tbuckley/cabot-search huggingface dataset:
Immune-related adverse events and nivolumab outcomes in non-small cell lung cancer patients: A multi-institutional, retrospective cohort study.
Authors: Rebecca Jane Moor, Kate Elizabeth Roberts, Robert Mason, Ben Gunawan, Sophie Feng, Jun Hee Hong, Mitchell Von Itzstein, Brett Gordon Maxwell Hughes, Zarnie Lwin, Vikram Kumar Jain, Kieron James Bigby, Mary W. F. Azer, Jasotha Sanmugarajah, Kenneth John O'Byrne
Journal: Journal of Clinical Oncology (2018)

9067 Background: Immune checkpoint inhibitors are routinely used in Non Small Cell Lung Cancer (NSCLC) patients following progression on first-line therapy. Immune-related Adverse Events (IrAEs) have been associated with the efficacy of PD-1 inhibitors in melanoma. The association between the development of IrAEs and efficacy of nivolumab remains unclear in NSCLC. Methods: We retrospectively collected data from patients who received nivolumab for advanced NSCLC on an Open Access Program across seven oncology institutions in Queensland, Australia, and analyzed whether there was an association between outcomes and the development of immune-related toxicity. Results: One hundred and ninety six patients were enrolled to this ethics committee approved audit – 77 females (39%) and 119 (61%) males; PS 0-1 (62%); PS 2-3 (38%); median age 67 (range 42-84). An objective response was recorded in 24% of patients; partial response (47/196) with one complete response, in addition 28% (55/196) had stable disease. The median overall survival was 9.2 months; 13.4 months in PS 0-1 patients and 4.2 months in PS 2-3 patients. At 1 year, the overall survival rate was 42%; 57% in patients with PS 0-1 and 18% in PS 2-3 patients. The presence of IrAEs of any grade occurred in 36% of patients and was associated with a longer median PFS of 5.9 months versus 2.3 months (P value < 0.01, 95% CI) in patients with no immune toxicity on Kaplan Meier analysis. The median OS of patients experiencing an IrAE was 24.3 months compared with 6.5 months without (P value < 0.01, 95% CI). A durable clinical benefit was observed in 72% of patients who developed at least one IrAE versus 37% in those without any immune mediated toxicity. Analysis of the prognostic relevance of routine histological, hematological and biochemical parameters is ongoing with a multivariate analysis planned. Conclusions: Nivolumab had clinically significant long-term benefits in the treatment of locally advanced and metastatic NSCLC with 12 month survival rates in keeping with clinical trials in PS 0-1 patients. The development of IrAEs was associated with improved outcomes including median PFS, OS and higher rates of clinical response in this cohort.
Prediction of malignant progression of Barrett’s oesophagus: A complete systematic review and meta-analysis.
Authors: Kiran Altaf, Jun-Jie Xiong, Lorraine Hickey, Anil Kaul
Journal: Journal of Clinical Oncology (2016)

4024 Background: Barrett’s Oesophagus (BO) is a precursor for Oesophageal Adenocarcinoma (OAC). Currently, there are no biomarkers in clinical practice that predict the malignant progression in BO. We sought to clarify the effectiveness of common genetic aberrations as potential biomarkers through a systematic review and meta-analyses. Methods: MEDLINE, EMBASE and the Cochrane Library were searched by two independent reviewers to identify all clinical studies that assessed efficacy of p53, p16, Ki-67 and DNA content abnormalities as prognostic markers in BO. The main outcome measure was development of OAC. Results: 104 clinical studies, with 12,353 samples were identified. Mutation [DOR 10.91 (2.46-48.42), sensitivity 47% (41-53%), specificity 92% (90-94%), PLR 4.71 (1.73-12.78), NLR 0.65 (0.50-0.85), AUC 0.7921] and loss of p53 [DOR 16.16 (6.09-42.88), sensitivity 31% (25-38%), specificity 98% (97-98%), PLR 6.66 (4.51-9.84), NLR 0.41 (0.11-1.47), AUC 0.9228] were found to be superior to the other p53 abnormalities (Loss of heterozygosity and Over-expression). Ki-67 was also noted to have high sensitivity in identifying high risk patients [DOR 5.54 (3.40-9.05), sensitivity 82% (78-85%), specificity 48% (44-52%), PLR 1.59 (1.20-2.10), NLR 0.42 (0.34-0.51), AUC 0.7607]. Aneuploidy [DOR 12.08 (8.09-18.03), sensitivity 53% (50-57%), specificity 87% (85-88%), PLR 4.26 (2.92-6.20), NLR 0.42 (0.32-0.55), AUC 0.8461], tetraploidy [DOR 5.87(2.56-13.4), sensitivity 46% (39-53%), specificity 85% (82-87%), PLR 3.47 (1.98-6.05), NLR 0.65 (0.45-0.94), AUC 0.7926] and loss of Y chromosome [DOR 9.23 (4.34-19.63), sensitivity 68% (56-79%), specificity 80% (73-86%), PLR 2.67 (1.29-5.50), NLR 0.49 (0.35-0.68), AUC 0.8073] also predicted the malignant development with respectable accuracy but p16 aberrations (Hyper-methylation, Mutation and Loss) failed to demonstrate any advantage over the other biomarkers studied. Conclusions: Loss and mutation of p53 and Ki-67 effectively predict malignant progression in BO. A panel of biomarkers would be more suited to be included in surveillance programme. This will need to be confirmed in large, prospective clinical trials with cost- efficiency analyses.
P53 Cryptococom as a Differential Diagnosis of Pulmonary Metastase in a Patient with Challenging Adenocarcinoma: Case Report
Authors: N. Silva, W. Schmidt Aguiar, D. Simões, C. Amorim, K. Vasconcelos, R. Moreira, G. De Souto, A. Vital
Journal: Journal of Thoracic Oncology (2018)
BMA should evaluate Dutch experience with euthanasia
Authors: M. Irwin
Journal: BMJ (1995)

EDITOR,—When I retired to England early last year one of my main reasons for doing so was that I preferred, as I grew older, to receive medical care in Britain rather than in the United States, where I had lived for 31 years. Therefore, the three articles in the Christmas issue on the suffering experienced by several patients during the final weeks of their lives made depressing reading.1 …
Analysis of prognostic factors for gallbladder cancer (GBC) of patients assisted in an academic hospital in Chile.
Authors: Luis Villanueva, Rodrigo Uribe, Olga Barajas, Barbara Nuñez, Alex Renner, Rodrigo Vasquez, Oscar Aguilera, Renato Muñoz, Monica Ahumada
Journal: Journal of Clinical Oncology (2018)

e16127 Background: Chile is the country with highest incidence and mortality rates of the GBC in the world. The GBC is an aggressive cancer with poor survival. Many studies include GBC in the group of biliary tract cancers, but the study as its own entity has been limited. The aim of this study is to evaluate the prognostic factors associated with overall survival (OS) in patients (pts) with the diagnosis of GBC. Methods: Retrospective study that includes pts with diagnosis of GBC confirmed by biopsy, classified according to images or surgical procedures. They were treated in Hospital Clinico Universidad de Chile between January 2010 to December 2015. The analysis was according to demographic, clinical and pathological variables and related to chemotherapeutic treatment (CT). Results: There were 130 pts, 82 women and 48 men. The mean age was 63 (35-96) years. Histopathological diagnosis was adenocarcinoma NOS in 67% of the cases. Seventy-one pts (56%) debuted with IV stage disease. Twenty-one pts (27,6%) received first line of CT. 90% of this pts received gemcitabine with cisplatin, mean cycles was 5.5 (1-19) cycles. OS of stage IV group that received first line CT was 13.6 months (ms) vs 4,2 ms in pts not treated with CT (HR: 0,58, 95% CI 0,35-0,95, p = 0,04). There were 18 pts with stage IIIA and 13 pts with stage IIIB. They did not present statistical significant (ns) in OS (10,9 vs 8,1 ms, respectively, p = ns). Only 5 pts received adjuvant treatment. Our analysis showed factors that determined a better OS were ECOG 0-1 vs ≥ 2 with OS 10 vs 2,2 ms (HR 0.38, 95% CI 0,18-0,79; p = 0,0001). Albumin ≥3,5 showed better OS than albumin < 3,5 g/dl (OS 9,1 vs 5,6 ms; p = ns). The women treated with CT had a superior OS than men (17,2 versus 13,5 ms; p = ns). There were not statistically differences in the OS according to gender, BMI, hemoglobin nor age in all group. Conclusions: In our analysis, pts with ECOG 0-1 and levels of albumin ≥3,5 g/dl demonstrated a better OS due to good functional and nutritional status. Women who received chemotherapy had a better prognosis. Perhaps, this finding is due to early consultation. The absence of adjuvant therapy could explain the poor results obtained in stage III pts.
