tbuckley/cabot-search huggingface dataset:
Oncologic safety of laparoscopy in the surgical treatment of type II endometrial cancer.
Authors: Giovanni Favero, Cristina Anton, Xin Le, Christhardt Köhler, Tatiana Pfiffer, Nasuh Utku Dogan, Edmund Chada Baracat, Alexandre Silva Silva, Jesus Paula Carvalho
Journal: Journal of Clinical Oncology (2016)

e17017 Background: Laparoscopy is considered the method of choice in the operative treatment of type I endometrial carcinoma (EC). However, there is a paucity of data regarding the safety of endoscopy for type II EC since these malignancies have several biological similarities with ovarian cancer. The objectives of the study is to evaluate feasibility, operative and oncological safety of laparoscopic surgery in patients with type II EC. Methods: Retrospective study with histologically confirmed serous or clear-cell EC treated by laparoscopy (G1) or laparotomy (G2). Results: From 2009 to 2015, 89 patients were included. Fifty-three women underwent laparoscopy and thirty-six laparotomy. No relevant epidemiologic or oncologic difference between groups was observed.The mean number of removed pelvic nodes was 16 [+10] and 12 [+13] in the group 1 (G1) and group 2 (G2), respectively (p-0.127). The mean number of dissected paraaortic nodes was significantly greater in the laparoscopic group (11 [+9] versus 6 [+9], p-0.006). Paraaortic metastasis was significantly more often observed in the endoscopy group (26% versus 13%, p-0.04). Adjuvant therapies were given to 86% of the patients in the study and 75% in the control group (p-0.157). No excessive blood loss, casualty related to surgery, intraoperative complication or conversion to laparotomy occurred in G1. Ten women (18%) from the G1 and 36% (13/36) in the G2 developed relevant postoperative complications (p-0.03). The median duration of follow-up was 38 months for the laparoscopy and 47 months for the open surgery (p-0.12). The 5-year overall and disease-free survival were similar, 86% versus 78% and 58% versus 51% for G1 and G2, respectively (p-0.312). Conclusions: Laparoscopy is oncologically at least not inferior to laparotomy for the surgical treatment of type II endometrial cancer. Endoscopic techniques are feasible, effective, result in significantly less morbidity and improved quality staging. Although statistical
Bevacizumab plus chemotherapy as first-line therapy for elderly patients with metastatic colorectal cancer: Interim results of the noninterventional CASSIOPEE study.
Authors: Eric Francois, Stefano Chong Hun Kim, Franck Burki, Philippe Laplaige, Denis Michel Smith, Sophie Gourgou, Florence Rollot, Vanessa Barue, Sophie Gandon, Laurent Mineur
Journal: Journal of Clinical Oncology (2016)

3555 Background: Approximately half of the patients (pts) with metastatic colorectal cancer (mCRC) are elderly. A real-life setting study was conducted in elderly pts (≥ 75 years-old) with mCRC treated in daily practice with bevacizumab (bev) plus chemotherapy, in order to improve the knowledge on this population and to contribute in optimizing treatment strategy. Methods: CASSIOPEE is a prospective, multicenter, French, non-interventional study conducted over 24 months. Pts aged 75 years or older with mCRC and treated in 1stline with bev and chemotherapy were eligible. The primary objective was to describe progression-free survival (PFS). Secondary objectives included the description of pts characteristics, overall survival, bev regimen, safety and autonomy criteria such as Lawton Instrumental Activities of Daily Living Scale (IADL 4 items) and Balducci score. Results of a planned interim analysis after 12 months of follow-up are presented (except for PFS on a longer period). Results: Between March 2012 and June 2014, 403 pts were included. Out of the 351 pts (efficacy population), 52% were men, mean age 81 (±4), 80% had primary tumor located in the colon, the main metastatic sites were liver (65%), including liver only (38%). Median PFS was 9.2 months [8.4;10.4] in the efficacy population and 9.8 months for pts aged < 80, 9.2 months for pts aged ≥ 80 or ≤ 85 and 8.3 months for pts aged > 85. The PFS rate at 12 months was 35.3%. On the IADL scale, change from baseline to 6 months was stable (61%), improvement (28%) and deterioration (10%). Balducci score was stable from baseline to 6 months: harmonious (38% vs. 36%), intermediate (21% vs. 23%) and frail (3% vs. 4%), respectively. In the safety population (n = 382), adverse events grade ≥ 3 occurred in 34% pts, of which 28% bev related. Overall, 3% pts died of an AE, of which 25% bev related. Conclusions: CASSIOPEE, a non-interventional real-life setting study, showed treatment benefit andacceptable safety of 1st line bev combined with chemotherapy in elderly pts. After 12 months of follow-up, PFS was 9.2 months, that is comparable with PFS of randomized studies. Clinical trial information: NCT01555762.
