bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adoptive T-cell therapy combined with intra-lesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients.
Authors: Khammari Amir , Limacher Jean-Marc , NGuyen Jean-Michel , Saint-Jean Melanie , Quereux Gaelle , Brocard Anabelle , Peuvrel Lucie , Knol Anne-Chantal , Saiagh Soraya , Bataille Vincent , Dreno Brigitte 
Published: March 2020

e20022 Background: The purpose of this study was to evaluate the feasibility, safety and efficacy of adding intra-tumoral injections of TG1042 (Adenovirus 5 expressing Interferon-γ) to adoptive T cell therapy in patients with advanced stage melanoma. Methods: This was a monocentric phase I/II study. The main inclusion criteria were: stage IIIc/IV melanoma, age 18 to 75, at least one injectable metastasis. Tumor infiltrating lymphocytes (TILs) produced from a surgical biopsy of a lesion were infused on days 1 and 29 followed by IL2 injections (6M UI daily) for 10 days. TG1042 was injected at the dose of 5x1010 viral particles per lesion (in up to 6 lesions) every 2 weeks from day -15 to month 2 and then every month up to month 11 or progression. Primary objective was the safety of the procedure; secondary objectives included response according to RECIST and translational research. Results: Eighteen patients have been included. The TILs production was successful in 16 of them. Minor erythema at the TG1042 injection site as well as minor to moderate flu-like symptoms linked to IL2 injections were the most frequent adverse events observed. No grade 3 or 4 treatment related adverse events was recorded. Among the 13 patients evaluable for tumor response 4 patients (31%) had an overall objective response (2 complete, 2 partial), 1patient had a stable disease and 8 progressed. When considering only the injected lesions 6 (46%) had an objective response (3 complete, 3 partial), 3 had a stable disease and 4 progressed. Distant responses in non-injected lesions were observed for 2 patients. Translational research on cutaneous biopsies before and after injections (3 months) showed an increase of CD8 T lymphocytes, IFN-γ and STAT 1 expression in 3 patients. Conclusions: This study demonstrates that co-delivery of TILs and intra lesional TG1042 is feasible and safe. Stimulation of innate immunity by adenovirus expressing interferon-γ could contribute to reverse the immunotolerant profile of the tumour environment. These results support to further explore combined immunotherapies in the treatment of melanoma. Clinical trial information: NCT01082887.
Use of preoperative ultrasound (US)-guided fine needle aspiration cytology (FNAC) to identify positive sentinel nodes (SN) in melanoma.
Authors: Van Akkooi Alexander Christopher Jonathan , Siegel Petra , Gooskens Saskia , Schoengen Alfred , Sterry Wolfram , Eggermont Alexander M. , Voit Christiane A. 
Published: March 2020

e20035 Background: The surgical Sentinel Node (SN) is standard of care worldwide for the staging of AJCC stage I/II melanoma patients. It remains unclear if SN followed by early lymph node dissection in case of metastasis can lead to a survival benefit. Unlike other cancers, US-guided-FNAC has not been proven effective in melanoma. Aim was to analyze sensitivity (sens), specificity (spec), positive (PPV) and Negative (NPV) predictive values with use of the Berlin Morphology criteria, a low threshold for performing repeated FNAC and overnight cytology reports. Methods: Between 2001 and 2010 over 1,000 stage I / II consecutive melanoma pts have undergone US-FNAC prior to SN. All patients underwent lymphoscintigraphy prior to US-FNAC. Peripheral Perfusion (PP), Loss of Central Echoes (LCE), Balloon Shaped (BS) are the Berlin Morphology Criteria, which were registered. FNAC was performed (3-4x) in case any of these factors were seen. SN tumor burden was measured according to the Rotterdam Criteria. All patients underwent SN or LND in case of positive FNAC. Results: Mean/med Breslow thickness 2.59/1.57 mm (0.2 – 44 mm). Mean/med follow-up 39 / 32 months (0 – 115). Ulceration (ulc) present in 24 %. SN pos rate was 20.8 % (208 / 1000). 34.2% underwent FNAC. 8.9% was FNAC positive; this was 26% of all FNAC. Sens was 51%. Spec, PPV and NPV were 99%, 95% and 89%. Sensitivity was highest for T4 (76%) and in ulc (63%) tumors. PP, LCE, BS had sens of 51%, 37%, 24%. Sens of US-FNAC increased with increasing SN tumor burden (12% in < 0.1 mm to 61% in > 1 mm). PP was an early sign of metastasis (58% in < 0.1 mm mets). Threshold for pos FNAC was 0.4 mm in maximum diameter. 5-yr survival correlated to US-FNAC status (93% in neg, 51% in pos). 5-yr survival of pts with PP was 82% vs. 46% in BS vs. 92% in neg pts (P=0.001). Conclusions: US-FNAC according to the Berlin Morphology criteria can correctly identify half of the positive SNs, prior to the surgical SN procedure. PP is an early sign of metastasis, BS is a late sign. US-FNAC can significantly reduce the amount of unnecessary surgical SN procedures. US-FNAC sensitivity correlated with increasing T-stage, increasing SN tumor burden and ulc. US-FNAC can accurately predict survival.
Vemurafenib-associated bullous DRESS syndrome: A very severe cutaneous reaction.
Authors: Gey Aurelia , Jouary Thomas , Mateus Christine , Robert Caroline , Perro Gerard , Milpied Brigitte 
Published: March 2020

