tbuckley/cabot-search huggingface dataset:
Nivolumab-Induced Pneumonitis in Patient With Metastatic Melanoma Showing Complete Remission on 18F-FDG PET/CT
Authors: Micheline Razzouk-Cadet, Alexandra Picard, Caroline Grangeon-Chapon, Jean-Philippe Lacour, Henri Montaudié
Journal: Clinical Nuclear Medicine (2019)

Abstract A 49-year-old patient with metastatic melanoma was treated with nivolumab (Opdivo). An early 18 F-FDG PET/CT after 2 cycles showed a progressive metabolic disease. A 4-month optimal follow-up 18 F-FDG PET/CT showed a complete metabolic response. The treatment was stopped after 22 cycles because of immunotherapy-related pneumonitis. After discontinuation of treatment, PET/CT examinations demonstrated a metabolic complete remission during 2 years. The metabolic pattern on early PET was suggestive of pseudoprogression, which is a rare phenomenon reflecting an activation of inflammatory cells within the tumor microenvironment causing lesions to increase in size and to accumulate FDG until a sufficient immune response is developed.
GX-G3, a long-acting G-CSF, compared with pegfilgrastim in reducing duration of severe neutropenia after chemotherapy for non-Hodgkin’s lymphoma.
Authors: Senem Ertan-Ahmed, Michael G. Kiehl, Atanas Radinoff, Vasko Graklanov, Nikolay Tzvetkov, Rodica Mihăescu, Düzgün Özatlı, Figen Atalay, Burhan Turgut, Seok-Gu Cho, Grygoriy Rekhtman, Adem Sahin, Hatice Oncel, Yuri Choi, Sang-In Yang, Yoon-Jeong Choi, MinKyu Heo, Young Chul Sung
Journal: Journal of Clinical Oncology (2019)

e19065 Background: G-CSF is used in patients at significant risk for developing severe neutropenia (neutrophil count &lt; 0.5 × 10 9 /L or grade 4 neutropenia) following myelosuppresive chemotherapy. GX-G3, human G-CSF fused to hyFc is a proposed alternative to Neulasta. Methods: An open-label, randomized, phase II study was designed to compare the effects of subcutaneous (SC) injection of GX-G3 (a long-acting G-CSF) at doses of 150, 250 and 350 μg/kg with Neulasta 6 mg administered SC in patients receiving R-CHOP for advanced NHL (n = 65). The primary objective was to assess the duration of severe neutropenia after 1 st cycle of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). The following parameters were also assessed: duration of severe neutropenia after 2 nd cycle of chemotherapy, optimal time for GX-G3 intervention (two GX-G3 250 μg/kg cohorts; administered 24 and 72 hours after R-CHOP), incidence of severe neutropenia and febrile neutropenia post R-CHOP, pharmacokinetics, and safety. Patients were randomly assigned to receive GX-G3 or reference drug, Neulasta, one dose after 1 st and 2 nd cycle of R-CHOP for a total of 2 doses. Results: The mean duration of severe neutropenia after 1 st cycle was shortest in GX-G3 350 μg/kg group [GX-G3 150, 250 (24h, 72h), 350 μg/kg and Neulasta®; 3.2, 2.3, 2.0, 1.3 and 2.4 days, respectively]. The results of all GX-G3 groups and Neulasta were not significantly different for duration of severe neutropenia after 2 nd cycle of R-CHOP, incidence of severe neutropenia and febrile neutropenia, or toxicity profile. The elimination half-life of GX-G3 and Neulasta ranged from 29.8 to 66 hours and 19.2 to 76.8 hours, respectively. Conclusions: GX-G3, in all tested dosage regimen, was safe and well tolerated in this patient population. A single injection of GX-G3 per chemotherapy cycle provided neutrophil support with safety and efficacy similar to that provided by Neulasta. GX-G3 administration after 24 hours, compared to 72 hours post R-CHOP treatment resulted in relatively shorter duration of severe neutropenia. Clinical trial information: 2015-002693-20.
Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database
Authors: Shuang-Jiang Li, Wen-Yu Lv, Heng Du, Yong-Jiang Li, Wen-Biao Zhang, Guo-Wei Che, Lun-Xu Liu
Journal: International Journal of Surgery (2019)
Role for immune checkpoint blockade in <i>BRCA2</i>-mutant prostate cancer.
Authors: Anshuman Panda, Mark N. Stein, Gregory Riedlinger, Gyan Bhanot, Shridar Ganesan
Journal: Journal of Clinical Oncology (2019)