Metastatic clear cell renal cell carcinoma: Proangiogenic gene expression and outcome on sunitinib.
Authors: Annelies Verbiest, Benoit Beuselinck, Gabrielle Couchy, Sylvie Job, Aurelien De Reynies, Clément Meiller, Maarten Albersen, Virginie Verkarre, Evelyne Lerut, Arnaud Mejean, Jean-Jacques Patard, Brigitte Laguerre, Nathalie Rioux-Leclercq, Patrick Schöffski, Stephane Oudard, Jessica Zucman-Rossi
Journal: Journal of Clinical Oncology (2017)

e16085 Background: Clear cell renal cell carcinomas (ccRCC) are hypervascular tumors that respond to vascular endothelial growth factor receptor (VEGFR) inhibitors such as sunitinib. They can be divided into 4 mRNA-expression based subgroups (ccrcc 1-4) with different outcomes on sunitinib. We hypothesized that the expression of proangiogenic genes is predictive for response to sunitinib. Methods: Retrospective series of metastatic ccRCC-patients treated with sunitinib as first line targeted therapy (n = 104). We studied expression of genes involved in angiogenesis and the immune-suppressive microenvironment (qRT-PCR) and mutational status of Von Hippel Lindau and Polybromo (PBRM) 1 (sequencing) on primary tumor samples. Outcome parameters were response rate (Response Evaluation Criteria in Solid Tumors), progression free survival (PFS) and overall survival (OS). Gene expression levels were tested in multivariate analysis (MV) against the IMDC risk criteria, presence of bone metastases and sarcomatoid dedifferentiation ≥25%. Results: Expression of Hypoxia Inducible Factor (HIF) 2A, Platelet Derived Growth Factor Receptor B, VEGFC, VEGFR1 and VEGFR2 was significantly correlated with PFS on MV and expression of HIF1A, HIF2A and VEGFR2 with OS. VEGFR2-expression was also correlated with partial response (p = 0.03) and anti-correlated with early progressive disease (p = 0.008). HIF2A, VEGFA, VEGFR1, VEGFR2 and VEGFR3-expression was higher in ccrcc2-tumors compared to others. Expression of genes involved in angiogenesis and in the immune-suppressive microenvironment was not directly correlated nor anti-correlated. In tumors with a bi-allelic PBRM1-inactivation, HIF2A, VEGFA, VEGFR1 and VEGFR2-expression were higher compared to tumors with 1 or 2 functional PBRM1-alleles. This did not translate in different outcome on sunitinib. Conclusions: Tumoral expression of genes involved in the HIF-VEGF-VEGFR proangiogenic pathway, especially VEGFR2, is associated with favorable outcome on sunitinib in metastatic ccRCC. Expression of these genes was high in the molecular ccrcc2-subgroup, known to be sensitive to sunitinib. These findings could be used for patient selection in future clinical trials.
