tbuckley/cabot-search huggingface dataset:
Skin test results with common and melanoma antigens compared to clinical outcomes of melanoma patients treated with intralesional (IL) dinitrochorobenzene (DNCB) or IL bacillus Calmette-Guerin (BCG).
Authors: Max H. Cohen, Ronald B. Herberman: Deceased
Journal: Journal of Clinical Oncology (2017)

59 Background: In a previous study involving in vitro serial testing in patients receiving IL BCG or IL DNCB we determined that measurements of serial in vitro phytohemagglutinin stimulation levels correlated with the patients’ clinical courses. The current evaluation attempted to determine which in vivo skin test studies were useful in this setting. Methods: All patients had locally progressive melanoma satellosis, or in-transit metastases, but no evidence of distant metastasis past regional lymph nodes. Patients had been randomized to repeatedly receive either IL BCG (9 patients), or IL DNCB (9 patients) into cutaneous or subcutaneous metastases. A "BCG worse outcome group" consisted of 6 patients in whom distant metastasis was detected within 2 to 20 months, and who died within 9 to 24 months. A "BCG better outcome group" consisted of 3 patients who were alive and in whom no distant metastases were detected after 12 to 39 months. Similarly, the 9 patients randomized to be treated with intralesional DNCB were also subsequently divided into two groups: A "DNCB worse outcome group" consisted of 6 patients in whom distant metastasis was detected within 5 to 11 months, and who died within 6 to 12 months. A "DNCB better outcome group" consisted of 3 patients who were alive and in whom no distant metastases were detected after 8 to 20 months. Following informed consent, patients were serially skin tested, as possible, with Purified Protein Derivative antigen (PPD), Mumps antigen, Streptokinase/Streptodornase (SKSD), and inactivated melanoma extracts, using coded syringes. Results: In comparing the two "better outcome" groups with the two "worse outcome" groups, patients who prior to treatment had a positive reaction to melanoma extracts appeared to fare better than those who did not. All patient groups tended to react positively to SKSD, a general sign of immune capability. Conclusions: Among the skin tests compared, testing with melanoma extract appeared to correlate best with clinical courses in patients undergoing BCG or DNCB intralesional treatments for progressive melanoma satellosis or in-transit metastases.
Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC).
Authors: John Yi, Jeffrey Melson Clarke, Patrick Healy, Xiaofei F. Wang, Debra Shoemaker, Mark W. Onaitis, Chelsae Dumbauld, Robyn Osborne, Jeffrey Crawford, David Harpole, Thomas A. D'Amico, Frank Dunphy, Jared Christensen, Neal Ready, Kent Weinhold
Journal: Journal of Clinical Oncology (2017)

26 Background: Ipilimumab (Ipi) is a humanized CTLA-4 antibody that blocks binding of CTLA-4 to B7, permitting T cell activation through CD28. Phased in Ipi added to chemotherapy (C) may enhance efficacy in NSCLC. Methods: Patients with stage 2 or 3A NSCLC received neoadjuvant carboplatin AUC6 plus paclitaxel 200 mg/m 2 every 21 days for 3 cycles and Ipi (10 mg/kg) was given on day 1 for cycles 2 and 3. Blood for immune profiling of circulating T cells was collected at baseline, after chemotherapy alone, and after chemotherapy plus Ipi. Tumor infiltrating lymphocytes (TIL) were derived from 7 available tumors. Polychromatic flow cytometry (PFC) analyses were performed on peripheral blood mononuclear cells (PBMC) and TIL. Objective response rates were assessed according to RECIST 1.1 criteria. Results: Of the 24 patients enrolled on this study, objective responses after 3 cycles of neoadjuvant C plus ipi included 2 PD, 8 SD, and 14 PR. Phenotypic analyses revealed that PBMC from all 24 patients were highly activated following two cycles of Ipi (cycle 3) as evidenced by significantly increased frequencies of CD28, ICOS, HLA-DR, PD-1, and CTLA-4 expressing CD4+ cells; and ICOS, HLA-DR, and CTLA-4 expressing CD8+ cells. The frequencies of Tregs were highly variable among the 24 participants. Two of the 24 participants had levels of MDSC cells above 15%. TIL contained far greater frequencies of activated CD4+ and CD8+ cells than found in the PBMC at cycle 3. Tumor associated antigen (TAA)-specific CD4+ or CD8+ cells were detected at baseline in 4 patients (24%), but their relative frequencies remained unaltered by Ipi therapy. No patients developed detectable de novo TAA reactivities while on Ipi therapy. Conclusions: Combined neoadjuvant Ipi plus chemotherapy produced significantly increased frequencies of highly activated CD4+ and CD8+ populations in the peripheral blood and the tumor microenvironment. TAA-specific CD4+ or CD8+ cells were detected in PBMC at baseline in a subset of patients. No TAA-reactive T cells were detected among the 7 TIL samples analyzed. Analysis for predictive or pharmacodynamic biomarkers is ongoing. Clinical trial information: NCT01820754.
Thyroid Function Screening in Children With Alopecia Areata
Authors: Alison S. Rustagi, Noel S. Weiss
Journal: JAMA Dermatology (2018)

