bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictable clinical responses to sorafenib in stage IV uveal melanoma.
Authors: Kaempgen Eckhart , Schmid Martina , Erdmann Michael , Keikavoussi Petra , Strobel Deike , Schuler-Thurner Beatrice , Schuler Gerold 
Published: March 2020

e19032 Background: Uveal melanoma is an orphan disease with poor prognosis, once metastasized. There is currently no approved systemic treatment and all clinical trials so far failed to significantly improve OS in stage IV uveal melanoma patients (see results of the EORTC 18021 trial, abstract 95725). Sorafenib is a pleiotropic kinase inhibitor targeting tumor metabolism and related neoangiogenesis. Although sorafenib failed as monotherapy in metastasized melanoma, results from small phase II trials have indicated synergism with chemotherapy in some patients. We therefore offered compassionate use treatment with sorafenib to patients with documented progressive stage IV uveal melanoma after fotemustine iv or HIA treatment (EORTC 18021 trial). Methods: Sorafenib 400 mg orally bid was combined with fotemustine 100 mg/m² at 3 week intervals to treat a total of 7 patients with metastatic uveal melanoma. Patients were closely followed by repeated analyses of serum tumor markers and ultrasound scans of liver metastases. Complete staging by CT/MR scans was done every 3 months. Results: 3 of 7 patients with initially elevated tumormarkers showed an early rapid drop in serum MIA and/or S100 within two weeks of sorafenib treatment followed by partial responses and long term stabilization of the disease up to 20 months. Responder patients could also be identified by a rapid drop in tumorperfusion as shown by contrast enhanced ultrasound of liver metastases. Due to hematologic toxicity treatment had to be modified in all responder patients. Neither reduction of sorafenib dosage to 200 mg orally bid nor omittance of fotemustine treatment resulted in early disease progression, pinpointing potential high sorafenib responsiveness in uveal melanoma patients. Conclusions: Patients with stage IV uveal melanoma may benefit from treatment with the kinase inhibitor sorafenib. Our observations suggest selection of responder patients by early drop of elevated tumor markers S100 / MIA and early drop in tumor perfusion. Stimulated by these data a first phase II trial investigating sorafenib in uveal melanoma patients has been initiated in Germany (ClinicalTrials.gov NCT0137702: A Study of Sorafenib in Patients With Chemonaive Metastatic Uveal Melanoma (STREAM).
Analysis of BRAF, NRAS, cKIT, and EGFR alterations in melanoma lung metastases.
Authors: Ulivieri Alessandra , Cardillo Giuseppe , Manente Liborio , Mancuso Andrea Petricca , Vigna Leonardo , Gasbarra Rita , Leone Alvaro 
Published: March 2020

e19033 Background: About 25% of pts will eventually develop lung metastases from primary melanoma. Activating mutations in BRAF, NRAS, CKIT and EGFR genes are involved in melanoma progression. Trials with drugs targeting oncogenic BRAF in melanoma have shown that a V600E mutation may identify a subgroup of pts with a high response rate. Methods: We analysedtheprevalence of BRAF, NRAS and CKIT mutations by direct sequencing and of EGFR copy number alterations by FISH, in pts affected by melanoma lung metastases, and explored their correlation with lung metastasis-free survival (LMFS) and post surgical progression-free survival (psPFS). Results: Over 10 years, 33 cases of pts with melanoma lung metastases were diagnosed at our institution, of which 22 underwent surgery with curative intent. The mean age was 64 years, and 19 (57.5%) were male. 51% carried a BRAF V600E mutation while 18% had a NRAS codon 61 mutation. The two events were mutually exclusive. No alterations were observed in exon 11 of the CKIT gene. FISH analysis indicated an EGFR low amplification in 3 cases and chromosome 7 polysomy in 13 cases. The presence of a BRAF V600E mutation was associated with a longer LMFS (median 6.1 vs 4.4 years, p<0.05), but it had no impact on psPFS (26.9 vs 29.6 months, p=0.6). NRAS mutations were associated with a reduction in both LMFS (3.7 years vs 4.7 years, p = 0.008) and, more significantly, in psPFS (12,5 months vs 41,1 months, p = 0.005; hazard ratio, 2.7). Conclusions: The frequency of mutations in BRAF (51%) and NRAS (18%) observed in lung metastatic melanomas was similar to the rates reported in other metastatic sites. BRAF mutations don't appear to be related with a more aggressive clinical course, while NRAS might be an independent negative prognostic factor after resection of melanoma lung metastases. The presence of BRAF mutations should be tested in melanoma lung metastases to identify the patients eligible for anti BRAF targeted therapy.
An imaging study of vemurafenib in patients with BRAFV600-mutated metastatic melanoma.
Authors: Lastoria Secondo , Grimaldi Antonio M , Aloj Luigi , Simeone Ester , Romano Anna , Caraco Corradina , Curvietto Marcello , Esposito Assunta , Caraco Corrado , Mozzillo Nicola , Torri Valter , Ascierto Paolo Antonio 
Published: March 2020

