tbuckley/cabot-search huggingface dataset:
Clinical features and survival among patients with standard-onset versus early-onset colorectal cancer by age groups.
Authors: Ana Acuna Villaorduna, Nishi Shah, Sanjay Goel
Journal: Journal of Clinical Oncology (2019)

3614 Background: Colorectal cancer (CRC) incidence is increasing in patients younger than 50 years old. Currently, there are discordant recommendations regarding CRC screening: while the American Cancer Society favors to start at age 45, the National Comprehensive Cancer Network and the US Preventive Task Force suggest starting at age 50. This study is aimed to compare the incidence, clinical characteristics and survival of patients diagnosed with standard-onset CRC (SO) versus early-onset colorectal cancer by age-groups. Methods: Patients diagnosed with CRC at ages older than 35 were identified using the SEER registry and categorized into four groups based on age at diagnosis. EO1 (35-39), EO2 (40-44), EO3 (45-49) and SO (&gt;50) years, respectively. Incidence, clinical features and survival were compared among groups. Results: 178 678 patients were identified. 9.2% were diagnosed before 50 years. Of these, 1.4%, 2.8% and 5.1% were EO1, EO2 and EO3; respectively. Patients with early-onset CRC (EO) had higher frequency of Hispanics (13.9% vs. 8.4%, p&lt;0.01), stage IV (24.8% vs. 17.3%, p&lt;0.01), left-sided tumors (74.1% vs. 56.9%, p&lt;0.01) and better survival compared to SO. Among EO groups, the frequency of poor/anaplastic grade was inversely proportional to age; stage IV was similar between EO2 and EO3 and lower in EO1. Black race, grade and stage were predictors of mortality for all EO groups; laterality was a mortality predictor in EO2 and EO3. Conclusions: EO-CRC and SO-CRC have different pathological features that should be considered for CRC screening. Higher rates of stage IV disease are encountered in patients between 40-49 years old; hence early screening should be considered. Given higher rates of left-sided tumors, sigmoidoscopy might be an adequate tool for most patients with EO-CRC. [Table: see text]
Outbreak of Shiga toxin-producing Escherichia coli (STEC) O26 paediatric haemolytic uraemic syndrome (HUS) cases associated with the consumption of soft raw cow’s milk cheeses, France, March to May 2019
Authors: Gabrielle Jones, Sophie Lefèvre, Marie-Pierre Donguy, Athinna Nisavanh, Garance Terpant, Erica Fougère, Emmanuelle Vaissière, Anne Guinard, Alexandra Mailles, Henriette de Valk, Marc Fila, Corentin Tanné, Caroline Le Borgne, François-Xavier Weill, Stéphane Bonacorsi, Nathalie Jourdan-Da Silva, Patricia Mariani-Kurkdjian
Journal: Eurosurveillance (2019)

We report an outbreak of Shiga toxin-producing Escherichia coli (STEC) associated paediatric haemolytic uraemic syndrome linked to the consumption of raw cow's milk soft cheeses. From 25 March to 27 May 2019, 16 outbreak cases infected with STEC O26 (median age: 22 months) were identified. Interviews and trace-back investigations using loyalty cards identified the consumption of raw milk cheeses from a single producer. Trace-forward investigations revealed that these cheeses were internationally distributed.
