tbuckley/cabot-search huggingface dataset:
Effect of female-dominant support networks on end-of-life decision making among women with advanced or recurrent cancer.
Authors: Katina Robison, Ashley Stuckey, Don S. Dizon, Michelle Rogers, Miles Ott, Susan Miller, Mary C. Politi, Melissa Clark
Journal: Journal of Clinical Oncology (2013)

6590 Background: Improved understanding of the factors that influence a woman’s end of life (EOL) decisions while confronting cancer is needed. The objective of this study was to determine if the composition of one’s social network was associated with advance care planning (ACP) among women with metastatic or recurrent gynecologic or breast cancer. Methods: Women were recruited from a program in women’s oncology in the northeast. Women with an established diagnosis of recurrent or metastatic cancer for ≥3 months duration were eligible. We asked women with advanced or recurrent cancer about their support networks and end-of-life decisions. Interviews were conducted by research staff. Clinical characteristics and documentation of EOL decisions of enrolled women were obtained through chart reviews. Multivariable logistic models were computed. The study protocol was approved by the hospital and university Institutional Review Boards. Results: 200 women were enrolled in the study. The majority had gynecologic malignancies (65.5%). Older age was associated with having an advanced directive (AD) (p&lt;.0001) and a health care proxy (HCP) (p=0.002). Additionally, having more females than males in one’s support network was associated with an AD (p=0.005) and a HCP (p=0.012). Women with gynecologic cancer were more likely to self-report a HCP compared to those with breast cancer (p=0.040).A female support person was 1.57 times more likely to be trusted to make a medical decision (p=0.002) and a female support person was 1.33 times more likely to be someone a woman spoke with about her end of life decision than a male support person (p=0.037). Neither naming a HCP or having an AD were associated with number of support persons named, total number of female support persons, number of friends, number of children, or presence of an intimate partner. Conclusions: Women with more females than males in their social network were more likely to have an advance care directive or health care proxy. In addition, women were more likely to trust and talk with a female support person about end of life decisions than a male support person. However, the composition of the network was not associated with the likelihood of having completed ACP.
Impact of baseline mutations on response to ponatinib and end of treatment mutation analysis in patients with chronic myeloid leukemia.
Authors: Michael W. N. Deininger, Jorge E. Cortes, Dong-Wook Kim, Franck E. Nicolini, Moshe Talpaz, Michele Baccarani, Martin C. Müller, Stephanie Lustgarten, Victor M. Rivera, Tim Clackson, Christopher D. Turner, Frank G. Haluska, Francois Guilhot, Andreas Hochhaus, John M. Goldman, Neil P. Shah, Hagop M. Kantarjian, Timothy P. Hughes
Journal: Journal of Clinical Oncology (2013)

7001 Background: BCR-ABL kinase domain mutations frequently cause tyrosine kinase inhibitor (TKI) failure in chronic myeloid leukemia (CML). Ponatinib, a potent oral pan-BCR-ABL TKI, has shown preclinical activity against all single mutants tested, including T315I. The impact of baseline (BL) mutations on response to ponatinib (45 mg once daily) and end of treatment (EOT) mutations in pts discontinuing treatment were evaluated in the phase II PACE trial. Methods: Heavily pretreated chronic phase (CP) CML pts (93% received ≥2 prior TKIs, 60% ≥3) resistant or intolerant to dasatinib or nilotinib (N=203) or with T315I confirmed at BL (N=64) were enrolled. The primary endpt was major cytogenetic response (MCyR). Min follow up at analysis (9 Nov 2012) was 12 mos (median 15 [0.1-25]). Sanger sequencing was done at one central laboratory. Results: At BL, no mutations were detected in 51% of pts, 1 mutation in 39%, and ≥2 mutations in 10%; 26 unique mutations were observed. Responses were observed regardless of BL mutation status. MCyR rates were: 56% overall, 49% in pts with no mutations, 64% 1 mutation, 62% ≥2 mutations; 57% in pts with mutation(s) other than T315I, 74% T315I only, 57% T315I + other mutation(s). Responses were seen against each of the 15 mutations present in &gt;1 pt at BL, including T315I, E255V, F359V, Y253H. 99 pts discontinued, 56 had EOT mutations assessed. 5 pts lost a mutation, 46 had no change, 5 gained mutations (Table). 11 pts lost MCyR (none with T315I); of the 6 discontinuing, 4 had EOT mutations assessed and no changes from BL were seen. Conclusions: Responses to ponatinib were observed regardless of BL mutation status. No single mutation conferring resistance to ponatinib in CP-CML has been observed to date. Data with a minimum follow up of 18 mos, including pts with advanced disease, will be presented. Clinical trial information: NCT01207440. [Table: see text]
Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors.
Authors: Lisa Derosa, Bertrand Routy, David Enot, Giulia Baciarello, Christophe Massard, Yohann Loriot, Karim Fizazi, Bernard J. Escudier, Laurence Zitvogel, Laurence Albiges
Journal: Journal of Clinical Oncology (2017)

