tbuckley/cabot-search huggingface dataset:
Influence of treatment received in long surviving patients of head and neck cancer.
Authors: Miren Taberna, Cinta Hierro, Marc Diez, Jaime Canellas, Mivael Olivera, Silvia Vazquez, Valentín Navarro-Perez, Manuel Manos, Alicia Lozano, Ester Vilajosana, Ricard Mesia
Journal: Journal of Clinical Oncology (2013)

e17010 Background: Modification of radiotherapy (RT) schedules or the addition of CT/biologics in patients (pts) with locally advanced head-and-neck carcinomas (LAHNC) have resulted in improving survival, although this means increased morbidity. Our aim was to analyze late toxic effects that present our long survivors pts and how much these may affect their lives. Methods: We have prospectively assessed late toxicity based on the RTOG scoring system in 152 consecutive LAHNC long-term survivors treated from 1994 to 2009 in an outpatient clinic. All of them had received concomitant treatment or fractionated RT with or without induction. Multivariate logistic regressions (logit link) for toxicity were performed to detect toxicity factors, p-values and confidence intervals at 95 % level (CI). Pts also answered about the degree of life-affecting by these sequelae. Results: Median age 63 (29-78), 136 men. All received radical treatment with: RT alone (21%), concomitant RT with cisplatin (P) (51%) or cetuximab (C) (28%). Previous induction platinum-based CT was administered in 56% pts. Median dose RT: 70 Gy (60-80), with different fractionations. All pts had at least one grade 1-2 late effect and 21% experienced grade 3-4 toxicity. The most common toxicities are shown in the Table. Concomitant C was found to be an independent risk factor of decreasing late toxicity compared with P in the adjusted analysis by RT fraction: Grade 1-2 toxicity OR 0.292 (CI: 0.125-0.680, p: ,04) and grade 3-4 toxicity OR 0.299 (CI: 0.0909-0.999, p: ,05). 41% of pts felt their quality of life as no disabling and 17% as very disabling. Conclusions: Having chronic toxicity in long survivors with a LAHNC is very common, but the vast majority of them learn to adapt to it. The type of treatment performed clearly affect this late toxicity: pts treated with concomitant P have significant more late toxicity compared with the association with C. [Table: see text]
Phase II study of everolimus (E) with imatinib (IM) in patients with previously-treated renal carcinoma (RCC)
Authors: C. W. Ryan, J. Vuky, J. S. Chan, T. M. Beer, M. Rothkopf
Journal: Journal of Clinical Oncology (2009)

e16075 Background: Inhibitors of mTOR improve progression-free survival (PFS) in advanced RCC. We hypothesized that co-administration of the mTOR inhibitor E with an upstream receptor tyrosine kinase inhibitor could augment activity in advanced RCC. We chose to study IM due to its inhibition of PDGFR, a relevant target for RCC with potential activity at both the tumor cell and the pericyte. Methods: Eligible patients had metastatic or unresectable clear cell renal carcinoma, at least one prior systemic therapy, no prior mTOR inhibitor therapy, performance status 0–2, and measurable disease. Treatment consisted of E 2.5 mg p.o. daily and IM 600 mg p.o. daily, a dose determined from a phase I study in GIST. A two-stage design was employed to test for a 3-month PFS of ≥ 70% vs. ≤ 50%. Results: 19 subjects were evaluable for toxicity and 18 for response. Median age 65; number of prior systemic therapies 1:2:3+ (47%:32%:21%); prior sorafenib and/or sunitinib 89%; MSKCC prognostic categories favorable:intermediate:poor (42%:47%:11%). There were no objective responses. Best response was stable disease (67%) and progressive disease (33%). The 3-month PFS rate was 49% (95% C.I. 23%, 72%). The median PFS was 2.9 months (95% C.I. 1.9, 6.2) and the median overall survival was 14.4 months (95% C.I. 11.3, N.R.). Toxicities and lab abnormalities affecting &gt;50% of subjects were: nausea, elevated creatinine, edema, anemia, hypocalcemia, fatigue, diarrhea, vomiting, and dyspnea, and leucopenia. Most common grade 3+ events were: fatigue (16%), pleural effusion (16%), edema (11%), and renal failure (11%). The study was closed after the first stage as the 3-month PFS did not meet continuation criteria. Conclusions: The combination of E 2.5 mg with IM 600 mg in previously-treated patients with advanced RCC did not meet the study-defined level of activity to warrant further investigation. The natural history assumptions for this pretreated RCC population may have been overly optimistic. While the observed PFS is comparable to that reported with E 10mg monotherapy, there appears to be no advantage to combination IM therapy and the incidence of adverse events is high. Further development of this regimen for RCC is not recommended. [Table: see text]
Effect of early palliative care on health care costs in patients with metastatic NSCLC.
Authors: Joseph A. Greer, Pamela M McMahon, Angela Tramontano, Emily R. Gallagher, William F. Pirl, Vicki A. Jackson, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2012)

