tbuckley/cabot-search huggingface dataset:
The metabolic clinical risk score (mCRS) as a new prognostic model for surgical decision in patients with colorectal liver metastases.
Authors: Ivan Duran Derijckere, Hugo Levillain, Ali Bohlok, Celine Mathey, Jonathan Nezri, Raoul Muteganya, Valerio Lucidi, Fikri Bouazza, Gaetan Van Simaeys, Serge Goldman, Alain Hendlisz, Patrick Flamen, Vincent Donckier
Journal: Journal of Clinical Oncology (2019)

e15094 Background: Selection for surgery in patients with colorectal liver metastases (CRLM) remains poorly accurate. We evaluated if baseline metabolic characteristics of CRLM, as assessed by [18]-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography ( 18 FDG-PET/CT), may predict the postoperative outcome in patients operated for CRLM. Methods: In a series of 450 patients operated for CRLM, we retrospectively identified 2 groups: The long-term survival (LTS), as defined by postoperative recurrence-free survival (RFS)≥5 years, and the early relapse groups (ER), as defined by RFS &lt; 1 year. Clinicopathologic characteristics, Clinical Risk Score (CRS) and baseline 18 FDG-PET/CT metabolic parameters were analyzed. Baseline 18 FDG-PET/CT was performed at the time of diagnosis of CRLM, before any preoperative treatment. Low and high-risk CRS were defined by scores of 0 to 2 and 3 to 5, respectively. Metabolic CRS (mCRS) was implemented, using 1 additional point to the standard CRS when the highest tumor standardized uptake value (SUV max ) and normal liver mean SUV (SUV mean(liver) ) ratio was &gt; 4.3. Low and high-risk mCRS were defined by scores of 0 to 2 and 3 to 6, respectively. Results: We analyzed 53 patients. No difference was observed between LTS (n = 23) and ER (n = 30) groups for clinicopathologic parameters related to the primary tumor and CRLM, CRS and rates of low/high risk CRS. All metabolic parameters analyzed, including SUV max and SUV peak , at the exception of metabolic tumor volume, were significantly increased in ER group. Median SUV max /SUV mean(liver) ratio was significantly increased in the ER vs LTS, respectively of 4.2 and 2.8 (p = 0.008). mCRS was significantly higher in ER as compared to LTS patients (p = 0.024), while 61% of the LTS patients had a low-risk mCRS and 73% of the ER patients had a high-risk mCRS (p = 0.023). Conclusions: Baseline 18 FDG-PET/CT characteristics demonstrate an increased tumor glucose uptake in patients who rapidly recur after curative-intent surgery for CRLM. The introduction of these data into clinical risk model may represent a new tool to improve selection for surgery in patients with CRLM.
Outcomes of patients (pts) with metastatic urothelial cancer (mUC) and poor performance status (PS) receiving anti-PD(L)1 agents.
Authors: Ali Raza Khaki, Leonidas Nikolaos Diamantopoulos, Ang Li, Michael Edward Devitt, Alexandra Drakaki, Evan Shreck, Monika Joshi, Pedro Isaacsson Velho, Lucia Alonso, Ariel Ann Nelson, Sandy Liu, Marcus W. Moses, Pedro C. Barata, Christopher J. Hoimes, Matt D. Galsky, Guru Sonpavde, Evan Y. Yu, Veena Shankaran, Gary H. Lyman, Petros Grivas
Journal: Journal of Clinical Oncology (2019)