462 Background: Preclinical data demonstrated that microbiota modulates activity of immune checkpoint inhibitors (ICB) and broad-spectrum antibiotics (ATB) damper their efficacy. However, the impact of ATB in patients (pts) treated with ICB remains unknown. Our study evaluates the effect of ATB use in metastatic renal cell carcinoma (mRCC) pts treated with ICB. Methods: We conducted a retrospective analysis of mRCC pts treated in prospective trials at Gustave Roussy with PD1/PD-L1 inhibitors alone or in combination. ATB (+)/(-) group were defined as pts treated or not with ATB at baseline (up to 1 month prior to the 1st injection of ICB). Progression-Free survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS) were compared in each group (ATB (+) vs ATB (-)). Statistical analyses were performed using Kaplan-Meier method and Cox regression adjusted for risk factors. Results: We enrolled 80 mRCC pts treated with anti-PD-1/PD-L1 monotherapy (n=67), anti-PD-1 plus CTLA-4 (n=10) or anti-PD-L1 plus bevacizumab (n=3) with available data on ATB. Majority of pts were male (65%), clear-cell histology (88%), and had prior nephrectomy (80%). With regard to IMDC risk groups, 21%, 57%, and 22% had favorable, intermediate, and poor-risk disease, respectively. Sixteen (20%) pts belonged to the ATB (+) group (mostly receiving beta-lactamases and fluoroquinolones). ATB (+) had decreased PFS compared to ATB (-), 2.3 vs. 8.1 months, p&lt;0.001. This statistical association was maintained after multivariate analysis adjusted for age, gender, IMDC risk groups, tumour burden and proton pomp inhibitors. In addition, ORR was lower in ATB (+) compared with ATB (-) (p&lt;0.002). Even though it is too early to conclude on OS (median follow-up &lt;6 months), there was already a negative trend driven in ATB (+). Conclusions: This is the first analysis evaluating the impact of ATB in mRCC pts treated in the era of ICB. Recent use of ATB prior to ICB, negatively influences responses even after multivariable analysis for prognostic risk factors. Further studies are warranted to investigate whether the alteration of gut microbiota compositions is responsible for this different outcome.
Prevalence of renal insufficiency (RI) in cancer (Ca) patients (pts) with bone metastases (BM).
Authors: Kristina S Chen, Rohini Khorana Hernandez, Jane M Quigley, Melissa A. Pirolli, David Quach, Alexander Liede, Jorge Arellano
Journal: Journal of Clinical Oncology (2013)

e12508 Background: Upon diagnosis of BM, cancer pts are at increased risk of serious debilitating bone complications. Of the U.S. approved bone-modifying agents (BMAs) [bisphosphonates (BPs), RANKL inhibitor] for the prevention of skeletal-related events (SREs) in these pts, BPs are nephrotoxic and may require dose adjustment or discontinuation. As low persistence to BMAs is associated with higher rates of SREs (Hatoum et al 2008), understanding the extent of RI in a real-world setting is warranted. K/DOQI guidelines recommend monitoring renal function using estimated glomerular filtration rate (eGFR) along with serum creatinine (SCr). Methods: Oncology Services Comprehensive Electronic Records (OSCER), a large electronic medical record database from U.S oncology clinics, was used. Cancer pts (age ≥ 18) with BM diagnosis in 2008 – 2012 were identified excluding acute renal failure, end-stage renal disease, and multiple myeloma. RI prevalence was examined using SCr and eGFR calculated with aMDRD and Cockroft-Gault formula. RI was defined as elevated SCr &gt; 1.2 mg/dl or eGFR &lt; 60 and &lt; 90 ml/min/1.73m 2 . The analysis was also performed in the subgroup receiving BMAs. Results: The cohort included 15,623 pts (mean age 67.1±12.0, weight 76.5±18.5 kg; female; 56%). Using highest SCr during follow-up, 36% had elevated SCr, 87% eGFR &lt; 90, and 47% eGFR &lt; 60. Among pts with BM diagnosis in 2011 (n=3,839) and normal SCr (taken 1 month before or 3 months after diagnosis; n=3,192), almost 60% of the pts had mildly decreased renal function (eGFR &lt; 90), and 8% had moderately decreased renal function (eGFR &lt; 60) (table). Rates of RI based on eGFR estimated by both formulas were consistent. Conclusions: Nearly half of the cancer pts with BM had RI (eGFR &lt; 60) during the course of their disease. As the risk of renal impairment is high in this population, assessment of renal function using eGFR and careful treatment consideration is imperative to achieve optimal therapeutic outcomes. [Table: see text]
Phase I study combining MLN8237 with nab-paclitaxel in patients with advanced solid malignancies.
Authors: Kian-Huat Lim, Albert C. Lockhart, Saiama Naheed Waqar, Ramaswamy Govindan, Daniel Morgensztern, Joel Picus, Benjamin R. Tan, Maria Quintos Baggstrom, Emily Ratchford, Samantha Marquez, Andrea Wang-Gillam
Journal: Journal of Clinical Oncology (2017)

