tbuckley/cabot-search huggingface dataset:
Expert consensus on the development of quality care measures for kidney cancer in Spain.
Authors: Vicente Guillem, Carlos Camps, Miguel Angel Climent Duran, Aránzazu Gonzalez del Alba, Martín Emilio Lázaro Quintela, María José Mendez Vidal, Alvaro Pinto, Javier Puente, Fernando Caballero, Francisco J Campos, Ignacio Duran, Enrique Gallardo Diaz
Journal: Journal of Clinical Oncology (2020)

e19180 Background: To promote the continuous improvement of kidney cancer healthcare by proposing quality care measures (with respective indicators and standards) for its diagnosis, treatment and follow-up care that can be used by the corresponding professionals and that can be applied across the Spanish healthcare system. Methods: 1. a) Bibliographic review of international research (previous 5 years) on the quality of kidney cancer care; b) Multidisciplinary nominal group (9 oncology experts from the ECO Foundation –Excellence and Quality in Oncology Foundation – and 2 university methodologists – Francisco de Vitoria University Faculty of Medicine) to identify and select possible quality measures that can be applied in Spain; c) Modified Delphi Consensus (two rounds, remotely) by a panel of 55 oncologists subspecialized in kidney cancer, selected by a geographically stratified snowball sample. The ASCO (American Society of Clinical Oncology) /QOPI (Quality Oncology Practice Initiative) model is followed for the drafting of each item: definition of measures, indicators, information sources, exclusions, clarifications, categorization, acceptable standards. Results: The nominal group proposed 43 possible quality measures to the Delphi panel. Consensus participation rate = 84.5% (47 specialists). A unanimous consensus was achieved for 40 quality measures, grouped into the following areas: 4 structural, 33 regarding treatment process and 3 regarding clinical results. Conclusions: The level of consensus among Spanish oncologists subspecialized in kidney cancer on the proposed care measure for the management of said cancer is very high (93%). These results indicate widespread acceptance and applicability of said measures in the Spanish National Healthcare System and, with this in mind, they will henceforth be a valuable tool for the comparative evaluation of the quality and fairness of the oncological care of kidney cancer patients in Spain.
Micro-learning: A new approach to upskilling and professional development on the management of patients on immunotherapy.
Authors: Helen Winter, Jessica Bal, Gemma Shaw, Nick Leney, Christopher Herbert
Journal: Journal of Clinical Oncology (2020)

11036 Background: Advances in cancer management are rapidly evolving . The introduction of immunotherapy across many tumour types and the potential of effector T cell therapies for patients requires upskilling in the wider health care team. This requires developing learning aimed at understanding the new mechanisms of action, potential side effects and how we educate and manage our patients receiving these therapies. Methods: Five stand alone micro-learning sessions on Immunotherapy were designed aimed at the acquisition of new skills and knowledge in a concise and targeted way. These sessions covered the key areas identified by the Systemic Therapy Day and Acute Oncology Units. These topics developed covered: What is Immunotherapy (IO) (its not chemo); How to interpret thyroid function for patients on IO; Get to know your Cortisol levels and adrenal insufficiency in patients with IO; Proactive management of IO Colitis; Liver function for patients on IO. These were delivered and evaluated during the working day in brief bite-sized sessions. Results: Attendance at formal training sessions - including annual study days and monthly study sessions are not keeping pace with the requirements for upskilling of staff. We present the evaluation of micro-learning delivered within the working day in short sessions. Conclusions: In the era of precision medicine, immunotherapy and effector T cell therapies a new approach to learning and upskilling in the wider health care team is needed. An integrated approach to learning on-the -job with short micro-learning sessions may embed the acquisition of new skills. More importantly, vocational education seeks to change habits, behaviour and culture. This needs to be accessible and flexible to adapt to the current patterns of work.
Clinical value of plasma level of tissue factor in patient with coronary heart disease
Authors: Xiao-yan Wu, Jiang-hua Ren
Journal: BMJ (2008)