Differential elevation of TERT activity and sensitivity to temozolomide by type of TERT mutation in MGMT promoter-methylated glioblastoma.
Authors: Michael Weller, Alexandros Papachristodoulou, Bettina Hentschel, Dorothee Gramatzki, Joerg Felsberg, Markus Loeffler, Gabriele Schackert, Manfred Westphal, Joerg Tonn, Manuela Silginer, Andreas von Deimling, Torsten Pietsch, Guido Reifenberger, Patrick Roth
Journal: Journal of Clinical Oncology (2018)

2013 Background: Benefit from temozolomide chemotherapy in glioblastoma is essentially limited to patients with tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. The impact of the MGMT status on chemosensitivity may be modulated by telomerase reverse transcriptase (TERT) promoter mutations which affect two regions of the TERT promoter, designated as C228T and C250T. Methods: TERT promoter mutation status and TERT activity were determined in a panel of glioma cell lines and correlated with sensitivity to irradiation or temozolomide. TERT status alterations were induced using sh-mediated gene TERT silencing or wildtype TERT overexpression. TERT mutation and MGMT promoter methylation status were also determined in a clinical patient cohort from the German Glioma Network. Results: C228T-mutant glioma cell lines (n = 8) express higher levels of TERT mRNA (mean 0.046±0.012 vs 0.012±0.004 arbitrary units, p = 0.049) and exhibit higher TERT catalytic activity (mean 122±16 vs 53±11 arbitrary units, p = 0.022) than C250T-mutant glioma cell lines (n = 5). C228T-mutant glioma cell lines are also more sensitive to irradiation (mean ED90 4.6±0.7 versus 7.1±0.8 Gy, p = 0.039) or temozolomide (mean EC50 101.6±58.5 versus 295.2±53.8 µM, p = 0.045) in vitro. Targeted alterations of TERT status result in profound changes in radiosensitivity and chemosensitivity: TERT gene silencing is protective whereas TERT overexpression sensitizes to either genotoxic treatment. Consistent with these preclinical observations, patients with C228T TERT mutation and MGMT promoter methylation appeared to derive more benefit from temozolomide chemoradiotherapy (median overall survival 26.5 months, 95% CI 20.3-32.7) than patients with the C250T mutation (median overall survival 16.2 months, 95% CI 8.5-23.8) or patients without TERT mutation (median overall survival 23.7 months, 95% CI 18.7-28.8). Conclusions: These data refine current models on how TERT and MGMT interact to determine outcome in human glioblastoma and illustrate how future targeted interventions focusing on TERT and MGMT may help to tailor pharmacotherapy of glioblastoma.
The impact of marital status on racial disparities in esophageal cancer care.
