tbuckley/cabot-search huggingface dataset:
Long-term results of breast conservation therapy for pateints with early-stage breast cancer: A large community-based experience.
Authors: May Lin Tao, Beatrice Delhey Mautner, Herman E Ray, Mona Vadecha Sanghani, Leslie E. Botnick
Journal: Journal of Clinical Oncology (2014)

e12027 Background: We reviewed our large, community hospital experience treating early stage breast cancer patients to determine rates of breast-conserving therapy (BCT), overall survival, and risk factors for survival. Methods: A hospital tumor registry was used to identify T1-2, N0 breast cancer cases diagnosed between January 1, 1997 and December 31, 2007. Rates of BCT and adjuvant radiotherapy were examined. For survival analyses, cases were limited to only those patients who had definitive BCT and were diagnosed at least 8 years earlier than the time of analysis, i.e. had at least 8 years of actual or potential follow-up. Median follow-up was 10.6 years. Cox proportional hazards models were done to assess influence of age at diagnosis, tumor grade, biomarker status (ER, PR and Her-2 neu amplification), margin status, receipt of hormones, radiation or chemotherapy on overall survival. Results: The rate of BCT was 89.5%, and the rate of radiation after breast conserving surgery was 91.7%. For the subset of 1065 T1-2 N0 patients treated with BCT who had at least 8 yrs of follow-up, median age was 59 years old, 14.5% had triple negative status, 1.7% had positive final margins (defined as tumor on ink), 49.2% got hormones, 26.7% got chemotherapy. Median whole breast dose was 5040 cGy, 895 (81.2%) received a supplemental dose to the lumpectomy cavity (median dose, 1400 cGy). Receipt of radiation and age were the only significant factors in the multivariate survival analysis. Given the potentially confounding impact of age on both the likelihood of receiving radiation and vital status, patients were stratified into age groups and receipt of RT or not. Conclusions: The large majority of patients in this community were treated with BCT and most received radiotherapy. Overall survival is excellent and compares favorably to that seen in large academic centers. Receipt of radiation seems to have a beneficial impact on survival, particularly in older patients. Age group (years old) Receipt of adjuvant radiation 10 year survival estimate 95% CI 50-< 70 No 92.86% 74.4-98.2 50-< 70 Yes 96.00% 94-97.4 <= 50 No 87.50% 38.7-98.1 <=50 Yes 98.25% 95.4-99.3 >= 70 No 50.49% 31.8-66.6 >= 70 Yes 77.48% 71.3-82.5* * p < 0.001
A phase I study of a yeast-based therapeutic cancer vaccine, GI-6301, targeting brachyury in patients with metastatic carcinoma.
Authors: Harpreet Singh, Christopher Ryan Heery, Jennifer L. Marte, Benedetto Farsaci, Ravi Amrit Madan, Geraldine Helen O'Sullivan Coyne, Claudia Palena, Timothy C. Rodell, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2014)

e14026 Background: Saccharomyces cerevisiae has been genetically modified to express Brachyury (Br) protein and developed under a CRADA with GlobeImmune/NCI as a heat-killed therapeutic cancer vaccine (GI-6301). Br is a member of the T-box family of transcription factors, characterized by a highly conserved DNA-binding domain designated as T-domain. Expression of Br confers on epithelial tumor cells a mesenchymal phenotype, as well as migratory and invasive abilities and enhances treatment resistance. Preclinical work has demonstrated Br specific T cells can lyse human cancer cells expressing Br in an MHC restricted fashion. Methods: This phase I study (NCT01519817) enrolled 27 patients with advanced cancers. Patients received escalating doses of vaccine every 2 weeks x 7 and then monthly with restaging scans every 2 months while on study. The primary endpoint was safety. Tumor-associated antigen immune responses were also analyzed. Immune response was measured by flow-cytometry intracellular staining (ICS) of CD4 and CD8 T lymphocytes for the cytokines interferon gamma, tumor necrosis factor, and interleukin 2. Results: Treatment was well tolerated with 191 vaccine cycles given. There were no grade 3 or greater adverse events related to therapy. Only 7 cycles were associated with transient grade 2 adverse events. PBMC were available from 21 pts for immune response analysis with 7 demonstrating a Br-specific CD8+ and/or CD4+ T cell response post vs. pre-vaccination. Median time on study was 74 days (range). A patient with metastatic colon cancer had stable disease for 15 months. Conclusions: A phase I study with GI-6301 vaccine demonstrated safety and generated immune response in some patients. These results demonstrate, for the first time in humans, that a transcription factor can be targeted immunologically via vaccination. Clinical trial information: NCT01519817.
Incidence and Risk Factors of Central Nervous System Relapse in Localized Extranodal NK/T-Cell Lymphoma, Nasal Type: An Analysis of Nkea Study
Authors: Kana Miyazaki, Senzo Taguchi, Masahiko Oguchi, Ritsuro Suzuki, Naoko Asano, Yasuhito Terui, Nobuko Kubota, Yoshihiro Saito, Takeshi Maeda, Satoshi Itasaka, Yukio Kobayashi, Jun Itami, Jun Amaki, Takeshi Akiba, Tohru Murayama, Noriko Ii, Toshinori Soejima, Motoko Yamaguchi, Naoyuki Katayama
Journal: Blood (2018)
Insurance and outcomes for classical Hodgkin lymphoma.
Authors: George Yaghmour, Benny C. Johnson, Ronald D. Lawson, Michael Gary Martin
Journal: Journal of Clinical Oncology (2014)

