bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the epigenetic modulator BORIS on sensitivity of melanoma cells to UV-induced DNA damage.
Authors: Janssen Sanne , Van Kempen Leon , Elchebly Mounib , M'Boutchou Marie-Noel , Spatz Alan 
Published: September 2018

e21077 Background: Cutaneous melanomas display considerably higher mutational load compared to other solid tumors, mainly due to DNA damage and absent/defective repair. Chromatin organization plays an important role in these processes, with open chromatin conferring a higher sensitivity to DNA damage. BORIS is an epigenetic modifier that is correlated with open chromatin and is abnormally expressed in primary and metastatic melanoma. Here we set out to obtain a better understanding of BORIS’s role in chromatin organization and DNA damage in melanoma. Methods: A panel of melanoma cell lines was selected and BORIS mRNA expression was determined using qPCR. Cellular localization of BORIS was assessed by immunofluorescence. Ectopic BORIS expression was established exploiting a doxycycline inducible expression vector and proliferation was assessed using crystal violet and Hoechst staining. DNA damage was induced by exposure to 60 J/m2 UVC followed by apoptosis and cell cycle analysis using flow cytometry. Results: We confirmed aberrant BORIS expression in 61% of our melanoma cell line panel and observed nuclear BORIS localization in areas of low chromatin density. Forced expression of BORIS in BORIS low/intermediate cell lines resulted in a significant reduction in cell growth and increased cell death. Interestingly, BORIS overexpressing cells exposed to UV irradiation displayed a higher degree of cell cycle alterations and increased level of apoptosis compared to BORIS low/intermediate cells. Conclusions: Our results demonstrate that BORIS is increased in melanoma, localized in areas of open chromatin, and increased sensitivity to UV-induced DNA damage. Taken together, this indicates a role for BORIS in directing the chromatin state into a more open conformation, allowing increased sensitivity to DNA damage. Currently, we are analyzing DNA damage in BORIS overexpressing cells and are further investigating BORIS’s role in directing chromatin state by exploiting ATAC-seq and ChIP-seq for various epigenetic marks.
Effect of some cytokine combinations on growth and metastasis of experimental melanoma.
Authors: Zlatnik Elena Yurievna , Zolotareva Ekaterina I. , Nepomnyashchaya Evgeniya M. , Shulgina Oksana G. , Novikova Inna Arnoldovna , Przhedetskiy Yury Valentinovich , Pozdnyakova Victoria V. , Kochuev Sergey , Przhedetskaya Viktoria 
Published: September 2018

e21081 Background: The purpose of the study was development and experimental validation of new methods of melanoma immunotherapy involving cytokines. Methods: The study included 30 С57Bl/6 mice with transplantable B16 melanoma. Dynamics of tumor growth, melanoma metastases to the lungs and spleen, morphology of melanoma, spleen and thymus and lymphocyte subsets in the blood and spleen after injected combinations of immunomodulators based on recombinant cytokines – IL-2 (Roncoleukin), IFN-γ (Ingaron) and TNF-α with thymosin (Refnot) – were studied. Results: Roncoleukin+Ingaron was the most effective combination that inhibited tumor growth during the therapy and after it by 30-38% and had a marked antimetastatic effect, up to complete absence of metastases in all animals. Morphological study demonstrated that thymus was the most active in this group of mice (a well-developed cortex with densely packed thymocytes); apparently, it was the cause for the increased levels of T-cells in the blood and Th (CD3e+CD4+) in the spleen of tumor-bearing mice compared to controls. The spleen of the mice showed a well-developed white pulp with large follicles, and Th level was the maximal – 47.9±1.5%, while in other groups it ranged from 15 to 35%. Morphological study of tumors revealed extensive necrosis (up to 2/3 of the tumor area), leukocyte infiltration, bleeds, blood clots in the vessel lumen and degenerative changes in tumor cells in all combinations of immunomodulators. Melanoma structure in the control group was typical, and most mice developed small and large metastases, sometimes multiple ones with extensive lung lesions; spleen metastases were observed in some mice. Conclusions: The study demonstrated the benefits of a search for optimal combinations of cytokine-based immune drugs to influence effectively an experimental transplantable tumor.
Clinical features and factors associated with survival in mucosal melanoma.
Authors: Aliaga Llerena Karina Mayra , Muñiz Johana , Gomez Henry Leonidas , Neciosup Silvia P. 
Published: September 2018

