tbuckley/cabot-search huggingface dataset:
Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential
Authors: Ingrid Spaan, Reinier A. Raymakers, Anja van de Stolpe, Victor Peperzak
Journal: Journal of Hematology & Oncology (2018)

Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic bone disease, which is associated with bone pain and pathological fractures and was reported to facilitate disease progression. More recently, cumulative evidence also indicates the importance of intrinsic Wnt signaling in the survival of multiple myeloma cells. However, Wnt pathway-activating gene mutations could not be identified. The search for factors or processes responsible for Wnt pathway activation currently focuses on aberrant ligand levels in the bone marrow microenvironment, increased expression of Wnt transcriptional co-factors and associated micro-RNAs, and disturbed epigenetics and post-translational modification processes. Furthermore, Wnt pathway activation is associated with acquired cell adhesion-mediated resistance of multiple myeloma cells to conventional drug therapies, including doxorubicin and lenalidomide. In this review, we present an overview of the relevance of Wnt signaling in multiple myeloma and highlight the Wnt pathway as a potential therapeutic target for this disease.
Contralateral recurrence of inflammatory myofibroblastic tumour of the lung 10 years after pneumonectomy
Authors: Daniel C Vis, Margaret M Kelly, Andrew G Lee, Gary Gelfand, Kerri A Johannson
Journal: Thorax (2018)

Inflammatory myofibroblastic tumour (IMT) is a rare form of inflammatory pseudotumour of the lung. Complete surgical resection is the treatment of choice, with corticosteroid-based medical therapy reserved for cases where complete resection is not possible.1 To date, the majority of recurrent cases have occurred subsequent to incomplete resection or after discontinuation of steroids when used as primary therapy.1 2 There is a paucity of data guiding the follow-up of patients who undergo complete resection. In addition, the efficacy of oral steroids in the treatment of IMT remains poorly characterised and the optimal duration of therapy is unknown.

A 46-year-old lifetime non-smoker presented in December 2015 with dyspnoea, fatigue, night sweats and weight loss. A chest X-ray demonstrated a new left lower lobe mass. His history was significant only for a right pneumonectomy in June 2005 for a large inflammatory pseudotumour. This pneumonectomy was performed for definitive surgical management, as the mass was adjacent to …
Galactocele, Pitfall for the Evaluation by 18F-FDG PET/CT
Authors: Quentin Ceyrat, Caroline Ziade, Ghoufrane Tlili, Philippe Fernandez, Marie Meyer
Journal: Clinical Nuclear Medicine (2018)

Abstract A high 18 F-FDG uptake was found in mammary lesions in a 36-year-old woman who underwent a PET/CT scan for initial staging of diffuse large B-cell lymphoma. The patient has given birth 2 months ago and was breastfeeding. Ultrasound-guided fine-needle aspiration of 1 lesion yielded creamy liquid consistent with milk and confirmed the diagnosis of galactocele.
Factors affecting survival in upfront metastatic breast carcinoma patients.
Authors: Ummugul Uyeturk, Burcin Budakoglu, Ibrahim Turker, Kaan Helvaci, Ozlem Uysal Sonmez, Ülkü Yalçintas Arslan, Omur Berna Oksuzoglu
Journal: Journal of Clinical Oncology (2012)