59 Background: Except for rare cases with microsatellite instability, prostate cancer has low mutation burden and low response rate to immune checkpoint blockade (ICB). Genomic correlates of response to ICB in microsatellite stable (MSS) prostate cancer are currently unknown. Here we describe an exceptional response to ICB in BRCA2-mutant prostate cancer and explore immunologic features of BRCA-mutant tumors. Methods: A patient with BRCA2-mutant MSS prostate cancer who progressed on PARP inhibitor therapy was treated with pembrolizumab. Another 8 cases of BRCA2-mutant prostate cancer were evaluated for lymphocyte infiltration and PD-L1 expression by a pathologist. The Cancer Genome Atlas (TCGA) dataset was used to evaluate BRCA-mutant tumors from multiple histology. Presence of putative pathogenic mutations in BRCA1/2 were tested for association with mRNA levels of CD8 + T cell marker ( CD8A), immune checkpoint genes (in PD-1, CTLA-4 pathways), and expression of endogenous retroviruses (ERV). Markers of homologous recombination (HR) defects, namely number of Signature 3 mutations and large ( &gt; 3bp) indels, were also analyzed. Results: Initial patient with BRCA2-mutant MSS prostate cancer had a rapid and ongoing response to pembrolizumab. Analysis of local cohort will be presented. In the TCGA prostate cancer dataset, BRCA2-mutant tumors showed significant overexpression of CD8A, PD-1 and CTLA-4 pathway genes, and ERV3-2. Similar results were observed in BRCA1-mutant (but not BRCA2-mutant) ER+ HER2− breast cancer, but not in BRCA-mutant triple-negative breast and ovarian cancer. Analyses of HR defect markers corroborated these observations. Conclusions: BRCA-mutation accompanied by ERV3-2 overexpression, observed in BRCA2-mutant prostate and BRCA1-mutant ER+ HER2− breast cancer, is associated with CD8 + T cell infiltration and checkpoint pathway upregulation. The effect of BRCA1/2 mutation on immunogenicity may be very tissue and/or cell-of-origin specific, with different cancer types having different levels of immune activation. The association between ERV expression and BRCA2-mutation in prostate cancer requires further investigation. BRCA2-mutant prostate cancers are a class of MSS tumors that may be sensitive to ICB.
CONFINED: distinguishing biological from technical sources of variation by leveraging multiple methylation datasets
Authors: Mike Thompson, Zeyuan Johnson Chen, Elior Rahmani, Eran Halperin
Journal: Genome biology (2019)

Methylation datasets are affected by innumerable sources of variability, both biological (cell-type composition, genetics) and technical (batch effects). Here, we propose a reference-free method based on sparse canonical correlation analysis to separate the biological from technical sources of variability. We show through simulations and real data that our method, CONFINED, is not only more accurate than the state-of-the-art reference-free methods for capturing known, replicable biological variability, but it is also considerably more robust to dataset-specific technical variability than previous approaches. CONFINED is available as an R package as detailed at .
Abstract 16608: Interleukin-1 Receptor Antagonist Deficiency Promotes Angiotensin II-Induced hypertension and Renal Damage
Authors: Sarasa Isobe, Tomiharu Niida, Takehiko Kujiraoka, Yasunaga Shiraishi, Yuko Nakaya, Kouji Akita, Kikuo Isoda
Journal: Circulation (2013)

Background: Angiotensin II (AngII), the main effecter of the rennin-angiotensin system, increases arterial pressure, and activates components of the inflammatory cascade. The interleukin-1 receptor...
Post-partum family planning in Burkina Faso (Yam Daabo): a two group, multi-intervention, single-blinded, cluster-randomised controlled trial
Authors: Nguyen Toan Tran, Armando Seuc, Abou Coulibaly, Sihem Landoulsi, Tieba Millogo, Fatou Sissoko, Wambi Maurice E Yameogo, Souleymane Zan, Asa Cuzin-Kihl, James Kiarie, Mary Eluned Gaffield, Blandine Thieba, Seni Kouanda
Journal: The Lancet Global Health (2019)

