bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical prognostic factors in advanced lung adenocarcinoma patients with different EGFR mutation subtype.
Authors: Wang Yudong , Yan Jianzhu , Zuo Jing , Fan Zhisong , Wang Long , Xu Xiaoli , Liu Fengling , Wei Suju , Jiang Da 
Published: May 2019

e20680 Background: The prognostic factors of advanced NSCLC patients with EGFR mutation subtypes remains controversial. This study aimed to investgate the association of clinical prognostic factors with EGFR-TKI efficacy in advanced lung adenocacinoma patients with different EGFR mutation subtypes. Methods: The clinical characteristics, treatment and survival data of advanced lung adenocarcinoma patients with EGFR sensitive mutations who were treated with Icotinib (Betta Pharmaceuticals, China) from January 2011 to December 2017 in our medical center were reviewed. The prognositic factors of patients between with EGFR exon 19 deletion (19-Del) and exon 21 Leu858Arg mutation (L858R) were retrospectively analyzed by using the Kaplan-Meier method, the chi-square test, and multivariate Cox hazards model. Results: A total of 187 patients were enrolled in the study, including 104 patients with EGFR19-Del and 83 patients with EGFR21-L858R. The results showed that no significant difference in mPFS between the two groups (19-Del vs. L858R: 15.0 months, 95% CI 17.2-32.8months vs. 13.0 months 95% CI 11.7-14.3 months, p = 0.347), while the mOS of patients with 19-Del (35months, 95% CI 28.6-41.4 months) was significantly better than that of patients with EGFR21-L858R (25 months, 95%CI 17.2-32.8 months, p = 0.020). For PFS, liver metastasis was an independent prognostic factor in EGFR19-DEL patients (HR 5.009, 95%CI 1.296-19.354, p = 0.019), while gender (HR 5.881, 95%CI 2.105-16.431, p = 0.001), smoking status (HR 6.972, 95%CI 2.851-17.049, p = 0.001), lymph node metastasis (HR 2.676, 95%CI 1.002-7.148, p = 0.050) were independent prognostic factors in patients with L858R. As for OS, age (HR 1.080, 95%CI 1.017-1.147, p = 0.012), brain metastases (HR 23.166, 95%CI 3.946-136.009, p = 0.001), liver metastases (HR 14.088, 95%CI 1.782-111.385, p = 0.012), renal or adrenal metastasis (HR 10.558, 95%CI 1.480-75.326, p = 0.019), TKI initial efficacy (HR 6.638, 95%CI 2.743-16.067, p = 0.001) were independent prognostic factors in patients with 19-del, however, the initial efficacy of TKI (HR 6.089, 95% CI 2.669-13.893, p = 0.001) was an independent prognostic factor in patients with L858R. Conclusions: The mOS of patients with EGFR 19-Del treated with Icotinib was significantly better than that of patients with L858R, while the mPFS of both were similar. Moreover, there are significant differences in prognostic factors of advanced lung adenocarcinoma patients between with 19-Del and L858R subtypes, which may be helpful for the clinical treatment strategy of EGFR-TKI.
Overcoming acquired osimertinib-resistance in EGFR-mutant advanced non-small lung cancer mediated by activating BRAF V600E mutation.
Authors: Abdulla Diana S.Y. , Scheffler Matthias , Kobe Carsten , Persigehl Thorsten , Schmidt Matthias , Fassunke Jana , Merkelbach-Bruse Sabine , Michels Sebastian Yves Friedrich , Nogova Lucia , Koleczko Sophia , Fischer Rieke Nila , Riedel Richard , Drzezga Alexander , Büttner Reinhard , Wolf Juergen 
Published: May 2019

