tbuckley/cabot-search huggingface dataset:
SP0019 PRES HPR: DONT DELAY, COLLABORATE TODAY
Authors: Jeannette Cappon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The Pediatric Rheumatology European Society (PReS) is an international organization based in Europe which is dedicated to advance the care and improve the health and well-being of children and young people with rheumatic conditions, helping them to reach their full potential. Full PReS membership is extended to individuals from all European countries, whether they are within the EU or not, and includes countries in the middle east and from other parts of the world as associate members to enrich the collective experience and knowledge. PReS welcomes every practitioner/researcher in the field of pediatric rheumatology. The PReS committee for Health Professionals in Pediatric Rheumatology aims to bring together nurses, physical therapists, occupational therapists, social workers, psychologists, podiatrists and other health professionals(HP) to foster dialogue, to set standards of clinical practice, education and research. Collaboration between PReS and Eular Health Professionals starts today, here in Madrid. Collaboration in general starts with a shared goal to work on together. Our young patients of today might be your patients of tomorrow: what should you know about what they have been through? Your patients of today might have been our young patients of yesterday: what can we learn from their experiences of the past being a child with a rheumatic condition? Did they receive comprehensive care that sustained into their adulthood? <h3>Objectives:</h3> To find shared goals between HP Eular and HP PReS to deliver comprehensive care for people with rheumatic diseases during their full life. To find common interests to discuss between HP Eular and HP PReS <h3>Methods:</h3> Examples of common interests e.g. supporting self management of pain and health and illness education are presented. Shared goals for collaboration are proposed and collected from the audience. Opportunities to connect for Eular HP and PReS HP in Madrid and Prague September 2020 are listed and benefits are mentioned. <h3>Results:</h3> Health Professionals from Eular and PReS experience common interests and shared goals. Positive relations are expected to develop upcoming years. <h3>Conclusion:</h3> CollaboRelation between HP Eular and HP PReS can start today <h3>Disclosure of Interests:</h3> None declared
Survival trends in elderly patients with malignant mesothelioma: An analysis utilizing Surveillance, Epidemiology, and End Results database.
Authors: Lubina Arjyal, Yazhini Vallatharasu, Amir Bista, Michael Olayiwola Ojelabi
Journal: Journal of Clinical Oncology (2019)

e18164 Background: Malignant mesothelioma is a highly aggressive tumor arising from the mesothelial surface. Treatment for malignant mesothelioma has not changed significantly in recent years. Better patient care may have improved survival in malignant mesothelioma patients. We conducted this study to evaluate the relative survival rates in elderly patients with malignant mesothelioma over the last one and half decades in the United States. Methods: Elderly patients (age≥65 years) diagnosed with malignant mesothelioma were selected from the Surveillance, Epidemiology, and End Results (SEER-18) database. We used Z-test to compare 1- year relative survival rates (RS) between the two time frames: 2000-2009 and 2010-2014. Several cohorts categorized by race (Caucasians and African-Americans) and gender were stratified. The survival rates were accompanied by standard errors. Results: In total, the SEER-18 database identified 6,346 patients (4,210 from 2000-2009 and 2,136 from 2010-2014; 78.3% were males, 92.6% were Caucasians). Overall, there was no improvement in survival in recent years (1-year RS: 35.4 ± 0.8 vs 36.5 ± 1.2, Z score = 1.910 on 2000-2009 &amp; 2010-2014 respectively). This was true for most of the cohort including those for males: 1-year RS: 35.0±0.9 vs 36.1±1.3, Z score = 1.569; females: 1-year RS: 37.0±1.7 vs 37.8±2.5, Z score = 1.116 and Caucasians: 1-year RS: 35.8± 0.8 vs 36.6.± 1.2, Z score = 1.512 on 2000-2009 &amp; 2010-2014 respectively. There was significant improvement in relative survival among African Americans: 1-year RS: 25.3±3.6 vs 38.6±5.6, Z score = 2.362. Conclusions: Our analysis of real-world data showed an improvement in relative survival rates for African American patients with malignant mesothelioma in recent years. This is likely related to improved delivery of care. Overall prognosis continues to remain poor and there is a strong need for novel therapeutic agents.
Efficacy of immune checkpoint inhibitors (ICI) and genomic characterization of sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC).
Authors: Ziad Bakouny, Natalie Vokes, Xin Gao, Amin Nassar, Sarah Abou Alaiwi, Ronan Flippot, Gabrielle Bouchard, John A. Steinharter, Pier Nuzzo, Wenting Pan, Abdallah Flaifel, Gwo-Shu Mary Lee, David A. Braun, Xiao X. Wei, Sabina Signoretti, Bradley Alexander McGregor, Lauren Christine Harshman, Eliezer Mendel Van Allen, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2019)