6004 Background: Introducing palliative care soon after diagnosis for patients with metastatic non-small cell lung cancer (NSCLC) leads to improvements in quality of life, mood, end-of-life care, and possibly survival. We sought to investigate whether early palliative care is also associated with health care cost savings. Methods: This secondary analysis is based on a randomized controlled trial of 151 patients with newly-diagnosed, metastatic NSCLC presenting to an outpatient clinic at a tertiary cancer center between 6/2006 and 7/2009. Participants received either early palliative care integrated with standard oncology care or standard oncology care alone. We queried participants’ electronic health records as well as our institution’s billing database to collect data on frequency and costs of outpatient clinic visits, inpatient hospitalizations, chemotherapy administration, and hospice services. The primary outcome was the difference in average resource use costs during the final month of life between groups. Results: By 18-month follow up, 133 (88.1%) participants had died, and 125 (82.8%) had available data for this analysis. Participants in the early palliative care group had a mean cost savings of $2,282 (median=$2,432) per patient in total health care expenditures during the final month of life compared to the standard care group. The difference was primarily accounted for by lower costs for inpatient visits (mean saving per patient=$3,110) and chemotherapy administration (mean saving per patient=$640). Although expenditures for outpatient clinic visits were similar between groups, the costs for hospice services were greater for the early palliative care group because of the longer lengths of stay in hospice care (mean cost per patient=$1,125). Conclusions: Early palliative care for individuals diagnosed with metastatic NSCLC not only improves multiple patient outcomes but also may be associated with lower hospital resource use costs, primarily through decreased inpatient visits and chemotherapy administration at the end of life.
The Impact of Sotagliflozin on Renal Function, Albuminuria, Blood Pressure, and Hematocrit in Adults With Type 1 Diabetes
Authors: Daniël H. van Raalte, Petter Bjornstad, Frederik Persson, David R. Powell, Rita de Cassia Castro, Ping Stella Wang, Minzhi Liu, Hiddo J.L. Heerspink, David Cherney
Journal: Diabetes Care (2019)

OBJECTIVE In people with type 2 diabetes, sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular risk and progression of diabetic kidney disease. Our aim was to determine whether sotagliflozin (SOTA), a dual SGLT1i and SGLT2i, had favorable effects on clinical biomarkers suggestive of kidney protection in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS In this 52-week pooled analysis, 1,575 adults enrolled in the inTandem1 and inTandem2 trials were randomized to SOTA 200 mg, 400 mg, or placebo in addition to optimized insulin therapy. Changes in cardiorenal biomarkers were assessed. RESULTS At 52 weeks, in response to SOTA 200 and 400 mg, the placebo-corrected least squares mean change from baseline in estimated glomerular filtration rate was −2.0 mL/min/1.73 m2 (P = 0.010) and −0.5 mL/min/1.73 m2 (P = 0.52), respectively. Systolic blood pressure difference was −2.9 and −3.6 mmHg (P &amp;lt; 0.0001 for both); diastolic blood pressure changed by −1.4 (P = 0.0033) and −1.6 mmHg (P = 0.0008). In participants with baseline urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g, UACR decreased by 23.7% (P = 0.054) and 18.3% (P = 0.18) for SOTA 200 and SOTA 400 mg, respectively, versus placebo. Increases in serum albumin and hematocrit and reductions in uric acid were observed throughout 52 weeks with both SOTA doses. CONCLUSIONS SOTA was associated with short- and long-term renal hemodynamic changes, which were similar to those seen with SGLT2i in type 2 diabetes. Further investigation around cardiorenal effects of SOTA in people with type 1 diabetes is justified.
Kit-stem cell factor (kit ligand) axis in GIST patients treated with imatinib
Authors: J. C. McAuliffe, A. Lazar, D. Steinert, S. Patel, R. Benjamin, J. C. Trent
Journal: Journal of Clinical Oncology (2007)

