tbuckley/cabot-search huggingface dataset:
Postmastectomy radiotherapy for patients with one to three positive lymph nodes: Utilization and benefit.
Authors: Dezheng Huo, Ningqi Hou, Nora T. Jaskowiak, Yasmin Hasan, David J. Winchester, David Porter Winchester, Katharine Yao
Journal: Journal of Clinical Oncology (2012)

1116 Background: The use of postmastectomy radiotherapy (PMRT) for patients with pT1-2pN1 tumors is controversial and ASCO guidelines indicate that there is insufficient evidence to make recommendation. We hypothesized that the use of PMRT in this patient group was low and has minimal impact on survival. Methods: The study includes 83,742 invasive breast cancer patients from the National Cancer Data Base who underwent mastectomy with pT1-2 and pN1 disease from 1998-2007. Neoadjuvant cases were excluded. We investigated factors related to PMRT use using cross tables and logistic regression. Survival analysis was conducted using Cox models in patients diagnosed from 1998-2002, with a median follow-up of 5.5 years. Results: The proportion of N1 patients undergoing PMRT remained stable from 1998 to 2007, at approximately 20%. PMRT use increased with larger tumor size (15.4% in T1N1 and 24.4% in T2N1), and with increasing positive lymph nodes (14.6%, 23.7%, and 35.2% for patients with one, two, or three positive nodes, respectively). Age was significantly inversely correlated with PMRT use: the proportion of patients receiving PMRT was 31.3% for age &lt;40 years and 8.2% for 80+ years (p&lt;0.001). Asians are more likely to receive PMRT (25.5%), compared to other races (20.3% white, 20.7% black, and 20.6% Hispanic; p&lt;0.001). PMRT also varied considerably by facility location, the highest in the Northeast at 31.3%, and the lowest in the South at 15.8% (p&lt;0.001). There was only minor difference in PMRT use between different types of cancer centers. Insurance status, income and education level were not associated with PMRT use. After adjusting for prognostic factors in the Cox models, PMRT use was associated with a reduced mortality (hazard ratio=0.87, 95% CI: 0.81-0.93; p&lt;0.001). The multivariable-adjusted 5-year death rate was 16.1% in patients receiving PMRT and 18.1% in patients not receiving PMRT. For pT1N1 tumors the absolute benefit was 1.3% compared to 2.7% for pT2N1 tumors. Conclusions: PMRT use varies with facility and clinicopathologic factors, but not socioeconomic factors. The risks of radiation need to be weighed against the 2% absolute survival benefit when deciding on whether to use PMRT for pT1-2N1 patients.
THU0671 PULMONARY INVOLVEMENT IN RHEUMATOID ARTHRITIS: PATTERNS AND EPIDEMIOLOGICAL CHARACTERISTICS FROM A MONOCENTRIC COHORT STUDY
Authors: Evripidis Kaltsonoudis, Eleftherios Pelechas, Paraskevi V. Voulgari, Alexandros Drosos
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Extra-articular manifestations (EAM) are not an uncommon finding in patients with Rheumatoid Arthritis (RA). Pulmonary involvement is a potential life-threatening EAM with deleterious effects on the quality of life and is reported in different occurrence among studies. <h3>Objectives:</h3> To evaluate the frequency of pulmonary involvement in RA patients followed-up in a 15-years period. <h3>Methods:</h3> 549 RA patients were diagnosed according to the ACR/EULAR classification criteria since 2003. A full clinical examination as well as a detailed laboratory and immunological evaluation has been carried-out at baseline. Furthermore, chest, hand and wrist but also feet radiographs had been obtained. All patients were followed-up at predefined times and were treated appropriately with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biologic (b)DMARDs. Any laboratory abnormalities or comorbidities were recorded and investigated appropriately at every visit. In addition, the disease activity score (DAS) using the 28-joints count (DAS-28) was recorded. <h3>Results:</h3> Initial evaluation revealed 15 patients as having pulmonary abnormalities. Thus, these patients were excluded. From the rest, 37 (6.7%) patients manifested lung involvement. There were 26 males and 11 females, with mean age of 62.9 ±3.4 years and disease duration of 8.5 ±2.2 years. 