e19034 Background: Targeted therapy against the mutated form of BRAF V600 is a proven effective therapy for melanoma. Objective of this exploratory study was to describe the change over time of PET-scan results and verify the association of PET-scan examination with the objective response (OR) (defined by RECIST criteria) in melanoma pts treated with vemurafenib. These preliminary results reported here regards the description of changes over time of PET-scan. Methods: Patients treated with vemurafenib at our institution were considered eligible. Patients were evaluated with PET-scan at baseline and at day 7, 15 and 30 from the start of therapy. Maximal Standardized Uptake Value (SUVmax) and Total Lesion Glycolysis (mean SUV x lesion volume) were recorded and compared for single lesions in the 4 exams. Differences between each PET-scan performed during therapy and baseline were calculated and coded as yes/no response basing on predefined criteria. Association of PET responses and achievement of OR were estimated by means of logistic regression models. Odds ratio and C statistics were used to define strength of association and discriminant capability. C statistics obtained with PET/CT at different timepoints were compared. Results: As of January 2012, 7 out of 20 required pts have been enrolled. A total of 48 lesions were available for evaluation. A reduction in lesion SUVmax and TLG values compared to baseline was evident in all the post-therapy studies (reduction in SUV max at day 7 – 51 ± 28 %, day 14 – 67 ± 24 % and day 30 –69 ± 29 %, reduction in TLG at day 7 – 41 ± 83 %, day 14 – 69 ± 35 % and day 30 – 68 ± 37 %). A comparison of the day 15 and day 30 studies showed essentially stable uptake values (SUV max variation -3 ± 41 %, TLG 5 ± 56 %). However, 14/23 lesions in 3 patients showed increased SUV max and TLG values between the day 15 and day 30 studies likely indicating early signs of treatment resistance. Conclusions: Our preliminary results suggest that PET/CT may be an early surrogate marker of treatment response to vemurafenib. Sequential monitoring of targeted therapy with PET/CT may be useful in identification of treatment resistance, aid in tailoring alternative strategies and deserves further investigation.
Nab-paclitaxel salvage chemotherapy for metastatic ocular melanoma.
Authors: Guminski Alexander David , Lee Adrian , Lumba Sumit , Maher Richard 
Published: March 2020

e19042 Background: Metastatic ocular melanoma is an incurable malignancy characterised by liver predominant involvement. Conventional systemic chemotherapy using drugs such as fotemustine or dacarbizine have low response rates. In liver only disease hepatic arterial infusion of fotemustine has reported a higher response rate. Methods: We report four prospectively followed patients who all received salvage treatment with Nab-paclitaxel after previous intra-arterial fotemustine for metasatic ocular melanoma. Results: One patient who did not respond to to intra-arterial chemotherapy had a radiological response to Nab-paclitaxel with a duration of six months (5 cycles of treatment) with subsequent progression inliver and CNS. Another patient had rapidly progressing liver, peritoneal and nodal metastases with elevated bilirubin. He received dose reduced Nab-paclitaxel sith significant biochemical, radiological and functional improvement. He continues on Nab-paclitaxel in ongoing partial remission and remains clinically improved after six months. Two patients with similarly advanced disease, including one with abnormal bilirubin, did not respond. Subsequent treatments for the three patients progressing after Nab-paclitaxel have been SIR-Spheres followed by Ipilumumab, Ipilumumab and palliation respectively. Typical side effects of Nab-paclitaxel have occurred including alopecia, fatigue, peripheral neuropathy and neutropenia. Conclusions: In summary we have seen clinically useful responses in two of four patients treated. We continue to recruit further patients to better understand the role of Nab-paclitaxel as salvage chemotherapy for metastatic ocular melanoma.
Surgery, radiation, and systemic therapies in patients with metastatic melanoma.
Authors: Wang Song , Zhao Zhongyun , Barber Beth , Wagner Volker Jean 
Published: March 2020

