tbuckley/cabot-search huggingface dataset:
Phase II study of biomarker guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on EGFR-mutation status.
Authors: Wenzhao Zhong, Xue-Ning Yang, Xuchao Zhang, Jian Su, Hong-Hong Yan, Zhihong Chen, Riqiang Liao, Qiang Nie, Song Dong, Yi-Long Wu
Journal: Journal of Clinical Oncology (2014)

7572 Background: Neoadjuvant EGFR-TKI therapy and customized adjuvant therapy are appealing but controversial strategy in patients with IIIA-N2 NSCLC. The purpose of this study was to evaluate the role of biomarker guided neo-adjuvant treatment strategy in patients with IIIA-N2 non-small cell lung cancer (NSCLC) stratified by epidermal growth factor receptor (EGFR) mutation status. Methods: Patients with resectable histologically documented stage IIIA-N2 NSCLC were assigned to either a neoadjuvant erlotinib arm or a gemcitabine/carboplatin (GC) arm based on EGFR mutation status (NCT00600587). The primary endpoint of this phase II study was response rate (RR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Twenty-four patients with IIIA-N2 NSCLC were enrolled in the trial from January 2008 until May 2011. The overall RR was 42%, and 58.3% (7/12) for the erlotinib arm with mutant EGFR, 25.0% (4/12) for the GC arm with wild-type EGFR (P = 0.18). Six cases in the erlotinib arm and seven cases in the GC arm received surgical resection. Median PFS was 6.9 months for the erlotinib arm and 9.0 months for the GC arm (P = 0.071). Median OS was 14.5 months for the erlotinib arm and 29.3 monthsfor the GC arm (P = 0.304). The median OS of the resected patients was 28.9 months for the erlotinib arm and 55.8 months for the GC arm (P = 0.218). In the overall population, the PFS and OS were 7.9 and 24.1 months, respectively. In addition, all six cases in the erlotinib arm that underwent resection gained partial response to tyrosine kinase inhibitor (TKI) re-treatment after progression, with a 2nd median PFS of 11 months. Conclusions: Biomarker guided neo-adjuvant treatment strategy in patients with IIIA-N2 NSCLC is feasible. Erlotinib had a tendency to improve the response, while the benefit did not transfer to better PFS or OS in this subgroup. Further randomized controlled studies of neoadjuvant combined with adjuvant EGFR-TKI are required to establish the role of perioperative TKI therapy in patients with IIIA-N2 NSCLC. Clinical trial information: NCT00600587.
A phase I trial of PEGylated glutaminase (PEG-PGA) in combination with 6-diazo-5-oxo-L-norleucine (DON) in advanced, refractory, solid tumors
Authors: C. Mueller, S. Al-Batran, E. Jaeger, M. Bausch, N. Sethuraman, C. Unger
Journal: Journal of Clinical Oncology (2007)

14040 Background: Tumor cells are avid glutamine consumers and highly dependent on extracellular glutamine supply. Based on a competitive mechanism, the effectiveness of the glutamine analogue DON is enhanced if the available pool of glutamine is significantly (below 10% of baseline) depleted by PEG-PGA. Methods: The study was designed to determine the maximal tolerable dose (MTD) of DON in combination with PEG-PGA. The patients received intravenous PEG-PGA 120 I.U./m 2 in combination with DON twice weekly for six weeks followed by a tumor assessment according to RECIST. DON dose was escalated from 5 to 185 mg/m 2 using modified Fibonacci design and traditional 3-patient cohorts. Results: Fifty-eight pts (23f/35m) received at least 1 drug administration and were evaluable for the analysis. Median age was 62 (range 43–79) and median Karnofsky PS was 90% (range 70%-100%). Median treatment duration was 29 days (range 1–106). Nausea and vomiting represented the most common non-hematological grade 3 toxicities, being observed in 6.9% and 10.3% of pts, respectively. Hematological side effects were G4 leuco- and neutropenia (1.7%) and G3 thrombocytopenia (1.7%). The treatment was very well tolerated with all other grade 3 or 4 toxicities affecting less than 5% of patients. Forty-six pts were evaluable for efficacy. Stable disease was observed in 20 (43.5%) pts, including MR (&gt;10%) in 5 (10.8%) pts. The efficacy was dose depended. Conclusions: The combination of PEG-PGA and DON is active and has a favorable toxicity profile. The MTD is now investigated in a Phase IIa trial in patients with refractory colorectal, renal or non small cell lung cancer. The accrual will be finished by January 2007. No significant financial relationships to disclose.
Estimating Quality of Life for Patients with GIST based on patient-reported EQ-5D Scores and Swedish Utility Weights in order to inform a Cost-Effectiveness Model for regorafenib.
Authors: Zinajda Zolic, Vincent Heller, Martin Stausholm Knudsen
Journal: Journal of Clinical Oncology (2015)