4525 Background: Anti-PD(L)1 immune checkpoint inhibitors (ICI) prolong overall survival (OS) after platinum chemotherapy in mUC. However, clinical outcomes in pts with poor PS at time of ICI initiation are unknown. We hypothesized that ICI initiation in pts with ECOG PS 2-3 would be associated with worse outcomes vs. pts with ECOG PS &lt; 2, and impact death location. Methods: A retrospective cohort study in 8 institutions identified pts with mUC who received ICI. Demographic, clinicopathologic, treatment (tx) patterns, tx response, and outcomes were collected. Primary endpoint: overall response rate (ORR). Secondary endpoints: median (m) OS in pts receiving ICI as 1 st and 2 nd line (1L, 2L); odds of dying in hospital (vs elsewhere) for pts receiving ICI (vs no tx) within 30 days of death; and estimated drug cost for pts with ICI within 30 days of death based on average wholesale price. Unadjusted logistic regression was used to assess association between ORR and ECOG PS (2-3 vs &lt; 2) and wald test was used to compare mOS between ECOG PS (2-3 vs &lt; 2). Results: 194 consecutive pts (30% women, 41% never smokers, median age at diagnosis 69) treated with ICI for mUC were identified. Median number of total tx lines was 2; all pts received ≥1 ICI line (6 pts received 2 ICI lines); 97, 79, 17 and 7 pts received ICI in 1L, 2L, 3L and 4L, respectively; 26% pts with ICI in 1L and 2L had ECOG PS 2-3. ORR and mOS are shown in table. Among 106 pts who died, 96 had available death location; of those, 8% received ICI within 30 days of death. Starting ICI within 30 days of death (vs no tx) was associated with higher odds of hospital death (OR 6.05, 95%CI 1.3-27.6). Estimated average ICI cost/pt within 30 days of death was $1400.58. Conclusions: Pts with ECOG PS 2-3 at time of ICI initiation had similar ORR vs ECOG PS &lt; 2 but worse mOS. ICI initiation within 30 days from death was associated with higher likelihood of hospital death. ICI may not circumvent the negative prognostic role of poor PS, so biomarker-based pt selection is critical. Limitations include lack of adjustment for selection bias and other confounders at time of ICI initiation; data validation is ongoing. [Table: see text]
Influence of the new FIGO classification for cervical cancer on patients’ survival: Retrospective analysis of 265 histologically confirmed cases with FIGO stages Ia to IIb.
Authors: Nikolaus de Gregorio, Amelie De Gregorio, Florian Ebner, Fabienne Schochter, Thomas W. P. Friedl, Jens Bodo Huober, Wolfgang Janni, Peter Widschwendter
Journal: Journal of Clinical Oncology (2019)

e17006 Background: End of 2018 a new FIGO Classification for cervical cancer was published, mainly revising stage Ib and introducing a new stage IIIc, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. Methods: We retrospectively analyzed all cases of cervical cancer stage I to IIb who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome parameters according to the new stage. Results: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage Ib and from any stage to stage IIIc1. Kaplan Meier curves for new stages showed a significant difference for stages I vs. II vs. III (log rank test, p &lt; 0.001). Overall, patients that were upstaged had a significant worse PFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive Ib or IIb tumors were upstaged to IIIc tumors. Conclusions: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.
c-Met expression and response to telisotuzumab vedotin (teliso-v) in patients with non-small cell lung cancer.
Authors: Rebecca Suk Heist, Monica Motwani, Fabrice Barlesi, Jonathan Wade Goldman, Karen Kelly, Yan Sun, Jun Wu, Bruce Allen Bach, D. Ross Camidge
Journal: Journal of Clinical Oncology (2019)

9023 Background: c-Met overexpression (OE) and MET amplification (amp) are prognostic of poor outcome for non-small cell lung cancer (NSCLC). Telisotuzumab vedotin (ABBV-399; teliso-v [T]), an anti–c-Met Ab and monomethyl auristatin E drug conjugate, showed efficacy as monotherapy (mono) and combined with erlotinib (T+Er) in a phase 1/1b trial (NCT02099058) in NSCLC patients (pts) with c-Met OE. Here, c-Met OE (by immunohistochemistry [IHC]) and its association with T efficacy were explored. IHC, mRNA, and amp platforms for MET were also compared. Methods: Archival tissue from pts with NSCLC in the phase 1/1b trial was examined. c-Met was assessed centrally by IHC with SP44 Ab (Ventana Medical Systems) and pts with c-Met OE (membrane H-score [H-S] of ≥150) were enrolled. MET mRNA expression was analyzed from total RNA and sequenced on HiSeq 3000 (Illumina). MET amp was analyzed by FISH ( MET/ CEP7 ratio of ≥2) or whole-exome sequencing (copy number ≥2). Efficacy in the T mono every 2 (TQ2W) or 3 (TQ3W) weeks and the T+Er EGFR mutant cohorts was assessed for IHC H-S ≥150 and ≥225. Results: As of Dec 2018, 238 pts with NSCLC were screened centrally for c-Met OE. Of these, 118 pts were enrolled. For screened pts, 76%/37% of nonsquamous (NSQ, n = 201) and 58%/16% of squamous (SQ, n = 32) pts had H-S ≥150/≥225; 75%/41% of NSQ and 55%/16% of SQ NSCLC pts had ≥50% cells with 2+/3+ staining intensity. MET amp was reported for 5 pts, all with high H-S (≥270); there was an association between MET amp and MET RNA levels (n = 4) (t-test p value: 0.0002). See Table for ORR and median PFS by H-S and T treatment. Conclusions: c-Met expression prevalence in NSCLC showed a similar trend as in previous reports. In T+Er-treated pts, ORR was higher for those with c-Met H-S ≥225 than ≥150– &lt; 225, suggesting that biomarker expression may act as an effect size multiplier. Optimization of the c-Met IHC cutoff warrants further investigation. Clinical trial information: NCT02099058. [Table: see text]
Health crisis in Venezuela: Status of communicable diseases and implications for the European Union and European Economic Area, May 2019
Authors: Laura Espinosa, Grazina Mirinaviciute
Journal: Eurosurveillance (2019)