e21082 Background: Mucosal melanoma (MM) is a rare, aggressive and poorly prognostic neoplasm compared to cutaneous melanoma (MC), probably due to the lack of knowledge about its pathogenesis, biology, risk factors, staging and treatment not yet well established. Our objective is to identify the epidemiological, clinical and pathological characteristics of mm and ocular melanoma (OM) as well as its relation with survival. Methods: Observational, descriptive and retrospective study. We analyzed data from 219 patients who met the selection criteria. Overall survival (OS) was estimated using the Kaplan-Meier method and the differences were assessed using the log rank test. In the statistical analysis SPSS 19 software was used and a p < 0.05 was considered statistically significant. Results: The mm represented 0.2% (219/98361) of the total number of patients diagnosed with cancer. MC represented 89% (N = 1598), mm 10% (N = 195) and MO only 1% (N = 24). mm predominated in females (N = 118 60%) with a median age of 63 years for both sexes. The most frequent sites were head and neck (N = 91 46.7%), anorectal (N = 68 34.9%) and vulva-vagina (N = 20 10.2%). The 5-year OS was 19.6% with a median of 21 months in the mm and 49.6%, with a median of 38 months in OM. Breslow > 4mm (p = 0.004), location (p = 0.019), distant disease (p = 0.004) and treatment type (p = 0.003) were considered as factors associated with survival. Conclusions: The MM, in the era of immunotherapy, is still considered one of the neoplasias with poor prognosis and poorly studied. It is vital to incorporate these patients into clinical trials in order to obtain real information on treatment efficacy, given the limited data available at the time.
Palliative care referrals and related outcomes among advanced cancer patients: A study revealing our institutional shortcomings.
Authors: Sedhom Ramy , Barile David 
Published: September 2018

e21506 Background: Palliative care (PC) has an important role in the care of cancer patients at the end of life. Unfortunately, referral occurs very late in the illness trajectory, often within days of patient death. We examined palliative care referral among advanced cancer patients and associated outcomes during their final 2 weeks of life at our academic medical center. Methods: We reviewed the medical records of 269 cancer inpatients with solid malignancies that died in the past three years at our institution. We retrospectively compared patients who accessed palliative care services with those who did not. A multivariate logistic regression model including age, gender, type of cancer and metastatic status was conducted. Results: 74/269 patients (28%) had a palliative care consult prior to death. The most common cancer types were respiratory (26%) and gastrointestinal (21%). Patients with breast and gynecologic malignancies had significantly greater referral to palliative care services. The overall aggressiveness of care for the last year was significantly less (p = 0.003) for patients who were referred to palliative care. Patients referred to PC received less chemotherapy in the last 2 weeks of life (8% versus 21%, p < 0.001). We found that patients who were not referred to palliative care services experienced death more frequently in the ICU (16% versus 2%, p < 0.001), and in the emergency room (12% versus 1%), p < 0.001). Conclusions: Despite increased awareness of the importance of palliative care, and their overall improvement in survival among cancer patients, there are still disparities regarding access to palliative care and location of death. Patients receiving palliative services receive less aggressive interventions during their 2 last weeks of life and are less likely to die in the intensive care unit or emergency room. Quality improvement projects are underway addressing our shortcomings to palliative care services for our patients with advanced malignancies.
Participation of elderly gynecological cancer patients in clinical trials.
Authors: Prieske Katharina , Trillsch Fabian , Oskay-Oezcelik Gulten , Chekerov Radoslav , Schoening Eva-Maria , Oliveira-Ferrer Leticia , Grimm Donata , Kuerti Sasha , Suling Anna , Schmalfeldt Barbara , Sehouli Jalid , Mahner Sven , Woelber Linn Lena 
Published: September 2018

