PFS and OS was analyzed by the minimum p value method and the results were 256 days and 221 days, respectively. Conclusions: Platinum-free interval is a predictor of survival after second-line platinum-based chemotherapy in patients with recurrent cervical cancer. We will conduct a prospective study which will evaluate the validation of this result to apply the concept of platinum sensitivity to recurrent cervical cancer.
A randomized phase II study of chemoradiation (CRT) +/- nivolumab (Nivo) with sequential safety evaluations of Nivo +/- lirilumab (Liri) or ipilumumab (Ipi) concomitant with (C) RT in intermediate (IR) and high-risk (HR) head and neck squamous cell carcinoma (HNSCC) (RTOG 3504, NCT02764593).
Authors: Maura L. Gillison, Robert L. Ferris, Qiang Zhang, A. Dimitrios Colevas, Loren K. Mell, Christina Kong, Richard Jordan, Kevin Moore, Minh Tam Truong, Claudia Kirsch, Mitchell Machtay, Walter John Curran, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2017)

TPS6097 Background: Nivolumab (Nivo), a monoclonal antibody to the programmed death-1 (PD-1) immune checkpoint receptor, improved overall survival (OS) for patients (pts) with platinum-refractory, recurrent/metastatic HNSCC compared with standard therapy. A placebo controlled phase IIR trial was designed to investigate the hypothesis that Nivo added to platinum-based CRT will improve progression free survival (PFS) for pts with newly diagnosed IR/HR HNSCC. Methods: Eligibility includes IR HNSCC (p16+, oropharynx T1-2N2b-N3/T3-4N0-3, &gt; 10 pack-years (pys) or T4N0-N3, T1-3N3 ≤ 10 pys) and HR HNSCC (oral cavity, larynx, hypopharynx, or p16(-) oropharynx, stage T1-2N2a-N3 or T3-4N0-3). After safety evaluation in 8 evaluable pts, 176 pts will be randomized (1:1) to cisplatin (40 mg/m 2 /week X 7) with radiation (IMRT, 70 Gy in 7 weeks) +/- Nivo/placebo (240 mgs q14 days X 5, then 480 mgs q28 X3). Primary endpoint is PFS. Secondary endpoints include OS, acute and chronic toxicity, quality of life and biomarkers (tumor PD-L1 expression; E6/7 seroreactivity and frequency of functional circulating and intraumoral T cells). Parallel with Phase IIR are sequential safety evaluations (see Table) in platinum eligible and ineligible ( &gt; 70 years; ≥3 grade neuropathy; ≥2 hearing loss; or CrCl &lt; 60 ml/min) cohorts (N = 10-20) of Nivo +/- Liri (anti-KIR) or Ipi (anti-CTLA4) concomitant with RT alone, cisplatin-RT or cetuximab-RT platforms followed by 3 months of adjuvant immunotherapy. The primary endpoint is safety and feasibility. With 8 evaluable pts, the probability of treatment assessed as toxic is &gt; 78% when the true toxicity rate is &gt; 45% and treatment assessed tolerable is &gt; 80% if the true toxicity rate is &lt; 20%. Clinical trial information: NCT02764593. [Table: see text]
SP0101 Understanding the language of epidemiology articles
Authors: W.G. Dixon
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> 'Clinical and Epidemiological Research' is one of two headings for original articles in the Annals of Rheumatic Disease. But what <i>is</i> epidemiological research? What do all those different types of bias mean? And what do all of those bizarre statistical terms mean? How can I make sense of the research, and how is it relevant to my practice? Answer: Attend the lecture and find out. <h3>Disclosure of Interest</h3> W. Dixon Consultant for: Google, Bayer
P01.138 Radio-chemotherapy with temozolomide in elderly patients with glioblastoma: our experience
Authors: A Molinari, F Pasqualetti, A Gonnelli, M Cantarella, S Montrone, P Cocuzza, M Fabrini, F Paiar
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and the second most common brain cancer after meningioma with a peak of incidence on the fifthy decades of life. Due to the progressive ageing of the developed country population, more than a half of new cases occurs in patients older than 65 years. The aim of the present study was to evaluate the clinical outcome of radio-chemotherapy with temozolomide in patients with glioblastoma aged more than 65 years. Sixty-three patients treated with radiotherapy and chemotherapy at Pisa University Hospital between September 2004 and November 2017 were enrolled in this retrospective analysis. All patients had a proven diagnosis of glioblastoma grade IV WHO, ECOG PS 0–2, age ≥ 65. Radiotherapy was delivered in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy. During radiotherapy, temozolomide was administered at a dose of 75 mg per square meter of body-surface area per day from the first to the last day of radiotherapy. 