bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of venous thromboembolic events (VTE) in multiple myeloma patients receiving lenalidomide (LEN) with and without dexamethasone (DEX).
Authors: Brandenburg Nancy A. , Knight Tyler , Anastassopoulos Kathryn P. , Minton Neil , Knight Robert D. 
Published: March 2020

e18559 Background: LEN showed significant efficacy and was generally well tolerated when combined with DEX in two randomized, double-blind, pivotal phase 3 registration trials in relapsed or refractory multiple myeloma (MM). VTEs have been associated with LEN and DEX combination (LEN+DEX) regimens in patients (pts) who may have other risk factors for VTE. Fewer VTEs have been reported among pts receiving low dose DEX. This study examined the incidence of first VTE and associated risk factors among MM pts receiving LEN and LEN+DEX. Methods: An exploratory, retrospective, claims-based study of pts diagnosed with MM and receiving LEN from Jan 2006 – June 2008 was performed using OptumInsight’s Invision Data Mart Multiplan database. Pts receiving additional MM chemotherapies were excluded. DEX dose level was defined over the first four 28-day cycles of LEN as: low (≤160 mg), medium (>160 mg to <480 mg), or high (≥ 480 mg). Cumulative incidence of first VTE (deep vein thrombosis or pulmonary embolism) within 120 days of initiating LEN treatment was calculated from Kaplan-Meier curves. Risk factors for VTE were examined using hazard ratios (HRs) from a Cox model that included demographics, prior MM therapy, comorbid conditions, DEX dose, and prophylactic use of anti-thrombotics. Results: 643 LEN-treated MM pts were identified (mean age 60 years, 60% male, 13.5% with prior VTE). Cumulative incidence of first VTE at 120 days from first LEN dose was 6.1% overall (95% CI 4.4-8.3%) and 7.2% (5.1-10.2%) in LEN+DEX. VTE risk for LEN without DEX (n=190; 66 with other steroids) was 3.4% (1.5-7.5%). VTE risk by DEX dose level was 5.9% (3.6-9.7%) for low DEX (n=286), 7.5% (3.6-15.1%) for medium DEX (n=99), and 12.3% (6.3-23.1%) for high DEX (n=66). Significant risk factors for VTE were prior VTE (HR=3.9; p<0.001), recent surgery (HR=2.1; p=0.047), renal failure (HR=2.2; p=0.023), and high dose DEX (HR=2.3; p=0.045). Conclusions: Incommunity-based MM pts treated with LEN+DEX, VTE risk increases with the dose of DEX. The exact mechanism by which DEX intensity impacts VTE is not clear. In addition to high dose DEX, other known VTE risk factors were observed.
Summary of treatment-emergent renal events from patients treated with single-agent carfilzomib from four phase II studies in relapsed and/or refractory multiple myeloma.
Authors: Harvey R Donald , Lonial Sagar , Patel Priti , McCulloch Leanne , Niesvizky Ruben , Kaufman Jonathan L. 
Published: March 2020

e18569 Background: Patients (pts) with multiple myeloma (MM) are vulnerable to renal injury and impairment both from their disease and treatment-related adverse events (AEs). Carfilzomib (CFZ) is a selective proteasome inhibitor with proven efficacy in MM. Safety data have been compiled from over 700 pts who have received single-agent CFZ. All were pretreated and included individuals with varying degrees of renal function, including hemodialysis pts. Herein we present an analysis of the incidence and severity of CFZ treatment-emergent renal events from 526 pts in four phase 2 trials. Methods: Pts from the 003-A0, 003-A1, 004, and 005 trials were included in this analysis. In all studies, CFZ was dosed on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle (C). Doses were 20 mg/m2 in C1 for all studies escalating to 27 mg/m2 in C2 per individual protocol, except 005 (15 mg/m2 in C1, 20 mg/m2 in C2, and 27 mg/m2 in C3). Renal AEs—the incidence, frequency, and resolution of episodes of worsening renal function, defined minimally as a doubling of serum creatinine from baseline—and shifts in other laboratory parameters were tabulated and summarized based on NCI CTCAE v.3 criteria. Results: The majority of pts (71%) had renal dysfunction (CrCl <50 mL/min) at baseline. Overall, 87% experienced no significant worsening of renal function during the course of treatment. Transient worsening was reported in 31 pts (6%) with a median duration of 1.4 weeks and a median of 1.0 episode per patient; non-transient worsening was reported in 37 pts (7%) with 8 (2%) of those permanently discontinuing treatment due to a renal dysfunction AE. 38 patients (7.2%) experienced Grade 3/4 acute renal failure, of which 31 were Grade 3. The percentage of patients in 003-A0, 003-A1, and 004 whose creatinine levels shifted to Grade 3 or 4 from any lower grade was <5%. Results from 005 showed no major PK differences in pts with a wide range of renal function. Conclusions: Treatment-emergent renal events resulting in CFZ discontinuation were uncommon. Based on the findings from this cross trial analysis, CFZ dose and schedule need not be adjusted in pts with baseline renal dysfunction, including pts on hemodialysis.
Clinical implication of PET/CT and skeletal bone survey in evaluation of multiple myeloma and related monoclonal disorders.
Authors: Popalzai Muhammad Jawad , Alkaied Homam , Mansoor Maryah , Brenner Arnold , Dai Qun 
Published: March 2020

