tbuckley/cabot-search huggingface dataset:
Progress Toward Poliovirus Containment Implementation — Worldwide, 2017–2018
Authors: Jacqueline Fournier-Caruana, Nicoletta Previsani, Harpal Singh, Liliane Boualam, Joseph Swan, Anna Llewellyn, Roland W. Sutter, Michel Zaffran
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Substantial progress has been made since the World Health Assembly (WHA) resolved to eradicate poliomyelitis in 1988 (1). Among the three wild poliovirus (WPV) types, type 2 (WPV2) was declared eradicated in 2015, and type 3 (WPV3) has not been reported since 2012 (1). In 2017 and 2018, only Afghanistan and Pakistan have reported WPV type 1 (WPV1) transmission (1). When global eradication of poliomyelitis is achieved, facilities retaining poliovirus materials need to minimize the risk for reintroduction of poliovirus into communities and reestablishment of transmission. Poliovirus containment includes biorisk management requirements for laboratories, vaccine production sites, and other facilities that retain polioviruses after eradication; the initial milestones are for containment of type 2 polioviruses (PV2s). At the 71st WHA in 2018, World Health Organization (WHO) Member States adopted a resolution urging acceleration of poliovirus containment activities globally, including establishment by the end of 2018 of national authorities for containment (NACs) to oversee poliovirus containment (2). This report summarizes containment progress since the previous report (3) and outlines remaining challenges. As of August 2018, 29 countries had designated 81 facilities to retain PV2 materials; 22 of these countries had established NACs. Although there has been substantial progress, intensification of containment measures is needed.
A phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): First results of the GORTEC 2015-01 “PembroRad” trial.
Authors: Xu Shan Sun, Christian Sire, Yungan Tao, Laurent Martin, Marc Alfonsi, Jean Briac Prevost, Michel Rives, Cedrik Lafond, Jean-Marc Tourani, Julian Biau, Lionnel Geoffrois, Alexandre Coutte, Xavier Liem, Elodie Vauleon, Franck Drouet, Jean-François Ramee, Gabriel Waksi, Laura Sinigaglia, Anne Auperin, Jean Bourhis
Journal: Journal of Clinical Oncology (2018)

6018 Background: Based on the hypothesis of a potential synergistic effect of the anti-PD1 pembrolizumab when combined with RT, this new combination was tested in a phase II randomized trial against the SoC cetuximab-RT in LA-SCCHN. Methods: Patients (pts) were randomized between cetuximab (Arm A : 400 mg/m2 loading dose and 250 mg/m2 weekly) and Pembrolizumab (Arm B : 200 mg Q3W during RT). In both arms, patients received IRMT (69.96 Gy in 33 fractions). Main Inclusion criteria were : pts unfit for high dose cisplatin, non operable stage III-IVa-b SCC of oral cavity, oropharynx, hypopharynx and larynx. Treatment allocation was performed by randomization 1:1, stratified on N stage (N0-1 vs N2-3) , tumor location and p16 status. To detect a difference between arms of 60% to 80% in loco-regional control at 15 months (primary endpoint), inclusion of 66 pts per arm was required to achieve a power of at least 0.85 at 2-sided significance level of 0.20, with less than 15% unevaluable pts. Results: from 05/16 to 10/17, 133 pts were randomized in 27 centers, 66 in Arm A and 67 in Arm B. Median age was 65 years, 92% were smokers, 60% of oropharynx, 28% p16+ and 26%, 56% and 19% of stage III, IVa and IVb respectively. Both arms were well balanced. At the time of the abstract writing, full and cleaned safety and compliance data were available for 77 pts (58%). Data for all the randomized pts will be presented at the meeting. In Arm A and B, 25 and 18 Serious Adverse Events (SAE) occurred and 94% and 78% pts had at least one CTCAE v4 grade 3 AE in arm A and B respectively. The compliance to RT was not different (full total dose received by 86% and 88% pts in Arm A and B respectively). Mucositis >= grade 3 was observed in 57% (Arm A) versus 24% (Arm B) of pts (p = 0.004) (but no difference in dysphagia, 34% versus 39%). In radiation field dermatitis >= grade 3 occurred more frequently in Arm A (49% versus 17%) (p=0.003). Conclusions: Preliminary data indicate that tolerance of pembrolizumab-RT was good when compared to cetuximab-RT in LA-SCCHN. Updated and complete safety results will be presented at the meeting. Clinical trial information: NCT02707588.
Matched targeted therapy for pediatric patients with relapsed, refractory or high-risk leukemias: A report from the LEAP consortium.