e20041 Background: Vemurafenib, a selective BRAF inhibitor, has recently demonstrated improved overall survival in metastatic melanoma. Frequent cutaneous side effects have been reported with vemurafenib, mostly non severe. We report the first case of bullous DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) related to vemurafenib. Methods: Case report: A 69 year old man presented with a BRAF mutated multimetasatic melanoma. Vemurafenib, 960 mg orally twice daily, was started in August 2012. Treatment was discontinued 1 month later because of a grade 2 rash and nausea. Treatment was re-introduced 10 days later with reduction of the dose, 480 mg twice daily. Four days later, the patient had fever, diffuse rash with pustular blistering and eosinophilia up to 1000/mm3. Despite withdrawal of vemurafenib, skin detachment appeared with extension on more than 90% of the body surface and erosions involving oral and genital mucosa requiring admission in intensive care burn unit. A skin biopsy revealed infiltration of the epidermis and the upper dermis with lymphocytic lichenoid vasculitis and focal necrolytic keratinocytes. Intravenous steroids were provided and lesions rapidly resolved with total epithelisation within 15 days. To date, the patient is still alive and undergoes active palliative care. Results: Discussion: DRESS syndrome is a severe drug reaction defined as an acute and severe heterogeneous rash with general symptoms, biological abnormalities, and visceral damages. It occurs from 3 to 6 weeks after drug administration. With a Kardaun score of 4, there were several arguments for a DRESS syndrome to vemurafenib: diffuse and acute rash occurring after 5 weeks of treatment, initial eosinophilia, aggravation of skin lesions despite withdrawal of the culprit drug, histological features and rapid improvement after steroid treatment. With more than 90% of body surface skin detachment, requiring treatment in burn center, the diagnosis was a very severe bullous DRESS syndrome. Vemurafenib was the only culprit drug in our case, as the patient did not received any other drug. Conclusions: Though toxic epidermal necrolysis has been reported yet with vemurafenib, no case of DRESS syndrome has been described to date.
Effect of microRNA-206 on G1 arrest by inhibition of CDK4, cyclin C, and cyclin D in melanoma cells.
Authors: Georgantas Robert W , Streicher Katie , Luo Xiaobing , Zhu Wei , Liu Zheng , Brohawn Philip , Morehouse Chris , Higgs Brandon W , Richman Laura , Jallal Bahija , Yao Yihong , Ranade Koustubh 
Published: March 2020