Publisher Correction: Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability
Authors: Pirro G. Hysi, Ana M. Valdes, Fan Liu, Nicholas A. Furlotte, David M. Evans, Veronique Bataille, Alessia Visconti, Gibran Hemani, George McMahon, Susan M. Ring, George Davey Smith, David L. Duffy, Gu Zhu, Scott D. Gordon, Sarah E. Medland, Bochao D. Lin, Gonneke Willemsen, Jouke Jan Hottenga, Dragana Vuckovic, Giorgia Girotto, Ilaria Gandin, Cinzia Sala, Maria Pina Concas, Marco Brumat, Paolo Gasparini, Daniela Toniolo, Massimiliano Cocca, Antonietta Robino, Seyhan Yazar, Alex W. Hewitt, Yan Chen, Changqing Zeng, Andre G. Uitterlinden, M. Arfan Ikram, Merel A. Hamer, Cornelia M. van Duijn, Tamar Nijsten, David A. Mackey, Mario Falchi, Dorret I. Boomsma, Nicholas G. Martin, David A. Hinds, Manfred Kayser, Timothy D. Spector
Journal: Nature Genetics (2019)
Specialty Drug Pricing and Out-of-Pocket Spending on Orally Administered Anticancer Drugs in Medicare Part D, 2010 to 2019
Authors: Stacie B. Dusetzina, Haiden A. Huskamp, Nancy L. Keating
Journal: JAMA (2019)

This study describes point-of-sale prices for orally administered anticancer drugs offered through Medicare Part D and out-of-pocket changes in spending as a result of decreasing coinsurance and price changes between 2010 and 2019.
Exploratory analysis of the effect of taselisib on downstream pathway modulation and correlation with tumor response in ER-positive/HER2-negative early-stage breast cancer from the LORELEI trial.
Authors: Paolo Nuciforo, Dominik Hlauschek, Cristina Saura, Evandro de Azambuja, Roberta Fasani, Patricia Villagrasa, Karoline Muehlbacher, Christos Sotiriou, Aleix Prat, Georg Pfeiler, Florentine Hilbers, Timothy R. Wilson, Junko Aimi, Thomas Stout, Vicente Valero, Christian Fesl, Jose Baselga, Michael Gnant, Martine Piccart, Fabrice Andre
Journal: Journal of Clinical Oncology (2019)

1050 Background: Taselisib (T) is an oral, potent, selective inhibitor of Class I PI3-kinase with enhanced activity against PIK3CA mutant cancer cells. Results from the LORELEI trial have demonstrated a significant improvement in ORR (objective response rate) by centrally assessed magnetic resonance imaging in all randomized patients as well as in the PIK3CA mutant (MT) cohort treated with neoadjuvant T plus letrozole (L) compared to placebo (P) plus L. Here we present the results of exploratory analyses of selected pathway-related phosphoproteins. Methods: Baseline (BL) and week3 (W3) tumor biopsies were obtained from 334 patients enrolled in the trial. Phosphoproteins (pAKT, pPRAS40 and pS6) were analyzed by IHC. BL levels as well as changes from BL to W3 were correlated with response assessed either by ORR or cell cycle arrest (Ki67 at W3 &lt; 2.7%). Results: In the overall population, BL phosphoproteins levels were similar between the T and P arms. Higher pAKT (p &lt; 0.001) and pPRAS40 (p = 0.004) levels were observed in MT vs wild-type (WT), whereas the opposite result was found for pS6 (p = 0.03). Treatment-induced absolute changes of phosphoproteins adjusted for BL levels were not significantly different between the T and P arms in the overall population, except for pPRAS40 with higher decrease in the T arm (p = 0.014). After stratification for PIK3CA genotype, a significantly greater decrease in expression levels was observed for pPRAS40 (p &lt; 0.001) and pS6 (p = 0.020) in MT tumors treated with T. The treatment effects were not significantly different in the WT population. A trend for an association between decrease in pS6 levels at W3 and improved ORR was observed in the MT (p = 0.08) and T (p = 0.09) subgroups. The magnitude of pS6 suppression at W3 was higher in tumors achieving a cell cycle arrest in the MT/T subgroup (biserial correlation = -0.473). Conclusions: Exploratory analyses of phosphoproteins showed bioactivity of taselisib as indicated by downstream pathway suppression. Translational research aiming to integrate these results with additional exploratory biomarkers data is currently ongoing. Clinical trial information: NCT02273973.
Recovery of symptom burden and functioning for patients with late discharge after an open surgery for GYN tumors.