e19505 Background: It is unclear how insurance status interacts with outcomes and traditional risk factors in Classical Hodgkin lymphoma (HL). Methods: Using case listing session of SEER 18 (1973-2010) we examined outcomes for patients with HL 18 years of age and older with known stage and insurance status (limiting analysis to 2007-2010). Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007 and GraphPad Prism 6. Comparisons were made using the Fisher’s exact test and log rank test (Mantel-Cox); all p-values were 2-sided. Results: 6395 patients (pts) were identified; 77% had private insurance, 15% had Medicaid and 8% were uninsured. Insured pts were older (42) than Medicaid pts (37, p<0.01), who were older than uninsured pts (31, p<0.01). Insured pts were more likely to present with localized/regional disease (dz) (59%) than uninsured (52%; p<0.01) or Medicaid pts (50%; p<0.01). For pts with localized dz insured pts were more likely to receive radiation (43%) than Medicaid (35%; p<0.01) or uninsured pts (32%; p<0.01). Overall Survival (OS) was equivalent between insured and the younger uninsured pts while both were superior to Medicaid pts (p<0.01; 47 m OS Medicaid 71%, Insured 84%, Uninsured 88%). This was true of pts with localized dz (p<0.01; 47 m OS Medicaid 78%, Insured 91%, Uninsured 90%) as well as distant dz (p<0.01; 47 m OS Medicaid 63%, Insured 76%, Uninsured 87%). Conclusions: HL pts with Medicaid had inferior outcomes by stage than patients with private insurance.
Phase 1 trial of MM-151, a novel oligoclonal anti-EGFR antibody combination in patients with refractory solid tumors.
Authors: Christopher Hanyoung Lieu, Wael A. Harb, Muralidhar Beeram, Lindsey Power, Jeffrey D. Kearns, Rachel Nering, Victor M. Moyo, Beni B. Wolf, Alex A. Adjei
Journal: Journal of Clinical Oncology (2014)

2518 Background: MM-151 is a novel oligoclonal anti-EGFR antibody combination designed to overcome key challenges of the EGFR network: ligand redundancy and signal amplification. Preclinical studies confirm MM-151's potent ligand antagonism and signal inhibition. A Phase 1, first-in-human study was initiated to assess the safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary clinical activity of MM-151 in patients with refractory solid tumors. Methods: 57 patients were enrolled on 3 schedules (QW, Q2W, or Q3W) at escalating doses using a standard 3+3 design. Response was assessed per RECIST criteria every 8 weeks. Patients continued on study until disease progression or unacceptable toxicity. Results: Results presented are based on preliminary data collected as of Dec. 4, 2013. 57 patients (median age 63 years, 30 male, 27 female) have been enrolled (27 QW, 16 Q2W and 14 Q3W) at escalating dose levels, with 56 evaluable for safety and 31 evaluable for efficacy. The most common tumor types were colorectal cancer (CRC) (26 [46%]), pancreatic cancer (5 [9%]), and NSCLC (6 [11%]). An MTD has not been reached and dose escalation continues. Most adverse events (86%) were CTCAE grades 1 and 2. Infusion related reaction (IRR) was the most common AE (43 [76.8%]); however, this was managed to good effect with premedication and an optimized infusion schedule. The most common non-IRR AEs were comprised of EGFR-pathway toxicities, including rash (45 [80%]), hypomagnesemia (12 [21%]), mucositis (6 [11%]) and diarrhea (13 [23%]). Partial responses were observed in 2 CRC patients and a total of 8 (30% of mCRC) patients had SD for > 4 months (2 of the 8 had SD for 20.1 and 19.8 months, respectively). Conclusions: Results to date show that MM-151 has an acceptable safety profile and objective clinical activity in CRC. Clinical trial information: NCT01520389.
Temsirolimus in women with platinum-resistant ovarian cancer or advanced/recurrent endometrial cancer: A multicenter phase II trial of the AGO Study Group (AGO-GYN 8).
Authors: Guenter Emons, Christian Kurzeder, Barbara Schmalfeldt, Alexander Reuss, Nikolaus de Gregorio, Jacobus Pfisterer, Tjoung-Won Park-Simon, Sven Mahner, Willibald Schroeder, Hans-Joachim Lueck, Martin Leonhard Heubner, Lars Christian Hanker, Falk Thiel, Felix Hilpert
Journal: Journal of Clinical Oncology (2014)