14 were smokers and 10 ex-smokers. Dry cough and dyspnea on exertion were the main pulmonary symptoms. High resolution computed tomography (HRCT) scan of the chest revealed interstitial lung disease (ILD). More specifically, 23 patients showed usual interstitial pneumonia (UIP), 10 patients had nonspecific interstitial pneumonia (NSIP), while 4 had a mixed pattern. Six patients died 4 years after ILD development. ILD was associated with high DAS-28, seropositivity and male gender. <h3>Conclusion:</h3> ILD is not a frequent EAM in patients with RA, but it carries a poor prognosis with high morbidity and mortality and it is associated with RA disease activity and male gender. UIP is the most prevalent pattern of ILD in RA patients. <h3>Disclosure of Interests:</h3> None declared
SAT0245 CHOROIDAL EVALUATION IN PATIENTS WITH CHILDHOOD POLYARTERITIS NODOSA (PAN) ANDADENOSINE DEAMINASE-2 DEFICIENCY (DADA-2)
Authors: Hafize Emine Sonmez, Abdullah Ağin, Sibel Kadayifçilar, Ata Baytaroğlu, Özge Deliktaş, Selcan Demir, Yelda Bilginer, Bora Eldem, Seza Özen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis affecting small or medium arteries with a negative ANCA serology and no evidence of glomerulonephritis. <h3>Objectives</h3> The aim of this study was to evaluate the choroid with optical coherence tomography (OCT) in children with polyarteritis nodosa (PAN) and adenosine deaminase-2 deficiency (DADA-2). <h3>Methods</h3> The study included all PAN and DADA-2 patients (n=15), examined between June 2017 and September 2018, and an age and gender-matched control group (n=15). After ocular examination, choroidal images taken with sd-OCT (Heidelberg Spectralis) were evaluated with regard to choroidal thickness (ChT) at five points (750 and 1500 microns from the center of the fovea both in the temporal, nasal quadrant and under the fovea), total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI). <h3>Results</h3> None of the patients had active ocular complaints or findings. The mean (±SD) age was 8.4 ± 3.69 years. ChT at 3 points, TCA, LA, and SA were found to be higher in patients with PAN and DADA-2. The CVI values were similar in both groups. No correlations were found between the OCT findings, activity score index (PVAS) and the biochemical parameters (Erythrocyte sedimentation rate, leukocyte, C-Reactive Protein). <h3>Conclusion</h3> The results of this study showed that the choroid was thicker in patients with PAN and DADA-2 than in the control group, suggesting that PAN and DADA-2 may affect the choroid. Ophthalmologic evaluation is important in PAN and DADA-2 patients, even in the absence of relevant complaints. <h3>References</h3> [1] Ozen S, Anton J, Arisoy N, et al. Juvenile polyarteritis: results of a multicenter survey of 110 children. J Pediatr. 2004;145(4):517-522. [2] Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res. 2012;31(5):377-406. <h3>Acknowledgement</h3> None <h3>Disclosure of Interests</h3> Hafize Emine Sonmez: None declared, Abdullah Ağin: None declared, Sibel Kadayifçilar: None declared, Ata Baytaroğlu: None declared, Özge Deliktaş: None declared, Selcan Demir: None declared, Yelda Bilginer: None declared, Bora Eldem: None declared, Seza Özen Consultant for: Seza Ozen is receiving consultancy fees from Novartis, Speakers bureau: Roche
Patients’ and health professionals’ perspectives on the outcomes, conduct, and medico-legal implications of multidisciplinary cancer meetings (MDMs).
