tbuckley/cabot-search huggingface dataset:
Prognosis of non-small cell lung carcinoma in patients with previous gastric cancer.
Authors: Norifumi Tsubokawa, Takahiro Mimae, Keiju Aokage, Aritoshi Hattori, Kenji Suzuki, Kanji Nagai, Masahiro Tsuboi, Morihito Okada
Journal: Journal of Clinical Oncology (2014)

e18533 Background: Although the incidence of non-small cell lung cancer (NSCLC) as a second malignancy is increasing, the prognosis remains controversial. Therefore, this study aimed to disclose the prognosis of patients with NSCLC who had previously been treated for gastric cancer (PGC). Methods: Retrospectively 4,651 patients who underwent complete surgical resection for NSCLC in three institutions from 2000 to 2013 were evaluated. Results: One hundred (2.1%) were patients with PGC and 4,551 (97.9%) were patients with NSCLC who had not previously been treated for gastric cancer (NGC). The population of older patients (P < 0.001), males (P < 0.001), limited resection for NSCLC (P = 0.015), and non-adenocarcinoma (P = 0.024) were significantly higher in the PGC, than in the NGC group. Overall survival (OS) did not significantly differ between the PGC and NGC groups (76.4% vs. 74.5% P = 0.82). Multivariate cox regression analysis revealed that being older, male, having a higher serum carcinoembryonic antigen level (CEA), more advanced clinical stage of lung cancer, and non-adenocarcinoma were independent factors for a poor prognosis, whereas a history of gastric cancer was not. None of the factors related with gastric cancer affected the survival of patients with PGC. Conclusions: A history of gastric cancer treatment does not affect survival after lung cancer resection and no factors related to gastric cancer influence the results of surgical treatment for lung cancer. Curative surgery for NSCLCshould be recommended when previously treated gastric cancer is well-controlled. Multivariate HR 95%CI P Age (≥ 75 vs. < 75 year) 1.79 1.54 - 2.07 <0.001 Sex (male vs. female) 1.56 1.33 - 1.84 <0.001 CEA (> 5.0 vs. ≤ 5.0 ng/mL) 1.71 1.50 - 1.95 <0.001 cStage of lung cancer (II + III vs. I) 2.17 1.88 - 2.50 <0.001 History of gastric cancer (without vs. with) 1.17 0.71 - 1.92 0.528 Lung cancer (non-ad vs. ad) 1.29 1.10- 1.46 0.001 Adjuvant for lung cancer (yes vs. no) 1.13 0.92 - 1.39 0.233 Multivariate Cox regression analysis of OS.
Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Relapsed or Refractory Myelodysplastic Syndrome: Results from a Phase 1 Dose Escalation and Expansion Study
Authors: Courtney D. DiNardo, Justin M. Watts, Eytan M. Stein, Stephane de Botton, Amir T. Fathi, Gabrielle T. Prince, Anthony S. Stein, James M. Foran, Richard M. Stone, Prapti A. Patel, Martin S. Tallman, Sung Choe, Hongfang Wang, Vickie Zhang, David Dai, Bin Fan, Katharine E. Yen, Stephanie M. Kapsalis, Denice Hickman, Samuel V. Agresta, Hua Liu, Bin Wu, Eyal C. Attar, Hagop M. Kantarjian
Journal: Blood (2018)
Phase I study of proteasome inhibitor bortezomib in combination with irinotecan in patients with relapsed/refractory neuroblatoma.
