bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-center experience with ipilimumab in patients with pretreated advanced melanoma.
Authors: Wilgenhof Sofie , Seghers Amelie Clementine , Du Four Stephanie , Lienard Danielle , Salmon Isabelle , Del Marmol Veronique , Neyns Bart 
Published: March 2020

e19026 Background: Ipilimumab (IPI) is a CTLA-4 blocking mAb with established activity in patients (pts) with advanced melanoma. Methods: Observational study on the outcome of advanced melanoma pts treated with IPI in an expanded access program (EAP) at a single-center. Results: Fifty pts initiated IPI (3 mg/kg q3wks x4, allowing for reinduction after a PFS of >24 wks). Baseline characteristics: 28M/22F, m50y, Stage: 1x IV-M1a, 2x -M1b, 47x -M1c; 44 pts skin-, 2x mucosal-, and 4x unknown primary melanoma; WHO-PS 0/1/2: 17-, 25-, 8 pts; LDH >ULN 33 pts; CRP >ULN 29 pts; ALC<1000/mm³ 15 pts; all pts were pretreated with dacarbazine and 16 pts for brain metastases. Thirty-one pts completed IPI-induction; 8/11 pts offered reinduction completed the planned 4 administrations (treatment ongoing in 1pt). Most immune-related adverse events (irAE) were generally mild/reversible; CTCAE gr3 irAE: diarrhea/colitis (3), hepatitis (1), hypophysitis (1), pancreatitis (1) and Guillain-Barré syndrome (1); no grade 4/5 irAE. BORR by mWHO-criteria: 1 CR, 3 PR and 4 SD (disease control rate [DCR]: 16%). BORR by immune-related response criteria (irRC): additional 2 PR and 3 SD (DCR: 26%). In 5/10 evaluable pts a similar or lower total tumor burden was obtained following reinduction. Two pts who experienced gr3 irAE during induction did not experience the same irAE at reinduction. After a median follow-up of 18 mths (range 7.5-19.3), 32 pts have died. Six- and 12-mths OS were 53% (95% CI 40-67) and 45% (95%CI 31-59) respectively. Disease control with IPI has been maintained in 8 pts (of which 4 received reinduction) after a median follow-up of 17 mths (range 12-17). Elevated CRP (>5x the upper limit of normal [ULN]) was the only independent baseline co-variable (HR 0,10; 95% CI 0,04-0,25; p 0.001). An ALC of <800/mm³ at week 7 and disease-control by irRC post-induction significantly correlated with OS. Conclusions: This single-center experience with IPI in an EAP for pts with advanced pretreated melanoma is comparable with that of prospective studies. Reinduction therapy seems important for long-term disease control in responding pts. Baseline CRP and ALC at week 7 deserve further evaluation as a prognostic and/or predictive (surrogate) markers.
C-kit, B-raf, and N-ras mutations in melanoma subtypes.
Authors: Pracht Marc , Mogha Ariane , Fautrel Alain , Lespagnol Alexandra , Mouchet Nicolas , Le Gall Francois , Oger Emmanuel , Galibert Marie-Dominique , Lesimple Thierry 
Published: March 2020

e19037 Background: The recent understanding of melanomas’ molecular pathways improved their classification and clinical strategies. Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alterations being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are present at low rate (20-40%) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skins. C-kit mutation pattern is complex with four exons being affected leading to numerous mutations. Because c-Kit targeted therapy is a critical clinical issue, we aimed to identify the most frequent mutations to propose appropriate screening test and adapted therapy. Methods: 186 melanoma samples corresponding to an homogeneous white-caucasian population (Brittany, France) were screened. c-Kit exons 11, 13,17 and 18 were sequenced, c-Kit copy number was quantified by q-PCR and level of c-Kit determined by immunohistochemistry (CD117). Samples were also analyzed for B-Raf mutations (codon 464, 466, 469, 600) and for N-Ras mutations (codon 12, 13, 61) by pyrosequencing. Results: Detectedmutations are shown in the table. Uveal melanomas (n=13) were never mutated. These mutations were never overlaped and comparable profiles were obtained between the primary tumour, nodes or metastatic lesions from a same patient. Conclusions: C-Kit mutations are much less common than in other previously described populations especially for MM or ALM. B-Raf/N-Ras mutations appeared also less frequent than waited in non-CSD , reaching 46% in SSM. Interestingly our population presents a high incidence of N-Ras mutations, especially in SSM and NM. Screening of B-Raf/N-Ras mutations is fundamental not only for SSM but also for NM, CSD and ALM for prescribing targeted therapies such as MEK-inhibitors. [Table: see text]
Clinical behavior and prognosis of lymph-nodal Merkel cell carcinoma (MCC) in the absence of a primary tumor.
Authors: Albertelli Manuela , Faggiano Antongiulio , Grimaldi Franco , Ameri Pietro , Palmieri Giovannella , Scarpelli Giovanni , Federico Piera , Bellevicine Claudio , Troncone Giancarlo , Grillo Federica , Minuto Francesco , Crino Lucio , Colao Annamaria , Ferone Diego , Ferolla Piero 
Published: March 2020