e20682 Background: There is growing insight in the mechanisms underlying resistance to the 3rdgeneration EGFR inhibitor osimertinib. Unlike resistance to 1stgeneration inhibitors, these mechanisms not necessarily lead to sequential targeted therapy approaches. Here we report on the treatment of two patients with acquired resistance to osimertinib with a new detected BRAF V600E mutation as resistance mechanism. Methods: We identified two patients with EGFR-T790M-mutant advanced NSCLC with progression on osimertinib and detection of a new BRAFV600E mutation in a tumor rebiopsy by next-generation sequencing (NGS). No other known resistance mechanism beside T790M loss in one patient was found. Osimertinib was discontinued and BRAF-targeted combination therapy with dabrafenib and trametinib at standard dose was initiated. We monitored the clinical course with sequential 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) / computed tomography (CT) assessing maximum standard uptake value (SUVmax), sequencing based liquid biopsies and tumor marker assessment. Results: Patient (1) with EGFR del19 (E746_A750del), preserved T790M mutation and acquired BRAF V600E mutation showed reduction in FDG uptake of 18% after 2 weeks of dabrafenib/trametinib that demonstrated a slight increase of 12% in a FDG-PET/CT scan 4 weeks thereafter and combination treatment has been continued. Patient (2) with EGFR del19 (E746_A750del), T790M loss and new BRAF V600E mutation showed continuous metabolic (+8% and + 39%, respectively) and morphologic progression after 2 and 4 weeks of dabrafenib and trametinib. A tumor rebiopsy showed no additional molecular changes. We changed the treatment to osimertinib and dabrafenib combination and observed an impressive metabolic response (-33%) after 2 weeks by FDG-PET/CT. Conclusions: BRAF V600E mutation has recently been described as a novel molecular resistance mechanism in osimertinib-resistant EGFR-mutant NSCLC. We describe one patient where combined BRAF/MEK inhibition with no additional EGFR-inhibition resulted in a preliminary feasible tumor control, but confirmatory CT staging is pending. In a second patient, co-inhibition of EGFR and BRAF pathway with osimertinib and dabrafenib was needed to overcome BRAF-mediated osimertinib resistance resulting in an impressive early tumor response that was not observed to either single-target inhibition of EGFR or BRAF. FDG-PET/CT was able to monitor tumor dynamics. Updated data will be presented.
The interplay between PD-L1 and vimentin in NSCLC patients: An exploratory analysis.
Authors: Bronte Giuseppe , Puccetti Maurizio , Cravero Paola , Ravaioli Sara , Tumedei Maria Maddalena , Ulivi Paola , Burgio Marco Angelo , Verlicchi Alberto , Delmonte Angelo , Cappuzzo Federico , Crino Lucio , Bravaccini Sara 
Published: May 2019

e20688 Background: The immune modulation is emerging as a key strategy in non-small cell lung cancer (NSCLC) patients management. PD-L1 has been the only biomarker validated for immunotherapy but it holds many limitations. Vimentin is one of the marker for epithelial-to-mesenchymal transition (EMT), a biological process which favors immune escape. We explored two issues: the correlation between PD-L1 and Vimentin expression in NSCLC samples and the prognostic value of PD-L1 and vimentin concordance in NSCLC patients. Methods: We collected all the NSCLC samples evaluable for both PD-L1 and Vimentin and recorded the relative available clinical and survival data, if written informed consent was present. PD-L1 and Vimentin were retrospectively assessed through immunohistochemistry (IHC) by using prediluted antibodies clones SP263 (Ventana Medical Systems, Tucson, AZ, USA) and anti Vimentin V9 (Ventana Medical Systems) on Benchmark XT Platform (Ventana Medical Systems). Biomarker expression was detected and semiquantitatively quantified as the percentage of immunopositive tumor cells on the total of tumor cells. We correlated PD-L1 and Vimentin expression through linear regression. We compared survival of patients with both PD-L1 and Vimentin 0% and all the others via Kaplan-Meier method by using MedCalc software version 18.11.3. Results: Ninety-nine samples underwent PD-L1 and Vimentin IHC analysis. A weak positive statistically significant correlation was found between the 2 biomarkers (r = 0.41; p < 0.001). For 40 patients survival data (from first NSCLC diagnosis) were available. Survival analysis showed that PD-L1 and Vimentin negative patients (n = 12) experienced not statistically significant longer survival (HR = 0.35; 95%CI: 0.08-1.51; p = 0.16). Conclusions: These preliminary findings suggest that an interplay can exist between PD-L1 and vimentin in NSCLC, but analysis in a wider population is necessary. Studies on the significance of this interplay for immunotherapy efficacy should be designed.
End-of-life care and prognosis of elderly patients with advanced cancer in palliative care unit.
Authors: Hiramoto Shuji , Tamaki Tomoko , Tetsuo Hori , Kikuchi Ayako , Yoshioka Akira , Kirishima Toshihiko 
Published: May 2019