Abstract 16595: Insulin Replacement Attenuates Autonomic Impairment but Did Not Prevent Early Diastolic Dysfunction in a Model of Type 1 Diabetes
Authors: Sarah C Freitas, Paulo M Dourado, Iris C Sanches, Jacqueline F machi, Maria C Irigoyen, Kátia De angelis
Journal: Circulation (2015)

Introduction: Insulin replacement is the most widely used therapy for treatment of patients with Type 1 Diabetes Mellitus. However, despite a restricted glycemic control, diabetic patients are prone to chronic complications, such as cardiovascular disease. The mechanisms underlying this increased risk are not well understood. Hypothesis: The insulin replacement therapy can prevent the cardiac and autonomic dysfunctions in a model of type 1 diabetes. Methods: 18 male Wistar rats (230-260g) were divided into 3 groups (n=6/group): control (C), diabetic (D, streptozotocin 50 mg/kg) and diabetic treated daily with insulin subcutaneously (DTI). At 30 days, cardiac function was assessed by echocardiogram and after the rats were cannulated and arterial pressure (AP) was recorded. Results: The diabetic groups showed hyperglycemia (&gt;350mg/dl) at the beginning of the protocol. Insulin therapy normalized the glycemia (DTI: 94±28 and C: 126±8 vs. D: 533±67 mg/dl). There was a reduction in the posterior wall thickness of the left ventricle at diastole (PWD) and in the relative wall thickness (RWT) in D group and these changes were not observed in DTI group (PWD- C: 0.122±0.008 and DTI: 0.126±0.004 vs. D: 0.086±0.006 cm and RWT- C: 0.42±0.021 and DTI: 0.4±0.013 vs. D: 0.35±0.014). Left ventricular mass was reduced in D group (D: 0.393±0.0510 vs. C: 0.581±0,054 and DTI: 0.586±0.049). The systolic function was not different (shortening fraction) between the groups. Regarding diastolic function, the isovolumetric relaxation time was not different between the groups, but there was a decrease in E/A wave ratio in the group of diabetic rats, which was not reversed by insulin treatment (D: 1.53±0.104 and DTI: 1.69±0.178 vs. C: 2.45±0.380). The baroreflex sensitivity was impaired in D group in relation to C and DTI groups (D: 1.05±0.110 vs. C: 1.39±0.100 and DTI: 1.36±0.09 bpm/mmHg). The insulin treatment normalized mean AP (DTI: 118±3.34 and C: 110±3.28 vs. D: 99±5.48 mmHg). Conclusions: Treatment with insulin despite normalize blood glucose, baroreflex sensitivity, hemodynamics and cardiac morphometry, was not able to attenuate diastolic dysfunction, suggesting a remaining cardiovascular risk even after insulin replacement in this model of experimental diabetes type I.
The relationship between statins and breast cancer prognosis varies by statin type and exposure time: A meta-analysis.