Re-emerging diseases outbreaks are being reported in Venezuela since 2012/13, following ongoing political and economic crisis. Healthcare system collapse has led to an increasing incidence and mortality from communicable diseases. Increasing movement of people between Venezuela and the European Union and European Economic Area (EU/EEA) creates a need for increased awareness of the infectious disease risks and requirements for appropriate investigation and treatment of individuals arriving from Venezuela; overall risk for EU/EEA citizens is low.
SP0078 CASE PRESENTER: LONGSTANDING NEURO LUPUS IN ADULT LIFE
Authors: Antonis Fanouriakis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Juvenile-onset systemic lupus erythematosus (SLE) poses significant challenges for paediatric and adult rheumatologists. Longstanding disease in adult life carries the sequelae of the protracted course of the disease, as well as of the various treatments received. <h3>Objectives:</h3> To present a didactic case of long-standing SLE of childhood onset, with the purpose to familiarise the audience with the multifaceted aspects of the disease, following transition from adolescence into adulthood. <h3>Methods:</h3> Report of an illustrative juvenile-onset SLE patient after transition in adulthood. <h3>Results:</h3> A 25-year old lady was diagnosed with SLE at the age of 9, due to generalised tonic-clonic seizures (status epilepticus), photosensitive rash and positive serology for SLE (ANA, anti-dsDNA, low complements). She was treated with high-dose glucocorticoids and cyclophosphamide with a good neurologic response. At the age of 15, she developed hematuria and nephrotic proteinuria; a kidney biopsy was compatible with class IV lupus nephritis (LN), with few crescents. She received mycophenolate mofetil (MMF), again with glucocorticoids, with complete response at 12 months. After entering adulthood, 5 years later, at the age of 21, she had a severe renal flare with recurrence of nephrotic proteinuria and active urinary sediment. A second kidney biopsy was performed, which showed histologic transformation into mixed class IV + V LN, and increase in chronicity index. Readministration of MMF failed to provide at least partial response; to this end, high-dose intravenous cyclophosphamide was administered, again with no response after 6 months. Finally, the patient was treated with rituximab, in combination with MMF, which managed to achieve partial remission, with proteinuria levels &amp;x223C; 1.5 gr/day and normal renal function. Sixteen years following her initial diagnosis, apart from her ongoing renal inflammation, our patient has suffered significant side-effects from long-term glucocorticoid therapy and her quality of life is significantly affected. <h3>Conclusion:</h3> This case illustrates the formidable challenges faced by both patients and treating physicians, for a patient diagnosed with SLE in childhood and had frequent flares during transition into adulthood and later in adult life. <h3>Disclosure of Interests:</h3> Antonis Fanouriakis Paid instructor for: Amgen, GSK, Speakers bureau: Abbvie, Enorasis, Genesis Pharma
Trends in the prevalence of obesity among young Thai men and associated factors: from 2009 to 2016
Authors: Panadda Hatthachote, Ram Rangsin, Mathirut Mungthin, Boonsub Sakboonyarat
Journal: Military Medical Research (2019)