Authors: Rajen Mody, Gregory A Yanik, Valerie Castle
Journal: Journal of Clinical Oncology (2014)

10051 Background: Despite recent progress in neuroblastoma (NBL) therapy, prognosis for relapsed/ refractory NBL remains poor. Bortezomib, a proteasome inhibitor has been shown to be effective by our group and others, against NBL in vitro and in vivo, either as a single agent or in combination with cytotoxic agents including irinotecan. Methods: Eligible patients high risk NBL, with primary refractory (n=8) or relapsed (n=10) disease. Bortezomib (1.2 mg/m2/day) was administered on days 1, 4, 8 and 11 intravenously (IV), with irinotecan 35, 40, or 45 mg/m2/day (Dose Level (DL) 1,2, and 3 respectively) administered IV days 1-5 of each 21day course. The maximum tolerated dose (MTD), dose limiting toxicity (DLT), and response were examined. Results: Eighteen patients with relapsed/ refractory, high risk NBL were treated, of which17 were evaluable. Three patients were treated at DL-1, 9 patients at DL-2 and 6 patients at DL-3. A total of 149 courses were delivered (mean of 8.2 and median of 2) with 2 patients receiving > 40 courses of therapy. Therapy was very well tolerated and MTD was not reached. Two dose limiting toxicities (DLT) were reported, including grade 3 thrombocytopenia (n=1) and grade 3 irritability (n=1), at dose levels 2 and 3 respectively. Other grade 3 toxicities included neuropathy (n=1) after 34 cycles of therapy, and reversible hematologic toxicities (n=9). None of the patients experienced serious infection. DL-3 is the recommended dose for Phase-II studies. Two out of seventeen (12%) evaluable patients showed sustained objective responses lasting > 40 courses, including 1 partial remission (PR) and 1 complete remission (CR). Four additional patients (23%) had prolonged stable disease (SD) lasting 6 courses or more with a total of 35% patients having prolonged SD or better. Conclusions: The combination of bortezomib with irinotecan was extremely well tolerated by patients with relapsed/ refractory NBL and exhibited very favorable toxicity profile. It showed promising clinical activity with 35% patients experiencing prolonged clinical benefit and merits further testing in Phase-II studies. Clinical trial information: NCT00644696.
Risk Factors Associated With Boys’ and Girls’ Developmental Trajectories of Physical Aggression From Early Childhood Through Early Adolescence
Authors: Ali Teymoori, Sylvana M. Côté, Bobby L. Jones, Daniel S. Nagin, Michel Boivin, Frank Vitaro, Massimiliano Orri, Richard E. Tremblay
Journal: JAMA Network Open (2018)

<h3>Importance</h3> This study used multitrajectory modeling to identify distinct trajectories of physical aggression from ages 1.5 to 13 years for boys and girls. <h3>Objectives</h3> To trace the development of boys' and girls' physical aggression problems from infancy to adolescence using mother ratings, teacher ratings, and self-ratings and to identify early family predictors of children on the high physical aggression trajectories. <h3>Design, Setting, and Participants</h3> This cohort study used data from the Quebec Longitudinal Study of Child Development (QLSCD), a study of a representative, population-based sample of 2223 infants born in 1997 and 1998 in the Canadian province of Quebec. The dates of analysis were January 2017 to January 2018. <h3>Main Outcomes and Measures</h3> Trained research assistants conducted 7 interviews (at child ages 1.5, 2.5, 3.5, 4.5, 5, 6, and 8 years) with the person most knowledgeable about the child (mothers in 99.6% [2214 of 2223] of cases). Teachers assessed the child's behavior at ages 6, 7, 8, 10, 12, and 13 years. Self-reports of behavior problems were obtained from the child at ages 10, 12, and 13 years. <h3>Results</h3> The sample included 2223 participants, 51.2% of whom were boys and 91.2% of whom were of white race/ethnicity. The mean response rate for mother ratings of physical aggression during the first 8 years of life was 80.9% (range, 65.1%-91.7%). For teacher ratings of physical aggression from ages 6 to 13 years, the mean response rate was 45.7% (range, 35.4%-56.9%), while the mean response rate of physical aggression assessment from self-ratings between ages 10 and 13 years was 57.9% (range, 55.2%-60.5%). Attrition was higher among families with low socioeconomic status and single-parent families, as well as among young mothers and mothers who were not fluent in French or English. A statistical analysis to examine the consequences of attrition was included. For boys and girls, the frequency of physical aggressions increased from age 1.5 years (2039 [91.7%]) to age 3.5 years (1941 [87.3%]) and then substantially decreased until age 13 years (1228 [55.2%]). Three distinct developmental trajectories of physical aggression were observed for girls and 5 for boys. Most family characteristics measured at 5 months after the child's birth were associated with a high physical aggression trajectory for boys and girls. <h3>Conclusions and Relevance</h3> Family characteristics at 5 months after the child's birth could be used to target preschool interventions aimed at preventing the development of boys' and girls' chronic physical aggression problems.