e18574 Background: Whole body skeletal x-ray is considered a gold standard for detecting bone lesions in patients with plasma cell disorders. PET/CT has been increasingly used but its role is yet to be defined. We conducted this study to compare the role of these two imaging modalities in evaluation of plasma cell disorders. Methods: This is single institution, retrospective study to evaluate the role of skeletal survey and PET/CT in patients with multiple myeloma, smoldering myeloma and MGUS. Patients’ records, imaging reports and subsequent management plan were reviewed and compared. Results: A total of 16 patients were reviewed. Among them, 11 patients had multiple myeloma, 2 had smoldering myeloma, and 3 had MGUS. 7/11 patients with multiple myeloma had concordant findings on skeletal survey and PET. 3 of these patients had negative skeletal surveys but had positive finding on PET/CT. PET/CT also identified plasmacytomas in 2 patients. In 2 patients with smoldering myeloma, both skeletal survey and PET/CT were negative. 2/3 patients with MGUS had lytic lesions on skeletal surveys which were not revealed by subsequent PET/CT’s. Both patients were observed without treatment and at 2 years follow up did not show disease progression. Conclusions: Our retrospective analysis showed that skeletal survey is still important for base-line evaluation of bone lesions in multiple myeloma and related monoclonal disorders. PET/CT is more sensitive for detection of bone lesions and can also detect extraosseous lesions such as plasmacytomas. Using tumor metabolic activity, PET/CT may improve diagnostic accuracy and is complementary to conventional skeletal survey. [Table: see text]
Sentinel lymph node evaluation among elderly melanoma patients: Missed opportunities?
Authors: Shah Dhruvil R , Yang Anthony D , Maverakis Emanual , Martinez Steve R. 
Published: March 2020

e19001 Background: Elderly patients may not receive indicated therapies offered to younger patients. We hypothesized that elderly patients with intermediate thickness cutaneous melanoma would be less likely to receive a sentinel lymph node biopsy than their younger counterparts. Methods: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for intermediate thickness cutaneous melanoma (Breslow thickness 0.75 to 4.00 mm) from 2004 to 2008. We excluded patients with mucosal melanoma, those without a biopsy-proven diagnosis, and those diagnosed at autopsy. Patients were categorized according to age by decade. We used multivariate logistic regression models to predict use of sentinel lymph node biopsy. Additional covariates other than age included sex, race/ethnicity, T stage, tumor histology, tumor location, ulceration, and LDH status. Likelihood of undergoing sentinel lymph node biopsy was reported as odds ratios (OR) with 95% confidence intervals (CI); significance was set at p ≤ 0.05. Results: Among 12,283 patients with intermediate thickness cutaneous melanoma, 12,206 had complete information regarding the use of sentinel lymph node biopsy. Of these, 6,642 (54.4%) underwent sentinel node biopsy. On multivariate analysis, patients in the two oldest age categories were less likely to receive sentinel node biopsies (age 70 to 79 years OR 0.65, CI 0.55-0.76 and age 80 years or more OR 0.29, CI 0.24-0.35). Additional factors associated with a decreased likelihood of receiving a sentinel node biopsy included head and neck primary tumor site (OR 0.57, CI 0.51-0.64), high (OR 0.45, CI 0.31-0.65) or unknown (OR 0.32, CI 0.28-0.36) serum LDH, Asian (OR 0.58, CI 0.36-0.94) or unknown (OR 0.51, CI 0.36-0.72) race, and lentigo histology (OR 0.79, CI 0.66-0.95). Conclusions: Elderly patients with intermediate thickness melanoma are less likely to receive sentinel node biopsy than their younger counterparts. The elderly may benefit from sentinel node biopsy, and efforts should be made to increase performance of this procedure in this population. Further research to assess reasons why the elderly are less likely to receive sentinel node biopsy are needed.
Sentinel node biopsy in melanoma patients: The role of day surgery and local anaesthetic approach for quality-of-life and effective cost reduction.
Authors: Ricci Fabio , Saralli Erminio , Capuano Loreto Giovanni , Dorkin Maurizio , Valleriani Mario , D'Achille Anna Maria , Di Emma Veronica , Greco Luigi , Violante Assunta , Filippi Luca , Natali Maurilio , Pacchiarotti Alberto , Annetta Alessandro 
Published: March 2020