e17705 Background: Often diagnosed in an advanced metastatic stage, GIST has a substantial impact on patients’ quality of life. Regorafenib, a novel oral compound, has been shown to extend the time to progression of GIST. The absolute reduction of health utility can vary between countries, and, as result, country specific utility weights increase the accuracy of health economic analyses. Methods: Experience based health states (EQ-5D) reported by patients in the GRID trial (an international phase III trial comparing regorafenib against placebo, NCT01271712) were combined with utility weights derived from a Swedish population. A total of 185 subjects and 806 observations were included. Statistical analysis included a paired samples comparison (t-test) and multivariate regression analysis (repeated measures). Hypothesis tests were performed to investigate differences in both treatment effect (treatment or placebo) and health state (progressed or non-progressed). The multivariate analysis used a stepwise approach to identify potential confounding variables. Results: Based on the paired samples analysis, the progression-free state is associated with a utility of 0.872, while the post progression state is associated with a utility of 0.806. The difference of 0.066 is significant at p = 0.0117. A utility of 0.850 for the progression-free state and 0.814 for the progressed disease state was estimated using the simplest repeated measures model, not including variables for treatment effect. Conclusions: Data from the GRID trial provided robust utility estimates for a cost-utility model based on preferences reported by a Swedish population. Extension of the time to progression in a population treated for GIST will be associated with a QALY gain in range of 0.035 to 0.066 per year. This method effectively estimates health utility values for GIST patients in Sweden, and can serve as data inputs in a cost-utility model.
Neoadjuvant treatment of colorectal liver metastases (CRLM) with drug eluting beads trans-arterial chemoembolization (DEBIRI-TACE): A multi-institute phase II study in resectable metastases.
Authors: Robert Peter Jones, Hassan Zakria Malik, Stephen W Fenwick, Clare Byrne, Monica Terlizzo, Elizabeth O'Grady, Stefan Stremitzer, Thomas Gruenberger, Graeme John Poston
Journal: Journal of Clinical Oncology (2012)

3613 Background: Perioperative chemotherapy confers 3-year progression free survival advantage following resection of CRLM and good pathologic response is associated with improved overall survival. However, systemic neoadjuvant chemotherapy can increase postoperative morbidity and mortality. TACE using preloaded Irinotecan eluting beads gives sustained delivery of drug directly to tumor, thereby maximising response and reducing systemic exposure. This study examined the feasibility and safety of neoadjuvant DEBIRI-TACE before CRLM resection. Methods: Patients with resectable CRLM received single DEBIRI-TACE (up to 200mg) 1 month pre-hepatectomy. Primary end-point: tumor resectability, secondary end-points: safety, radiologic response (RECIST) and pathologic tumor response. Results: TACE attempted in 49 patients, successful in 40. Reasons for failed TACE included consent withdrawal (n=2), bilobar disease (n=2), tumour involving gallbladder wall (n=1), suspected hepatoma (n=1), arterial access difficulty (n=2), contrast medium allergy (n=1). Post-TACE complications: 1 acute pancreatitis (3%); 4 post-embolization syndromes (10%). Imaging at 4 weeks post-TACE (30 patients): complete response 0/40 (0%); partial response 1/40 (3%); stable disease 19/40 (48%); ‘progressive’ disease 10/40 (25%). 40 patients proceeded to surgery, 38 underwent hepatectomy (2 peritoneal disease, resectability rate 95%). 30-day post-operative mortality 5% (n=2), neither death TACE related (1 intraoperative pneumomediastinum, 1 aspiration pneumonia). 63 lesions (median 2 per patient) targeted with TACE. Histology: no residual disease 17%; 1-49% residual disease 59%; &gt;50% residual disease 22%; no response 2%. Conclusions: Resection after neoadjuvant DEBIRI-TACE for CRLM is feasible and safe. Single treatment with DEBIRI-TACE resulted in tumor pathologic response similar to that seen after protracted systemic chemotherapy.
Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis
Authors: Yu Kawazoe, Kyohei Miyamoto, Takeshi Morimoto, Tomonori Yamamoto, Akihiro Fuke, Atsunori Hashimoto, Hiroyuki Koami, Satoru Beppu, Yoichi Katayama, Makoto Itoh, Yoshinori Ohta, Hitoshi Yamamura
Journal: JAMA (2017)

Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis.To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation.Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours.Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam.The co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes.Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively.Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further.clinicaltrials.gov Identifier: NCT01760967.
ANÁLISIS DE COMPLICACIONES CARDIO-RESPIRATORIAS EN LA SEDACIÓN CON PROPOFOL. EXPERIENCIA EN NUESTRO HOSPITAL DE NIVEL II EN LOS ÚLTIMOS 5 AÑOS
Authors: S Maestro Antolin, K De Jesus, A Germade, B Moreira, C Sanchez, F Santos, F Igea, J Barcenilla, A Santamaria, E Saracibar, RE Madrigal, AG Perez-Millán
Journal: Endoscopy (2015)

Introducción: La sedación con propofol controlada por endoscopista es sin duda la mejor estrategia en las exploraciones convencionales. No obstante aún está en duda su eficacia y perfil de seguridad en la endoscopia avanzada (USE y CPRE). Su uso sistemático aún no está extendido en estas técnicas avanzadas y persiste cierta controversia sobre la necesidad o no de contar con anestesistas en estos casos.
Results of the first interim analysis of the CARMA study to investigate efficacy and safety profile of catumaxomab in clinical practice.
Authors: Volker Kunzmann, Jalid Sehouli, Barbara Schmalfeldt, Pauline Wimberger, Christian M. Kurbacher, G.-F. Tempelhoff, Udo J. Vanhoefer, P. Ebeling, F. Breuer, Holger Schulz, Manfred Welslau, Dominique Finas, Jaqueline Sagasser, M. Kiehl, S. Fruehauf
Journal: Journal of Clinical Oncology (2012)

e13100^ Background: The trifunctional antibody catumaxomab is approved in the EU for intraperitoneal (i.p.) treatment of malignant ascites in patients (pts) with EpCAM-positive carcinomas. Clinical data for catumaxomab are based on the pivotal trial and several phase I/II trials. So far, the routine use of catumaxomab in clinical practice has not been evaluated systematically. Therefore, a large prospective observational study was started in 2010. The study investigates the administration of catumaxomab in a total of 160 pts with malignant ascites under routine conditions in daily clinical practice. Here we show the results of the first pre-planned interim analysis. Methods: The analysis included 49 pts with malignant ascites due to EpCAM-positive carcinomas treated with i.p. catumaxomab under routine conditions in clinical practice. Participating centres were hospitals and practices of oncologists in Germany. Primary endpoint was puncture-free interval (PFI), secondary endpoints included safety and overall survival (OS). Results: At inclusion into the study pts already had undergone a median number of 9 ascites punctures. Malignant ascites had been diagnosed for the first time 3.3 months before (median). Patients suffered from typical ascites symptoms as follows: swelling (79.6%), pain (44.9%), dyspnea (26.5%), anorexia (26.5%), obstipation (12.2%). 49 pts were treated with catumaxomab, of whom 30 pts received all 4 infusions (61.2%). Median PFI was 108 days (d), the median OS was 102 d. Most frequent adverse events were fever, nausea and diarrhoe. Conclusions: This is the first systematic report on routine use of catumaxomab in clinical practice.. Although The study population mainly comprised patients with advanced tumor diseaset a clinical benefit after catumaxomab therapy could be demonstrated. The treatment showed an acceptable safety profile Theseresults are consistent with the data of the pivotal trial. The data will be evaluated in further analyses including larger patient numbers.
Short- and long-term outcomes of salvage lymph node dissection in patients with clinically recurrent prostate cancer.
Authors: Giorgio Gandaglia, Nicola Fossati, Armando Stabile, Marco Bandini, Emanuele Zaffuto, Paolo Dell'oglio, Nazareno Suardi, Francesco Montorsi, Alberto Briganti
Journal: Journal of Clinical Oncology (2017)