Authors: Bianca Alix Devitt, Jennifer Philip, Madhu Sudan Singh, Linda R. Mileshkin, Sue-Anne McLachlan
Journal: Journal of Clinical Oncology (2012)

e16562 Background: Multidisciplinary cancer meetings (MDMs) are a fundamental component of multidisciplinary cancer care. Guidelines relating to their conduct are largely based on expert opinion rather than empirical evidence. We examined patients and health professionals’ (HPs) attitudes to the outcomes, conduct and medico-legal implications of MDMs. Methods: Two study-specific questionnaires were developed based on qualitative research, published literature and guidelines, for health professionals who attend MDMs and patients with a current or previous diagnosis of cancer. The questionnaires were administered at 4 health services encompassing tertiary and regional centres in Victoria, Australia. Results: 170 HPs (response rate 62%) and 110 patients (response rate 83%) completed the questionnaire. 92% of patients want their case discussed at an MDM. HPs believe the focus of MDMs is to consider different treatment modalities (99%) and ensure patients receive evidence-based care (83%) rather than address psychosocial issues (52%). Similarly, patients allocated 71% of MDM discussion time to discussing possible treatment options, 15% to relevant social issues and 14% to psychological issues. More than 70% of patients and HPs thought no formal patient consent was required prior to discussion at MDM. 75% of HPs agreed MDMs provided them with increased medico-legal protection. 93% of HPs thought MDM discussions should result in a consensus on the proposed management plan. Patients would prefer to discuss the outcomes of the MDM personally with their treating doctor (81%) and 75% also desired written documentation. Conclusions: Patients and HPs agree the focus of MDMs is predominately medical with emphasis on treatment planning rather than the psychosocial needs of patients. Both groups believe MDM discussion forms part of standard care and formal consent is not required. HPs aim to develop an individualized, evidence-based management plan, agreed to by consensus. Strategies to improve communication of this plan to patients should be developed. This is the first empirical evidence on MDMs’ conduct and should help inform the development of future guidelines.
Heated tobacco and politics in Italy
Authors: Giulio Formoso, Maria Grazia Celani, Silvia Minozzi, Michela Cinquini, Paola Mosconi, Vanna Pistotti, Teresa Cantisani, Roberto D’Amico
Journal: BMJ (2019)

Big tobacco companies using political links to foster their business is concerning.1 In Italy, a “sunshine act” proposal to make financial links between healthcare professionals and industry more transparent has been approved by the …
Preclinical therapeutic targets in diffuse midline glioma
Authors: Michaël Hananja Meel, Gertjan J.L. Kaspers, Esther Hulleman
Journal: Drug Resistance Updates (2019)

Diffuse midline gliomas (DMG) are rapidly fatal tumors of the midbrain in children, characterized by a diffuse growing pattern and high levels of intrinsic resistance to therapy. The location of these tumors, residing behind the blood-brain barrier (BBB), and the limited knowledge about the biology of these tumors, has hindered the development of effective treatment strategies. However, the introduction of diagnostic biopsies and the implementation of autopsy protocols in several large centers world-wide has allowed for a detailed characterization of these rare tumors. This has resulted in the identification of novel therapeutic targets, as well as major advances in understanding the biology of DMG in relation to therapy resistance. We here provide an overview of the cellular pathways and tumor-specific aberrations that have been targeted in preclinical DMG research, and discuss the advantages and limitations of these therapeutic strategies in relation to therapy resistance and BBB-penetration. Therewith, we aim to provide researchers with a framework for successful preclinical therapy development.
SAT0059 APOLIPOPROTEIN B DERIVED PEPTIDES INHIBIT PRODUCTION OF PRO-INFLAMMATORY CYTOKINES IN PBMC OF RHEUMATOID ARTHRITIS (RA) PATIENTS AND IMPROVE ARTHRITIS IN ANIMAL MODEL OF RA
Authors: Ji Soo Park, Joo Youn Lee, Hyun Jung Yoo, Jeong Yeon Kim, Ji Hye Lee, Seon Uk Kim, Ra Ham Kim, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Eugene C. Yi, Yeong Wook Song
