bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble VEGF-A and lymphangiogenesis in metastatic malignant melanoma patients
Authors: Soubrane C. , Mouawad R. , Sultan V. , Spano J. , Khayat D. , Rixe O. 
Published: April 2020

8049 Background: Vascular endothelial growth factor (VEGF-A) and its circulating form (sVEGF-A) play a major role in tumor progression and angiogenesis. However, the clinical implications of circulating VEGF-A in metastatic malignant melanoma patients and its role in tumor-associated lymphangiogenesis and lymphatic metastasis remained unclear. Objectives: The aim of this study is to evaluate the potential role of circulating VEGF-A levels in lymphangiogenesis and its usefulness in metastatic malignant melanoma patients. Methods and Patients: using a sensitive enzyme-linked immunosorbent assays, VEGF-A level was measured in sera of 65 patients treated by biochemotherapy with a fully documented history of disease in comparison with 30 healthy controls. Results: A wide range (0- 566 pg/ml) of pretreatment sVEGF-A level was detected in the serum of MMM patients and the median level (40.5 pg/ml) was significantly higher (p=0.0007) than that of healthy donors (7.5 pg/ml). Age, gender and LDH were not associated with sVEGF-A levels. Regarding tumor burden, median pretreatment sVEGF-A level was higher in patients with high tumor burden (n= 40) as compared to patients with low tumor burden (n=25). Furthermore, the most surprising finding of our study was that patients with only lymph node metastasis (n=23) had a significantly (p= 0.021) higher median sVEGF-A levels (45.7 pg/ml) as compared to the 42 patients with different metastatic sites (16.6 pg/ml). Conclusion: these results suggest that sVEGF-A levels may predict lymph node metastasis in metastatic malignant melanoma patients. In addition, it may be promising targets for new therapeutic strategies in melanoma disease. No significant financial relationships to disclose.
Immunophenotype of regionally recurrent melanoma of the extremity in patients before isolated limb infusion (ILI)
Authors: Brady M. S. , Gnjatic S. , Ritter G. , Jungbluth A. A. 
Published: April 2020

8052 Background: ILI is an effective, though palliative, treatment for patients with regionally recurrent melanoma of the extremity. Tumor-associated antigens such as the Cancer Testis (CT) antigens and melanocyte differentiation antigens (MDAs) have been used successfully as targets for vaccine-based immunotherapy trials in patients with recurrent melanoma. Little is known about expression of these antigens in patients with regional disease. Methods: Samples of regionally recurrent melanoma were obtained from patients prior to ILI as part of an ongoing clinical trial. 22 available samples were formalin-fixed, paraffin-embedded and analyzed by IHC for the following antigens (using the following monoclonal antibodies): CT antigens (MAGE-A1 [MA454], MAGE-A3 [M3H67], MAGE-A4 [57B], NY-ESO-1 [E978], CT7/MAGE-C1 [CT-33], GAGE) and MDAs (gp100 [HMB45], Melan-A/MART-1 [A103], tyrosinase [T311]). The presence of antibodies to CT antigens was analyzed by ELISA. Results: The antigen expression profile was as follows (positive/total): MAGE-A1 9/22 (41%); MAGE-A3 13/22 (59%), MAGE-A4 11/22 (50%), CT7 14/22 (64%), NY-ESO-1 8/22 (36%), GAGE 12/22 (55%), Melan-A 20/22 (91%), tyrosinase 20/22 (91%), gp100 19/22 (86%). The expression pattern was homogeneous for the vast majority of MDAs and for most CT antigens. No serologic response to any of the tested CT antigens was found in any of the patients. Conclusions: Regionally recurrent melanoma exhibits a homogeneous expression of melanocyte differentiation and CT antigens indicating expression similar to distant metastases. Despite the often prolonged course of patients with regionally recurrent disease, there is no evidence of an effective immune response to CT antigens. No significant financial relationships to disclose.
The value of multi-marker reverse transcriptase-polymerase chain reaction (MM RT-PCR) assay in lymphatic drainage (LY) and peripheral blood (BL) for molecular staging of melanoma patients (pts) after lymph node dissection (LND)
Authors: Ruka W. , Nowecki Z. I. , Rutkowski P. , Kulik J. , Lorenc E. , Nasierowska-Guttmejer A. , Zurawski Z. , Zdzienicki M. , Siedlecki J. A. 
Published: April 2020