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150P Correlation between erlotinib-induced rash and efficacy in first-line therapy of patients with advanced non-small cell lung cancer (NSCLC) expressing epidermal growth factor receptor (EGFR)-mutation: A prospective, multi-center, open-label, single-arm, phase II study
Authors: M. Gottfried, S. Keren Rosenberg, J. Dudnik, M. Wollner, J. Bar, A. Onn, O. Frenkel, N. Maimon
Journal: Journal of Thoracic Oncology (2018)
Cancer mortality in Serbia, 1991–2015: an age‐period‐cohort and joinpoint regression analysis
Authors: Milena Ilic, Irena Ilic
Journal: Cancer Communications (2018)

Abstract Background As the result of dramatic political changes, civil wars, and a long‐term refugee crisis from the end of the last to beginning of this century, the population of Serbia has experienced significant health problems. The aim of this study was to assess cancer mortality trends in Serbia. Methods This nationwide study was carried out to analyze cancer mortality in Serbia during 1991–2015 using official data. The age‐standardized mortality rates (per 100,000) were calculated by direct standardization, using the world standard population by Segi. The average annual percent change (AAPC) and corresponding 95% confidence interval (CI) were computed using joinpoint regression analysis. Age‐period‐cohort analysis was performed to address the possible underlying reasons for the observed temporal trends. Results Over the 25‐year study period, there were 466,075 cancer deaths (266,043 males and 200,032 females) in Serbia. Overall cancer mortality increased between 1991 and 2009 in both males (by + 0.9% per year) and females (by + 0.8% per year) and has been decreasing since then, by − 0.9% annually in both sexes. For almost all major cancers except stomach cancer, cancer mortality in Serbia demonstrated upward trends during the study period. The largest increases were noted in lung cancer among females (AAPC = + 3.7, 95% CI 3.5–3.9) and prostate cancer in males (AAPC = + 1.9, 95% CI 1.4–2.3). Conclusions After two decades of increase, cancer mortality rates are finally declining in Serbia. Despite this, these rates place Serbia among the countries with the highest cancer mortality in the world.
Treating Second Breast Events After Breast-Conserving Surgery for Ductal Carcinoma in Situ
Authors: Michael J. Hassett, Wei Jiang, Melissa E. Hughes, Stephen Edge, Sara H. Javid, Joyce C. Niland, Richard Theriault, Yu-Ning Wong, Deborah Schrag, Rinaa S. Punglia
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor–positive SBE contingent on AET use for the initial DCIS diagnosis.
Infographic. The effect of high-speed running on hamstring strain injury risk
Authors: Steven John Duhig, Anthony J Shield, David Opar, Tim J Gabbett, Cameron Ferguson, Morgan Williams
Journal: British Journal of Sports Medicine (2018)

Australian rules football is a challenging contact sport requiring high levels of fitness and skill. In the last two decades, hamstring strain injuries have remained an ongoing problematic issue, constituting a large proportion of soft tissue injuries sustained in the elite Australian Football League (AFL).1 The predominant injury mechanism for hamstring strain injuries is sprinting,2 …
Malignant ureteric obstruction decompression: how much gain for how much pain? A narrative review
Authors: Joanna Prentice, Tarik Amer, Ali Tasleem, Omar Aboumarzouk
Journal: Journal of the Royal Society of Medicine (2018)