e19002 Background: Sentinel node biopsy (SNB) is used in the management of melanoma patients without nodal metastases. Methods: From January 1, 1998 to December 31, 2011 we performed 182 SNBs at St. M. Goretti Hospital. Patients presented a primary melanoma, Breslow thickness equal to or higher than 1 mm, lower than 1 mm with regression and/or ulceration, and/or IV-V Clark level, and/or mitotic rate ≥ 1/mm2, according to the 7th edition melanoma staging system. All patients underwent pre-operative lymphoscintigraphy with intradermal injection of 50-70 MBq 99 mTc colloidal albumina particles, 50-80 nm size range, in 0.1-0.2 ml saline solution. We never used blue dye. All patients underwent surgical treatment 4-12 h. later. We performed SNB in day-surgery (DS) under local anaesthesia (LA). Surgery incision was 3-4 cm. This study was approved by an ethics committee, discussed with all patients and informed consent was obtained. Purpose of the study is to investigate the validity of this approach for quality of life and cost reduction. Results: 165 patients underwent SNB, 64 (38.7%) in the inguinal region, 83 (50.3%) in axilla, 1 (0.6%) in the popliteal region, 4 (2.4%) patients showed inguinal bilateral sentinel lymph-node (SLN), 6 (3.6%) axillary bilateral SLN, 4 (2.4%) axillary and 3 (1.8%) inguinal double SLN. The SLN identification rate was 100%. After surgery we distributed a questionnaire to the patients about the acceptability of this approach. In 32 patients SLN was positive. In these patients we performed radical lymphoadenectomy, 12 (37.5%) inguinal and 20 (62.5%) axillary. Conclusions: The results achieved are extremely accurate. This procedure is safe, well accepted by patients (98%), reported better quality of life. The oncological results are absolutely reliable. As regards hospital logistics, operations in DS and LA can be easily managed, leading to a significant cost reduction, 42.15% less expensive than the same operation performed under general anaesthesia.
Prospective pilot study of Merkel cell carcinoma.
Authors: Orlova Kristina Vyacheslavovna , Markovich Alla Anatolievna , Selchuk Vladimir Yur'evich , Demidov Lev V. , Orel Nadezhda Fedorovna , Subramanian Somasundaram 
Published: March 2020

e19005 Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. The annual incidence for MCC, based on SEER database, was 0.6 cases per 100,000 in 2006 (0.15 cases per 100,000 in 1986), with slightly more males affected (60%). Due to its rarity, data on its clinico-pathological features and impact of therapy are limited. Aim: To characterize MCC based on immunohistochemical (IHC) features and serum levels of biochemical markers such as chromogranin A (CgA) and serotonin and select treatment options. Methods: This prospective pilot study included 7 patients (pts) since 2009 and their age, sex, primary site, IHC features and serum levels of biochemical markers, progression-free-survival (PFS) were recorded. Median of overall survival was not achieved. Results: Pts characteristics were: age 44–67 years (mean 57), male–female ratio = 4:3. Most common primary sites were extremities (5pts), lymphnode metastases from unknown primary (1pt) and genitals (1pt). IHC showed diffuse positivity for CgA (6pts), dot-like staining for cytokeratin 20 (7pts), synaptophysin (6pts), Ki-67 (40%-1pt, 50%-1pt, 60–70%-5pts). The tumors did not express vimentin, TTF1. Serum levels of Cg A (2pts) and serotonin (1pt) were above normal. Treatment: Local disease – surgery, either alone (1pt) or as part of multimodality plan (2pts); Locoregional disease – surgery plus chemotherapy (2pts) and chemotherapy alone (1pt); Distant disease – chemotherapy plus surgery (1pt). Median of PFS was 16 months.Two patients with improvement of biochemical markers continue to receive maintenance therapy with somatostatin (SST) analogues for 16 and 24 months with complete remission. Conclusions: SST analogues facilitates treatment of MCC without reducing quality of life and increase PFS in patients with high CgA serum level. In spite of recent advances in understanding the biology of MCC, many molecular mechanisms that influence behavior stills are unknown.
Final results of a phase II immunotherapy trial for stage III and IV melanoma patients.
Authors: Riker Adam Irwin , Rossi Gabriela R. , Alsfeld Leonard C , Denham Fiona , Tennant Lucinda , Ramsey William Jay , Link Charles J. , Harrison Marilynn , Vahanian Nicholas N. 
Published: March 2020

