bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health behaviors and survivorship needs of short- versus long-term melanoma survivors.
Authors: Swetter Susan M. , Gerry Arianna Aldridge , Bugos Kelly , Greco Ralph Steven , McGurk Katherine L. , Palesh Oxana 
Published: March 2020

9061 Background: Little is known about melanoma survivors and their long-term symptoms, sun protection practices and support needs from health professionals. Methods: Melanoma survivors previously treated at Stanford Cancer Center completed a quality improvement survey to explore the value of a melanoma survivorship clinic, as part of the Stanford Cancer Survivorship Program. The survey period ranged from July 2012 to September 2012, and 17% of the 893 invited survivors responded. We compared responses of melanoma survivors diagnosed between 2006-2011 (short-term) and 1995-2005 (long-term). Results: 153 cancer survivors (41% short- and 59% long-term) completed the survey. On average, they were 62 years of age (SD=15.1), 94% Caucasian, 47% female, and 68% underwent local excision alone. Long- vs. short-term survivors were less likely to receive routine skin screening every 3-6 months (38% vs. 83%, p<0.001) or follow-up for their melanoma in the last 6 months (54% vs. 76% p=0.045). Sun protection practices were similar between groups; however, long-term survivors decreased their use of tanning beds (33% vs. 18%, p=0.03) and time seeking a tan relative to short-term survivors (72% vs. 48%, p=0.002). Overall, survivors rated anxiety as the most prevalent symptom (33%), followed by numbness of the scar site (31%), forgetfulness (26%), sleep problems and depression (23%), pain and fatigue (17%). Sixty-eight percent of all survivors reported their symptoms were not addressed by their health provider, and of those stating their provider addressed their symptoms (32%), the survivor initiated the conversation 71% of the time. In general, survivors desired education about the long-term effects of melanoma (41%), family risk of skin cancer (28%), and protecting their skin from further damage (20%). Twenty percent of all survivors requested treatment for the long term effects of melanoma, and 12% wanted emotional support. Conclusions: Melanoma survivors experience continuing symptoms long after treatment, namely anxiety, and express a need for information about long-term melanoma effects, psychosocial support, and prevention of further skin cancer. Clinicians should routinely assess survivorship needs to improve quality of life.
Efficacy, safety, and pharmacokinetics (PK) of the BRAF inhibitor dabrafenib (D) hydroxypropyl methylcellulose (HPMC) capsule formulation in combination with the MEK1/2 inhibitor trametinib (T) in patients (pts) with BRAF mutation-positive metastatic melanoma (MM).
Authors: Schuchter Lynn Mara , Kudchadkar Ragini Reiney , Gonzalez Rene , Lawrence Donald P. , Sosman Jeffrey Alan , Infante Jeffrey R. , Daud Adil , Kefford Richard , Cebon Jonathan S. , Sharfman William Howard , Amaravadi Ravi K. , Boasberg Peter D. , Lewis Karl D. , Flaherty Keith , Ouellet Danielle , Little Shonda M , Clark Jennifer , Gibney Geoffrey Thomas , Patel Kiran , Hamid Omid 
Published: March 2020

9066 Background: Preclinical studies ofD + T show enhanced activity in BRAF mutant MM vs either drug alone. D + T safety and efficacy were evaluated in a 4-part (A–D) phase I/II study. Part D assessed the impact on efficacy, safety and PK of a more stable HPMC capsule formulation of D alone, and in combination with T, instead of the gelatin capsule used in Parts A–C. Methods: 110BRAFV600E/KMM pts with RECIST measurable disease were randomized to 4 cohorts. Dose-limiting toxicities (DLTs) were evaluated for the first 3 weeks of treatment. PK sampling was done on Days 1 and 21. Primary endpoints were PK and safety; secondary endpoints were response rate (RR) and overall survival (OS). Results: Median age was 54 years, 58% male, 65% ECOG PS 0, 88% V600E, 68% M1c stage, 97% no prior brain metastases, and 45% LDH > ULN. Treatment (tx) with D HPMC + T had little impact on ratio of D Cmax (1.16) and D AUC (1.23) vs D tx alone; but led to higher ratio of D Cmax(1.51) but similar D AUC (1.10) vs D gelatin + T seen in Part B. Median progression-free survival (PFS) and RR are in Table. Median PFS not reached in D4. No DLTs occurred in the first 15 subjects enrolled in D4. Most common AEs (≥40%) for all cohorts were pyrexia, nausea, chills, vomiting, arthralgia, and fatigue. Most common grade >3 AEs (all 5%) were hypertension, pyrexia, increased GGT, and hyponatremia. 11% of pts discontinued treatment due to an AE. There were no major differences in toxicities between cohorts and Parts A–C. Conclusions: The D + T combination had an acceptable safety profile with clinically manageable side effects. D HPMC + T had little impact on D Cmax and D AUC vs D alone. D HPMC led to higher D Cmaxbut similar D AUC vs gelatin + T. Meaningful clinical activity was seen in all dose combinations with D HPMC +T; PFS, RR, and duration of response were consistent with other study parts. Phase 3 studies with D HPMC + T are ongoing. Clinical trial information: NCT01072175. [Table: see text]
A phase I study of high-dose calcitriol in combination with temozolomide for patients (Pts) with metastatic melanoma (MM).
Authors: Pettijohn Erin , Rademaker Alfred , Martone Brenda K. , Poast Erica , Weitner Bing Bing , Eklund John W. , Kuzel Timothy 
Published: March 2020