4514 Background: S/R mRCC are poorly characterized rapidly progressing tumors associated with poor prognosis. Although conventional therapies are less effective for these tumors, emerging data suggests that ICIs may be especially effective. Our aim was to characterize the genomic alterations (GA) in S/R mRCC tumors and evaluate their response to ICIs. Methods: We retrospectively compared the activity of first-line ICIs to non-ICI-based therapies for S/R mRCC patients (pts) treated at DFCI and analyzed sequencing data from an NGS panel (275-447 genes) on a subset of these patients (matched by histology to non-S/R mRCC). For S/R mRCC pts treated with ICI vs non-ICI therapies, overall survival (OS) and time to treatment failure (TTF) were compared by Cox regression and objective response rate (ORR) by logistic regression. GA frequencies were compared by Fisher’s test and tumor mutational burden (TMB) by Mann Whitney U between S/R and non-S/R mRCC. Results were considered statistically significant if p &lt; 0.05 or q &lt; 0.10. Results: 125 S/R mRCC pts were included (88 S, 23 R, 14 S&amp;R) among which 103 were clear cell and 48 had sequencing data. GA in BAP1 were significantly more frequent in S/R vs non-S/R (25% vs 4.3%; q = 0.096) while other GA had similar frequencies and TMB (median [IQR]) was similar (7.2 [5.2-8.4] vs 6.8 [5.3-9.1] mut/Mb; p = 0.98). Median follow-up was 35.4 (95% CI = 24.9 – 46.0) months (m). On multivariable analysis, S/R mRCC pts treated with ICI had significantly better clinical outcomes (Table). Conclusions: Pts with S/R mRCC have a higher frequency of BAP1 GA and better outcomes on ICIs compared to non-ICI-based therapies. Future studies should determine the molecular mechanisms underlying the improved response to ICIs in S/R mRCC. [Table: see text]
Complementary medicine and cancer: A French multicenter survey.
Authors: Florian Correard, Françoise Blanc-léger, Clarisse Roux, Florence Lobrot, Frédéric Pinguet, Xavier Pourrat, Bertrand Pourroy, Catherine Donamaria, Jacques Kopferschmitt
Journal: Journal of Clinical Oncology (2019)

e23127 Background: There have been few reports about Complementary Therapy (TC) use in outpatients who are on active cancer chemotherapy in France. TC may interact with cancer treatments, reduce efficacy, or enhance adverse effects. Methods: This is a cross-sectional survey on TC use in 7 French hospitals (outpatient chemotherapy, conventional hospitalization and medical consultation departments). Eligible patients had to be followed for a cancer and be over 18. Results: 415 patients answered the questionnaire. 54% were female, More than 80% of patients were over 50. 230 patients (55.4%) reported using TCs. TCs were prescribed or recommended for 180 patients. The main TC users were patients with melanoma or other cutaneous cancer (90% of them) and bone and soft tissues sarcomas (86% of them). Most patients used only one TC (52.6%). The most used TCs were Phytotherapy (48%), Homeopathy (40%), supplemental dietary (35%) and aromatherapy (21%). 110 patients (47, 8% of patients with TC) used phytotherapy. The most used plants (≥5% of use) were: Curcuma and its derivative curcumine (13.9%), desmodium (7.4%), thymus (5%). 93 patients used homeopathy (40.4% of patients with TC). Only 48 patients used aromatherapy (20.9% of patients with TCM or 11.6% of the whole population). 81 patients used Supplemental dietary (35.2% of patients with TCM or 19.5% of the whole population). Only 27 patients used oligo-elements (11.7% of patients with TCM or 6.5% of the whole population),). Interestingly, 20% of patients declared to use others TCs (Physical activity, Acupuncture, Somatotherapy, Sophrology, Chinese traditional Medecine, Specific diet, Psychotherapy…). Patient who used TC were mainly under chemotherapy regimen.For each TC, most patients considered that they were useful or very useful. The main reasons for using TCs were “Wellbeing and psychological support” (35.8%), “Clinical symptoms and chemotherapy tolerance improvement” (34.6%) and “Treatment of cancer” (17.7%). Conclusions: To protect cancer patients from the potential hazard of combining their cancer treatment with TCs, patients should systematically be encouraged to report their TC use, while oncologists and pharmacists should be trained on evidence of TC, and patient guidance for a safer TC use.
The Upcoming U.S. Health Care Cost Debate — The Public’s Views
Authors: Robert J. Blendon, John M. Benson, Caitlin L. McMurtry
Journal: New England Journal of Medicine (2019)

