bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability and validity of the Functional Assessment of Cancer Therapy-melanoma (FACT-M)
Authors: Cormier J. N. , Webster K. , Cella D. , Ross M. I. , Gershenwald J. E. , Lee J. E. , Mansfield P. F. , Kim K. B. , Camacho L. H. , Palmer J. L. 
Published: March 2020

8554 Background: Our group has developed a disease-specific module for the Functional Assessment of Cancer Therapy (FACT) instrument to assess quality of life (QOL) in melanoma patients. The purpose of this study was to assess the reliability and validity of the melanoma subscale (MS) and melanoma surgery subscales (MSS) as well as the total FACT-M, which includes the FACT combined with the MS and MSS. Methods: 273 melanoma patients (stages I-IV) attending an outpatient melanoma clinic completed a battery of questionnaires at baseline assessment. The scores from the MS, MSS, and total FACT-M were compared to patient performance status (ECOG and Karnofsky scales), disease stage, treatment status, and other instruments with related domains including the Profile of Mood States, Marlowe-Crowne Social Desirability Scale, and the EORTC Quality of Life Questionnaire - melanoma module. Patients were assessed 1 week after baseline to assess test-retest reliability, and 163 patients completed assessments at 3 months to evaluate the responsiveness to change in performance status. Results: Internal consistency and test-retest reliability for the MS (Cronbach's a = 0.85, r = 0.81), MSS (a = 0.85, r = 0.82), and the total FACT-M (a = 0.95, r = 0.90) were excellent. Overall, the scales correlated with other measures and correlations were in the hypothesized direction. As predicted, FACT-M, MS, and MSS scores were lower for patients with advanced (stage III/IV) melanoma, patients with poor performance status, and patients who were receiving active treatment. In addition, total FACT-M, MS, and MSS scores were highly sensitive to changes in performance status (p = 0.0012, 0.0004, and 0.0006, respectively). Conclusions: The FACT-M is a reliable and valid QOL assessment tool for patients with melanoma. This disease-specific instrument should be utilized for melanoma QOL assessment in clinical trials. No significant financial relationships to disclose.
Patient-specific vaccines derived from proliferating autologous tumor cell lines and dendritic cells: Results of a phase II trial in metastatic melanoma
Authors: Dillman R. O. , Selvan S. R. , Schiltz P. M. , DePriest C. , Peterson C. , DeLeon C. , McClay E. F. , Barth N. M. , Sheehy P. F. , Allen K. 
Published: March 2020

8555 Background: Patient-specific vaccines utilizing proliferating tumor cells, or tumor stem cells, may be the ideal products for active specific immunotherapy. Methods: Eligible patients had recurrent or metastatic melanoma from which a cell line was established, expanded to 200 million cells, incubated with interferon-gamma, irradiated and cryopreserved. Autologous dendritic cells (DC) were derived from peripheral blood mononuclear cells cultured in IL-4 and GM-CSF. DC were incubated with the irradiated tumor cells, then cryopreserved in 20- million-cell aliquots, which were thawed, washed and suspended in 500 micrograms of GM-CSF for injection. Treatment consisted of s.c. injections weekly × 3, then monthly × 5 in a 2-stage phase II trial with two stratifications. Patients were characterized as having objectively measurable disease (OMD) or non-measurable disease (NMD). Plans were to enroll 30 to 80 patients: 15 to 40 with OMD, 15 to 40 with MD. Objectives were to determine safety, frequency of conversion of delayed type hypersensitivity (DTH) reactions to irradiated autologous tumor cells, objective response rate (ORR) using RECIST criteria, progression-free survival (PFS), overall survival (OS), and comparison to a historical control group. Results: Between January 2001 and April 2006, 55 patients were enrolled; 53 were eligible and evaluable. The 30 men and 23 women had a median age of 50 years; 15 had OMD and 38 NMD. Patients received an average of 7.4 vaccinations out of a possible 8. Treatment was well- tolerated. 25% had a positive tumor DTH test: 1 at baseline, 7 after 3 injections, 5 after 8 injections. ORR was 0/15. Follow up for the 39 surviving patients ranges from 7 to 67 months with a median of 30 months. Median PFS is 7.1 months with 24 patients remaining progression-free. Only 14 patients have died; median OS has not been reached. 5-year projected survival is 70%; 20 patients are alive 2.5 to 5.5 years from start of vaccine. OS is better than observed for 48 comparable patients that we treated previously in a trial with irradiated tumor cells without DC (p=0.016). Conclusion: This patient-specific vaccine approach is feasible, safe, associated with encouraging survival, and warrants further investigation. No significant financial relationships to disclose.
Safety data on adjuvant treatment of cutaneous melanoma patients with interferon-alpha2b and pegylated interferon-alpha2b: An interim analysis of 285 patients treated in Germany
Authors: Eigentler T. K. , Gutzmer R. , Hauschild A. , Vogt T. , Linse R. , Garbe C. 
Published: March 2020