Authors: Alan Paniagua Cruz, Karlie L. Haug, Lili Zhao, Priya Wadhera, Rishinda Reddy
Journal: Journal of Clinical Oncology (2017)

4056 Background: It is well known that racial disparities exist in cancer treatment and outcomes. The present study examined the impact of marital status as a surrogate for social support on esophageal cancer (EsC) care. Methods: We performed a secondary analysis of data collected from a state cancer registry. We included individuals with an EsC diagnosis between January 1, 2000 and December 31, 2013. A Chi-square test and Fisher’s exact test was used to analyze categorical variables and two-sample t-tests to compare continuous variables. Results: 8754 patients (Caucasian (C) or African American (AA) only) were included, with 88.4% C and 11.6% AA. Staging at diagnosis in C and AA patients revealed that 30.6% vs 28.6% had localized disease, followed by 33.8% vs 32.0% with regional, and 35.6% vs 40.0% with metastatic, respectively (p = .0155). Rates of chemotherapy (53.6% vs 53.5%) and radiation therapy (54.1% vs 56.2%) administration were found to be similar between C and AA patients. In contrast, surgery rates were significantly different between the two groups, with 29.7% of C undergoing surgical resection in comparison to only 12.0% of AA patients (p &lt; .0001). When evaluating marital status, 63.3% of C were married, compared to 33.4% of AA patients (p &lt; .0001). In the AA group, 20.1% of married patients underwent surgery in contrast to only 7.6% of single AAs (p &lt; .0001). Similarly, in the C group, married patients underwent surgery at a rate of 34.5%, while single patients went to surgery at a rate of 22.2% (p &lt; .0001). Surgery contraindication (CI) rates were found to be similar across all groups (5.6% married Cs, 5.2% married AAs, 6.6% single Cs, and 6.5% single AAs) along with surgery refusal rates (1.56% single Cs vs 2.68% married Cs (p = .052), and 1.04% single AAs vs 2.81% married AAs (p = .210)). Conclusions: African American patients receive chemotherapy and radiotherapy at comparable rates to Caucasian patients, but the rates of surgery are significantly lower. Being married was associated with an almost three-fold increase in surgery rates for AA patients, and cause a significant increase in Caucasians too.
P01.085 Experience with TTFields (Optune®) in pediatric high grade glioma patients in Israel
Authors: H Toledano, G Abebe Campino, R Dvir, S Postovsky, M Yalon, T Siegal
Journal: Neuro-Oncology (2018)

TTFields are an established treatment for newly diagnosed or recurrent GBM in adults. TTFields have been shown to prolong OS, PFS and long term survival with minimal side effects in GBM. This treatment is not yet approved for children under 18 years and the device (Optune®, Manufacturer Novocure™) was provided on a compassionate basis to all patients in this case series. We report our experience with TTFields at 4 major pediatric oncology centers in Israel. Since September 2017 the device has been offered to 7 pediatric patients of whom 5 (3 female, 2 male) gave consent immediately. These 5 patients were aged 11.1 - 17.7 years at the time of diagnosis. 4/5 had a midline diffuse glioma H3.3K27M positive and started Optune® together with temozolomide following biopsy/subtotal resection and radiation. The fifth patient had a gross total resection of a right parietal GBM positive for the H3.3G34R mutation. He was treated with radiation and adjuvant temozolomide and had a multifocal right sided relapse at 20 months, and was then treated with avastin and Optune®. Two of the five patients reported device-related mild itchy skin, which was easily treated topically. Four of the five patients continued all normal activities despite carrying the device during school attendance, trips abroad and even at a waitressing job. One male refused to attend school and continues home learning. Three of the 5 patients had programmable shunts and the Optune® device did not interfere with the settings in any of them. Compliance was >90% in 3 patients (77–150 days follow up), 80% in 1 individual (86 days) and 60% in the relapsed patient (39 days). Two of the 5 patients have stopped treatment due to progression after 86 and 142 days on Optune®, however all patients are still alive at the time of the report. In summary TTFields is a feasible and tolerable treatment even in children as young as 11 years. TTFields had no additional systemic side effects and showed good acceptance rate within this population. Further studies in pediatric patients are needed to evaluate efficacy in pediatric high-grade glioma patients.
Pembrolizumab (pembro) vs paclitaxel (PTX) for previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer: Phase 3 KEYNOTE-061 trial.