More than two thirds (69%) of the U.S. public has said that reducing health care costs should be a top priority for the president and Congress. A review of 14 national opinion polls elucidates the public's perspective on the problems and solutions.
SeqPlus sequencing methodology enables robust whole-genome sequencing, true variant detection, and novel genomic insights from archival esophageal carcinoma FFPE samples.
Authors: Shannon Terrell Bailey, Belynda Hicks, Bin Zhu, Nan Hu, Phil R. Taylor, Jeffery R Gulcher, Hongye Sun, Jim Lund, Kelly Oliner, Richard T. Williams, Stephen J. Chanock, Alisa M. Goldstein
Journal: Journal of Clinical Oncology (2019)

e13016 Background: Whole-genome sequencing (WGS) of formalin-fixed, paraffin-embedded (FFPE) samples could enable novel insights from archival sample collections, yet robust FFPE WGS is challenged by fragmented DNA, uneven genomic coverage &amp; sequencing artifacts attributed to FFPE fixation. We report our proprietary extraction &amp; library preparation methodology (SeqPlus) with high quality, uniform WGS sequencing performance comparable to that from fresh-frozen samples. Methods: We analyzed 20 paired esophageal carcinoma (EC) samples i.e., primary tumors &amp; matched germline samples to assess SeqPlus performance on 10-15-year-old FFPE tissues, measure variant concordance between WGS and a high-depth sequencing panel (269 genes, 400x coverage) &amp; identify novel genomic features. Results: At a targeted 70x WGS tumor sequencing depth, 93% of the genome was covered by ³ 20 reads, 99% of bases had 10x coverage &amp; average duplicate reads were 31%. We noted similar transition/transversion ratios &amp; mutational spectra as from fresh-frozen EC specimens, suggesting that extraction &amp; library preparation contributes to prior FFPE artifacts. Concordance of tumor-specific SNVs &amp; indels derived from WGS &amp; targeted panel was high at 86%. All 76 targeted panel-detected variants above the WGS limit of detection (mutant allele frequency [MAF] &gt; 10%) were detected by WGS, 2 variants (2 tumors) were detected only by WGS, and 12 variants at MAF ≤ 6% (9 tumors) were only detected by the targeted panel. Tumor WGS yielded SNV, indels &amp; CNV findings beyond variants detected by targeted sequencing. WGS enabled detection of 10.4 putative cancer variants per tumor compared to 12 variants per patient from frozen specimens and a median of 7 (up to 16) cancer-associated variants in genes outside the targeted panel. WGS copy number analysis revealed CCND1, EGFR, TP63, and SOX2amplification, CDKN2A/B deletion and additional unrecognized genomic aberrations. Conclusions: Our study reinforces the utility of high-quality, uniform WGS sequencing of archival FFPE cancer samples with SeqPlus and unlocks the potential for massive-scale retrospective genomic analysis of archived pathology samples with associated clinical &amp; outcomes data.
Efficacy and safety of FOLFIRINOX in elderly patients with advanced pancreatic adenocarcinoma.
Authors: Jae Hyup Jung, Jingu Kang, Jong-Chan Lee, Jin-Hyeok Hwang
Journal: Journal of Clinical Oncology (2019)