Authors: Charles S. Cleeland, Qiuling Shi, Larissa Meyer, Ting-Yu Chen, Araceli Garcia-Gonzalez, Maria Iniesta-Donate, Tsun Hsuan Chen, Donna Griffin, Xin Shelley Wang
Journal: Journal of Clinical Oncology (2019)

e18083 Background: The symptom burden and functional recovery of patients after hospital discharge is important to understand in order to provide more patient centered care. This study evaluated longitudinal quantitative patient-reported outcome (PRO) data using a validated PRO symptom and functional interference measure after hospital discharge from open gynecologic surgery. Methods: Patients with GYN tumors scheduled for laparotomy at MD Anderson Cancer Center were recruited prospectively. The MD Anderson Symptom Inventory gynecology perioperative care module (MDASI-PeriOp-GYN) was used to assess symptoms post discharge on Day 3, 7, and weekly up to 6 weeks. Median survival time and log-rank test was used for comparing time to return to no or mild level (≤3 in a 0-10 scale) of symptoms during the post discharge period between groups who discharged within and beyond the median length of stay (LOS) days. Results: From Feb 2018–Dec 2018, 83 patients were evaluable. The median LOS was 3 days. Compared to patients who were discharged within 3 days (70% of sample), 30% patients were discharged after 3 days after surgery (range of 4-10 days). Except distress, all other PROs on MDASI-PeriOp-GYN were not significantly different between the two groups on the day of discharge. However, those late discharged patients had significantly delayed recovery on fatigue (median recovery time &gt; 56 days vs. 17 days), dry mouth (10 days vs. 6 days) (both P&lt; .01), and drowsiness (12 days vs. 6 days, P&lt; .05). The recovery of physical functioning (MDASI general activity interference item) was prolonged among late discharged patients compared to patients who were discharge within 3 days ( &gt; 56 days vs. 30 days, P&lt; .01). Conclusions: Even though all patients were under a standardized Enhanced Recovery Program, about 30% of patients post GYN open surgery were discharged beyond the median LOS. Patients in this group continued to have delayed recovery after hospital discharge as evidenced by persistent fatigue and slower return of physical functioning. Implementation of post-discharge PROs may help identify patients at risk for prolonged recovery and help triage patients to more intensive supportive care.
Prognostic impact of mutation profiling in Chinese patients with colorectal liver metastases.
Authors: Kun Wang, Yadong Yang, Xiaoyu Zhang, Juan Li, Quan Bao, Hongwei Wang, Kemin Jin, Ming Liu, Wei Liu, Xiaoluan Yan, Lijun Wang, Xu Da, Baocai Xing
Journal: Journal of Clinical Oncology (2019)

e15157 Background: To investigate mutation profiling in Chinese patients with colorectal liver metastases and explore new prognostic biomarkers. Methods: We investigated 197 patients who underwent surgery for colorectal liver metastases at Beijing Cancer Hospital between January 2015 and February 2017. Tumor DNA was isolated from FFPE tissues from liver metastatic lesions. Mutation spectrum was obtained by targeted deep sequencing of 620 selected genes. Tumor mutational burden (TMB) was defined as the number of non-synonymous mutations per 1Mbp and divided into quartiles. MSI status was tested with next-generation sequencing. Studies of impacts of mutation status on disease-free survival (DFS) and overall survival (OS) were performed with Kaplan-Meier analysis. Results: Mutation significance analysis confirmed enrichment in colorectal cancer driver gene mutations of TP53, APC, KRAS, SMAD4, SOX9, FBXW7 and PIK3CA in 72%, 61%, 29%, 14%, 10%, 10% and 9% of liver metastases, with no BRAF mutation found in any of these patients. Additionally, we observed frequent gene-level copy number variations, including amplifications of MYC, BRCA2, ERBB2, CCND2 and deletion of APC. Among 197 patients, only three showed MSI-high, who also exhibited high TMBs. Moreover, KRAS, MXRA5, and SETD2 mutations were significantly associated with shorter DFS ( KRAS mt vs wt: 8 months vs 11 months, p = 0.0086; MXRA5 mt vs wt: 6 months vs 11 months, p = 0.0178; SETD2 mt vs wt: 8 months vs 11 months, p = 0.0381), but KMT2A mutation associated with longer DFS (mt vs wt: 31.5 months vs 10 months, p = 0.0409). SPEN, GNAS, CTNNB1, SETD2 and FANCM mutations were significantly associated with poor OS ( SPEN mt vs wt: 23 months vs 30 months, p = 0.0047; GNAS mt vs wt: 24.5 months vs 30 months, p = 0.0386; CTNNB1 mt vs wt: 20 months vs 30 months, p = 0.0001; SETD2 mt vs wt: 20 months vs 30 months, p = 0.0026; FANCM mt vs wt: 13 months vs 30 months, p = 0.0007). Conclusions: Our study has found a novel panel of prognostic biomarkers in colorectal liver metastases. The clinical significance of mutations of MXRA5, SETD2, KMT2A, SPEN, GNAS, CTNNB1, FANCM needs to be confirmed on a larger scale.