8561 Background: A multicenter, prospective randomized, phase III trial (EADO 2002/CMII) evaluating efficacy of interferon-a2b (IFNa) and of pegylated interferon-a2b (PEGIFNa) was carried out in cutaneous melanoma patients. Patients were eligible for this trial after local excision of an intermediate risk cutaneous melanoma (tumor thickness >1,5mm) & the absence of regional nodal macrometastases). Methods: Interferon-a2b (IFNa) for 18 months (3x3MIU sc/week), and pegylated interferon-a2b (PEGIFNa) for 36 months (100 μg sc/week) were evaluated in 285 patients treated in Germany; 141 pts treated with PEGIFNa and 144 pts with IFNa. Safety data was analyzed and adverse events of the IFN-a treatment were monitored. Results: All relevant AEs appeared within the first year of treatment. The leading clinical adverse events observed in both arms were fatigue (27.7%) & myalgia (19.7%) (NCI-CTC2–3). There were no significant differences between both treatment arms in frequency and intensity for depression, fever, weight loss, erythema at injection site, nausea, constipation, hair loss, pain, cardiovascular function, pulmonal & nervous status (NCI-CTC2–3). There were no significant differences in terms of anemia, thrombocytopenia, bilirubinaemia, SGOT, SGPT, BUN & proteinaemia (NCI-CTC3). Leukocytopenia (NCI-CTC3) occurred in 2.4% of all cases, and was observed more frequently in the PEGIFNa arm (3.1% vs. 0.8%; p=0.09). Granulocytopenia (NCI-CTC3) was present in 6.7% of all treated patients, appearing more frequent in the PEGIFNa arm (11.0% vs. 2.3%; p=0.05), also. One patient in the PEGIFNa arm developed a grade 4 leuko- and granulocytopenia. In another case in the IFNa arm a grade 4 increase of the SGPT was observed. In 23.7% of all treated patients a dose reduction was performed. Conclusions: Both PEGIFNa and IFNa are well tolerated using these regimens for these treatment durations. There were few differences in the tolerability between PEGIFNa 100 μg sc/week and IFNa 3x3MIU sc/week. Only an increased myelosuppressive effects such as leuko- and granulocytopenia have been observed. A prolongation of PEGIFNa treatment to 3 years was not associated with an increase in AEs. No significant financial relationships to disclose.
Prognostic factors for survival after embolization of hepatic metastases in uveal melanoma
Authors: Yamamoto A. , Chervoneva I. , Sullivan K. , Eschelman D. , Gonsalves C. , Mastrangelo M. J. , Berd D. , Feeney K. , Terai M. , Sato T. 
Published: March 2020

8562 Background: Liver is the most common site of metastasis (>80%) in patients with uveal melanoma. Embolization of the hepatic artery has been used to control hepatic metastases. Methods: Uveal melanoma patients with hepatic metastases embolized with iodized poppy seed oil and gelatin sponge, and either BCNU (chemoembolization, CE) or GM-CSF (immunoembolization, IE) during periods when each of these drugs was the agent of first choice, were evaluated. Prognostic factors that predict OS and progression free survival (PFS) in the liver (PFS-L) and in the extra-hepatic systemic organs (PFS-S) were analyzed univariately using the log-rank test and multivariately using Cox proportional hazards model. The following parameters were evaluated: age, gender, pre-existing extrahepatic metastases (EHM), LDH, AST, ALP, and treatment modality (CE or IE). Results: A total of 53 uveal melanoma patients with < 50% liver involvement with melanoma were analyzed. In comparison to the 19 patients (14 males/5 females) who underwent CE, the 34 patients who underwent IE (12 males/22 females) have significantly better OS (14.1 vs. 9.7 months, p=0.012) and PFS-S (10.2 vs. 4.8 months, P=0.013) in univariate analyses. Female patients outlived male patients (14.2 vs. 9.7 months, p=0.005). In Cox model, the shorter OS was associated with male gender (hazard ratio (HR)=2.1; 95% CI, 1.1–4.0; p=0.020), and marginally related to EHM (HR=1.8; 95% CI, 1.0–3.4; p=0.052). Independent predictors of shorter PFS-S included older age (HR=1.04 per year; 95% CI: 1.01–1.06; p=0.007), EHM (HR=2.1; 95% CI, 1.1–3.8; p=0.017), and CE (HR=2.1; 95% CI, 1.2–3.8; p=0.012). The gender-by-treatment interaction was also considered in all Cox models, but it was not significant. None of the covariates was a predictor of PFS-L in univariate or multivariate analyses. Conclusions: IE and female gender were found to be positive prognostic factors for survival after embolization of hepatic metastases. No significant financial relationships to disclose.
Effect of granulocyte macrophage-colony stimulating factor (GM-CSF, sargramostim) administration on serum S100B and its subtypes in melanoma patients
Authors: De Gast B. , Korse C. , Weber R. , Trautveter S. , Bonfrer J. , Spitler L. 
Published: March 2020