Authors: Charles S. Fuchs, Mustafa Ozguroglu, Yung-Jue Bang, Maria Di Bartolomeo, Mario Mandala, Min-Hee Ryu, Lorenzo Fornaro, Tomasz Olesiński, Christian Caglevic, Hyun Cheol Chung, Kei Muro, Eray Goekkurt, Wasat Mansoor, Raymond S. McDermott, Einat Shacham-Shmueli, Xinqun Chen, S. Peter Kang, Carlos Alberto Mayo, Atsushi Ohtsu, Kohei Shitara
Journal: Journal of Clinical Oncology (2018)

4062 Background: Pembro has shown promising antitumor activity in patients (pts) with pretreated G/GEJ cancer. KEYNOTE-061 (NCT02370498) was a global phase 3 study of pembro vs PTX for previously treated advanced G/GEJ adenocarcinoma that progressed after first-line chemo containing platinum and fluoropyrimidine. Methods: Eligible pts were randomized to pembro 200 mg Q3W or standard-dose PTX. Randomization was stratified by geographic region, TTP on first-line therapy, and PD-L1 combined positive score (CPS). Primary end points were OS (efficacy boundary, one-sided P = .0135) and PFS in the CPS ≥1 population. Results: 395/592 pts enrolled had PD-L1 CPS ≥1: 196 assigned to pembro, 199 to PTX. After median follow-up of 8 mo, 7.8% of pts completed or remained on pembro vs 0% on PTX. Median OS was 9.1 mo with pembro vs 8.3 mo with PTX (HR 0.82, one-sided P = .042) (Table). 12-mo OS rates were 39.8% vs 27.1%; 18-mo rates were 25.7% vs 14.8%. There was no difference in PFS or ORR, but pembro responses were more durable (Table). Pembro treatment effect was more evident in pts with ECOG PS 0 (HR 0.69; 95% CI 0.49-0.97) or GEJ tumors (HR 0.61; 95% CI 0.41-0.90). In post-hoc analysis, the pembro treatment effect for OS was greater for CPS ≥5 (HR 0.73; 95% CI 0.52-1.03) and ≥10 (HR 0.64; 95% CI 0.41-1.02). In all pts, grade 3-5 drug-related AE incidence was 14.3% with pembro vs 34.8% with PTX; 3.1% vs 5.4% discontinued due to drug-related AEs. Conclusions: Pembro reduced the risk of death by 18% vs PTX in pts with previously treated G/GEJ cancer and PD-L1 CPS ≥1, although this difference was not statistically significant. Pembro had a better safety profile than PTX. Pembro treatment effect was more evident in pts with ECOG PS 0 and with increasing PD-L1 expression. Trials of pembro in G/GEJ cancer are ongoing. Clinical trial information: NCT02370498. Pembro N = 196 PTX N = 199 OS Median (95% CI), mo 9.1 (6.2-10.7) 8.3 (7.6-9.0) HR (95% CI) 0.82 (0.66-1.03) P .042 PFSa Median (95% CI), mo 1.5 (1.4-2.0) 4.1 (3.1-4.2) HR (95% CI) 1.27 (1.03-1.57) P .98 ORR,a % (95% CI) 15.8 (11.0-21.7) 13.6 (9.1-19.1) DOR,a median (range) 18.0 (1.4+ to 26.0+) 5.2 (1.3+ to 16.8) ≥12 mo, % 59.5 29.5 aAssessed per RECIST v1.1 by blinded, independent central review.
Diagnosing idiopathic pulmonary fibrosis in 2018: bridging recommendations made by experts serving different societies
Authors: Luca Richeldi, Kevin C. Wilson, Ganesh Raghu
Journal: European Respiratory Journal (2018)

Two guidance documents for the diagnosis of idiopathic pulmonary fibrosis (IPF) have been recently published by international experts representing major respiratory and radiological societies [1, 2]. Similar documents from other societies are anticipated. This is clearly a positive sign of the increasing attention being paid by the scientific community to a group of fibrotic lung diseases of which IPF is the prototype. Two new documents on the diagnosis of IPF have been published in 2018: their similarities and differences are described and discussed <http://ow.ly/856P30lnB2O>
Metformin to treat prostate cancer (PCa) and prevent metabolic syndrome associated with androgen deprivation therapy (ADT): Results of a randomized double-blind placebo-controlled study of metformin in non-diabetic men initiating ADT for advanced PCa.