e23011 Background: Prognosis of end-of-life characteristics, which are indicators of palliative care, especially in elderly cancer patients, remains unclear. Methods: We retrospectively analyzed 510 patients who died of advanced cancer at our hospital from August 2011 to August 2016. The patients were divided into two groups: elderly patients (over 80 years old, N = 140) and non-elderly patients (under 80 years old, N = 370). The number of patients (306 male and 204 female) with gastro-esophageal, biliary-pancreatic, colorectal, lung, breast, urological, gynecological, hepatocellular, and other cancers were 114, 98, 82, 84, 25, 36, 20 and 51, respectively. The primary endpoint of the study was to analyze the relationship of end-of-life symptoms, treatment, and chemotherapy with age. The secondary endpoint was to identify the prognostic factors in elderly patients with advanced cancer at the end-of-life. Results: ECOG Performance Status of 0.1 was recorded for 12 patients and 2-4 for 498 patients. The prevalence rate of cancer pain in elderly patients was 19.3%, which was significantly lower than that in non-elderly patients (31.4%). Fatigue in elderly patients was 27.9%, which was significantly lower than that in non-elderly patients (37.6%). Continuous deep sedation usage in elderly patients was 12.9%, which was significantly lower than that in non-elderly patients (28.9%). The mean opioid dose in elderly patients was 23.3mg/day, which was significantly lower than that that in non-elderly patients (43.8mg/day). The rate of more than one line of chemotherapy for elderly patients was 44.4%, which was lower than that for non-elderly patients (65.4%). The rate of use of more than one type of cytotoxic agent in the last regimen for elderly patients was 13.3%, which was lower than that for non-elderly patients (30.8%). Consciousness level was recognized as a significant prognostic factor (HR 1.714, p = 0.048) using multivariate analysis of prognosis in elderly patients at the end-of-life. Conclusions: End-of-life symptoms and the intensity of end-of-life treatment, including chemotherapy, were lesser in elderly patients as compared to non-elderly patients. Consciousness level was a significant prognostic factor in elderly patients at the end-of-life.
Treatment and outcome of elderly patients with PCNSL: A Beaumont experience.
Authors: Pang Yifan , Gbadamosi, MD. Bolanle , Bakhsh Saaquib , Gaikazian Susanna S. , Jaiyesimi Ishmael A. 
Published: May 2019

e23012 Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy. Prognosis remains poor, and data on clinical characteristics or outcomes are limited, particularly in the elderly. In the literature, age over 50 is a major poor prognostic factor. Herein, we report our experience of PCNSL in elderly patients. Methods: The electronic medical records from 2007 to 2015 of the Beaumont Health System were analyzed. Patients with non-Hodgkin’s Lymphoma (NHL) were reviewed and those with PCNSL were identified. Results: Of the 617 NHL patients, 21 (3.4%) had PCNSL, 12 (57.1%) were male and 17 (81.0%) Caucasian. Median age was 76 (range, 55 to 83), and the majority 18 (85.7%) were above age 65. Deep brain lesions occurred in 11 (52.4%) patients. Eighteen (85.7%) received treatment, including 3/18 (16.7%) with high-dose methotrexate (HD-MTX) only, 5/18 (27.8%) HD-MTX plus rituximab (MR), 2/18 (11.1%) HD-MTX with vincristine and procarbazine, 7/18 (38.9%) MR and other chemotherapy, and 1/18 (5.6%) temozolomide and rituximab. MTX dose ranged from 1.8 to 8 g/m2 (median, 3.5 g/m2). The number of treatment cycles ranged from 1 to 11 (median, 3). Whole brain radiation was given to 4 (22.2%) patients with refractory disease after systemic chemotherapy. None of the patients received definitive radiation. Overall response rate was 44.4%, including 4/18 (22.2%) CR and 4/18 (22.2%) PR. Median survival was 4.0 months (95% CI, 2.3 to 5.7 months). At the time of data collection (November, 2018), only four patients were alive. Causes of death included disease progression (58.8%), neutropenic sepsis (23.5%), and MTX toxicity, predominantly acute kidney injury and severe gastrointestinal mucositis (17.7%). Age, lesion depth, treatment, and other clinical characteristics did not impact survival (all p > 0.05). Conclusions: Although HD-MTX remained the backbone of therapy for most patients, we observed a heterogeneous treatment pattern in our elderly patient population. More than 50% had primary refractory diseases, while about 40% had treatment related mortality. This study further emphasized the need for more trials enrolling elderly patients with PCNSL, utilizing novel agents, and investigating molecular prognostic markers.
Estimating survival time in older adults receiving chemotherapy for advanced cancer.
Authors: Moth Erin , Blinman Prunella , Stefanic Natalie , Naganathan Vasi , Martin Andrew James , Grimison Peter S. , Stockler Martin R. , Beale Philip James , Kiely Belinda Emma 
Published: May 2019

