tbuckley/cabot-search huggingface dataset:
A randomized phase III trial of cisplatin with or without S-1 in patients with FIGO IVB, recurrent, or persistent cervical cancer: An Asian study.
Authors: Soyi Lim, Kazunori Ochiai, Yoichi Aoki, Daisuke Aoki, Shoji Kamiura, Hao Lin, Yasuhiro Fujiwara, Soon Do Cha, Jae Hoon Kim, Byoung Kim, Yasuyuki Hirashima, Keiichi Fujiwara, Young Tak Kim, Seok-Mo Kim, Hyun Hoon Chung, Ting-Chang Chang, Toshiharu Kamura, Ken Takizawa, Masahiro Takeuchi, Soon-Beom Kang
Journal: Journal of Clinical Oncology (2017)

5527 Background: A combination of S-1, an oral fluoropyrimidine, plus cisplatin has been used for advanced gastric cancer in Asia and EU, and lung cancer in Japan. It also evaluated in advanced or recurrent cervical cancer in a phase II setting. We conducted a randomized phase III trial to compare the efficacy and safety of S-1 plus cisplatin with those of cisplatin alone in recurrent or persistent after treatment and FIGO IVB cervical cancer patients. Methods: Stage IVB, recurrent or persistent cervical cancer patients aged ≥ 20 years, ECOG PS 0–1 and adequate organ function were randomly assigned (1:1) to receive S-1 (80–120 mg daily, according to BSA, day 1–14) plus cisplatin (50 mg/m 2 on day 1) (study group) or cisplatin alone (50 mg/m 2 on day 1) (control group) every 3 weeks. Treatment was continued until disease progression. In all, 360 patients (at least 296 events) with a hazard ratio (HR) for death of 0.72 were required for a two-sided alpha of 5% and power of 80% under 2 years of recruitment and 1.5 years of follow-up. Stratification factors included recurrence in previously irradiated field, previous platinum-based therapy, and institution. Primary endpoint was OS based on intent-to-treat principle, and secondary endpoints were PFS, overall response rate (ORR), and safety. Results: In all, 375 patients were assigned to the study (n = 189) and control (n = 186) groups. Rate of previous platinum-based therapy was 64%. The median survival time was 21.9 and 19.5 months (95% CI, 18.6–25.8 and 17.0–24.3) with the use of unstratified log-rank test in the study and control groups, respectively (log-rank P = 0.125; HR, 0.84; 95% CI, 0.67–1.05). Significant increases in median PFS (7.3 vs. 4.9 months; log-rank P &lt; 0.001; HR, 0.62) and ORR (43.8 vs. 20.1%, P &lt; 0.001) were observed in the study group. Adverse events (grade≥3) were frequent in the study group (80.9 vs. 41.7%) with neutropenia (52.7%), anemia (34.6%), and leukopenia (32.4%) being the most common events. Conclusions: Compared with cisplatin alone, S-1 plus cisplatin did not significantly improve OS but increased ORR, prolonged PFS, and had tolerable safety of patients with stage IVB, recurrent or persistent cervical cancer. Clinical trial information: NCT00770874.
Efficacy and immune modulation by BXCL701 a dipeptidyl peptidase inhibitor, NKTR-214 a CD122-biased immune agonist with PD1 blockade in murine pancreatic tumors.
Authors: Luca Rastelli, Snigdha Gupta, Zeenia Jagga, Deborah H. Charych, Jonathan Zalevsky
Journal: Journal of Clinical Oncology (2018)