Authors: Devalingam Mahalingam, Hanni Salih, Christos Fountzilas, Joel Michalek, John Sarantopoulos, Paromita Datta, Ofelia Romero, Sureshkumar Mulampurath Achutan Pillai, John G. Kuhn, Michael N. Pollak, Ian Murchie Thompson
Journal: Journal of Clinical Oncology (2017)

e16502 Background: ADT results in metabolic syndrome, characterized by hyperinsulinemia, insulin resistance and obesity. The hyperinsulinemia may result in ADT resistance; therefore preventing metabolic syndrome could have a therapeutic impact on PCa. In diabetes, metformin (MET) decreases glucose &amp; insulin by inhibiting hepatic gluconeogenesis. There is preclinical evidence for additional antineoplastic activity due to mTOR inhibition secondary to AMPK activation. Methods: Men with biochemical relapse or advanced PCa due to receive ADT were randomized 1:1 in a double blind manner to MET (500mg TID) or placebo (P). Subjects required normal oral glucose tolerance test at baseline, with fasting serum insulin/glucose, PSA, MET, weight and waist circumference (WC) monitored at baseline, week 12 and 28. The primary endpoint of study was the metabolic consequences of MET vs P. Secondary endpoints were PSA response and PBMC analysis of downstream target of mTOR, phospho-S6 kinase. Results: 36 men were randomized to MET or P, mean age 68.4; biochemical failure (n = 15) &amp; metastatic disease (n = 21). Mean weight, WC and insulin at baseline in MET cohort was 187 lbs, 41.14 cm and 10.03 mIU/L respectively, and 177.65 lbs, 40.52 cm and 8.02 mIU/L in P cohort. An increase in mean weight, WC and insulin levels was seen in both cohorts. At wk 12 and 28, no statistical difference in weight, WC and insulin was observe in either cohort. 4 men randomized to MET had undetectable serum drug levels despite drug-diary suggesting compliance; excluding them did not result in significant metabolic change. Assessing efficacy, 50% in MET and 53.3% in P cohort achieved undetectable PSA at wk 28; difference not statistically significant. PBMC analysis demonstrated variable down-regulation of phospho-S6 kinase in the metformin cohort. Conclusions: This study detected no impact of MET addition to ADT on the risk of metabolic syndrome and no additional anti-tumor effects. Control of hyperinsulinemia related to diabetes by MET does not necessarily imply MET has a similar action on hyperinsulinemia due to ADT. Clinical trial information: NCT02620423.
Preoperative gemcitabine-nab-paclitaxel (G-NP) for (borderline) resectable (BLR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC): Feasibility results and early response monitoring by Diffusion-Weighted (DW) MR.
