tbuckley/cabot-search huggingface dataset:
How to better help cancer patients face their coming death?
Authors: Francois-Xavier Goudot, Milena Maglio, Sandrine Bretonniere
Journal: Journal of Clinical Oncology (2017)

e21505 Background: According to literature and medical experience, the doctor-patient relationship becomes strained when oncologists tell their patients that they have no more curative treatments to offer them. Patients often resist when they are told that it is in their best interest to meet with the palliative teams. Little is known about how to meet patients’ expectations at this advanced stage. Methods: We conducted a multicenter qualitative research in an oncology department, a hospital at home service and in an inpatient hospice care center. We met 47 patients (M = 21, F = 27, mean age = 65 yrs, mean disease duration = 5 yrs) for in-depth face to face interviews performed by a multi-disciplinary ethics team. Interviews were carried out between 1 and 3 months before death. Results: Qualitative analysis revealed 4 main results. 1/ For respondents, palliative care introduction meant impending death. 2/ Palliative care introduction meant loss of hope. Without hope, the cancer trajectory is impossible to sustain, they said. 3/ Hope was intricately interwoven with the request for more chemotherapy, even if doctors had clearly refused to provide it. 4/ The oncologist remained the referent physician, even for patients in hospice care. Patients for which the mean duration between cancer diagnosis and interview was 5 years or more, were more willing to talk about death and better accepted palliative care than patients for which the mean duration of cancer was inferior to 3 yrs. For patients with fast progressing cancer (n = 11), 10 were not willing to talk about death and 7 strongly resisted palliative care introduction. There was no difference between patients according to age, sex, type of cancer or center of inclusion. Conclusions: In the terminal phase of cancer, patients are unwilling to talk about death and are reluctant to meet with palliative care teams. Short disease duration strongly reinforces this attitude. If patients resist discussions about their impending death, should physicians continue to consider it good practice to introduce such discussions? Is it beneficent for patients?
Incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients (pts) with a germline (g) <i>BRCA</i> mutation (m) and platinum-sensitive relapsed ovarian cancer (PSR OC) receiving maintenance olaparib in SOLO2: Impact of prior lines of platinum therapy.
Authors: Jacob Korach, Simon Turner, Tsveta Milenkova, Iulian Alecu, Emma McMurtry, Ralph Bloomfield, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2018)

5548 Background: Olaparib has been investigated and subsequently approved as maintenance treatment after response to platinum-based chemotherapy in pts with relapsed OC. A relationship between increasing dose and duration of platinum therapy and an increased risk of MDS/AML has been reported (Travis et al. N Engl J Med 1999). Events of MDS/AML have been reported in pts treated with olaparib, but a causal relationship has not been established. The results of a post hoc analysis evaluating the incidence of MDS/AML by prior lines of platinum therapy in pts with gBCRAm PSR OC receiving maintenance olaparib or placebo in the Phase III SOLO2 trial (ENGOT Ov-21; NCT01874353; Pujade-Lauraine et al. Lancet Oncol 2017) are reported here. Methods: The safety analysis set comprised 195 pts who received olaparib tablets (300 mg twice daily) and 99 pts who received placebo. The median duration of follow-up in the olaparib and placebo groups (pts censored at time of primary analysis) was 25.3 and 25.1 months, respectively. Results: The overall incidence of MDS/AML was similar in the olaparib and placebo groups (2.1% vs 4.0%; Table). With both olaparib and placebo, the incidence of MDS/AML appeared to increase with an increasing number of lines of prior platinum therapy. This trend did not appear to be driven by pt age. This trend was also observed in a larger pooled analysis of olaparib clinical studies. Clinical trial information: NCT01874353. Conclusions: Olaparib did not increase the risk of MDS/AML vs placebo in SOLO2. Rather, a trend was seen for a higher incidence of MDS/AML with an increasing number of prior lines of platinum therapy. A limitation of this analysis is the small number of events that occurred in each group; however, results of a separate, larger pooled analysis of trial data support these findings. MDS/AML incidence and pt age by number of prior lines of platinum therapy. MDS/AML incidence, n/N (%) Median pt age, years Olaparib Placebo Olaparib Placebo 2 1/110 (0.9) 2/62 (3.2) 56.0 55.0 3 1/60 (1.7) 1/20 (5.0) 56.5 58.5 ≥4 2/25 (8.0) 1/17 (5.9) 57.0 61.0 Overall 4/195 (2.1) 4/99 (4.0) 56.0 56.0
Gene expression analysis of tumor biopsies from a trial of durvalumab to identify subsets of NSCLC with shared immune pathways.
Authors: Katie Streicher, Chris Morehouse, Yinong Sebastian, Michael Kuziora, Brandon W. Higgs, Koustubh Ranade
Journal: Journal of Clinical Oncology (2017)