5565 Background: Inhibition of mTOR with temsirolimus (T) might be an efficacious treatment of patients with epithelial ovarian cancer (OC) or endometrial cancer (EC). Methods: Patients (pts) with platinum and taxane resistant OC (n = 22) or with advanced/recurrent EC, who had not received previous chemotherapy (n = 22) were treated with weekly IV infusions of T (25 mg). Primary endpoint was progression free survival after 4 months (OC) or 6 months (EC). A two stage design was used with second stage of accrual if < 10 of the first 22 pts (OC) or < 7 of the first 22 pts (EC) had progressive disease after the first 8 weeks of T-treatment. Results: 22 pts each were treated in the OC and the EC cohort respectively. Median age was 56 years (OC) or 63 years (EC). After 8 weeks of treatment with T, 10 pts in the OC cohort and 7 pts in the EC group had progressive disease. Toxicity of T was mild: grade 4: 1 ileus (OC), grade 3: anemia 1, abdominal pain 1, ALT elevation 1, ascites 3 (OC), diarrhea 1, vomiting 2. Conclusions: T-treatment was well tolerated in our patients. It did, however, not meet the predefined efficacy criteria with 10 of 22 pts (OC) and 7 of 22 pts (EC) having progressive disease after 8 weeks of treatment. Clinical trial information: EudraCT Nr. 2011-000299-33.
Articular fibrocartilage - Why does hyaline cartilage fail to repair?
Authors: Angela R. Armiento, Mauro Alini, Martin J. Stoddart
Journal: Advanced Drug Delivery Reviews (2018)

Once damaged, articular cartilage has a limited potential to repair. Clinically, a repair tissue is formed, yet, it is often mechanically inferior fibrocartilage. The use of monolayer expanded versus naïve cells may explain one of the biggest discrepancies in mesenchymal stromal/stem cell (MSC) based cartilage regeneration. Namely, studies utilizing monolayer expanded MSCs, as indicated by numerous in vitro studies, report as a main limitation the induction of type X collagen and hypertrophy, a phenotype associated with endochondral bone formation. However, marrow stimulation and transfer studies report a mechanically inferior collagen I/II fibrocartilage as the main outcome. Therefore, this review will highlight the collagen species produced during the different therapeutic approaches. New developments in scaffold design and delivery of therapeutic molecules will be described. Potential future directions towards clinical translation will be discussed. New delivery mechanisms are being developed and they offer new hope in targeted therapeutic delivery.
Correlation of multiplex measurement of mRNA expression from FFPE tissues with protein expression.
Authors: Scott A. Shell, Christine M. Martersteck, Karen J. Pry, Raphael Borok, Sarah S. Bacus
Journal: Journal of Clinical Oncology (2014)