Authors: Binliang Liu, Zongbi Yi, Xiuwen Guan, Fei Ma, Yi-Xin Zeng
Journal: Journal of Clinical Oncology (2017)

e21606 Background:Breast cancer is the most common cancer in females. The effects of statins on breast cancer prognosis have long been controversial, so it is important to investigate the relationship between statin type, exposure time, and breast cancer prognosis. This study sought to explore the effect of statins on breast cancer prognosis. Methods:We searched the MEDLINE, EMBASE, Cochrane Library between October 15, 2016 and January 20, 2017. Searches combined the terms “breast neoplasms[MeSH]”, “statins”, “prognosis” or “survival” or “mortality” with no limit on publication date. Data were analyzed using Stata/SE 11.0. Results: 7 studies finally met the selection criteria and 197,048 included women. Overall statin use was associated with lower cancer-specific mortality and all-cause mortality (HR 0.73, 95% CI 0.59-0.92, P = 0.000 and HR 0.72, 95% CI 0.58-0.89, P = 0.000). Lipophilic statins were associated with decreased breast cancer-specific and all-cause mortality (HR 0.57, 95% CI 0.46-0.70, P = 0.000 and HR 0.57, 95% CI 0.48-0.69, P = 0.000); however, hydrophilic statins were weakly protective against only all-cause mortality (HR 0.79, 95% CI 0.65-0.97, P = 0.132) and not breast cancer-specific mortality (HR 0.94, 95% CI 0.76-1.17, P = 0.174). Of note, more than four years of follow-up did not show a significant correlation between statin use and cancer-specific mortality or all-cause mortality (HR 0.84, 95% CI 0.71-1.00, P = 0.616 and HR 0.95, 95% CI 0.75-1.19, P = 0.181), while groups with less than four years of follow-up still showed the protective effect of statins against cancer-specific mortality and all-cause mortality (HR 0.62, 95% CI 0.44-0.87, P = 0.000 and HR 0.61, 95% CI 0.45-0.80, P = 0.000). Conclusions:Although statins can reduce breast cancer patient mortality, the benefit appears to be constrained by statin type and follow-up time. Lipophilic statins showed a strong protective function in breast cancer patients, while hydrophilic statins only slightly improved all-cause mortality. Finally, the protective effect of statins could only be observed in groups with less than four years of follow-up.
PROMs and PREMs in Dutch integrated head and neck cancer care.
Authors: Rosella Hermens, Lydia Francisca Jacoba van Overveld, Robert P. Takes, Jozé C.C. Braspenning, Ludi E Smeele, Matthias A.W. Merkx
Journal: Journal of Clinical Oncology (2017)

6570 Background: Providing patient-centred care is an essential component of high quality integrated care. A method to get insight in patients perspectives about the quality of health care they received, is measuring Patient Reported Outcome Measures (PROMs) and Patient Reported Experience Measures (PREMs). We aimed to determine the outcomes of, and differences between PROs and PREs over time and between treatment groups for patients with head and neck cancer (HNC). Methods: Patientswere recruited from nine hospitals participating in the DHNA. Validated questionnaires were distributed at baseline, 3, 6 and 12 months follow-up. Included PROMs were EuroQol 5 Dimension 3 Level (EQ-5D-3L), EORTC QLQ-C30 and -H&amp;N35. Included PREMs, Consumer Quality index for Oncologic care (CQO) and Radiotherapeutic care (CQR), have similar domains with different questions. With descriptive analysis, ANOVA and mixed model analysis, differences over time and between treatment groups were analyzed. Results: Questionnaires were filled in by 426 patients. Pain decreased significantly at 6 and 12 months follow-up (14 and 21 points on a scale of 0-100) and dry mouth increased significantly at 3, 6 and 12 months follow-up compared to baseline (35, 27 and 20 points). Sticky Salvia, problems with social eating and sense problems increased at 3 and 6 months follow-up, but were similar to the baseline score at 12 months follow-up. Pain and sticky saliva differed between radiotherapy and chemoradiotherapy or surgery and radiotherapy respectively (p≤0.05). Regarding the CQO domain scores, all treatment groups differed significantly from each other (p≤0.05), especially for the domain Personal input. There was no difference regarding the CQR domain scores. Recognizing the emotional side of HNC and guidance after the treatment scored low in patients. Conclusions: This study gives clues to improve healthcare according the experiences of the patient and we can predict more carefully the outcomes of the patients with different treatment types. PROMs according to the ICHOM criteria and PREMs are promising for measuring and improving quality and personalization of HNC care. However, recognizing the emotional side of HNC and intensifying guidance after the treatment period needs improvement.
Growth differentiation factor‐15 is not modified by sacubitril/valsartan and is an independent marker of risk in patients with heart failure and reduced ejection fraction: the PARADIGM‐HF trial
Authors: Nadia Bouabdallaoui, Brian Claggett, Michael R. Zile, John J.V. McMurray, Eileen O'Meara, Milton Packer, Margarett F. Prescott, Karl Swedberg, Scott D. Solomon, Jean L. Rouleau
Journal: European Journal of Heart Failure (2018)
Molecular profiling-selected treatment in metastatic gastric and oesophageal cancer: Real-life clinical experience.