Over the last thirty years, the management of Malignant Ureteric Obstruction (MUO) has evolved from a single disciplinary decision to a multi-disciplinary approach. Careful consideration must be given to the risks and benefits of decompression of hydronephrosis for an individual patient. There is a lack of consensus of opinion as well as strong evidence to support the decision process. Outcomes that were identified amongst patients undergoing treatment for MUO included prognosis, quality of life (QOL), complications, morbidity and prognostication tools. A total of 63 papers were included. Median survival was 6.4 months in the 53 papers that stated this outcome. Significant predictors to poor outcomes included low serum albumin, hyponatremia, the number of malignancy related events, and performance status of 2 or worse on the European cooperative cancer group. We propose a multi-centre review of outcomes to enable evidence-based consultations for patients and their families.
112O Primary result of an investigator-initiated phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study (NCCH1505)
Authors: T. Seto, Y. Katsuya, H. Horinouchi, S. Umemura, Y. Hosomi, M. Satouchi, A. Kuchiba, Y. Ohe
Journal: Journal of Thoracic Oncology (2018)
217P Impact of VEGF and CD74 expression on response and survival of malignant pleural mesothelioma patients treated with gemcitabine and cisplatin: A phase II retrospective study
Authors: D.A. Soliman, M.A.A. Ellithy, A.S. Saad, M.S. Jassim, H. Abou Gabal, W. Osman
Journal: Journal of Thoracic Oncology (2018)
Tumour infiltrating lymphocyte expression of PD-1 as a favourable prognostic factor in patients with mismatch repair competent colorectal cancer.
Authors: James Hugh Park, Lauren Grant, Jean A Quinn, Campbell SD Roxburgh, Donald C McMillan, Joanne Edwards
Journal: Journal of Clinical Oncology (2018)

631 Background: Immune checkpoint activation is recognised in mismatch repair (MMR) deficient colorectal cancer (CRC), and Programmed Cell Death Protein-1 (PD-1) inhibitors have been shown to have therapeutic benefit in this patient group. However, the role of PD-1 and PD Ligand-1 (PDL-1) in patients with MMR competent CRC remains unclear. The present study examined the relationship between tumor infiltrating lymphocyte (TIL) PD-1 and tumour PDL-1 expression, tumour microenvironment (TME) characteristics and cancer-specific survival (CSS) of patients with MMR competent CRC. Methods: The presence of TIL PD-1 and tumour cell PDL-1 expression was examined in patients who had undergone resection of TNM I-III CRC using a tissue microarray. Relationship with clinicopathological characteristics and the TME (Klintrup-Makinen (KM) grade, Immunoscore, tumour stroma percentage (TSP) and Glasgow Microenvironment Score (GMS)) and CSS was examined. Results: 189 patients were included; 64% were older than 65 and 52% were male. PDL-1 expression was not associated with clinicopathological or TME characteristics. Lymphocyte PD-1 expression was not associated with clinicopathological characteristics, but was associated with a high KM grade ( P&lt; 0.001), high Immunoscore ( P&lt; 0.001), low TSP ( P= 0.068) and a low GMS ( P&lt; 0.001). On multivariate survival analysis, high TIL PD-1 expression was associated with improved CSS (HR 0.60, P= 0.016) independent of Immunoscore (HR 0.74, P= 0.03) and TSP (HR 1.91, P= 0.027). PDL1 expression was not associated with CSS on univariate or multivariate analysis. Pre-operative aspirin use was known for 131 patients. Aspirin use showed a trend towards improved 5-year CSS in patients with low PDL-1 expression (100% vs. 77%, P= 0.103) but worse 5-year CSS in those with high expression (55% vs. 82%, P= 0.045). Conclusions: The presence of PD-1 expressing TILs is a favourable prognostic factor in MMR competent CRC independent of other TME characteristics. Furthermore, the relationship between aspirin and CSS may be dependent on PDL-1 expression. Both PD-1 and PDL-1 may be potential prognostic and predictive markers in patients with MMR competent CRC.
Ribosome Profiling Uncovers Selective mRNA Translation Associated with eIF2 Phosphorylation in Erythrocyte Progenitors
Authors: Paolini Nahuel, Moore Kat, di Summa Franca, Fokkema Ivo, Jansen Sjoert, 't Hoen Peter-Bram, Marieke Von Lindern
Journal: Blood (2016)
109O Health-related quality of life (QoL) after prophylactic cranial irradiation (PCI) vs no PCI for stage III NSCLC patients: Results from the NVALT-11/DLCRG-02 study
Authors: W. Witlox, B. Ramaekers, H. Groen, A.-M. Dingemans, J. Praag, J. Belderbos, V. Van Der Noort, H. Van Tinteren, M. Joore, D. De Ruysscher
Journal: Journal of Thoracic Oncology (2018)
Auto-antibody detection of ovarian cancer with paraneoplastic antigens.
Authors: Laura C. Hurley
Journal: Journal of Clinical Oncology (2017)