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Alpha-enolase (ENO1) is a multifunctional glycolytic enzyme. The cell-surface expression of ENO1 is increased in monocytes isolated from peripheral blood mononuclear cells (PBMCs) of RA patients. In previous experiments, we reported apolipoprotein B (apoB) to be as a novel ligand of cell surface expressed ENO1 and to enhance chronic inflammation in RA (1). <h3>Objectives:</h3> This study was performed to evaluate agonistic or antagonistic function of peptide sequences within apoB, which modulated severity of arthritis in K/BxN serum transfer arthritis mouse model. <h3>Methods:</h3> Peptides binding to ENO1 were evaluated by peptide microarray. Peptides were designed to have twelve amino acids lengths with ten amino acids overlap. Levels of pro-inflammatory cytokines produced by PBMCs were measured after treatment with peptides in RA patients and healthy controls (HCs). To evaluate the antagonistic function of peptides, RA PBMCs pre-treated with peptides were stimulated with apoB and pro-inflammatory cytokines were measured in culture supernatant. Peptides were injected in K/BxN serum transfer mice and we measured the thickness of ankles and arthritis score to determine whether peptides could reduce arthritis severity. <h3>Results:</h3> Among eighty five peptides from apoB, five peptides exhibited strong binding to ENO1. Two peptides increased production of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α, but three peptides did not change levels of pro-inflammatory cytokines in RA and HC PBMCs. However the three peptides reduced production of pro-inflammatory cytokines in RA PBMCs stimulated with apoB. These three peptides were named IP (inhibitory peptide)1, IP2 and IP3. IPs were injected after induction of the arthritis in K/BxN serum transfer mice in vivo. Ankle thickness and arthritis scores were substantially reduced in IPs treated group than control group, and synovial inflammation, bone erosion and cartilage damage of arthritis were less severe in the IPs-treated groups. Especially, IP2 showed the most significant effect. <h3>Conclusion:</h3> The apoB derived peptides interacting with ENO1 could have novel therapeutic effect in RA. <h3>Reference</h3> [1] Lee, J. Y., et al. (2018). "Apolipoprotein B binds to enolase-1 and aggravates inflammation in rheumatoid arthritis."Ann Rheum Dis77(10): 1480-1489 <h3>Disclosure of Interests:</h3> None declared
Rebalancing Protein Homeostasis Enhances Tumor Antigen Presentation
Authors: Alex M. Jaeger, Lauren Stopfer, Sunmin Lee, Giorgio Gaglia, Demi Sandel, Sandro Santagata, Nancy U. Lin, Jane B. Trepel, Forest White, Tyler Jacks, Susan Lindquist, Luke Whitesell
Journal: Clinical Cancer Research (2019)

Despite the accumulation of extensive genomic alterations, many cancers fail to be recognized as "foreign" and escape destruction by the host immune system. Immunotherapies designed to address this problem by directly stimulating immune effector cells have led to some remarkable clinical outcomes, but unfortunately, most cancers fail to respond, prompting the need to identify additional immunomodulatory treatment options.Experimental Design: We elucidated the effect of a novel treatment paradigm using sustained, low-dose HSP90 inhibition in vitro and in syngeneic mouse models using genetic and pharmacologic tools. Profiling of treatment-associated tumor cell antigens was performed using immunoprecipitation followed by peptide mass spectrometry.We show that sustained, low-level inhibition of HSP90 both amplifies and diversifies the antigenic repertoire presented by tumor cells on MHC-I molecules through an IFNγ-independent mechanism. In stark contrast, we find that acute, high-dose exposure to HSP90 inhibitors, the only approach studied in the clinic to date, is broadly immunosuppressive in cell culture and in patients with cancer. In mice, chronic non-heat shock-inducing HSP90 inhibition slowed progression of colon cancer implants, but only in syngeneic animals with intact immune function. Addition of a single dose of nonspecific immune adjuvant to the regimen dramatically increased efficacy, curing a subset of mice receiving combination therapy.These highly translatable observations support reconsideration of the most effective strategy for targeting HSP90 to treat cancers and suggest a practical approach to repurposing current orally bioavailable HSP90 inhibitors as a new immunotherapeutic strategy.See related commentary by Srivastava and Callahan, p. 6277.
Targeting Topoisomerase I in the Era of Precision Medicine
Authors: Anish Thomas, Yves Pommier
Journal: Clinical Cancer Research (2019)

Irinotecan and topotecan have been widely used as anticancer drugs for the past 20 years. Because of their selectivity as topoisomerase I (TOP1) inhibitors that trap TOP1 cleavage complexes, camptothecins are also widely used to elucidate the DNA repair pathways associated with DNA-protein cross-links and replication stress. This review summarizes the basic molecular mechanisms of action of TOP1 inhibitors, their current use, and limitations as anticancer agents. We introduce new therapeutic strategies based on novel TOP1 inhibitor chemical scaffolds including the indenoisoquinolines LMP400 (indotecan), LMP776 (indimitecan), and LMP744, and on tumor-targeted delivery TOP1 inhibitors using liposome, PEGylation, and antibody-drug conjugates. We also address how tumor-specific determinants such as homologous recombination defects (HRD and BRCAness) and Schlafen 11 (SLFN11) expression can be used to guide clinical application of TOP1 inhibitors in combination with DNA damage response inhibitors including PARP, ATR, CHEK1, and ATM inhibitors.