Objective To study the relationship between plasma level of tissue factor(TF)and severity of coronary heart disease(CHD).Methods Coronary angiography was performed in 237 patients with suspected CHD,with 149 diagnosed as CHD and 88 excluded.Seventy of stenosis of coronary arteries (CA)was evaluated by modified Gensini score on the basis of angiographic imaging.Blood glucose,serum levels of total cholesterol(TC),triglycerides(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),lipoprotein(a)[Lp(a)],uric acid,high sensitivity C-reactive protein(Hs-CRP),fibrinogen(FIB)and plasma level of TF were determined for all the subjects.Relationship between plasma level of TF and severity of pathological changes in CA was evaluated by linear correlation and multiple regression analyses for controlling other relevant factors.Results Plasma level of TF in patients with CHD[(138±39)ng/L]was significantly higher than that in controls[(61±19)ng/L](P＜0.01).Plasma level of TF obviously correlated with severity of pathological changes in CA(r=0.710,P＜0.01).Partial correlation analysis showed a positive correlation between plasma TF and severity of pathological changes in CA,independent of other potential influential factors,with a partial coefficient of correlation of 0.509(P＜0.01).Multiple stepwise regression analysis indicated that plasma level of TF associated with severity of pathological changes in CA,as well as with diabetes,LDL-C,Lp(a),Hs-CRP and FIB,with coefficients of correlation of 0.172,0.180,0.147,0.308 and 0.175,respectively(P＜0.05).Conclusion Elevated plasma level of TF may be one of important risk factors for CHD,which reflects severity of pathological changes in CA.

Key words: 
Coronary heart disease; Tissue factor;  Risk factorsEmail:wuxiaoyan299@yahoo.com.cn
Health plan expenditures young adults with newly-diagnosed Hodgkin lymphoma (HL) by care at NCI-designated comprehensive cancer centers (CCC) vs. other treatment sites (non-CCC).
Authors: Julie Anna Wolfson, Smita Bhatia, Jill P. Ginsberg, Laura Becker, David Bernstein, Henry J. Henk, Gary H. Lyman, Paul C. Nathan, Diane Puccetti, Jennifer J Wilkes, Lena Winestone, Kelly Kenzik
Journal: Journal of Clinical Oncology (2020)

7081 Background: Patients diagnosed with HL between 22-39y have worse outcomes than younger patients (≤21y); we previously reported that treatment at a CCC mitigates these disparities [Wolfson, Leukemia 2017]. While there is general consensus that CCC care is expensive, expenditures for managing young adults with HL in CCC vs. non-CCC are not known. Methods: Cancer-related expenditures were examined in HL patients diagnosed between 2001-2014 at age 22-39y and treated at CCC and non-CCC sites using commercial insurance claims data (OptumLabs Data Warehouse). Multivariable generalized linear models with log link modeled average monthly health plan paid expenditures, adjusting for sociodemographics, stage, adverse events, pre-existing comorbidities, and diagnostic era. Results: Of the 1501 HL patients, 33% (n = 489) were treated at a CCC. Patients treated at CCC vs. non-CCC did not differ with respect to race, sex, income, diagnostic era or comorbidities (p≥0.3). Mean duration of enrollment was longer in CCC than non-CCC (25 vs. 23 mos; p &lt; 0.001) patients. During the first year after HL diagnosis, total average monthly expenditures were higher in CCC ($9,111) than non-CCC ($7,834, p = 0.001), including those related to inpatient (CCC: $1,790 vs. non-CCC: $1,011; p = 0.001) and outpatient (CCC: $6,971 vs. non-CCC: $6,487; p = 0.001) expenditures. The higher CCC expenditures were associated with higher monthly rates of inpatient admissions (IRR = 1.3, p = 0.001) and outpatient visits (IRR = 1.1, p = 0.02) at CCC. Rates of chemotherapy-related inpatient admissions were higher (IRR = 2.3, p = 0.001) in CCC than non-CCC patients, while outpatient chemotherapy visit rates were lower (IRR = 0.9, p = 0.001) in CCC. During Years 2-3, total average monthly expenditures were higher in CCC ($19,259) than non-CCC ($4,145, p = 0.002) patients. Outpatient expenditures were higher in CCC ($10,164) vs. non-CCC ($2,901, p = 0.001), with higher monthly outpatient visit rates (IRR = 1.7, p = 0.001) at CCC. Conclusions: Inpatient and outpatient cancer-related expenditures in young adults with HL were higher at CCC than non-CCCs. Higher outpatient expenditures at CCC were associated with only higher monthly visit rates. Higher inpatient expenditures were in the setting of higher admission rates, including those related to chemotherapy. Additional work is necessary to understand whether these higher expenditures at CCC are related to supportive care and/or differences in facility structure and billing practices.
Disease characteristics and outcome of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received a beta emitter (177Lu-PSMA) after an alpha emitter (radium-223).
Authors: A. Oliver Sartor, Christian la Fougère, Markus Essler, Samer Ezziddin, Gero Kramer, Jörg Ellinger, Luke T. Nordquist, John Sylvester, Giovanni Paganelli, Avivit Peer, Martin Boegemann, Jeffrey Meltzer, Per Sandstrom, Danny Song
Journal: Journal of Clinical Oncology (2020)