Safety and efficacy of nivolumab plus ipilimumab (NIVO+IPI) in patients with advanced renal cell carcinoma (aRCC) with brain metastases: Interim analysis of CheckMate 920.
Authors: Hamid Emamekhoo, Mark Olsen, Bradley Curtis Carthon, Alexandra Drakaki, Ivor John Percent, Ana M. Molina, Daniel C. Cho, Johanna C. Bendell, Lucio N. Gordan, Arash Rezazadeh Kalebasty, Daniel J. George, Thomas E. Hutson, Richard J. Lee, Tina C. Young, Jennifer Johansen, Scott S. Tykodi
Journal: Journal of Clinical Oncology (2019)

4517 Background: Previous clinical trials of patients (pts) with aRCC, including CheckMate 214, have mostly excluded pts with brain metastases. However, antitumor activity in pts with brain metastases has been observed in pts with melanoma treated with NIVO 1 mg/kg + IPI 3mg/kg and pts with non-small cell lung cancer treated with NIVO 240 mg + IPI 1mg/kg. CheckMate 920 is an ongoing, phase 3b/4 clinical trial of NIVO + IPI treatment in pts with aRCC with a high unmet medical need. Here, we present the safety and efficacy interim results for the cohort of pts with brain metastases. Methods: Pts with previously untreated aRCC of any histology, with asymptomatic brain metastases (not on corticosteroids or receiving radiation), and Karnofsky performance status ≥70% were assigned to treatment with NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 doses, followed by NIVO 480 mg every 4 weeks. Pts were treated until disease progression, unacceptable toxicity, or for a maximum of 2 years. The primary endpoint was the incidence of high-grade immune-mediated adverse events (IMAEs). Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 per investigator. Exploratory endpoints included additional safety analyses and overall survival (OS). Results: Overall, 28 patients were enrolled in the brain metastases cohort. With a minimum follow-up of 6.47 months, grade 3-4 IMAEs within 100 days of last dose were reported in 6 cases. The grade 3-4 IMAEs observed in ≥ 1 patient were diarrhea, colitis, diabetic ketoacidosis, immune-mediated hepatitis, hypophysitis, and rash of any type (n = 1 each). No treatment-related grade 5 IMAEs were reported. ORR by RECIST v1.1 per investigator in all treated subjects was 28.6% (95% CI 13.2–48.7). Median PFS in all treated subjects was 9.0 months (95% CI 2.9–not estimable [NE]). Median OS has not been reached (95% CI 13.1–NE). Conclusions: In pts with aRCC and brain metastases who are often excluded from clinical trials, NIVO + IPI treatment showed a safety profile consistent with previous reports of this dosing regimen, with encouraging antitumor activity. Clinical trial information: NCT02982954.
Results of the VENUS study: Bevacizumab efficacy and safety in platinum-sensitive recurrent ovarian cancer (OC)—A real-life ambispective study.
