tbuckley/cabot-search huggingface dataset:
Gemcitabine versus FOLFIRINOX in patients with advanced hENT1<sup>+ve</sup> pancreatic adenocarcinoma.
Authors: Maria Alessandra Calegari, Armando Orlandi, Giulia Indellicati, Maurizio Martini, Alessandra Cocomazzi, Cinzia Bagalà, Valeria Zurlo, Carmela Di Dio, Rosalba Barile, Santa Monterisi, Alessandra Cassano, Antonio Astone, Carlo Barone
Journal: Journal of Clinical Oncology (2015)

e15295 Background: Human equilibrative nucleoside transporter 1 (hENT1) is a transmembrane protein which acts as a nucleoside transporter and represents the main mediator of gemcitabine (GEM) uptake into human cells. Several studies showed a possible role of hENT1 expression as a predictor of response to GEM in pancreatic adenocarcinoma (PAC) mainly in adjuvant setting. For the first time, in this retrospective study we compared GEM versus FOLFIRINOX in a selected population affected by advanced PAC (a-PAC) hENT1 positive (hENT1+ve). Methods: 149 patients affected by a-PAC, treated at our institution from 2009 to 2013, have been screened in this retrospective study. 71 patients, treated with GEM or FOLFIRINOX first line therapy, fulfilled clinical inclusion criteria for survival analysis. 31 patients, whose stored tumor samples were available and contained sufficient DNA for hENT1 expression by RT-PCR, underwent exploratory analysis. The primary endpoint was OS and the secondary endpoint was PFS. Grade 3-4 adverse events (AE) were reported. Results: The survival analysis regardless of hENT1 expression (71 patients) showed a longer OS (11 vs 8 months; HR 0.66, p = 0.03) and PFS (6 vs 3 months; HR 0.76, p = 0.1) in the FOLFIRINOX group compared to GEM. The incidence of G3-4 AE was higher in the FOLFIRINOX group (febrile neutropenia 8.7% vs 1.1%, thrombocytopenia 11.4% vs 5.5%, diarrhea 10.5% vs 1.1%, sensory neuropathy 8.7% vs 0%). Within the exploratory analysis (31 patients) no differences were found in hENT1+ve patients treated with FOLFIRINOX compared to GEM in terms of OS (8.5 vs 7 months, HR: 0.89, p = 0.8) and PFS (5.5 vs 5 months, HR: 0.8, p = 0.61). GEM-treated hENT1+ve compared to hENT1-ve showed a statistical significant improvement both in terms of OS (8 vs 2 months; p = 0.0012) and PFS (5 vs 1 months; p = 0.0004). FOLFIRINOX-treated hENT1+ve compared to hENT1-ve did not demonstrate a statistical significant benefit. Conclusions: GEM seems as effective as FOLFIRINOX in terms of survival with a better safety profile in hENT1+ve a-PAC. Whether confirmed in prospective studies, GEM monotherapy or GEM-based therapy might be the standard first-line regimen in this selected population
Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation
Authors: Wallis C. Y. Lau, Esther W. Chan, Ching-Lung Cheung, Chor Wing Sing, Kenneth K. C. Man, Gregory Y. H. Lip, Chung-Wah Siu, Joanne K. Y. Lam, Alan C. H. Lee, Ian C. K. Wong
Journal: JAMA (2017)

<h3>Importance</h3> The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown. <h3>Objective</h3> To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF. <h3>Design, Setting, and Participants</h3> Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016. <h3>Exposures</h3> Dabigatran or warfarin use during the study period. <h3>Main Outcomes and Measures</h3> Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated. <h3>Results</h3> Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, −0.68 [95% CI, −0.38 to −0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, −3.15 [95% CI, −2.40 to −3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, −0.04 [95% CI, 0.67 to −0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (<i>P</i>value for interaction, &lt;.001). <h3>Conclusions and Relevance</h3> Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.
Impact of hemoglobin level on the outcome of advanced non-small-cell lung cancer (NSCLC) treated with cisplatin and gemcitabine
Authors: O. Juan Vidal, V. Alberola, J. Muñoz, R. De Las Peñas, C. Camps, B. Massutí, R. Garcia Gómez, M. Provencio, D. Isla, J. Sánchez
Journal: Journal of Clinical Oncology (2006)