The prevalence of obesity has been increasing in both males and females worldwide. In Thailand, the National Health Examination Surveys reported that the prevalence of obesity (body mass index (BMI) ≥30 kg/m2) among Thai male adults aged 20–59 years increased from 1.7% in 1991 to 6.8% in 2009. Obesity has been confirmed to lead to health problems, including noncommunicable diseases. In the present study, we report trends in the prevalence of obesity among new conscripts from 2009 to 2016. We also investigated the associated factors of obesity. Serial cross-sectional studies were conducted from 2009 to 2016 among male Royal Thai Army (RTA) conscripts whose weight and height had been measured to determine BMI after being inducted. Each subject completed a detailed risk factor questionnaire. Obesity was defined as BMI ≥ 30 kg/m2. A total of 26,540 young Thai males conscripted into the RTA were included in this study. The prevalence of obesity was 2.2% in 2009, 3.4% in 2010, 2.5% in 2011, 2.9% in 2012, 3.4% in 2013, 4.4% in 2014, 5.0% in 2015, and 4.8% in 2016 (P for trend < 0.0001). The independent risk factors for obesity were coming from the north central and south regions compared with the northeast, higher education level, indoor occupation and no regular exercise. Our data emphasized that obesity constitutes a serious problem among young Thai men. We could apply these findings in military units to other groups at any age. Regular exercise should be provided to young adults and other age groups to slow the process of obesity, so that associated complications, especially noncommunicable diseases, will cease.
Prevalence of Female Authors in Case Reports Published in the Medical Literature
Authors: David Hsiehchen, Antony Hsieh, Magdalena Espinoza
Journal: JAMA Network Open (2019)

Underrepresentation of female authors in research publications is prevalent, but it is unclear whether this is attributable to sex disparities in research conduct or authorship practices. Case reports are a poorly understood component of the biomedical corpus, and the production of anecdotal observations is not confounded by factors associated with disparities in female representation in research publications. Whether female authorship disparities exist in nonresearch publications of clinical information is unknown.
HER2-positive breast cancer: Combined <sup>18</sup>F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after preoperative chemotherapy with trastuzumab.
Authors: Laura Vincent, Clémentine Jankowski, Marion Cortet, Laurent Arnould, Sylvain Ladoire, Bruno P. Coudert, Isabelle Desmoulins, Celine Charon-Barra, Françoise Beltjens, Roman Rouzier, Fabien Reyal, Olivier Humbert, Alexandre Cochet, Charles Coutant
Journal: Journal of Clinical Oncology (2019)

e12095 Background: The aim of this study was to compare the value of 18 F-fluorodesoxyglucose positron emission tomography ( 18 F-FDG PET/CT) with CGFL/Curie nomogram to predict a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor 2 (HER2)-positive breast cancer treated by trastuzumab. Methods: Fifty-one women with HER2-positive breast cancer treated with trastuzumab plus taxane-based NAC, were retrospectively included from January 2005 to December 2015. For 18 F-FDG PET/CT, the analyzed predictor was the maximum standardized uptake value of the primary tumor and axillary nodes after the first course of NAC (PET 2 .SUV max ). pCR was defined by no residual infiltrative tumor but in situ tumor was accepted. Accuracy of CGFL/Curie nomogram and PET 2 .SUV max was evaluated measuring sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). For each predictor, receiver operating characteristic (ROC) curve was created. To evaluate the correlation between predictors, the Spearman coefficient was calculated. Combined prediction was evaluated testing predictor’s associations. Results: For CGFL/Curie nomogram’s performances, Se, Sp, PPV and NPV were respectively: 76% (CI95%: 58-90%), 57% (CI95%: 43-66%), 55% (CI95%: 42-65), 77% (CI95%: 59-90%). For PET 2 .SUV max ’s performances, Se, Sp, PPV and NPV were respectively: 67% (CI95%: 48-81%), 77% (CI95%: 64-97%), 67% (CI95%: 48-82%), 77% (CI95%: 64-87%). ROC curves for these predictors were similar; the areas under the curve were 0.6 (CI95%: 0.56-0.64) for PET 2 .SUV max and 0.55 (CI95%: 0.50-0.59) for CGFL/Curie nomogram. Spearman coefficient was 0.23. Combined prediction was more efficient with Se at 80%, VPN at 76%, Sp at 78% and VPP at 81 %. Conclusions: CGFL/Curie nomogram and PET 2 .SUV max were two efficient predictors of pCR in patients with HER2-positive breast cancer. Combined prediction has an improved accuracy.
Incidence of Infection-related mortality in cancer patients: Trend and survival analysis.
Authors: Muhammed Khaled Elfaituri, Sara Morsy, Gehad Mohamed Tawfik, Abdelaziz Abdelaal, Amr Ehab El-Qushayri, Hazem Abdelkarem Faraj, Truong Hong Hieu, Nguyen Tien Huy
Journal: Journal of Clinical Oncology (2019)