Post-partum family planning services can prevent maternal and child morbidity and mortality in low-resource settings. We assessed the effect of a family planning intervention package on modern contraceptive use at 12 months post partum in predominantly rural Burkina Faso.Yam Daabo was a two group, multi-intervention, single-blinded, cluster randomised controlled trial. Primary health-care centres were randomly allocated to intervention or control clusters in a 1:1 ratio with only data analysts masked to the allocation assignment. Interventions comprised refresher training for the provider, a counselling tool, supportive supervision, availability of contraceptive services 7 days a week, client appointment cards, and invitation letters for partners. The primary outcome was modern contraceptive prevalence at 12 months, and secondary outcomes were modern contraceptive prevalence at 6 weeks and 6 months post partum. Analysis was by modified intention to treat. Prevalence ratios were adjusted for cluster effects and baseline characteristics. This study was registered with the Pan-African Clinical Trials Registry (PACTR201609001784334).From July 27-Oct 17, 2016, eight clinics were randomised and 571 women were enrolled and allocated: 286 to four intervention clusters and 285 to four control clusters. Of these, 523 completed the 12-month study exit interview (260 in the intervention group, 263 in the control group) and 523 were included in the intention-to-treat analysis. At 12 months, modern contraceptive prevalence was 55% among women who received the package and 29% among those who received routine care in control clusters (adjusted prevalence ratio 1·79, 95% CI 1·30-2·47). Significant differences in modern contraceptive prevalence were also seen between intervention and control groups at 6 weeks (42% and 10%, respectively; adjusted prevalence ratio 3·88, 95% CI 1·46-10·35) and 6 months (59% and 24%, respectively; 2·31, 1·44-3·71).A package of six low-technology interventions, aimed at strengthening existing primary health-care services and enhancing demand for these services, can effectively increase modern contraceptive use for up to a year post partum in rural settings in Burkina Faso and has the potential to be suitable in similar settings in this country and others.Government of France.
Healthcare resource utilization in first-line immunotherapies for patients with metastatic melanoma.
Authors: Frank Xiaoqing Liu, Andrew Klink, Bruce A. Feinberg, Sama Ahsan, Damion Nero, Bartosz Chmielowski
Journal: Journal of Clinical Oncology (2019)

137 Background: Immunotherapies (I/Os) have demonstrated improved overall survival vs. chemotherapy for patients (pts) with metastatic melanoma (MM). However, little is known about the comparative health care resource utilization (HCRU) among different I/Os. This study examined the real world HCRU across different I/Os: PD-1 inhibitors (pembrolizumab (PEM) or nivolumab (NIVO), PD-1), CTLA-4 inhibitor (ipilimumab, IPI), and combination of I/Os (IPI+NIVO). Methods: A retrospective observational study was conducted using a large US payer claims data. Adults with ≥2 claims for MM and ≥1 claim for metastasis were identified between 1/1/2012 and 6/30/2017 and followed through 9/30/2017. All pts had pharmacy and medical claims and ≥6 months pre-index enrollment. HCRU was calculated per pt per month (PPPM) and by percentages across PD-1, IPI, IPI+NIVO from Index date until the first occurrence of: change in regimen, end of continuous enrollment, or end of study period. Adjusted odds ratios (OR) for HCRU were estimated using logistic regressions to control for baseline patient characteristics. Results: On average, pts in the PD-1 cohort (n = 255) were older than those in IPI (n = 555) and IPI+NIVO (n = 88) cohorts (mean 68 vs 63 and 63, both p &lt; 0.05) and had less brain metastasis (22% vs 34% and 31%, p &lt; 0.05 and p = 0.11, respectively). During 1L therapy, fewer PD-1 pts had any hospitalization (HOSP, 25.9% vs 39.8% and 45.5%, both p &lt; 0.05), fewer HOSPs PPPM (mean 0.06 vs 0.10 and 0.14, both p &lt; 0.05), and fewer ER visits PPPM (mean 0.09 vs 0.13 and 0.18, both p &lt; 0.05) compared to IPI and IPI+NIVO, respectively. Any 30-day re-HOSP and ER visits were numerically lower with PD-1 compared with IPI and IPI+NIVO, but not statistically significant (13.7% vs 19.1% and 18.2%; 40.0% vs 47.0% and 50.0% respectively). Adjusting for baseline characteristics, pts treated with IPI and IPI+NIVO were more likely to have a HOSP than PD-1s (OR = 2.10, 95% CI, 1.44-3.07; and 2.35; 95% CI, 1.32-4.12, both p &lt; 0.01). Conclusions: Pts treated with IPI or IPI+NIVO had significantly increased odds of being hospitalized and higher HOSP and ER visits PPPM compared to PD-1s. Further studies are warranted to confirm these findings.
Antiproliferative activity of angiotensin II receptor blocker through cross-talk between stromal and prostate cancer cells
Authors: Hiroji Uemura, Hitoshi Ishiguro, Noboru Nakaigawa, Yoji Nagashima, Yoshinobu Kubota
Journal: Cancer Research (2005)