e19044 Background: To describe treatment patterns with surgery, radiation, and systemic (drug) therapies in patients with metastatic melanoma in the U.S. Methods: Using a large U.S. medical claims database, patients were identified between 2005 and 2010 using ≥2 melanoma diagnoses (ICD-9-CM: 172.xx, V10.82) and ≥2 diagnoses for metastasis (ICD-9-CM: 197.xx, 198.xx). The index date was the first date of metastasis diagnosis. Patients were followed from the index date to death, disenrollment, or end of the study period (6/30/2010), whichever occurred first. Surgery, radiation, and systemic therapies were examined descriptively. Factors influencing treatment were examined using a logistic regression separately for surgery, radiation, and systemic therapy. Results: A total of 2,546 patients with metastatic melanoma were included in the analyses. Mean (± standard deviation) age was 60.6 (± 14.0) years old with 22.8% under 50 and 36.5% were female. Overall, 66.8% of patients had cancer treatment related surgery, 38.7% received systemic therapies, 44.7% received radiation, and 17.7% of patients received all three treatments. Logistic regressions revealed that patients with lung (p <.0001), brain (p <.0001), liver (p <.0001), or bone (p <.0001) metastases were less likely to have surgeries; patients with lung (p = 0.04), brain (p < 0.001), or liver metastases (p = 0.03) were more likely to receive systemic therapies; as expected patients with brain (p < 0.0001) or bone metastases (p < 0.0001) were more likely to have radiation therapy. Patients being treated by oncologists were more likely to receive systemic therapy (p < 0.0001) or radiation (p < 0.0001) while patients being treated by dermatologists were more likely to receive surgery subsequently (p = 0.002). Older age and female gender were associated with a lower likelihood to receive surgery, systemic, or radiation therapy. Conclusions: Sites of metastases and treating physician specialty might influence treatments for patients with metastatic melanoma.
Association of pyrexia and durable response in advanced melanoma patients treated with the combination of dabrafenib and trametinib.
Authors: Cha Edward , Kantor Andrea , Algazi Alain Patrick , Hwang Jimmy , Luan Jennifer , Venook Alan Paul , Ziani Leslie , Little Shonda M , Patel Kiran , Daud Adil 
Published: March 2020

e19046 Background: Pyrexia (fever) is a common adverse event associated with combined BRAF and MEK inhibition (dabrafenib and trametinib). Although the mechanism of fever is unclear, we explore pyrexia as a pharmacodynamic marker for clinical response. Methods: A phase II international trial with dabrafenib and trametinib in metastatic melanoma (MM) and colorectal cancers (CRC) harboring BRAF mutations is ongoing. Twenty-nine patients (pts) were enrolled at UCSF between January 2011 and January 2012. Fevers were graded based on temperature and coinciding symptoms, and an episode of pyrexia was defined as a temperature of >100 °F at least once a day for one or more consecutive days. Tumor assessments were performed every 8 weeks (wks). Results: To date, 13 pts with MM and 5 with CRC had tumor assessments up to 24 wks. In MM, pyrexia was reported 2 or more times in 7 pts; 5 had none, and 1 reported one episode of Grade 1 pyrexia. Episodes occurred 2-4 wks after starting treatment, and time between subsequent recurrences ranged from 1 to 25 wks. Neutrophil counts showed early fluctuations, but none had neutropenia. Of the 7 pts with recurring fevers, 5 had partial responses and 2 had stable disease at 8 wks. Of the 6 pts with nonrecurring or no fevers, 2 had partial responses at 8 wks, and 1 progressed. At 24 wks, all 7 pts with ≥ 2 fever episodes remained progression-free, whereas 0/6 pts with < 2 fever episodes were progression-free (p < 0.001). Pts without progression continued to have recurring fevers (median = 4). There were no differences by disease stage (12 of 13 with M1c) or mutation status (10 with V600E; 2 with V600K; 1 with V600E + V601I). While pts with CRC had pyrexia, no association between pyrexia and response was noted; however, only 5 pts are included in this analysis. Conclusions: In this limited analysis of pts with MM, recurrent fevers were associated with durable response (≥ 24 wks). These results suggest that pyrexia could be a marker for inflammation and antitumor activity. Further studies are underway to characterize cytokine profiles and immune responses. [Table: see text]
Metabolic state of perifocal zone and resection line of skin melanoma.
Authors: Frantziyantz Elena , Dzhabarov Farkhad , Rosenko Liudmila , Pozdnyakova Victoria , Komarova Ekaterina 
Published: March 2020