e21520 Background: Elderly patients (pts) are underrepresented in clinical trials in gynecological cancer, even though they are disproportionally often affected. This study aimed to evaluate disposition and apprehension of elderly pts towards study participation. Methods: 112 elderly gynecological cancer pts (median age 70; range 65-92) were surveyed in a multicenter cross-sectional study. Besides fitness, state of disease, education and domestic situation, questions aimed at the general willingness to participate in a clinical trial. Personal reasons for rejection and suspected advantages/disadvantages that might evolve from participation were inquired. Results: Willingness to participate in a study was generally high (66.1%, 74/112). 42/112 (37.5%) had given their consent to participation in a study before, 12.5% (6/48) refused even though they were offered participation. Reasons for potential study participation were: ‘better monitoring of the disease’ (51/112), ‘better medical care’ (35/112), ‘to help medical research’ (31/112), ‘better medication’ (27/112) and ‘because of my doctor’s recommendation’ (17/112). Reasons for potential refusal were: ‘too time consuming’ (19/112), ‘fear of side effects’ (17/112), ‘misuse as experimental animal’ (14/112), ‘long distance to clinic’ (11/112) and ‘too little or unclear information’ (7/112). 26.1% (29/112) of pts stated, that they had ‘no objection’ against study participation. The question if pts anticipated having a longer life due to study participation was answered with ‘yes’ or ‘rather yes’ in 33.9% (38/112), 23.2% answered ‘no’ or ‘rather no’ (23.2% undecided). No relation between willingness to participate in a study and general fitness (p = 0.311), education (p = 0.631) or domestic situation (p = 0.195) could be observed. However, with increasing age, willingness decreased (p = 0.029). Conclusions: Elderly pts are generally willing to participate in clinical studies regardless of their fitness or educational background. Benefits of participation seem to be unclear among a majority of potential study participants. Therefore it might be decisive to provide more general information regarding benefits and safety for the elderly pts in a clinical trial.
The association of comorbid conditions and BMI on overall survival in geriatric breast cancer patients.
Authors: Desai Meghna R. , Iqbal Muhammad , Manthri Sukesh , Robinson Kathy , Mocharnuk Robert S. 
Published: September 2018

e21525 Background: Breast cancer is the most common cancer and the second leading cause of cancer death in women. More than one-half of all women diagnosed with breast cancer are older than 65 years, and the incidence increases with age. Geriatric cancer patients also have higher comorbidity than the general cancer population. Patients with 3 or more comorbid conditions had a 20-fold higher rate of mortality from causes other than breast cancer. The purpose of this study was to determine whether specific comorbidities associated with specific organ systems, in addition to increased BMI, resulted in decreased survival. Methods: In this retrospective analysis, 269 patients with histologically confirmed invasive or in-situ breast cancer and above 65 years of age at the time of diagnosis were eligible. Patient comorbidities were recorded by system, including cardiovascular, renal, pulmonary, endocrine, neurologic, psychiatric and other systems. Patient BMI was also recorded. The primary outcome was overall survival (OS). Survival analysis was conducted by Kaplan Meier estimation and Cox proportional hazards regression analysis. Results: Patients with renal comorbidities were found to have decreased OS, disease free and progression free survival compared with rest of the population (HR 2.65, p = 0.023; HR 2.71, p = 0.021; HR 27.5, p = 0.019). For patients with cardiovascular (HR 1.46, p = 0.479), pulmonary (HR 1.63, p = 0.176), endocrine (HR 0.99, p = 0.991), neurologic (HR 1.92, p = 0.15) and psychiatric (HR 1.68, p = 0.187) comorbidities, there was no significant difference in OS compared with their counterparts. Patients with 4 or more systemic comorbidities had decreased OS compared with patients with either 1 or 2 systemic comorbidities (HR 0.178, p = 0.012; HR 0.404, p = 0.038). There was no significant change in OS with increased BMI (HR 0.998, p = 0.871). Conclusions: In patients with newly diagnosed breast cancer age 65 or older, those with renal comorbidities were found to have decreased OS, DFS and PFS. Patients with 4 or more systemic comorbidities also had decreased OS compared with those who had 1 or 2 comorbidities. Other comorbidities and BMI did not affect OS in these patients.
Tumor biologic characteristics and clinical outcomes in geriatric patients with breast cancer.
Authors: Manthri Sukesh , Iqbal Muhammad , Robinson Kathy , Mocharnuk Robert S. , Desai Meghna R. 
Published: September 2018

