tbuckley/cabot-search huggingface dataset:
Critical Issues in Surgical Approach and Isolation Site for Islet Autotransplantation
Authors: Chirag S. Desai, Khalid M. Khan
Journal: JAMA Surgery (2017)

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Is PET scan conversion from positive to negative a prognostic indicator for patients receiving therapy for unresectable liver metastases from colorectal carcinoma (CRC)?
Authors: G. J. Maddox, J. F. Chou, M. Capanu, D. Patel, M. I. D'Angelica, N. E. Kemeny
Journal: Journal of Clinical Oncology (2011)

e14053 Background: Studies suggest preop PET can exclude extrahepatic disease and improve survival in patients (pts) who can undergo liver resection; however, the role of PET conversion as a prognostic test is less clear. Methods: 34 pts with unresectable liver metastases from CRC were treated with HAI FUDR + systemic therapy (56% were previously treated). FDG PET scans were done at baseline (all pts were positive) and at 3 months. Overall survival (OS) and progression free survival (PFS) were calculated from date of first treatment to date of progression or death: Kaplan-Meier method used. To correlate PET and CEA with survivals, OS and PFS were calculated from date of first follow-up PET scans and compared by log-rank test. Correlation between PET and resectability was examined by Fisher-Exact Test. Results: Median OS was 37.4 months (95% CI: 21.4-NA) for entire group (including unresected pts). Two-year OS for all pts with conversion to negative PET (SUV <3) was 89% vs 59 % if PET still positive (p=0.0469). Two year PFS 37% vs 8%, for conversion to negative vs still positive PET, respectively (p=0.1326). The correlation between CEA and OS and PFS was not significant (p=0.422). 18/34 (53%) pts were resected. Conversion to PET negative was seen in 44.4% of resected pts and 37.5% of non-resected pts (p=0.73). Of the 4 who recurred in the liver, 3 had positive PET prior to resection and in 2/4 who reoccurred outside of the liver PET remained positive. 10/18 (56%) of resected pts are NED, and 5 had a negative PET prior to resection. 17/18 pts resected are still alive and PFS was the same whether PET positive or negative. CEA reduction to ≤ 5 was achieved in 50% of resected pts and in 25% non-resected pts (p=0.17). Conclusions: For patients with unresectable CRC liver mets receiving (HAI + SYS) those whose PET scan becomes negative have a longer survival, 89% (95% CI:43-98) at 2 years, versus 59% (95%CI 29-79) for those who do not convert to a negative PET. 1 year (%) 2 year (%) P value Survival (all pts) 93 70 PET negative/positive 100 / 84 89 / 59 0.0469 CEA ≤ 5 / > 5 100 / 84 78 / 66 0.2065 PFS ( all pts) 58 25 PET Negative / Positive 61 / 42 37 / 8 0.1326 CEA ≤ 5 / > 5 48 / 53 29 / 10 0.4222
Response to Tyrosine Kinase Inhibitors Therapy and Donor Lymphocyte Infusion In Patients with Chronic Myelogenous Leukemia Relapsing After Allogenic Hematopoietic Stem Cell Transplantation.
Authors: Malgorzata Sobczyk-Kruszelnicka, Tomasz Czerw, Anna Waclawik, Ryszard Wichary, Wlodzimierz Mendrek, Slawomira Kyrcz-Krzemien
Journal: Blood (2010)
Identification of risk factors for stage II colon cancer.
Authors: Sho Sawazaki, Manabu Shiozawa, Koji Numata, Masakatsu Numata, Teni Godai, Naoto Yamamoto, Soichiro Morinaga, Yasushi Rino, Munetaka Masuda, Makoto Akaike
Journal: Journal of Clinical Oncology (2013)