e15729 Background: Although FOLFIRINOX showed improved efficacy in advanced pancreatic ductal adenocarcinoma (PDA), physicians still hesitate to administrate FOLFIRINOX in elderly patients despite of being in a good performance status. We investigated the efficacy and toxicity of FOLFIRINOX in elderly patients with advanced PDA. Methods: We retrospectively reviewed electronic medical records of advanced PDA patients administrated a first-line FOLFIRINOX from January 2012 to July 2017 in a single tertiary teaching hospital. All the patients were divided into two groups: non-elderly group A (age &lt; 70) and elderly group B (age≥70). Overall survival (OS), progression free survival (PFS) and toxicities were compared between two groups using Cox proportional hazard model. Results: A total of 214 patients (Group A 176; B 38) met the eligible criteria. Median age was 61 years old (29-80, group A 59; B 73) and median cycle of FOLFIRINOX was 7.0 (1–75, group A and B 7.0). Median OS and PFS did not differ between group A and B (OS, 11.8 vs 12.0 months, hazard ratio [HR] 1.165, 95% confidence interval [CI] 0.785–1.728; PFS 6.5 vs 7.3 months, HR 1.003, 95% CI 0.694–1.451, respectively). When we analyzed OS according to tumor stage (locally advanced and metastatic), group A and B showed comparable median OS (15.8 vs 13.5 months in locally advanced PDA; 8.6 vs 9.8 months in metastatic PDA, respectively) There were no significant differences in terms of hematologic toxicities except Gr 3 or 4 thrombocytopenia (Group A 3.4%; B 13.2%, P = 0.028). Fatigue and diarrhea were observed more often in Group B than in group A (47.4% vs 10.2%, P = 0.000; 18.4% vs 4.5%, P = 0.010, respectively), all of which were manageable. More patients in group B received dose adjusted FOLFIRINOX than in group A, although there was no statitical significance. Conclusions: FOLFIRINOX could be considered as the first-line chemotherapy for elderly patients with advanced PDA as well as non-elderly patients when dosage modified appropriately, given comparable efficacies and acceptable and manageable toxicities. More studies are warranted to confirm this issue.
Changes in skeletal muscle mass during PD-1 and PD-L1 checkpoint inhibitor therapy in advanced-stage non-small cell lung cancer patients.
Authors: Maneet Multani, Imad Tarhoni, Ibdihaj Fughhi, Sanjib Basu, Marta Batus, Philip D. Bonomi, Mary J. Fidler, Jeffrey Allen Borgia, Palmi Shah
Journal: Journal of Clinical Oncology (2019)

e14061 Background: Severe skeletal muscle loss (sarcopenia) is a principle property of cancer cachexia and is found to be a hallmark of poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). With the latest advancements of PD-1 and PD-L1 checkpoint immunotherapy, we aim to examine changes in sarcopenia before and after treatment with these agents. Methods: : In this study, patients with stage IIIB/IV NSCLC receiving PD-1 and PD-L1 immune checkpoint inhibitors were evaluated. CT images obtained before and after treatment were used for skeletal muscle analyses with the SliceOmatic software (Tomovision) at the level of the first lumbar vertebra. Skeletal muscle index (SMI) was assessed by measuring the cross-sectional muscle area, normalized to patient height. Height, weight, disease progression status, and overall survival (OS) was extracted from EPIC under an IRB-approved protocol. Data was then compared with baseline and clinical outcome was used for survival analysis. Results: In 100 pre-treatment subjects (48% women, mean age of 68), patients with &lt; 32 cm 2 /m 2 SMI had a significantly lower OS (median OS = 1.41 mo, n = 16) compared to those with SMI &gt; 32 cm 2 /m 2 (median OS = 9.44 mo, n = 84, p = 0.024). In 74 patients with pre- and post-treatment data, (avg 2.66 mo interval) an increase of &gt; 5% SMI from baseline occurred in 17 (23%) patients, while a decrease of &gt; 5% SMI from baseline occurred in 26 (35%) patients. Mean reduction in SMI from pre- to post-immunotherapy was 0.921 cm 2 /m 2 while median reduction in SMI was 1.087 cm 2 /m 2 . Conclusions: Patients with high pretreatment SMI had a significantly greater overall survival when compared to those with low pretreatment SMI. Two-thirds of patients experienced stability or increase in SMI during immunotherapy. These results suggest that immune checkpoint inhibitors may dampen mechanisms of cancer cachexia in some patients.
A phase Ia/b study of TIM-3/PD-L1 bispecific antibody in patients with advanced solid tumors.
Authors: Matthew David Hellmann, Toshio Shimizu, Toshihiko Doi, F. Stephen Hodi, Sylvie Rottey, Philippe Georges Aftimos, Zhuqing Tina Liu, Nieves Velez de Mendizabal, Anna M. Szpurka, Yongzhe Piao, Burkhard Vangerow, Leena Gandhi, Ching Ching Leow
Journal: Journal of Clinical Oncology (2019)