Authors: Jean-Luc Van Laethem, Maria Antonietta Bali, Ivan Borbath, Gontran Verset, Anne Demols, Francesco Puleo, Marc Peeters, Laurence Annet, Antonino Ceratti, Axelle Ghilain, Mina Komuta, Pieter Demetter, Raphael Maréchal
Journal: Journal of Clinical Oncology (2016)

4116 Background: G-NP has recently emerged as an effective combination treatment for metastatic PDAC. We aimed to evaluate tolerability and activity of induction/neoadjuvant G-NP before surgery. In addition, we evaluated DW-MR imaging to monitor tumoral changes and to predict early response to chemotherapy compared with RECIST evaluation. Methods: Patients (pts) with ECOG PS 0/1, cytologically proven PDAC, normal bilirubin level and BLR or LA disease were included and received at least one cycle of G 1000 mg/m2 and NP 125 mg/m2, weekly 3week/4. Additional cycles were indicated according to sequential tumor restaging for resectability evaluation; complementary chemoradiation (CRT) (50.4 Gy/28 fr) with capecitabine (825 mg/m2 BID) was administered in case of persisting non resectability. Sequential DW-MR was performed at baseline and weekly during cycle 1 and monthly for subsequent cycles. DW-derived quantitative parameters (DW tumour volume and histogram based apparent diffusion coefficient (H-ADC) and pure diffusivity (H-D)) were compared between responders and non-responders, based on clinical/biochemical (CA 19.9) morphological and pathological response (pR) Results: 23 pts received therapy (M/F: 13/10; median age: 63, ECOG 0/1: 12/23), 13 BLR and 10 LA PDAC; median number of cycles: 3. Eight pts received CRT. Related grade III and IV toxicity occurred in 15 and 1 pts. No death occurred during the whole sequence. Best RECIST responses were 8 PR, 12 SD and 3 PD. Ten/16 pts (62%) with an elevated CA19.9 level at baseline decreased CA 19.9 levels by at least 50 %. R0 (n = 7)/R1(n = 6) resection was performed in 13/23 pts (56%).There were 0 pCR, 3 major pR and 10 minor/no pR. In 16 analyzed pts for DW-MR images, DW tumor volume, H-ADC and H-D variations were significantly different between responders and non-responders at the end of cycle 1. Conclusions: Induction chemotherapy with G-NP is feasible and active before surgery; our data suggest a potential interest of monitoring response to preop G-NP chemotherapy by using DW-MR for the early discrimination of responders/non-responders. Clinical trial information: NCT01715142.
Computer-Based Intensity Measurement Assists Pathologists in Scoring Phosphatase and Tensin Homolog Immunohistochemistry — Clinical Associations in NSCLC Patients of the European Thoracic Oncology Platform Lungscape Cohort
Authors: Undine Rulle, Zoi Tsourti, Ruben Casanova, Karl-Friedrich Deml, Eric Verbeken, Erik Thunnissen, Arne Warth, Richard Cheney, Aleksandra Sejda, Ernst Jan Speel, Line Bille Madsen, Daisuke Nonaka, Atilio Navarro, Irene Sansano, Antonio Marchetti, Stephen P. Finn, Kim Monkhorst, Keith M. Kerr, Martina Haberecker, Chengguang Wu, Panagiota Zygoura, Roswitha Kammler, Thomas Geiger, Steven Gendreau, Katja Schulze, Bart Vrugt, Peter Wild, Holger Moch, Walter Weder, Ata Tuna Ciftlik, Urania Dafni, Solange Peters, Lukas Bubendorf, Rolf A. Stahel, Alex Soltermann
Journal: Journal of Thoracic Oncology (2018)

IntroductionPhosphatase and tensin homolog (PTEN) loss is frequently observed in NSCLC and associated with both phosphoinositide 3-kinase activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable readout, but lacks standardized staining protocol and cutoff value.MethodsAfter an external quality assessment using SP218, 138G6 and 6H2.1 anti-PTEN antibodies, scored on webbook and tissue microarray, the European Thoracic Oncology Platform cohort samples (n = 2245 NSCLC patients, 8980 tissue microarray cores) were stained with SP218. All cores were H-scored by pathologists and by computerized pixel-based intensity measurements calibrated by pathologists.ResultsAll three antibodies differentiated six PTEN+ versus six PTEN- cases on external quality assessment. For 138G6 and SP218, high sensitivity and specificity was found for all H-score threshold values including prospectively defined 0, calculated 8 (pathologists), and calculated 5 (computer). High concordance among pathologists in setting computer-based intensities and between pathologists and computer in H-scoring was observed. Because of over-integration of the human eye, pixel-based computer H-scores were overall 54% lower. For all cutoff values, PTEN- was associated with smoking history, squamous cell histology, and higher tumor stage (p < 0.001). In adenocarcinomas, PTEN- was associated with poor survival.ConclusionCalibration of immunoreactivity intensities by pathologists following computerized H-score measurements has the potential to improve reproducibility and homogeneity of biomarker detection regarding epitope validation in multicenter studies.