tbuckley/cabot-search huggingface dataset:
MK-0646 (MK), insulin growth factor 1 receptor (IGF-1R) antibody combined with pemetrexed (P) and cisplatin (C) in stage IIIb or IV metastatic nonsquamous lung cancer (NSQL).
Authors: Chao Hui Huang, Karen Kelly, Stephen K. Williamson, Prakash Neupane, Sarah A. Taylor, Ace Allen, Jo Wick, Peter J. Van Veldhuizen
Journal: Journal of Clinical Oncology (2012)

e13551 Background: IGF-1R regulates cell growth, proliferation and apoptosis. Adenocarcinoma and never smokers have higher expression of IGF-1R and it is associated with worse survival. MK is a humanized monoclonal antibody that targets IGF-1R. P has higher activity in NSQL. We initiated a randomized phase II trial to evaluate the combination of P and C +/- MK in NSQL. Methods: Eligibility criteria: untreated NSQL stage IIIB or IV, ECOG 0 or 1, measurable disease, adequate organ function and no other intercurrent illness. Standard B12 and folic acid were given. P at 500mg/m2 and C at 75mg/m2 IV were given every 3 weeks. MK was given at the dose of 10mg/kg IV weekly on days 1, 8 and 15 of every 3 week cycle in the experimental group. The patients had radiographic assessment after every 2 cycles and treated for a maximum of 6 cycles if there was either response or stable disease. The primary objective of the study was to estimate the individual response rate of standard and experimental arm. IRB reviewed and approved the study at participating institutions. Results: From 1/2009 to 2/2011, the study accrued 26 patients, 16 male, 10 female, median age 59 yo. 14 patients were treated with PC and 12 patients were treated with PC +MK. In the PC arm we observed 2 partial responses (PR), 7 stable disease (SD), 3 had progression (PD) and 2 were not evaluable (NE). In the MK arm there were 3 PRs, 4 SD, 4 PD and 1 NE. In both arms, hematologic adverse events(AE) observed were: grade 3 neutropenia(5), hemoglobin (3), febrile neutropenia (2), platelet (2) leukopenia (1), lymphopenia (1); grade 4 platelet (2), hemoglobin (1); Grade 3 non-hematological AE were: hyperglycemia (4) and 1 occurrence each of hearing deficit, pain in extremity, hyponatremia, urinary tract infection, fatigue, dyspnea, laboratory, hypokalemia, esophageal stenosis, hypoxia, dysphagia and muscle weakness; Grade 4 hypoxia and hyperglycemia. The study was closed due to termination of funding. Conclusions: PC with MK had a similar response rate to PC. There was a higher rate of hyperglycemia in the MK group. Identification of a response predictive marker would be critical in order to continue the study of this agent.
Assessment of γH2AX levels in circulating tumor cells in patients treated with veliparib in combination with doxorubicin and cyclophosphamide in metastatic breast cancer.