17010 Background: Negative impact of anemia on survival has been described in NSCLC patients (pts) treated with radiotherapy (RT) or concurrent radiochemotherapy, but scarcely data exist in NSCLC treated with chemotherapy (CT). PURPOUSE: To evaluate the prognosis value of baseline hemoglobin (Hb) among pts with advanced NSCLC treated with cisplatin and gemcitabine. Methods: 433 pts included in two trials conducted by the Spanish Lung Cancer Group (176 pts from the arm A of a randomized phase III trial comparing 3 regimens of CT and 257 pts from a phase II trial) were included in this analysis. No significant differences in baseline characteristics, response and survival (median 8.73 and 9.87 months, p=0.46) were observed between pts of the two trials. The baseline Hb and other potential risk factors for survival were analyzed with Cox Proportional Hazards model in an univariate an multivariate analysis. Results: Stage IIIB with positive pleural effusion (25%), stage IV (75%). 85% had ECOG PS 0–1. Median age: 60 years (range 31–82). 89% male. Histology: 41% adenocarcinoma, 39% squamous cell, 6.5% large cell, 14.5% NSCLC not otherwise specified. Median number of cycles received was 4 (range 1–8). Mean Hb level prior CT was 13.2 g/dl (range 8 to 19.6 g/dl). Response rate was 41% and median survival was 9.57 months (95% CI: 8.57–11–57). No statistically differences in survival were observed by stage (IIIB vs IV), age and gender. In the univariate analysis, number of cycles received (≤3 vs. &gt;3 cycles), ECOG (2 vs 0–1), response (SD+PD vs CR+PR), baseline Hb (≤11 vs &gt;11 gr/dl); minimum Hb during the CT (&lt;10 vs ≥10) and second line CT (No vs Yes) emerged as prognostic factors for survival and were introduced in the multivariate model (see Table ). Conclusions: Hb level at the initiation of CT is an independent prognostic factor of survival this homogenous group of advanced NSCLC treated with cisplatin and gemcitabine. Baseline Hb should be considered as prognosis factor for survival in addition to ECOG. [Table: see text] No significant financial relationships to disclose.
Oxytocin drives prosocial biases in favor of attractive people
Authors: René Hurlemann, Dirk Scheele, Wolfgang Maier, Johannes Schultz
Journal: Behavioral and Brain Sciences (2017)

Abstract Current perspectives on attractiveness-related prosocial biases emphasize the contribution of evolutionarily shaped mating drives. Here, we extend these concepts by highlighting the pivotal role of the hypothalamic peptide oxytocin in augmenting the salience and rewarding value of social stimuli, including the partner's face, thereby fostering social bonding in general and the stability of monogamous pair bonds and offspring care in particular.
Phase I trials of PS-341 (bortezomib, B) in combination with topotecan (T) in advanced solid tumors: A potential pharmacokinetic (PK) interaction.
Authors: Robert Morgan, Frances Valdes, Timothy W. Synold, Paul Henry Frankel, Christopher Ruel, Mary I. Carroll, Dean Lim, Mihaela C. Cristea, Marianna Koczywas, Lucille A. Leong, Vincent M. Chung, Karen L. Reckamp, Stephen Shibata, Jana Portnow, Warren Allen Chow, Przemyslaw Twardowski, Thehang H. Luu, George Somlo
Journal: Journal of Clinical Oncology (2012)

