tbuckley/cabot-search huggingface dataset:
How important is the axillary nodal status for adjuvant treatment decisions at a breast cancer multidisciplinary tumor board? A survival analysis
Authors: T. Reimer, R. Fietkau, S. Markmann, A. Stachs, B. Gerber
Journal: Journal of Clinical Oncology (2007)

11041 Background: Postoperative tumor board recommendations for breast cancer are mainly based on patient characteristics and tumor parameters such as size, histologic grade, lymphovascular invasion (LVI), hormone receptor and HER2/neu status. In the era of potential avoidance of axillary surgery in clinically node-negative patients we evaluate the impact of pathologic nodal status for adjuvant treatment decisions. Methods: The postoperative tumor board records of 207 consecutive breast cancer patients over a 1-year period were rediscussed without knowledge of pathologic nodal status. Differences between the two board recommendations for each patient were classified as major (chemo- and/or radiotherapy: present/absent) or minor (different chemotherapeutic protocols) discrepancies. The disease-free and overall survival rates among subgroups with different recommendations were calculated using Adjuvant! Online tool. The binary logistic regression was performed to analyze the impact of factors for prediction the major discrepancy subgroup. Results: The tumor board without information of pathologic nodal status resulted in treatment changes in 72 of the 207 patients studied (34.8%). Major discrepancies were observed in 37 patients (17.9%) leading to a complete shift of postoperative management. Disease-free and overall survival rates were not significantly different due to a balanced over- and undertreatment in this subgroup (21 cases with under-, 16 cases with overtreatment). The major discrepancies were related to LVI (P=0.001), postmenopausal status (P=0.047), and positive hormone receptor status (P=0.17) in the univariate setting. LVI was an independent parameter to predict the subgroup with major discrepancies performing a multivariate analysis (P=0.006; RR=4.5 [95%CI: 1.5–13.4]). Conclusions: The knowledge of pathologic nodal status is important for postoperative chemotherapy and postmastectomy radiotherapy indications. There is a risk for one third of all patients when avoiding axillary surgery to get an adjuvant therapy which differ from the current treatment guidelines. It is mandatory to know the nodal status for breast tumors with LVI. No significant financial relationships to disclose.
The impact of time of medical oncologist visit on survival among elderly patients with stage IV prostate cancer: An analysis using SEER-Medicare data
Authors: C. D. Mullins, E. Onukwugha, B. Seal, A. Hussain, A. Hussain
Journal: Journal of Clinical Oncology (2009)

e17509 Background: The association between physician referrals and treatment receipt has been established in other disease settings. The impact of time to a medical oncologist or hematologist/oncologist (MOH) visit on survival has not been examined in patients (pts) with advanced prostate cancer (A-PC). The objective of this study is to determine whether the time to a MOH visit is associated with survival. Methods: The SEER-Medicare database was used for the analysis. Pts aged &gt;65 diagnosed with A-PC between 1994 and 2002 and who visited a urologist post-diagnosis were included. Pts who saw a MOH before the urologist visit were excluded. For pts who saw a MOH, time to a MOH visit was identified using the diagnosis date and the urologist visit as starting points. Survival models were used to examine the effect of the time (in months) to MOH visit on survival, controlling for demographic, clinical, continuity-of-care, and ecological measures. Results: There were 6,498 pts in the sample (mean age 76 years, 82% White race). PC-specific mortality was 38%. Two-thirds (67%) of patients did not visit a MOH after visiting a urologist. Among those with a visit to a MOH, an additional month from diagnosis till the MOH visit was positively associated with PC mortality (HR: 1.03; p &lt; 0.001) - i.e. a shorter time to a MOH visit was associated with PC survival. Similar results were obtained using the month of the urologist visit as the starting point (HR: 1.02; p &lt; 0.001). Conclusions: Among A-PC patients who are referred to an oncologist, each additional month between diagnosis/urologist visit and the oncologist visit is associated with an increased relative risk of mortality. [Table: see text]
Oncology nurses’ views of oncologists’ prognosis-related communication (PRC)
Authors: P. R. Helft, C. Terry, A. R. Chamness, M. M. Uhrich
Journal: Journal of Clinical Oncology (2009)

