bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of hepato-pulmonary metastasis and their impact on clinical outcomes in uveal melanoma.
Authors: Javed Asad , Al Saleh Abdullah S. , Block Matthew Stephen , McWilliams Robert R. , Yan Yiyi , Kottschade Lisa A. , Markovic Svetomir 
Published: May 2020

e22052 Background: Metastatic Uveal Melanoma (MUM) is a rare tumor with poor prognosis following development of liver metastasis. We hypothesized that patterns of metastasis in Uveal Melanoma correlate with clinical outcomes. Methods: We retrospectively reviewed patients with MUM at Mayo Clinic, Rochester from January 1999 to August 2019. Patients were stratified into two groups based on the pattern of hepatic and pulmonary metastasis at the time of diagnosis of metastatic disease: Group 1 (≤5 liver metastasis or lung metastasis) and Group 2 ( > 5 liver metastasis without lung metastasis). Baseline characteristics were compared between both groups. Survival analysis was performed using the Kaplan Meier method. Univariate and multivariate analysis were performed for Overall Survival (OS). Results: 147 patients were included in the study (n = 67 Group 1; n = 80 Group 2). In Group 1, 49/67 patients presented with ≤5 liver metastasis and 18/67 had lung metastasis without liver metastasis. Median OS for Group 1 was significantly longer than Group 2 (38 vs. 15 months; p < 0.0001) (Table). On univariate analysis, predictors for OS were: Pattern of Metastasis, ECOG PS > 0, Time to metastasis > 60 months, and Surgical metastatectomy. Pattern of Metastasis was an independent predictor for OS in a multivariate model that included these predictors (p = 0.0004). Group 1 patients were more likely to undergo surgical metastatectomy compared to group 2 (21.5% vs. 1.3%; p < 0.0001). Interestingly, the median time to metastasis from diagnosis of UM was significantly longer for Group 1 as compared to Group 2 (67 vs. 24.5 months; p < 0.0001). Conclusions: Limited (≤5) liver metastasis or lung metastasis (without liver metastasis) at diagnosis predict favorable clinical outcomes in MUM. The occurrence of such metastasis following a significantly longer time from primary diagnosis suggests the existence of a distinct sub-type of metastatic disease with relatively indolent behavior. [Table: see text]
Patient-reported outcomes among patients with resected high-risk melanoma (AJCC7 IIIB, IIIC, M1a, M1b) randomized to low- or high-dose adjuvant Ipilimumab (ipi) versus high-dose interferon alfa-2b (HDI): Health-related quality of life (HRQL) analysis of ECOG-ACRIN E1609.
Authors: Tarhini Ahmad A. , Zheng Yue , Lee Sandra J. , Hodi F. Stephen , Rao Uma , Cohen Gary Irvin , Sondak Vernon K. , Kirkwood John M. , Wagner Lynne I. 
Published: May 2020

e22078 Background: The primary objective of the patient-reported outcomes (PRO) study of E1609 patients (pts) was to compare overall HRQL among pts receiving ipi (ipi10, ipi3) or HDI. We hypothesized that ipi would be superior to HDI in HRQL. Secondary analyses compared HRQL and GI distress between ipi10 and ipi3. Methods: PROs were administered among pts enrolled from NCI Community Oncology Research Program (NCORP) sites at baseline, every 12 weeks (wks) during treatment, and every 24 wks off-treatment for one year. Differences between ipi arms and HDI in overall HRQL at 12 wks (completion of ipi induction) was defined a priori as the primary outcome. HRQL was assessed using the 27-item Functional Assessment of Cancer Therapy –General (FACT-G) total score. GI toxicity was a secondary outcome measured by the 11-item FACIT-Diarrhea (FACIT-D) scale. Two sample t-test was used to compare scores between arms. Results: 548 pts completed PROs at baseline and 334 at 12 wks. Among 322 (59%) pts with PRO data at both time points, mean FACT-G total change scores from baseline to 12 wks were significantly lower (indicating less decline in HRQL) among pts randomized to ipi10 (-4.9,SD:14.1) or ipi3 (-3.4 points,SD:13.2) vs. HDI (-12.9, SD:14.1), p < 0.05 for both ipi10 vs. HDI and ipi3 vs. HDI. Mean FACIT-D change scores indicated higher GI distress from baseline to 12 wks among pts randomized to ipi10 (-3.7, SD:6.9) or ipi3 (-2.2, SD:5.1) vs HDI (-0.7, SD:2.7), p < 0.05 for both comparisons. In comparing ipi10 to ipi3, FACT-G total and FACIT-D total change scores from baseline to wk 12 were comparable. Conclusions: Overall decline in HRQL from baseline to completion of ipi induction was less among pts receiving ipi compared to HDI. Pts randomized to ipi reported a greater increase in diarrhea compared to HDI. HRQL and diarrhea were comparable between ipi3 and ipi10. Our findings are based on PRO data, thus increase our confidence in capturing pts’ experience with treatment from the pt’s perspective. Clinical trial information: NCT01274338. [Table: see text]
Local hormonal status of tumor and adjacent tissues in patients with melanoma depending on their gender.
Authors: Bandovkina Valeria A. , Frantsiyants Elena M. , Rozenko Ludmila Ya. , Pozdnyakova Viktoria V. , Ilchenko Maria G. , Agarkova Elena I. , Maksimova Natalia A. , Przhedetskiy Yuriy V. , Kit Oleg I. 
Published: May 2020