8053 Background: We assessed the presence of melanoma cells in LY and BL in melanoma pts after LND with MM RT-PCR assay for the evaluation of disease outcomes. Methods: Between 05/2002 and 06/2005 we collected 24-hr LY in 207 stage III melanoma patients after radical LND (91 - completion LND after positive sentinel node biopsy - CLND and 116 - therapeutic LND for clinically/cytologically detected regional lymph node (LN) metastases - TLND). In 101 pts (since 02/2004) we have simultaneously collected a 5 ml sample of BL. In order to detect melanoma cells, RT-PCR assays with primers specific for tyrosinase, MART1 (MelanA) and uMAGE mRNA were applied. The drain fluid or BL sample was assumed to be positive if the presence of at least 1 marker was detected in the assay. Median follow-up time for survivors was 13 months (range: 4 - 39 months). Results: The LY MM RT-PCR assay results were positive in 57/207 pts (27.5%) - in 13 for tyrosinase only, in 17 for MART1 only, in 10 for uMAGE only, in 13 for a combination of the two markers and in 4 simultaneously for all three markers. We observed a significantly higher rate of recurrences in pts with positive LY MM RT-PCR results (44/57 cases; 77%) than in those with negative results (72/150 cases; 48%; p=0.0004). Positive results of the LY MM RT-PCR correlated with established predictive factors: the number of involved lymph nodes (p=0.03), extracapsular extension of LN metastases (p=0.004) and type of LND (CLND vs. TLND; p = 0.0004). We observed a significant relationship between positive LY MM RT-PCR results and shorter overall (OS) and disease free survival (DFS), both in univariate and multivariate analyses. In 107 pts, in whom the LY and BL MM RT-PCR assays were analyzed concurrently, we found positive results of the LY RT-PCR assay in 33 cases (32.7%) and the BL RT-PCR assay in 24 cases (23.7%) (17 of these positive results were detected in both tests), but longer follow-up time is necessary to perform a survival analysis in this group. Conclusions: We observed positive results of MM RT-PCR assay for melanoma cells in approximately 28% of LY after LND, which correlated significantly with early melanoma recurrences and shorter survival. No significant financial relationships to disclose.
Impact of age and gender in patients with thin melanoma
Authors: Chang C. K. , Liu S. K. , Choi J. S. , Liu R. C. , Fuchshuber P. F. 
Published: April 2020

8056 Background: The incidence of thin melanoma (≤ 1mm) continues to increase. The purpose of this study was to characterize the incidence and prognosis of thin melanoma among the various age groups. We analyzed the records of 15,267 patients diagnosed with melanoma of these we were able to identify 5573 patients with thin melanoma (≤ 1mm). Methods: A retrospective review was undertaken to identify patients with thin melanoma (<1mm) treated at all the Northern California Kaiser Permanente facilities. All patients received their treatment between January 1998 and December 2004. Univariate and multivariate analyses of predictive factors were evaluated with the log-rank test and Cox regression. In addition chi-square test of relevant clinicopathologic factors determined which factors were predictive of overall survival (OS). Results: Mean age was 55 years (range 8–101). Mean follow-up was 74 months (range 3–209) and 54% were male. Primaries were on the trunk (34%), lower extremities (19%), upper extremities (26%), or head/neck (20%). Mean thickness was 0.4 ± 0.25 mm. The most common histology was superficial spreading (88%). The overall 5 and 10 year survival were 89 and 79, respectively. By univariate analysis age, sex, location and histology were predictive of OS however by multivariate analysis only age and sex were predictive of OS. The female/male ratio was 2 in patients diagnosed before the 3rd decade, and this ratio approached 1 in the mid-5th decade. However, the female/male ratio was 0.5 among patients diagnosed with melanoma in their 8th decade. Conclusions: Females are more susceptible than men to the risk of melanoma at a younger age however this susceptibility changes with increasing age. Our results demonstrate that the incidence of melanoma may be influenced by age and gender. No significant financial relationships to disclose.
Sentinel lymph node biopsy (SLNB) in melanoma and a simple prognostic score in a prospective cohort with long term follow-up
Authors: Nasroulah F. , Gonzalez A. , Kaplan J. , Tajer C. , O'connor J. M. , Chacon M. R. , Costanzo M. V. , Sade J. P. , Varela M. M. , Chacon R. D. 
Published: April 2020