6602 Background: PRC is critical to care, treatment, and decision-making for advanced cancer patients (ACP). Deficits in oncologists’ (MDs) PRC have previously been identified. The role oncology nurses (RNs) play in PRC and their views and experiences of PRC among MDs with whom they work is unknown. Methods: Mail survey of a random sample of Oncology Nursing Society members with at least one year of experience working with cancer patients (pts). Questionnaire was sent to 1338 members of ONS. 394 completed surveys were returned. Overall RR was 29.4%. Significance, if noted, implies p&lt;0.001. Results: Respondent demographics: median age 49.2, 96.6% female, 88.5% Caucasian, median years (yrs) as an RN 18, median yrs working with cancer patients 12, 69.1% had a BSN or ASN, 34.1% inpt RNs, 38.6% outpt RNs. 46% of RNs always/often cared for ACPs who did not appear to understand their prognosis, and 58.6% of RNs always/often encountered questions that suggested pts wanted more prognosis related information (PRI). 26.1% disagreed that the MDs they worked with were skilled at PRC. 72% agreed that MD discomfort with giving bad news is a major barrier to helping pts understand their prognosis. 54.9% of RNs always/often/sometimes felt pressured not to provide pts PRI because they did not want to contradict what MDs had said. 25.1% of RNs felt that MDs rarely or never kept them informed about their PRC with pts (frequency positively associated with yrs as an RN, yrs working with cancer pts, education level). RNs with at least an MSN were more likely to report that MDs more frequently kept them informed about their PRC. 30.2% of RNs felt that MDs rarely or never addressed end of life issues early in the course of their illness. 32.8% of RNs agreed that, when pts did not appear to understand their prognosis, it was because MDs had not discussed it fully (positively associated with working in an inpt setting). 42.6% of RNs were rarely or never present when PRI was discussed (negatively associated with working in an outpt setting and amount of formal education regarding PRC). Conclusions: Oncology RNs identify several deficits in MDs’ PRC with ACPs, including provision of information early in the course of illness, gaps in sharing content of PRC with RNs, and communicative aspects of team-based pt care. No significant financial relationships to disclose.
Patient Co-Morbidity Profile Should Drive PI3K Inhibitor Selection for Relapsed Follicular Lymphoma
Authors: Farrukh T. Awan, Rebecca J Chan, Wei Ye, Guan Xing, Caroline Roudet, Bianca Ruzicka, Martin Dreyling, Pier Luigi Zinzani, Ajay K. Gopal
Journal: Blood (2018)
Effect of donor, component, and recipient characteristics on hemoglobin increments following red blood cell transfusion
Authors: Nareg H. Roubinian, Colleen Plimier, Jennifer P. Woo, Catherine Lee, Roberta Bruhn, Vincent X. Liu, Gabriel J. Escobar, Steven H. Kleinman, Darrell J. Triulzi, Edward L. Murphy, Michael P. Busch
Journal: Blood (2019)
Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders
Authors: Siemon C. de Lange, Lianne H. Scholtens, Leonard H. van den Berg, Marco P. Boks, Marco Bozzali, Wiepke Cahn, Udo Dannlowski, Sarah Durston, Elbert Geuze, Neeltje E. M. van Haren, Manon H. J. Hillegers, Kathrin Koch, María Ángeles Jurado, Matteo Mancini, Idoia Marqués-Iturria, Susanne Meinert, Roel A. Ophoff, Tim J. Reess, Jonathan Repple, René S. Kahn, Martijn P. van den Heuvel
Journal: Nature Human Behaviour (2019)
The risk of thrombotic events in patients with primary versus secondary hepatic malignancies who are undergoing surgical resection
Authors: T. J. Yates, M. Abouljoud, A. Lambing, P. Kuriakose
Journal: Journal of Clinical Oncology (2007)