e17592 Background: Ra-223, a targeted alpha therapy, showed an overall survival (OS) benefit and favorable safety profile in mCRPC pts in a phase 3 trial. 177Lu-PSMA radioligand is an investigational agent for mCRPC. REASSURE (NCT02141438) is a global, prospective, observational study investigating Ra-223 safety in routine clinical practice over 7 years’ follow-up in mCRPC pts. Data from the second prespecified interim analysis (IA) were used to investigate safety and outcomes of pts who received 177Lu-PSMA after Ra-223 therapy. Methods: Data cut-off for the second prespecified IA was March 2019, and included pts who had subsequent 177Lu-PSMA after the last Ra-223 dose. Disease characteristics, adverse events (AEs) after last Ra-223 dose, and OS are described. Results: Of 1465 pts overall, 26 received 177Lu-PSMA subsequent to Ra-223. In this subgroup, pts received multiple anticancer therapies prior to 177Lu-PSMA. 13 pts (50%) received Ra-223 as combination therapy at second line (metastatic setting). Pts received a median of six Ra-223 doses. After Ra-223 treatment ended, 3 pts (12%) had drug-related serious AEs, 9 pts (35%) had grade 3/4 bone marrow suppression-relevant hematologic AEs. Median duration of 177Lu-PSMA treatment was 3.5 months. 19 pts (73%) received 177Lu-PSMA as fourth-line therapy or onwards. OS was 28.0 months from start of Ra-223 and 13.2 months from start of 177Lu-PSMA. Conclusions: In this select population receiving a sequence of multiple lines of therapy with different modes of action, grade 3/4 hematologic AEs after Ra-223 were low. Treatment with subsequent 177Lu-PSMA seems feasible, based on duration of 177Lu-PSMA and survival. Clinical trial information: NCT02141438 . [Table: see text]
CD68+ tumor-associated myeloid cells as the target of adenosine-induced gene products and predictor of response to adenosine blockade with ciforadenant (cifo) in renal cell cancer (RCC).
Authors: Martin H Voss, Andrew N. Hotson, Stephen Willingham, Brett Gordon Maxwell Hughes, Jaime R. Merchan, Lawrence Fong, Michael Chu, Saby George, Brian Munneke, Mehrdad Mobasher, Richard A. Miller
Journal: Journal of Clinical Oncology (2020)

5025 Background: Adenosine in the tumor microenvironment (TME) is immunosuppressive and may play a role in resistance to immunotherapy. We described an adenosine induced gene expression signature (AS, Fong, Cancer Disc 2020) that correlates with response to therapy with cifo, an adenosine A2A receptor antagonist, as monotherapy or in combination with atezolizumab in refractory RCC. These genes express chemokines that signal through CCR2 and CXCR2 to recruit myeloid cells including immunosuppressive tumor associated-M2 macrophages, which are thought to mediate resistance to anti-PD(L)1 treatment. We now identify tumor infiltrating CD68 + myeloid cells as the effector cell for adenosine mediated immunosuppression. Methods: 82 RCC pts have been treated in an ongoing Phase 1/1b trial evaluating cifo (100mg po bid) monotherapy or combination with atezolizumab (840mg IV q 2 weeks). Tumor biopsies, obtained at screening and on therapy, are available for analysis in 32 pts to date. RNA expression was measured in tumors using Nanostring. Immunohistochemistry (IHC) for CD68 was performed on biopsies with CD68+ tumors defined as &gt; 4% tumor area containing CD68+ cells. Results: Pt characteristics are median age 63; median prior therapies 3, with 72% failing prior anti-PD(L)1. Gene expression of M2 markers consisting of CD68 (p = 0.0008) and CD163 (p = 0.03) was higher in baseline samples from AS+ compared to AS- pts. By IHC, 10 pts had CD68+ cells infiltrating the tumor; 9 of 10 AS+. Tumor regression was observed in 6 of 10 CD68+ pts (N = 3 monotherapy and 3 combination) including 4 partial responses (PR, RECIST). No PRs and 2 minor responses were seen in 22 pts who were CD68- (p &lt; 0.005). Median time to progression was not reached for CD68+ vs 2 mo for CD68-. Paired biopsies showed a significant reduction in infiltrating CD68+ cells (p = 0.03) with treatment including 2 of 2 evaluable PRs. Conclusions: Adenosine immunosuppression is mediated by M2 macrophages, which can be reversed by cifo. Enumerating tumor infiltrating CD68+ cells may be a valuable biomarker for identifying pts that will respond to adenosine blockade. Clinical trial information: NCT02655822 .
Comparison of treatment outcomes in patients with metastatic lung cancer who did or did not develop EGFR T790M mutation.
Authors: Zhen Wang, Jason Sandler, Kevin Shieh, Lan Mo, Yiwu Huang, William B. Solomon, Kevin Douglas Becker, Yiqing Xu
Journal: Journal of Clinical Oncology (2020)