9087 Background: Temozolomide (Tem) has demonstrated efficacy as an oral alternative for pts with MM on traditional and extended dosing schedules. Calcitriol has known antiproliferative properties in vitro, and has shown synergistic effects with chemotherapy. Additionally, vitamin D receptor (VDR) polymorphisms are associated with alterations in melanoma susceptibility and disease progression. Specifically, the VDR genotype tt/ff (Taq1 and Fok1 polymorphisms) has been associated with tumors >3.5mm, though no studies have focused on survival. Methods: Tem 150mg/m2was administered on days 2-8 and 16-22 every 28 days until progression or significant toxicity. Calcitriol was given on days 1 and 15 every 28 days with 3 pts at a dose of 0.2mcg/kg, 3 pts at 0.3mcg/kg, 3 pts at 0.5mcg/kg, and an additional 11 pts at a maximum dose of 0.5mcg/kg. VDR gene analysis was completed on 17/20 pts using PCR-RFLP based assays. Tolerability was the primary objective with secondary objectives of time to progression (PFS) and overall survival (OS), both as a whole and by VDR genotype. Results: Twenty pts (males=15) with MM treated with at least one prior systemic therapy or who were not candidates for interleukin-2 (conducted pre BRAF and anti CTLA agents), were accrued. Median age was 58. The regimen was well-tolerated with leukopenia, lymphopenia, thrombocytopenia, anemia, and thrombosis as the most common grade 3 or 4 toxicities at 10% incidence each, less than observed in prior studies (Patel et al Eur J Ca 2011). Obj RR was 10%. Median PFS was 1.8 mo with a mean of 2.7 cycles given. Pts with low-risk VDR genotype non-tt or ff (n= 11) had a median OS of 7.4 mo compared to 3.8 mo for tt or ff or both (n=6)(median ratio=1.95) from time of enrollment, although not statistically significant given small sample sizes. Conclusions: The extended dosing of Tem with calcitriol is a well-tolerated oral regimen in MM. The trend toward improved OS in non-tt/ff VDR genotypes is consistent with prior studies associating the tt/ff genotype with biologic aggressiveness. Whether this represents a benefit of the inclusion of calcitriol should be studied further. Clinical trial information: NCT00301067.
Frequency of BRAF V600E variant in circulating free DNA compared with the single melanoma biopsy.
Authors: Di Guardo Lorenza , Vallacchi Viviana , Frigerio Simona , Cova Agata , Squarcina Paola , Giardino Felicetta , Frati Paola , Colonna Valentina , Patuzzo Roberto , De Braud Filippo G. , Santinami Mario , Rivoltini Licia , Rodolfo Monica 
Published: March 2020

