bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous side effects (cAE) of vemurafenib (V): Single-center cohort study of 28 metastatic melanoma (mM) patients (pts).
Authors: Goldinger Simone M. , Rinderknecht Jeannine Desiree , Belloni Benedetta , Eggmann Nina , Dummer Reinhard 
Published: March 2020

e19017 Background: V is a potent BRAF inhibitor with significant impact on progression-free and overall survival in mM pts. cAE are very common. This single-center observation analyses the clinical and histological spectrum of this new class-specific cAE in 28 pts treated with V in different clinical trials. Methods: 28 mM pts stage IV were treated with V 960mg b.i.d. in local ethic committees approved clinical trials. Occurring side effects were collected and documented prospectively. 65 biopsies were analysed. cAE were classified by reaction pattern as inflammatory diseases, hair and nail changes, keratinocytic proliferations, melanocytic disorders and proliferations. Results: V was well tolerated; in 2 pts dose reduction was necessary due to arthragia. 26/28 pts (93%) experienced cAE. UVA dependent photosensitivity and maculopapular exanthema were observed in 16 and 14 pts respectively. The histology of the rash demonstrated alteration of eccrine and follicular structures with mild inflammation and no increased keratinocytic apoptosis, thus differing from the rash of MEK inhibitors. Pruritus was observed in 8, folliculitis in 5, and burning feet in 3 pts. Hair thinning and alopecia occurred in 8 pts, 2 pts presented with curly hair. Follicular hyperkeratosis and acanthopapilloma were common skin reactions (n=12/n=13), as well as plantar hyperkeratosis (n=4), keratoacanthoma (n=5) and invasive squamous cell carcinoma (n=4). Histology of the acanthopapilloma (n=39) showed marked hyperkeratosis and acanthosis with koilocytes and mitosis, suggesting viral association. Single observations of morbus Bowen, Bowen carcinoma, basal cell carcinoma and a warty dyskeratoma were documented. 1 pt developed after more than 4 months of therapy a secondary primary melanoma on the capillitium (BRAF and RAS wildtype). Conclusions: V has a broad and particular cAE profile involving epidermis and adnexals. Regular skin examination by experienced dermatologists is crucial under V to detect and treat the possible side effects promptly. The treatment is very well tolerated but can have an impact in quality of life; ergo the pts have to be well informed. UVA optimized photoprotection is essential.
Ipilimumab use in a named-patient program in metastatic melanoma: Experiences in 185 German patients.
Authors: Eichhorn Christoph , Schlaak Max , Hassel Jessica C. , Loquai Carmen , Stoffels Ingo , Gutzmer Ralf , Paetzold Sylvie , Keller Ulrich , Ulrich Jens , Tsianakas Athanasios , Egberts Friederike , Janssen Eva , Garbe Claus , Eigentler Thomas K. 
Published: March 2020

e19031 Background: The monoclonal antibody ipilimumab (ipi) showed a survival benefit in patients (pts) with unrespectable metastatic melanoma leading to its approval in 2011. Methods: Ipi was available in Germany before its approval in a Named-Patient Program for pts with unrespectable stage IV/IIIC melanoma. Pts were eligible if they failed at least one prior systemic treatment or were intolerant and did not suffer from auto-immune diseases. Ipi was administered at a dosage of 3mg/kg iv (4 cycles, q21). A re-induction was possible in case of progressive disease after initial clinical benefit. Results: Data from 185 pts (114 male; 71 female, median age: 60 [18-88Y]) of 12 German centers was evaluable. 175 pts actually received ipilimumab (100 pts received all 4 cycles). Reasons for early termination were: Reduced general condition (44%), tumor progression (28%), toxicity or wish of pts (11% each), and incompliance (6%). Response was evaluable in 161 pts. Objective response was observed in 17 pts (1 CR+16 PR), SD in 19 pts (disease control rate 22%). PD was diagnosed in 125 pts. Responding pts were characterized by less organs involved (p=0.028). Median survival for all pts was 8.1 months, 1-year overall survival was 36.4%. Median survival is not yet reached for pts with disease control (94% alive at last observation), whereas it was 5.5 for pts with PD (40% alive at last observation). Treatment was generally well tolerated. Severe (Grade 3+4) auto-immune related toxicities were diarrhea (15 pts), skin rash (1 pt) and hepatitis (1 pt). Aseptic meningitis was observed in 1 pt; and hypophysitis (Grade 2) likewise in 1 pt. Conclusions: Data coming from these 161 patients appear to be consistent with safety and efficacy profiles determined in large clinical trials. Tumor responses were induced in a subset of pts and associated with prolonged survival.
Surgery in stage IV melanoma patients: Results from a single institution.
Authors: Pennacchioli Elisabetta , Gandini Sara , Verrecchia Francesco , Tosti Giulio , Baldini Federica , Mosconi Massimo , Spadola Giuseppe , Ferrucci Pier Francesco , Latiano Tiziana , Testori Alessandro 
Published: March 2020