e21658 Background: First-line treatment of lung cancer patients with EGFR mutation with early generation tyrosine kinase inhibitors (TKIs) renders a median progression-free survival (mPFS) of 11 months (m), and for the patients who subsequently develop the T790M mutation, osimertinib provides an additional mPFS of 10 m. First-line treatment with osimertinib showed mPFS of 18.9 m and none developed T790M at the time of progression (FLAURA trial). We hypothesized that the mPFS for patients who developed T790M mutation might be longer than those who did not and the prognosis and outcome might be different between these two groups. Methods: This is a retrospective study on patients who were diagnosed with metastatic, EGFR-mutated NSCLC and treated at Maimonides Cancer Center between 1/1/2011 and 9/30/2019. Patients were divided into two cohorts: those who did not develop T790M mutation (group 1), and those who did (including 1 patient who had de novo mutation, group 2). Results: Fifty-six patients were identified, with median age of 70 years (range 40-93). All patients had adenocarcinoma. Thirty-nine (70%) were Chinese. There were 31 (55%) exon 19 deletion, 22 (39%) L858R, 1 E709A, 1 G719S and 1 de novo T790M mutations. Forty-five patients (80%) never developed T790M (group 1), 10 (18%) did and 1 had primary mutation (group 2). The median time to developing T790M mutation was 22 m. In group 1, 8 patients received first-line osimertinib, while other 37 received erlotinib (23), gefitinib (4) and afatinib (10). Among the 37 patients, 12 were switched to osimertinib in subsequent lines, 5 due to toxicity and 7 due to progression. In group 2, 8 patients received osimertinib at identification of T790M and 1 for de novo mutation. At 22 m median follow up, the mPFS for group 1 was 14 m (95% CI 9.3-19); the mPFS for group 2 was 21.6 m (95% CI 7.4-49.1) up to the time of identification of T790M, and 31.2 m (95% CI 4.9-45.4) until disease progression after osimertinib. The mPFS of the entire cohort was 17.1 m (95% 11.1-25.9), and mOS was 22.0 m (95% 15.6-29.6). The mOS was 19.0 m (95% CI 11.4 – 25.2), and 39.9 m (95% CI 13.3 – 62.1) for group 1 and 2 respectively. Conclusions: Patients who developed the T790M mutation appeared to have a longer PFS than those who did not and the mean duration to detection of T790M was 22 m. The development of T790M may confer a slower growth pattern and longer PFS. This question should be further explored in larger studies.
Histological–ultrasonographical correlation of pulmonary involvement in severe COVID-19
Authors: Renata Aparecida Almeida Monteiro, Ellen Pierre de Oliveira, Paulo Hilário Nascimento Saldiva, Marisa Dolhnikoff, Amaro Nunes Duarte-Neto, Luiz Fernando Ferraz da Silva, Thais Mauad, Glaucia Aparecida Bento dos Santos, Thábata Larissa Luciano Ferreira Leite, Catia Sales de Moura, Jair Theodoro Filho, Kely Cristina Soares Bispo, Angela B. G. dos Santos, Sandra de Moraes Fernezlian, Reginaldo Silva do Nascimento
Journal: Intensive Care Medicine (2020)
Influence of denosumab on disseminated tumor cells (DTC) in the bone marrow of breast cancer (BC) patients with neoadjuvant treatment: A GeparX translational substudy.
Authors: Pauline Wimberger, Jens U. Blohmer, Petra Krabisch, Theresa Link, Marianne Just, Bruno Valentin Sinn, Eike Simon, Christine Solbach, Tanja N. Fehm, Carsten Denkert, Cristin Kühn, Kerstin Rhiem, Hans Tesch, Sherko Kümmel, Andrea Petzold, Oliver J. Stoetzer, Cornelia Meisel, Jan Dominik Kuhlmann, Valentina Nekljudova, Sibylle Loibl
Journal: Journal of Clinical Oncology (2020)