9092 Background: To select melanoma patients for treatment with BRAF inhibitors, the BRAF mutational status is determined in the most recent tumor biopsy. However, tumor specimens are not always available for the analysis, and relying on a single biopsy specimen can potentially exclude from treatment patients with heterogeneity among metastatic tumors due to polyclonality of BRAF mutation, which appears as a rather common condition. As an alternative approach we explored a blood-based mutation detection assay. Methods: We developed a method including enrichment for the BRAV600E variant by selective elimination of the wild type allele by TspRI digestion and BRAFV600E detection by TaqMan Mutation Detection Assay (BRAF_476_mu, Life Technologies). Sensitivity testing showed that BRAFV600E variant was detected starting from 6.25X10-5 ng of DNA, and specificity testing showed that the variant can be detected when diluted in 8X105 copies of wild-type alleles. Results: Mutational analysis performed by Sanger sequencing of exon15 in 114 melanoma biopsies showed that 4 (3%) harbored the c.1798_1799GT>AA (V600K) mutation, 1 (1%) the c.1799_1800TG>AA mutation (V600E), and 56 (49%) the most common c.1799T>A mutation (V600E), while by the novel method the latter mutation was detected in 9 additional specimens (8% increment) and confirmed by sequencing the PCR product after TspRI digestion. Pre-surgery plasma was available for 50/114 patients at advanced stages, 26/50 (52%) showing a mutated specimen, including 4 with a double nucleotide substitution (V600K and V600E). The matched plasma samples resulted mutated in 25/26 cases with mutated biopsy and in further 14/25 samples with biopsy resulting wild type; in contrast, plasma of 50 healthy controls tested negative. Taken together, these results indicate that V600E circulating variant was detectable in 39/50 (78%) plasma samples and in 22/50 (44%) tumor specimens. Conclusions: Detection of BRAF V600E variant in circulating free DNA may represent a more sensitive approach for patient selection and decision making process during the treatment with BRAF inhibitors.
Identification of functional DNA methylation aberrations associated with outcome in melanoma patients with brain metastasis.
Authors: Marzese Diego M , Huynh Jamie L , Huang Sharon , Hirose Hajime , Kiyohara Eiji , Morton Donald L. , Kelly Daniel F. , Hoon Dave S. B. 
Published: March 2020

9095 Background: Brain metastasis (MBM) represents one of the most significant causes of death in melanoma patients. Identification of clinically relevant markers is necessary to recognize patients with high risk of MBM development. Alterations in DNA methylation patterns have been recognized as a major epigenetic hallmark of metastasis initiation and progression. Methods: To generate a comprehensive genomic DNA methylation landscape of MBM, we performed genome-wide data integrative analyses examining the DNA methylation (Illumina HumanMethylation 450K), gene expression (Affymetrix HumanExon 1.0), and genotype (Affymetrix SNP 6.0) of specimens related to melanoma progression from normal to MBM (n=65). Results: We observed significant genome-wide hypomethylation and CpG island hypermethylation according to melanoma progression to the brain. To identify significant differentially methylated CpG sites between lymph node metastasis and MBM, we applied a strict statistical threshold (β-value difference >0.3 and FDR-corrected p <0.005). We identified the homeobox D (HOXD) gene family members amongst the most significantly affected genes. The influence on gene expression and the frequency of HOXD hypermethylation were verified using integrative analysis of publicly available data generated from 168 melanoma specimens. In a cohort of clinically annotated melanoma patients (n = 159), we demonstrated that hypermethylation of a genomic region in the HOXD gene cluster was significantly associated with shorter disease-free survival (p = 0.004) and overall survival (p = 0.002).Multivariate analysis confirmed the association with poorer survival (p = 0.01 and HR = 2.8; CI95%: 1.3-6.1). Conclusions: The use of genome-wide DNA methylation, gene expression, and genotyping integrative analyses allowed the identification of novel markers with functional and clinical implications for melanoma patients with brain metastasis.
What is the behavior of Breslow’s thickness?
Authors: Mendes Gelcio L. Q. , Koifman Sergio 
Published: March 2020