e11540 Background: Metastatic breast cancer is a heterogenous disease. There are several subgroups according to pathological, biological and molecular behaviours of the tumor. Recurrent metastatic breast carcinoma (RMBC) and upfront metastatic breast carcinoma (UMBC) may differ according to clinical and prognostic characteristics. Intrinsic genetic heterogeneity may be responsible for these differences. To date, little is known about the clinical features and outcome of patients with UMBC. Methods: Patients were considered to have UMBC if patients were admitted to the clinics with stage IV disease. Patients were considered to have RMBC if metastases had developed during followup for localized breast carcinoma. Between September 2007 and May 2011, 102 of 2478 (4.1%) UMBC patients who was admitted to Department of Medical Oncology Clinic, was included in this retrospective trial. Patients’ characteristics, treatment schedules and survival data were evaluated. Results: All patients were female. Median age was 50.0 (range: 26-90). More than half of patients (58.8%) were postmenopausal. Frequent histological type was invasive ductal carcinoma (89.2%). Most of the patients had grade 3 (57.8%) tumor. Hormone receptor (HR) and HER2 positivity were76.5% and 42.2%, respectively. Metastatic sites were visceral, isolated bone-soft tissue and combination in 20%, 42% and 37%, respectively. Most of visceral metastatic patients were HR negative and HER2 positive. Median PFS and OS were 30 and 66 months, respectively. Both PFS and OS were affected from HR status, HER2 status, sites of metastatic disease and chemotherapy (log-rank p=0.006, 0.04, 0.02, 0.004, 0.03 and log-rank p= 0.04, 0.04, 0.01, 0.03, 0.01 respectively). Both PFS and OS were not affected by age, menopausal status, performance status, histology and grade of the tumor. OS were longest in patients group who received chemotherapy (76 months) and shortest in patients group who received chemotherapy and targeted therapy combinations (23 months). Conclusions: Factors affecting survival were comparable to previous studies in UMBC patient population similiar to results RMBC studies. This finding should be confirmed with prospective trials in larger study populations.
Gerald Ernest Moore
Authors: Adrian Moore
Journal: BMJ (2018)

Gerald Ernest Moore was a qualified oral surgeon who practised in Harley Street from 1967 until he retired in 1987. He also had other dental practices in south London. In the mid-1960s he was cofounder of the Cavendish Bio Medical Centre.

Before turning to medicine, Gerald had enjoyed a promising career as a child actor, appearing in films with Petula Clark, Thora Hird, and Irene Handl. He appeared in many Ealing production films, including Went the day well? in 1942. He was a published …
Implementation of survivorship care plans in the pediatric oncology clinic.
Authors: Christine Moore Smith, Barron L. Patterson, Debra L. Friedman
Journal: Journal of Clinical Oncology (2018)

55 Background: Quality survivorship care and follow up have been well described in the pediatric oncology population to improve overall health of cancer survivors. Typically, a key component is the delivery of a survivorship care plan (SCP) in a dedicated survivorship program. Creation of an SCP in the immediate post-treatment period has not been commonly adopted. To address the Commission on Cancer's (CoC) requirement to provide SCPs within six months of ending therapy, our pediatric oncology clinic has used quality improvement (QI) methods to incorporate SCPs into clinic workflow with subsequent survivorship program referral. Our aim is to meet the CoC’s benchmark of 50% of eligible patients receiving SCPs by December 31, 2017. Our secondary goal is to improve the timeliness of delivery to patients, families, and primary care providers (PCP). Methods: Registry data from our cancer center was utilized to identify eligible patients. Upcoming appointments were then identified for a panel of eligible patients using the electronic medical record (EMR). Providers use a standardized SCP template which includes the components required by the CoC. The SCP is then reviewed with families, electronically sent to the PCP, and saved in the EMR. Evaluation of the process included subjective feedback from providers and Plan-Do-Study-Act cycles. Based on this feedback and cycles, iterations of the template have been progressively streamlined and the EMR panel has been updated. Results: Care plan creation and delivery is ongoing. At baseline, 28% of eligible patients had SCPs previously created in the survivorship program. After implementation of our QI methods, to date, we have increased the proportion of eligible patients with an SCP to 40.3%, approaching our goal of 50% by December 31, 2017. We have also decreased the time from end of therapy to delivery of a care plan from 22.9 months to 14 months. This is expected to further improve as the process continues. Conclusions: The QI process has been successful in implementing a new standard of care for delivery of SCPs. Ongoing use of QI methods will increase compliance with the CoC standards and result in improved survivorship care.
Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination
Authors: Jun Gong, Thang Q. Le, Erminia Massarelli, Andrew E. Hendifar, Richard Tuli
Journal: Journal for ImmunoTherapy of Cancer (2018)

Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers. In this review, we highlight the preclinical and clinical development of combined RT and PD-1/PD-L1 blockade to date. In addition to a comprehensive evaluation of available safety and efficacy data, we discuss important points of consideration in clinical trial design for this promising combination.
Creation of an APN-led cancer survivorship clinic in a community cancer center.
Authors: Pamela Jane Vetter
Journal: Journal of Clinical Oncology (2018)

61 Background: The Institute of Medicine (IOM) report From Cancer Patient to Cancer Survivor: Lost in Transition, noted cancer patients often lacked the ability to successfully navigate the transition from patient to survivor (2006). To assist patients with understanding their disease and follow up, managing side effects and connecting with resources, the IOM recommends a survivorship care plan (SCP). The Commission on Cancer (CoC) is requiring accredited cancer programs provide SCPs to curative patients while giving them full discretion on structuring these programs. Methods: After researching survivorship components, a consultative model serving the adult cancer patients curatively treated at my facility was chosen. My goals included increasing patient satisfaction and connection to resources, fulfilling accreditation requirements, as well as financial benefits. I secured champions and procured budgetary approval. An assessment tool was created, a SCP program chosen, and a schedule created with IT. I gathered resources, reviewed side effect management, chose evaluation metrics and created educational materials and a tracking system. Results: 235 patients were seen in the first year of the clinic. Through nine months of 2017, 67.9% of eligible patients were provided with a SCP. Downstream revenue included patients changing to an Aspirus Primary Care Provider and referrals to various providers. Patients were connected to community and facility resources. Side effect assistance given; multiple medical issues addressed; additional Advanced Care Plans completed. Patients and Primary Care Providers are complimentary of the service. Conclusions: Successful start to survivorship clinic; will meet CoC accreditation. Many eligible patients who did not receive a SCP were seen at an unaffiliated Urology clinic. Moving forward, plan to work with their clinic to provide SCPs. Other challenges included time spent tracking patients, which should ease with a newly implemented electronic medical record.
Abstract 2779: Two- Dimentional Imaging Of Lipids Deposited In The Coronary Plaques By Near-infrared Fluorescence Angioscopy
Authors: Yasumi Uchida
Journal: Circulation (2007)

Background: The lipids deposited deep in the vascular wall are hardly detectable by any available imaging modalities including IVUS and OCT. Since near-infrared (NIR) light penetrates relatively deeply into the tissues, we devised a near-infrared fluorescence angioscope (NIRFA) for two dimensional imaging of lipids deposited even in deep layers of vascular wall. Aim: To examine feasibility of NIRFA for imaging of lipids in coronary arterial wall in man. Methods: NIRFA is composed of a quartz fiberscope incorporated in 5F balloon catheter, fluorescence exciter, fluorescence emitter, ICCD and recorder. NIR exciter filter of 710nm and emitter filter of 780nm were employed since among the major 30 substances composing atherosclerotic plaques, free cholesterol and cholesteryl esters alone exhibit NIR autofluorescence while oxLDL and TG not. In vitro study: Coronary artery removed from human cadaver was perfused with saline and an angioscope was introduced into it for imaging of lipids and the obtained NIR images were compared with histology. Clinical study: During routine coronary angiography, lipid deposition in the coronary artery was surveyed by NIRFA in 7 patients with coronary artery disease. Results: In vitro study. Coronary segments without lipid deposition by histology did not exhibit autofluorescence. Those with lipid deposition by histology, the lipids deposited within 700μm in depth from luminal surface exhibited autofluorescence. Deposited lipids not forming lipid pool exhibited strong and homogenous autofluorescence. Lipid pool exhibited no or weak autofluorescence surrounded by strong ones, indicating it is filled with oxLDL and/or TG. Clinical study. Autofluorescence was frequently detected not only in yellow plaques but also in white plaques by conventional angioscopy and hard plaques by IVUS. Also, autofluorescence was frequently detected in apparently normal coronary segments. Conclusion: The results indicate that this NIRFA is feasible for two dimensional imaging of lipids deposited even in deep layers of coronary arterial wall which are not detectable by conventional angioscopy, OCT and IVUS.
Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial
Authors: Gunter von Minckwitz, Marco Colleoni, Hans-Christian Kolberg, Serafin Morales, Patricia Santi, Zorica Tomasevic, Nan Zhang, Vladimir Hanes
Journal: The Lancet Oncology (2018)
Evaluation of the positional differences between bone matching and fiducial marker matching in target localization of the expiratory breath-hold radiation therapy for pancreatic cancer.
Authors: Ryo Ashida, Yoko Goto, Mami Akimoto, Nobutaka Mukumoto, Takahiro Kishi, Katsuyuki Sakanaka, Mitsuhiro Nakamura, Michio Yoshimura, Takashi Mizowaki
Journal: Journal of Clinical Oncology (2018)