e19049 Background: The state of metabolism in perifocal zone and morphologically intact skin along resection line is of importance for the processes of neoplasm metastasizing and relapse, including skin melanoma. Normalization of the state of free-radical processes, first of all along resection line, and then in neoplasm perifocal zone, should be a characteristic of pathogenically substantiated neoadjuvant influence. Methods: to study activity of free-radical processes in tissue of skin melanoma relapse, its perifocal zone (PZ) (1 cm from tumour edge) and in skin along resection line (3-5 cm from tumour edge) we investigated concentration of vitamins E and A, activity of superoxide dismutase (SOD), catalase, summary peroxidase activity (SPA), and malonic dialdehyde level (MDA) in patients with skin melanoma (pT2-3N1-2M0). The study group included 54 samples after treatment (chemotherapy and radiation). Control groups: 45 samples before treatment (CG1) and 27 samples of intact skin after plastic operations (CG2). Results: After treatment MDA concentration in tumour tissue increased by 33.4% in comparison with the CG1, but remained 17.7% lower than in CG2. Average increase in concentration of vitamins E and A was equal to 1.8 times, catalase activity decreased by 30.3% in comparison with parameters before treatment (p<0.05). SOD/catalase coefficient was 1.3 times higher than in the CG1, but 3.4 times lower than CG2.More manifested changes in activity of free-radical processes were observed in PZ: MDA concentration level after treatment increased by 30% in comparison with the CG1, and differed from the one in CG2 only by 10% (p<0.05). Catalase activity decreased by 1.5 times and didn’t significantly differ from the corresponding parameter in tumour tissue after treatment. Normalization of concentration level of vitamins A and E without change of their ratio was observed. There was 1.6-fold increase of SOD/SPA coefficient in comparison with the CG1, however it was 2.4 times lower than CG2 (p<0.05). All parameters under study along resection line after treatment didn’t significantly differ from parameters in CG2. Conclusions: The performed treatment completely restores broken metabolism in skin along resection line, partially–in tumour perifocal zone.
Biosimilar medicines in oncology: Single-center experience with biosimilar G-CSF.
Authors: Salesi Nello , Di Cocco Barbara , Veltri Enzo 
Published: March 2020

e19501 Background: A biosimilar medicine is one with proven similarity to a reference biological product for which the patent has expired and whose active ingredient is produced or derived from a living organism. Recombinant granulocyte colony-stimulating growth factors (G-CSF) are used for the prophylaxis of febrile neutropenia. Methods: In this observational study a total of 48 patients with solid tumours were treated with biosimilar Zarzio, a new biosimilar G-CSF for 4−14 days from the day following the end of chemotherapy. The primary prophylaxis group was composed of 10 patients with breast carcinoma receiving adjuvant chemotherapy (CEF: 5-fluorouracil 600 mg/m2, epirubicin 100 mg/m2 G1, cyclophosphamide 600 mg/m2 G1, q 21 for 4 cycles à docetaxel 100 mg/m2 G1, q 21); 17 patients with locally advanced or metastatic lung carcinoma (66% adenocarcinoma, 34% squamous) receiving 4–6 cycles of platinum-based chemotherapy; 6 patients with metastatic gastric adenocarcinoma treated with TCF (Taxotere 75 mg/m2, cisplatin 75 mg/m2, 5-fluorouracil 300 mg/m2 by continuous 24 hour infusion for 5 days, q 21) for 4–6 cycles; 4 patients with prostate adenocarcinoma treated with Docetaxel 75 mg/m2 G1, q 21 in 6 cycles. The secondary prophylaxis group was composed of 11 patients with colorectal adenocarcinoma (54.5% treated with adjuvant XELOX therapy: Xeloda 2000 mg/m2 G1à14, oxaliplatin 130 mg/m2 G1, q 21, and the remainder treated with first-line metastatic FOLFOXIRI therapy [CPT-11 165mg/m2 G1, 5-FU 3200 mg/m2 continuous infusion for 48 hours, oxaliplatin 85 mg/m2 G1, q 14]). Results: Three cases of febrile neutropenia were reported: two in patients with prostate adenocarcinoma and one case in a patient with pulmonary squamous cell carcinoma and multiple secondary skeletal lesions. These patients were treated with antibiotics with resolution of the clinical picture without hospitalization after 24 hours. Conclusions: Our experience indicates that the use of biosimilar G-CSF is safe and effective at reducing neutropenic complications in patients with mixed tumors and is associated with cost savings.
Therapy Management Patient Consensus (TheMaPaC): A patient perspective on published therapy management recommendations for TKI-treated patients with a special focus on sunitinib.
Authors: Eberhardt-Wetherington Berit , Gall Valerie , Lang Melanie , Schmidinger Manuela , Gruenwald Viktor , Claussen Christina , Wartenberg Markus , Kalanovic Daniel 
Published: March 2020