10046 Background: Gastrointestinal stromal tumors (GISTs) represent the majority of GI mesenchymal neoplasms. Imatinib (Gleevec; STI571; Novartis, Basel, Switzerland) has marked efficacy in the management of GIST; however, little is known of its exact mechanism in GIST. We sought to elucidate expression patterns of stem cell factor (SCF, Kit ligand) and the Kit receptor tyrosine kinase in GIST and tumor-associated endothelial cells (TECs) from patients treated with imatinib. Methods: We constructed a 54 GIST specimen tissue array from patients with GIST surgically resected who received 400–800 mg/day adjuvant imatinib. Arrays were stained for SCF by immunohistochemistry and scored for expression as 0 (none), 1 (weak), or 2 (strong). Expression was correlated to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier methods. In a second study we collected pre-imatinib core needle biopsies from 15 patients on a phase II prospective, randomized clinical trial of neo-adjuvant and adjuvant imatinib (600mg/day) for the treatment of primary or advanced, resectable GIST. Specimens were stained for phosphorylated-Kit and CD31 and visualized by immunofluorescence and confocal microscopy. Co-localization of markers was correlated to radiographic response by positron emission tomography (PET) and dynamic computed tomography (dCT). Results: 47 of 54 tumors (87%) expressed SCF but there was no significant correlation between SCF expression or intensity with PFS and OS. Interestingly, the majority of GIST tissue from patients on the prospective clinical trial contained pre-imatinib TECs expressing phosphorylated-Kit. 69% and 79% of patients receiving 3–7 days of imatinib responded by PET scan or dCT, respectively. Conclusions: The majority of GISTs express SCF while pre-imatinib TECs were found to express phosphorylated-Kit. Therefore, our results suggest that within the tumor microenvironment there may be Kit/SCF crosstalk between tumor cells and TECs. Whether disruption of this crosstalk plays a role in tumor response or anti-vascular efficacy requires additional investigation. No significant financial relationships to disclose.
The German quality assurance system for the molecular-pathological detection of KRAS-mutations in colorectal cancer
Authors: A. Jung, G. Baretton, M. Dietel, H. Gabbert, H. Kreipe, W. Schlake, A. Tannapfel, M. von Knebel Döberitz, T. Kirchner
Journal: Journal of Clinical Oncology (2009)

4018 Background: In the beginning of 2008 the EMEA (European Medicines Agency) approved with panitumumab for the first time an EGFR (epidermal growth factor receptor) targeting therapy for patients with metastatic colorectal cancer overexpressing the EGFR and showing wildtypic sequences in the KRAS gene as a predictive biomarker. Thus, the need for assuring the quality of laboratories emerged. The German Society for Pathology in cooperation with the Federation of the German Pathologist supported by an unrestricted financial grant of Amgen Germany arranged a quality assurance system (QAS). In this context two round- robin tests were carried out which results are presented here. Methods: Collection of results from two round -robin tests and their statistical analysis applying binary classification tests. Results: Test sets of 4 histological sections from ten different cases of colorectal tumors with known mutational status of the KRAS gene were prepared for the round-robin tests. The method for the mutation detection was unrestricted. A total of 74 participants from universities (44 - 59.5 %) or other institutions (30 - 40.5 %) attended the tests. 11 participants (14.8 %) failed the test (6 universities: 13.6 %, 5 institutions: 16.6 %). For the analysis didesoxy-sequencing (DDS: 55 - 66.2 %), ARMS®-PCR (8 - 10.4 %), melting-point analysis (MPA: 7 - 9.1 %), pyrosequencing (PS: 6 - 7.8 %), hybridization (HYB: 4 - 5.2 %), or SSCP (1 - 1.3 %) were used, in which some participants (3) used more than one method. It turned out that all methods employed for the testing gave similar results when comparing the rate of correct or wrong hits or the rate of false positive detection: DDS (0.92, 0.07, 0.02), ARMS®-PCR (0.91, 0.08, 0.05), MPA (0.94, 0.06, 0.04), PS (0.95, 0.05, 0.03) or HYB (0.90, 0.10, 0.08). Conclusions: The quality of the molecular-pathological detection of KRAS mutations as precondition for an EGFR targeted therapy should be tested since about 15 % of laboratories did not meet a sufficient grade. For the mutation detection no method seemed superior. [Table: see text]
Classification of subtype using IHC patterns for treatment decision of DCIS.
Authors: Yuko Date, Masafumi Takimoto, Toshio Morohoshi, Seigo Nakamura
Journal: Journal of Clinical Oncology (2013)