70 Background: The high mortality rate of ovarian cancer (OVCA) is due to late detection and high incidence of recurrence. Autoantibody diagnostic tests for early detection and prediction of recurrence have the potential to improve patient outcome. Paraneoplastic neurological syndromes (PNSs) are rare disorders due to remote effects of the immune response against a tumor, targeting both the tumor and healthy tissues such as muscle, brain, and nervous system. Symptoms of PNSs generally precede detection of a tumor; therefore paraneoplastic antibodies are a logical resource for the early detection of cancer. Two PNSs associated with OVCA are myositis and paraneoplastic cerebellar degeneration (PCD), which target muscle and purkinje cells, respectively. Our laboratory has detected the presence of several myositis and PCD associated paraneoplastic antibodies in the sera of patients with OVCA. Methods: Incubation of OVCA patient sera with commercially available paraneoplastic diagnostic line blots indicated presence of paraneoplastic antibodies. OVCA specific epitopes discovered previously in our laboratory by phage-display biopanning were evaluated for both homology to paraneoplastic antigens and for reactivity with PNS patient sera. Selected paraneoplastic antigens reactive with OVCA sera and OVCA specific epitopes homologous with paraneoplastic antigens or reactive with PNS patient sera were evaluated on western blot with OVCA sera, healthy control sera, and sera from patients with benign gynecological conditions. The sera screening will be replicated on ELISA. Recently identified paraneoplastic antigens associated with myositis and PCD that are expressed in OVCA tissue are being evaluated for reactivity with OVCA sera on western blot. Results: We have established a panel of four paraneoplastic antigens that in combination are able to discriminate OVCA sera from healthy patient sera and sera from patients with benign gynecological conditions. Conclusions: Although paraneoplastic syndromes are rare, paraneoplastic antibodies can be present in patients with ovarian cancer without PNS. A panel of paraneoplastic antigens for the autoantibody detection of ovarian cancer has the potential for development of a clinical test.
Distinct Accumbens Shell Output Pathways Promote versus Prevent Relapse to Alcohol Seeking
Authors: Gabrielle D. Gibson, Asheeta A. Prasad, Philip Jean-Richard-dit-Bressel, Joanna O.Y. Yau, E. Zayra Millan, Yu Liu, Erin J. Campbell, Jun Lim, Nathan J. Marchant, John M. Power, Simon Killcross, Andrew J. Lawrence, Gavan P. McNally
Journal: Neuron (2018)
PD-1 inhibitor-related pneumonitis in advanced cancer patients.
Authors: Mizuki Nishino, Nikhil H. Ramaiya, Mark M. Awad, Jennifer A Maattala, Myriam Taibi, Hiroto Hatabu, Patrick Alexander Ott, Philippe Armand, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2016)