Authors: Ofer Purim, Alexander Beny, Moshe J. Inbar, Baruch Brenner, Elizabeth Dudnik, Felix Bokstein, Mark Temper, Dror Limon, David Sarid, Valeriya Semenisty, Ronen Mordechay Brenner, Tamar Peretz, Efraim Idelevich, Sharon Pelles, Amichay Meirovitz, Kenneth Russell, Andreas Voss, Addie Dvir, Lior Soussan-Gutman, Ayala Hubert
Journal: Journal of Clinical Oncology (2017)

e15537 Background: We evaluated real-life clinical experience with molecular profiling (MP)-guided therapy in metastatic gastric and oesophageal cancer in Israel Methods: This multicenter retrospective cohort study included patients with metastatic gastric or oesophageal cancer who were treated in the participating institutions and underwent MP (Caris Molecular Intelligence). Treatment was considered as having benefit if the ratio between the longest progression-free survival (PFS) post MP and the last PFS pre MP was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Results: The analysis included 46 patients (61% males; median age, 58 years; 57% with poorly-differentiated tumours). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified per patient. Immunohistochemistry was performed on all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy post MP (1-4 lines). In the 1 st -line post MP, 5 patients (18%) achieved partial response and 5 (18%) stable disease; the median (range) PFS was 4.3 (0.4-38.5) months. Twenty-four patients were evaluable for PFS ratio analysis; in 7 (29.2%), the ratio was ≥1.3. In one-sided exact binomial test vs. the null hypothesis, P = 0.019; therefore, the null hypothesis was rejected. Conclusions: Our findings demonstrated that implementing MP is feasible and that MP could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or oesophageal cancer.
Psychological distress before and after surgical resection of orofacial tumours.
Authors: Azeez Fashina, Olatunji Francis Aina, Wasiu Lanre Adeyemo
Journal: Journal of Clinical Oncology (2018)

e18043 Background: The aim of the study was to determine the presence and level of psychological distress in subjects before and after the resection of orofacial tumours. Methods: Hospital Anxiety and Depression Scale (HADS) and Rosenberg Self Esteem Scale (RSES) questionnaires were administered to subjects before surgery, 1 week, 2 weeks and 6 weeks after surgery. The HADS and RSES scores at intervals were compared using simple proportions and percentages. The differences between preoperative and postoperative HADS and RSES scores were assessed using the paired t-test. The relationship between variables and psychological distress was tested using chi square test and logistic regression analysis. Results: A total of 37 subjects took part in the study. Abnormal levels of anxiety were recorded in 29.7% of subjects before surgery while 13.5% reported abnormal depression levels before surgery. Proportion of subjects with abnormal anxiety levels rose to 37.8% 1 week after surgery, 40.5% 2 weeks after surgery and 35.1% 6 weeks after surgery. About 16% of subjects reported abnormal depression levels one week after surgery while 13.5% had abnormal depression levels at 2 weeks and 6 weeks after surgery. No subject reported abnormal self-esteem levels preoperatively and post-operatively. The mean anxiety scores 1 week, 2 weeks and 6 weeks after surgery were significantly higher than mean anxiety score before surgery. Depression and self-esteem showed no statistically significant differences when mean values before surgery were compared with mean values after surgery. Level of education was found to be significantly associated with anxiety before surgery, 1 week after surgery, 2 weeks after surgery and 6 weeks after surgery. Size of lesion was also statistically significantly associated with anxiety at 6 weeks after surgery with a P-value of 0.037. Conclusions: Abnormal anxiety and depression are present in some subjects with orofacial tumours and these tend to increase after surgery. Educational status of subject and size of tumour appear to affect anxiety and depression levels both before and after surgery for an orofacial tumour. Therefore, psychological evaluation should be incorporated into the management of patients with orofacial tumours.