Phase 1b/2 Combination Study of APR-246 and Azacitidine (AZA) in Patients with TP53 mutant Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)
Authors: David A Sallman, Amy E. DeZern, David P. Steensma, Kendra L. Sweet, Thomas Cluzeau, Mikkael A. Sekeres, Guillermo Garcia-Manero, Gail J. Roboz, Amy F McLemore, Kathy L McGraw, John Puskas, Ling Zhang, Chirag K Bhagat, Jiqiang Yao, Najla Al Ali, Eric Padron, Roger Tell, Jeffrey E. Lancet, Pierre Fenaux, Alan F. List, Rami S. Komrokji
Journal: Blood (2018)
Peripheral T-Cell Lymphomas in Spain: Profiling Clinical, Phenotypic and Genetic Characteristics in Spanish Population
Authors: Raul Cordoba, María Socorro Rodriguez-Pinilla, Narvaez Javier, Fina Climent, Joaquin Sanchez, Carlos Perez Seoane, Javier Lopez Jimenez, Monica Garcia Cosio, Dolores Caballero, Óscar Javier Blanco Núñez, Cecilia Carpio, Josep Castellvi, Antonio Martinez Pozo, Ivan Dlouhy, Angeles Bendaña, Carlos Aliste, Ana Julia Gonzalez, María Soledad Fernandez, Sonia González de Villambrosia, Miguel A. Piris, Jose Gomez Codina, Empar Mayordomo, Belén Navarro, Carmen Bellas, Guillermo Rodríguez, Juan José Borrero, Ana Ruiz-Zorrilla, Carmen Montoto
Journal: Blood (2018)
Prognostic scores after resection of colorectal liver metastases: Has the picture changed?
Authors: Frank Ulrich, Teresa Schreckenbach, Guido Woeste, Patrizia Malkomes, Andreas Schnitzbauer, Wolf O. Bechstein
Journal: Journal of Clinical Oncology (2014)

e14519 Background: The clinical risk scores (CRSs) described by Nordlinger and Fong have been widely used to predict the outcome of patients with colorectal liver metastases (CRLM) after liver resection. Both scores were developed before neoadjuvant chemotherapy of CRLMs was introduced into clinical practice. This study investigated whether the two CRSs were able to predict overall survival (OS) in patients with CRLM with or without neoadjuvant chemotherapy prior to resection. Methods: Between August 2002 and October 2011 all patients undergoing liver resection for CRLM were retrospectively analyzed: 114 patients received neoadjuvant chemotherapy (group A) while 70 patients did not (group B). The database comprises data on age, gender, primary tumor site and stage, time between detection of primary cancer and CRLM, localization, number and size of CRLM, extent and duration of resection, carcinoembryonic antigen (CEA) levels, resection margin, complications and follow up. CRSs were calculated for both groups and compared. Results: A total of 184 patients underwent complete (R0) resection of CRLM during the study period. The median age was 63 (range 34 – 85) years and the median follow up was 24 (range 0 – 107) months. The median OS of the entire study population was 52 (95% CI 44 – 59) months (mo). Group A demonstrated a median OS of 52 (95% CI 36 – 67) mo compared to 47 (95% CI 43 – 69) mo in group B. The Fong score was prognostic only for those patients, who did not receive neoadjuvant chemotherapy (group B) (P = 0.02). It was not prognostic in group A, showing a median OS of 59 mo (95% CI 33-84) in the low risk group and 52 mo (95% CI 0-113) in the high risk group (P = 0.69). The Nordlinger Score was not prognostic in either group. Comparing the risk score groups of patients, receiving neoadjuvant chemotherapy revealed a median survival of 50 mo in the low risk group and 52 mo in the intermediate and high risk group(P = 0.71). Conclusions: The CRSs of Fong and Nordlinger are not reliable prognostic tools in patients undergoing neoadjuvant chemotherapy before liver resection. In our study, the Fong Score was prognostic for patients without neoadjuvant chemotherapy only. The Nordlinger Score seems to be no longer of prognostic value in the age of modern chemotherapy.