8058 Background: Outcome of early stage melanoma is related to pathological and clinical findings like SLNB status, but a systematic approach to risk stratification is lacking. Objectives: To assess outcome, and clinico-pathological criteria associated to recurrence and death of patients (pts) who underwent SLNB Methods: From 11/1994 to 5/2005, 286 clinical stages I/II melanoma pts underwent SLNB in our Institution. Median follow up was 38 months. Prognostic factors were analysed with Logranktest and proportional hazard regression. Survival curves with Kaplan-Meier method. A score was derived from coefficients of multivariate analysis and evaluated with ROC curves on 259 pts with complete data. Results: Median age: 48yr; male sex: 54%; median Breslow (Br): 1.8mm. SLNB +: 46 pts (16.1%). Ulcerated: 31%. 5-yr overall survival was 56% in SLNB+ vs 84% in SLNB-, p=0.0002. Five-yr relapse free survival was 52% in SLNB+ vs 73% in SLNB-, p=0.0017. SLNB status, Br, Clark level, Age>50yr, male sex, and ulceration were related to death by univariate analysis, but in multivariate analysis, only SLNB status (HR 2.36), Br (HR 1.66 for each T level of TNM staging) and ulceration (HR 2.35) remained. The score derived from the model was: 5 points (p) for SLNB +; 4p for ulceration; and 0p for Br<1mm, 2p for Br 1–2mm, 4p for Br 2–4mm, and 6p for Br>4mm. Conclusions: SLNB status, Br, and ulceration were, in concordance with literature, statistically significant prognostic factors. This allowed us to build a simple score with good correlation with prognosis (c index: 0.79). This score could be a useful tool for clinical practice and for future clinical trials, but validation in different populations is required. [Table: see text] No significant financial relationships to disclose.
Results of FRESH START: A randomized controlled trial to improve diet and exercise behaviors in breast and prostate cancer survivors
Authors: Demark-Wahnefried W. , Clipp E. , Lipkus I. , Lobach D. , Peterson B. , Snyder D. , Sloane R. , Macri J. , McBride C. , Kraus W. 
Published: April 2020

8503 Background: Cancer survivors are at increased risk for cardiovascular disease, diabetes, osteoporosis and other cancers. A healthy diet and regular exercise may improve the health and well-being of survivors and ultimately reduce health risks. Methods: 543 individuals within 9-mths of diagnosis with locoregional breast or prostate cancer were referred by 445 providers and recruited from 39 states and 2 provinces within North America. Subjects were randomized to an arm that received a 10-mth program of tailored mailed print materials to promote fruit and vegetable (F&V) consumption, reduce total/saturated fat intake and/or increase exercise or an arm that received a 10-mth program of non-tailored mailed materials on diet and exercise available in the public domain. Telephone surveys conducted at baseline and 1-yr follow-up assessed body mass index (BMI), and responses to the Diet History Questionnaire, the 7-Day Physical Activity Recall and psychosocial/behavioral indices. Anthropometric data were obtained on a 22% subsample to validate self-reports. Results: Complete baseline and follow-up data were obtained on 519 participants (4% attrition). Sample demographics were as follows: mean age = 57 (range: 22–85), 85% white, 56% female, and 64% overweight/obese (none were underweight). Uncontrolled analyses (t-tests) indicate that both arms significantly improved their diet and exercise behaviors (p’s <.05) over the 1-year study period; however significantly greater changes occurred in the experimental arm (see table). Conclusion: The FRESH START intervention was successful in changing the behaviors of individuals with newly diagnosed cancers. Serum assays and collection of 2-yr follow-up data (to determine the durability of longer term behavior change) are currently underway. Further study is needed to determine if the effects of this intervention generalize to other populations of cancer survivors (i.e., other cancers and individuals further-out from diagnosis). [Table: see text] No significant financial relationships to disclose.
Multicenter, randomized, double-blind, ondansetron (ond)-controlled, dose-ranging, parallel group trial of the neurokinin-1 receptor antagonist (NK-1 RA) casopitant mesylate for chemotherapy-induced nausea/vomiting (CINV) in patients (pts) receiving moderately emetogenic chemotherapy (MEC)
Authors: Arpornwirat W. , Albert I. , Hansen V. L. , Russo M. A. , Ross G. A. , Pence C. D. , Bandekar R. R. , Grunberg S. M. 
Published: April 2020