3041 Background: We previously reported that NSCLC pts with high pretreatment tumoral IFNG mRNA signature (sig) expression have improved outcomes (ORR, PFS, OS) to the anti-PD-L1 therapy durvalumab (D). To explore the relationship of other immunotherapy targets with the IFNG sig, we evaluated expression of CD137, PD1, PDL1, CTLA4, GITR, OX40, TLR7, TLR8, CD73, TIM3, NKG2A, IDO1, CD40, LAG3, A2AR, CXCR4, iNOS, ARG1, and STAT3 in D-treated NSCLC. Methods: CP1108/NCT01693562 was a nonrandomized phase 1/2 trial evaluating D (10 mg/kg Q2W) in advanced NSCLC. As of 24OCT16, 304 primarily previously-treated pts were enrolled. RNA sequencing was conducted on available tumor specimens from 98 pts. ORR was evaluated using RECIST v1.1. 19 genes were z-scored, scaled and clustered across pt tumors. Each gene was coded binary using 0 as a cut point. The proportion of tumors with concordant or discordant over-expression between a gene and the IFNG sig was calculated. Results: In 43% of evaluable NSCLC pts, mRNAs for PD-1, IDO1, PD-L1, CD40, CTLA4, LAG3, TIM3, TLR8, NKG2A, and CD137 were co-expressed with IFNG sig (Spearman’s rho &gt; = 0.7). In 34% of evaluable pts, TLR7, OX40, GITR, A2AR, and CXCR4 mRNAs had moderate concordance with IFNG sig (0.5 &lt; rho &lt; 0.7) and in 23% of evaluable pts iNOS, CD73, ARG1, and STAT3 had low concordance (rho &lt; 0.5). Within the cluster of pts including high IFNG sig, a small subset expressed high iNOS and CD73; however, pts with high STAT3 or ARG1 formed a distinct cluster within the low IFNG sig subset. The subset with high IFNG sig had an ORR of 24% compared to only 10% in all other subsets combined. Conclusions: Our findings enrich understanding of the immune microenvironment of NSCLC by identifying three broad categories of tumors: tumors with pre-existing immunity that have high IFNg sig and select other IO pathways with enhanced responses to D; tumors with moderate expression of IO genes in which the local microenvironment is crucial; finally a distinct “cold” subset of tumors with high expression of STAT3 or ARG1 and characterized by low or no expression of IFNG sig and other IO genes. These results may aid in identifying the right pts for anti-PD-L1 and in prioritizing immunotherapy combinations.
Distinct evolution of biliary tree tumors.
Authors: Elizabeth Santana dos Santos, Luciana Franco Do Prado De Carvalho, Artur Rodrigues Ferreira, Brenda Pires Gumz, Tiago de Castro Sanchez Basseres, Marcel Autran Machado, Rodrigo Canada Trofo Surjan, Adriana Paula Barrichello Caldeira, Bruna Migliavacca Zucchetti, Tatiana Zanesco, Paulo Hoff, Frederico Costa
Journal: Journal of Clinical Oncology (2016)