e19038 Background: MCC is a rare cutaneous neuroendocrine neoplasm characterized by an aggressive behavior and a high recurrence rate, generally associated with poor prognosis. Nodal and distant metastases are frequent. Aim of this study was to report histological, clinical and prognostic features of a series of 12 patients with nodal MCC in the lack of evidence of a primary. Methods: The cases were collected from a multicentric database: mean age at diagnosis was 67 years; F:M ratio was 1:1.4; mean follow up was 54 months (8-108). Involved nodal sites were: inguinal (9) and axillar (3). All cases had typical MCC immunoprofile: neuroendocrine (CgA, NSE, Syn) and epithelial (CK 20 dot-like) marker positivity. Complete and extensive clinical, dermatologic, radiologic and endoscopic work-up was performed. All patients underwent surgical excision; in one case chemotherapy, in another case biotherapy and in one further case radiotherapy was administered. Results: All cases were in stage III of disease, according to AJCC. All patients were alive without recurrence at the time of the study. The overall mean survival was 52 months. The 4-yr survival was 100%. Conclusions: In patients with nodal metastases of MCC in the absence of a primary lesion, survival seems to be more similar to stage I rather than stage III, since 4-yr survival is reported about 60% for stage III disease in MCC. This finding must still be completely explained. Regression of a small skin primary with nodal metastases or alternatively a primary nodal MCC might be hypothesized. In conclusion, the unknown primary nodal metastatic skin MCC seems to be associated with a more favorable prognosis.
Preferential enrichment of myeloid-derived suppressor cell subsets in patients with metastatic melanoma.
Authors: Meyer Christiane , Cagnon Laurene , Montandon Nicole , Berthod Grégoire , Leyvraz Loredana , Michielin Olivier , Romano Emanuela , Speiser Daniel E 
Published: March 2020

e19050 Background: Myeloid derived suppressor cells (MDSC) are key immunosuppressive cells enriched in peripheral blood during chronic inflammation. While these cells have been extensively studied in mice, their human counterparts are less well characterized. Several MDSC populations have been identified in cancer patients, depending on tumor type and experimental settings. MDSC include immature macrophages, granulocytes and dendritic cells, at different degree of maturation, from immature CD33+, to mature CD14+ and CD15+HLA-DR- cells. The goal of this study was to characterize myeloid cells in melanoma patients compared with healthy donors (HD) to identify inflammation-mediated alterations involved in melanoma progression. Methods: PBMC were isolated by Lymphoprep gradient centrifugation from fresh blood samples of patients with malignant melanoma. We performed 9-color FACS staining of the freshly isolated cells. Results: CD15+ granulocytic MDSC are enriched in the mononuclear cell layer after gradient centrifugation, together with the CD14+ monocytic MDSCs. They display significantly different sedimentation abilities compared with neutrophils. Furthermore, CD14 and CD15 were partially co-expressed by the monocytic and granulocytic MDSC subsets, respectively. Our data show that CD14+HLA-DR- monocytic and CD15+HLA-DR- granulocytic MDSC were significantly enriched in peripheral blood of metastatic melanoma patients, regardless of whether or not they received any prior therapy for metastatic melanoma. The more immature CD33+CD11b- subset was found at significantly lower frequencies in melanoma patients compared with HD. We found a trend for accumulation of non-classical CD14+CD16+ monocytes. However, the increased percentages did not differ significantly from HD. The frequencies of classical CD14+CD16- monocytes were unchanged. Conclusions: Melanoma is associated with increased frequencies of CD14+ monocytic and CD15+ granulocytic MDSC, and decreased frequencies of the more immature CD33+CD11b- cells. This finding demonstrates tumor-mediated changes in the composition of myeloid cells, which could influence response to treatment and clinical behavior of the disease.
Mechanism of action of ingenol mebutate gel in reconstructed human skin assessed by transcriptomics.
Authors: Zibert John Robert , Hoeyer-Hansen Maria Helena , Eriksson Andre Huss , Loevendorf Marianne Begtson , Matthews Josselyn , Litman Thomas 
Published: March 2020