375 Background: The use of adjuvant chemotherapy remains controversial in Stage II colon cancer. However, patients with specific clinicopathological features are thought to have high risk for recurrence. The aim of this study was to identify the subgroup of patients at great risk, by investigating the clinicopathological features associated with poor survived in Stage II. Methods: A total of 282 patients with Stage II colon cancer who underwent curative resection from January 1990 to September 2007 at Kanagawa Cancer Center were enrolled. Then, the clinicopathological data of the patients were retrospectively evaluated. Disease-free survival rates were calculated by the Kaplan-Meier method, and survival curves were compared by the log-rank test. Cox’s regression analysis was used for multivariate analyses. P values &lt;0.05 were considered to be statistically significant. Results: The median follow up was 62.5 months. The 5-year disease-free survival was 92.2% in the study group as a whole. Among the recurrent patients (n=23), the most recurrent site was the liver (n=11, 44%), followed by lung (n=6, 24%), and peritoneum (n=5, 20%). Univariate analysis for 5-year disease-free survival identified two factors; tumor diameter (&gt;5cm vs…5cm, p=0.018), and lymphatic invasion (p=0.009). Multivariate analysis for 5-year disease-free survival identified two independent factors; tumor diameter (hazard ratio [HR], 4.82; 95% CI, 1.55-15.0; p=0.006), and lymphatic invasion (HR, 4.15; 95% CI, 1.68-10.2; p=0.002). The 5-year disease-free survival differed significantly among patients with neither of these prognostic factors (98.6%), those with only 1 factor (93.3%), and those with 2 factors (76.6%, p=0.000). Conclusions: Patients with stage II colon cancer who have both 5cm in diameter and lymphatic invasion are at high risk for recurrence. The use of adjuvant chemotherapy should be considered in this subgroup of patients.
STAT-3 and Β-catenin expression in metastatic clear cell renal cell carcinoma (mRCC).
Authors: Aline Fusco Fares, Isabela Cunha, Daniel Vilarim Araujo, Leonardo de Azevedo Boente, Daniel Garcia, Jose A. Rinck, Maria Nirvana Cruz Formiga
Journal: Journal of Clinical Oncology (2016)

583 Background: In mRCC, there are no prospectively validated biomarkers to guide the treatment and therapy decision is based on prognostic scores and histology. STAT-3 and Wnt/b-cateninare cell proliferation pathways and have already been related to prognostic in renal cell carcinoma. Objective: to evaluate the role of STAT-3 and b-catenin expression as prognostic biomarkers in clear cell mRCC. Methods: 684 medical records of renal cell carcinoma patients treated at AC Camargo Cancer Center from 2007 to 2015 were reviewed. 86 out of 684 patients fulfilled the study criteria: metastatic clear cell carcinoma, no sarcomatoid features, previous systemic therapy, previous nephrectomy and available tumor specimens from metastatic site. Pathological samples were arranged in a TMA. The number of positive stainings cells for each antibody in each core was categorized as low positive or negative versus highly positive expression. Results: We had available tissue blocks from 47 tumors. 32/45 patients (71,1%) had highly positive membrane b-catenin and none of the patients was positive for nuclear b-catenin. 27 /45 (60%) were categorized as low positive or negative STAT-3. There was no statistically significant association between STAT-3 and b-catenin expression with clinical prognostic criteria (MSKCC and Heng criteria). In the multivariate analysis, KPS &lt; 80% (p = 0.02; HR: 2.7), time from nephrectomy to metastasis &lt; 1 year (p = 0.04; HR: 2.1), no hypothyroidism (p = 0.05; HR: 2.4) and MSKCC criteria (p = 0.02; HR: 2.5) were confirmed as negative prognostic factors. Associative analysis showed that none of the patients with negative membrane b-catenin had response to systemic therapy (p=0.02). OS was 35.5 months (IC 22.2-48.8) and PFS was 12.5 months (IC 10.0-14.0). Conclusions: in our cohort, STAT-3 and B-catenin expression are not associated with the prognostic criteria (MSKCC and Heng). The loss of B-catenin expression is associated to a worse response rate to antiangiogenic therapy in metastatic clear cell renal cancer. [Table: see text]
Genomic landscape of metastatic platin-resistant urothelial cancer patients.
Authors: Yohann Loriot, Christophe Massard, Celine Lefebvre, Semih Dogan, Elena Ileanaecaterina, Ludovic Lacroix, Bastien Job, Maud Ngo-camus, Karim Fizazi, Nathalie Auger, Catherine Richon, Valerie Koubi-Pick, Antoine Hollebecque, Thierry De Baere, Philippe Vielh, Marie-cecile Ledeley, Gilles Vassal, Alexander M. Eggermont, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2015)