e20047 Background: MiR-206 has been implicated in a large number of cancers. However, its role in tumor biology is unknown and its biological function has yet to be fully characterized. To examine the role of miR-206 in cancer, we examined the expression of miR-206 in melanoma and identified potential target transcriptss that could be important for the progression of this disease. Methods: Using quantitative RT-PCR we compared expression of 364 microRNAs in melanoma skin biopsies skin from normal donors, melanoma cell lines, and normal melanocytes. The effects of miR-206 on cell growth, apoptosis, and cellular migration/invasion were determined using in vitro assays comparing melanoma cell lines to normal melanocytes. Putative mRNA targets of miR-206 were bioinfomatically identified, and empirically tested by luciferase-3’UTR reporter assays. The effect of miR-206 on the cell cycle of melanoma cells was assayed by flow cytometry. Results: Expression profiling of microRNAs in melanoma lesional skin biopsies compared to normal donor skin biopsies revealed numerous differentially regulated miRs. One such microRNA, miR-206, was significantly highly down-regulated in melanoma biopsies (-75.4-fold, p=1.7x10-4) compared to normal skin and normal melanocytes. Functional analysis showed that miR-206 substantially reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatic analysis identified the cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate mRNA targets of miR-206. Luciferase reporter gene assays revealed that miR-206 inhibits translation of CDK4, Cyclin D1, and Cyclin C. Consistent with this inhibition of CDK4 and Cyclin D1, miR-206 transfection induced robust G1 arrest in multiple melanoma cell lines. Conclusions: MiR-206 expression was decreased in melanoma tissue and cell lines compared to normal skin and melanocytes, respectively. Inhibition of Cyclin C, Cyclin D1 and CDK4 by miR-206 highlights its role in regulating cell cycle progression, a key aspect of melanoma progression. These observations support miR-206 as a potential tumor suppressor in melanoma, and possibly other cancers.
Outcomes and clinical markers associated with benefit from ipilimumab (Ipi) in patients with advanced melanoma: A retrospective single-institution study.
Authors: Zimmerman Zachary Franklin , Storer Barry , Godara Amandeep , Thompson John A. , Margolin Kim Allyson , Tykodi Scott S. , Rockhill Jason K. , Lee Sylvia Mina , Brown Anna , Patel Amila , Smith Jon , Bhatia Shailender 
Published: March 2020

e20048 Background: Ipi (anti-CTLA4 antibody) is associated with improved survival and durable responses in a subset of melanoma pts. However, the optimal dose and schedule remain unclear and an unmet need to identify predictors of clinical benefit exists. This retrospective study of pts at the University of Washington aims at gaining further insight into these questions. Methods: Efficacy and safety outcomes and baseline characteristics of 126 pts receiving single agent Ipi from 2006-2012 were subjected to univariate analysis. Efficacy endpoints included OS, PFS, ORR and Duration of Clinical Benefit (DCB) defined as the time from Ipi initiation until documented progression or change in therapy (to capture outcomes on non-trial pts). Immune-related adverse events (IRAEs), absolute lymphocyte count (ALC), concordance of disease response by metastatic site, and use of radiation therapy (RT) were also analyzed. Results: The median age was 57.7 yrs. The 3 mg/kg (N=84; 67%) and 10 mg/kg (N=42; 33%) cohorts matched well for standard prognostic criteria. The efficacy endpoints, including OS, PFS, DCB, and ORR (see table) were not significantly different for the 3 mg/kg and 10 mg/kg cohorts. However, grade III/IV IRAEs were more frequent in the 10 mg/kg group (33% vs 17%, p=0.04). There was a significant correlation between efficacy outcomes and development of IRAEs (see table). Baseline ALC or changes in ALC at 7 weeks post-therapy and concurrent RT administration did not significantly correlate with improved outcomes. Responses were concordant between CNS and non-CNS sites. Conclusions: Our data supports the currently approved dose of 3mg/kg. The development of IRAEs was significantly associated with clinical benefit and further confirmation of this association is warranted. Results of other exploratory analyses will be presented at the meeting. [Table: see text]
Maintenance interleukin-2 (IL-2) and sargramostim (GM-CSF) following high-dose IL-2 (HD IL-2) therapy for metastatic melanoma.
Authors: Chu Melinda Bernabe , Fesler Mark , Armbrecht Eric , Fosko Scott , Hsueh Eddy C. , Richart John M. 
Published: March 2020