e22084 Background: Gender is an important independent prognostic factor for cutaneous melanoma incidence, and survival in women is better. The purpose of the study was to determine the content of sex steroids and prolactin in tumor, perifocal and resection line tissues in male and female patients with melanoma. Methods: The study included 13 men and 22 women with cutaneous melanoma (M) pT1-2N0M0. Levels of free testosterone (fT), estradiol (E2), estrone (E1), progesterone and prolactin were measured by ELISA in M, perifocal (P) and resection line (RL) tissues after surgical treatment. The average age of patients was in men 54±3.56 years (median age 53, 32-81), in women 65±2.67 years (median age 63, 39-82). Skin tissues obtained from 20 non-cancer patients after plastic surgery served as the control. Results: In M of women, levels of fT, E2 and E1 were elevated on average by 1.3 times, while in men fT was decreased by 1.7 times, and estrogens were increased – E2 by 1.7 and E1 by 3.7 times, compared to the corresponding control levels. In women, fT in P tissues was increased by 1.6 times, while parameters in RL were similar to control values. In men, fT in P and RL tissues was decreased by 3.8 and 2.3 times respectively, and E2 was increased by 1.6 and 1.3 times respectively. E1 in P tissues was decreased by 1.7 times, in RL – similar to control levels. Conclusions: M in patients of both genders has an altered hormonal profile characterized by hyperestrogenia, with the prevalence of E1 and androgen deficiency in men. The expansion of the “tumor field” due to changes in the hormonal profile of P and even RL tissues was established only in male patients with the same morphological prevalence of the process, which may be one of the reasons for the more aggressive tumor course.
Relationship of chronic neurogenic pain and fibrinolysis in the blood of patients with melanoma.
Authors: Rozenko Ludmila Ya. , Frantsiyants Elena M. , Bandovkina Valeria A. , Pogorelova Yulia A. , Cheryarina Natalia D. , Gusareva Marina A. , Kit Oleg I. 
Published: May 2020

e22085 Background: The plasminogen regulation system is critical in triggering proteolysis to cleave the extracellular matrix and basement membrane. The “uPA-uPAR” system is involved in extravascular fibrinolysis and is responsible for the formation of plasmin associated with invasion and metastasis. The purpose of the study was to analyze levels of factors of the plasminogen regulation system in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of PAP, uPA, uPAR and PAI-1 were measured by ELISA in patients with Т3-4NxM0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: Blood levels of PAP in women with M+CNP were twice higher than in patients with M without CNP, the levels in men with M+CNP did not change; uPA content increased in both women and men with M without CNP by 1.4 and 1.5 times, uPA activity was elevated only in women by 2.4 times, in men it was reduced by 2 times; uPAR was increased by 1.5 times in women and men compared to the values in both female and male patients with M without CNP. PAI-1 content in women and men with M+CNP was similar to control values, and its activity was increased in women by 1.5 times and decreased in men by 2.5 times. Conclusions: The study gives significant additional information on the effect of CNP on relationships in the plasminogen activation system in a combination of cutaneous melanoma and CNB showing marked gender differences. The results should be taken into account in the special treatment of patients with melanoma.
AMBLor: A prognostic and stratifying biomarker for adjuvant immunotherapy of AJCC stage II melanomas.
Authors: Labus Marie , Ellis Robert , Ewen Tom , Podlipnik Sebastian , Greenwood Alison , McConnell Ashleigh , Long Anna , Ness Tom , Jones Claire , Stefanos Niki , Sloan Philip , Husain Akhtar , Barrett Paul , Puig Susana , McArthur Grant A. , Lovat Penny 
Published: May 2020