8563 Background: Serum S100B is a tumor marker for malignant melanoma (MM) and is also a histological marker for Dendritic Cells (DC). Previously study we found that DC only expressed the S100BB subtype, whereas MM expressed both the S100A1B and BB subtypes. As GM-CSF can induce activation of DC, we studied if such therapy also increased serum S100B and analysed the subtype of the increased S100B. Methods: Forty-three patients with MM were treated after surgical cytoreduction with adjuvant GM-CSF, 125 μg/m2 subcutaneously for up to 1 year in 28-day cycles of 14 days on followed by 14 days rest. Serum S100B was measured before therapy (d0), following 14 days on GM-CSF (d15), and after 14 days off GM-CSF (d29), as well as d155. If serum S100B was increased, subtype analysis was performed with immunoassays for S100A1B and S100BB. Results: In 39 patients with a normal serum S100B at d0 (mean 0.04 ± sd 0.02 μg/l), a significant rise of serum S100B occurred at d15 (mean 0.09 ± sd 0.04 μg/l), returning to normal at d29 (mean 0.05 ± sd 0.02, p<0.001 for d15 versus d0 and d29). Analysis of the increased S100B at d15 showed increased levels of S100BB in 7/13 patients and no increase in the levels of S100A1B. In 4 patients S100B was increased at d0, of the S100A1B subtype in 2 with rapidly progressive disease. The other 2 had only increased S100BB levels. In 28 patients a significant increase occurred at d155. Overall, 18 patients have remained without evidence of disease all without S100A1B. Four patients developed metastatic disease and had increased levels of S100A1B; however 6 additional patients also developed metastasis without an increase in S100A1B. Conclusions: Administration of GM- CSF causes an increase of S100BB suggestive of activation of DC. Increased levels of S100A1B were indicative of active MM, but the absence of elevated S100A1B did not exclude metastasis. No significant financial relationships to disclose.
A pharmacokinetic comparison of the Marqibo 3 and 5 vial injection kits in metatastic melanoma patients
Authors: Hwu P. , Papadopoulos N. , Kim K. , Vardeleon A. G. , Campbell S. , Namdari R. , Choy G. , Berk G. , Bedikian A. 
Published: March 2020