5–6 weeks after the end of radiotherapy, adjuvant temozolomide was administered at 150–200 mg per square meter for five consecutive days, every 28 days. A maximum of 12 cycles were prescribed if MRI showed no disease progression and temozolomide was well tolerated. Data analysis was performed in April 2018. The present study was performed in 37 male and 26 female patients with a median age at diagnosis of 72,5 years (range=65–89). Fifty-seven patients underwent surgical resection, four patients stereotactic diagnostic biopsy, two patients had a radiologic diagnosis only. During follow up, we recorded 46 cases of disease progression with a median progression-free survival (PFS) of 12 months (range 1–88 months). Median overall survival (OS) were 25 months (range 1–107 months); at data analysis, 65 patients were died. After disease recurrence, based on ECOG, tumor burden and age, patients were treated with surgery (15 cases), chemotherapy (30 cases) and re-irradiation (11 cases). In our experience, progression free survival and overall survival were similar to those reported in literature for younger patients. We think that radiochemotherapy is a good option for older patients with a good performance status in glioblastoma treatment.
MC1463: Avatar-directed chemotherapy in platinum-resistant ovarian cancer.
Authors: Beverly Long, Xiaonan Hou, Marc Becker, Jamison VanBlaricom, Evans Bradley, Andrea Elisabeth Wahner Hendrickson, Ann L. Oberg, Matthew John Maurer, Ethan Heinzen, John Kelly Camoriano, Gerardo Colon-Otero, Jill K. Burton, Kimberly Kalli, Nathan R. Foster, Paul Haluska, Saravut John Weroha
Journal: Journal of Clinical Oncology (2016)

TPS5609 Background: Response rates for 2nd line therapies in recurrent platinum resistant ovarian cancer (PROC) are low, and ex-vivo assays do not reliably predict individual response. To improve response rates to 2nd line agents, clinical trial MC1463 (#NCT02312245) uses patient-derived xenografts (PDX or Avatars) to assign therapy based on the matched Avatar in vivo response. Our experience confirms platinum response correlation between patients and Avatars (1); however a predictive assay for PROC will be more clinically relevant given the time required for Avatar development and recurrence pattern of ovarian cancer. Methods: Tumor collected from consenting patients is injected into immunodeficient mice. After tumor expansion, Avatars are treated with intraperitoneal (IP) carboplatin/paclitaxel (Phase 1) prior to randomization to additional IP treatment (Phase 2) with gemcitabine, topotecan, paclitaxel, or liposomal doxorubicin for 28 days. Change in tumor diameter is quantitated by ultrasound. To maintain confidentiality, a user-limited web-based portal links clinicians to Avatar development progress. Prior to treatment for platinum resistant recurrence, defined as measurable or non-measurable disease (including persistently elevated CA-125) within 6 months of completing of a platinum-based regimen, patients consent to pre-registration, and the most effective therapy is chosen by an Avatar tumor board composed of medical oncologists, biostatisticians, and lab scientists. Avatar drug performance is assessed graphically and via linear mixed models and non-parametric methods. Both Avatar and patient factors are considered by the board. The patient is then registered and treated with the assigned regimen. Patients are excluded for Avatar engraftment failure, prior cytotoxic therapy for PROC, poor performance status, or concurrent cancer. Primary endpoint is percentage of patients with response to assigned therapy based on RECIST criteria. Secondary endpoints include PFS, OS, and adverse events. Currently, 114 Avatars are in progress, and Phase 1 and 2 are complete for 27 and 18 models, respectively. One patient has been enrolled and randomized to Avatar-directed chemotherapy. Weroha SJ et al. Clin Cancer Res. 2014. Clinical trial information: NCT02312245.