e19056 Background: Ingenol mebutate (IM) gel topical applied once daily for 2-3 consecutive days, has recently been approved by FDA in treating actinic keratoses (AK), as a safe, tolerable and effective treatment. IM, a highly active biological diterpene ester, has shown in vitro and in vivo to induce a dual mechanism of action characterized by, first, cell death induced at high micromolar concentrations and, second, a protein kinase C dependent immune activation in the nanomolar range. The aim of this study was to investigate the mechanism of action of IM in reconstructed human skin (RHS). Methods: IM 0.05% gel or vehicle was applied topically to RHS (EpiDermFT) and normal pigskin and IM concentrations were measured after 2 and 24 hrs. In RHS, biopsies were obtained 1, 6 and 24 hrs after treatment and global transcriptomic profiling (Affymetrix HG 1.0 ST) was assessed. The analysis included transcription factor binding site (TFBS) and gene set enrichment analysis (GSEA). Results: We compared IM’s penetration through normal skin to RHS and found a 10-fold higher permeability in RHS, which likely models the increased permeability of AK lesions. Consequently we further investigated IM’s effects on RHS. Based on GSEA, we identified the major effects of IM to comprise: cell death, inflammation and wound healing responses, indicated by differential expression of e.g. caspases, DAPK1, chemokine ligands, HAS2, MMPs, SERPINs, ILs (and their receptors). A TFBS analysis identified E2F regulated genes as overrepresented, albeit in opposite directions in dermis (up-regulated) compared to epidermis (down-regulated). IM transiently activates PKC, and via this activation causes transcriptional silencing of E2F-responsive genes. The differential effect on dermis and epidermis could be due to different levels of PKC isoforms in the different skin layers. Indeed, a specific, inflammatory response was observed and several genes, including MMP10 and IL1R2, displayed a time-dependent increase in expression, reaching a maximum at 24h. Conclusions: In conclusion, IM displays pleiotropic effects, of which many are identified on a transcriptional level. Our data suggest involvement of in particular PKC, ERK2, and E2F regulated genes.
Performance status of patients with advanced melanoma over time in routine clinical practice.
Authors: Sadetsky Natalia , Zhao Zhongyun , Barber Beth , Wagner Volker Jean 
Published: March 2020

e19060 Background: Measurements of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) are widely used to assess disease progression, determine appropriate treatment and prognosis; however, ECOG-PS over time in routine clinical practice is rarely published. This study examined ECOG-PS in patients with stage III and IV melanoma during 1-year from diagnosis in community oncology clinics. Methods: Electronic medical records from 47 oncology clinics across the US were used for this analysis. Patients who had melanoma diagnosis, stage information, and ECOG-PS scores were included. Patient clinical, demographic, and treatment characteristics were described. ECOG-PS at diagnosis of stage III and IV melanoma and at every three months were analyzed. Mixed model analysis was undertaken to examine changes in ECOG-PS over time. Results: A total of 266 patients (102 stage III and 164 stage IV) were included in this study. At baseline, stage IV patients had significantly worse mean ECOG-PS scores than stage III patients (0.79 versus 0.35, p=0.001). In patients with both baseline and at least one post-diagnosis assessment (84 and 110 patients with stage III and IV, respectively), mixed model estimated mean ECOG-PS scores changed from 0.69 at baseline to 1.14 at 1-year for stage IV patients and were relatively stable for stage III patients (0.47 (baseline) and 0.54 (1-year)). There were 25 stage III and 43 stage IV patients who received drug treatments for melanoma. The majority of stage III patients (84%) received Interferon only; while 44.2% of stage IV patients received carboplatin+paclitaxel, 32.6% dacarbazine, and 11.6 % cisplatin. Among drug treated patients with stage IV, worsening ECOG-PS over time (from 0.87 at baseline to 1.14 at one year) was observed. Conclusions: In patients with advanced melanoma treated in community oncology practices, worse ECOG-PS scores and faster deterioration were observed for patients diagnosed with stage IV compared to stage III. Even in patients treated with systemic therapies, worsening ECOG-PS was also observed over time.
Assessing the value of an optional radiation oncology clinical rotation during the core clerkships in medical school.
Authors: Zaorsky Nicholas George , Malatesta Theresa Maria , Den Robert Benjamin , Wuthrick Evan John , Werner-Wasik Maria , Shi Wenyin , Ahn Peter H. , Dicker Adam , Anne Pramila R. , Bar-Ad Voichita , Showalter Timothy Norman 
Published: March 2020