e22094 Background: The success of adjuvant therapy for patients with AJCC stage III melanomas coupled with the increased risk of mortality for patients with AJCC stage IIB compared to IIIA tumours has paved the way to adjuvant immunotherapy trials for patients with sentinel lymph node (SLNB) –ve AJCC stage II disease. However, the lack of biomarkers able to appropriately stratify high-risk tumour subsets limits patient recruitment. We have recently identified the combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas as a robust prognostic biomarker and valuable pre SLNB test. Methods: Retrospective analysis of AMBLor was performed in three geographically distinct cohorts of AJCC stage II melanomas using a clinically validated automated IHC assay and semi quantitative binary scoring analysis to define high vs low risk subgroups. Results: Data revealed loss of AMBLor overlying non-ulcerated high risk AJCC stage IIA or B tumours correlated with a significant reduction in disease free survival (DFS) at 12 years to 55% compared to 89% for patients with AMBLor low risk tumours (P = 0.015; HR 4.83, 95% CI: 2.29-10.14). Sub-cohort multivariate analysis of 80 non ulcerated stage IIB tumours also revealed reduced DFS at 12 years to 68% in AMBLor high-risk compared to 83% in AMBLor low-risk tumour subsets, with an assay sensitivity of 97% and a negative predictive value of 90%. Furthermore, sub-cohort analysis of SLNB –ve AJCC stage IIA or B tumours additionally identified 5 genuinely low risk cases in which DFS at 10 years was 100% compared to only 36% in 37 patients in which AMBLor was lost. Conclusions: Collectively these data indicate AMBLor as a novel prognostic biomarker for patients with non-ulcerated AJCC stage II melanomas as well as companion/stratifying biomarker for adjuvant immunotherapy, the use of which will increase clinician confidence for patient recruitment as well as reduce patient morbidity.
Adjuvant therapy in non-metastatic melanoma result from a Brazilian cohort.
Authors: Silva Sinara Figueiredo , Tavares Monique Celeste , De Barros E Silva Milton Jos , Rinck José Augusto , Lima Joao Paulo SN , Garcia Daniel , Calsavara Vinicius Fernando 
Published: May 2020

e22095 Background: The PD-1–blocking antibodies, combination of target therapy and anti-CTLA4 have shown a favorable safety profile with better efficacy than high-dose interferon in the adjuvant setting. However, in Brazil only a minority of patients in private institutions have access to new therapies in adjuvants. Here, we describe the evolution of patients with non metastatic melanoma who received anti-PD1 or target therapy adjuvant or only followed. Methods: This is an observational, descriptive, retrospective cohort, which included patients diagnosed with cutaneous, mucous or acral melanoma (operated stage III or stage IVa) submitted or not they undergoing adjuvant chemotherapy between January 2013 and December 2019 at AC, São Paulo, Brazil. Results: We evaluated 82 patients with a median age of 54 years, 62.2% of the patients were male, the majority, 81.1%, white. In 29.3% had primary ulceration and presence of satellites was observed in 18.3% and the average Breslow value of the cases was 3,3mm. We found that 18.3% of patients were classified as stage IIIA, 4.9% IIIB, 22% IIIC, 8.5% IIID and 9.8% stage IV operated. The 44.6% of patients completed 1 year of adjuvant treatment. Related to the presence of ulceration, we observed a progression-free survival of 36.3 months for cases with ulceration versus 47.1 months for cases with absent ulceration, ( p= 0.449). Patients with satellite presence had a progression-free survival of 29.9 months versus 49.1 months for cases of missing satellite, ( p= 0.118). Patients who underwent lymph node dissection had a progression-free survival of 50.3 versus 36.4 months, those who did not undergo ( p= 0.201). Patients who completed 1 year of adjuvant therapy achieved a recurrence-free survival of 66.1 versus 27.9 months who did not complete, ( p= 0.003). Considering the tumor staging, patients classified T1a-T2a had a progression-free survival of 59.8 months, T2b-T3b of 42 months and those grouped as T4a, T4b, of 29.9 months, ( p = 0.021). The median progression-free survival was 44 months, 40.6 months for patients who received adjuvant treatment versus 27.2 months for those who did not ( p = 0.271) with a reduced risk of progression in the order of 33% for patients who received adjuvant. Conclusions: The presence of ulceration, satellites and advanced T staging were associated with a worse outcome with a greater chance of recurrence. Emptying of the lymph node chain, receiving adjuvant treatment and completing 1 year of adjuvant treatment were directly associated with improved survival
Preoperative treatment for marginally resectable metastatic melanoma: A single center experience in China.
Authors: Xu Yu , Shen Xuxia , Sun Wei , Kong Yunyi , Chen Yong , Yan Wangjun 
Published: May 2020