e15633 Background: Biliary tumors is a group of related but distinct malignancies, accounting for only 3% of gastrointestinal cancers. Little is known about their biological behavior, pattern of failure and patients outcomes. Surgery is the only potentially curable option but existing literature regarding post resection treatment consist mainly in small single-institution retrospective series. Methods: All cases of cholangiocarcinomas treated in Sirio-Libanês Hospital from January 1995 to January 2015, were analysed retrospectively, with emphasis in the search for prognostic factors. Results: 230 patients diagnosed with malignant billiary tumors were identified (51% intrahepatic, 7% hilar, 25% gallbladder, 17% duodenal papilla). The median age of the cohorts was 61 years and the majority of the patient were women (53%). At diagnosis, 51% of the tumors were considered resectables, 14% locally advanced and 35% were metastatic. Patients with localized disease typically underwent surgery, while those presenting metastatic spread received platin based palliative chemotherapy. During the evolution, the main sites of metastasis were the liver, lymph nodes and peritoneum. The median overall survival (OS) was 12 months. Surgical procedure ( radical x palliative x none), surgical margin status and the location of the tumor showed statistically significant value for survival. Patients with operable tumors presented better OS than those with locally advanced or metastatic tumors (20 months x 6months x 7months respectively, p < 0,001). Gallbladder cancer presented the worst OS (8months). The OS for intrahepatic, hilar and duodenal papilla were 12, 20 and 17 month, respectively. Conclusions: We described one of the largest retrospective single-institution series of biliary tumors. We confirmed the surgical margin status (R0) as a prognostic factor.The evolution of the biliary tract carcinomas varies according to the place of origin and gallbladder tumors present the worst survival data. Although they are treated as a group, biliary tumors are entities with different clinical features. Further molecular analysis is needed in order to explain the biological rational of these different patterns of behavior.
Use of dedicated gene panel sequencing using next generation sequencing to improve the personalized care of lung cancer.
Authors: Coureche-Guillaume Kaderbhai, Francois Ghiringhelli, Romain Boidot, Françoise Beltjens, Sandy Chevrier, Laurent Arnould, Laure Favier, Aurelie Lagrange, Bruno P. Coudert
Journal: Journal of Clinical Oncology (2016)

e20523 Background: Recent advances in lung cancer biology underline that a diverse array of somatic genomic aberrations could drive cancer growth and be potential “drugable” targets. Advances in Next Generation Sequencing (NGS) technologies have improved the ability to detect potentially targetable mutations. However, the integration of NGS into clinical management in an individualized manner for lung cancer remains challenging. In this report, we evaluated the use of integrative clinical sequencing and molecular counseling in the treatment of patients with advanced metastatic lung cancer. Methods: In this single-center observational study, we performed dedicated a NGS panel studying 41 cancer-related genes in 50 consecutive patients with metastatic non-small-cell lung cancer between May 2012 and October 2014. Participants underwent integrative dedicated sequencing using TruSeq Custom Amplicon designs followed by molecular counseling. Results were discussed by a Molecular Tumor Board, which made recommendations to the treating physicians. Results: In this cohort of 50 patients, molecular analysis could be performed in 48 patients with a good quality check. One hundred and twenty-four mutations were detected. At least one mutation was found in 46 patients. In 58% of cases, the Molecular Tumor Board (MTB) was able to recommend treatment with a targeted agent based on the evaluation of the tumor genetic profile and treatment history. Eight patients (16%) were subsequently treated with an MTB-recommended targeted therapy; four patients experienced a clinical benefit with a partial response or stabilization lasting more than 4 months. Conclusions: In this single-center case series involving patients with metastatic non-small cell lung cancer in a reference cancer center, including integrative clinical sequencing data into clinical management was feasible, revealed potentially actionable findings in 58% of patients, and was associated with a treatment modification in 16% of patients. Further analysis with a larger number of patients and control group will be required to determine whether better clinical outcomes result from this approach.
Fatigue and health behaviors in cancer survivors: A cross-sectional population based study.
Authors: Margarida Matias, Giulia Baciarello, Mohamed Neji, Stefan Michiels, Ann H. Partridge, Marc Karim Bendiane, Karim Fizazi, Michel Ducreux, Fabrice Andre, Ines Maria Vaz Duarte Luis
Journal: Journal of Clinical Oncology (2017)