316 Background: Although several studies have reported genomic characterisation of primary urothelial carcinoma (UC), little is known about the genomic alterations of the metastatic cisplatin-resistant UC. We sought to define the prevalence and co-occurrence of actionable genomic alterations in patients with metastatic cisplatin-resistant lethal UC. Methods: Patients with metastatic UC, who progressed after at least one line of standard therapy, were enrolled in a prospective molecular screening trial (MOSCATO 01) at Gustave Roussy. CT-Scan or ultrasound-guided biopsies were performed in metastases to carry out a comprehensive molecular characterization. DNA was extracted from fresh tumor samples and analyzed by comparative genomic hybridization (CGH) (≥ 30% tumor cells) and by Next Generation Sequencing (NGS) for up to 74 target genes (≥ 10% tumor cells). Whole-exome (WES) and RNA seq sequencing were performed retrospectively in selected cases. Results: From 12/2011 to 12/2013, 30 heavily pretreated patients with metastatic UC were included. Median age was 61 (37-73); all patients had been treated with platin-based chemotherapy with a median number of lines of 2.5 (1-5). A tumor biopsy could be performed in 26 patients (87%). CGH and targeted exome sequencing profiles were assessed in 19 (73%) and 23 (88%) of them, respectively. A total of 19 patients (73%) were profiled for both sequencing and CGH. WES and RNA seq was performed in 16 (62%) pairs of metastatic tissue and normal DNA (Integragen Inc, Hiseq platform). Our analyses identified potential therapeutic targets in 61 % of the tumours, including 31% with targets in the PI3K/AKT/mTOR pathway, 35% with targets in the FGF/FGFR pathway and 15% with targets in the RTK/MAPK pathway (including ERBB2). Others frequent aberrations were found in the chromatin regulatory genes (MLL gene family) and cell-cycle regulatory genes (E2F3, CDKN2A/B genes). FGFR gene fusions were found in 1 out of 16 screened patients (6%) Conclusions: Lethal platin-resistant UC exhibit high-level of genomic heterogeneity. The majority of these tumors harbour actionable genomic alterations that can be targeted with selective agents currently in clinical development (phase I trials) or registered.
Efficacy and safety of FOLFOX biweekly cetuximab as first-line therapy for patients with nonresectable metastatic colorectal cancer (CELINE trial): Multicenter phase II trial.
Authors: Ken Kondo, Masanori Kotake, Kenji Doden, Yoshinori Munemoto, Kenji Kobayashi, Genichi Nishimura, Kazuhiko Omote, Junichi Sakamoto
Journal: Journal of Clinical Oncology (2014)

645 Background: Efficacy and safety of FOLFOX{Bi-weekly cetuximab as first-line therapy for patients with nonresectable metastatic colorectal cancer (mCRC) were examined. Methods: The multicentre phase II trial had began from September 2011. Inclusion criteria were an age of 20 years or older, adenocarcinoma of the colon or rectum, first occurrence of metastatic disease with KRAS wild type tumor that could not be resected, performance status score (ECOG) of 1 or less, and adequate hematologic, hepatic, and renal function. Patients received mFOLFOX6/Cetuximab 500 mg/‡u/biweekly 120min until PD, unacceptable adverse effects, or withdrawal of consent occurred. In the event of grade 2 adverse effects, suspension of Oxaliplatin only was permitted. Primary endpoint was Response Rate, secondary endpoint was anti-tumor effect at week 8, PFS, OS, safety, and efficacy of 5-FU{LV{Cetuximab therapy. Results: 60 patients were screened and 59 underwent the treatment by March 2013. Age 64.5 (38-82), male/female: 47/13, PS 0/1: 51/9, rectal/colon: 31/29 and metastasis in liver/lung/ lymph node/ the other: 51/15/19/7. Data had been analyzed to date showed high response rate, 64% with disese control in 96% -PR 38pts (64%), SD 19 pts (32%). Incident rate of grade 3 or 4 adverse events were neuropenia 19%, peripheral sensory neuropathy 4.8% and rash 8.1%. Conclusions: FOLFOX{Bi-weekly cetuximab therapy benefited in safety administration with high response rate. Therefore it can be considered as a beneficial treatment. Clinical trial information: UMIN000006402.
Breast surgeons' attitudes towards bilateral risk-reducing mastectomy: A National Survey of American Surgeons.
Authors: Narendra Nath Basu, Mariska Den Heijer, Christi J van Asperen, Hilary Harris, Irmgard Nippert, Joerg Schmidtke, Anne Deborah Bouhnik, Claire Julian-Reynier, Peter D. Beitsch, Aad Tibben, James Hodson, D. Gareth Evans
Journal: Journal of Clinical Oncology (2015)