e19008 Background: Patients with metastatic melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment option for high risk, resected stage III, recurrent, refractory or stage IV melanoma patients. Methods: We completed a phase II clinical trial of HyperAcute-Melanoma vaccine (HAM, NLG12036, NewLink Genetics) combined with pegylated interferon (Sylatron, Merck). Trial design was a 12-week regimen with the initial 4 weekly treatments consisting of HAM alone (intradermally) followed by 8 additional treatments of HAM + Sylatron (subcutaneously, 6 µg/kg). Trial endpoints include clinical response, overall safety and correlative findings for observed anti-tumor effect. Results: N=25, median age 60, 68% male with 21 patients completing the trial, 4 stopped due to progressive disease (PD). HAM-related common side effects include erythema and induration at the injection site, without significant grade 3 or 4 toxicities associated with the vaccine. By RECIST criteria, of 16 stage IV patients, there were 2 complete responders (CR), 2 with stable disease (SD) and 3 with no evidence of disease (NED) after resection. For stage III patients, 3/9 remain NED, 1 patient with slowly progressive disease remaining alive for over 30 months. The median overall survival is 29 months, with 50% of the patients surviving for 2 years and 12/25 (48%) still alive. The anti-αGal Ab values increased after vaccination in 24/25 patients by up to 100-fold (median 15, range 3-127). All evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Anti-tyrosinase Ab’s developed in 7/23 correlating with 1 CR and 1 patient NED. Vitiligo developed in 4/25 patients, correlating with 2 CR and 2 NED. Conclusions: Combinatorial immunotherapy with HAM plus Sylatron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and addition of other potentially synergistic agents should be explored to further enhance the benefit of this immunotherapeutic approach.
Prevalence of sentinel lymph node evaluation in patients with thick primary cutaneous melanoma.
Authors: Olusanya Abimbola O , Shah Dhruvil R , Yang Anthony D , Maverakis Emanual , Canter Robert J. , Martinez Steve R. 
Published: March 2020

e19013 Background: Sentinel lymph node biopsy (SLNB) was developed for intermediate thickness melanoma. Its use for thick cutaneous melanoma is controversial. We aimed to report on clinical and pathologic factors associated with the overuse of SLNB for thick primary cutaneous melanoma. Methods: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for thick primary cutaneous melanoma (known Breslow thickness > 4.00 mm) from 2004 to 2008. We excluded patients with mucosal melanoma, those without a biopsy-proven diagnosis, those diagnosed at autopsy, patients whose lymph node evaluation was unknown or other than SLNB “yes” or SLNB “no”. We used multivariate logistic regression models to predict use of SLNB. Covariates examined included: age sex, race/ethnicity, Breslow depth, tumor histology, tumor location, and ulceration status. Likelihood of undergoing sentinel lymph node biopsy was reported as odds ratios (OR) with 95% confidence intervals (CI); significance was set at p ≤ 0.05. Results: Among 1,981 patients with thick cutaneous melanoma, 1,158 (58.2%) received a SLNB. On multivariate analysis, patients with primary melanomas of the arm (OR 2.07, CI 1.56-2.75; p<0.001), leg (OR 2.40, CI 1.70-3.40; p<0.001) and trunk (OR 1.82, CI 1.38-2.40; p<0.001) had an increased likelihood of receiving a SLNB, as did those with desmoplastic histology (OR 1.47, CI 1.11-1.96; p=0.008). Conclusions: A significant number of patients with thick melanomas receive a SLNB, even though this procedure was not developed for this patient population. We have identified predictors associated with the use of SLNB. These include: arm, leg and trunk primary sites and desmoplastic histology. Further research to assess whether use of SLNB in this population is detrimental or beneficial is needed.
The prognostic utility of LDH and CRP for survival after melanoma metastasectomy in the urogenital tract.
Authors: Gakis Georgios , Abdelhafez Mohamed F , Todenhoefer Tilman , Renninger Markus , Schwentner Christian , Stenzl Arnulf 
Published: March 2020