10069 Background: A substantial proportion of breast, colo-rectal and prostate cancer patients (pts) can expect long term disease free survival after their primary treatment. Among those, fatigue commonly persists after diagnosis (dx) and can be debilitating. In this study, we evaluated the incidence of fatigue 2 years (y) after cancer dx and its association with health behaviors. Methods: We used a French population based cross-sectional study, which included a representative sample of pts from 12 cancer types (VICAN2). VICAN2 surveyed 4347 pts 2 y after dx. There is a 99% completion rate of fatigue related questions. For this study, we included 2017 pts with breast (1237), colo-rectal (348) and prostate (432) cancer without evidence of metastases at dx or relapse 2y after dx and with fatigue information. Severe fatigue was defined as average score of EORTC QLQC30 fatigue subscale ≥40 at 2y after dx. There were &lt;1% of missing values in the evaluated covariates. Multivariate logistic regression models looked at associations of fatigue with heatlh behaviors (Δ in exercise since dx, exercise at diagnosis, body mass index (BMI), Δ since dx, smoking), age, gender, comorbidities, education, employment, cancer type, radiation, chemotherapy, hormonal therapy. Results: 52% of pts reported severe fatigue at 2 y after dx (median fatique score: 44, range: 0-100). 2 y after dx, 47% of pts either stopped or decrease exercise and 16% had a ≥ 10% change in BMI. Factors associated with fatigue included health behaviors (Table), but also age (adjusted odds ratio [ aOR] for severe fatigue, 95% confidence interval [95% CI]: 0.97, 0.96-0.98), gender ( aOR, 95 CI male vs. female: 0.5, 0.3-0.8), comorbidities ( aOR, 95 CI yes vs. no: 2.0, 1.6-2.4) and treatment type ( aOR, 95 CI radiation vs. no: 1.5, 1.1-2.0). Conclusions: Fatigue continues to be a substantial problem for cancer survivors 2 y after dx. Some factors that may contribute to persistent fatigue (health behaviors) may be amenable to interventions. [Table: see text]
IND.210: A randomized phase 2 trial of FOLFOX6/bevacizumab with or without reovirus (Reo) in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Patricia A. Tang, Derek J. Jonker, Hagen F. Kennecke, Stephen Welch, M. Christine Cripps, Timothy R. Asmis, Haji I. Chalchal, Anna T. Tomiak, Yoo-Joung Ko, Eric Chen, Thierry Alcindor, John R. Goffin, Ashley Theis, George M. Gill, Dongsheng Tu, Lesley Seymour
Journal: Journal of Clinical Oncology (2016)

3546 Background: Reo, a serotype 3 reovirus, may preferentially infect and destroy cells with RAS activation. This trial evaluated the progression-free survival (PFS) of untreated mCRC pts treated with FOLFOX6/bevacizumab (q2 weekly) alone or with Reo (3x1010TCID50 on day 1-5 [cycles 1, 2, 4, 6, 8 then alternate cycles]). Methods: The trial had 80% power to detect improvement in PFS from 8.5 to 15.5 mo [Hazard ratio (HR) 0.55, α = 0.1]. Primary analysis adjusted for stratification factors (prior adjuvant chemotherapy, KRAS status) with sensitivity analyses (SA) adjusted for additional prespecified factors (gender, age, baseline LDH and Alk Phos). Secondary endpoints included overall response rate (RR), quality of life (EORTC QLQ C30), overall survival (OS). Results: Following safety run-in of 6 pts, 103 pts were randomized to FOLFOX6/bevacizumab with (n = 51) or without (n = 52) Reo. Pt characteristics: median age 60 (range 31-79), male (61.2%), ECOG 0: 45.6%, 1: 50.5% and 2: 3.9%. At median follow-up 13 months, PFS was significantly shorter in the Reo arm [median 7.3 vs 9.1 mo, HR 1.59 (95% CI 1.00 - 2.53) p = 0.046; SA HR 1.65, p = 0.04]. RR was higher in Reo treated pts [52.9 vs 34.6%, OR 2.09 (95% CI 0.96-4.55), p = 0.06; SA p = 0.03], but with a shorter median duration of response (5.1 versus 8.5 mo, p = 0.028). In subgroup analysis female pts had higher RR and longer OS than male pts but test for interaction was significant only for RR. There was no significant difference in hepatectomy rate (Reo 7.8% vs 3.8%), median OS (p = 0.48), or relative dose intensity of FOLFOX6 or bevacizumab. Reo pts had worse QLQ C30 physical functioning (mean change score from baseline -3.9 vs. 1.94; p = 0.008). The most common adverse events (AEs) of any grade attributed to Reo were fatigue (51%), fever (49%), chills (44%), and anorexia (33%). With respect to grade 3+ AEs, pts on Reo experienced more hypertension (26.3 vs 3.8%, p = 0.001), more proteinuria (22.8 vs 1.9%, p = 0.001); and less abdominal pain (3.5 vs 17.3, p = 0.02) than the control arm. Conclusions: While the addition of Reo to FOLFOX6/bevacizumab increased RR; PFS, toxicity and QoL were significantly worse. Further follow-up of maturing OS data is planned. Clinical trial information: NCT01622543.
TCT-185 Glasgow Rotational Atherectomy Efficiency (GRACE) study: Safety of a Minimalist Approach
Authors: Tom Ford, Kieran Docherty, Alice Jackson, Adnan Khan, Rajib Alam, Eric Yii, Hany Eteiba, Mitchell Lindsay, Stuart Watkins, Richard Good, Stuart Hood, Keith Robertson, Aadil Shaukat, Mark Petrie, Keith Oldroyd, Colin Berry, Margaret McEntegart, Paul Rocchiccioli
Journal: Journal of the American College of Cardiology (2018)
Cytogenetic and fluorescence in situ hybridization testing in veterans with chronic lymphocytic leukemia.
Authors: Ahmad Sami Halwani, Zachary Burningham, Kelli Marie Rasmussen, Vikas Patil, Clarke Alan Low, Brian Meissner, Tatyana Kapustyan, Nicole Lawrence, Jodi Walker, Holger Keim, Brian C Sauer
Journal: Journal of Clinical Oncology (2017)