25 Background: Bilateral risk-reducing mastectomy (BRRM) confers the greatest risk-reduction in women at high-risk of developing breast cancer. Uptake of BRRM is influenced by the attitudes of these women as well as the breast surgeons offering these procedures. We surveyed surgeon members of the American Society of Breast Surgeons to assess their attitudes and knowledge. Methods: An International Cancer Risk Communication Study (InCRisC) questionnaire, previously used to assess attitudes of European physicians and surgeons was sent to 2648 members. Personal and occupational characteristics were recorded and knowledge of cancer genetics and attitudes to BRRM were assessed using clinical vignettes. Results: 439 breast surgeons responded. 98% of surgeons actively took a family history of the father. Almost 100% of surgeons reported a positive attitude towards BRRM. Female surgeons and those treating greater than 100 breast cancers a year were predictors of knowledge of breast cancer genetics and a positive attitude towards BRRM. Conclusions: Multiple factors contribute to surgeons' attitudes towards BRRM. Gender of surgeon and workload contribute to theses observed variations.
Gene Expression Profiling in the Classification of Acute Leukemia Brazilian Patients
Authors: Carolina Pereira de Souza Melo, Catharina Brant Campos, Alvaro Pimenta Dutra, Angelo Atalla, Mara Albonei Dudeque Pianovski, Edna Kakitani Carbone, Luciana Quintão Lares, Hélio Moraes Souza, Shirlei Octacilio Silva, Alessandro Clayton de Souza Ferreira, Juliana Godoy Assumpcao
Journal: Blood (2014)
Burden of high-risk oral HPV infection in men in the United States and implications for oropharyngeal cancer screening: NHANES (1999-2012).
Authors: Erin Dunn, Kevin J. Moore, Tulay Koru-Sengul
Journal: Journal of Clinical Oncology (2015)

55 Background: In men high-risk human papilloma viruses (HPVs) have been implicated in causing cancer of the penis, anus, and oropharynx. HPV infection, specifically HPV 16, is currently one of the most common causes of oropharyngeal cancer. National population-based surveys provide estimates of population-specific prevalence, trend, and determinants to identify the burden of high-risk HPV in the oropharynx of men. Methods: We calculated HPV infection prevalence by oral testing in the US from 1999-2012 National Health and Nutrition Examination Survey (NHANES) to obtain a representative sample of non-institutionalized civilian population. We provided epidemiology of HPV infection for both females and males with prevalence estimates, unadjusted odds ratio (OR) with 95% confidence interval (95%CI). Analysis was performed by SAS v9.3 with complex sampling design. Results: Among HPV-positive persons, high-risk HPV infection (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) was more prevalent for men (79.4%) than for women (20.6%). Men also had the highest prevalence for each high-risk type tested. Notably, men held 84.9% of the HPV 16 burden, which has the highest risk for orophargyngeal cancer. Mexican-American men had lower odds of high-risk HPV infection than White men (OR=0.47; 95%CI=0.261, 0.86). Further, divorced/separated/widowed men had lower (0.48; 0.26, 0.88) and never married men had greater (1.76; 1.01, 3.07) odds of high-risk HPV compared to men who are married/living with partner. Conclusions: Using a large population-based survey, our results show increased prevalence of high-risk HPV infection in men. Stratification by ethnicity and marital status will increase understanding and awareness of the burden and demographic disparities of potentially oncogenic HPV infections in men and may provide a base for culturally and gender competent oropharyngeal cancer screening programs. Recognizing demographic disparities and behaviors could guide further research into risk factors and conditions that guide the prevalence of HPV infection and oropharyngeal cancer in specific male populations.
A phase I pharmacokinetics trial comparing PF-05280014 (a potential biosimilar) and trastuzumab in healthy volunteers (REFLECTIONS B327-01).
Authors: Donghua Yin, Kerry B Barker, Ruifeng Li, Xu Meng, Steven D Reich, Alejandro D Ricart, Dan Rudin, Carrie T Taylor, Charles M. Zacharchuk, Arne G Hansson
Journal: Journal of Clinical Oncology (2013)