517 Background: In radiation therapy, the accuracy of target localization is very important to increase the agreement between the planned treatment and the actual dose delivered to the patient. Therefore, image-guided techniques, such as bone matching, soft-tissue matching, fiducial marker (FM) matching and so on, are used to improve the precision and effectiveness of radiation therapy. In this study, we evaluate the positional differences of the target localization between bone matching and FM matching in the expiratory breath-hold radiation therapy (BH-RT) for pancreatic cancer. Methods: We analyzed 15 patients who underwent BH-RT for pancreatic cancer using FM matching between July 2016 and August 2017 in our institution. The FMs were implanted in the pancreatic cancer using endoscopic ultrasound. Prior to each treatment session, bone matching using orthogonal kilovolt x-ray images and FM matching using cone beam computed tomography at end-exhalation (BH-CBCT) was performed. A total of 226 matching data from 15 patients was analyzed. The positional differences of these matching were evaluated in the left - right (LR), anterior - posterior (AP) and superior - inferior (SI) directions. Results: The systematic and random errors between bone matching and FM matching were 3.6 and 3.0 mm, 3.3 and 2.0 mm, and 3.7 and 3.5 mm in the LR, AP and SI directions, respectively. Absolute positional differences of &gt; 5 mm were observed in 78 fractions (34.5%), 40 fractions (17.7%), and 69 fractions (30.5%), and those of even &gt; 10 mm were observed in 14 fractions (6.2%), 2fractions (0.6%), and 11 fractions (4.9%) in each direction, respectively. There were no significant correlations between positional differences in SI and both LR and AP. Conclusions: In pancreatic irradiation using BH-RT, it was considered that bone matching alone was insufficient for accurate target localization and other target matching techniques, such as FM matching, were required to achieve effective treatment.
Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study.
Authors: Gilberto Lopes, Yi-Long Wu, Iveta Kudaba, Dariusz Kowalski, Byoung Chul Cho, Gilberto Castro, Vichien Srimuninnimit, Igor Bondarenko, Kaoru Kubota, Gregory M. Lubiniecki, Jin Zhang, Debra A. Kush, Tony Mok
Journal: Journal of Clinical Oncology (2018)