3108 Background: Preclinical data has demonstrated that B when combined with camptothecins enhances apoptotic effects which may be independent of NF-κB status and dependent on the sequence of exposure to the proteasome inhibitor. Other data suggests PK interactions of B with some chemotherapeutic agents. It is hypothesized that B will act synergistically with T and enhance the apoptotic effects of T. Conflicting data exists regarding schedule dependent synergistic cytotoxicity of the combination. This study examined both sequences of administration and determined the PK of each sequence. Methods: A standard 3 + 3 schedule was used in both sequences (S). The dose of B was fixed with escalating doses of T. S1: B 1.3 mg/m 2 on days 1, 4, 8, and 11. T 2 to 3.5 mg/m 2 on days 1 and 8 was given 6 h before B. S2: B 1.3 mg/m 2 on days 1, 4, 8, 11 followed by T 2 to 3 mg/m 2 given 6 h after B. Cycle length was q28 days. PK sampling for both sequences was performed. Results: 54 pts (S1: 27, S2: 27) received a median of 2 cycles (range 1-7) of therapy. Pts were heavily pre-treated. For S1, the maximum tolerated dose (MTD) of B and T were 1.3 and 3 mg/m 2 respectively. For S2, the MTD of B and T were 1.3 and 2.5 mg/m 2 respectively. Dose-limiting toxicities (2 pt in each sequence) were gr 3 thrombocytopenia in S1, and gr 4 thrombocytopenia in S2. Stable disease was seen in 6/27 pts in S1, and 6/27 in S2. PK results for S2 show no significant difference between the day 1 and day 8 PKs. However, the mean AUC (454±150 mg/Lxhr) and Cmax (123±51 mg/L) at the MTD of 2.5 mg/m 2 reached on this trial is similar to those reported with single agent doses of 4 mg/m 2 given over 30 minutes weekly x 3. As a result, the estimated topotecan clearance (11.3±5 L/hr) when given following bortezomib is approximately one half of the reported clearance for the single agent. (Curtis et al, J Clin Pharmacol, 50:268, 2010). Conclusions: The tolerability and toxicity of both sequences was similar. MTD differs with S2 having a lower tolerated dose of T. PK results suggest a possible drug-drug interaction with decreased clearance of T with S2. PK results for S1 are pending. Supported by CCSG CA62505.
Left ventricular ejection fraction (LVEF) monitoring in breast cancer patients treated by trastuzumab: A 7-year retrospective study confirms interest of testing.
Authors: Jean-Baptiste Rey, Soizic Masson, Laurent Masson, Helene Larbre, Dimitri Papathanassiou
Journal: Journal of Clinical Oncology (2014)

e20647 Background: Cardiotoxicity induced by trastuzumab (TTZ) may require discontinuation. Regular measurement of the LVEF by radionuclide ventriculography is a method to assess cardiotoxicity. The isotopic method for measuring LVEF is a frequently used method for its reliability and reproducibility. Cardiotoxicity of TTZ is reversible, unlike that of anthracyclines. The reversibility usually appears at the end of treatment, but can occur spontaneously. The decision to stop and reinstate TTZ should be taken on a case by case basis. Methods: A retrospective study was conducted in patients treated with TTZ for breast cancer between 2005 and 2012 in our center. Data were extracted from the chemotherapy software and scintigraphic reports giving the LVEF results. LVEF was performed using radioactive 99mTc-Albumin. Results: From 2005 to 2012, 272 patients received TTZ for breast neoplasia. Regular monitoring of LVEF every 3 months was performed in 86% of cases. In 117 patients, measurement of LVEF was not performed in our center. 155 patients performed LVEF in our centre. Risk factors (age, BMI, CardioVascular risk factors) and associated treatments (chemotherapy, radiotherapy, hormonotherapy) were compared between both groups and no significant difference was found. The interest of the quarterly monitoring of LVEF in patients receiving TTZ is strongly confirmed since in 25% of cases a significant decrease in LVEF or result below 50% were detected. Among those, the therapeutic management was changed in more than 4 out of 10 cases. They consisted mainly of cases where LVEF fell below 50%. All decrease in LVEF below 50% led to a change in clinical management (TTZ interruption). Conclusions: Regular monitoring of LVEF in TTZ is essential as it can detect many cases of heart failure and treat these episodes accordingly. Nb of patients Normal LVEF LVEF decrease > 10 % LVEF performed in centre 116 (75%) 39 (25 %) Mean age 54.4 52.9 Signs of heart failure 6 / 39 (15%) Definitive TTZ discontinuation 7 / 39 (6 patients with LVEF < 50%) Therapeutic break (stop and go) 11 / 39 (8 patients with LVEF < 50%) No change in treatment 21 / 39 (5 patients with LVEF < 50%)
Changes in hormonal therapy during the first 24 months of treatment: A longitudinal cohort study.
Authors: Thierry Lebret, Dominique Rossi, Marc Zerbib, Jean Luc Moreau, Alain Ruffion, Yann Neuzillet, Christophe Hennequin
Journal: Journal of Clinical Oncology (2017)