3053 Background: PD-1 inhibitor-related pneumonitis is an uncommon but serious immune-related adverse event (irAE). Details of radiographic patterns of this entity remain to be investigated. Methods: Patients (pts) who developed PD-1 inhibitor-related pneumonitis were identified among those treated in trials of nivolumab for advanced melanoma, lung cancer, and lymphoma. Chest CTs were reviewed by a consensus of 3 radiologists to assess CT findings and radiographic patterns of pneumonitis according to ATS/ERS classification of interstitial pneumonias, which were compared across tumor types and treatment regimens. Results: Among 170 pts treated in 10 different trials of nivolumab, either alone or in combination, 20 pts developed pneumonitis as an irAE (Grade: 1 in 5; 2 in 10; 3 in 5 pts). Of these, 13 (65%) were female, median age was 52 (range 28-71); 5 received nivolumab alone and 15 received combination therapy (with ipilimumab in 12, lirilumab in 3). Ten pts had melanoma, 6 had lymphoma, and 4 had lung cancer. Median time from therapy initiation to pneumonitis was 2.6 months (range 0.5-11.5), and was shorter in lung cancer than others (1.1 vs. 3.1 months; p = 0.008). Most pts (17/20; 85%) received corticosteroids; 3 (15%) also required infliximab. Among 19 pts with available CT, ground glass opacities were noted in all pts, with consolidation in 11. The most common distribution was multifocal (n = 9), followed by peripheral and lower (n = 3) and diffuse (n = 3). Radiographic pattern was cryptogenic organizing pneumonia (COP) in 12, non-specific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 pts. AIP/ARDS pattern had the highest pneumonitis grade, followed by COP, while NSIP and HP had lower grade (median Grade: 3, 2, 1, 1, respectively; p = 0.005). COP was the most common pattern in all tumors and treatment regimens. Conclusions: PD-1 pneumonitis showed a spectrum of radiographic patterns, which were associated with toxicity grades of pneumonitis. COP was the most common pattern across tumor types and therapeutic regimens. The radiographic pattern-based approach may contribute to better diagnose, categorize, and prognosticate in this entity.
Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms
Authors: Ofir Wolach, Rob S. Sellar, Kimberly Martinod, Deya Cherpokova, Marie McConkey, Ryan J. Chappell, Alexander J. Silver, Dylan Adams, Cecilia A. Castellano, Rebekka K. Schneider, Robert F. Padera, Daniel J. DeAngelo, Martha Wadleigh, David P. Steensma, Ilene Galinsky, Richard M. Stone, Giulio Genovese, Steven A. McCarroll, Bozenna Iliadou, Christina Hultman, Donna Neuberg, Ann Mullally, Denisa D. Wagner, Benjamin L. Ebert
Journal: Science Translational Medicine (2018)

Thrombosis in myeloproliferative neoplasms is associated with increased NETosis that can be targeted with JAK inhibitors.
High prevalence rate of digestive tract bacteria in duodenoscopes: a nationwide study
Authors: Arjan W Rauwers, Anne F Voor in ’t holt, Jolanda G Buijs, Woutrinus de Groot, Bettina E Hansen, Marco J Bruno, Margreet C Vos
Journal: Gut (2018)

Increasing numbers of outbreaks caused by contaminated duodenoscopes used for Endoscopic Retrograde Cholangiopancreatography (ERCP) procedures have been reported, some with fatal outcomes. We conducted a nationwide cross-sectional study to determine the prevalence of bacterial contamination of reprocessed duodenoscopes in The Netherlands.All 73 Dutch ERCP centres were invited to sample ≥2 duodenoscopes using centrally distributed kits according to uniform sampling methods, explained by video instructions. Depending on duodenoscope type, four to six sites were sampled and centrally cultured. Contamination was defined as (1) any microorganism with ≥20 colony forming units (CFU)/20 mL (AM20) and (2) presence of microorganisms with gastrointestinal or oral origin, independent of CFU count (MGO).Sixty-seven out of 73 centres (92%) sampled 745 sites of 155 duodenoscopes. Ten different duodenoscope types from three distinct manufacturers were sampled including 69 (46%) Olympus TJF-Q180V, 43 (29%) Olympus TJF-160VR, 11 (7%) Pentax ED34-i10T, 8 (5%) Pentax ED-3490TK and 5 (3%) Fujifilm ED-530XT8. Thirty-three (22%) duodenoscopes from 26 (39%) centres were contaminated (AM20). On 23 (15%) duodenoscopes MGO were detected, including Enterobacter cloacae, Escherichia coli, Klebsiella pneumonia and yeasts. For both definitions, contamination was not duodenoscope type dependent (p values: 0.20 and higher).In 39% of all Dutch ERCP centres, at least one AM20-contaminated patient-ready duodenoscope was identified. Fifteen per cent of the duodenoscopes harboured MGO, indicating residual organic material of previous patients, that is, failing of disinfection. These results suggest that the present reprocessing and process control procedures are not adequate and safe.