e22141 Background: The use of biomarkers has been a successful strategy in the approval of targeted therapies in oncology. Albeit successful, these approaches tend to focus on one biomarker representing one biological pathway. As the complexities of tumor sub-types and mechanisms of therapies increase, the need to investigate several biomarkers from multiple cellular pathways simultaneously from one sample grows. A common method to evaluate tumor biomarkers is immunohistochemistry (IHC). Unfortunately, using this method to detect multiple biomarkers can be hindered by limited tumor material or lack of multiplexed IHC methods. \The Edge System from HTG Molecular is an automated testing platform that supports normalized mRNA quantitation of a panel of biomarkers from as little as one section of FFPE material. Methods: The Top Oncogene Assay (TOA) kit was used to measure the mRNA expression of 32 genes including estrogen receptor (ER), progesterone receptor (PR), and ErbB2 (HER2) from 14 breast carcinomas on the Edge System. Target gene expression values were normalized to 7 housekeeper genes also in the TOA kit. The same samples were sectioned and stained for ER and PR (Dako FLEX IVD kits), and HER2 (Dako HercepTest kit). Slides were evaluated for positive or negative staining of ER and PR, and HER2 based on interpretation guidelines for each assay. Results: The clinical classification of ER, PR, and HER2 positive breast cancer was assigned to each sample followed by sorting the samples for each biomarker separately from lowest to highest normalized mRNA expression. 14/14 samples for HER2, 14/14 for ER, and 13/14 for PR that demonstrated clinical positivity had mRNA expression for that biomarker higher than all other samples that were clinically classified as negative for that biomarker. Conclusions: From the correlations observed between IHC for protein detection and the Edge System for mRNA quantitation, we conclude that the Edge System and related mRNA quantitation chemistry has merit to measure a multitude of exploratory biomarkers simultaneously from limited amounts of FFPE tissues. This methodology can support the analysis of many biomarkers from limited amounts of material in the exploratory phases of clinical trials.
Prognostic value of pretreatment MRI in breast cancer related leptomeningeal metastases.
Authors: Emilie Le Rhun, Thomas Boulanger, Patrick Devos, Sophie Taillibert, Yves-Marie Robin, Jacques Bonneterre, Isabelle Rodrigues, Fahed Zairi, Nicolas Reyns, Marc C. Chamberlain
Journal: Journal of Clinical Oncology (2014)

2067 Background: The National Comprehensive Cancer Network (NCCN) guidelines considers radiographic bulky disease as assesed by MRI as a negative prognostic factor in leptomeningeal metastases (LM). Our aim was to determine the prognostic value of pre-treatment MRI in patients with breast cancer (BC) related LM. Methods: We retrospectively evaluated pretreatment MRI in a cohort of 60 women with BC and LM to determine the correlation between CNS MRI abnormalities and survival. All images were reviewed by a neuroradiologist and a neuro-oncologist. Statistical analyses were performed using SAS software V9.3. Results: At LM diagnosis, patient median age was 56 (range, 35-81) and ECOG performance status was 0-2 in 64.5%. Breast cancers were invasive ductal carcinoma in 70.5%. Estrogen receptor and progesterone receptor were present in 71.5% and 56.5% respectively. 25% of tumors were HER2 positive and 16.5% were triple negative. Malignant cells were observed in the CSF in 64%. Brain MRI showed abnormalities consistent with LM in 73% including ; hydrocephalus (10% of all patients), focal (29%) or a diffuse (35.5%) linear leptomeningeal contrast enhancement (CE), subependymal CE (27%), sulci (35.5%), folia (46%) and cranial nerve (30.5%) CE and intracranial nodules (12.5%). Spine MRI revealed the following : linear focal (8.5%) or diffuse (54%) CE (71%) and subarachnoid nodules (16.5%). The cauda equina showed enhancement in 71% of patients. 91.5% of patients received intra-CSF chemotherapy, 59.5% systemic therapy and 18% radiotherapy. All but one patient died. Survival was less than 2 months in 33.5% and greater than 6 months in 36%. Median progression free survival (PFS) was 2.5 months (range, 0.03-3.3). Median overall survival was 4 months (0.03 – 34.88). Patients with linear focal leptomeningeal CE had a significantly better PFS (p=0.02) however no other MRI characteristic was associated with survival. Conclusions: In this retrospective cohort of patients with BC and LM, linear focal leptomeningeal CE by pre-treatment MRI was the only significant radiographic abnormality that correlated with survival. These data will be confirmed in a larger cohort of patients.
Chemotherapy or combined modality therapy for early-stage Hodgkin lymphoma: A comparative, population-based study.
Authors: Rajesh Shrestha, Jorge J. Castillo, Adam J. Olszewski
Journal: Journal of Clinical Oncology (2014)