TPS2654 Background: Programmed cell death 1 immune checkpoint inhibitors (anti-PD-1, anti-PD-L1) have demonstrated clinical benefit in a subset of patients with manageable safety across a variety of tumor types. T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) can be co-expressed with PD-1 on exhausted T-cells and may be upregulated in tumors refractory to anti-PD-1 therapy (Koyama et al. 2016). Pre-clinical studies demonstrated that blockade of both PD-1 and TIM-3 improved survival of tumor-bearing mice compared to blocking anti-PD-1 only (Koyama et al. 2016). LY3415244 is a TIM-3/PD-L1 bispecific antibody that has the ability to target and inhibit both TIM-3 and PD-L1 and the potential to overcome primary and acquired anti-PD-(L)1 resistance by a novel mechanism to bridge TIM-3- and PD-L1-expressing cells. Methods: Study JZDA is a multicenter, nonrandomized, open-label, Phase 1a/1b study of LY3415244 in patients with advanced solid tumors. In Phase 1a, subjects with any tumor type who are either PD-(L)1 inhibitor-naïve or exposed are eligible. In Phase 1b, expansion cohorts are planned in subjects with PD-(L)1-experienced NSCLC, urothelial carcinoma, and melanoma. Patients with malignant mesothelioma are not required to have received prior anti-PD-(L)1 therapy. The primary objective is to assess safety and tolerability of LY3415244 and identify the recommended Phase 2 dose (RP2D) in Phase 1a (dose escalation). Safety and tolerability of the RP2D will be assessed in Phase 1b (dose expansion). The secondary objectives are to assess the pharmacokinetics of LY3415244 in Phase 1a/1b and assess early antitumor activity of LY3415244 in Phase 1b cohorts. Pre- and on-treatment biopsies will be obtained to explore potential biomarkers of response. During Phase 1a, dose escalation cohorts will proceed via a modified toxicity probability interval-2 (mTPI-2) design with a 1-cycle (28-day) dose-limiting toxicity (DLT) observation period. LY3415244 will be dosed intravenously every 2 weeks. Data from Phase 1a will determine the RP2D, which will be used for all cohorts in Phase 1b. The study is currently open to enrollment. Clinical trial information: NCT03752177.
Personalized TPF induction chemotherapy on the basis of stathmin expression in patients with locally advanced oral squamous cell carcinoma.
Authors: Lai-Ping Zhong, Wu-tong Ju, Hai-long Ma, Tong-chao Zhao, Zhi-yuan Zhang
Journal: Journal of Clinical Oncology (2019)

6040 Background: A randomized phase 3 trial failed to demonstrate a survival advantage for TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in the overall study population of patients with locally advanced and resectable oral squamous cell carcinoma (OSCC). It is possible that personalized TPF-based induction chemotherapy might improve outcomes in biomarker-defined subsets of patients. Methods: Immunohistochemical staining against stathmin was performed in pre-treatment biopsy specimens in 170 OSCC patients from our randomized trial. Chemoresistance to TPF chemotherapy drugs regulated by stathmin expression was investigated. The anti-cancer activity of TPF chemotherapy drugs alone, a combination of TPF drugs and PI3K-AKT-mTOR pathway inhibitors, and vincristine were investigated using in vitro and in vivo OSCC models. Results: OSCC patients with low stathmin expression benefited from TPF induction chemotherapy in terms of overall survival (HR = 0.102, 95% CI:0.013-0.781, P = 0.028), disease-free survival (HR = 0.070, 95% CI:0.009-0.525, P = 0.010), locoregional recurrence-free survival (HR = 0.070, 95% CI:0.009-0.524, P = 0.010), and distant metastasis-free survival (HR = 0.101, 95% CI:0.013-0.767, P = 0.027). Stathmin overexpression promoted cellular proliferation and chemoresistance to TPF drugs in OSCC (P &lt; 0.05). PI3K pathway inhibitors decreased stathmin expression and phosphorylation, and improved the chemosensitivity to TPF drugs in vitro and in vivo (P &lt; 0.05). Vincristine decreased stathmin expression and phosphorylation, and OSCC lines were significantly sensitive to vincristine in vitro and in vivo (P &lt; 0.01). Conclusions: Our results suggest a potential personalized TPF induction chemotherapy on the basis of stathmin expression in OSCC patients: patients with low stathmin expression in the biopsy samples are suggested to receive TPF induction chemotherapy followed by surgical resection and post-operative radiotherapy. For patients with stathmin overexpression PI3K inhibitor is a good choice to improve the inductive effect of TPF chemotherapy drugs; vincristine is a potential alternative for a chemotherapy drug when a patient is chemoresistant to or unsuitable to receive TPF chemotherapy drugs; however, more clinical trials are warranted to verify this optimization protocol.