e21526 Background: The probability of dying from breast cancer increases from 0.2% to 2% annually for women once they reach 70 years of age. However there is limited age-related information available about tumor biologic characteristics (TBCs) and clinical outcomes among elderly patients (pts). The purpose of this study was to analyze the impact of TBCs on clinical outcomes in a single institution's geriatric breast cancer pts. Methods: An institutional database of a total of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 years or older at the time of diagnosis was reviewed in an IRB approved fashion. Tumors were assessed for Nottingham grade, stage, ER/PR status, HER-2 status, tumor histology, lymphovascular invasion and nodal status. Kaplan-Meyer and Cox proportional hazards methods were used to calculate overall survival (OS). Results: Breast cancer was seen equally in both breasts: left n = 130 (48.3%), right n = 132 (49.1%). Most tumors were located in the upper outer quadrant (n = 122, 45.35%). TNM clinical stage Tlc was identified in 79 pts (29.36%), Tlb in 55 pts (20.44%), T2 in 54 pts (20.07%) and no nodal involvement in 146 pts (54.27%). Nottingham Grade 2 (n = 120, 44.60%) and invasive ductal carcinomas (n = 152, 56.50%) were diagnosed most often. Tumors were more frequently ER+ (n = 237, 88.10%), PR+ (n = 210, 78.06%), and HER2-negative (n = 219, 81.41%). There was no statistically significant increase in OS based on location of tumor (P = 0.9796) and tumor histology (invasive ductal vs invasive lobular cancers, P = 0.1143). Node negative breast cancers were associated with increased OS (P = 0.0014). Grade 2 tumors were associated with increased OS compared to Grade 3 tumors (P = 0.0112). ER+ and PR-negative tumors were associated with decreased OS in both short term and long term follow up (P = 0.0083 & P = 0.0254). Conclusions: In pts 65 years of age or older with newly diagnosed breast cancer, lack of nodal involvement is associated with increased OS. Prognosis for ER+ and PR-negative tumors is worse compared to ER+ and PR+ tumors. Nottingham Grade 2 tumors have better OS compared to Grade 3 tumors. Location of tumor and tumor histology are not associated with increased OS.
Endoscopic ultrasound: A safe procedure for elderly oncology patients?
Authors: John Elizabeth S. , Razjouyan Hadi , Singhal Nakul , Chokhavatia Sita , Tilara Amy 
Published: September 2018

e21531 Background: Endoscopic ultrasound (EUS) has many indications in the management of gastrointestinal tumors, and has become pivotal in guiding therapy. While studies show that surgery in the elderly with malignancy causes increased morbidity and costs, no studies exist to assess the safety of EUS in this group. Methods: A single center retrospective analysis of patients who underwent EUS by two advanced endoscopists from April 2015 to December 2015 was performed. Patient demographics, procedure indications, final diagnoses, procedure length, sedation type, ASA classification, and intra-procedural complications, peri-procedural (immediate) complications, and post-procedural (24 hours after) complications were collected. Statistical analysis was done with Chi-square and comparison of mean tests. Results: 111 patients were identified with either a confirmed or suspected gastrointestinal malignancy out of 200 total patients included in the study. These patients included 38 with suspected pancreatic adenocarcinoma, one of which revealed pancreatic gastrinoma; 27 with suspected gastric adenocarcinoma or for staging; 17 with suspicious esophageal masses or for staging of squamous cell carcinoma or adenocarcinoma; 9 duodenal masses, 3 colorectal masses, 2 mediastinal masses, 1 biliary mass, 3 potential metastatic lesions to the GI system, and 8 patients with abdominal lymphadenopathy suspicious for malignancy. Patients over 65 years tended to have a lower risk of intra-procedure complications compared to those under 65, irrespective of all other factors including gender, performing endoscopist, and length of procedure (8.3% vs. 18.3%, p = 0.09). No significant differences were found in peri- and post-procedural complications between the over age 65 and under age 65 groups (4.0% vs. 1.6%, p = 0.44; 5.9% vs. 15.2%, p = 0.19). Conclusions: Due to the poor performance status often seen in the elderly oncology population, complications often arise from invasive procedures leading to increased morbidity, mortality, and costs. EUS aids in diagnosis, staging, and therapeutic decision-making of patients with gastrointestinal malignancies, and as this study shows, can be performed in older patients without incurring increased risks.
Basal physical inactivity as an independent risk factor for early death in elderly cancer patients: A prospective Brazilian cohort study with 608 patients.
Authors: Telles O Lima Jurema , Mello Maria Julia Gonçalves , Bergmann Anke , Bezerra Mirella Rebello , Cavalcanti Zilda , Sales Letícia telles , Thuler Luiz Claudio Santos 
Published: September 2018