e12035 Background: Ductal carcinoma in situ (DCIS) is a heterogenous group of breast lesion and demands a broad range of surgical management techniques. Previous studies reported the importance of receptor expression and referred to the risk of recurrence.We classified ductal carcinoma in situ (DCIS) into 4 subtypes using IHC staining (ER, PgR, HER2 and Ki-67) and investigated the frequency and their characteristics. Also we investigated whether this classification is related to the risk of recurrence. Methods: 117 women who underwent operation between 2010 and 2012 were included our study. We defined 4 subtypes as follows; luminal A (LA), ER and/or PgR (HR)(+) HER2(-) Ki-67(low), luminal B (LB), HR(+) HER2(-) Ki-67(high) or HR(+) HER2(+),HER2(H), HR(-) HER2(+), and basal-like(BL), HR(-) HER2(-).We also evaluated the risk of recurrence using Van Nuys Prognostic Index (VNPI), an algorithm based on DCIS size, nuclear grade (NG), necrosis, margin width and patient age. Results: The frequency of subtype was as follows; LA 77 cases (65.8%), LB 18 (15.3%), H 14 (12.0%) and BL 8 (6.8%). LA tended to smaller size (average: 3.2cm, range: 0.2-12), low NG (NG1 was 97.4%). In a contrary, H and BL were larger size (average: 3.7cm (H), 4.5cm (BL)) and high NG (these percentages of NG3 were 64.3% (H) and 50.0% (BL)). All of the BL had necrosis. About half of the LA was VNPI 6 and 7, but many of the other subtypes were more than VNPI 7 (p=0.02). Conclusions: Classification of subtypes using IHC patterns is simple, useful and, moreover, that are related to the risk of recurrence. Though it is important whether the woman is BRCA1/2 mutation carrier, we might be determined a treatment of DCIS by the subtype.
Targeting Myeloperoxidase Disrupts Mitochondrial Redox Balance and Overcomes Cytarabine Resistance in Human Acute Myeloid Leukemia
Authors: Mohsen Hosseini, Hamid Reza Rezvani, Nesrine Aroua, Claudie Bosc, Thomas Farge, Estelle Saland, Véronique Guyonnet-Dupérat, Sonia Zaghdoudi, Latifa Jarrou, Clément Larrue, Marie Sabatier, Pierre Luc Mouchel, Mathilde Gotanègre, Marc Piechaczyk, Guillaume Bossis, Christian Récher, Jean-Emmanuel Sarry
Journal: Cancer Research (2019)

Chemotherapies alter cellular redox balance and reactive oxygen species (ROS) content. Recent studies have reported that chemoresistant cells have an increased oxidative state in hematologic malignancies. In this study, we demonstrated that chemoresistant acute myeloid leukemia (AML) cells had a lower level of mitochondrial and cytosolic ROS in response to cytarabine (AraC) and overexpressed myeloperoxidase (MPO), a heme protein that converts hydrogen peroxide to hypochlorous acid (HOCl), compared with sensitive AML cells. High MPO-expressing AML cells were less sensitive to AraC in vitro and in vivo. They also produced higher levels of HOCl and exhibited an increased rate of mitochondrial oxygen consumption when compared with low MPO-expressing AML cells. Targeting MPO expression or enzyme activity sensitized AML cells to AraC treatment by triggering oxidative damage and sustaining oxidative stress, particularly in high MPO-expressing AML cells. This sensitization stemmed from mitochondrial superoxide accumulation, which impaired oxidative phosphorylation and cellular energetic balance, driving apoptotic death and selective eradication of chemoresistant AML cells in vitro and in vivo. Altogether, this study uncovers a noncanonical function of MPO enzyme in maintaining redox balance and mitochondrial energetic metabolism, therefore affecting downstream pathways involved in AML chemoresistance. SIGNIFICANCE: These findings demonstrate the role of myeloperoxidase in the regulation of ROS levels and sensitivity of AML cells to cytarabine, an essential chemotherapeutic backbone in the therapy of AML.
Protein tyrosine phosphatase receptor type delta (PTPRD) is expressed in normal and cutaneous squamous cell carcinoma-derived keratinocytes
Authors: K. J. Purdie, C. A. Harwood, T. Chaplin, K. Gibbon, N. Singh, B. D. Young, J. B. Cazier, I. M. Leigh, C. M. Proby
Journal: British Journal of Dermatology (2010)
Detecting lower in addition to the highest Gleason score prostate cancer on core biopsy and the risk of prostate cancer-specific mortality.
Authors: Ayal A. Aizer, John Phillips, Ming-Hui Chen, Danjie Zhang, Marian Loffredo, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2013)

