bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon alfa-2b treatment following therapeutic vaccination with mRNA electroporated dendritic cells results in skin depigmentation and tumor regression in patients with advanced melanoma
Authors: Neyns B. , Corthals J. , Thielemans K. 
Published: March 2020

8537 Background: Therapeutic vaccination with autologous dendritic cells (DC) and Interferon alfa-2b (IFNa) both have low activity in patients with advanced melanoma. Combination therapy might be advantageous because of their complementary mechanism of action. Methods: We are investigating the safety and activity of an autologous DC-based melanoma vaccine in patients with advanced melanoma in a single institution phase IB clinical trial. Following leucapheresis and enrichment in a semi-closed culture system, adherent PBMC are cultured in IL-4 and GM-CSF supplemented medium for 6 days and cryo-preserved. Upon thawing, 15.106 DC are electroporated with synthetic mRNA that encodes a fusion protein between LAMP and one of 6 melanoma associated antigens (MAGE.A-1, MAGE.A-3, MAGE.C2, MELANA/MART1, Tyrosinase and gp100). DC vaccines are administered by 6 bi-weekly ID/SC injections and every 6–8w thereafter. Results: 15 pts (10M/5F; median age 52, range 27–72) with stage IIIC-IV melanoma have been recruited. Ten pts were able to receive ≥ 6 vaccinations. Toxicity was limited to grade 1 or 2 local skin reactions at the vaccine administration sites in all pts. Two pts had a regression of subcutaneous (sc) metastases during DC vaccination and one of these pts remains disease-free after 18 mths of follow-up (following the resection of a single residual metastasis). An additional pt remains disease-free following surgery of in transit metastases at 8 months of follow-up. Three out of four pts who were treated with IFNa-2b (5 106 U 3x/week sc) at progression developed skin depigmentation (leucoderma punctata) and in 2 of these pts an objective tumor response was documented (PR and CR, including complete regression of skin, lymph, liver and skeletal metastases). Both responses are ongoing at 9 and 11 months of follow-up. Conclusions: These preliminary observations indicate a potential for IFNa-2b to mediate auto-immune breakthrough and tumor regression in advanced melanoma patients vacinated with a mRNA electroporated DC-vaccine. Further investigation of this combination immunotherapy in advanced melanoma patients is ongoing. No significant financial relationships to disclose.
Primary invasive melanoma on the head and neck: Distribution, ultraviolet exposure and histological subtype in 1,298 Australian patients
Authors: Long G. V. , Armstrong B. K. , Colman M. H. , Shaw H. M. , Thompson J. F. , Crotty K. A. 
Published: March 2020

8541 Background: The aim of this study was to determine the subsite distribution of invasive cutaneous melanoma of the head and neck and correlate this with the melanoma histologic type and ultraviolet exposure (UVE) at each particular subsite. Methods: This study comprised 1,298 patients seen at the Sydney Melanoma Unit (SMU) between 1990 and 2000. In each case, the histopathologic diagnosis of invasive melanoma was established by highly experienced SMU histopathologists. Histologic details, gender and patient age at diagnosis were available in all patients except in 5% in whom Breslow thickness could not be determined. Nine head and neck subsites were assigned: scalp, forehead, eyelids, nose, lips, chin, ears, face and neck. The relative tumour density (RTD) at each subsite was then examined in relation to gender and age of the patient and the relative UVE at this subsite. Relative UVE values as determined using polyusulphone UV dosimeters were used. Results: There was a direct correlation between high UVE and RTD at each subsite except the forehead (135 patients) and neck (335 patients), particularly in women, with the neck subsite prevailing in patients <50 years of age. Superficial spreading melanoma was the most common histologic type at all subsites except the lips (15 patients), nose (53 patients) and chin (15 patients), where desmoplastic melanoma predominated. Lentigo maligna melanoma was not more common on subsites having high UVE, nor was there an obvious association between melanoma thickness and UVE. Conclusions: The UVE was an important determinant of melanoma distribution on the head and neck. The lower RTDs at the forehead and neck subsites in women were possibly due to gender differences in hairstyles. Paradoxically, lentigo maligna melanoma, commonly considered to occur almost exclusively on sun-damaged skin, was not more common on areas of high UVE. No significant financial relationships to disclose.
BAY 43–9006 (sorafenib-BAY) alters proliferation pathways and mutant specific-PCR (MS-PCR) improves detection of BRAF mutations in metastatic melanoma (MM)
Authors: Pavlick A. C. , Liebes L. , Brooks P. , Yoon J. , Hamilton A. , Yee H. , Polsky D. , Buckley M. , Wright J. , Osman I. 
Published: March 2020