2367   We previously demonstrated that angiotensin II (Ang-II) activated the proliferation of prostate cancer cells, and that Ang-II receptor blockers (ARB) could inhibit it. In the present study we investigated whether Ang-II exerts mitogenic effects on the cross-talk between stromal and cancer cells, and whether an ARB can inhibit tumor growth through actions on stromal cells. [Materials and Methods] Cell proliferation and IL-6 secretion of prostate stromal PrSC cells were examined when these cells were stimulated with Ang-II, TNFα or EGF in the absence and presence of ARB. Further, we examined the effect of ARB on MAPK phosphorylation of PrSC cells and of PC-3 cells treated with conditioned medium (CM) of PrSC cells, and determined the effect of ARB on tumor growth induced by paracrine factors from PrSC cells. [Results] Ang-II activated the cell proliferation and IL-6 secretion of PrSC cells, and ARB inhibited it. Ang-II, TNFα or EGF induced MAPK and STAT3 phosphorylation in PrSC cells, and this phosphorylation was inhibited by ARB. CM of PrSC cells with Ang-II activated MAPK phosphorylation in PC-3 cells, and ARB-treated CM of PrSC cells inhibited it. The tumor growth and angiogenesis of a mixture of PC-3 with PrSC were inhibited by ARB administration, while those of PC-3 xenografts were not inhibited. [Discussion] It is well known that prostatic stromal cells, especially fibroblasts, are involved in the development of hormone-refractory prostate cancer accompanied by the secretion of several growth factors. We confirmed that Ang-II augmented the secretion of IL-6 and another cytokines from prostatic stromal cells and ARB inhibited it. ARB exerted an antiproliferative effect on prostate cancer through paracrine factors from stromal cells. Because prostate stromal cells are thought to be involved in the initiation and development of prostate cancer, the present data suggest the possibility that ARBs are a novel therapeutic class of agents for prostate cancer.
Variation in the efficacy of low-dose computed tomographic lung screening based on risk of lung cancer mortality in the National Lung Screening Trial.
Authors: Hormuzd A. Katki, Stephanie A Kovalchik, Martin Tammemagi, Christine D. Berg, Neil Caporaso, Tom Riley, Mary Korch, Gerard A. Silvestri, Anil Chaturvedi
Journal: Journal of Clinical Oncology (2013)

1523 Background: Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the National Lung Screening Trial (NLST). The efficacy of LDCT screening could be improved by targeting smokers at highest risk of lung cancer death, provided that the efficacy of LDCT screening increases with lung cancer mortality risk. Methods: We evaluated the efficacy of LDCT screening as compared to chest radiography in the NLST across groups defined by participants’ 5-year risk of lung cancer mortality at randomization, which was estimated using a validated prediction model. Across quintiles of 5-year lung cancer mortality risk [Q1: 0.15%-0.55%, Q2: 0.56%-0.84%, Q3: 0.85%-1.24%, Q4: 1.24%-2.0%, Q5: &gt;2.0%], we estimated the number of participants with false positive screens, the number of prevented lung cancer deaths, and their ratio. Results: The number of prevented lung cancer deaths due to LDCT screening increased in tandem with lung cancer mortality risk (Q1=0.2, Q2=3.5, Q3=5.1, Q4=11.0, Q5=12.0 per 10,000 person-years; P-trend=0.01). The number of participants with false positive screens per lung cancer death prevented, a measure of screening efficiency, significantly decreased with increasing risk (Q1=1,648, Q2=181, Q3=147, Q4=64, Q5=65, P-trend&lt;0.001). The 60% of participants at highest 5-year lung cancer mortality risk (0.85% or greater) accounted for 88% of LDCT-preventable lung cancer deaths and included only 64% of participants with a false positive screen. The 20% of participants at lowest lung cancer mortality risk (0.15%-0.55%) accounted for only 1% of LDCT-preventable lung cancer deaths. Conclusions: In the NLST, LDCT screening prevented the most lung cancer mortality among those at highest lung cancer mortality risk and prevented almost no mortality among those at lowest risk, providing empirical support for risk-based targeting of smokers to improve the efficacy of LDCT screening.
Mesothelioma: Scientific clues for prevention, diagnosis, and therapy
Authors: Michele Carbone, Prasad S. Adusumilli, H. Richard Alexander, Paul Baas, Fabrizio Bardelli, Angela Bononi, Raphael Bueno, Emanuela Felley‐Bosco, Francoise Galateau‐Salle, David Jablons, Aaron S. Mansfield, Michael Minaai, Marc de Perrot, Patricia Pesavento, Valerie Rusch, David T. Severson, Emanuela Taioli, Anne Tsao, Gavitt Woodard, Haining Yang, Marjorie G. Zauderer, Harvey I. Pass
Journal: CA A Cancer Journal for Clinicians (2019)