3085 Background: BXCL701 targets DPP8/9 and stimulates migration and cytotoxicity of T and NK cells in addition to targeting fibroblast activator protein (FAP) which forms an immunological barrier to the tumor microenvironment. NKTR-214 is a CD122-biased agonist designed to provide sustained signaling through the heterodimeric IL2 receptor pathway (IL2Rβɣ) to preferentially activate and expand effector CD8+ T and NK cells. NKTR-214 has demonstrated robust anti-tumor activity when combined with anti-PD1 in multiple murine tumor models and recently, with nivolumab in multiple human cancers. We hypothesized that BXCL701 could further potentiate NKTR-214/anti-PD1 anti-tumor activity by removing fibrotic barriers to immune cells. Methods: NKTR-214, BXCL701 and anti-PD1 were dosed in mice bearing established (~100mm3) murine pancreatic tumors (Pan02) as single agents, doublets and the triplet (0.8mg/kg q9d, 20µg qd, and 200 µg qw2 respectively). Tumors were profiled using IHC and multiplex serum cytokine/chemokine analysis. Tumor-free mice were re-challenged with either Pan02 or murine lung tumor (LLC). Results: Of the mice treated with the triplet combination, 100% became tumor-free (9/9) by day 21. These animals remained tumor free for more than 60 days when a subset were re-challenged with new tumor cells. Of these, 5/6 mice rejected tumor regrowth suggesting durable immunity after the triplet therapy. IHC of the tumors from satellite animals sacrificed on day 3 revealed that the triplet significantly reduced FAP expression while increasing the number of immune cell infiltrates in the tumor. Conclusions: The triplet of NKTR-214, BXCL701 and anti-PD1 provided 100% tumor-free mice in established pancreatic tumors with concomitant reduction in FAP expression. The results suggest that removal of fibrotic barriers to immune infiltration is an important mechanism for overcoming immune escape by tumors otherwise resistant to immune therapy. These results provide therapeutic rationale for treatment of pancreatic cancer patients with this triple combination.
Early prediction of therapy response to abiraterone acetate using PSA subforms in patients with castration resistant prostate cancer.
Authors: Katrin Schlack, Laura-Maria Krabbe, Andres Jan Schrader, Axel Semjonow, Martin Boegemann
Journal: Journal of Clinical Oncology (2016)

e16586 Background: Biomarkers to predict therapy response of Abiraterone acetate (AA) are rare. Due to their additive function for the detection of clinical relevant prostate cancer we evaluated the prognostic ability of free PSA (fPSA), [-2]proPSA and the prostate health index (PHI), next to total PSA (tPSA), under therapy with AA. Methods: In 25 men with mCRPC, PSA subforms were analyzed as predictors of progression free survival (PFS) and overall survival (OS) before and at 8-12 weeks under therapy with AA. Alterations of baseline values, presented as relative median changes, were compared by Mann-Whitney-Wilcoxon-test (MWW). Survival probabilities were estimated with Kaplan-Meier-analysis (KM). Results: In MWW, the relative median change of tPSA (-0.1% vs. -86.8%) and fPSA (12.1% vs. -55.3%) differed significantly (p = 0.02 and 0.03) between patients with a PFS < or ≥ 12 months. A similar trend was shown for decreasing [-2]proPSA (8.1% vs. -59.3%; p = 0.05). There were no significant differences in PHI between patients with a PFS < or ≥ 12 months. For men with ≤ or > 15 months of OS there was a non-significant trend for a difference in the relative median change of fPSA (17.0% vs. -46.3%; p = 0.06). Considering OS, the MWW did not evaluate conclusive changes for tPSA, [-2]proPSA and PHI. In KM-analysis declining fPSA was associated with a median PFS of 13 months (95%CI: 9.6-16.4) compared to 10 months (95%CI: 3.5-16.5) in patients with increasing values (p = 0.11). Correspondingly, a decreasing fPSA indicated an OS of 32 months compared to 21 months in men with rising fPSA (p = 0.14). In univariate cox-regression analysis rising [-2]proPSA and fPSA were non-significant predictors of poor OS (Hazard ratio (HR) = 2.5 (p = 0.16) , respectively). Conclusions: When added to tPSA, which is traditionally used as response indicator due to a lack of other available parameters, changes of fPSA and [-2]proPSA at 8-12 weeks of AA therapy may be a promising therapy control marker to help making meaningful decisions whether to stop or to continue AA-therapy in men with mCRPC. Due to its better availability the measurement of fPSA seems to be more feasible and thus more promising compared to [-2]proPSA.
Induction chemotherapy (IC) with EXTREME study regimen for locally advanced head and neck cancer (LAHNC) frail patients.
Authors: Valérie Cochin, Erwan De-Mones-Del-Pujol, Laurence Digue, Muriel Garcia-Ramirez, Charles Dupin, Claire Majoufre-Lefebvre, Amaury Daste
Journal: Journal of Clinical Oncology (2017)