e19021 Background: Recent studies suggest that serum lactate dehydrogenase (LDH) and serum C-reactive protein (CRP) are risk factors for survival in patients with metastatic melanoma. However, due to the relatively low tropism of metastatic melanoma lesions in the urogenital tract the clinical benefit of metastasectomy in this highly selective group of patients remains uncertain. The objective of this study was to address the role of LDH and CRP as preoperative serological risk factors for survival in patients with solitary or concomitant metastatic melanoma lesions in the urogenital tract. Methods: All patients who were referred for metastasectomy in the urogenital tract in a tertiary center within 1999-2008 were considered for this analysis. Demographic, disease and survival data were collected. Elevated LDH activity was defined as >250U/l and elevated serum CRP>0.5mg/dl. The primary endpoint was overall survival (OS), calculated using Kaplan-Meier method with log-rank test and multivariate Cox-regression analysis. Results: Of a total of 21 patients,16 (76%) had solitary urogenital metastases and 5 patients (24%) concomittant non-urogenital metastases.Median OS after metastasectomy was 23 months (range: 3-59 months). LDH>250U/l was significantly associated with decreased OS (27.6 vs. 6.0 months; p=0.001), but elevated CRP did not (24.1 vs. 20.7 months; p=0.93). No further significant differences in survival were found for age (p=0.76), gender (p=0.83), number of urogenital metastatic sites (0.97) and preoperative solitary vs. concomitant distant metastases (p=0.48). In multivariate analysis, adjusted for the TNM-stage grouping (M1a-c) and CRP level, elevated LDH maintained significance as negative prognostic factor for overall survival (p=0.0015). Conclusions: To our knowledge, this is the first study addressing the prognostic role of LDH and CRP in patients with melanoma urogenital metastases. If confirmed in large prospective studies, LDH level may be used for preoperative risk stratification in patients scheduled for melanoma metastasectomy in the urogenital tract to identify those patients who profit most from the surgical approach.
The impact of sun protective behavior and vitamin D supplementation on vitamin D level in melanoma patients.
Authors: Kumar Rachit , Khanna Sarika , Reutemann Patricia , Wenk Kurt S , Venna Suraj S. , Jang Sekwon 
Published: March 2020

e19025 Background: Vitamin D (VitD) is synthesized in the skin as a result of exposure to sunlight and its deficiency is common in the general population as well as in cancer patients. Sun protection is strongly recommended for patients after a melanoma diagnosis. We conducted a pilot study to assess the prevalence of VitD deficiency and the impact of both sun protective behavior and VitD supplementation on VitD levels in melanoma patients Methods: Adult patients with AJCC Stage 0-III melanoma were recruited from the Washington Cancer Institute between July 2011 and January 2012. Subjects completed a questionnaire asking about oral VitD supplementation and sun protective behaviors. VitD deficiency was defined by a 25-hydroxyvitamin D (25(OH)D) level less than 30ng/mL. Pearson Chi-square test and multivariate logistic regression were used to determine predictors of VitD deficiency. Results: A total of 49 participants (20 males, 29 females) completed the questionnaire and provided a blood sample for 25(OH)D determinations. Median age was 52 years (23-82), and most (n=48, 98%) were Caucasian. The majority had either stage 0 (n= 13, 27%) or 1 (n=29, 59%) melanoma. Twenty-six (53%) reported regular use of VitD supplements, and the majority reported sun protective behaviors (n=36, 73%). The prevalence of VitD deficiency was 46% (n=23). VitD deficiency was more common in patients who were not taking VitD supplementation (73% vs. 26%, p<0.01). Other associations include: (1) BMI>25 vs. BMI ≤25 (57% vs. 33%, p=0.10); (2) winter vs. summer months(54% vs. 40%, p=0.34); (3) those who practiced sun protective behavior vs. not (50% vs. 38%, p=0.48). On multivariate analysis, the use or non-use of VitD supplementation remained the only significant predictor of VitD deficiency (OR=0.11, p<0.01). Conclusions: VitD deficiency is common in melanoma patients especially in those who are not on VitD supplementation.