e23017 Background: Best-case, worst-case, and typical scenarios for survival time, based on an oncologist’s estimate of expected survival time (EST), have proven accurate in a range of advanced cancers. We sought the accuracy and prognostic significance of such estimates, and of a simple, pragmatic rating of frailty, in older adults starting chemotherapy. Methods: Participants (pts) were aged 65 or older and starting a new line of chemotherapy for advanced cancer. For each pt at baseline, their treating oncologist recorded an individualised estimate of EST (median survival in a group of similar patients), ECOG performance status (PS), and rating of frailty with the single-item, Clinical Frailty Scale from the Canadian Study of Health and Aging. We hypothesised that estimates of EST would be unbiased (approximately 50% of pts would live longer than their EST); imprecise ( < 33% would live for 0.67 to 1.33 times their EST); and, that simple multiples of the EST would provide accurate individualised scenarios for survival time, i.e. approximately 10% of pts would die within ¼ of their EST, 10% would live longer than 3 times their EST, and 50% would live from half to double their EST. We identified independent predictors of observed survival time (OST) with multivariable Cox regression. Results: Baseline characteristics of the 102 pts were: median age 74 (range 65-86), 1st line chemotherapy in 67%, colorectal cancer in 33%, PS 0 or 1 in 80%, and frailty rating of vulnerable to frail in 35%. The median EST was 15 months (range 4-60), median follow-up time was 19 months (range 0-27), and median OST was 15 months (range 0.5-27+). As hypothesized, 54% of pts lived longer than their EST, 30% lived within 0.67 to 1.33 times their EST, 56% lived half to double their EST, and 9% lived ≤1/4 of their EST. Follow-up was too short to observe those who will live ≥3 times their EST. Independent predictors of OST were frailty (HR 2.8, 95%CI 1.6-4.9, p = 0.0004) and EST (HR 0.96, 95%CI 0.93-0.99, p = 0.03). Conclusions: Oncologists’ estimates of EST were unbiased, imprecise, and accurate for formulating scenarios for survival time. A simple, pragmatic rating of frailty by the treating oncologist was a strong predictor of OST even after accounting for their estimate of EST.
Evaluation of readmission rates for gastrointestinal bleeds in high risk oncologic patients.
Authors: Babar Laila , Bakalov Veli , Monga Dulabh K. , Chahine Zena , Ashraf Obaid 
Published: May 2019

e23031 Background: Gastrointestinal bleeding (GIB) results in high rates of hospital admissions, readmissions, significant morbidity and high healthcare cost. To lower readmission rates, Medicare mandates public reporting, however it does not differentiate between patient populations. GIB is a complex disease with treatment selection and patient outcome changing with different patient populations. We must identify vulnerable groups and high risk characteristics. Malignancy is a hypercoaguable disease and when combined with atrial fibrillation or history of clots, it can increase stroke and pulmonary embolism risk. These patients require anticoagulation putting them at a higher risk of bleeding. In our study, we identified cancer patients with atrial fibrillation and evaluated reasons for differences in readmission rates for GIB. Methods: We queried our EMR for a list of patients from April 2016-April 2018. Inclusion criteria was admission for GIB, a history of cancer, atrial fibrillation, DVT or PE. Patients were divided into groups with and without readmission for GIB, and differences in characteristics were analyzed. Odds ratios(OR) with p-value 0.05 and confidence interval (CI) 95% were calculated. Results: Of 111 patients, 57 met our inclusion criteria, 32 male and 25 female with average age 78.8 years. 18 patients required readmission, 12 for GIB. 32% of our population was readmitted within 30 days of discharge, 21% was readmitted for a GIB. BMI > 30(OR:0.28; CI 0.15-0.54; p = 0.0002), ICU admission during hospitalization(OR:0.083; CI 0.019-037; p = 0.0011), and lower GI tract as site of bleeding (OR:0.54; CI 0.30-0.98; p = 0.04) were associated with a lower incidence of readmission for GIB. Administration of blood transfusion (OR:2.80; CI 1.58-4.99; p = 0.0004)and discharge disposition to skilled facility(OR:1.93; CI 1.04-3.57; p = 0.036) was associated with a higher incidence of readmission. There was no difference with type of anticoagulation. Conclusions: The readmission rates for GIB in our population (32%) was higher than the national average (12%). Cancer patients requiring anticoagulation have a drastically different hospital course and outcomes than healthy patients and should have different quality metrics and treatment algorithms. This will also make Medicare penalties more accurate.
Elderly patients have limited access to systemic therapy for metastatic renal cell carcinoma (mRCC) and shorter overall survival in Russia, Belarus and Kazakhstan.
Authors: Tsimafeyeu Ilya , Krasny Sergei , Nurgaliyev Nurzhan , Varlamov Ilya , Petkau Vladislav , Safina Sufia , Zukov Ruslan , Mazhbich Mikhail , Statsenko Galina , Novikova Olga , Zaitsev Igor , Kaidarova Dilara , Shatkovskaya Oxana , Moiseyev Pavel , Rolevich Alexander , Evmenenko Alesya , Popova Irina L. , Vladimirova Liubov Yu 
Published: May 2019