8575 Background: In nonclinical and clinical studies, liposomal encapsulation of vincristine sulfate (VCR) increased the circulation time and accumulation of VCR at the tumor site, and thus improved antitumor efficacy in comparison to VCR. Marqibo (vincristine sulfate liposomes injection) may be administered safely at doses exceeding that typically employed by VCR, with a manageable pattern of clinical toxicities consistent with VCR. Methods: We conducted a phase I, single-center, open-label, randomized, 2-arm crossover study designed to compare the pharmacokinetics (PK) of Marqibo utilizing the 3- and 5-vial kits administered 2 mg/m2 IV infusion once every 2 weeks in histologically confirmed, surgically nonresectable Stage III or IV metastatic cutaneous, mucosal, or choroidal melanoma patients. Patients randomized to receive the 3-vial kit at Cycle 1 were crossed over to receive the 5-vial kit at Cycle 2 or vice versa. The 3-vial kit was used for all patients at all cycles from Cycle 3 to end of treatment. Antitumor activity was assessed by CT scan every 4 cycles. Blood samples for PK analysis was collected at pretreatment, during infusion, end of infusion, and at various time points within 96 hours post end of infusion at Cycles 1 and 2. Total VCR concentration and released vincristine concentration was measured using HPLC-MS/MS method. Results: Fifteen patients were enrolled and treated; 11 were evaluable for the PK analysis. Median number of cycles received was 4 (1- 24). Objective response was observed in 13% (1 CR, 1 PR) or stable disease (20%, 3 SD) as their best response. The 90% CI (0.83–1.12) on the ratio of the means of the AUC0-inf of the 3- and 5-vial kits was within the interval of 0.80–1.25 confirming the bioequivalence of the two kits. Seventy-three percent discontinued treatment due to disease progression and 13% discontinued due to adverse events. Adverse events included hypoesthesia or paresthesia, constipation, numbness, weakness, fatigue, nausea, vomiting. Conclusions: Single agent Marqibo demonstrated moderate activity in advanced Stage IV melanoma patients and was generally well tolerated with similar adverse event profile to VCR. The 3- and 5-vial kits produced similar bioequivalent PK profiles. No significant financial relationships to disclose.
Improved long-term survival in patients with intermediate thickness primary melanoma managed by sentinel node biopsy
Authors: Scheri R. P. , Wanek L. , Essner R. , Morton D. 
Published: March 2020

8576 Background: Although improved disease-free survival (DFS) with sentinel node biopsy (SNB) for clinically localized melanoma was observed at the interim analysis from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) there was not yet an improvement in overall survival (OS). We hypothesize this was due to the few observed early deaths. To investigate this we simulated the MSLT-1 protocol using our institutional database. Methods: 3,800 patients undergoing wide excision with or without SNB were matched by primary stage/ulceration/site and patient demographics. Patients with positive sentinel nodes (SN) underwent immediate completion lymphadenectomy (CLND) whereas non-SNB patients managed by nodal observation underwent delayed CLND at nodal recurrence. Survival was determined by the Kaplan-Meier method. Significance was determined using log-rank and Cox regression analysis. Results: Among matched pairs of SNB and non-SNB patients with 1.2–3.5 mm primaries, projected 10-year OS was 76% with SNB versus 63% without SNB (p=0.0008). There was no corresponding statistically significant difference between all 2001 SNB patients and 1799 non-SNB patients, or within the thin primary and thicker primary groups. By multivariate analysis, only SN status (p<0.0001), Breslow thickness (p<0.0001) and ulceration (p=0.0001) were independently predictive of OS. Conclusions: Our long-term data suggest that performing SNB will improve OS in patients with intermediate thickness melanoma but not with thicker or thinner melanomas as compared to observation and delayed CLND. No significant financial relationships to disclose. [Table: see text]
What do redox metabolism, printers/lithographers, and hip replacements have to do with the prevention of melanoma?
Authors: Meyskens F. 
Published: March 2020

8583 Our studies of the properties of reactive oxygen species(ROS) in melanomagenesis led us to explore the role of heavy metals in this process. A systematic experimental exploration of the effect of ROS on melanin and melanosomes in melanocytes and melanoma cells using biophysical techniques including electroparamagnetic resonance to measure free radicals and electron microscopy suggests that the conversion of melanin from an anti-oxidant and reducing agent to a pro-oxidant and photoreactive compound is an early pathogenic event that is accompanied by melanosomal disruption that serves as an ongoing organelle source of free radical generation. The involvement of selected heavy metals enhances this process and in conjunction with ultraviolet light can lead to phenotypic changes in normal human melanocytes that resemble dysplatic nevi melanocytes in culture. A re-examination of the non-genetic risk factors for melanoma has identified a large(and neglected) epidemiology that implicates heavy metals and includes markedly increased risks for melanoma in printers/lithographers(4 large studies), electrical industry workers (3 large studies), and hip replacements patients(a large meta-analyses and 2 cohort studies). High levels of cobalt are present in this latter group post-replacement that lasts for years (?indefinitely) Clinical observations (imaging studies) and studies that document the importance of metallothionein expression in primary melanoma and prognosis also offers ancillary support for the involvement of metals in the pathogenesis of melanoma Based on these considerations and the role of copper in the melanin synthesis pathway and the binding characteristics of metals to melanin we propose that the most likely culprits that accounts for a significant contribution to the etiology and pathogenesis of melanoma are Cu+2 and Co+2 and suggests that chelation may be a reasonable strategy for the prevention of melanoma. No significant financial relationships to disclose.
Role of low molecular weight heparin (LMWH) in central venous catheter antithrombotic prophylaxis
Authors: Tassinari D. , Scarpi E. , Rupoli S. , Leoni P. 
Published: March 2020