8512 Background: Casopitant mesylate is a potent, selective, oral NK-1 RA, which has shown activity in preventing CINV in preclinical studies. Based on phase I positron emission tomography (PET) studies, casopitant doses from 50–150 mg result in 70–95% saturation of NK-1 receptors. This phase II trial evaluated the addition of casopitant to standard prophylaxis (ond + dexamethasone [dex]) in pts receiving MEC. Methods: MEC regimens included ≥ 1 of the following (in mg/m2): cyclophosphamide (ctx) 500–1,500 with other MEC; ctx alone 750–1,500; oxaliplatin ≥ 85; doxorubicin ≥ 60; epirubicin ≥ 90; or carboplatin AUC ≥ 5. Pts were stratified by gender and taxane use. Pts in the first 5 arms received ond 8 mg BID days (D) 1–3 + dex 8 mg IV D1 with either placebo, casopitant 50 mg QD D1–3, casopitant 100 mg QD D1–3, casopitant 150 mg QD D1–3, or casopitant 150 mg D1. Arm 6 received a different ond regimen (16 mg QD D1–3) + dex 8 mg IV D1 + casopitant 150 mg QD D1–3. Primary endpoints were rates of complete response (CR [no vomiting, retching, rescue meds or premature withdrawal]) and no significant nausea (SN, assessed by visual analogue scale) during the first 120 h after initiation of MEC. Arms 5/6 were exploratory and not included in primary analysis. Planned enrollment was 118 pts/arm for intent-to-treat (ITT) analysis. Results: ITT group includes 719 pts (60% male, 40% female). CR rate (120h) was 70% with ond control; 81% for casopitant 50mg; 79% for 100mg; and 85% for 150mg (p=.012, Cochran-Armitage trend test). CR rates (24h) and no SN (120h) were similar among all groups. CR and no SN rates in the exploratory arms were 80% and 66%, respectively, in arm 5 and 84% and 70% in arm 6. Adverse events were similar across all arms, with nausea, fatigue, and neutropenia (≤ 24%) as most common. All casopitant doses were generally well tolerated. Conclusions: Casopitant demonstrated activity in control of CINV at all doses, with the 1-day dose of particular interest, when added to a standard ond + dex regimen in both male and female pts receiving a variety of MEC regimens. [Table: see text]
Emotional responses of oncologists when disclosing prognostic information to patients with terminal disease: Results of qualitative data from a mailed survey to ASCO members
Authors: Wallace J. A. , Hlubocky F. J. , Daugherty C. K. 
Published: April 2020

8520 Background: Prior studies describe physician reluctance to reveal prognostic information to advanced cancer patients (acp), but little data exists describing their actual disclosure practices. Methods: A mailed survey was conducted to assess medical oncologists’ (MOs) self-reported behaviors, beliefs, and attitudes regarding prognostic conversations with terminally ill acp. Following letter pre-notification, surveys were mailed to a systematic sample of 1,222 MOs with U.S. addresses listed in the 2004 ASCO Membership Directory. Surveys contained a $25 gift card. The survey included qualitative questions eliciting emotional responses when communicating prognostic information to acp. Results: 729 surveys were completed and returned (60% response rate) with 654 providing qualitative responses (90%). The median age was 51 (range, 34–80) with male predominance (80%). Practice representation was: 56% (private), 23% (academic-based) and 20% (other active practice). MOs most commonly (47%) expressed negative emotions including sadness, pain, depression, heartache, feelings of loss, guilt, anxiety, stress, and finally discomfort with how their patient might react. They reported these conversations as unhappy, unpleasant, frustrating, and bothersome. They also described them as difficult, hard, exhausting and/or draining. 31% of MOs reported empathy, sympathy, compassion, caring, supportiveness, comfort, or being calm during prognostic disclosure. 14% reported positive feelings including optimism, hope, helpfulness, gratification, reward, or relief. 11% related emotional objectivity, detachment, control, or neutrality. Finally, MOs responses listed younger acp age as being a determinant of negative emotions. Conclusions: Negative emotions are more commonly described by MOs when asked to discuss their feelings toward prognostic disclosure. A lesser proportion described objectivity or a lack of emotion. Some related positive emotions. This qualitative data provides a greater explanation for MOs reluctance to disclose prognostic information. No significant financial relationships to disclose.
Assessment and quantification of taxane-induced neurotoxicity in a phase III randomized trial of breast cancer (AC followed by PAC/DOC vs. PAC/DOC alone): N-SAS BC 02
Authors: Shimozuma K. , Ohashi Y. , Takeuchi A. , Aranishi T. , Morita S. , Kuroi K. , Ohsumi S. , Makino H. , Watanabe T. , Hausheer F. H. 
Published: April 2020