8542 Background: Approximately 60% of melanomas carry BRAF mutations (mut). BAY is a multi-kinase inhibitor that inhibits the BRAF pathway. A phase II trial of BAY in MM is being conducted to: 1) determine if treatment (tx) with BAY can alter proliferation as measured by cyclin D1, Ki-67 and ERK, 2) assess for differential anti-tumor responses and 3) to assess a newly developed fluorescent-based PCR assay to detect mutant BRAF. Methods: Eligibility criteria: Biopsy (bx)-accessible, untreated MM. Measurable disease (RECIST). Stratification of tumor BRAF status determined by routine PCR sequencing for codon 600 mut prior to tx and fluorescent MS-PCR sequencing for confirmation. MS-PCR specifically amplified the M-BRAF allele without amplifying the wild-type (WT)allele. Tx: BAY 400 mg po BID D1–28 q4w. Repeat bx on Day 28. Bx assessed for Ki-67, cyclin-D1 and ERK. Serum collagen cryptic epitopes were measured serially. Re-imaging was done every 2 cycles and pts treated until POD. Results: 29 pts (9-M1a, 8-M1b, 12-M1c) enrolled. 26 wild type (WT) and 3 mutant (M) BRAF by routine PCR. Due to the low yield of mut on routine PCR, MS-PCR was done. 6 mutants were detected in the first 16 pts with MS-PCR compared to 2 with routine sequencing. Median age: 68 (range 22–91). 8 pts with LDH ≥ 1.5 × nl. Tox: Gr I-diarrhea(7), alopecia(4), rash(6), mucositis(4), nausea(4), pain(4), hand-foot(2); Gr II- HTN(4), fatigue(2),mucositis(1), rash(3), pain(3), hand-foot(2); Gr III-hand-foot(1), rash(1), fatigue(1) and intestinal perforation(1). Responses: 12 NE (2 WD, 8 early POD, 1 tox, 1 too early); M BRAF- 1 PR (lymph nodes and large SQ arm masses) and 2 PD; WT BRAF- 1 PR, 7 POD after 2 cycles, 6 SD. Matched paired biopsies demonstrated down regulation of tumor ki-67, erk and cyclin-D1. Collagen cryptic epitopes correlated with tumor responses. Conclusions: MM patients with tumors that were molecularly characterized for BRAF mutational status were entered on this single agent BAY trial and responses were seen in both M and WT arms. Down-regulation of Ki-67, cyclin D1 and ERK was demonstrated and MS-PCR improved the sensitivity to detect BRAF mut. Supported by NCI N01-CM17103 and TRI. No significant financial relationships to disclose.
Clinical prognostic factors for distant metastases and survival in patients with primary uveal melanoma: A 10-year follow-up of a single center cohort study
Authors: Schmittel A. H. , Bechrakis N. E. , Martus P. , Gudacker G. , Mutlu D. , Scheibenbogen C. , Bornfeld N. , Foerster M. H. , Thiel E. , Keilholz U. 
Published: March 2020

8546 Background: Metastases from uveal melanoma have an extremely poor prognosis. Factors predicting development of metastases and survival are of critical importance for future adjuvant trials investigating innovative immunotherapeutic approaches in patients with uveal melanoma. Methods: We reanalyzed all patients with uveal melanoma, who received primary treatment in 1994 and 1995 in our hospital, from whom we previously had reported 5-year follow-up data. Data on primary tumor, local therapy and follow-up were collected. Results: Of 271 patients 78.2% of patients were available for 10 years follow up. Median follow-up was 123 months. A total of 68 patients (25.1%) developed metastases. Kaplan-Meier analysis revealed a 10-year progression free survival (PFS) of 65% for the whole patient cohort. 10-year PFS was 25% in patients with extraocular tumor growth (EOG). Patients with ciliary body involvement (CBI) or a largest tumor diameter (LTD) > 14 mm had a 10-year PFS of 56.3% and 52%, respectively, which was significantly lower than in patients without ciliary body involvement or LTD < 14 mm. 10-year overall survival was 57.5% for the whole patient cohort. 10-year survival was 20% in patients with EOG and 42.3% in patients with CBI and 43.2% in patients with LTD > 14 mm. Univariate analysis revealed EOG, CBI and LTD > 14 mm to be predictive for overall survival (p < 0.02, log-rank test for all variables). Conclusions: This study confirmed our previous 5-year follow-up data and determined determined ciliary body involvement and a largest tumor diameter > 14 mm to be the most important clinical risk factor for metastases and survival. Therefore patients with ciliary body involvement and LTD > 14 mm are candidates for adjuvant therapeutic interventions within future trials. No significant financial relationships to disclose.
Differential expression of insulin like growth factor binding protein-4 (IGFBP4) in melanoma progression
Authors: Yu J. Z. , Yee H. , Warycha M. , Christos P. , Shapiro R. , Berman R. , Pavlick A. , Liebes L. , Brooks P. , Osman I. 
Published: March 2020