e23033 Background: Russia, Belarus and Kazakhstan are countries of the Eurasian Economic Union with upper-middle-income economies. Limited sources of the healthcare system could affect the treatment of individual cancer patients. The data on the treatment outcomes of elderly patients with mRCC are limited in these countries. RENSUR3 registry study assessed real-world data on the use of therapies in mRCC and overall survival (OS) in this population. Methods: Patients from Russia, Belarus and Kazakhstan were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were OS, patient characteristics and treatment patterns. Results: 1,094 adult mRCC patients were identified. Mean age at diagnosis of mRCC was 62.3 (SD, 11.2) years. 447 (41%) patients were 65 years and older. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients were not treated compared to 37% of younger patients. Cytokines were the most commonly used treatment in elderly patients (115 of 189 patients, 61%) while targeted therapy was more widely used in younger patients (223 of 406, 55%). Median OS was 12.7 months (95% CI 11.3-14.1) and 9.3 months (7.7-9.9) for patients aged < 65 and ≥65 years, respectively (P < 0.0001). Conclusions: More than half of elderly patients received no systemic therapy or had only cytokines for mRCC in Russia, Belarus and Kazakhstan which doubtless negatively affected OS in this population. Novel therapies should be considered as life-saving and a priority in elderly patients.
Spiritual and psychological distress in older and the oldest-old living with advanced cancer patients (O-OOAdCa) in a comprehensive cancer center.
Authors: Delgado-Guay Marvin Omar , De La Cruz Maxine Grace Jaucian , Pang Linda , Williams Janet L. , Bruera Eduardo 
Published: May 2019

e23041 Background: Older adults living with cancer may experience multiple physical, emotional and spiritual symptoms. Limited literature describing the frequency of psychological and spiritual distress in O-OOAdCa. Methods: Retrospective chart review of patients seen by the Palliative Care team from January 2013 to December 2016. We randomly sampled 200 patients aged < 65, 200 patients aged 65 - < 85) and 41 consecutive patients ≥85). Using the ESAS-FS, determined the frequency, and correlates of self-reported Spiritual Pain (SP) and Anxiety (Anx) and Depression (Dep) among these patients. Psycho-spiritual distress was defined as the presence of SP ≥1/10, Anx ≥2/10, and Dep ≥2/10. Results: 52% were female, 61% white, and 48% with ECOG of 2 in the group < 65, 48% were female, 61% white, and 43% an ECOG of 2 from group 65 to 84, and 49% were female, and 83% white, and 49% an ECOG of 3 from the group > 85 years. Spiritual Pain was present in 101/200 (51%) in the group < 65 vs. 61/187 (36%) in group 65-84 vs. 15/54 (29%) in ≥85, p = 0.004. Anxiety was present in 130/200 (65%), vs. 120/187 (65%), vs. 35/54(65%) per group respectively, p = NS. Depression was present in 109/200 (55%), vs. 100/187 (54%), vs. 29/54 (54%), respectively per group, p = NS. Psycho-spiritual distress was present in 65/200 (33%), vs. 44/187 (24%), vs. 11/54 (20%) per group respectively, P = NS. Logistic regression showed gender female correlated with higher psycho-spiritual distress (OR:2.08, p = 0.012), fatigue OR:1.32, p = 0.01, Well-Being OR:1.32, p = 0.02, Financial Distress OR:1.63, p = 0.00, age group < 65, OR:9.24, p = 0.03. Conclusions: High prevalence of Anxiety, Depression and Spiritual Pain in O-OOAdCa. Less frequency of Spiritual Pain in the Oldest-Old when compared with the rest of the population. Highlights the importance of an integrative Psycho-spiritual care to this population. More research is needed.