Authors: Antoinette R. Tan, Deborah Toppmeyer, Serena Tsan-Lai Wong, Hongxia Lin, Murugesan Gounder, Rebecca Anne Moss, Mark N. Stein, Janice M. Mehnert, Sinae Kim, Alice P. Chen, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2013)

2582 Background: Veliparib (V) is a potent PARP inhibitor that delays repair of DNA damage induced by chemotherapeutic agents. In metastatic breast cancer pts, we evaluated V with doxorubicin (A) and cyclophosphamide (C) given both on day 1 with V at 100 mg po BID for 7 days post-chemotherapy every 21 days, to increase DNA damage. We report use of γH2AX, (phosphorylated histone protein), a marker of DNA double-strand breaks, in circulating tumor cells (CTCs) to assess DNA damage. We evaluated number of CTCs and percentage of γH2AX-positive CTCs pre- and post-treatment. Methods: Eligibility included prior A ≤ 300 mg/m 2 and EF ≥ 50%. Further A was omitted after a cumulative dose of 420 mg/m 2 . Primary objective was to assess DNA damage response to treatment by measuring γH2AX-positive CTCs during cycle 1 on days 1 (pre-treatment), 2, 7, and 14. Cell Search System was used to enumerate CTCs. γH2AX was quantitated using a validated assay. Results: Eleven pts enrolled. Median age was 53 (34 – 73); median ECOG PS 1 (0 – 2); there were 1 ER-negative/HER2+, 4 triple-negative (BRCA2+, n =1), and 6 ER+/PR+/HER2-negative (BRCA2+, n =2) tumors. Most common drug-related toxicities were grade (gr) 4 neutropenia, gr 2 anemia and thrombocytopenia, and gr 1 nausea and vomiting. In BRCA2+ pts, there were 2 PRs and 1 SD. In BRCA wt or unknown status, 5 pts had SD ≥ 3 mo and there were 3 PDs. CTCs (≥ 8) were detected in 10/11 pts on days 1 and 2. Day 7 samples were not obtainable in 2 pts. On day 7, 1/8 pts had 0 CTCs and rest had ≥ 3 CTCs. A decrease in CTCs (p &lt; 0.0001) occurred from day 1 (median: 22, range, 8-1216) to day 7 (median: 5, range 3-37). At baseline, 7 pts had ≥ 10% γH2AX-positive CTCs. Fraction of CTCs positive for γH2AX increased to ≥ 50% by day 7 in 6/7 pts and persisted to day 14 in 5 pts. Conclusions: The toxicity profile of V 100 mg BID days 1-7 with AC (60/600 mg/m 2 ) on day 1 on a 21-day cycle was expected. Objective antitumor activity was seen in BRCA mutation carriers. CTCs decreased and percentage of γH2AX-positive CTCs increased after combination treatment with a PARP inhibitor and chemotherapy. This observation is notable and we plan to extend dosing of V to 14 days. This work is supported by NCI U01-CA132194. Clinical trial information: NCT00740805.
The importance of surgical margins for biochemical recurrence in high-risk prostate cancer patients.
Authors: Victor Srougi, Rafael Sanchez-Salas, Fernando P. Secin, Igor Nunes-Silva, Mohammed Baghdadi, Silvia Garcia Barreras, Gregory Rembeyo, Francois Rozet, Marc Galiano, Eric Barret, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2017)

75 Background: High-risk prostate cancer (PCa) is associated with greater risk of biochemical recurrence and cancer specific lethality. A multi-modal treatment is required for this group of patients, comprising surgery as part of it. However, the role of surgery as monotherapy is still under investigation. The purpose of this study is to analyze the influence of surgical margins on biochemical recurrence (BCR) among patients with high-risk prostate cancer (PCa) treated with robot assisted radical prostatectomy (RARP) since the start of our robotic program. Methods: We retrospectively analyzed our prospectively collected database of 5695 minimally invasive prostatectomies performed between 2000 and 2015. Clinical, pathological and oncological outcomes were evaluated in patients fulfilling Damico´s high risk characteristics. Primary endpoint was BCR, defined as post-operative PSA ≥ 0,2. Patients with neoadjuvant or adjuvant therapy were excluded. BCR was estimated with Kaplan-Meier curves. Cox proportional hazards regression was used to estimate variables associated with BCR. Results: We identified 199 high-risk PCa patients treated with RARP during the study period. Gleason score ≥ 8, PSA ≥ 20 and clinical stage ≥ T2c were present in 44%, 35% and 11% of the patients, respectively. The rate of positive surgical margins was 25%. With a median follow-up of 23 months (interquartile 12 – 34 months), 31% of the patients had BCR. Five-year BCR-free survival was 34,5%. Gleason score ≥ 8, PSA ≥ 20 and positive surgical margins were not predictors of BCR. A positive correlation of pathological stage ≥ T3 and BCR was found with (HR = 2.9; 95% CI = 1.2-6.9). Conclusions: The 5-years BCR-free survival was poor despite a low rate of positive surgical margins, when compared to historical series. We found that pathological stage ≥ T3 has a significant correlation with the BCR and that negative surgical margins do not assure good prognosis for high-risk patients.