15178 Background: The increased risk of thromboses is well documented in patients with malignancies, and those undergoing abdominal surgery. Furthermore, patients requiring hepatic resection for underlying malignant disease have been reported to be at increased risk for thrombotic complications. However, guidelines for thromboprophylaxis in this patient population are still under investigation. A cursory review performed at our institution determined the incidence of thrombotic events to be comparable to that reported in the literature. We, therefore, went further to study if there was a difference in the risk of thromboses between those undergoing resection for primary hepatic cancer, versus metastatic disease. Methods: We performed a retrospective chart review of patients undergoing surgical resection for hepatic malignancies. The primary end point was to determine whether there was a difference in the incidence of thrombotic events between primary and secondary malignancies. Results: A total of 99 patients at our institution underwent surgical resection for either primary or secondary hepatic malignancies in the past 5 years. There were 7 patients who developed thrombotic events within three months of their resection. Of these patients, all 7 underwent resection for secondary hepatic malignancies. Based on the nature of this study, and its lack of standardized thromboprophylaxis, statistical analysis was not performed. Conclusions: Patients undergoing surgical resection of hepatic malignancies appear to be at increased risk of thrombotic events, and may require more specific standardization of their thromboprophylaxis. Furthermore, based on our observation it appears those associated with metastatic disease may derive an even greater benefit from this. Future prospective studies will be required to evaluate this difference in thromboses, and to better define the guidelines for thromboprophylaxis. No significant financial relationships to disclose.
Phase III study of investigational MLN8237 (alisertib) versus investigator’s choice in patients (pts) with relapsed/refractory (rel/ref) peripheral T-cell lymphoma (PTCL).
Authors: Owen O'Connor, E. Jane Leonard, Ely Benaim
Journal: Journal of Clinical Oncology (2012)

TPS8110 Background: PTCL is a rare form of aggressive non-Hodgkin lymphoma (NHL), accounting for 5–20% of NHL diagnoses. Standard NHL therapies developed primarily for B-cell lymphomas are not optimal for PTCL and early relapse is common. Current treatments for rel/ref PTCL include pralatrexate, romidepsin, and gemcitabine; however, outcomes remain poor. The oral, investigational drug, MLN8237, is a selective inhibitor of Aurora A kinase (AAK) – a key mitotic regulator that is overexpressed or amplified in various human tumors. Emerging clinical data from a phase II study of single agent MLN8237 in rel/ref aggressive T-cell lymphoma (Friedberg et al, ASH 2011) support further clinical evaluation in this indication. Methods: In this open-label, randomized, phase III study, a maximum of 354 adults with rel/ref PTCL after ≥1 prior systemic cytotoxic therapies will be enrolled at approximately 140 centers worldwide. Pts will be randomized 1:1 to MLN8237 50 mg twice daily as an enteric coated tablet on days 1–7 of 21-day cycles, or to investigator’s choice of: pralatrexate 30 mg/m 2 IV once weekly for 6 weeks in 7-week cycles; romidepsin 14 mg/m 2 IV on days 1, 8, and 15 of 28-day cycles; or gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 of 28-day cycles. Pts with disease response/stabilization will be able to continue treatment provided that clinical benefit is demonstrated and treatment is tolerable. The expected study duration is 44 months. Primary endpoints are overall response rate (complete response [CR] + partial response) and progression free survival by International Working Group criteria (Cheson et al, 2007). Secondary endpoints include CR rate, overall survival, time to progression, time to response, duration of response, safety, and quality of life. Exploratory endpoints include an evaluation of candidate biomarkers (such as AAK protein expression levels and gene amplification, and the tumor proliferative marker Ki-67) in tumor biopsies. This study is registered at ClinicalTrials.gov: #NCT01482962.
Aromatase inhibitor-induced joint symptom in patients with breast cancer
Authors: Y. Yamamoto, T. Kawasoe, M. Ibusuki, K. Kai, S. Tomita, H. Iwase
Journal: Journal of Clinical Oncology (2007)