LBA4 Background: In KEYNOTE-024, pembro significantly improved PFS (primary end point) and OS (secondary end-point) over chemo as first-line therapy for metastatic NSCLC without targetable alterations and PD-L1 TPS ≥50%. In KEYNOTE-042, we compared pembro with chemo at the lower TPS of ≥1% (NCT02220894). Methods: Eligible patients (pts) were randomized 1:1 to ≤35 cycles of pembro 200 mg Q3W or investigator’s choice of ≤6 cycles of paclitaxel + carboplatin or pemetrexed (peme) + carboplatin with optional peme maintenance (nonsquamous only). Randomization was stratified by region (east Asia vs non-east Asia), ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and TPS (≥50% vs 1-49%). Primary end-points were OS in pts with TPS ≥50%, ≥20%, and ≥1%. OS differences were assessed sequentially using the stratified log-rank test. Efficacy boundaries at the prespecified second interim analysis were one-sided P = .0122, .01198, and .01238, respectively. Results: 1274 pts were randomized: 637 to each arm. 599 pts (47.0%) had TPS ≥50%, 818 (64.2%) had TPS ≥20%. After 12.8-mo median follow-up, 13.7% were still on pembro and 4.9% were receiving peme maintenance. Pembro significantly improved OS in pts with TPS ≥50% (HR 0.69), TPS ≥20% (HR 0.77), and TPS ≥1% (HR 0.81) (Table). Grade 3-5 drug-related AEs were less frequent with pembro (17.8% vs 41.0%). The external DMC recommended continuing the trial to evaluate PFS (secondary end-point). Conclusion: KEYNOTE-042 is the first study with a primary end-point of OS to demonstrate superiority of pembro over platinum-based chemo in pts with previously untreated advanced/metastatic NSCLC without sensitizing EGFR or ALK alterations and a PD-L1 TPS ≥1%. These data confirm and potentially extend the role of pembro monotherapy as a standard first-line treatment for PD-L1-expressing advanced/metastatic NSCLC. Clinical trial information: NCT02220894. [Table: see text]
Final overall survival (OS) analysis of PHEREXA: A randomized phase III trial of trastuzumab (H) + capecitabine (X) ± pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) who experienced disease progression during or after H-based therapy.
Authors: Ander Urruticoechea, Mohammed Rizwanullah, Seock-Ah Im, Antonio Carlos Sánchez Ruiz, Istvan Lang, Gianluca Tomasello, Hannah Douthwaite, Tanja Badovinac Crnjevic, Sarah Heeson, Jennifer Eng-Wong, Montserrat Munoz
Journal: Journal of Clinical Oncology (2018)

1013 Background: In PHEREXA (NCT01026142), adding P to H + X did not significantly improve independent review facility-assessed progression-free survival (IRF-PFS; primary endpoint) in patients with HER2-positive MBC who received a prior taxane and progressed during or after H-based therapy (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.65–1.02; p= .0731). An 8-month increase in median OS to 36.1 months was observed with P, but due to hierarchical testing of IRF-PFS, and subsequently of OS, statistical significance could not be claimed. No new safety signals were identified. We now report the final prespecified analysis. Methods: Randomization arms were A: intravenous H 8 mg/kg→6 mg/kg every 3 weeks (q3w) + oral X 1250 mg/m2 twice daily (2 weeks on, 1 week off q3w) and B: intravenous P 840 mg→420 mg q3w + intravenous H per Arm A + oral X 1000 mg/m2 (same schedule as Arm A). Treatment was given until disease progression, unmanageable toxicity, or patient request for discontinuation. OS and investigator-assessed PFS (INV-PFS) were assessed in the intent-to-treat population (all randomly assigned patients); adverse events (AEs), in the safety population (patients who received ≥1 dose of study drug). Results are descriptive. Results: At clinical cutoff (20-Sep-17), median time on study, including follow-up, was 23 months in Arm A and 33 months in Arm B. Efficacy is shown in the table. There was a small increase in AE incidence with longer follow-up, and no new symptomatic left ventricular systemic dysfunction (0 patients in Arm A and 5 [2.2%] in Arm B). Conclusions: While final OS results of PHEREXA are descriptive, median OS of 37.3 months in Arm B, with a 9.1-month increase versus Arm A, shows that clinical efficacy of H + P is maintained with longer follow-up. There were no new safety signals and no evidence of late cardiac toxicity. Clinical trial information: NCT01026142. Arm A H + X n = 224 Arm B P + H + X n = 228 OS Events, n (%) 136 (60.7) 134 (58.8) Median, months 28.1 37.2 ∆, months 9.1 HR (95% CI) 0.76 (0.60–0.98) INV- PFS Events, n (%) 182 (81.3) 201 (88.2) Median, months 9.0 11.8 ∆, months 2.8 HR (95% CI) 0.83 (0.68–1.02)