e17564 Background: IC with TPF (docetaxel, cisplatin, 5FU) in LAHNC is limited to fit patients (pts). We conducted a retrospective cohort study to evaluate the use of EXTREME regimen (platinum, 5FU, cetuximab) as IC in LAHNC frail pts. Methods: Retrospective analysis of all consecutive pts with unresectable LAHNC treated with EXTREME regimen with or without 5FU as IC from two French centers from 2008 to 2015. We evaluated the rate of realization of the complete sequence (at least 2 cycles of IC and all radiation courses). Tolerance and efficacy, including clinical benefice, median progression free survival (PFS) and median overall survival (OS) were estimated. Results: We included 34 pts with average age of 56 years [46-70] (Table). Patients presented decreased weight (10% in one month or 15% in 6 months): 74% (n=25), pain: 76% (n=26), feeding tube: 82% (n=28), tracheotomy: 15% (n=4), fistula: 15% (n=4) and low albumin &lt;35g/l: 41% (n=14), &lt;25g/l: 12% (n=4). Six pts (17%) not received 5FU (cardiovascular history). Grade 3 toxicities were seen in 50% pts principally due to cisplatin. 5FU dose was decreased in 9% (n=3) and cisplatin switched to carboplatin in 15% (n=4). The sequence was achieved for 76% (n=26) of pts and 80% (n=27) presented clinical response with improvement of symptoms (increased weight: 32%, n=11). Six pts (17%) have a progression disease (PD) under IC, one patient (3%) died during bioradiotherapy (BRT) (stomach perforation) and one (3%) stopped IC after one cycle (infection) but achieved BRT. BRT with cetuximab was used in 85% (n=23) (average of 6 cycles [2-8]). PET-FDG at 3 months showed 9% (n=3) of complete response (CR) and 44% (n=15) of PD. Median PFS and OS were 5.7 and 15.5 months respectively. PD at 3 months was associated with decreased median OS: 21.9 versus 13.6 months, p=0.01. Conclusions: This is the first report of use of the EXTREME regimen as IC. This IC was used in a very frail population and the majority achieved sequence with significant clinical benefice. [Table: see text]
TCT-51 Long-term Mortality Comparison of Patients With Acute Myocardial Infarction and Cardiogenic Shock Treated With Culprit-Only or Multivessel Percutaneous Coronary Intervention
Authors: Ruben Vergara, Elisa Vignini, Michele Ciabatti, Angela Migliorini, Renato Valenti
Journal: Journal of the American College of Cardiology (2018)
Early integrated palliative care to improve family caregivers (FC) outcomes for patients with gastrointestinal and lung cancer.
Authors: Areej El-Jawahri, Vicki A. Jackson, Joseph A. Greer, William F. Pirl, Elyse R. Park, Anthony Back, Emily R. Gallagher, Alona Muzikansky, Mihir M. Kamdar, Simone Rinaldi, Juliet Jacobsen, Joel Fishbein, Justin Eusebio, Harry VanDusen, Ryan David Nipp, David P. Ryan, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2016)

10131Background: Patients with newly diagnosed advanced cancers who receive early palliative care (PC) integrated with oncology care report improvement in their quality of life (QOL) and mood. Whil...
Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study
Authors: Paolo C. Colombo, Mandeep R. Mehra, Daniel J. Goldstein, Jerry D. Estep, Christopher Salerno, Ulrich P. Jorde, Jennifer A. Cowger, Joseph C. Cleveland, Nir Uriel, Gabriel Sayer, Eric R. Skipper, Francis X. Downey, Masahiro Ono, Robert Hooker, Anelechi C. Anyanwu, Michael M. Givertz, Claudius Mahr, Ia Topuria, Sami I. Somo, Daniel L. Crandall, Douglas A. Horstmanshof
Journal: Circulation (2019)