The Lysine-Specific Demethylase 1 (LSD1) Inhibitor Tranylcypromine (TCP) in Combination with ATRA Is Tolerable and Has Anti-Leukemic Activity in Adult Patients with Relapsed/Refractory AML and MDS
Authors: Justin M Watts, Terrence J Bradley, Amber Thomassen, Yvonne Trang Dinh, Dalissa Tejera, Kristen Englund, Sorab Boga, Randy Astaiza, Charles J Chen, Malika Abdur-Rahman, Marinescu Ion, Aymee Perez, Masoumeh Tayari, Lluis Morey, Maria E. Figueroa, Ramin Shiekhattar, Arthur Zelent, Ronan Swords
Journal: Blood (2018)
A multicenter randomized study comparing temozolomide (TMZ) versus TMZ-plus-bevacizumab (BEV) before standard treatment in unresectable glioblastoma (GBM) patients (p): The GENOM 009 study by the GEINO group.
Authors: Carmen Balana, Ramon De Las Penas, Juan Manuel Sepúlveda, Miguel J. Gil Gil, Raquel Luque, Oscar Gallego, Gaspar Reynes, Ana Herrero, Pedro Pérez-Segura, Alfonso Berrocal, Jose Maria Vieitez de Prado, Almudena Garcia, Sergio Vazquez-Estevez, Sergi Peralta, Isaura Fernandez, Maria Martinez Garcia, Cristina Carrato, Carolina Sanz, Salvador Villà
Journal: Journal of Clinical Oncology (2014)

2028 Background: We compared the efficacy and safety of treatment with TMZ or TMZ+BEVprior to and concomitant with radiotherapy in unresectable(GBM) patients. Methods: Between December 2009 and April 2013, p with unresectable GBM, PS<3 and MMS ≥25 were randomly assigned to receive eitherTMZ (85 mg/m², days 1–21, for 2, 28-day cycles), followed by standard TMZ with concomitant radiotherapy (60Gy) and then adjuvant TMZ for 6 cycles (TMZ Arm), or the same regimen but with the addition of BEV (10mg/kg /15 days) during pre-radiotherapy and concomitant treatment (BEV Arm). The primary endpoint was response according to RANO criteria after the 2 pre-radiotherapy cycles.The study was powered to detect a 30% difference between arms (α and β errors of 0.05 and 0.20). Secondary endpoints included toxicity, neurological deterioration before radiation, progression-free survival (PFS), overall survival (OS) and 1-year survival. Results: 103 p were registered and 93 randomized – 45 to the TMZArm and 48 to the BEV Arm.Partial response (PR) was attained in 7.1% of p in the TMZ Arm vs 25.6% in the BEVArm(P=0.001), and clinical benefit (PR + stable disease) in 26.1% vs 65%, respectively Neurological deterioration before radiotherapy was more frequent in the TMZ Arm (48.9% vs 20.8% of p; P=0.004). PFS was 2.2 months (m) in the TMZ Arm vs 4.8 m in the BEV Arm (HR, 0.79; P=0.29). OS was 7.7 m vs 10.8 m (HR, 0.71; P=0.12) and 1-year survival was 29.6% vs 48.9% (HR, 0.60; P=0.06), respectively. MGMT methylation was an independent prognostic factorfor longer PFS (P=0.01), OS (P=0.001) and 1-year survival(P=0.004). More toxicities occurred in the BEV Arm, but a significant difference was observed only for stomatitis (P=0.02). Conclusions: The primary endpoint was met. The response rate was significantly higher in the BEV Arm. A tendency towards improved PFS, OS and 1-year survival was also observed in the BEV Arm, but the trial was not powered to detect statistical significance for these outcomes.TMZ+BEV is a feasible and effective option for unresectable GBM p. Clinical trial information: NCT01102595.