255 Background: Salvage lymph node dissection (sLND) has been proposed to improve oncologic outcomes in nodal recurrence after radical prostatectomy (RP). We aimed at reporting the results of sLND in patients with recurrent PCa limited to the nodes. Methods: 140 patients treated with sLND for nodal recurrence after RP documented by PET/CT scan between 2002 and 2016 were identified. Transfusions, length of stay (LoS), and 30-day complications were analyzed. Biochemical response (BR) was defined as PSA &lt; 0.2ng/ml at 40-day. Clinical recurrence (CR) was defined as positive findings at postoperative imaging. Kaplan-Meier and Cox regression analyses were used. Results: Median age sLND was 66 years. Median PSA at sLND was 2.0ng/ml. Overall, 58.6, 14.4, and 15.0% patients had positive spots in the pelvic, retroperitoneal, and pelvic + retroperitoneal regions. Overall, 19.3, 2.9, and 77.8% patients received a LND in the pelvic, retroperitoneal, and pelvic + retroperitoneal regions. The median number of nodes removed was 27. Overall, 107 (76.4%) patients had positive nodes at sLND. Overall, 10 (7.1%) experienced grade 3-5 complications according to Clavien-Dindo and 12 (11.8%) patients received blood transfusions. Median LoS was 7 days. Median follow-up was 71 months. Overall, 54 (38.6%) patients achieved BR. The 8-year BCR free-survival rate in patients with BR was 44.7%. CR and CMS was observed in 50 and 25 patients. The 8-year CR and CSM-free-survival rates were 43.2 and 66.4%. In the preoperative model, retroperitoneal spots (Hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.02-3.69) and the number of positive spots (HR: 1.26; 95%CI: 1.04-1.57) were predictors of CR. In the postoperative model, BR (HR: 0.33; 95%CI: 0.17-0.72), retroperitoneal involvement (HR: 3.48; 95%CI: 1.22-8.19), and the number of positive nodes (HR: 1.03; 95%CI: 1.01-1-06) were predictors of CR. Conclusions: sLND was associated with a low rate of high-grade complications. At 8-year, more than 40% of patients were free from CR. Retroperitoneal involvement and nodal burden were predictors of response. sLND might represent a therapeutic option for selected patients with nodal recurrence after RP.
CHARTA: FOLFOX+bevacizumab +/- irinotecan in advanced colorectal cancer (CRC)—Final results of the randomized phase II trial of the AIO (KRK 0209).
Authors: Hans-Joachim Schmoll, Benjamin Garlipp, Christian Junghanss, Malte Leithaeuser, Arndt Vogel, Michael Schaefers, Ulrich Kaiser, Heinz-Gert Hoeffkes, Axel Florschütz, Jörn Rüssel, Stephan Kanzler, Thomas Edelmann, Helmut Forstbauer, Thomas Goehler, Carla Hannig, Bert Hildebrandt, Jörg Steighardt, Fabian Maximilian Meinert, Franziska Cygon, Alexander Stein
Journal: Journal of Clinical Oncology (2017)