11070 Background: Aromatase inhibitor (AI) are superior to tamoxifen (TAM) for postmenopausal women with estrogen receptor (ER)-positive breast cancer. Toxic profiles are different between AI and TAM. The frequency of bone fracture and joint symptom are high in AI compared with TAM. However, there is little report concerning a detailed joint symptom. Methods: From January 2002 to March 2006, 120 postmenopausal women with ER-positive breast cancer were treated with anastrozole 1mg or exemestane 25mg daily at our hospital. We studied retrospectively the incidence, onset, type, sites, grade, and change of joint symptom. We also investigated the incidence of discontinuation due to joint symptoms and correlation between patient’s characteristics and joint symptoms. Results: Median follow-up time is 590 days and median age is 63 years old. Forty-seven (39.1%) of 120 patients complained of joint symptom. Median onset time of the symptom was 90 days of starting AI. All cases with the symptom complained of joint stiffness and 33 (70.2%) of 47 patients with the symptom have joint pain. In decreasing order, the most commonly affected sites were hand, knee, wrist, ankle, shoulder and elbow. The joint symptom was mostly grade 1/2, and most symptom ware resolved with exercise. Most common feature is morning digital stiffness like initial symptom of rheumatoid arthritis. Some patients experienced severe joint symptom. Subsequently, 15 (12.5%) patients had to discontinue AI because of the severe symptom. Discontinuation of AI led to improvement of symptoms, and patients received TAM in stead of AI also led to resolution of symptoms. AI-induced joint symptom was significantly correlated with young age, prior chemotherapy and switching from TAM to AI. Conclusions: Most AI-induced joint symptom is modest, and this symptom can lead to resolution with exercise. However, some patients lead to discontinue AI because of AI-induced severe joint symptom. We should inform patients treated with AI about AI- induced joint symptom and observe patient’s symptom in detail because severe joint symptom can prevent maintenance of quality of life and compliance. No significant financial relationships to disclose.
Clinical and molecular characteristics of lymphoplasmacytic lymphoma not associated with an IgM monoclonal protein: A multicentric study of the Rete Ematologica Lombarda (REL) network
Authors: Marzia Varettoni, Emanuela Boveri, Silvia Zibellini, Alessandra Tedeschi, Chiara Candido, Virginia Valeria Ferretti, Ettore Rizzo, Elisa Doni, Michele Merli, Lucia Farina, Maria Goldaniga, Anna Gallì, Sara Rattotti, Anna Maria Frustaci, Marina Deodato, Laura Bandiera, Giuseppe Isimbaldi, Silvia Uccella, Antonello Domenico Cabras, Umberto Gianelli, Luca Baldini, Marco Paulli, Luca Arcaini
Journal: American Journal of Hematology (2019)

Abstract Lymphoplasmacytic lymphoma (LPL) is usually associated with a serum IgM paraprotein, corresponding to Waldenström's Macroglobulinemia (WM). Cases presenting with IgG or IgA, or without a monoclonal protein are extremely rare. We analyzed clinical characteristics, frontline treatment, and the outcome of 45 patients with non‐IgM LPL, and compared them with a control group of WM patients. The median age was similar, with significantly higher prevalence of females in non‐IgM LPL, than in WM patients (60% vs 39%, P = .016). Patients with non‐IgM LPL more frequently presented with lymphadenopathies (53% vs 15%, P &lt; .001), splenomegaly (22% vs 8%, P = .015) or extranodal involvement (20% vs 8%, P = .05). In non‐IgM LPL a serum monoclonal protein and bone marrow infiltration were less common than in WM patients (69% and 84% of cases respectively, P &lt; .001 for both comparisons). The MYD88 (L265P) mutation was found in 8/19 patients using allele‐specific polymerase chain reaction. A CXCR4 mutation was found in 4/17 cases using Sanger. In 16 patients we performed targeted next‐generation sequencing of genes MYD88, CXCR4, ARID1‐A, KMT2D, NOTCH2, TP53, PRDM1, CD79B, TRAF3, MYBBP1A, TNFAIP3 . Seven patients (44%) had a MYD88 mutation (S219C in one), four (25%) a CXCR4 mutation, three (19%) a KMT2D mutation, one (6%) a TP53 mutation and one (6%) a TRAF3 mutation. With a median follow‐up of 55.7 months, 36 non‐IgM LPL patients (80%) were treated. Non‐IgM LPL patients received more frequently anthracycline‐containing regimens, as compared with WM patients, who mainly received alkylating‐based therapies. Five‐year overall survival (OS) was 84%, similar to that of WM patients.
Infographic. Strength training–induced adaptations associated with improved running economy: potential mechanisms and training recommendations
Authors: Leonardo Coelho Rabello Lima, Richard Blagrove
Journal: British Journal of Sports Medicine (2019)

Running economy (RE) is an important determinant of distance running performance that expresses running efficiency as the oxygen uptake necessary to sustain a fixed submaximal running speed.1 Many interventions have been proposed to improve RE (ie, reduce oxygen uptake), with strength training (ST) being one of the most frequently investigated training strategies.1 2 The literature indicates that 6 to 14 weeks of ST intervention is likely to improve RE, especially when it emphasises the …
Health care costs associated with venous thromboembolism in select high-risk ambulatory solid tumor patients in the United States.
Authors: Alok A. Khorana, Mehul Dalal, Jay Lin, Gregory Clayton Connolly
Journal: Journal of Clinical Oncology (2012)