Authors: Isabelle Laure Ray-Coquard, Jerome Alexandre, Francois Goldwasser, Jean-Philippe Spano, Dominique Berton-Rigaud, Aude-Marie Savoye, Michel Fabbro, Fernando Bazan, Elsa Kalbacher, Nadia Raban, Claire Giraud, Virginie Pottier, Frédéric Selle, Anne Patsouris, Claire Garnier-Tixidre, Anne Mercier Blas, Jocelyne Provencal, Fabien Brocard, Jessica Berdougo-Tritz, Vincent Launay-Vacher
Journal: Journal of Clinical Oncology (2019)

5540 Background: The VENUS study reports on the efficacy/safety of bevacizumab (Bev) in patients (pts) treated in the real-life setting. Methods: In this multicentric observational ambispective VENUS study, all Pts were naive of any antiVEGF and received Bev +/- chemotherapy. Pts were followed until progression or death, for a maximum of 3 years since Bev initiation. De novo side effects were defined as symptoms for which patients were naïve at baseline. Results: 148 OC pts were included (27 centres), 10 excluded and 8 were lost of follow-up. 52 were retrospective. Median age 64 years (55-70). 84.1% were advanced. Median duration of Bev was 8.6 months, min 1 max 36 months. Initial Bev dose was 15 mg/kg Q3W for 65.3%, 10.0 for 22.5%, 7.5 for 10.2% and 5.0 for 2%. 2 pts presented with thrombotic micro-angiopathy (1.4%). Before Bev, hypertension (HTN) was present in 28.9%; proteinuria in 11.3%. Incidence of de novo HTN was 25%. 43 pts (31.2%) experienced de novo Grade 1-2 Pu, for a total of 56 events, no grade 3-4 was observed. A total of 12 Grade 4 events occurred: 9 neutropenia and 3 thrombopenia. Mean overall survival (OS) and progression free survival (PFS) were 30.0 and 13.3 months, respectively. Conclusions: 1) 1/3 of pts were treated at low doses in this real-life study; 2) safety of Bev in real-life was manageable and as expected, 3) OS and PFS were consistent with those reported in the OCEANS study: PFS 12.4 and OS 33.6 months but lower than in the GOG-0213 study: PFS 13.8 and OS 42.6 months. De novo events recorded during follow-up. [Table: see text]
Neoadjuvant FOLFIRINOX versus adjuvant gemcitabine in pancreatic cancer.
Authors: Adam R Wolfe, Eric David Miller, Laith I. Abushahin, Jordan Cloyd, Adrei Manilchuck, Mary Dillhoff, Dayssy Alexandra Diaz Pardo, Anne M. Noonan, Terence M Williams
Journal: Journal of Clinical Oncology (2019)

4123 Background: In the metastatic or adjuvant setting for pancreatic cancer, the combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) resulted in longer overall survival (OS) compared to gemcitabine therapy. We conducted an institutional study to compare the efficacy of neoadjuvant modified FOLFIRINOX (neo-mFOLFIRINOX) to adjuvant gemcitabine (adj-gem) for pancreatic cancer patients who completed resection. Methods: The study retrospectively enrolled patients from 2006 to 2017 from Ohio State University. While patients who received adjuvant gemcitabine were considered to be resectable upfront, patients who received neo-mFOLFIRINOX were either staged as borderline resectable (BR) or un-resectable (UR) by the institutional tumor board group. 111 patients received adj-gem (average cycles, 5.5) and 52 patients received neo-mFOLFIRINOX (average cycles, 3.5). The survival rates were determined by the Kaplan-Meier method and analyzed using Cox regression and log-rank test. Results: At a median follow up of 21.3 months, the median OS was 35.4 months in the neo-mFOLFIRINOX group and 21.8 months in the adj-gem group (hazard ratio, 0.56, 95% confidence interval (CI), 0.37-0.84 p = 0.005). The OS rate at 3 years was 46% in the neo-mFOLFIRINOX group and 22% in the adjuvant gemcitabine group (p = 0.001). The median disease free survival (DFS) was 18.6 months in the neo-mFOLFIRINOX group and 12.0 months in the adj-gem group (hazard ratio, 0.63, 95% CI, 0.43-0.93 p = 0.022). The DFS rate at 3 years was 17% in the neo-mFOLFIRINOX group and 11% in the adj-gem group (p = 0.02). On surgical pathological specimen review, the neo-mFOLFIRINOX group had statistically (p &lt; 0.05) lower tumor grade, lower rates of perineural invasion and lymphovascular invasion, lower pathological T stage, lower pathological N stage, and lower number of nodes positive compared to the adj-gem group. Frequencies of obtaining R0 resections were higher in the neo-mFOLFIRINOX versus adj-gem groups but not statistically different (51.9% vs 40.4, p = 0.2). The average age and performance status were similar between the two groups. Conclusions: At our institution, BR and UR pancreatic cancer patients who received neo-mFOLFIRINOX and completed resection had longer OS, DFS, and more favorable pathological indicators compared to those patients who had upfront surgery and adjuvant gemcitabine. Randomized clinical trials comparing neoadjuvant versus adjuvant FOLFIRINOX are needed to validate these findings.