658 Background: The 4-drug-regimen FOLFOXIRI+Bevacizumab (Bev) was superior to FOLFIRI+Bev (TRIBE F.Loupakis, NEJM 2014). CHARTA investigates the same 4-drug-regimen vs. FOLFOX+Bev. Methods: 250 patients were randomized from 7/11 to 12/14 to standard FOLFOX+Bev (A) vs. FOLFOXIRI+Bev (B), with dose/schedule as in TRIBE, 25% dose reduction in cycle 1 + 2, if necessary. Incl.criteria: ECOG 0-2, ≥ 1 measurable lesion &gt; 1cm; stratified by ESMO-Group 1, 2, 3 (HJ Schmoll et. al., Ann Oncol 2012). Induction: 6 months, maintenance Capecitabine+Bev until progression or max. of 12 months, with reinduction by individual decision. Primary EP: significant improvement of PFS-rate at 9 months (p&lt;0.1, 2-sided Fisher’s-exact test); secondary EP: RR- rate, PFS, OS, sec. resection. Results: Evaluable 241 pts. (1 not elig., 8 prot. violation); m/f: 65%/35%, age 61 yrs. (21-82), left/right: left A: 51, 5%, B: 48, 5%; right A: 45%, B: 55%; ECOG 0-1/2: 96% / 4%, ESMO-group 1/2/3: 29%/ 55%/ 16%. Primary endpoint was met: significantly improved PFS at 9 months 56% vs. 68% (p= 0,086). Preliminary PFS 9,76 vs. 12,0 months (HR 0.77, p=0.61), identical to TRIBE: 9.7 vs. 12.1. Response (A/B): CR: 5/5%, CR/PR 60/70%, SD 25/21%, PD 14/9%; sec. resection: 21/23%. Subgroup - analyses did not show significant differences, except CR / PR left/right (A/B): left 59/68%, right 63/73%; PFS (months) left 10.4/12 (HR 0.69, p=0.03), right: 8.2 /10.7); non-significant improvement in ESMO-group 3 (HR 0.51), RAS-wt (HR 0.67), Koehne-Score High risk HR 0.58; ECOG 1: HR 0.69. QL-Global- Health-Score: slightly worse in A, vs. improved in B. Dose-intensity &lt;70%/ 70-90%/ &gt;90% (A/B): 39/37%/ 18/26%/ 41%/36%; initial dose-reduction 17% of pts. Toxicity: low to moderate without major differences between A &amp;B, except grade ¾ diarrhea 12/16%, neutrophils 14/20%, GI 12/20%. Conclusions: The 4-drug-regimen has superior activity with the same outcome as TRIBE and is well tolerated, without a negative effect of initial dose-reduction, and an improvement of global QoL-Score. Final PFS, OS data and detailed subgroup/multivariate analysis, including Quality of life data, will be presented. Clinical trial information: NCT01321957.
Neutrophil-lymphocyte relationship and its association with overall survival in advanced melanoma.
Authors: Martin Richardet, Matias Nicolas Cortes, Pablo Companys, Matias Molina, Eugenia Pacher, Aldo Alejandro Riso, Patricia Hernandez, Luciano Salvador Dicalbo, Luciana Paola Acosta
Journal: Journal of Clinical Oncology (2015)

e20052 Background: The neutrophil-lymphocyte relationship (NLR) has been associated with lower survival rate in many tumors. The mechanisms underlying this association are poorly understood. An NRL > 4 would modify the inflammatory response, in which neutrophils suppress cytolytic activity of immune cells such as lymphocytes, activated T cells and natural killer cells, which correlate with a good prognosis in other tumors. A high NRL ( > 4) has also been associated to peri tumor infiltration by macrophages, interleukins, various cytokines (IL1-6-7-8-9-12) and interferons. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4 and thrombospondin; therefore, the ratio of Platelet-lymphocytes (PLR) > 194 would be associated with worse prognosis. Our primary objective is to determine if values > 4 of the NLR are associated with worse overall survival (OS), at diagnosis of Advanced Melanoma. The secondary objective is to determine if the PLR are associated with OS and to analyze the relationship of other clinical variables (such as age, sex, performance status, ulceration, mitosis, LDH value and location) with the value of NLR. Methods: Retrospective and analytical study in which 71 patients diagnosed with Advanced Melanoma, in last 7 years were selected and whose NLR value (Low: < 4 or High > 4) and PLR value (Low < 194 or High > 194) was evaluated in relation to overall survival. Statistical analysis was performed using Kaplan-Meier test and univariate statistical analysis (Chi-square test). Results: Median overall survival was 7,4 months. Patientes with NLR > 4 had an OS of 6,4 months, whereas in those with NLR < 4, it was 8,9 months (p = 0,027). There were no significant differences in OS among patients according to PLR. There was no association between clinical variables evaluated and NLR/PLR. Conclusions: NLR > 4 levels at diagnosis of advanced skin melanoma were significantly associated with a lower survival. The PLR > 194 was not significantly associated with worse prognosis in this disease. NLR value could be a factor prognostic valuable.