8557 Background: Members of the IGFBP family are thought to regulate tumor progression through both IGF-dependent and independent mechanisms. Moreover, IGFBPs may exhibit distinct functions depending on whether they are present locally in tissue or systemically. Our preclinical data suggest that IGFBP4 serves as an endogenous inhibitor of angiogenesis and melanoma tumor growth. To examine the clinical validity of our observations, we compared IGFBP4 expression in tissue and sera in primary melanoma patients with a low risk of metastases versus patients with established metastatic disease. Methods: Eighty-nine melanoma patients (primary stage IA, n=57; metastatic, n=32; 44 M, 45 F; Median Age=56) prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group at the NYU School of Medicine were studied. IGFBP4 protein expression in tumors was assessed in 83 patients using goat anti-human IGFBP4 antibody (R&D Systems) in an immunohistochemical assay. For each case, the percentage of tumor cells that stained positively was estimated. IGFBP4 concentration in the serum was measured in 64 patients by an ELISA assay (Diagnostic Systems Laboratories, Inc.). Fifty-eight patients had both sera and tumor specimens available for correlation. Results: The median IGFBP4 expression in tumor specimens from primary patients was 70% compared to 5% in metastatic patients (P=0.002, Wilcoxon rank-sum test). The median concentration of IGFBP4 in sera was 43.8 ng/ul in primary patients versus 41.0 ng/ul in metastatic patients (P=0.83). A weak association between IGFBP4 expression in tissue and IGFBP4 shedding in sera was observed (Spearman correlation coefficient=0.16, P=0.24) in the 58 cases with both sera and tissue available. Conclusions: Our data demonstrate that IGFBP4 expression in melanoma clinical specimens decreases in the progression from primary to metastatic melanoma, consistent with its potential role as an inhibitor of angiogenesis. Data also suggest that IGFBP4 tissue expression may be more clinically relevant than its sera shedding. Future studies using a larger sample size and extended follow up are needed to further define the role of IGFBP4 in melanoma progression. No significant financial relationships to disclose.
Phase II trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma
Authors: Perez D. G. , Suman V. , Amatruda T. , Gornet M. , Morton R. , Jilani S. , Constantinou C. , Egner J. , Markovic S. 
Published: March 2020

8560 Background: In patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets vascular endothelial growth factor (VEGF) might be able to control tumor growth and progression much more effectively than chemotherapy alone. Methods: A two-stage phase II clinical trial was conducted in patients with unresectable stage IV melanoma to assess the anti-tumor activity and toxicity profile of the combination of paclitaxel (80 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle), carboplatin (AUC = 6 IV on day 1) and bevacizumab (10 mg/kg IV on days 1 and 15). The primary end point of the study was the 8-week progression-free survival rate (PFS). Enrollment to the second stage of the study was opened if 8 or more of the first 20 patients enrolled remained progression-free at 8 weeks. Eligible patients had measurable disease by RECIST criteria, a performance status (PS) of 0–2 and acceptable pre-registration organ function. Exclusion criteria included: brain metastases, significant recent bleeding, uncontrolled hypertension and ongoing anticoagulation. The study opened in February 2006 and completed full study accrual in August 2006. Data from the 20 patients enrolled in the first stage are presented here. Results: Patients (60% male) had a median age of 63 and had a good performance status (85% had PS of 0). M1c disease was present in 45% of patients and 35% had undergone previous chemotherapy for stage IV melanoma (50% prior immunotherapy). Only 6 patients did not complete more than 2 cycles of chemotherapy due to refusal (3), desire for alternative treatment (1) or progression (2). Median follow-up among the 15 patients still alive was 5.5 months (range: 6 weeks - 9 months). The 8-week PFS rate was 70% (14/20). The median time to progression was 163 days. One partial response was observed. There were 3 disease-related deaths at 65, 120 and 190 days post-registration. The most common toxicities were neutropenia (95%; 45% = grade 3), anemia (95%; 15% = grade 3), fatigue (90%; 5% = grade 3), leukopenia (85%; 25% = grade 3), and thrombocytopenia (75%; 5% = grade 3). Conclusions: The combination of paclitaxel, carboplatin and bevacizumab appears to be well tolerated and clinically active in patients with stage IV melanoma. No significant financial relationships to disclose.
Best supportive care in combination with polychemotherapy versus best supportive care alone as second-line therapy in stage IV metastatic melanoma (DeCOG MM-PAL 8)
Authors: Ulrich J. , Trefzer U. , Tilgen W. , Schadendorf D. , Kaatz M. , Mohr P. , Garbe C. , Hauschild A. 
Published: March 2020