e599 Background: Data are limited showing changes in patients’ use of androgen deprivation therapy (ADT) in routine clinical practice. Methods: In this non-interventional, longitudinal cohort study, we assessed the number and type of modifications of ADT during the first 24 months of treatment in France. At baseline and every 6 months, we collected clinical, biological and therapeutic data and any changes of ADT modality. Results: Between July 2011 and January 2015, 891 pts were evaluable at 24 months. Mean age was 74.1±8.7 years. Indications for ADT were: biochemical relapse after local treatment (21.4%), adjuvant to radiotherapy (RT) (31.6%), metastases (24.2%) and locally advanced tumor without local treatment (20.6%). Gleason score was &gt; 7, 7(4+3), 7 (3+4) and &lt; 7 in 33.6%, 23.1%, 26% and 17.3%, respectively. At 24 months, modification of ADT was reported in 390 pts (43.8%). Modifications of ADT according to indications are summarized in table below. The main types of modification concerned the formulation (molecule or duration of action) (61.3%), duration of ADT (10.5%), switch to intermittent treatment (10.0%), addition of chemotherapy (5.6%) or second line hormonal manipulation (9.0%). Clear explanation for adaptations was given for only 110 patients: disease progression: 55.5% ; patient request: 26.4%, tolerance: 12.7% and failure of castration: 7.3%. Conclusions: Change of initial modality of ADT is frequent in the first 24 months of treatment (43.8%) and numerically more frequent in presence of metastases or biochemical relapse than when ADT is added to RT. Surprisingly, the main type of modification is formulation. The main reason for modification is disease progression. [Table: see text]
Clinical features of long-term survivors (LTS) of advanced hepatocellular carcinoma undergoing molecular targeted therapy (MTT).
Authors: Li-Chun Lu, Yu Yun Shao, Soa-Yu Chan, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2013)

e15182 Background: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is generally dismal. However, some patients enjoyed long survival under MTT. This study sought to clarify the clinical features of these patients. Methods: Patients with advanced HCC (Barcelona-Clinic Liver Cancer stage C) who were enrolled in six clinical trials of first-line MTT between May 2005 and December 2010 at National Taiwan University Hospital, Taipei, Taiwan were included. LTS (&gt; 2 years) were identified, and their clinical variables were reviewed and analyzed. Results: Twenty-two LTS (11.6%), with a median age of 58.3 years, were identified from 189 patients. The median overall survival of LTS was 58.7 months. Among them, 17 (77.3%) patients were male, and 13 (59.1%) patients had chronic hepatitis B virus infection. Compared with patients who survived less than 2 years, LTS were less likely to have α-fetoprotein &gt; 400 ng/mL, liver involvement, or macrovascular invasion. LTS were more likely to have Okuda stage I disease, and lower Cancer of the Liver Italian Program scores. Regarding response to the first-line therapy, LTS had significantly higher response rates (50.0%) and disease control rates (86.4%). The median progression free survival of LTS was 13.0 months. After first-line treatment failure, 13 (59.1%) LTS received 2 nd -line or more systemic therapies, and 15 (68.2%) LTS underwent loco-regional therapy, such as surgery, radiofrequency ablation, or transarterial chemoembolization. Seven (31.8%) LTS who received salvage loco-regional treatments remained disease-free for a median time of 27.0 months. Conclusions: LTS of advanced HCC appear to be a group of patients who had less aggressive disease status and were able to receive further loco-regional therapy.
A phase 1/2 study of ipilimumab in women with metastatic or recurrent HPV-related cervical carcinoma: A study of the Princess Margaret and Chicago N01 Consortia.
Authors: Stephanie Lheureux, Marcus O. Butler, Gini F. Fleming, Hal W. Hirte, Mihaela C. Cristea, Prafull Ghatage, Lainie P. Martin, Helen Mackay, Neesha C. Dhani, Michelle Wilson, Cristina Martin-Lorente, Judy Quintos, Lisa Wang, Smitha Udagani, Amit M. Oza
Journal: Journal of Clinical Oncology (2014)