Authors: Yana Pikman, Sarah K. Tasian, Maria Luisa Sulis, Traci M. Blonquist, Kelly W. Maloney, Jennifer Lynn McNeer, Melinda Gordon Pauly, Neerav Narendra Shukla, Jeffrey Tyner, Peter D. Cole, Michael James Burke, Nathan Gossai, Patrick A. Brown, Lia Gore, Stephen Hunger, Todd Michael Cooper, Lewis B. Silverman, Marian H. Harris, Mignon L. Loh, Kimberly Stegmaier
Journal: Journal of Clinical Oncology (2018)

10518 Background: Despite the remarkable pace in characterizing the genomics of acute leukemias, integration of sequencing into clinical practice is lagging. With increased availability of targeted therapies, optimism exists in matching a patient's genetic lesion to a targeted drug with goals of improving survival and decreasing toxicity. Methods: We established the first pediatric leukemia genomics consortium, Leukemia Precision-based Therapy (LEAP) Consortium, which includes 13 major US pediatric cancer institutions. Using a combination of a next-generation sequencing panel and gene fusion testing, we are conducting a feasibility clinical trial aimed to identify, in real-time, actionable alterations with a matched targeted therapy for patients with high-risk leukemias. Results: To date, we have enrolled 84 pediatric patients. Based on targeted sequencing results, 68% of the patients had a recommendation for targeted therapy, tiered based on the level of evidence for the mutation within the patient's specific leukemia type. Of the 44 patients with clinical follow-up data, 5 (11%) have had changes in therapy based upon our genomic results. Targetable lesions identified include mutations resulting in RAS signaling pathway activation and mutations/translocations involving ABL1. These genomic data refined diagnosis and supported additional germline assessment in a subset of patients. We are establishing mouse patient-derived xenograft models in which to conduct correlative pre-clinical targeted therapy studies. We are further deploying in vitro drug and siRNA sensitivity assays to study response of leukemia cells to targeted therapies and to assess correlation with underlying genetic events. Conclusions: This first multi-institutional prospective pediatric leukemia genomics trial brings state-of-the-art clinical genetic testing to pediatric patients with leukemia, impacting diagnosis, treatment and selection of patients for germline testing. Moreover, our collaboration brings together cutting edge correlative biology studies to impact pediatric leukemia discovery and to inform future genomics-guided therapeutic trials and drug discovery efforts. Clinical trial information: NCT02670525.
Prognostic factors in patients with advanced thymic carcinoma treated with chemotherapy: A retrospective analysis of 289 patients from NEJ023 Study.
Authors: Yusuke Okuma, Ryo Ko, Takehito Shukuya, Kazunari Tateishi, Hisao Imai, Eisaku Miyauchi, Akiko Fujiwara, Tomohide Sugiyama, Keisuke Azuma, Keiko Muraki, Masahiro Yamasaki, Hisashi Tanaka, Yuta Takashima, Sayo Soda, Osamu Ishimoto, Nobuyuki Koyama, Shoichi Kuyama, Kyoko Murase, Satoshi Morita, Kazuhisa Takahashi
Journal: Journal of Clinical Oncology (2016)

8567 Background: Prognostic factors and efficacy of chemotherapy remain unclear in patients with advanced thymic carcinoma. Methods: We performed a multi-institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma, excluding thymoma type A/B. The patients with no indication for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions of the North East Japan Study Group (NEJSG). Data obtained from medical records included demographic, clinicopathologic, treatment, and outcome information. The Kaplan–Meier method was used to calculate overall survival (OS), and the Cox proportional hazards models were used to adjust for potential confounding factors. Results: Among 324 patients recruited, 289 patients were enrolled in this analysis. Patient characteristics were: median age 61 years (range 14–84); male/female 71%/29%; PS 0–1/2–3/unknown 87%/11%/2%; Masaoka stage IVa/IVb/postoperative recurrence/other 26%/50%/18%/6%; UICC TNM stage IV/postoperative recurrence/other 77%/18%/5%. The predominant histological type was squamous cell carcinoma (66%), followed by undifferentiated carcinoma (12%). First-line chemotherapy included platinum-based doublets in 62% of the patients, monotherapy in 4%, other multi-agent chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide: ADOC) in 34%. The median follow-up time was 25.9 months, and median OS from the start of chemotherapy was 30.7 (95% confidence interval, 25.9–35.9) months. There was no significant difference in OS among the different chemotherapy regimens. Age > 75 years (p = 0.011), Masaoka stage IVa (p < 0.001), and volume reduction surgery (p= 0.005) were independent prognostic factors in the multivariate analysis of OS. Conclusions: This is the largest study describing the outcomes of advanced thymic carcinoma in chemotherapy patients. Although Masaoka staging is useful in patients with advanced thymic carcinoma, most of Masaoka stages IVa and IVb patients are classified as stage IV in UICC TNM classification. Volume reduction surgery might prolong OS in advanced thymic carcinoma patients. Clinical trial information: UMIN000015649.