2553 Background: MLN8237 is a potent Aurora A kinase inhibitor which synergizes with paclitaxel in preclinical studies for various solid malignancies. Methods: We conducted a two-part, phase 1 study combining MLN8237 with nab-paclitaxel in patient with advanced, refractory solid malignancies (NCT01677559). The part 1, dose-escalation phase utilizes a standard a 3+3 design for determination of maximum tolerated dose (MTD) and dose limiting toxicities (DLTs), starting from nab-Paclitaxel 100mg/m2/week 3 out of a 4-week cycle, and MLN8237 20mg BID D1-3/week (denoted nP/M 100/20). In the part 2, dose-expansion cohort, patients with advanced pancreatic ductal adenocarcinoma (PDAC) or high grade neuroendocrine tumor (pNET) who progressed on standard chemotherapy were enrolled. Results: Totally 33 patients (17 in part 1 and 16 in part 2) with a median age of 61 were enrolled. In part 1, the most frequent treatment-related toxicities (all Grade/Grade 3-4) were: nausea (65%/6%), neutropenia (61%/18%), fatigue (47%/6%), anorexia (47%/0%), oral mucositis (53%/6%) and anemia (35%/18%). Two of 3 patients experienced a DLT at dose nP/M 100/50 (Grade 4 neutropenia; febrile neutropenia). No treatment-related mortality occurred. MTD was set at nP/M 100/40 for part 2. At data cutoff, totally 20 patients from the entire study were evaluable for treatment response. One patient with small cell lung cancer achieved partial response and is in cycle 29. Nine other patients (9/20, 45%) with the following tumor histology achieved stable disease after two cycles: 1 small cell lung cancer, 1 lung neuroendocrine carcinoma, 1 lung squamous cell carcinoma, 1 PDAC and 5 high grade pNET (range: 3 and ongoing ~ 18 cycles). Conclusions: MLN8237 plus nab-paclitaxel has manageable side effect profile with very promising activity in tumors with high grade neuroendocrine features, warranting further testing. Exploratory studies on pharmacodynamic markers are ongoing. Clinical trial information: NCT01677559.
Changes in prostate cancer detection rate of fusion versus systematic biopsy over time: A single center experience.
Authors: Brian P. Calio, Abhinav Sidana, Dordaneh Sugano, Amit L Jain, Mahir Maruf, Maria J Merino, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2017)

15 Background: To determine the effect of learning curves and changes in fusion platform during 9 years of NCI’s experience with multiparametric MRI (mpMRI)/TRUS fusion biopsy. Methods: A review was performed of a prospectively maintained database of patients undergoing mpMRI followed by fusion biopsy (Fbx) and systematic biopsy (Sbx) from 2007−2016. The patients were stratified based on the timing of first biopsy in 3 groups. Cohort 1 included patients biopsied between 7/2007−12/2010, accounting for learning curve at our institution. Cohort 2 included patients biopsied from 1/2011 up to the debut of UroNav (Invivo) platform in 5/2013. Cohort 3 included patients biopsied after 5/2013. Clinically significant (CS) disease was defined as Gleason 7 (3+4) or higher. Cancer detection rates (CDR) between Sbx and Fbx during different time periods were compared using McNemar’s test. Age and PSA standardized CDRs were calculated for comparison between 3 cohorts. Results: 1528 patients were included in the study with 219, 549 and 761 patients included in 3 respective cohorts. Mean age, PSA and race distribution were similar across 3 cohorts. In cohort 1 there was no significant difference between CDR of CS disease by Fbx (24.7%) vs Sbx (21.5%), p = 0.377. Fbx was significantly better than Sbx in detection of CS disease in cohort 2 and cohort 3 (31.5% vs 25.3%, p = 0.001; 36.5% vs 30.2%, p &lt; 0.001, respectively). There was significant decline in detection of low risk disease by Fbx compared to Sbx in the same period (cohort 2: 14.2% vs 20.9%, p &lt; 0.001; cohort 3: 12.5% vs 19.5%, p &lt; 0.001). Age and PSA standardized CDR of CS cancer by Fbx increased significantly between each successive cohort (cohort 1 and 2: 5.2%, 95% CI [2.1-8.5]), 2 and 3 (5.2%, 95% CI [1.8-8.6]). Conclusions: Our results show that after an early learning period using Fbx, CS prostate cancer was detected at significantly higher rates with Fbx than with Sbx, and low risk disease was detected at lower rates. Advances in software allowed for even greater detection of CS disease in the last cohort. This study shows that accuracy of Fbx is dependent on multiple factors; surgeon/radiologist experience and software improvements together produce improved accuracy.
Fatal outcome due to CO<sub>2</sub> emboli during direct cholangioscopy
Authors: Alexander Hann, Eugen Zizer, Klaus Egger, Hans-Dieter Allescher, Alexander Meining
Journal: Gut (2017)