TPS5631 Background: Cervical cancer (CC) is the second cause of cancer-related mortality in women worldwide. Response to second-line chemotherapy is infrequent and the poor outcome of patients with advanced disease (median survival 9 months) warrants novel therapeutic strategies that exploit abnormal tumor biology. Based on new evidence that host-dependent immunologic status and HPV-induced immune evasion are responsible for persistent HPV infection, the prime causal factor of CC, immunotherapy is an attractive emerging strategy to target this disease. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule that acts to downregulate the T cell immune response. Methods: A 2-step multicenter trial was designed to evaluate ipilimumab IV in metastatic or recurrent HPV-related CC (NCT01693783). Eligible patients require measurable disease progression and at least one previous platinum based line of chemotherapy. A safety phase I cohort was planned with ipilimumab 3 mg/kg every 21 days for four cycles in 6 evaluable patients. After demonstration of safety, a phase II trial was planned with ipilimumab 10 mg/kg at the same schedule; followed by four additional cycles maintenance therapy at the same dose every 12 weeks for patients with radiologic confirmed response or stabilization. The primary objective is to assess the safety and the objective response rate at the end of cycle 4. 18 evaluable patients are scheduled and if at least 1 partial response is seen, an additional 14 patients will be enrolled. Immune assessment studies are performed on peripheral blood collected prior to and following ipilimumab therapy and on archived and fresh tumour tissue obtained prior to treatment and within the first week of cycle 2. This trial was activated in September 2012. The phase I cohort is now completed, and 8 patients have been enrolled in the phase II. The overall median age of study subjects is 49 (range 36-60) with a majority of squamous histology type (13/14 patients). A median of 3 cycles have been administered, and 12 patients have undergone pre- and post-treatment biopsies. Clinical trial information: NCT01693783.
Optimal cycles of fluoropyrimidine-based adjuvant chemotherapy for patients with resectable gastric cancer.
Authors: Yunpeng Liu, Xiujuan Qu, Jinglei Qu, Jingdong Zhang, Jing Liu
Journal: Journal of Clinical Oncology (2013)

e15160 Background: Although several clinical trials have suggested that postoperative adjuvant chemotherapy could improve survival, there has no study on the optimal cycles of treatment. This retrospective analysis was carried out to evaluate the outcomes of gastric cancer patients treated with 5-6 cycles of FU-based treatment as compared to a cohort treated with 3-4 cycles or 7-8 cycles. Methods: We retrospective identified 254 patients with stage IB-IIIC gastric cancer who received 3-8 cycles of adjuvant chemotherapy after gastrectomy with D1 or D2 lymphadenectomy. The endpoint was overall survival. Factors associated with prognosis were also analyzed. Results: Of the 254 patients, 74 patients treated with 3-4 cycles, 112 patients treated with 5-6 cycles and 68 patients treated with 7-8 cycles. The 3-year OS rates for 3-4 cycles, 5-6 cycles and 7-8 cycles cohort was 56.6%, 73.9% and 67.7%, respectively. Patients who received 5-6 cycles were more likely to have better OS than those received 3-4 cycles (p=0.003), two further cycles of treatment did not improved OS (p=0.885). In the multivariate analysis, cycles of chemotherapy were associated with OS independent of clinical covariates (p=0.008). Subgroup analysis was suggested that for patients with older adult (age ≥60), FU-platinum combined chemotherapy, stage III, poorly differentiation, and gastrectomy with D2 lymph node dissection, 5-6 cycles of adjuvant chemotherapy was associated with a statistically significant benefit of OS (P&lt;0.05). Conclusions: Our result indicated that 5-6 cycles of adjuvant chemotherapy may lead to a favorable outcome for gastric cancer patients following primary surgical treatment. In view of the limited resources of medication, reduced incidences of toxicity and better quality-of-life with shorter duration of treatment, optimal cycles of adjuvant treatment should be explored further.