Predicting duration of response to EGFR TKI among EGFR-mutant NSCLC patients.
Authors: Lama Sakr, Goulnar Kasymjanova, David I. Small, Victor Cohen, Luisa Galvis, Carmela Pepe, Jason Scott Agulnik
Journal: Journal of Clinical Oncology (2016)

e20646 Background: Epidermal growth factor receptor (EGFR) mutation is a strong predictor of response to EGFR tyrosine kinase inhibitors (TKI). However, response duration is variable. The predictive value of EGFR mutation for response is superior to previously reported clinical predictors, namely female gender, Asian ethnicity, smoking status, and histology. It is unclear, however, whether any clinical characteristics have additive predictive value for duration of response to EGFR-TKI. Here, we attempted to identify clinical predictors of response duration to EGFR-TKI in EGFR-mutant NSCLC. Methods: Review of a prospectively collected lung cancer patients’ database at a tertiary care hospital was performed. Stage IV EGFR-mutant patients diagnosed between 2004 and 2015 who received EGFR-TKI for ≥ 3 months, at any line of treatment, were included. The following variables were collected for purpose of analysis: age, gender, smoking status, tumor histology, specific EGFR mutation (exon 19 versus 21 mutation), ECOG PS, line of TKI treatment, and serum CRP levels. Chi square and t-test were used where appropriate. Univariate and mutivariate modeling was used to explore the predictive power of covariates. Results: One hundred ten patients with EGFR mutant stage IV lung cancer were included in this study. Patients were predominantly female (77%), never or light smokers (57%), with non-squamous histology (93%) and an exon 19 mutation (66%). Mean duration of treatment with EGFR-TKI was 14.4 (range 3-86) months. In univariate analysis, never-smoking status, exon 19 mutation and low serum CRP were predictive of a longer EGFR-TKI treatment duration. However, in multivariate analysis only exon 19 and CRP level were significantly associated with longer duration of response to EGFR-TKI. Conclusions: Gender, smoking status and ethnicity- although initially identified as predictors of response to EGFR-TKI in an unselected population- do not confer additional predictive potential of treatment response duration in EGFR mutant NSCLC patients. Only serum CRP level- and exon 19 mutation status- are independently associated with duration of response to EGFR-TKI in this population.
Dynamics of immune-mediated thyroid dysfunction in patients with advanced renal cell carcinoma receiving checkpoint inhibitor therapy.
Authors: Juan Carlos Osorio, Sujata Patil, Devyn Taylor Coskey, Maria Isabel Carlo, Darren R. Feldman, Matthew David Hellmann, Martin Henner Voss
Journal: Journal of Clinical Oncology (2017)

e16071 Background: Checkpoint inhibitors (CPI) are quickly gaining relevance in the management of metastatic renal cell carcinoma (RCC). Treatment is generally well tolerated, but immune-induced thyroid dysfunction (TD) is reported in up to 10% of patients (pts) across trials. The dynamics of this phenomenon are undefined; hence there are no proposed standards for endocrine surveillance on therapy. Here we report on a cohort of RCC pts treated with CPI at Memorial Sloan Kettering Cancer Center with serial prospective assessment of thyroid function on therapy. Methods: Thyroid function tests (TFT) were assessed at baseline and serially on therapy. We recorded trends for hyper- and hypothyroidism and determined median time to development of TD by standard statistical methods. T4 replacement therapy was investigated by individual chart review. The association of TD with outcomes on CPI therapy was assessed by non-parametric tests. Results: Of 59 pts with serial TFT assessment, 20 were hypothyroid and 39 were euthyroid at baseline. 50% of previously hypothyroid pts required adjustment of T4 dosage. Thirteen of 39 euthyroid pts (36%) developed new TD requiring thyroid replacement. TD occurred early (median time to onset: 1.4 months, range 0.9-9.6), and in six of the 13 pts (46%), transient thyroiditis preceded hypothyroidism. None of the pts with thyroiditis required treatment, and the median duration from onset of thyroiditis to development of hypothyroidism was 1.5 months (range 0.7-2.8). All pts with hypothyroidism required replacement therapy; none required discontinuation of immunotherapy due to TD. TD was not associated with difference in objective response rate (fisher’s exact, p = 0.163), regression in target lesions (wilcoxon rank-sum, p = 0.135), or PFS (log rank p = 0.8214). Conclusions: TD is common in RCC pts receiving CPI therapy. In this cohort, onset of TD was early, thyroiditis was always transient, and no new cases were detected beyond 10 months. Confirming these findings in larger cohorts will provide meaningful data to guide management of TD when using this new class of agents outside of clinical trials.