Background: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. Methods: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score &gt;3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. Results: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1–733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181–730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08–0.63; P =0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). Conclusions: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (&gt;6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.
Treatment of Erdheim-Chester disease patients with the MEK inhibitor cobimetinib.
Authors: Fleur Cohen-Aubart, Jean-François Emile, Philippe Maksud, Frédéric Charlotte, Philippe Cluzel, Neïla Benameur, Olivier Aumaitre, Zahir Amoura, Julien Haroche
Journal: Journal of Clinical Oncology (2016)

e19074 Background: Approximately 60 % of Erdheim-Chester disease (ECD), a rare non-langerhans cell histiocytic disorder, harbor the BRAFV600E mutation. BRAF inhibitors have shown a dramatic efficacy in BRAF mutated histiocytoses. Efficacy of MEK inhibitors has recently been reported in 2 ECD patients with MAP2K1mutations, treated with trametinib and cobimetinib. Methods: We treated 3 wild-type BRAFV600E ECD refractory patients. The absence of BRAFV600E mutation was confirmed by high sensitivity picodroplet digital PCR. Two patients were previously treated with vemurafenib, prior to getting the BRAF status, with worsening of the target lesions in 18FDG PET scan, suggesting this drug may have a paradoxical effect in WT BRAFpatients. The need for cobimetinib was justified in these 3 patients by progression of renal failure and refractory arterial hypertension, medullar compression by a spinal dural lesion and circumferential pericardial effusion. Cobimetinib was given at the dose of 40 milligrams/day, 21 days/28, as a sole therapy. Results: Assessment at month (M) 1 by 18FDG PET scan showed that all patients were partial (n = 2) or complete (n = 1) metabolic responders (RECIST criteria). Creatinine level of patient #1 had significantly decreased (from 337 to 187 micromol/liter) and he fully recovered from refractory hypertension and diastolic heart failure. The pericardial effusion of patient #3 had totally disappeared. Patients #1 and #2 were reassessed respectively at M8 and M5 of cobimetinib therapy: both remained partial metabolic responders. CRP levels were high at baseline for patients #1 & 2 and decreased for both until last follow up. Spinal MRI of Patient #2 displayed a diminution of the dural histiocytic infiltration. Patient #1 experienced vomiting, and cycline responsive-acneiform rash. None had neither cardiac nor ocular complications. All patients remain on treatment at M8, M5 and M1. Conclusions: We report the efficacy of cobimetinib used as a sole regimen in WT-BRAF ECD patients for up to 8 months. The responses were assessed by 18 FDG PET scan and measurements of tumor size. The safety profile of this drug was good. Cobimetinib may be a valuable therapeutic option in WT-BRAF patients presenting with severe disease.
Cancer related insomnia and wireless technology: A pilot study.
Authors: Brenda O'Connor, Pauline Ui Dhuibhir, Declan Walsh
Journal: Journal of Clinical Oncology (2017)