9097 Background: Localized cutaneous melanomas (CM) have their clinical course predicted by microscopic findings in the tumor specimen, mostly Breslow’s thickness (BTL), ulceration and mitoses. It is not certain whether BTL has a linear relationship with overall survival (OS) or relapse-free survival (RFS). The aim of this study was to evaluate BTL´s linear (LC) and its non-linear component (NLC) with relation to survival. Methods: All consecutive cases of CM treated from 1997 to 2006 at a single institution were identified, individuals with stage I or II tumors, minimum follow up of one month and known BTL were selected, socio-demographic data, clinical and pathological findings, treatment and outcomes were abstracted. Information about ulceration was missing in more that 30% of cases and it was not evaluated, there was no information about mitotic rate. Survival was estimated by the Kaplan-Meier method. Multivariate analyses were performed by the Cox model. BTL was evaluated as a continuous variable, and the LC and NLC by the technique of smoothing, using p-splines. Results: There were 1465 cases of CM, 51 with no follow up, 137 had no information about BTL and 202 had advanced stages. This analysis is based on 1075 cases. In the Cox model, the variables associated OS were age [hazard ratio (HR) 1.02, 95% CI 1.01 to 1.03], sex (HR 1.56, 95% CI 1.2 to 2.04) and BTL (HR=1.079, 95% CI 1.065 to 1.094). The variables associated with RFS were age (HR 1.017, 95% CI 1.009 to 1.024), sex (HR 1.372, 95% CI 1.104 to 1.704) and BTL (1.068, 95% CI 1.057 to 1.080). In the analysis of LC and NLC of BTL, it was found that both LC and NLC were statistically significant for OS and RFS. There was an increase in the HR as BTL increased in those lesions thinner than 4mm, then such increase was not as evident and lesions with more than 10mm had a similar OS and RFS (plateau). Conclusions: BTL is one of the most powerful prognostic criteria of patients with stage I and II CM. The risk of death increases linearly for thin lesions up to 4mm, lesions thicker than 10mm behave as a uniform group with no further decrease in OS or RFS as the lesion becomes larger. In conclusion, BTL may not behave as a linear function, it has a LC for thinner lesions, but for thicker lesions, above 10mm, further increase in BTL may add no more risk.
Forecasting the efficiency of chemoradiotherapy in patients having disseminated melanoma of skin.
Authors: Komarova Yekaterina , Frantsiyants Yelena , Dzhabarov Farhad , Rozenko Ludmila , Pozdnyakova Victoria 
Published: March 2020

e20005 Background: Result of scientific research testify that particularities of endocrinal status might play a role in etiology and pathogenesis of illness. In connection to this, studying of particularities of hormonal homeostasis in patients having skin melanoma becomes relevant, as on the background of the former, the tumor develops this or that reaction to remedial measures. Methods: Content of triiodothyronine (T3) in peripheral blood was studied in 40 patients of both sexes having disseminated melanoma of skin (pT2-3N1-2M0) before and after chemoradiation. Chemotherapy consisted of dacarbazine in course dose of 1000 mg/m2, radiotherapy – total boost dose was 55+5,4 Gy. Results: Assessment of direct clinical result of the complex of antitumor measures has demonstrated that in the group of patients under control the treatment proved inefficient in 15 people and was not accompanied by decrease of tumor formation sizes, while in 25 people the curative effect was manifested in 25-50% (15 cases) regress of tumor lesions and in over 50% (10 cases) regress. Conclusions: The results of chemoradiation were analyzed depending on the initial content of general T3 in the blood of the patients. It has been discovered that absence of effect from treatment was featured in patients having low content of the hormone – from 0,52 to 1,10 nmole/l, normal oscillations of its level in healthy people being 1,2 to 2,8 nmole/l. Contrary to that, in patients having regress of tumor, the initial concentration of the hormone ranged from 1,35 to 1,70 nmole/l, i.e. within the physiological norm.
Different prevalence of BRAF and NRAS somatic mutations in melanomas according to the patients’ origin.
Authors: Palmieri Giuseppe , Lissia Amelia , Cossu Antonio , Ascierto Paolo Antonio , Botti Gerardo , Caraco Corrado , Mozzillo Nicola , Ayala Fabrizio , Anniciello Annamaria , De Giorgi Vincenzo , Massi Daniela , Stanganelli Ignazio , Rubino Corrado , Palomba Grazia , Sini MariaCristina , Manca Antonella , Colombino Maria 
Published: March 2020