Outcome of Patients with Myelofibrosis Relapsing after Allogeneic Stem Cell Transplant: A Retrospective Study By the Chronic Malignancies Working Party of EBMT
Authors: Donal McLornan, Richard Szydlo, Anja van Biezen, Linda Koster, Evgeny Klyuchnikov, Andrea Bacigalupo, Michael Schleuning, Jurgen Finke, Antonin Vitek, Andrew Peniket, Dietrich W. Beelen, Charles Craddock, Jane F. Apperley, Wolfgang Bethge, Didier Blaise, Dietger Niederwieser, Liisa Volin, Peter Dreger, Mauricette Michallet, Arnon Nagler, Renate Arnold, Eduardo Olavarria, Nicolaus Kroeger
Journal: Blood (2015)
Cetuximab combined with concurrent chemoradiotheray in Chinese patients with unresectable, locally advanced esophageal squamous cell carcinoma: A prospective, multicenter phase II trial.
Authors: Xue Meng, Jianhua Wang, Xindong Sun, Lvhua Wang, Ming Ye, Ping bo Feng, Guangying Zhu, You Lu, Chun Han, Shu chai Zhu, Zhongxing X. Liao, Jinming Yu
Journal: Journal of Clinical Oncology (2013)

e15030 Background: This multicenter phase II trial investigated cetuximab add to concurrent chemoradiotherapy for Chinese patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with unresectable locally advanced cervical, thoracic upper or mid-ESCC were eligible for this phase II trial. All patients received cetuximab (400 mg/m 2 day 1 before chemoradiotherapy and 250 mg/m 2 q1w × 7 weeks), paclitaxel (45 mg/m 2 q1w × 7 weeks) and cisplatin (20 mg/m 2 q1w × 7 weeks) with 59.4 Gy of radiation (1.8Gy/33f). The primary end point was response rate. Second end points included toxicity, overall survival (OS), progression-free survival (PFS), and KRAS mutation status. Results: Forty-five previously untreated patients (36 men, 9 women; median age, 59 year; performance status 0 or 1) with ESCC were treated and evaluated for clinical and radiographic response. After therapy, 29 patients (65%) achieved a complete response, and 15 (33%) patients achieved a partial response, the response rate was 97.7%. Non-hematological adverse events were generally grade 1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue (45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia (1.82%). The 1-year PFS and OS rates were 87.3% and 91.1%, 2-year OS were 83.02%, respectively. No mutations were detected at KRAS codons 12 or 13 in all specimens. Conclusions: Cetuximab can be safely administered with chemoradiation for Chinese patients with esophageal cancer and may improve the clinical response rate. KRAS mutations were too rare to be analyzed as a predictor of response. Clinical trial information: NCT00815308.
RECURRENCIA DE COLECISTITIS AGUDA LITIÁSICA EN PACIENTES NO COLECISTECTOMIZADOS TRATADOS CON CPRE Y ESFINTEROTOMÍA ENDOSCÓPICA O CON COLECISTOSTOMÍA PERCUTÁNEA
Authors: V Busto Bea, C De La Serna Higuera, P Díez Redondo, I Peñas Herrero, R Sánchez-Ocaña Hernández, H Núñez Rodríguez, P Gil Simón, F Santos Santamarta, A Loza Vargas Luz, R Amo Alonso, M De Benito Sanz, M Pérez-Miranda
Journal: Endoscopy (2015)

Introducción: El tratamiento de elección de la colecistitis aguda litiásica (CAL) es la colecistectomía laparoscópica, pero en algunos pacientes su riesgo no es asumible. La evidencia sobre si las técnicas no quirúrgicas de drenaje biliar son capaces de prevenir nuevos episodios de (CAL) en pacientes no candidatos a colecistectomía es todavía escasa.
Phase II trial of TI-CE high dose chemotherapy (HDCT) with drug monitoring for individual carboplatin dosing in patients with relapsed advanced germ cell tumors: A multicentric prospective GETUG trial.