e19507 Background: Few medical students are given proper clinical training in oncology, much less radiation oncology. We evaluate the value of adding a radiation oncology clinical rotation to the medical school curriculum. Methods: In July 2010, Jefferson Medical College offered a 3-week radiation oncology elective rotation for third-year medical students during the core surgical clerkship. During 2010-2012, 52 students chose to enroll in this rotation. The rotation included outpatient clinics, inpatient consults, didactic sessions, and case-based presentations by the students. Tests of students’ knowledge of radiation oncology were administered anonymously before and after the rotation to evaluate the educational effectiveness of the rotation. Students and radiation oncology faculty were given surveys to assess feedback about the rotation. Results: The students’ pre-rotation test scores had an average of 64% (95% confidence interval [CI]: 61%, 66%), which improved after the rotation to 82% (95% CI: 80%, 83%; 18% absolute improvement). In exam question analysis, scores improved in clinical oncology from 63% to 79%, in radiobiology from 70% to 77%, and in medical physics from 62% to 88%. Improvements in all sections but radiobiology were statistically significant. Students rated the usefulness of the rotation as 8.1 (scale 1-9, 95% CI: 7.3, 9.0), their understanding of radiation oncology as a result of the rotation as 8.8 (95% CI: 8.5, 9.1), and their recommendation of the rotation to a classmate as 8.2 (95% CI: 7.6, 9.0). Radiation oncology faculty rated their belief that this rotation would be valuable to students as 8.2 (scale 1-9), that students had appropriate responsibilities in the clinic as 7.9, and that the lectures and meetings that students attended were at an appropriate level as 8.1. Conclusions: Integrating a radiation oncology clinical rotation into the medical school curriculum improves student knowledge of radiation oncology, including aspects of clinical oncology, radiobiology, and medical physics. The rotation is appreciated by both students and faculty. We recommend including exposure to radiation oncology as part of the core clinical curriculum for all medical students.
Cancer patients in the hospital damaged by the Japan earthquake and tsunami.
Authors: Morikawa Naoto , Yanagisawa Satoru , Iwasashi Hajime , Tabata Toshiharu , ABE Tatsuya , Nakamura Ryuji , Tabayashi Koichi 
Published: March 2020

e19508 Background: On March 11, the Great East Japan Earthquake hit the Sendai City. Water supplies and electric facilities were damaged seriously in many establishments, and our hospital was no exception. Because our hospital wards itself were also in the danger of collapsing, whole the oncologic patients were to be discharged. We investigated what became of the patients with cancer after the earthquake. Methods: We extracted the medical records of the patients with cancer, who were hospitalized when an earthquake occurred. Then, we retrospectively analyzed the destinations after the discharge and prognosis of each patient. Results: Among the 400 patients admitted, there stayed 75 patients with cancer, on March 11. Of these, the 75 patients were discharged to their home later, and the 48 patients were transferred to the other hospitals. The remaining four patients died in the hospital, all of which were due to their primary cancer. The earthquake did not cause any death. Although, most of the patients with cancer were relatively in good physical condition, their discharge to the home did not go on smoothly. Some patients could not make any contacts with their families, and others lost their houses because of the earthquake or resultant tsunami, all of which prevented them to return home. Public networks such as Disaster Medical Assistance Team (DMAT) did not have use for coordinating where the patients should be transferred, because they gave the first priority to the acutely-ill patients, such as trauma patients. Transfer to another hospitals largely depended on the personal networking between each physicians. Conclusions: On the face of the national disasters, the current emergency care system must prioritize the acutely-ill patients, sometimes at the sacrifice of chronically-ill patients such as oncologic patients. It seems necessary to create the medical cooperation system for the patients with cancer.
Active combination with aprepitant, palonosetron, and dexamethasone for preventing emesis of anthracycline-containing regimens in patients with breast cancer.
Authors: Nakayama Yoshie , Ito Yoshinori , Takahashi Shunji , Hatake Kiyohiko 
Published: March 2020