e20013 Background: Genetic factors predisposing to melanoma at germline level have been demonstrated to be geographically heterogeneous. We here evaluated the spectrum of NRAS and BRAF mutations at somatic level, in a large subset of melanoma tissues from patients originating from different Italian geographical areas: Sardinia, whose population is genetically homogeneous, and Middle-South Italy, with a genetically heterogeneous population. Methods: Patients were enrolled consecutively between June 2008 and December 2012. Genomic DNA was isolated from tumor tissues [primary melanomas (N=439) and melanoma metastases (N=269)] or melanoma cell lines (N=32). Paired samples of primary melanomas (n=140) and synchronous or asynchronous metastases from the same patients (n=203) were included. The full coding sequences and splice junctions of NRAS (exons 2-3) and BRAF (exon 15) genes were screened for mutations through automated sequencing. Results: BRAF/NRAS mutations were identified in 63% of primary melanomas (48% BRAF; 15% NRAS), 67% melanoma metastases (51% BRAF; 16% NRAS), and 68% melanoma cell lines (56% BRAF; 12% NRAS). A non-significant increase in mutation frequency after progression from primary melanoma was observed. However, distribution of BRAF/NRAS mutations varied between in vivo tumors and melanoma cell lines, suggesting a preponderant role for BRAF activation in highly proliferating cultured melanoma cells. Among paired samples, consistency of BRAF/NRAS mutation patterns between metastatic and primary melanomas ranged from 71% (skin metastases) to about 90% (lymph node and visceral metastases). A significant inverse distribution of BRAF/NRAS mutation rates was observed in our series on the basis of the geographical origin of patients: for BRAF, 58% Sardinian vs. 42% non-Sardinian cases (p=0.045); for NRAS, 2% Sardinian vs. 21% non-Sardinian cases (p<0.001). Conclusions: Our findings provide additional insights into the spectrum and distribution of BRAF/NRAS mutations in melanoma; moreover, they support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in such cancer genes.
Do nonmelanoma skin cancer survivors use tanning beds more often than the general public?
Authors: Wiznia Lauren , Ferrucci Leah M , Mayne Susan T , Chagpar Anees B. 
Published: March 2020

e20017 Background: Tanning bed use increases the incidence of nonmelanoma skin cancer (NMSC), however utilization of indoor tanning after diagnosis in this population is not well-studied. We sought to determine if tanning bed use among NMSC survivors differed from the general population. Methods: The National Health Interview Survey is an annual population-based survey that is representative of the civilian US population. We utilized the 2010 cancer supplement to evaluate self-reported tanning bed use in the previous 12 months in self-reported NMSC survivors compared to individuals without a history of skin cancer. Results: In 2010, 24,941 people were surveyed, 1.85% of whom had a self-reported history of NMSC. On univariate analysis, NMSC survivors were significantly less likely to use tanning beds in the previous 12 months (2.16 vs. 5.61%, p < 0.001). On multivariate analysis, however, NMSC survivors were equally likely to use tanning beds as those who had never had skin cancer (see Table). Conclusions: When controlling for other sociodemographic factors, NMSC survivors were no less likely to use tanning beds than the general population. These findings suggest a need to better educate NMSC survivors about the increased risk of future skin cancers with ongoing tanning bed use. [Table: see text]
Prognosis of melanoma in Peru: An analysis of 410 cases.
Authors: Coras Natalia , Morales Domingo , Yabar Alejandro , Beltran Brady Ernesto 
Published: March 2020

e20023 Background: Little is known of the status of melanoma in developing countries. Our retrospective study was performed to determine the clinical characteristics and outcome of patients with melanoma in Peru. Methods: All cases with a pathological diagnosis of malignant melanoma from our institution between January 2002 and December 2011 were identified. Clinical data were extracted through retrospective chart review. Patients’ characteristics are presented using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were evaluated using log-rank and Cox proportional-hazard regression tests, respectively. Results: A total of 410 cases were evaluated. The median age at presentation was 66 years (range 4-97 years) with a male-to-female ratio was 1.1:1. There were 146 cases (35.6%) of acral lentiginous melanoma, 67 (16.3%) of nodular melanoma, 54 (16.3%) of mucosal melanoma, 39 (9.5%) of superficial spreading melanoma, 55 (13.4%) were lentigo maligno and 49 (12.0%) were unclassifiable. Melanoma of unknown primary occurred in 34 (8.3%) of cases. The proportion of patients with stage I, II, III and IV disease were 24.2%, 24.8%, 21.9% and 7.8%, respectively. Ulceration status of 320 cases of cutaneous melanoma was recorded and 138 (45.1%) had ulceration. The 5-year survival rate of 409 patients was 58.4% with a median survival time of 7.6 years. The 5-year survival rates of patients with stage I, II, III and IV disease were 88.2%, 67.8%, 39.3% and 17.8% respectively (p<0.001). Univariate analysis showed age >65 years (p=0.003), male sex (p=0.0001), stage (p<0.001), nodular histology type (p<0.001), ulceration (p<0.001), Breslow thickness (p<0.001), Clark level (p<0.001) and localization (mucosal vs. cutaneous) (p<0.001) were associated with survival. In the multivariate analysis, stage was associated with worst prognosis (p=0.01), while other factors had no statistical correlation with survival. Conclusions: Based on our report, acral lentiginous melanoma is the most common type of malignant melanoma in Peruvian patients, and clinical stage was the only independent prognostic factor associated with survival.