Authors: Christine Chevreau, Christophe Massard, Aude Flechon, Remy Delva, Gwenaelle Gravis, Jean-Pierre Lotz, Jacques-Olivier Bay, Marine Gross-Goupil, Karim Fizazi, Loic Mourey, Fabienne Thomas, Thomas Filleron, Pascale Olivier, Stephane Culine, Etienne Chatelut
Journal: Journal of Clinical Oncology (2017)

401 Background: HDCT is a valid option of treatment for relapsed advanced GCTs pts. The results of the TICE regimen as salvage therapy in poor risk pts demonstrated a 50% complete response (CR) but with very high variability of measured carboplatin area under the curve (AUC) (between 10.9-36.7 for target AUC = 24 mg.min/mL). We initiated a phase II trial of TICE with therapeutic drug monitoring (TDM) for individual carboplatin dosing in order to target the 3-day AUC to 24 mg/min/mL. Methods: Were included pts with unfavorable relapsed GCTs , secondarily classified according to the International Prognostic Factors Study Group. Pts were treated according the TICE regimen with two cycles combining paclitaxel and ifosfamide followed by three cycles HDCT: carboplatin plus etoposide with stem cell support. Carboplatin dose was adapted on day 3 based on carboplatin clearance (Cl) at day 1, in order to reach the target AUC. The primary endpoint was the CR rate (cCR sCR pCR). A Simon Minimax design was performed using the following hypothesis: p0 = 50%, p1 = 65 α = 5%, β = 10%. Results: Between 03/2009 and 11/2015 101 pts were accrued, 60 pts were treated in first relapse (34 classified as high and very high-risk) and 41 in 2 nd or more relapse. 72 pts (71%) received the whole treatment, 12 pts (10%) did not receive any cycle of HDCT. 29pts (26%) stopped treatment earlier, 8 for toxicity. Three pts died on treatment. 35/79 (44.3%) evaluable pts achieved a CR. 19 pts (24%) presented a PRm-. The mean observed carboplatin AUC was 24.5 mg.min/mL (between 18.9 and 28.8) at C1.Following TDM, the modification of the total carboplatin dose during C1 was comprised between -33% and +44%, showing the benefit of TDM in comparison with individual dosing based only on carboplatin Cl predicted according to patient’s renal characteristics. Conclusions: The CR rate observed in this very poor prognosis population was 44.3% and 69.6% CR + PRm-. Carboplatin dose individualization based on TDM allowed to reach more accurately the target AUC compared to previous reports. Clinical trial information: NCT00864318.
Experimental fertility preservation (FP) interventions in prepubertal (PP) boys with cancer: A report on preferences of teenage cancer survivors, parents, and providers.
Authors: Abha A. Gupta, Rachel Donen, Lillian Sung, Derek Stephens, Carol Portwine, Sheila Pritchard, Sina Hadipour-Lamehsari, Katherine Boydell, Kirk Lo, Armando J. Lorenzo
Journal: Journal of Clinical Oncology (2014)

6593 Background: Risk of infertility from cancer therapy is a source of great distress for young cancer survivors. FP can be a challenge in PP boys who are unable to produce bankable sperm through ejaculation. We sought to determine factors influencing patient, parental and provider preferences for testicular biopsy (TBx) even though the utility of PP tissue for FP remains experimental. Methods: Oncology providers, parents, and teenage cancer survivors were recruited from 3 pediatric centers in Canada. During participant surveys, a hypothetical decision was made between TBx and no TBx. Top factors influencing decisions were identified and willingness to accept complications, costs, risk of infertility, and chance of technology developing were used to measure strength of preference for TBx. Multiple regression was used to associate predictors with TBx desirability scores (under risk of infertility condition). Results: The proportion of respondents who preferred TBx (vs no TBx) were: 110/153 (72%) parents, 22/30 (73%) providers, and 52/77 (67%) cancer survivors. The top ranked factor influencing decisions for all groups was risk of infertility. For those that chose biopsy, a switch to no TBx occurred at very low chance technology developed (median 9%), highest cost point (median $500/year), and low risk of infertility (median 9.5%). Providers would accept much lower level of complications from TBx (median 21%), compared to parents (41%) and survivors (100%). Child age, type of cancer, ethnicity, or hospital were not significant factors associated with preference for TBx, but parents who reported a higher income were more likely to prefer TBx (p=.05). Some providers would not present TBx in cases of lower risk of infertility and poor prognosis. In contrast, parents (96%) and survivors (89%) wanted information on TBx before treatment began to ensure they had choice; no matter the factors of the case. Conclusions: Parents, survivors, and providers strongly favor TBx. Parental income was the only predictor of preferences under the risk of infertility condition. Addressing the costs associated with FP should remain an important focus of advocates for FP.