In this manuscript, we present two patients with fatal CO2 emboli who underwent direct peroral video cholangioscopy (POC). Emboli due to insufflation of air during such a procedure have been previously described. Because of its high solubility in blood, the use of CO2, but not of air, is strictly recommended to reduce the incidence of emboli. However, based on these fatal experiences, we would strongly suggest to refrain from performing direct cholangioscopy with uncontrolled insufflation of gas, even if CO2 was used, as in the two presented cases.

POC is a well-established technique for the diagnosis of bile duct alterations and the treatment of bile duct stones.1 The use of small calibre, transnasal, gastroscopes for direct visualisation of the common bile duct clearly improved the visualisation of bile duct pathologies and allow for obtaining targeted biopsies.2 Mild-to-moderate cholangitis represents the most common adverse event related to this procedure.3 But the most serious adverse events are emboli due to insufflation of air during the procedure. Different publications report fatal outcome of such events.4–7 Because of its high solubility in blood, the use of CO2, but not of air, is strictly recommended to reduce the incidence of such emboli.1 ,8 ,9 To our best knowledge, an embolism adverse event …
Novel risk factors for osteonecrosis of the jaw in multiple myeloma: A RADAR report.
Authors: Jaimee S Holbrook, Steven M Trifilio, June M. Mckoy, Seema Singhal, Alfred Rademaker, Jayesh Mehta, Steven M Belknap, Stefani Tica, Sarah Victoria Clark, Victoria Godinez-Puig, Beatrice Nardone, William John Gradishar, Dennis P. West, Beatrice J. Edwards
Journal: Journal of Clinical Oncology (2012)

6623 Background: Osteonecrosis of the jaw (ONJ) was identified in 2001 and is commonly seen in multiple myeloma (MM). The objective of this study is to evaluate novel risk factors in MM cases from a retrospective database. We hypothesized that ONJ may be related to stem cell transplant, chronic kidney disease and active smoking. Methods: We conducted a retrospective case-control study of 231 MM cases (from January 1, 1998 to September 30, 2010) identified from the electronic data warehouse (EDW) at Northwestern University (NU). The EDW is cross-institutional and integrates clinical data across NU. It comprises more than 2.3TB of data on roughly 2 million patients. The search terms used were: bisphosphonates, pamidronate, zoledronic acid, multiple myeloma, plasma cell disorders, osteonecrosis of the jaw, jaw abscess, dental abscess, among other terms described in literature. Data was abstracted onto a standardized form by 2 trained abstractors and validated by a clinician reviewer (BJE). Known and hypothesized new risk factors were abstracted, including duration of myeloma, treatment used, duration of bisphosphonate use, renal function indices, chemotherapy (vincristine, doxorubicin (A), dexamethasone (D) , thalidomide (T), cisplatin (P), cyclophosphamide (C), etoposide (E), novel agents [bevacizumab, sorafenib, angiostatin]) GCSF, smoking, and MM clinical stage. Analyses included T test, Wilcoxon, and log rank analysis. Results: ONJ occurring after MM diagnosis was identified in 33 cases out of a total of 233 cases of MM. ZOL, VAD, DT-PACE, and diabetes were more common in ONJ cases. Log rank analysis identified 2 risk factors for ONJ, the use of DT-PACE (p= 0.003), and complete and partial remission (p=0.007). Stem cell transplant and chronic kidney disease were not associated with ONJ. Conclusions: We identified novel risk factors for ONJ in MM, mainly partial or complete remission and use of DT-PACE. These results should prompt clinicians to heightened awareness and increased surveillance for the symptoms of ONJ for patients treated with DT-PACE.
Phase II study of the PI3K inhibitor BKM120 monotherapy in patients with advanced or recurrent endometrial carcinoma: ENDOPIK, GINECO Study.
Authors: Pierre-Etienne Heudel, Michel Fabbro, Celia Roemer-Becuwe, Isabelle Treilleux, Marie-Christine Kaminsky, Antoine Arnaud, Florence Joly, Sophie Roche Forestier, Robert Herve, Isabelle Ray-Coquard
Journal: Journal of Clinical Oncology (2015)