9010 Background: To assess the role of LMWH in antithrombotic prophylaxis in cancer patients with a central venous catheter. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 1966 to October 2006, using “anticoagulants/*administration & dosage” [MeSH term], “cancer patient” [MeSH term], “catheterization, central venous/*adverse effect” [MeSH term], “catheters, indwelling/adverse effects” “central venous catheter” [MeSH term], “dalteparin/*administration and dosage” [MeSH term], “enoxaparin/*administration and dosage” [MeSH term], “low molecular weight heparin/*administration and dosage” [MeSH term], “nadroparin/*administration and dosage” [MeSH term], “neoplasm/drug therapy” [MeSH term], “reviparin/*administration and dosage” [MeSH term], “venous thrombosis/*etiology/*prevention & control/radiography” [MeSH term], a search was performed independently by two authors (DT and ES). All the randomized phase III trials comparing LMWH and placebo were considered eligible and included into the analysis. The risk reduction (RR) of upper limb venous thrombosis (ULVT) was the primary outcome of the analysis. Heterogeneity between the trials was analysed using the Mantel-Haenszel test, and the outcome analysis was performed using a random effects model and an alpha error lower than 5%. Results: 5 trials met the selection criteria and were included into the analysis. The outcome of 1,367 patients (793 treated with LMWE and 574 treated with placebo) was compared in the pooled analysis. A significant heterogeneity was documented between the trials (p=0.005), while no heterogeneity was observed when a trial with a low quality in the presented data was excluded from the analysis (p=0.777). No significant differences in RR were observed both when all the trials were included into the analysis (RR=−2.4%, p=0.456) and when we excluded a trial for the low quality of presented data (RR=0.2%, p=0.896). Conclusion: Antithrombotic prophylaxis with LMWH does not reduce the risk of ULVT in oncologic patients with central venous catheter, and its routine use seems to be not-recommended in clinical practice. No significant financial relationships to disclose.
Aminoglycoside-induced deafness in leukemic patients: Cost-effectiveness of prevention by genetic testing
Authors: Bitner-Glindzicz M. , Osei-Lah V. , Colvin I. , Sirimanna T. , Lucas D. , MacArdle B. , Webb D. , Shankar A. , Kingston J. , Jenkins L. , Rahman S. 
Published: March 2020

9014 Background: Aminoglycosides are highly-effective, inexpensive antimicrobials widely used in empirical combination therapy for fever in children with severe neutropenia, including patients receiving treatment for acute leukemia. Some genetically predisposed individuals are exquisitely sensitive to the cochleotoxic effects of these drugs, even when levels are within the therapeutic range. This genetic susceptibility is maternally inherited and caused by mutation of the MT-RNR1 gene encoding mitochondrial 12S rRNA at base position 1555, termed m.1555A>G. Methods: Retrospective analysis of m.1555A>G positive cases in the Regional Diagnostic laboratory to determine how many were revealed by aminoglycoside treatment for cancer treatment-related sepsis. Results: Three unrelated mutation positive individuals were identified in a two year period. All were children with acute lymphoblastic leukemia who experienced rapidly progressive hearing loss during their treatment. Two of the three children have a post-lingual hearing loss of sufficient severity to merit cochlear implantation. None had a significant family history of deafness. Conclusions: Initial estimates of the prevalence of the m.1555A>G mutation were based upon extrapolation back from its contribution to the cause of hearing loss amongst hearing-impaired people and were thought to be low. However, recent small studies of the prevalence of m.1555A>G in the general population suggest that prevalence is much higher than previously calculated (1 in 206 in New Zealand (n=206), 1 in 1,161 in Texas (n=1,161)) but that penetrance, at least in the absence of aminoglycosides, is low. Using estimates of the lifetime cost of pediatric cochlear implantation we suggest that screening for the m.1555A>G mutation at the time of diagnosis of leukemia would be cost effective and therefore suggest that all children diagnosed with leukemia should be screened for this mutation prior to receiving aminoglycoside therapy. No significant financial relationships to disclose.