A snapshot of potentially personalized care: Molecular diagnostics in gynecologic cancer.
Authors: Elizabeth Sales, Richard T. Penson, Laura A Sullivan, Darrell R. Borger, Carolyn N. Krasner, Annekathryn Goodman, Marcela G del Carmen, Whitfield Board Growdon, John O. Schorge, David M. Boruta, Michael J. Birrer
Journal: Journal of Clinical Oncology (2012)

5029 Background: Genetic abnormalities underlie the development of cancer. It has been proposed that tumors be recategorized by gene mutation such as BRAF in LG serous, TP53 in HG serous, and PIK3CA in clear cell and endometrioid tumors. These targets potentially represent an opportunity for personalizing cancer therapy. Methods: Gynecologic Oncology patients at the MGH Cancer Center can have their tumor genotyped for a panel of mutations by SNaPshot, a validated, CLIA approved assay developed by MGH that uses DNA from FFPE tissue to interrogate 160 site-specific mutations across 15 genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2K1, NOTCH1, NRAS, PIK3CA, PTEN, TP53). At present SNaPshot has no validated endpoints in GYN Cancers but may help identify a useful clinical trial. Results: Between 5/17/10 and 10/17/11, 125 patients consented to SNaPshot genotyping. Patients had a median age of 59 (24-78) yrs. Tumors were ovarian 70(56%), uterine clear, UPSC, or MMMT 16(13%), uterine endometrioid 10(8%), fallopian tube 8(6%), PPC 7(6%), cervical 6(5%), uterine sarcomas (3), ACUP (2), vulvovaginal (2), metastatic (1). A mutation was identified in 41(33%), with 9 of these (23%) having 2 or 3 (n=2) mutations. In the 85 ovarian, FT, and PPC cancers 33% were +ve, but 50% were in TP53. The low mutation rate for TP53 is likely explained by copy number abnormalities (Amplification). 50% of the 10 uterine tumors were +ve, with 3 of those 5 having multiple mutations in the PIK3CA pathway, while 69% of the non-endometrioid uterine tumors had mutations. Only 20% of the vulvo-vaginal and Cx tumors had mutations, both PIK3CA. 19% of the purely serous tumors (n=58) had TP53 mutations, and 37% of the purely clear/endometrioid tumors (n=19) had mutations in PIK3CA, PTEN or AKT. Certain rare tumors did not have identifiable mutations: granulosa cell tumors (2), ovarian small cell (2). 5 pts with a PIK3CA mutation were enrolled on a clinical trial (2 phase II, 3 phase I, 3 uterine, 1 ovary, 1 cervix). Conclusions: SNaPshot can identify potentially important therapeutic targets. However, the incidence of "drugable" targets in ovarian cancer is low, and &lt;5% subjects eventually were treated on a relevant clinical trial.
What is the effect of health coaching on physical activity participation in people aged 60 years and over? A systematic review of randomised controlled trials
Authors: Juliana S Oliveira, Catherine Sherrington, Anita B Amorim, Amabile B Dario, Anne Tiedemann
Journal: British Journal of Sports Medicine (2017)

Physical inactivity is common in older age, yet increased activity benefits older people in terms of preventing chronic disease and maximising independence. Health coaching is a behaviour change intervention that has been shown to increase physical activity in clinical populations. This systematic review and meta-analysis investigated the effect of health coaching on physical activity, mobility, quality of life and mood in older people.MEDLINE, EMBASE, CENTRAL, PsycINFO, PEDro, SPORTDiscus, LILACS and CINAHL databases were used to identify randomised controlled trials which evaluated the effect of health coaching on physical activity (primary outcome) among people aged 60+. Secondary outcomes were mobility, quality of life and mood. We calculated standardised mean differences (SMDs, Hedges' g) with 95% CIs from random effects meta-analyses.27 eligible trials were included. Health coaching had a small, statistically significant effect on physical activity (27 studies; SMD = 0.27; 95% CI 0.18 to 0.37; p<0.001). There was no evidence of an effect of health coaching on mobility (eight studies; SMD = 0.10; 95% CI -0.03 to 0.23; p=0.13), quality of life (eight studies; SMD = 0.07; 95% CI -0.06 to 0.20; p<0.05) or mood (five studies; SMD = 0.02; 95% CI -0.12 to 0.16; p=0.83).Health coaching significantly increased physical activity in people aged 60+. There was no evidence of an effect of health coaching on quality of life, mobility and mood, so different approaches may be required to impact on these outcomes.
Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial
Authors: Paolo A Ascierto, Michele Del Vecchio, Caroline Robert, Andrzej Mackiewicz, Vanna Chiarion-Sileni, Ana Arance, Céleste Lebbé, Lars Bastholt, Omid Hamid, Piotr Rutkowski, Catriona McNeil, Claus Garbe, Carmen Loquai, Brigitte Dreno, Luc Thomas, Jean-Jacques Grob, Gabriella Liszkay, Marta Nyakas, Ralf Gutzmer, Joanna Pikiel, Florent Grange, Christoph Hoeller, Virginia Ferraresi, Michael Smylie, Dirk Schadendorf, Laurent Mortier, Inge Marie Svane, Delphine Hennicken, Anila Qureshi, Michele Maio
Journal: The Lancet Oncology (2017)
Copper metabolism MURR1 domain-containing10 (COMMD10) as a predictive factor in HBV-related hepatocellular carcinoma (HCC).
Authors: Jian Guan, Lu Li, Nanjie Xiao, Guoyang He, Xiaohui Zhu, Mi Yang, Min Chen, Y Zhang, Qinyang Li, Yongmei Dai, Chi Zhang, Li Liang, Longhua Chen
Journal: Journal of Clinical Oncology (2015)

e22254 Background: Copper metabolism MURR1 domain-containing10(COMMD10), a novel component of FCOMMD protein family, is a protein involved in multiple cellular pathways, including copper homeostasis, NF-κB and HIF signalling. However, its expression and role in HBV-related hepatocellular carcinoma remain unclear. Methods: The expression of COMMD10 was detected in clinical formalin-fixed paraffin-embedded (FFPE) hepatocellular carcinoma tissues by immunohistochemistry with clinicopathological analyses and determined in matched pairs of fresh frozen tissues by Quantitative Real time PCR or Western blot. Results: Immunohistochemistry staining was performed in 129 cases of clinical paraffin-embedded HCC tissues. The staining signal of COMMD10 was mainly observed in adjacent normal livers or cirrhotic livers. Meanwhile,no signals or only weak signals were detected in HCC tissues. Among 129 samples, 94 cases of them (72.9%) exhibited low-expression of COMMD10 (0 to 1+) and high-expression of COMMD10 (2+ to 3+) was found in the other 35 cases (27.1%). The expressions of COMMD10 were significantly lower in HCC tissues than in adjacent normal livers or cirrhotic livers, respectively (Z = 27.038, P = 0.001; Z = 25.047, P = 0.001). COMMD10 expression was strongly correlated with the differentiation(P = 0.041) and serum AFP level in clinic (P = 0.009). From univariate analysis, the significant prognostic factors were COMMD10 expression (P = 0.005), portal vein thrombosis(P = 0.001), differentiation (P = 0.001), dissemination (P = 0.001). Multivariate analysis results showed that COMMD10 expression, portal vein thrombosis, differentiation and dissemination might play a role in predicting the overall survival in HBV-related HCC patients (P = 0.05). Conclusions: In this study we identified COMMD10 downregulation significantly correlated with poor prognosis in HBV-related Hepatocellular carcinoma. COMMD10 status was considered as an independent significant prognostic factor and a possible target for the development of new drugs in HBV-related HCC.