580 Background: DTCs in the bone marrow are observed in up to 30% at primary diagnosis of BC and their presence is an independent prognostic factor for reduced survival. It was shown that antiresorptive therapy eradicates DTCs and improves prognosis in DTC-positive BC patients (pts). In the GeparX phase III prospective randomized trial, denosumab (a monoclonal IgG2-anti-RANKL-antibody) was investigated as add-on treatment to neoadjuvant chemotherapy (NACT) with two different nab-paclitaxel schedules in early high-risk primary BC. In a translational substudy, we analyzed for the first time the influence of short-term denosumab treatment (24 weeks) on the presence of DTCs. Methods: A total of 167 pts from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive pts were re-analyzed for DTCs after NACT±Denosumab. Results: Overall, 60/167 pts (35.9%) treated with NACT±Denosumab had a pathological complete response (pCR; 55.4% in TNBC, 43.3% in HER2+, 15.3% in HR+/HER2-). At baseline, 43/167 pts (25.7%) were DTC-positive and 41 of those were available for re-analysis of DTCs after NACT±Denosumab. DTC eradication was observed in 77.8% after NACT+Denosumab and in 69.6% after NACT alone (p = 0.726). Due to the limited number of pts eligible for DTC-re-analysis after NACT, a subtype specific analysis for the effect of denosumab was not possible. There was no significant association between pCR and i) the presence of DTCs at baseline (37.1% DTC-negative vs 32.6% positive, p = 0.71) or ii) the eradication of DTCs after NACT±Denosumab (36.7% vs 27.3%, p = 0.72). Notably, in TNBC, we observed a tendency that DTC-positivity at baseline or DTC-persistence after NACT could be associated with reduced pCR rate (40.0% in DTC-positive vs. 66.7% in DTC-negative pts, p = 0.16; 25% in DTC-persistent pts vs. 50% in DTC-eradicated pts, p = 0.59). Conclusions: Denosumab in addition to NACT does not improve pCR, but the suspected effect of denosumab on DTC eradication should be further analyzed in TNBC. Key words: GeparX trial, denosumab, disseminated tumor cells, bone marrow, neoadjuvant chemotherapy. Funding: GeparX and DTC substudy were financially supported by Amgen and Celgene. Clinical trial information: NCT02682693 .
The role of HPV vaccination as a cancer prevention agent.
Authors: N Mullai, Soleiman Osman, Joseph Rattenni
Journal: Journal of Clinical Oncology (2020)

e13566 Background: Human papilloma virus (HPV) is the most common sexually transmitted agent and has extensive association with many malignancies such as cervical, vaginal, vulvar, penile, and head and neck cancers. Vaccination helps prevent sexually transmitted diseases due to HPV. In addition, it provides protection against cancers caused by persistent, high-risk HPV infection in both male and female. Methods: Data collected from the medical records of patients diagnosed with anogenital, and head and neck cancers during 2017-2019 were studied retrospectively and the association of HPV infection was analyzed. Results: There were thirty-three cases of anogenital, and head and neck cancers diagnosed during the study period. The following were the occurrences: penile cancer 1, anal cancer 4, cervical/uterine/vaginal cancers 10, and head and neck cancer including tonsil, base of tongue, vocal cord, and glottis 18. HPV status was available in twenty-six (79%) patients. Fourteen patients were positive for high-risk 16/18 HPV strain, twelve were HPV negative, and HPV status was unknown for seven patients. Most of the patients were smokers and none of them had received HPV vaccination. The patients were treated appropriately with chemotherapy, radiation, and surgery. Conclusions: Human papilloma virus (HPV) infection type 16/18 is the most common sexually transmitted infection associated with significant anogenital and head and neck cancers.Vaccinations protect against persistent, high-risk HPV infection that may lead to malignancies. However, the HPV vaccination initiation and completion rates are only 41.7% and 21.6% respectively in males, and 60% and 39.7% respectively in females. The lack of opportunity does not appear to be a major reason for this low coverage. Some of the barriers for low adoption of HPV vaccination were concern about vaccine safety (70%), lack of knowledge about HPV related diseases (56%), very young to vaccinate (56%), fear of riskier sexual behavior (56%), and reluctance as not being included in the required immunization schedule (71%). In addition, several people refused HPV vaccination due to misinformation in social media. The primary purpose of HPV vaccination is to help prevent sexually transmitted diseases. Further, such vaccination can also prevent several cancers caused by persistent infection. Therefore, HPV vaccination has the potential to eliminate such risk if enforced at a young age in school. The above study and data stress this role and the importance of public awareness of the HPV vaccine as a cancer prevention agent.