e23095 Background: Infectious diseases are the second leading cause of death in the field of oncology. Around 60% of deaths are infection related to cancer patients, especially with underlying hematological malignancies. This study assesses the changing trends of mortality in cancer patients from infectious causes in the past 40 years. Methods: This is a retrospective analysis on 151440 cancer patients who died from infectious causes between 1973 and 2014, identified in the Surveillance, Epidemiology, and End Results (SEER) Program database. Results: Pneumonia and influenza were the most common infections (n = 72133) followed by parasitic diseases and other infections (n = 47310) and septicemia (n = 31119), respectively. The average survival was 65.31 months, while pneumonia and influenza had the highest survival of all. Prostate cancer was the most common cancer associated with infectious diseases (n = 20068) followed by breast cancer (n = 16676) and Kaposi sarcoma (n = 13046), respectively. During 1998-2001, an overshoot in infection-related mortality was significantly noted (APC = 26.74%; 95%CI = 3.7:54.9). However, since 1973, the greatest reduction in infection-related mortality was recorded during 2012-2014 (APC = -37.15; 95%CI = -48.6: -23.2). Compared to other infectious diseases, ‘parasitic and other infections including HIV’ accounted for the highest incidence (SIR = 1.77; 95% CI = 1.69:1.84), where blood vessel tumors occurred the most in this category (SIR = 88.83; 95%CI = 2.25:494.9). Afterward, septicemia was the second most common infectious disease (SIR = 0.84; 95%CI = 0.81:0.88). Except for leukemia, lymphoma, plasma cell tumors, and mast cell tumors, hematologic tumors revealed the highest incidence of septicemia (SIR = 51.9; 95%CI = 1.31:289.16). Gender, race, marital status, an infectious organism, and tumor characteristics (behavior and grade); all accounted for significant differences in survival (P &lt; 0.0001). The nomogram has outstanding discrimination ability (c-index = 0.85) with very minimal differences from the actual observations of 1-, 3-, and 5-year survival probabilities. Conclusions: Infection-related mortality in cancer patients declined from 1973 to 2014. The most common infections in cancer patients were Pneumonia and influenza, followed by parasitic diseases, other infections, and septicemia. Prostate cancer was the most common cancer associated with infectious diseases, followed by breast cancer and Kaposi sarcoma.
Tislelizumab, an investigational anti-PD-1 antibody, combined with chemotherapy as first-line treatment for lung cancer in Chinese patients.
Authors: Jie Wang, Jun Zhao, Zhijie Wang, Zhiyong Ma, Jiuwei Cui, Yongqian Shu, Zhe Liu, Ying Cheng, Shiangjiin Leaw, Fan Xia, Yanjie Wu, Liang Liang
Journal: Journal of Clinical Oncology (2019)

e14067 Background: Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports showed tislelizumab was generally well tolerated and had antitumor activity in patients (pts) with advanced solid tumors; 200 mg IV Q3W was established as the RP2D. Methods: This phase 2 clinical trial (NCT03432598) assessed tislelizumab (200 mg Q3W) with platinum (plt)-based chemotherapy (Q3W) as first-line treatment for Chinese pts with advanced lung cancer. All pts received tislelizumab + plt doublet (4–6 cycles) until disease progression. Nonsquamous (nsq) NSCLC pts received pemetrexed (PMX) + plt (4 cycles) followed by PMX maintenance; squamous (sq) NSCLC pts received A) paclitaxel (PXL) + plt or B) gemcitabine + plt; SCLC pts received etoposide + plt. Tumor response (RECIST v1.1) and safety/tolerability were evaluated. PD-L1 expression was retrospectively assessed with the VENTANA PD-L1 (SP263) assay. Results: As of 15 Oct 2018, 54 pts (median age 61 yr; 74% male; 72% current/former smokers; 31% with ≥10% PD-L1 expression on tumor cells) received tislelizumab; 24 pts remain on treatment. Confirmed PR was observed in 36 pts and most occurred within the first 2 assessments. Other efficacy estimates (eg, PFS) are maturing. Grade ≥3 AEs occurring in &gt; 15% of pts were decreased neutrophil counts (n = 25) and anemia (n = 9); immune-related AEs occurring in ≥2 pts were decreased triiodothyronine, hyperthyroidism, hypothyroidism, and pyrexia (n = 2 each). One sq-NSCLC pt ( A) experienced fatal myocarditis/myositis after 1 cycle; other AEs resolved with tislelizumab interruption (n = 30), discontinuation (n = 4), or other appropriate treatment. Conclusions: Tislelizumab in combination with standard of care plt-based chemotherapy was generally well tolerated and demonstrated antitumor activity. Clinical trial information: NCT03432598. [Table: see text]