Sweat retention anhidrosis associated with tubular aggregate myopathy
Authors: Y. Ishitsuka, S. Inoue, J. Furuta, H. Koguchi‐Yoshioka, Y. Nakamura, R. Watanabe, N. Okiyama, Y. Fujisawa, T. Enokizono, H. Fukushima, H. Suzuki, I. Nishino, K. Kosaki, M. Fujimoto
Journal: British Journal of Dermatology (2019)
Quality of end-of-life cancer care at minority-serving US cancer centers: A retrospective study of Medicare claims data.
Authors: Garrett Wasp, Shama S Alam, Gabriel A. Brooks, Inas S Khayal, Nirav S. Kapadia, Donald Q Carmicheal, Andrea M Austin, Amber Barnato
Journal: Journal of Clinical Oncology (2019)

6507 Background: Higher EOL treatment intensity is burdensome and has been defined as low-quality care. We explored cancer centers’ EOL quality outcomes among minority and white patients and evaluated whether minority-serving cancer centers had systematically lower EOL quality. Methods: We conducted a retrospective cohort study of Medicare beneficiaries with poor-prognosis cancers who died between April 1, 2016 and December 31 2016. We attributed patients’ EOL treatment to the cancer center where they received the preponderance of inpatient services during the last 6 months of life. We then compared age-sex-comorbidity adjusted center-level measures of EOL care (EOL chemotherapy, emergency department (ED) use, intensive care unit (ICU) admission, hospice use, life-sustaining treatment use, palliative care, and advance care planning) between minority (black, Hispanic, Asian, other) and non-Hispanic white (white) patients within the same center and across centers, grouped by concentration of minorities served (low: &lt; 15%, medium 15-30%, and high &gt; 30%). Results: Among 126,434 patients, 10,006 (21.4% minority) received treatment at one of 53 National Cancer Institute-designated and/or National Comprehensive Cancer Network-affiliated cancer centers. Only 4/8 quality measures had sufficient sample size to calculate a minority-specific rate for ≥10 centers. Those measures showed high within-center correlation for minority and white patients (ICU admission: r = 0.79,p &lt; 0.001; no hospice referral: r = 0.70,p &lt; 0.0001; life sustaining treatment: r = 0.73,p = 0.004; and palliative care: r = 0.78,p &lt; 0.0001), but the mean adjusted rate for minority versus white patients was significantly worse for two measures: no hospice referral (40.2% v. 37.2%; p &lt; 0.02) and life-sustaining treatments (21.8% v. 19.4%; p &lt; 0.02). When grouped by concentration of minorities served (low/medium/high), 5/8 measures showed systematically lower quality as the concentration of minorities increased: more than 1 ED visit (6.0/8.5/7.7%; p = 0.002), ICU admission (29.1/29.7/35.1%; p = 0.0004), no hospice referral (34.3/38.7/36.8% (p = 0.005), and life sustaining treatments (14.8/16.7/17.9%; p = 0.005). Conclusions: There were systematic differences in end-of-life quality measures across US cancer centers. For many measures, quality was lower at centers that served a greater concentration of minorities. However, EOL care quality for minority and white patients was similar for most but not all measures within any given center.