e22096 Background: Large randomized trials have proved that targeted therapy (TT) and immunotherapy (IT) can improve RFS for resectable Stage III melanoma. However, there is still a risk around 15%~25% of relapse within 1 year, especially worse for Stage IIID disease. Several neoadjuvant trials have shown a potentiality of long-term relapse-free after a pathologic complete response, especially for immunotherapy. We conducted a prospective study to investigate the impact of preoperative treatment on the anti-tumor efficacy and disease-free survival for Chinese melanoma. Methods: Stage IIID patients with matted nodes were recruited. For BRAF V600E-muted patients, Vemurafenib (V) was given for one months ahead of the surgery. For BRAF-wide-type patients, anti-PD1 antibody, Pembrolizumab(P) or Toripalimab (T) was given one dose per 3 weeks until response or intention-to-progression was observed. Pathologic assessment followed the principles for neoadjuvant therapy established by INMC. Results: Totally seven patients have been recruited. Detail information was listed in Table. Clinical ORR was 71%, however with no pCR observed. One patient in Vemurafenib group occurred brain mets within 1 month after surgery. All four patients in anti-PD1 group were relapse-free so far after median follow-up of 11 months. Conclusions: Preoperative BRAF targeted and anti-PD1 immunotherapy might guarantee a positive impact on anti-tumor response and local disease control for marginally resectable melanoma. However, the pathological criteria for neoadjuvant treatment might not be suitable to evaluate the matted or bulky specimen after preoperative treatment. [Table: see text]
Three times of intratumor injection of the sustained released by ROS with penicillin-combined chemotherapy drugs for the long of survival period of the tumor-bearing mouse.
Authors: Chen Dong , Fu Qiang , Zhang Jian , Han Yan , Li Bian , Zheng Guoqin , Zhao Ming , Yu Baofa ,   Shandong Baofa Cancer Therapeutics, Inc.
Published: May 2020

e22098 Background: To study the effect of sustained release by ROS with hapten for three intratumoral injections of chemical drugs on the survival of tumor-bearing mice. Methods: Mice bearing solid tumors of H22 liver cancer were randomly divided into groups with the longest tumor diameter of about 4-7 mm. They were administered intratumorally the next day, with a second interval of 7 days and an interval of 14 days (the 15th day of the experiment). During the period of administration and observation, the death of mice was observed daily, and the time of death was recorded to calculate the life extension rate. Results: The weight of mice in group Ⅲ and group Ⅳ was lower than that in control group, suggesting that chemotherapeutic drugs caused damage of mice and did not significantly increase body weight. Tumor size: Tumor volume experimental groups were different from the Control group, showing a significant anti-tumor effect; but there was no difference compared with Dox Control. Survival The survival rate of each group of mice is closely related to the tumor progression and drug treatment. The survival rate of each group after 45 days of treatment is significantly higher than that of the Control group. The average survival time of group Ⅳ, group Ⅰ and group Ⅱ was longer than that of control group with significant difference. Conclusions: After intratumoral injection 3 times, the survival time of mice is been prolonged.
Effect of urokinase gene knockout and chronic neurogenic pain on melanoma growth in the experiment.
Authors: Kaplieva Irina V. , Frantsiyants Elena M. , Surikova Ekaterina I. , Neskubina Irina V. , Bandovkina Valeria A. , Trepitaki Lidia K. , Lesovaya Natalia S. , Cheryarina Natalia D. , Nemashkalova Ludmila A. , Pozdnyakova Viktoria V. , Przhedetskiy Yuriy V. , Zakharova Natalia A. , Khokhlova Olga V. , Przhedetskaya Viktoria Yu. , Kit Oleg I. 
Published: May 2020