8523 Background: Chemotherapy-induced peripheral neuropathy (CIPN) commonly occurs during taxane chemotherapy (Tx). There is no standardized approach used in the assessment of CIPN. Physician-based instruments (e.g., NCI-CTC) are widely used for this purpose, but are associated with several important limitations. As current medical evidence suggests that physician-based assessments under-report the incidence and severity of subjective symptoms, they cannot reliably or accurately assess symptoms of CIPN. We prospectively assessed CIPN during Tx in a phase III randomized trial to evaluate the reliability and sensitivity of these different approaches. Methods: Three hundred breast cancer (BC) patients entered the National Surgical Adjuvant Study of Breast Cancer 02 (N-SAS BC 02), a phase III randomized trial comparing 4 cycles of AC followed by 4 cycles of Tx (paclitaxel [PAC] or docetaxel [DOC]) vs. 8 cycles of Tx alone in N+ BC patients after surgery. CIPN and QOL were secondary endpoints. Patient-based PNQ and FACT-Ntx were compared to the clinician-based NCI-CTC. Assessments were conducted at baseline, 3rd, 5th, 7th cycles, 8 months, and one year after starting adjuvant treatments. A linear mixed effect model was used to compare data in the two treatment groups across repeated cycles of treatment. Results: Average response rate of the instruments was > 90%. Sensory PNQ scores strongly correlated with sensory FACT-Ntx scores (r=0.70), while they weakly correlated (r=0.43) with NCI-CTC scores. NCI-CTC scores distributed between 0 and 2, while PNQ scores distributed between 0 and 4. Comparison of CIPN during the first 3 cycles showed that significantly higher overall incidence of sensory disturbance was observed in Tx compared with AC as assessed by both PNQ (PAC, P<0.0001; DOC, P=0.0007) and NCI-CTC (PAC, P<0.0001; DOC, P=0.0026). The PNQ appeared to detect more severe grades of sensory neuropathy compared to NCI-CTC. Conclusions: This study confirmed that physicians tended to underestimate CIPN, and patient-rated PNQ was a more reliable and valid instrument to assess CIPN. The development of new and reliable assessment methods would represent important medical advancements for cancer patients. [Table: see text]
The efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: A phase III randomized, double blind, placebo-controlled NCCTG trial, N01C3
Authors: Renno S. I. , Rao R. D. , Sloan J. , Wong G. , Johnson D. , Howard G. M. , Novotny P. , Patrick F. J. , Loprinzi C. L. 
Published: April 2020

8530 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose limiting complication of chemotherapy. Lamotrigine (an anti-convulsant drug) appears to have some benefit when used to treat pain from neuropathy due to various etiologies. Based on these data, we conducted a phase III randomized placebo controlled study to determine the efficacy of lamotrigine in treating symptoms from CIPN. Methods: Patients with CIPN for 1 month or more were randomly assigned to lamotrigine (target dose 300 mg/day, increased by 50 mg/2 weeks) or placebo for 10 weeks. The co-primary endpoints were differences in average CIPN symptoms assessed by pro-rated area under the curve (AUC) of a numerical pain rating scale (NRS) and the Eastern Cooperative Oncology Group sensory neuropathy (ESN) scale. Accrual of 60 patients per group provided t-tests with 80% power to detect a difference of 0.57 standard deviation for each co-primary endpoint (moderate effect size) with a type I error of 0.025. Results: 131patients were enrolled, with complete data available for analysis in 93 (72%). Analyses were limited to this cohort but will be updated. Chemotherapy drugs considered to be causative of the CIPN were vinca alkaloids (30%), taxanes (25%), platinum-agents (7%), combinations (34%), and others (3%). Patients were equally matched with regards to baseline characteristics. Patients who enrolled had severe symptoms, with a baseline median ESN at enrollment of 3 (out of 3) in both groups. Toxicities were similar in both groups, however, more patients discontinued lamotrigine due to toxicities/refusals than those on placebo (32% vs 13% resp; p=0.04) and were therefore less likely to complete the 10 weeks therapy (60% vs. 78% resp, p=0.08). Average AUC of NRS score for patients on lamotrigine and placebo was 30.5 and 33.7 resp (p=0.48). The corresponding average AUC of the ESN scores were 12.4 and 14.5 (p=0.23). The proportions of patients with a 10 point (of 100) improvement in worst pain score (39% vs 36%) and a 1 point change in ESN (25% vs 27%) were similar between the lamotrigine and placebo arms, resp. Conclusions: These results suggest that lamotrigine is not effective for managing pain and symptoms due to CIPN. No significant financial relationships to disclose.