T memory cells in the tumor invasive margins affect survival in colon cancer (CC) but not in breast cancer (BC).
Authors: Marco Carlo Merlano, Vincenzo Ricci, Ornella Garrone, Martina Ferrero, Daniela Vivenza, Cristina Granetto, Emanuela Miraglio, Carolina Cauchi, Nerina Denaro, Marcella Occelli, Elena Fea, Anna Maria Vandone, Paola Vanella, Gianna Di Costanzo, Ida Colantonio, Chiara Varamo, Laura Lattanzio, Cristiana Lo Nigro, Alberto Comino
Journal: Journal of Clinical Oncology (2016)

e23104 Background: TNM, stage and key biological markers, direct the choice of adjuvant chemotherapy. However, many patients behave different than expected notwithstanding the careful analysis of stage and markers to select treatment. Tumor infiltrating lymphocytes (TIL), their density and site of distribution, might explain the different outcome and offer additional information to select adjuvant treatment. Methods: We performed a case-control study based on 30 cases of CC and 30 cases of BC underwent to adjuvant therapy. Fifteen pts in each cohort relapsed and 15 did not. We analyzed the density of CD3+, CD8+ and CD45RO+ (CD45+)(memory cells) in the surgical samples after radical surgery by IHC in the center of the tumor (CT) and in its invasive margin (IM). Measurements were recorded by image analysis as the number of positive cells per tissue surface unit in square millimeters. Each cohort was then divided into two groups, high density (HD) and low density (LD). Cut-off between HD and LD was the median value observed in each cohort. DFS and OS between HD and LD were compared by Log Rank test. Results: We limit the present report to the cumulative analysis of each cohort. Colon cancer: density of CD3+, CD8+ and CD45+ in CT did not affect DFS and OS. On the contrary HD of CD3+, CD8+ and CD45+ in IM showed significant benefit in DFS compared to LD (p = 0.0003, p = 0.033 and p = 0.018 respectively). Similarly, we observed a significant gain in OS in pts with HD CD3+ and CD45+ (p = 0.011 and p = 0.049) but not CD8+ (p = 0.12) in IM. Breast Cancer: we did not observe any significant prognostic difference between HD and LD of CD3+, CD8+ and CD45+, neither in CT nor in IM. Conclusions: In our study HD CD3+, CD8+ and CD45+ in CT did not impact DFS or OS, both in CC and in BC. On the contrary HD CD3+, CD8+ and CD45+ in IM significantly improved DFS in CC. We observed a significant gain in OS in CC HD CD3+ and CD45+ in IM. All these observations suggest a more pronounced role of TIL in IM compared to CT in CC. We did not observe any relationship between prognosis and TIL in breast cancer. This might reflect the broad prognostic heterogeneity in breast cancer, probably requiring a larger sample population.
The effect of emergency presentation on survival of lung cancer patients.