e21645 Background: Cancer related insomnia (CRI) includes difficulty with sleep onset, maintenance or non-restorative sleep. CRI is common with prevalence up to 95%. Consequences include cognitive dysfunction, fatigue, increased hospitalisation and lost work productivity. Early detection may help. CRI remains under-investigated as objective assessment has needed specialised laboratories. Mobile technology may provide a solution. This study aimed to determine the feasibility and acceptability of a wireless bedside monitor (SleepMinder [ResMed Sensor Technologies Ltd, Dublin]) to evaluate CRI. Methods: A prospective observational study recruited 10 consecutive hospice inpatients (IP) and 20 consecutive community participants (CP) with cancer. Participants used a wireless non-contact bedside sleep monitor for 3 consecutive nights. Three insomnia features were examined (sleep onset, maintenance, early awakening). Computerised algorithm-generated metrics were compared to visual inspection of the monitor sleep/activity report. Acceptability questionnaires were completed by patient, nurse and family. Results: The device successfully recorded sleep patterns in all 30 participants. No technical difficulties were experienced. IP: Mean age was 63 +/- 9 years. 7/10 had one or more insomnia features with delayed sleep onset most common. The monitor over-estimated Sleep Latency (77% nights), Duration (77% nights) and Final Awakening (63% nights). CP: Mean age was 64 +/- 10 years. 15/20 had one or more insomnia features with poor sleep maintenance most common. The monitor overestimated Sleep Duration (62% nights) and Final Awakening (45% nights). Lower levels were noted in CP as they spent less time in bed. Patients, nurses and family members reported high (100%) device acceptability. Conclusions: A wireless bedside monitor effectively measured sleep in seriously ill cancer patients in both inpatient and outpatient settings without the use of a sleep laboratory High reliability and acceptability supports routine clinical use Sensitivity of wakefulness detection was reduced as the device incorrectly identified sleep during awake but motionless periods Concurrent use of sleep diary and a monitor is recommended for comprehensive assessment
TCT-425 Impact of External Elastic Lamina Diameter Based Sizing Versus Lumen Diameter Based Sizing on Early Vascular Healing
Authors: Wataru Sasaki, Masaru Ishida, Tomonori Itoh, Yohei Uchimura, Hideto Oda, Yuya Taguchi, Kyosuke Kaneko, Tsubasa Sakamoto, Iwao Goto, Masafumi Sakuma, Daisuke Terashita, None yoshiro tsukiyama, Hiromasa Otake, Toshiro Shinke, Yoshihiro Morino
Journal: Journal of the American College of Cardiology (2018)
Psychological distress in patients with moderate to severe chronic graft-versus-host disease (cGVHD).
Authors: Lauren Waldman, Lara Traeger, Sarah Fishman, Netana Markovitz, Julie Vanderklish, Yi-Bin Albert Chen, Thomas R. Spitzer, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2018)

e22137 Background: cGVHD is the leading causing of morbidity and mortality in allogeneic stem cell transplant survivors. However, studies assessing psychological distress in patients with cGVHD and exploring its relationship with their quality of life (QOL), physical functioning, symptom burden, and coping are lacking. Methods: We conducted a prospective observational study of patients with moderate to severe cGVHD. At the time of enrollment, we assessed patients’ psychological distress [Hospital Anxiety and Depression Scale (HADS)], QOL [Functional Assessment of Cancer Therapy – General], physical functioning [Human Activity Profile], cGVHD symptom burden [Lee Symptom Scale], and coping [Coping Inventory for Stressful Situations]. Using linear regression models adjusted for age, sex, and severity of cGVHD, we examined the relationship between patients’ depression symptoms (HADS-Depression) with their QOL, physical functioning, cGVHD symptoms, and coping strategies. Results: We enrolled 53 patients with moderate (71.7%, 38/53) or severe (28.3%, 15/53) cGVHD. The rate of clinically significant depression and anxiety symptoms were 32.1% (17/53) and 30.2% (16/53), respectively. In adjusted linear regression models, higher QOL [β = -0.18, SE = 0.02, P < 0.001] and physical functioning [β = -0.06, SE = 0.02, P = 0.006] were associated with lower depression symptoms, while higher cGVHD symptom burden [β = 0.07, SE = 0.02, P = 0.004] was associated with higher depression symptoms. The use of emotion-oriented coping (β = 0.22, SE = 0.06, P = 0.001) was associated with higher depression symptoms. In contrast, task-oriented coping (β = -0.10, SE = 0.04, P = 0.027) was associated with lower depression symptoms. Avoidance coping was not significantly associated with patients’ depression symptoms [β = -0.08, SE = 0.04, P = 0.063]. Conclusions: Patients with moderate to severe cGVHD experience substantial psychological distress, which is associated with worse QOL, physical function, and cGVHD symptom burden. The use of certain coping strategies is associated with patients’ depression symptoms. Psychological interventions to promote adaptive coping strategies in patients with cGVHD are critically needed.