e22099 Background: Studies have shown that the axis of the urokinase-type plasminogen activator (uPA–uPAR) has a pleiotropic effect in different stages of cancer. The purpose of the study was to reveal characteristics of the B16/F10 melanoma development in mice with the uPA gene knockout with and without chronic neurogenic pain (CNP). Methods: The study included male and female С57ВL/6 mice (n = 102) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice with the uPA gene knockout (n = 48). B16/F10 melanoma was transplanted subcutaneously to the animals in the main groups 2 weeks after bilateral sciatic nerve ligation (CNP model). Mice with the standard melanoma transplantation were the controls. Results: The survival of uPA gene-knockout mice with melanoma was similar to that in controls and was 1.5 times (p < 0.05) longer in females than in males; the melanoma onset in these mice was observed a week earlier; the dynamics of tumor growth showed a pronounced gender dependence: in females, the tumor practically did not grow, and its volume before the death did not exceed 1.0 cm3, while in males the tumor was characterized by an active growth with two peaks of the volume increase (weeks 2 and 4); melanoma metastasized weakly - single metastases to the lungs (in females) or no metastases but with hemorrhages in the lungs and heart (in males). CNP reduced the survival of uPA gene-knockout females, similar to mice with the normal genome, but did not affect the survival of males; primary tumors in uPA gene-knockout mice emerged a few days later than in the control, but grew more intensively, with gender differences smoothed out; increased metastasis was demonstrated by the initiation of metastatic lesions of the lungs and liver in males, while hemorrhages in the lungs maintained, and by an increased number of metastases in the lungs with the appearance of lung hemorrhages in females. Conclusions: The uPA gene knockout differently changes the course of B16/F10 melanoma in male and female mice. CNP enhances the tumor growth, erasing gender differences, and activates metastasis of melanoma.
Management of pyrexia in metastatic melanoma patients: A real-world clinical experience survey study.
Authors: Satija Ambika , Pickard A. Simon , Ionescu-Ittu Raluca , Laliberté François , Ling You-Li , Nakasato Antonio Reis , Kang Barinder , Duh Mei Sheng , Patel Jeetvan 
Published: May 2020

e22102 Background: Patients with BRAF+ metastatic melanoma (MM) have more options for treatment, including targeted therapy and immunotherapy. However, the risk of toxicities may contribute to lower treatment rates and duration. Pyrexia is a reversible adverse event commonly associated with BRAF/MEK inhibitors. However, little is known about the features, management strategies, as well as variations in pyrexia management in clinical practice. Methods: The study was conducted over two phases. Phase 1 was a qualitative study conducted with expert nurses to develop a pyrexia management questionnaire. The questionnaire was further enhanced through a pre-test with nurses to improve reliability and internal validity of the responses captured for this study. During Phase 2, a cross-sectional web-based questionnaire was administered to oncology registered nurses, nurse practitioners and physician assistants. All respondents were required to have managed pyrexia in patients with MM receiving dabrafenib+trametinib (D+T). Results: Respondents (N = 201, 57.2% academic center and 42.8% community based), on average, had 12.5 years of experience and >50% had managed more than 10 patients with BRAF-MEK inhibitor in the past 12 months. Almost all respondents (97.5%) discussed pyrexia with patients at D+T initiation. At the onset of the first episode of pyrexia in a patient, most respondents either try to keep patients on the starting dose (34.9% for D, 42.8% for T) or withhold the medication only temporarily (52.4% for D and 47.8% for T), even with a fever of 104°F. Mean time to treatment reinitiation was 1.5 days and, in more than half of the instances (52.3% for D and 51.4% for T), respondents would ask the patients to reinitiate at the starting dose. Respondents also asked patients to initiate antipyretics (87.5%) or corticosteroids (34.5%) to manage pyrexia symptoms. Even at pyrexia recurrence, respondents generally preferred keeping patients on treatment, with only 4.2% recommending permanent discontinuation. In general, respondents were very comfortable in managing pyrexia-related symptoms in their patients (mean score 7.8, 1 = very uncomfortable, 10 = very comfortable). Conclusions: In clinical practice, respondents were very comfortable in managing pyrexia. They tried to keep patients on D+T as long as possible. Experienced oncology nurses, nurse practitioners and physician assistants are able to manage pyrexia symptoms and keep patients on treatment for a longer duration to help obtain maximum clinical benefit.