e20049 Background: At our institution, patients with metastatic melanoma who achieve partial response (PR) to HD IL-2 therapy undergo monthly maintenance treatment with IL-2 and GM-CSF with the thought that the continuous stimulation of the immune system may improve response. Our aim was to describe our experience with maintenance treatment following HD IL-2 therapy. Methods: A retrospective chart review was performed on patients with metastatic melanoma seen at Saint Louis University from January 1999-June 2011 who were partial responders to HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) that received maintenance IL-2 therapy (continuous 42 hour infusion of three consecutive doses of 18,000,000 IU/m2 over 6, 12 hours, then 24 hours) and GM-CSF (daily subcutaneous injection of 125 mcg/m2 for 3 days) every 4 weeks for 13 cycles or until disease progression. Duration of response for this cohort was compared to established data for partial responders using the Mann-Whitney test. Results: Five patients were included in the analysis. Median duration of response was 9 months (3.9-53.4 months). Median overall survival was 20.6 months (15-53.4+ months). One patient who initially showed PR to HD IL-2 therapy converted to complete response during maintenance IL-2 and has the longest duration of response in the study dataset. Duration of response for the maintenance group (9 months) was longer than a benchmark of 5.9 months as reported in the literature and package insert for partial responders to HD IL-2 without maintenance therapy, p = 0.068. Conclusions: Subjects who received maintenance IL-2 and GM-CSF therapy had a longer duration of response compared to previous reports, which trended toward statistical significance in this small sample. Maintenance IL-2 and GM-CSF after HD IL-2 therapy may help to prolong partial response, possibly lead to conversion to complete response and is worthy of additional study.
The PI3K inhibitor BKM120 has potent antitumor activity in melanoma brain metastases in vitro and in vivo.
Authors: Meier Friedegund Elke , Niessner Heike , Schmitz Jennifer , Schmid Andreas , Calaminus Carsten , Pichler Bernd , Forschner Andrea , Flaherty Keith , Honegger Juergen Bernd , Dummer Reinhard , Tabatabai Ghazaleh , Weide Benjamin , Eigentler Thomas K. , Schadendorf Dirk , Quintanilla-Fend Leticia , Garbe Claus 
Published: March 2020

e20050 Background: In melanoma, the RAF-MEK-ERK and PI3K-AKT signaling pathways play a major role in melanoma progression and drug resistance. On the basis of significant improvement in overall survival, the BRAF inhibitor vemurafenib gained FDA approval for the treatment of patients with metastatic BRAFV600E mutated melanoma. However, vemurafenib appears to be less effective in melanoma brain metastases, and brain metastases are the most common cause of death in patients with metastatic melanoma. In our previous study we reported that the AKT survival pathway is hyperactivated in melanoma brain metastases. Methods: The current study aims to investigate the mechanisms of AKT hyperactivation and the antitumor activity of the PI3K inhibitor BKM120 in melanoma brain metastases in vitro and in vivo. Results: To simulate the tumor environment of brain metastases and extracerebral metastases, brain and matched extracerebral metastatic melanoma cells were stimulated by astrocyte- and fibroblast-conditioned medium, respectively. Both brain and extracerebral metastatic melanoma cells stimulated by astrocyte-conditioned medium showed higher AKT activation and invasiveness in a transwell matrigel invasion assay than cells stimulated by fibroblast-conditioned medium. The PI3K inhibitor BKM120 inhibited the phosphorylation of AKT and the growth of >10 newly isolated cell lines derived from melanoma brain metastases achieving growth inhibition rates of up to 80%. These effects did not depend on BRAF, NRAS or KIT mutation status. Furthermore, BKM120 potently induced apoptosis in brain metastatic melanoma cells and significantly inhibited the tumor growth of human brain metastatic melanoma cells in the brain of nude mice as shown by MRI scans. Conclusions: Brain-derived factors induce hyperactivation of the AKT survival pathway and promote invasiveness and drug resistance of melanoma cells in the brain. The PI3K inhibitor BKM120 inhibits activation of the AKT survival pathway and demonstrates potent antitumor activity in melanoma brain metastases in vitro and in vivo.
Circumvent anxiety of patients (CAP) while receiving chemotherapy at one-day hospital.
Authors: Kattan Joseph Gergi , Daher Alain , Assaker Lama jaoudat , Jreige Yolla Tanios , Aintouri Rachide Jamil , Eid Rouba 
Published: March 2020