Abstract Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high‐resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1‐asssociated protein 1 ( BAP1 ) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.
Fertility awareness based methods for pregnancy prevention
Authors: Rachel Peragallo Urrutia, Chelsea B Polis
Journal: BMJ (2019)

### What you need to know

Fertility awareness based methods of contraception are increasingly being used for pregnancy prevention.1 In the US, the proportion of contraceptive users who choose such methods has grown from 1% in 2008 to approximately 3% in 2014.12 Relative to other methods of pregnancy prevention, however, substantial misinformation exists around fertility awareness based methods of contraception, particularly about the effectiveness of specific methods and how to use them. Providers who offer family planning counselling can promote correct and consistent use of the chosen method by helping people find a method that best fits their individual lifestyle, preferences, and goals.3 This article aims to help clinicians counsel people about fertility awareness based methods for pregnancy prevention by explaining the different methods, the evidence base for their effectiveness, and practical considerations for use.

Fertility awareness based methods are devised on the premise that sexual intercourse can only lead to pregnancy during approximately 6-9 days of the menstrual cycle, commonly referred to as the “fertile window” (or fecund window, box 1).5 …
Horizons of nanotechnology applications in female specific cancers
Authors: Balney Rajitha, Rama Rao Malla, Ramakrishna Vadde, Prameswari Kasa, Ganji Lakshmi Vara Prasad, Batoul Farran, Seema Kumari, Eluri Pavitra, Mohammad Amjad Kamal, Ganji Seeta Rama Raju, Sujatha Peela, Ganji Purnachandra Nagaraju
Journal: Seminars in Cancer Biology (2019)
Results of a phase II study evaluating trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable (MSS) metastatic colorectal cancer (mCRC).
Authors: Manish R. Patel, Gerald Steven Falchook, Kensuke Hamada, Lukas Makris, Robert E. Winkler, Gilad Shalag Gordon, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2019)

48 Background: Patients (pts) with colorectal cancer (CRC) with microsatellite instability (MSI) have recently been shown to respond to anti–programmed death (PD)-1 drugs. Preclinical data suggest that trifluridine/tipiracil (FTD/TPI) treatment converts MSS CRC cells to MSI, sensitizing them to the activity of anti–PD-1 drugs. The aim of this phase 2 study was to evaluate this hypothesis. Methods: This was a multicenter, single-arm, safety lead-in, phase 2 study that used Simon’s 2-stage design to evaluate the safety and efficacy of FTD/TPI (35 mg/m 2 twice daily on days 1-5 and 8-12 every 28 days) plus nivolumab (3 mg/kg every 2 weeks) in pts with heavily pretreated MSS mCRC. Pts had histologically proven metastatic or locally advanced colorectal adenocarcinoma that was MSS (assessed by a local laboratory based on either previous or fresh biopsy), ≥1 measurable lesion for RECIST and immune-related response criteria (irRC) assessment, and failure of ≥2 previous lines of chemotherapy. Six pts were to be enrolled in the safety lead-in, and in order to proceed to Simon’s stage 2, ≥2 of the first 15 pts had to demonstrate a partial or complete response within 6 months based on irRC assessment. Results: The first 6 dose-limiting toxicity (DLT)-evaluable pts enrolled tolerated dosing with no DLTs. A total of 18 pretreated pts enrolled in the first stage (50% males; median age 56.5 yr), among whom 72% had colon cancer and 100% had MSS disease, 56% with RAS mutations. Pts received a median of 2.5 cycles of study therapy (range 1-8). The most common grade 3/4 adverse events (AEs) were neutropenia (28%); diarrhea (17%); and nausea, abdominal pain, fatigue, and anemia (11% each). No pts discontinued treatment due to AEs. No pts achieved a tumor response (either per RECIST or irRC), and the study did not progress to the second stage. Median (6-month) progression-free survival was 2.8 months (21%) per RECIST and 2.2 months (30%) per irRC. Conclusions: The combination of FTD/TPI and nivolumab was feasible and tolerated at the full dose of both compounds. Adding nivolumab to FTD/TPI did not provide additional clinical benefit in pts with previously treated MSS mCRC. Clinical trial information: NCT02860546.