6059 Background: Venous thromboembolism (VTE) is an increasingly common complication of cancer and its treatment, including chemotherapy. VTE has significant clinical consequences, including mortality. However, contemporary data on the healthcare costs of cancer-associated VTE are limited. We examined the real-world economic burden of VTE in ambulatory patients initiating chemotherapy for select common high-risk solid tumors. Methods: Healthcare claims data (2004-2009) from the IMS/PharMetrics Patient-Centric database were collected for propensity score-matched adult cancer (lung, colorectal, pancreas, stomach, bladder and ovary) patients with VTE (n=912) and without VTE (n=2,736) after initiating chemotherapy. Healthcare resource utilization (inpatient, outpatient medical, and outpatient prescription drug claims) and costs were compared between the two cohorts during 12 months’ follow-up after the index VTE event. Incremental costs of VTE were adjusted for demographic and clinical covariates. Results: Cancer patients with VTE had ~3-times as many all-cause hospitalizations (mean 1.38 vs. 0.55 per patient) and days in hospital (10.2 vs. 3.4 per patient), and more outpatient claims (331 vs. 206 per patient) than matched cancer patients without VTE (all P&lt;0.0001). Cancer patients with VTE incurred significantly higher overall (all-cause) inpatient costs (mean $21,299 vs. $7,459 per patient), outpatient costs (mean $53,660 vs. $34,232 per patient) and total healthcare costs (mean $74,959 vs. $41,691 per patient) than cancer patients without VTE (all P&lt;0.0001). Total VTE-related healthcare costs were (mean) $9,247 per VTE patient over 12 months. Adjusted incremental all-cause healthcare costs of VTE were (mean) $30,538 per patient across the selected tumors, ranging from $11,946 per patient for gastric cancer to $38,983 per patient for pancreatic cancer. Conclusions: VTE results in significant inpatient and outpatient resource utilization, and increased all-cause (in addition to VTE-related) healthcare costs. Measures to prevent outpatient cancer-associated VTE may reduce healthcare utilization and costs in high-risk cancer patients.
The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
Authors: Pablo E. Hollstein, Lillian J. Eichner, Sonja N. Brun, Anwesh Kamireddy, Robert U. Svensson, Liliana I. Vera, Debbie S. Ross, T.J. Rymoff, Amanda Hutchins, Hector M. Galvez, April E. Williams, Maxim N. Shokhirev, Robert A. Screaton, Rebecca Berdeaux, Reuben J. Shaw
Journal: Cancer Discovery (2019)

Abstract Mutations in the LKB1 (also known as STK11) tumor suppressor are the third most frequent genetic alteration in non–small cell lung cancer (NSCLC). LKB1 encodes a serine/threonine kinase that directly phosphorylates and activates 14 AMPK family kinases (“AMPKRs”). The function of many of the AMPKRs remains obscure, and which are most critical to the tumor-suppressive function of LKB1 remains unknown. Here, we combine CRISPR and genetic analysis of the AMPKR family in NSCLC cell lines and mouse models, revealing a surprising critical role for the SIK subfamily. Conditional genetic loss of Sik1 revealed increased tumor growth in mouse models of Kras-dependent lung cancer, which was further enhanced by loss of the related kinase Sik3. As most known substrates of the SIKs control transcription, gene-expression analysis was performed, revealing upregulation of AP1 and IL6 signaling in common between LKB1- and SIK1/3-deficient tumors. The SIK substrate CRTC2 was required for this effect, as well as for proliferation benefits from SIK loss. Significance: The tumor suppressor LKB1/STK11 encodes a serine/threonine kinase frequently inactivated in NSCLC. LKB1 activates 14 downstream kinases in the AMPK family controlling growth and metabolism, although which kinases are critical for LKB1 tumor-suppressor function has remained an enigma. Here we unexpectedly found that two understudied kinases, SIK1 and SIK3, are critical targets in lung cancer. This article is highlighted in the In This Issue feature, p. 1469