e20500 Background: Transforming patient anxiety to comfort during chemotherapy delivery is the desire of every cancer care givers. For the first time, a beauty clinic services are offered to adult cancer patients, while receiving one-day chemotherapy. Methods: One-day unit at Saint Joseph hospital is an independent department including 12 beds and serving around 160 chemotherapy sessions per month. A professional physiotherapist in beauty care and relaxation massage offers her services for every patient during 15 minutes session at his own bed. CAP program was approved by Saint Joseph ethical committee and supported by Jane Nassar institute. Evaluation questionnaires were filled by randomly selected patients. Results: CAP program was initiated in August 2012. Around 10 patients per day were included. 90% of our patients welcome the program and participate. The majority of patients who refused participation at the first visit accept it during the second session. Men choose hands or feet relaxation massage and women usually face beauty care. 22 patients were randomly selected to fill the CAP-evaluation questionnaire. Among these 22 patients, 2 (9%) refused to participate in the program, one of them did not have a clear reason, the other attributed to a state of uncomfortable and depression. Among the 20 who participated, 90% had at least two sessions, 100% would advise other patients to participate, 95% of them believe that this service adds an advantage to delivered care and provides a restful atmosphere, and all of them encourage the department to continue to provide this service. Conclusions: Psychosocial support is almost lacking in the management of our patients leading to increase their anxiety while receiving chemotherapy. CAP program represents a unique experience and temptation in adult patients to circumvent their anxiety.
Is routine administration of standardized questionnaires that assess aspects of patients’ quality of life justified in medical oncology clinics?
Authors: Al-Saleh Khalid A. 
Published: March 2020

e20501 Background: increasing interest in the Quality of Life outcomes in cancer patients led to increase implementation of their use in routine clinical practice. The aim of this study is to review the scientific evidence behind recommending the use of quality of life (QoL) scales routinely in outpatient evaluation. Methods: systematic review for all published randomized controlled trials in English language between January 1, 1990 till December 1, 2010. Out of 479 articles (468 identified by electronic search + 11 articles identified by manual search), six trials satisfied the eligibility criteria: 1) the study was a randomized controlled trial (RCT) with randomization of patients or health care providers; 2) the findings of the administered questionnaire or scale (the intervention) were given to health care provider, and compared to standard care with no questionnaire administered (the control); 3) study was conducted in outpatient oncology clinics; and 4) an outcome was measured that related to i) QoL improvement, ii) reduction in morbidity, iii) reduction in stress for the patients, iv) improvement in communication between patients and health care provider, or v) improved patient satisfaction. Assessment for the quality of the study was done using the GRADE methodology. Results: serious methodological issues were affecting most of the trials. Overall the evaluation of the quality of the evidence from these identified trials suggests that there is a weak recommendation to use QoL scales in routine oncology practice to improve communication between physicians and patients. Conclusions: The routine use of such tools in the outpatient settings at improving the patient outcome or satisfaction cannot be recommended based on the available evidence. The potential harm with the excess use of resources needed to implement, collect, store, analyse, and present such data to health care providers should be also considered. Further research and better designed trials is required using recent methodological techniques (such as item-response theory based questionnaire and cluster randomization) might help to reach an answer to this question.
Personality traits in Turkish patients with cancer.
Authors: Turhal Nazim S. , Satici Celal , Cinar Caner , Kinar Abdullah , Demirhan Salih 
Published: March 2020

e20502 Background: This study was planned to investigate the personality traits of cancer patients in different treatment settings, and to correlate the demographics with the personality features. Methods: A total of 237 patients referred either to Marmara University School of Medicine (MUSM) Oncology Outpatient Unit or to the private office of the faculty between March 10th and April 22nd, 2010 were enrolled in the study. Big Five Mini Test was used to evaluate the 40 personality traits filled by patients. Results: The study group consisted of 98 males (41.35%) and 139 females (58.65%) with a mean age of 51. Out of 237 patients, 73.9% had an educational level beyond the junior high school, and 47.3% of all patients reported a positive family history for cancer. A significant difference in terms of reconcilability, extraversion, and responsibility was observed between patients admitting to the university outpatient clinic and the private office (p<0.05). Reconcilability and extraversion were found to differ between genders significantly (p<0.05). The description of the patient by him/herself or by its relatives displayed a significant difference in terms of openness (p<0.05). Parameters such as educational level, family history of cancer, age and marital status showed no relevance with their characters. No discordance was observed between the self-analysis of the patient and the patient’s relatives. Conclusions: This is the first such study conducted in Turkish cancer patients and they found to be typically highly reconcilable and responsible, moderately stable, open and extraverted.