8567 Background: To date, there is no evidence of survival benefit from randomized trials in stage IV metastatic melanoma (MM) after disease progression to first-line therapy. Therefore, we initiated a phase III trial to evaluate the impact on survival of polychemotherapy in patients (pts.) receiving best supportive care (BSC) as second-line therapy. Methods: This prospective multicenter controlled study was conducted by the Dermatologic Cooperative Oncology Group (DeCOG) with 13 participating centers. Pts. with stage IV MM disease between 18 and 75 yrs. and a Karnofsky performance status (KPS) > 60 with progression after first-line chemotherapy or chemo-immunotherapy were offered to choose between polychemotherapy + BSC or BSC alone. Pts. were required to have adequate renal, liver and bone marrow function. The regimen consisted of cisplatin (50 mg/m2), vindesine (3 mg/m2) and dacarbacin (450 mg/m2) given on day 1 and 8 every 28 days (CVD). Reevaluation according to WHO response criteria were performed every 2 cycles. Primary endpoint was the median overall survival (OS). Secondary endpoints were overall response rate (OR) (only CVD arm) and quality of life (QOL). Results: Between 1/02 and 8/06 120 pts. were recruited, a minority of 35 pts. (29%) chose the BSC arm (A) and 85 (71%) the CVD + BSC arm (B). Five pts. were ineligible, and thus 115 pts. treated per protocol. There was a significant lower KPS in arm A at study entry. At the time of data analysis, 85% of the pts. had died from melanoma. There was no siginificant difference (p=0.093) in median OS between the two arms, 9.0 [95% CI: 3,9–14,1] months in arm A and 8.0 [95% CI: 6,5–9,5] months in arm B. The OR in arm B was 7.5% (2 CR, 3 PR). Conclusions: Polychemotherapy (CVD) + BSC as second-line therapy in stage IV MM does not improve overall survival as compared to BSC alone. No significant financial relationships to disclose.
Serum YKL-40 is elevated in a subgroup of patients after surgery for stage IIb-III melanoma
Authors: Jensen M. , Johansen J. S. , Christensen I. J. , Schmidt H. , Nørgaard P. H. , Bastholt L. 
Published: March 2020

8574 Background: High serum YKL-40 is associated with poor prognosis in patients with adeno- and squamous cell carcinoma, glioblastoma, and stage I-II and IV melanoma. YKL-40 is secreted by cancer cells, macrophages and neutrophils. YKL-40 is a growth and differentiation factor, and plays a role in tissue remodelling and angiogenesis. The aim of our study was to compare serum YKL-40 in patients after surgery for stage IIb-III melanoma with healthy individuals and with clinical and histological prognostic parameters. Methods: YKL-40 was determined by ELISA (Quidel, CA) in serum samples from 231 patients, with stage IIb-III melanoma. The 74 women and 157 men had a median age of 50 (range 22–76 years), and they were enrolled in a Nordic adjuvant protocol, randomizing to observation or interferon therapy (1 or 2 years). Baseline samples were drawn <70 days after primary biopsy, but prior to start of therapy. Results: Serum YKL-40 was increased (p=0.003) in the 231 patients (median 47 μg/l, range 20–1,416 μg/l) compared to healthy individuals (43 μg/l, range: 20–184 μg/l, n=245). Serum YKL-40 was higher than the age-corrected 95th percentile of s-YKL-40 in healthy individuals in 19% of the patients with melanoma thickness >4 mm and no lymph node metastasis (n=27), in 8% with sentinel lymph node metastasis (n=89) and in 14% with clinical lymph node metastasis at time of surgery or as recurrence in the follow-up period (n=111). Comparison of serum YKL-40 in the 3 groups showed no significant differences (p=0.22). No difference was found comparing serum YKL-40 between the three groups of Breslow thickness (< 1 mm, 1–2 mm, > 2 mm)(p=0.66), and the two groups of Clark′s level (II-III, IV-V)(p=0.88) was found. A weak association (p=0.045) was found between s-YKL-40 and localization of primary tumor, with trunc having the highest median concentration of s-YKL-40. No association between an elevated s-YKL-40 with number of positive lymph nodes (0.36), ulceration (p=0.81), extranodal growth (p=0.56), or histologic subtype of primary tumor (p=0.48) was observed. Conclusion: Serum YKL-40 is elevated in a subgroup of melanoma patients with stage IIb-III and not associated with classical clinical and histological parameters. It is not known if the increased YKL-40 reflects the biological behaviour of the disease. No significant financial relationships to disclose.
Phase II single institution study of sequential biochemotherapy (BCT) for patients (pts) with stage IV melanoma (M)
Authors: Bojanapally P. R. , Alexandrescu D. T. , Rusciano V. , Wiernik P. H. , Dutcher J. P. 
Published: March 2020