5051 Background: We evaluated the risk of prostate cancer-specific mortality (PCSM) following definitive treatment in men with at least one prostate biopsy core with a Gleason score (GS) lower than the highest GS identified. This pattern termed “ComboGS” in a concurrent submission was shown to be associated with a significant reduction in the odds of upgrading at radical prostatectomy (RP). Methods: In this validation cohort 666 men with localized or locally advanced prostate cancer, men were diagnosed via a transrectal, ultrasound-guided needle prostate biopsy (median 6, IQR 5-6 cores) and treated definitively between 1989-2000 with either RP or radiation (RT) or RT and hormones (HT) at a regional radiation oncology center. Patients could be referred into this center from 6 community based hospitals in Southeastern Massachusetts and Rhode Island. Community based pathologists from these 6 health care facilities assigned the biopsy GS used for the analyses in this study. Multivariable competing risks regression was performed (Table) to assess the impact of ComboGS on the risk of PCSM adjusting for age, established PC prognostic factors, and treatment. Results: After a median follow up of 4.6 years (IQR 2.5-6.7 years), 168 men (25.2%) died, 41 (24.4%) of PC. ComboGS was associated with a decreased risk of PCSM (Adjusted Hazard Ratio (AHR) 0.40, 95% Confidence Interval (CI) 0.19-0.85, p=.017). Estimates of PCSM were significantly lower in men with versus without ComboGS when the highest GS was ≥7 (p&lt;.001) but not 6 or less (p=.71). Specifically these 5-year estimates were 14.4% and 4.8% versus 1.9% and 2.7% respectively. Conclusions: In addition to lower odds of upgrading at RP, using an independent data set the ComboGS assessed by community based pathologists serving 6 hospitals was found to also be associated with a decreased risk of PCSM. [Table: see text]
Salvage MitraClip in severe secondary mitral regurgitation complicating acute myocardial infarction: data from a multicentre international study
Authors: Dan Haberman, Maurizio Taramasso, Andrew Czarnecki, Arthur Kerner, Michael Chrissoheris, Konstantinos Spargias, Lion Poles, Yoram Agmon, Salvatore Scianna, Ronen Beeri, Chaim Lotan, Francesco Maisano, Mony Shuvy
Journal: European Journal of Heart Failure (2019)
DTIC and GM-CSF in the treatment of patients with metastatic melanoma.
Authors: Beth Barber, Zhongyun Zhao, Song Wang, Volker Jean Wagner
Journal: Journal of Clinical Oncology (2012)

e19045 Background: To describe patients with metastatic melanoma being treated with mono-therapy, dacarbazine (DTIC) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Methods: Using a large U.S. medical claims database, patients were identified between 2005 and 2010 using ≥2 melanoma diagnoses (ICD-9-CM: 172.xx, V10.82) and ≥2 diagnoses for metastasis (ICD-9-CM: 197.xx, 198.xx). Patients who received mono-therapy with DTIC or GM-CSF as the first documented drug therapy after metastatic diagnosis were identified. Patient demographic and clinical characteristics and treatment duration were compared between patients treated with DTIC and those who received GM-CSF. Furthermore, comparisons were also made between the two treatment groups after 1-to-1 matching on age, gender, and baseline comorbidities. Results: A total of 81 patients with metastatic melanoma receiving first-line DTIC and 24 patients with metastatic melanoma receiving first-line GM-CSF were included in this analysis. On average, DTIC patients were 8.5 years older (p = 0.009) and had higher baseline Charlson Comorbidity Index scores (D0.43, p = 0.005) than GM-CSF patients. The mean duration of first line treatment was 94 days on DTIC and 135 days on GM-CSF. The mean length of follow-up from the start of first line was 257 days on DTIC and 451 days on GM-CSF. After each GM-CSF patient was matched with a DTIC patient on age, gender, and baseline Charlson Comorbidity Index score, the mean duration of first line treatment was 79 days on matched DTIC and 135 days on GM-CSF, and the mean length of follow-up from the start of first line was 317 days on matched DTIC and 451 days on GM-CSF. Conclusions: Patients with metastatic melanoma who received DTIC treatment were older and had higher comorbidity index scores but shorter treatment duration than those who received GM-CSF; the difference in treatment duration remained after DTIC patients were matched with GM-CSF patients on age, gender and comorbidity index scores.
Indoleamine 2,3-Dioxygenase-1 Expressing Dendritic Cell Populations Are Associated with Tumor-Induced Immune Tolerance &amp; Aggressive Disease Biology in Chronic Myelomonocytic Leukemia
Authors: Abhishek A. Mangaonkar, Kaaren K. Reichard, April Chiu, Matthew T Howard, Rebecca L King, Ryan M. Carr, Bonnie M Alver, Keith D. Robertson, Margot Cousin, Jose C Villasboas, Martin E. Fernandez-Zapico, Terra L. Lasho, Naseema Gangat, Aref Al-Kali, Michelle A. Elliott, William J. Hogan, Mark R. Litzow, Animesh Pardanani, Eric Solary, Ayalew Tefferi, Mrinal M. Patnaik
Journal: Blood (2018)