Authors: Marko Jakopovic, Lela Bitar, Ivona Markelic, Fran Seiwerth, Fedza Dzubur, Ana Hecimovic, Branka Cucevic, Ivica Mazuranic, Gzim Redzepi, Andrea Vukic Dugac, Mateja Jankovic Makek, Miroslav Samarzija
Journal: Journal of Clinical Oncology (2016)

e18041 Background: A significant proportion of lung cancer patients are diagnosed through emergency department (ED), which is usually associated with poorer prognosis. We investigated the assocation between diagnosis of lung cancer after presentation through emergency department due to symptoms associated to lung cancer. Methods: Medical charts of 1359 newly diagnosed lung cancer patients in years 2012 and 2013 from Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb were examined. Survival was calculated for overall lung cancer population and according to histology subtypes. Results: The medical charts of 951 males and 407 females, mean age 64 years (males 64.5, females 62) were reviewed. 292 out od 1359 patients (21,5%) were diagnosed with lung cancer after initial presentation through ED. The most common reasons for ED admissions were hemopytsis (in 31% of patients), pneumonia (16%), brain metastasis (15%), dyspnea (10%) and superior vena cava syndrome in 8% of patients. There were no differences in histology subptypes between two different routes of presentation (most common histology subtype was adenocarcinoma followed by squamous histology). Significantly higher proportion of patients diagnosed after initial diagnosis through ED were at presentation in stage IV (61 vs 44%, p < 0.0001), poorer performance status (ECOG 3-4 vs ECOG 0-1, p < 0.0001), significantly less patients underwent surgical resection (14 vs 5%, p < 0.0001) and radiotherapy (56 vs 73%, p < 0.0001). Median overall survival (mOS) was significantly lower in patients diagnosed through ED (6.0 vs 10.0 months, p < 0.0001). In patients with non-small cell lung cancer (NSCLC) results were similar (mOS 6.0 vs 10.0 months, p < 0.0001). In patients with small cell lung cancer (SCLC) mOS was also significantly worse (7.0 vs 9.0 months, p < 0.0001) in patients diagnosed through ED. Conclusions: Higher stage, reduced access to surgical resection and radiotherapy, and significantly lower overall survival regardless of histology subtypes among lung cancer patients who presents through emergency department, stress out the importance of earlier diagnosis of lung cancer patients so that initial presentation through emergancy department can be reduced.
Patterns of palliative care utilization in stage IV non-small cell lung cancer in the National Cancer Database.
Authors: Urshila Durani, Narjust Duma, Ryan D. Frank, Gaurav Goyal, Siddhartha Yadav, Aaron Scott Mansfield, Julian R. Molina, Sikander Ailawadhi, Timothy Jerome Moynihan, Ronald S. Go
Journal: Journal of Clinical Oncology (2018)

10109 Background: Early integration of Palliative Care (PC) improves survival in stage IV non-small cell lung cancer (NSCLC). Here we explore patterns in PC utilization in this group. Methods: We queried years 2004-2014 of the National Cancer Database for adults with stage IV NSCLC. Patients receiving pain management +/- other palliative procedures were PC utilizers. In addition to descriptive statistics, multivariable logistic regression models with interaction analyses identified predictors of PC utilization. Results: Of 341,993 patients, 3.2% received PC at initial treatment. PC utilization increased significantly from 2004-2006 to 2013-2014 (2.3% vs 4.2%, p < 0.01). Whites had higher PC utilization (3.3%) than blacks (2.6%) and Hispanics (2.3%, p < 0.01 for both). Significant predictors of PC on multivariable regression are listed in the Table. Interaction analyses found that Hispanics and Asians had a slower increase (p < 0.01) in PC utilization over time compared to Whites or Blacks. An additional 13.8% and 5.3% received palliative radiation or chemotherapy, respectively. 0.9% received palliative surgery, and 1.4% received some combination of the 3 modalities. Conclusions: PC utilization in stage IV NSCLC is markedly low and plagued by racial and socio-economic disparities despite guidelines advocating early PC integration. Multivariable regression of PC utilization in Stage IV NSCLC. Parameter Odds Ratio (95% CI) Race/Ethnicity White REF Black 0.8 (0.7-0.8) ** Hispanic 0.7 (0.6-0.8) ** Asian 1.0 (0.9-1.2) Age (per 10 years) 0.9 (0.9-1.0) * Year 2004-2006 REF 2007-2008 1.3 (1.2-1.3) ** 2009-2010 1.4 (1.3-1.5) ** 2011-2012 1.7 (1.6-1.8) ** 2013-2014 1.8 (1.7-1.9) ** Male 1.5 (1.2-2.0) ** Primary Payer Private REF Medicaid 1.8 (1.1-3.1) * Medicare 0.6 (0.4-0.9) ** Uninsured 0.9 (0.5-1.8) Median Income Quartile of Zip code 1 REF 2 0.9 (0.8-0.9) ** 3 0.8 (0.7-0.8) ** 4 0.7 (0.7-0.8) ** % No High School Degree > = 21% REF 13-20% 1.5 (1.0-2.1) * 7.0-12.9% 2.2 (1.6-3.2) ** < 7% 1.3 (0.8-1.9) Academic vs Community Facility 1.2 (1.1-1.3) ** Charlson/Deyo score 0 REF 1 1.4 (1.4-1.5) ** 2+ 1.5 (1.4-1.6) ** * P < .05 ** P < .01Grade, Histology, Primary site, Distance to facility, Region, and Rural status not shown