8546 Background: The choice between chemotherapy alone (Ct) and combined modality therapy (Ct with radiation, CMT) in early-stage Hodgkin lymphoma (HL) remains controversial. Identifying patients (pts) who could omit radiotherapy is an important research goal. We compared the two strategies using the National Cancer Data Base, which captures >70% of incident cancer cases in the United States. Methods: We extracted data on 20,600 pts with stage I-II classical HL treated between 2003 and 2011. We studied factors predicting the use of Ct or CMT using logistic regression. Treatment selection bias was addressed by balancing groups with a propensity score, immortal time bias by landmark analysis, missing data bias by multiple imputation, with a sensitivity analysis for unobserved confounding. Overall (OS) and relative survival (RS, a surrogate for disease-related mortality) were then compared using proportional hazard models. Results: Administration of CMT (50.5%) rather than Ct (49.5%) was significantly influenced by clinical factors (B symptoms, histology and comorbidities, all P<.0001), but also by demographic ones: age/sex (odds ratio, OR .85, P=.0007 for women vs. men <30 years old), race (OR .83, P=.0007 for black vs. white pts), lack of insurance (OR .71, P<.0001), treatment in an academic center (OR .81, P=.0001) or after 2006 (OR .63, P<.0001). After bias adjustment, CMT was associated with a better OS (hazard ratio, HR 0.56, 95% CI 0.49-0.64) and RS (HR 0.37, 95% CI 0.29-0.47) than Ct. The 5-year OS was 94.0% for CMT and 88.7% for Ct. There was no evident heterogeneity of the CMT benefit in subgroups defined by age, sex, histology, B-symptoms, stage, anatomical origin or hospital type (all P>.20). Conclusions: Treatment selection in early-stage HL is influenced by sociodemographic factors, which may lead to outcome disparities. In this comprehensive dataset, CMT was associated with the same survival advantage as in the prior meta-analysis (Herbst et al., Haematologica 2010, HR .41). No clinical factors (including some defining “early unfavorable” stratum) could identify subsets without advantage from CMT, so CMT should remain a standard of care pending further prospective studies.
In-Vitro Drug Sensitivity Screening in Chronic Lymphocytic Leukemia (CLL) Primary Patient Samples Identifies Drug Candidates for Precision Cancer Therapy
Authors: Deepak Balaji balaji Thimiri Govinda Raj, Andrea Cremaschi, Sigrid Strand Skånland, Alexandra Gade, Fredrik H. Schjesvold, Geir Erland Tjønnfjord, Ludvig A Munthe, Kjetil Tasken
Journal: Blood (2018)
AB0481 Transcutaneous vagus nerve stimulation in patients with rheumatoid arthritis
Authors: A. Mohr Drewes, C. Brock, S.E. Rasmussen, M. Pfeiffer Jensen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid Arthritis is a prevalent, autoimmune disease causing joint destruction and severe physical disability. In various studies the vagal nerve has been postulated to play a role in modulation of systemic inflammation. <h3>Objectives</h3> Our aim was to investigate the effect of transcutaneous stimulation of the vagal nerve (t-VNS) in patients with rheumatoid arthritis. We hypothesised that stimulation of the vagal nerve and thereby enhanced parasympathetic tone would increase the activity of the vagal nerve and improve experienced clinical pain. <h3>Methods</h3> Sixteen patients with rheumatoid arthritis and flare (DAS28-CRP&gt;3.2) and twenty without flare were recruited. Three bilateral electrical stimulations of the vagal nerve were done with a handheld device for 4 days. Cardiac vagal tone (CVT) was assessed with linear vagal scale (LVS) and DAS28-CRP were collected on the 1st, 2nd and 5th day. <h3>Results</h3> Cardiac vagal tone was significantly lower in patients with flare in comparison to patients without flare (3.2 vs. 4.9 LVS, p=0.03). t-VNS did not alter CVT in patients with flare, however decreased CVT in patients without flare (baseline: 4.9, 2nd day: 3.8 LVS, p=0.03). A decrease in DAS28-CRP in patients with flare was seen in response to t-VNS (baseline: 4.2, 5th day: 3.9, p=0.03), due to decrease in CRP (baseline: 8.2, 5th day: 6.0 mg/L, p=0.02) and number of swollen joints (baseline: 5.4, 5th day: 4.4, p=0.01) and tender joints (baseline: 3.7, 5th day: 2.8, p=0.02) in RA patients with flare. A negative association between baseline CVT and baseline DAS28-CRP was found in all RA patients, showing that lower CVT was associated to higher disease activity. <h3>Conclusions</h3> Baseline CVT was lower in RA patients with flare, possibly due to higher level of inflammation, and the observed decrease in DAS28-CRP was not associated to CVT modulation. <h3>Reference</h3> [1] Rasmussen SE, et al. Vagal influences in rheumatoid arthritis. Scandinavian Journal of Rheumatology2017. <h3>Disclosure of Interest</h3> None declared