e21534 Background:With the aging of the population, cancer in the elderly people is becoming an increasingly common and complex health problem, particularly in low-middle-income countries, where physical inactivity and obesity have also been challenging and correlated with cancer and aging. The aim of this study is to determine whether the baseline physical inactivity per International Physical Activity Questionnaire(IPAQ) is an independent factor of premature death in the first six months.Methods: prospective cohort study of elderly patients (≥ 60 years). Participants with a recent diagnosis of cancer were from eight community hospitals and one cancer center in Northeast Brazil and were recruited during their first medical appointment at the outpatient oncologic clinic. Sociodemographic and clinical variables were determined and baseline comprehensive geriatric assessment (CGA) was conducted including IPAQ and Time Up and Go test. Data were analyzed using multivariate Cox proportional hazards models, overall survival was estimated using the Kaplan–Meier method and survival curves were compared using the Log rank test. Results:From 2015-2016, 608 patients, mean age 71.9 (SD ±7.4; range 60-96), 50.7% male, were enrolled. Main diagnoses were prostate cancer (29.1%), digestive system cancer (25.5%) and breast cancer (16.0%). 40.3% were considered obese/overweight (BMI ≥ 27). 42.1% were considered physically inactive per IPAQ. The mean of the Time Up and Go test on the physically inactive group by IPAQ was of 13.11s (SD ± 6.5), and of 22.72s (SD± 16.7) on the physically active one. After adjustment for age, site of cancer and cancer stage, the multivariate regression Cox model showed that being physically inactive is an independent predictor for early death (HR = 2.35, 95% CI: 1.50‒ 3.66, p < 0.001).Conclusions:Physical inactivity at admission was identified as a significant predictor of risk for premature death in elderly cancer patients. The evaluation of the physical activity should be incorporated into regular geriatric assessment of elderly cancer patients.
Machine learning algorithm for predicting longer postoperative length of stay among older cancer patients.
Authors: Shahrokni Armin , Rokni Seyed Ali , Ghasemzadeh Hassan 
Published: September 2018

e21536 Background: To predict longer postoperative length of stay (LLOS) among older cancer patients, we have used a novel method to assess factors associated with this outcome. Methods: Our study was based on 47-item electronic Rapid Fitness Assessment (eRFA) data presented last year (Shahrokni, et al. (J Clin Oncol 34, 2016 (suppl; abstr 10011). LLOS was defined as LOS ≥8days.We used machine learning model to explore the relationship between > 70 pre, intra, and postoperative variables with LLOS. A filter-based variable selection algorithm was utilized to only identify the most important variables as defined by information gain. We computed the mutual information between each variable and the LOS, and ranked them from high to low gain. To create an interpretable machine learning model, we used decision tree classifier. The tree started with the most informative variable as the root and branches based on a threshold value such that the entropy decreases by most. Results: In a cohort of 492 postoperative older cancer patients (median age 80), the variable selection algorithm showed that only 5 variables are sufficient for predicting LLOS with an accuracy of 77.2%, sensitivity 81.6% and specificity 61.31% in all patients. The algorithm started with operation time (OT) of < or > 4 hrs. For example, patients with OT > 4 hours and social activity limitation (SAL) > 7 were 78% likely to have LLOS. Patients with SAL ≤ 7 and OT > 5 hours were 75% likely to have LLOS. Patients were 71% likely not to have LLOS if OT < 4 hours and SAL ≤ 7. To avoid the effect of potential data collection errors and increase the accuracy of the model, we used the Bootstrap Aggregating (bagging) method which ensembles the decision of a set small trees. Particularly, we generated 3 datasets from randomly sampling patients from current dataset with replacement and built 3 different trees. As a result of combining 3 short trees we reach the accuracy of 83.2% with sensitivity 83.9% and specificity 82.4%. Conclusions: Machine learning model could be helpful for predicting LLOS among older cancer patients. Prospective studies are needed to validate this method in different academic and community settings.