8580 Background: The utility of BCT for M remains controversial. A prospective phase II study was conducted to assess the clinical benefit of BCT in patients with stage IV M. Methods: Between March 2005 and March 2006 11 pts (6 Male and 5 Female with a median age of 54 (range 36 - 82)) with metastatic M were treated with paclitaxel 225 mg/m2 via continuous 24 hour IV infusion every 3 wks for 4 cycles or maximum benefit followed by HD IL2, 1.33 mg/m2 every 8 hours for 5 days of wk1 and wk3 based on pts tolerance to a maximum of 12 doses per wk. 2 Male pts received IL2 followed by paclitaxel. Pts had a ECOG performance status of 0 - 2, with a median time of 60 months since diagnosis of disease (range 7 to 240 months). 11 pts (92%) had multiple metastatic sites (50% had lung mets, 58% had liver mets) and 4 pts (33%) had prior chemotherapy or immunotherapy. Results: Of the 13 assessable pts one achieved a PR after paclitaxel and CR after IL2 continuing at 20+ months. One had SD for 1 year after receiving HD IL2 and SD for 6 months while on paclitaxel independently, One had PR for 6 months on paclitaxel and one had MR with paclitaxel for 3 months. 9 pts (69%) had PD on paclitaxel and again on IL2, with a median survival from treatment of 7 months, 2 of these got no IL2 due to rapid PD. An overall response rate of 30% (1 CR on paclitaxel + IL2 , 1 PR on paclitaxel, 2 SD (including MR) on paclitaxel) was seen with a median survival from treatment of 15 months. Conclusions: In this study there may be prolonged survival among responders, which may be due to synergy of sequential BCT, or may reflect single agent activity of each drug. BCT should still be considered as an experimental therapy and further evaluated. No significant financial relationships to disclose.
Financial burden from wage losses after early breast cancer: Extent and determinants among Canadian women
Authors: Lauzier S. , Maunsell E. , Drolet M. , Hébert-Croteau N. , Brisson J. , Coyle D. , Masse B. , Abdous B. , Robidoux A. , Robert J. 
Published: March 2020

9000 Background: Wage losses after breast cancer may result in considerable financial burden. More women now participate in the workforce and breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated the burden from wage losses and determinants among Canadian women in the first 12 months after newly diagnosed non-metastatic breast cancer. Methods: This prospective cohort study was conducted among 800 women from 8 hospitals (participation 83%) of whom 459 were working at diagnosis. For these latter women, information on potential determinants of wage losses, work absences, compensation received and perception of financial situation was collected by 3 telephone interviews over the year. Information on medical characteristics came from medical files. The main outcome was the relative loss, namely wages lost divided by annual wages the woman would have earned had she not been absent from work. ANOVA was used to identify determinants. Results: The median relative loss in the first year after diagnosis for the 403 women reporting an absence or reduced work hours was 19% or $5,502 (Can dollars). Multivariate analysis showed that the mean relative loss was 13% for women who reported that breast cancer was not at all costly compared to 22%, 33% and 38% among women who said that breast cancer was a bit, quite or very costly, respectively (ptrend<0.0001). A higher relative loss was significantly associated with a lower level of education (difference between lowest and highest levels = 8 %, ptrend=0.0016), living =50 km from the surgery hospital (diff = 6%, p=0.0697), lower social support (diff = 8%, p=0.0119), invasive disease (diff = 6%, p=0.0861), chemotherapy (diff = 17%, p<0.0001), self-employment (diff= 17%, p<0.0001), shorter tenure in the job (diff between lowest and highest levels = 12%, ptrend<0.0001) and part-time work (diff = 10%, p=0.0003). Conclusions: Financial effects of wage losses could add to the overall burden of breast cancer. Clinicians and policy makers should be sensitized further to the fact that financial burden may be important for working women having more aggressive treatment and precarious work situations. No significant financial relationships to disclose.