Abstract 18447: Peri-operative Atrial Fibrillation (POAF) Complicating Non-cardiothoracic Surgery: A Systematic Review
Authors: Joshua Wenner, Karan Bami, Himabindu Samardhi, Pablo Nery, David Birnie, Girish Nair, Calum Redpath
Journal: Circulation (2015)

Introduction: More than 37 million non cardiothoracic operations are performed in the USA per annum. Single studies have reported that peri-operative atrial fibrillation (POAF) complicates non-cardiac surgery in ≤12% of patients. It is not clear if POAF is associated with adverse outcomes. Purpose: We conducted a systematic review to determine the frequency and implications of POAF. Methods: We conducted a literature search of MEDLINE, Embase, HTA, Cochrane, and Pubmed databases. We defined POAF as a single episode of AF confirmed by ECG within 30 days of non cardiothoracic surgery. Inclusion criteria were published manuscripts and abstracts containing patient level information. We excluded studies which were not published in English, described cardiothoracic surgery, were missing patient-level AF data or included patients aged &lt;18 years. Results: Our search produced 4445 publications, from which 716 abstracts and 534 manuscripts were identified for review. After applying inclusion/exclusion criteria, 225 manuscripts were analysed. Combining all studies, POAF occurred in 18789/650120 patients (2.9%, n=172, median [IQR] 2.2% [0.9-5.8]). Among 37 prospective studies, POAF occurred in 517/10990 patients (4.7%, n=37, 3.23% [1.0-8.8]). AF was prospectively identified pre-op in 875/26596 (3.3%, n=18, 9.0% [5.5-13.1]) and post-op in 472/14719 (3.2%, n=18, 8.8% [5.5-13.0]). In 135 retrospective studies, POAF occurred in 18272/639130 patients (2.9% n=135, 2.13 [0.8-4.4]). In retrospective analyses, AF was pre-existent in 49756/2440489, (2.0%, n=44, 6.7% [4.3-13.1]) and de novo in 12043/1641875, (0.7%, n=23, 6.0% [1.6-12.3]). Stratifying by surgery type, POAF was most common in vascular (104/1380, 7.5%), followed by orthopaedic (128/2384, 5.4%), and neurosurgical (197/4390, 4.5%) patients. Patient outcomes were not systematically reported: at 1 year, mortality occurred in 927/4136 (22.4%) POAF patients, compared to 8498/63746 (13.3%) non-POAF patients (n=7). Conclusions: POAF occurred in 2.9% of 650120 patients and was associated with a 68% increase in mortality. Prospective research is required to determine whether any specific intervention(s) in POAF patients will improve outcomes.
Intake of alternative medicine during cancer treatment and possible drug interactions.
Authors: Elena Tenti, Andrea Casadei Gardini, Sebastiano Cumero, Martina Minguzzi, Flavia Foca, Dino Amadori
Journal: Journal of Clinical Oncology (2014)

e13540 Background: The number of cancer patients who undergo conventional anticancer treatment and take alternative medicines at the same time is increasing. This present study aimed to determine how widespread this practice is and to predict potential interactions between natural substances and conventional anticancer drugs Methods: One hundred and forty-three patients undergoing cancer treatment at our institute were interviewed to collect information on socio-demographic characteristics, cancer-related characteristics (site of disease), anti-cancer drugs received, intake of nervine substances, smoking habits, and use of non-conventional medicines. Results: 83.2% of patients reporting taking nervine substances on a daily basis, 35.7% took vitamin supplements or minerals, 22.4% took medicinal herbs and 4.9% took homeopathic remedies. 75% of patients using medicinal herbs were younger than 64 years and 78.1% had an average higher level of education (senior high school diploma, degree, doctoral degree). Conclusions: In our study, a significant number of cancer patients undergoing treatment with conventional anticancer drugs also took non-conventional medicines, mainly medicinal herbs. Although relatively few studies have analysed the properties of the herbs in question or their potential pharmacokinetic interactions and pharmacodynamics with the anticancer drugs administered, results obtained indicate a high probability of such interactions.