612 Background: PF-05280014, a proposed biosimilar to trastuzumab, has an identical amino acid sequence and similar physicochemical and in vitro functional properties to trastuzumab. This study was designed to demonstrate PK similarity of PF-05280014 to trastuzumab from the US (trastuzumab-US) and EU (trastuzumab-EU), and between the licensed drugs. Safety and immunogenicity were also evaluated. Methods: In this double-blind trial (NCT01603264), 105 healthy male volunteers, 18-55 years old were randomized 1:1:1 to receive a single 6 mg/kg IV dose of PF-05280014, trastuzumab-US or trastuzumab-EU. All subjects provided informed consent. PK, safety, and immunogenicity assessments were conducted for 70 days. PK similarity for a given test-to-reference comparison was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to the last time point (AUC T ) and maximum concentration (C max ) were within 80% – 125%. Results: The baseline demographics for the 101 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar characteristics of target-mediated disposition and similar PK parameters (Table). The 90% CI for the ratios of C max , AUC T , and AUC 0-∞ were within 80% – 125% for the comparisons of PF-05280014 to trastuzumab-EU or trastuzumab-US, and trastuzumab-EU to trastuzumab-US. Adverse events (AE) were similar for the 3 arms with treatment-related AEs reported by 71.4%, 68.6%, and 65.7% subjects in the PF-05280014, trastuzumab-EU and trastuzumab-US, respectively. No serious AEs were reported. Only 4 subjects had treatment interruptions; 2 discontinued. Only 1 subject (trastuzumab-EU) developed anti-drug antibodies after dosing. Conclusions: This study demonstrates PK similarity of PF-05280014 to both trastuzumab-US and trastuzumab-EU and of trastuzumab-EU to trastuzumab-US. The three study drugs also showed similar safety profiles. Clinical trial information: NCT01603264. [Table: see text]
Sorafenib and irinotecan combination for pre-treated RAS-mutated metastatic colorectal cancer patients: A multicentre randomized phase II trial (NEXIRI 2).
Authors: Emmanuelle Samalin, Christelle De La Fouchardiere, Simon Thezenas, Valérie Boige, Hélène Senellart, Rosine Guimbaud, Julien Taïeb, Eric Francois, Marie-Pierre Galais, Antoine Adenis, Astrid Lievre, Jean-François Seitz, Jean-Philippe Metges, Olivier Bouche, Marianne Fonck, Frédéric Di Fiore, Pascal Artru, Thomas Aparicio, Thibault Mazard, Marc Ychou
Journal: Journal of Clinical Oncology (2016)

635 Background: Sorafenib and irinotecan (NEXIRI regimen) showed promising activity with a disease control rate (DCR) of 65% in heavily pretreated mutated (mt) KRAS metastatic colorectal cancer (mCRC) patients in a phase I/II trial (Samalin et al. 2014).This multicentre randomized phase II trial aimed to determine the 2-month progression-free survival rate (2-PFS) of NEXIRI versus irinotecan or sorafenib monotherapy in mtRAS mCRC patients after failure of all approved active drugs at the time of the study. Methods: Patients PS ≤ 1 with progressive measurable and non-resectable mtKRAS (then RAS) mCRC pre-treated with irinotecan, oxaliplatin, fluoropyrimidines and bevacizumab (none regorafenib), were randomized in 3 arms: NEXIRI (irinotecan IV 120 (C1), 150 (C2) and 180mg/m² (C3) if diarrhea grade &lt; 1 in a biweekly regimen combined with a fixed dose of sorafenib, 400mg twice daily) versus irinotecan alone (180mg/m²) versus sorafenib alone until progression or toxicity, with cross over to NEXIRI at progression for the monotherapy arms. The primary endpoint was the 2-PFS (RECIST v1.1). Pharmacokinetic, pharmacogenetics and pathologic translational studies were undertaken. Results: We included 173 patients (median age 62 [31-82]; PS 0/1: 38/61%) between 2012/09 and 2014/07 in 17 French centres. Main results are shown below (median follow-up 17.5 months). Conclusions: We confirmed the NEXIRI regimen efficacy in a randomized study for refractory mtRAS mCRC patients. These results justify comparing this combination to regorafenib or TAS 102 monotherapies in this population. Ancillary studies are ongoing to identify biomarkers. Clinical trial information: NCT01715441. [Table: see text]