FRI0686 RELATIONSHIP BETWEEN VITAMIN D SUPPLEMENTATION AND MUSCULAR STRENGTH IN ELDEST POPULATION. A SISTEMATIC REVIEW
Authors: Maria Betina Nishishinya, Claudia Alejandra Pereda Testa, Adela Cristina Cis, Monica Solana-Tramunt, M Guerra-Balic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Sarcopenia is the loss of skeletal muscle mass, strength and function that occurs as a consequence of aging. This condition result in physical disability, which limits the capacity to walk, increases the risk of falls and osteoporotic fractures. Several studies suggested an inverse relation between 25OHD serum levels, muscular strength and physical performance in the eldest. <h3>Objectives</h3> To evaluate if vitamin D supplementation in patients &gt; 50 years improves muscle mass, strength and performance in older patients. <h3>Methods</h3> We performed a systematic review through Medline, Cochrane Library, and EMBASE. Inclusion criteria: 1) patients &gt; 50 years old, 2) receiving treatment with vitamin D 3) muscle mass and muscle strength measurements 4) systematic reviews (SR) 5) randomized clinical trials (RCT) 6) Papers written in English or Spanish. <h3>Results</h3> Five studies were included (4 SR and 1 RCT), n patients ranged from 121 to 5615. Patients mean age oscillated between 58-88 years, receiving variable vitamin D dose. Follow-up period fluctuated from 6 to 12 months. <h3>Conclusion</h3> · Vitamin D supplementation in patients &gt; 65 years with inadequate 25OHD serum levels, improve muscular strength. · There were no benefits in muscle mass or muscular performance. <h3>References</h3> [1] Beaudart C, Dawson A, Shaw S C, Harvey N H, Kanjis J A, Binkley N, et al. Nutrition and Physical activity in the prevention and treatment of sarcopenia.: systematic review. Osteopor Int2017; 28: 1817-1833. [2] Cangussu LM, Nahas-Neto J, Orsatti CL, Bueloni-Dias FN, Nahas EAP. Effect of Vitamin D supplementation alone on muscle function in postmenopausal women: a randomized double-blind, placebo-controlled clinical trial. Osteopor Int 2015; 26:2413-2421. <h3>Disclosure of Interests</h3> None declared
PB2151 HEPATITIS B VIRUS INFECTION MIGHT CONTRIBUTE TO MULTIPLE MYELOMA PROGRESSION THROUGH 1Q21 AMPLIFICATION
Authors: X. Peipei
Journal: HemaSphere (2019)

Background: Hepatitis B virus (HBV) is not only a hepatotropic virus but also a lymphotropic virus. The association between HBV and hematologic malignancies has also been described, but the correlation between HBV infection and multiple myeloma (MM) has remained controversial. Aims: This study aimed to assess the prevalence of HBV infection in patients with MM and investigate their characteristics and prognostic significance. Methods The clinical data of 165 patients with MM receiving at least four cycles of chemotherapy from April 2008 to February 2017 in Nanjing Drum Tower Hospital were collected. HBV markers were determined by an enzyme‐linked immunosorbent assay. Results: The rates of an acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12% and 26.06%, respectively. The gain of 1q21 was statistically significant in HBV‐positive and HBV‐negative patients (54% vs. 38.2%, P = 0.048), and the level of alanine transaminase (ALT) in HBV‐infected patients was significantly higher than that of the non‐infected group (63.29 vs. 24.66 U/L, P = 0.043). Lactate dehydrogenase, serum creatinine, and serum calcium levels were found as significant risk factors of overall survival. The progression‐free survival (PFS) of HBV‐positive patients was shorter than that of HBV‐negative patients (18.97 vs. 29.67 months P = 0.006), and HBV positive was considered an independent prognostic factor of PFS. Summary/Conclusion: HBV infection might contribute to MM progression through 1q21 amplification, and HBV markers should be closely monitored in patients with MM.