5588 Background: Patients (pts) with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of a pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. Methods: This multicenter, single-arm, Phase II, double strata (histological low grade (LG) vs. high grade (HG)) open-label study enrolled pts with histologically confirmed advanced or recurrent endometrial carcinoma, who had received no more than one prior chemotherapy regimen. Primary endpoints were proportion of pts with progression-free survival (PFS) at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. Initial BKM120 dosage was 100 mg tablets once daily. Results: 40 pts were enrolled, of which 16 pts had received BKM120 at 100 mg/d. Due to high rate of grade 3/4 toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%)), the IDMC proposed to stop recruitment at 100 mg but to continue the recruitment with a lower dose of 60 mg/d. 24 pts (median age 67 years old) were newly enrolled (14 in the LG strata, 10 in the HG strata). Rate of PFS > 2months in the HG strata was 70% and > 3months was 57% in the LG strata. Median PFS for all pts is 4.5 months (CI 95% 2.8 – 6.1); median PFS for LG strata is 8.3 months compared to 3.8 months for the HG strata. No objective response was reported. At 60 mg/d, 87% of patients experienced grade 3/4 toxicity. The most commonly reported treatment-related grade ≥ 3 AEs were cutaneous (13%), increased alanine aminotransferase (13%), HTA (17%), hyperglycemia (17%) and increased aspartate aminotransferase (21%). 5 patients (21%) stopped BKM120 for toxicity. Conclusions: BKM120 was associated with an unfavorable safety profile and minimal antitumor activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity. Clinical trial information: NCT01397877.
Long-term breast cancer outcomes in Canada with special analyses of cancer care access and mortality reduction.
Authors: Joseph Ragaz, Andy Coldman, Kenneth S. Wilson, Joel Fox, Shayan Shakeraneh, Hubert Wong, John Joseph Spinelli
Journal: Journal of Clinical Oncology (2014)

1601 Background: The objective of this study is to compare main Breast Cancer outcomes in two regions of Canada with different access to Provincial Guideline-based cancer care [GCC]. Since the 1960's, British Columbia has had a centralized provincially funded Cancer program, coordinating GCC care. Adjuvant therapies started in late 1970's; and of screening mammography in late 1980's. Both Programs were implemented province-wide, and at least a decade earlier than in Atlantic Provinces (Atl. Prov.). Both regions have had comparable BrCa registry since 1970. Methods: From 1970-2007 datawere obtained in collaboration with Public Health Agency of Canada and Canadian Cancer Registry database at Statistics Canada. Estimates for annual age standardized rates /100,000 [with Canada 1991 as population reference] were evaluated for BrCa in-situ [ASR-IS]; incidence of invasive BrCa [ASIRs]; and BrCa-specific mortality [ASMRs]. Results were averaged q 10 years. ASMRs were also expressed [in percent] relative to baseline years 1970-75. Results: See Table. Conclusions: (1) While in the 1970’s the rates of both in-situ and invasive BrCa in Atl. Prov. were significantly lower than in B.C., subsequently both rates have increased to approximate rates in B.C.( 20 ASMR reduction in B.C. is more substantial and observed many years earlier than in Atl. Prov. (3) These results show that uniform guideline-coordinated cancer care favorably impacts BrCa outcomes, and should be implemented in regions with unequal access to cancer care. Reference: Cancer Research: December 15, 2009; Volume 69, Issue 24, Supplement 3. Region Breast cancer outcomes Period 1970-1979 1980-1989 1990-1999 2000+ B.C. In-situ 3.8 5.4 11.0 13.1 ASIR 75.0 77.2 81.2 74.3 ASMR 22.5 [100%] 21.8 [94%] 18.8 [82%] 14.2 [63%] Atl. Prov. In-Situ 0.5 2.5 3.5 11.1 ASIR 59.3 64.1 77.3 76.5 ASMR 22.1 [100%] 23.1 [107%] 21.7 [102%] 16.2 [75%]