“Capacity”, “best interests”, “will and preferences” and the UN Convention on the Rights of Persons with Disabilities
Authors: George Szmukler
Journal: World Psychiatry (2019)

The United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD) is the most up‐to‐date international legal instrument concerning the rights of persons with disabilities. Such persons are taken to include those with serious mental disorders. According to an authoritative interpretation of a crucial Article (Article 12 ‐ Equal recognition before the law) by the UN CRPD Committee, involuntary detention and treatment of people with mental health disabilities are prohibited under the Convention. Both conventional mental health law and “capacity‐based” law are deemed to violate the Convention. However, some other UN bodies are not in full agreement (for example, the UN Human Rights Committee and the Subcommittee on Prevention of Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment), while others are less explicitly absolutist (for example, the Human Rights Council). Furthermore, strong criticisms of the position of the CRPD Committee have been mounted from a number of academic quarters. These criticisms center on whether the role of a person's ability to make a decision can be ignored, no matter the circumstances. Much of the above debate turns on the concept of “legal capacity” and the now often‐repeated precept that one must always respect the “will and preferences” of the person with a disability. However, “will and preferences” remains undefined. In this paper, I offer an analysis of “will and preferences” that can clarify interventions that may be acceptable or non‐acceptable under the terms of the UN Convention.
Racial/ethnic (RE) differences in the occurrence of HER2 and hormone receptor (HR)-defined breast cancer (BC) in California (CA).
Authors: Scarlett Lin Gomez, Lisa Wang, Laura Chu, Marjorie C. Green, Chunyan Song, Lisa M Moy, Juan Yang, Li Tao, Christina A Clarke
Journal: Journal of Clinical Oncology (2014)

634 Background: RE disparities in the occurrence and mortality of BC are long-standing and persistent. Examining differences in the occurrence of molecularly-defined BC subtypes by RE can inform reasons for its unequal burden and point to better targeted strategies for prevention.Objective: To describe BC subtype occurrence by RE in a contemporary, population-based cohort. Methods: We examined demographic and clinical factors associated with prevalence of 4 BC subtypes (HER2Neu, HR [based on estrogen and progesterone receptor status]) by RE among all female CA residents diagnosed with primary invasive BC between 1/1/2005 and 12/31/2011 in the California Cancer Registry. Results: A total of 131,450 BC pts (59.0% HR+/HER2-, 10.4% triple-negative (TN), 9.9% HR+/HER2+, 5.0% HR-/HER2+, and 15.6% unclassified) were identified. TN BC was substantially more likely to be diagnosed among Blacks and Hispanics (19.8% and 12.9%, respectively) than Whites and Asians/Pacific Islanders (API) (9.2% and 8.5%, respectively). However, HER2+ BC was more likely to be diagnosed among APIs than other RE groups (19.4% vs. 13-18%). TN and HER2+ BC were more common among women living in lower socioeconomic status (SES) neighborhoods (Table 1). These associations persisted in multivariate polytomous regression analysis adjusted for year, age, stage, grade, histology, marital status, and insurance status. Conclusions: The distribution of breast cancer subtypes vary markedly by RE and SES, with minority RE and low SES populations being more likely to have subtypes associated with worse survival. Distributions of BC subtypes by RE and SES, CA, 2005-2011. BC subtype (N=131,450) Total HR+/HER2+ n=13053 HR-/HER2+ n=6630 HR+/HER2- n=77577 TN n=13692 Unclassified n=20498 Race/ethnicity Non-Hispanic White 9.0% 4.2% 62.3% 9.2% 15.3% 82,242 Black 10.9% 5.4% 48.1% 19.8% 15.8% 8,255 Hispanic 11.5% 6.4% 53.9% 12.9% 15.4% 23,330 API 12.1% 7.3% 56.2% 8.5% 15.9% 15,878 Other 8.8% 4.0% 48.9% 7.6% 30.7% 1,745 SES quintile 1st (low) 10.9% 6.3% 51.3% 12.6% 19.0% 16,774 2nd 10.3% 5.5% 55.7% 11.3% 17.3% 22,959 3rd 9.9% 4.9% 58.4% 10.6% 16.1% 26,932 4th 9.8% 4.9% 60.7% 9.9% 14.7% 30,746 5th (high) 9.4% 4.3% 64.1% 9.0% 13.2% 34,039