7526 Background: The presence of deletion 17p (del17), determined by chromosome analysis and/or fluorescence in situ hybridization (FISH), is a strong negative prognostic marker in chronic lymphocytic leukemia (CLL). Prior to the introduction of novel agents (ibrutinib, venetoclax), the clinical utility of cytogenetics/FISH was limited by the absence of chemoimmunotherapy regimens that were proven effective in patients with del17. Testing practices for chromosomal aberrations since the introduction of novel agents have not been reported. We report cytogenetic/FISH trends in a nationwide cohort of veterans diagnosed with CLL. Methods: CLL patients diagnosed 2008-2015 and receiving care at VA were identified through the VA Clinical Cancer Registry. Electronic medical records were used to determine cytogenetic/FISH testing (lab records), treatment histories (pharmacy dispensation records), and evidence of system use (heme-onc notes). Cytogenetic/FISH testing was identified by presence of specific keywords in the test name or Logical Observation Identifiers Names and Codes (LOINC) descriptions, then validated by human annotation. The testing rates are reported for the entire cohort, at time of diagnosis, time of regimen initiation (including the 12 months preceding initiation), during the novel era (2014 – 2015) and prior (2008–2013). Results: From 2008 to 2015, 3,638 CLL patients were diagnosed and received care at VA. Documented records of treatment regimens were available for 1,562 patients who received a total of 2,929 treatment regimens. Only 24% (998) of patients were tested at any point in time during their care at the VA, 17% (622) were tested at time of diagnosis, and 19% (542) of treatment courses were preceded by cytogenetic/FISH testing. No testing differences existed following the introduction of the novel agents at diagnosis (both ~ 17%), or prior to regimen initiation (20% vs 16%). Conclusions: Our study suggests CLL patients diagnosed and receiving care at the VA are not routinely undergoing cytogenetics/FISH testing at diagnosis or prior to treatment. Changing this practice pattern will personalize treatments so that del17 CLL patients receive less toxic and more effective therapies.
TCT-624 A prospective multicenter randomized post-market trial evaluating a novel Cobalt Chrome Rapamycin Drug Eluting Stent: Subgroup Analysis of the TARGET All Comers Trial
Authors: Alexandra Lansky, William Wijns, Bo Xu, Henning Kelbaek, Niels van Royen, Ming Zheng, Laure Artus-Jacenko, Paul Knaapen, Ton Slagboom, Georgios Vlachojannis, Karin Arkenbout, Lene Holmvang, Luc Janssens, Andrzej Ochala, Salvatore Brugaletta, Oliver Bruder, Sergio Berti, Emanuele Barbato, Gabor Toth, Luc Maillard, Christian Valina, Piotr Buszman, Tom Johnson, Holger Thiele, Andreas Baumbach
Journal: Journal of the American College of Cardiology (2018)
P20 Molecular Characterization of Non–Small Cell Lung Cancer (NSCLC) Patients by Next Generation Sequencing: Preliminary Data
Authors: V. Wainsztein, G. Recondo, V. Denninghoff, M.T. Cuello, M. Greco, M. De La Vega, F. Galanternik, E. Rojas Bilbao, A. Avagnina, M. Castro, G. Recondo
Journal: Journal of Thoracic Oncology (2018)
Antibiotics for Sepsis—Finding the Equilibrium
Authors: Michael Klompas, Thierry Calandra, Mervyn Singer
Journal: JAMA (2018)

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