e19512 Background: Anthracycline and cyclophoshamaide containing regimens for breast cancer are classified as highly emetogenic chemotherapy. Aprepitant (A), palonosetron (P), granisetron (G) or dexamethasone(D) are recommended as antiemetic drugs. However, it is uncertain which combination would be best effective. We have retrospectively examined the efficacy of these antiemetic drugs. Methods: We reviewed the medical records of 501 patients with breast cancer treated with anthracycline and cyclophoshamaide containing regimens between August, 2009 and September, 2010. The combination of GD were G: 3 mg on day1 (i.v.), 2 mg on days 2-6 (p.o.) and D: 16.5 mg on day1 (i.v.), 8mg on days 2-4 (p.o.). The AGD were A: 125 mg on day1 (i.v.), 80 mg on days 2-3 (p.o.), G: 3 mg on day1 (i.v.), 2 mg on days 2-6 (p.o.), and D: 13.2 mg on day1 (i.v.), 4 mg on days 2-4 (p.o.). The APD were A: 125 mg on day1 (i.v.), 80 mg on days 2-3 (p.o.), P: 0.75 mg on day1 ( i.v.), and D: 13.2 mg on day1 (i.v.), 4 mg on days 2-4 (p.o.). Results: The number of patients who were treated with GD, AGD, and APD were 170, 159, and 172, respectively. Complete response (CR) rate in acute phase (0-24h) or delayed phase (24-120h) and complete control (CC) rate in acute or delayed phase in each regimens were summarized in the table. AGD or APD was significantly superior to GD in CR rate of acute or delayed phase (P<0.01). Of note, CC rate of APD in acute phase was significantly superior to AGD (P<0.01). AGD or APD was significantly superior to GD in CC rate in delayed phase. Conclusions: The combination with APD was the most effective antiemetic therapy in patients who were treated with anthracycline and cyclophosphamide containing regimens. [Table: see text]
Health resource utilization and patient burden associated with SREs in a randomized controlled trial setting.
Authors: Body Jean-Jacques , Von Moos Roger , Saad Fred , Richardson Gary Edward , Brown Janet Elizabeth , Lipton Allan , Fizazi Karim , Ying Wendy , Goessl Carsten Dietrich , Richhariya Akshara 
Published: March 2020

e19514 Background: Bone metastases (BM) are common in patients (pts) with solid tumors and may result in skeletal related events (SREs) such as spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiation to bone (RT). SREs result in significant morbidity, debilitating pain, decreased health-related quality of life and increased health resource utilization (HRU). Data from 3 registrational phase 3 trials that showed superiority of denosumab over zoledronic acid in patients with solid tumors and BM were combined to assess HRU associated with different SRE types. Methods: Data through 41 weeks for pts with solid tumors and ≥ 1 BM enrolled in these randomized, active-controlled trials were included in this posthoc analysis. HRU were evaluated by SRE type and data were compared between pts with ≥ 1 on-study SRE and those not experiencing an on-study SRE. The index date for pts with on-study SREs was defined as the date that the first SRE was reported. The median time from randomization to incidence of first SRE for each SRE type was used to establish an index date for the control (no SRE) group. The HRU window encompassed a 3-month period (i.e.1 month before and 2 months after the index date) and was assessed by mean number of various types of medical visits during this window. Results: Data from 5,543 pts were included. PF was the most common type of first SRE (n=1,017), followed by RT (n=940), SCC (n=156), and SB (n=74). 3,618 pts did not have an on-study SRE. For all types of medical visits, HRU was higher for pts with an on-study SRE than those without (Table). Conclusions: SREs are associated with increased health resource utilization, reflecting an increased burden for patients with solid tumors and bone metastases. [Table: see text]