e19502 Background: Therapy management is an essential component of patient care for RCC or GIST patients (pts) treated with TKI (e.g. Sunitinib). Preventive measures and early intervention can reduce or eliminate specific adverse events (AE) allowing for adequate therapy duration and improved quality of life. Published recommendations (RECs) for AE management often rely on theoretical aspects and limited evidence leading to heterogeneous or contradicting RECs. To overcome these issues, a collaborative approach of physicians, pts and Pfizer was established. Here we report on an extensive survey to deepen the knowledge on the validity and practicability of published RECs in 27 TKI treated pts (20 RCC; 7GIST). Methods: RECs (n = 221) for AE management in pts receiving sunitinib or other VEGFR-targeted TKIs were retrieved from the literature since 2006 (approval of sunitinib). RECs were transferred into a detailed questionnaire (QU) using patient-friendly language. Pts receiving sunitinib assigned one of 5 rating categories to each REC (positive experience (self/others); no information; negative experience (self/others). Results: 47 pts received the QU, 27 (15 female; median age 62 yrs) returned evaluable QUs. The pts have been on sunitinib therapy for a median of 16 months. On average, 49% of RECs received positive ratings; 44% based on individual experience. 20 RECs were rated positively by >80% of pts. The results indicate that patients had the most positive experience with RECs about patient/physician information on AEs, care/protection of feet, skin ointment use, food preference, hydration and fatigue reduction. Other REC ratings were heterogeneous, with a preference for measures that can be easily applied in daily life. It is notable that 47% of published RECs were unknown to the participants. Conclusions: To our knowledge, this is the first extensive patient survey on the validity and practicability of published RECs. The results identify a number of useful, established RECs from a real-life pts perspective. The results will be further evaluated and compared with an ongoing physician survey.
Meta-analysis of the effects on safety of front-loading (FL), every-2-week (Q2W), and Q3W dosing of darbepoetin alfa (DA) in patients (pts) with chemotherapy-induced anemia (CIA).
Authors: Glaspy John A. , Kotasek Dusan , Canon Jean-Luc , Tomita Dianne , Collins Helen , Schwartzberg Lee Steven 
Published: March 2020

e19511 Background: Several studies evaluated if alternate dosing could decrease the time to hemoglobin (Hb) response. With recent safety concerns, this is now of limited interest; however, these studies may contribute to the understanding of safety risks. This study-level meta-analysis examined effects of FL, Q2W, and Q3W dosing of DA vs epoetin alfa (EA) and weekly DA dosing on safety in pts with CIA. Methods: Data from 11 studies (4 FL, 5 Q2W, 1 Q3W, 1 Q2W/Q3W) conducted between 1999 and 2006 in which the comparison group received 3-times-per-week (TIW) or once-weekly (QW) EA or QW DA were included in the meta-analysis. FL dosing differed between the studies and was defined as DA 4.5 mcg/kg or 300 mg QW for 4 or 5 weeks or until Hb > 12 g/dL followed by either DA 4.5 mcg/kg Q3W or a lower QW dose. Endpoints included deaths on study; disease progression (PD); embolic, thrombotic, and thromboembolic events; and rapid Hb rise (1 g/dL within 14 days). Random effects odds ratios (ORs) are provided comparing FL, Q2W, or Q3W arms to either TIW or QW active control arms. Heterogeneity was assessed using I2 statistic. Results: No differences in ORs for death, PD, embolic, thrombotic, and thromboembolic events or evidence of a more rapid rate of Hb rise were observed in FL, Q2W, and Q3W arms compared with controls (table). Conclusions: Results of this meta-analysis suggested that these adverse events were not related to FL, Q2W, or Q3W dosing of DA. [Table: see text]