e19035 Background: There is no consensus regarding the appropriate management of melanoma patients at stage IV and resectable metastases. Methods: We conducted a systematic review and meta-analysis to examine the effect of surgery on overall survival (OS) in patients with resectable metastases. The systematic review was performed by searching MEDLINE, EMBASE, Cochrane and ISI Web of Science. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of OS were estimated and summary estimates were obtain through random effects model. Heterogeneity and publication bias were investigated by sensitivity analyses and funnel plot regression Results: Thirty-three retrospective studies evaluating survival from resected and unresected metastases were found from 1978 until 2010. In resected patients median follow-up is 1.5 years and 2-year OS is 27% whereas in unresected the median follow-up is 6 months and 2-year OS is 12%. Meta-analysis was carried out on the seven studies reporting information on visceral metastases and including 1,165 patients. We included also 93 patients at stage IV treated at the European Institute of Oncology, Milan, Italy. Surgery has shown an improvement in survival of patients managed with palliative resection of their visceral metastases: the summary estimate suggests a significant decrease in the risk of mortality of 40% for patients who undergo surgery, with no indication of heterogeneity (HR=0.6 (0.45-0.78); I2=0). However we found indication for publication bias (P=0.03) suggesting that small studies published only mainly if they found significant results. Conclusions: Our results suggest the benefit of surgical resection for advanced-stage melanoma. Patients with limited sites and numbers of metastases should be considered for curative resection regardless of the location of the disease.
Identification of novel melanoma gene expression signatures using a Bayesian approach to filter out gene expression noise from normal tissues.
Authors: Liebner David A. , Parvin Jeffrey , Huang Kun 
Published: March 2020

e19053 Background: Identification of pertinent gene expression signatures may be confounded by failure to account for admixture of tumor specimens with normal tissue. We propose a novel method for filtering out gene expression “noise” from normal tissues in a set of melanoma samples derived from the NCBI Gene Expression Omnibus (GEO) public database. Methods: Using customized software implemented in MATLAB, we performed a preliminary search of GEO using the query term “melanoma”. We manually identified 695 clinical samples within 19 different gene expression studies (median 43 samples per series). Gene expression results were merged across different platforms using rank normalization for the target gene of the respective probes. Standardized gene expression signatures for 36 normal tissues were identified in GEO (GSE2361). We performed a modified sparse Bayesian factor regression analysis that incorporated signatures of normal tissues. Additional regression allowed for discovery of latent factors characteristic of melanoma subtypes. Pathway analysis was performed using Ingenuity Pathway Analysis (IPA) on characteristic genes for inferred melanoma-specific latent factors. Results: Normal tissue contributed significantly to the reported gene expression profiles, explaining a median of 11.5% of specimen variability (range 1.3-55.0%). In a subset analysis of 40 primary or in situ melanoma lesions versus 16 metastatic lesions (GSE7553), primary lesions were more likely contaminated with genes characteristic of normal skin (p<0.001). The top 5 latent factors explained a median of 17.0% of residual sample variance (range 0.6-64%). On IPA analysis, latent factor 1 was strongly associated with dermatologic disease (p = 7.46 e-36), latent factor 2 was associated with inflammatory response (p = 9.71e-25), and latent factor 3 was associated with upregulation of the MITF transcription factor regulation (p = 4.16e-19). Conclusions: Appropriate methods that filter out normal tissue contamination of melanoma specimens can improve our understanding of gene expression patterns in melanoma subtypes, and potentially improve future translational studies.
Survival for melanoma patients with pre-existing chronic lymphocytic leukemia.
Authors: Whitman Eric D. , Bustami Rami 
Published: March 2020

e19057 Background: Recent successes in melanoma drug development have rekindled interest in immunotherapy for melanoma (MM). Patients (pts) with chronic lymphocytic leukemia (CLL), a malignant expansion of B-lymphocytes, have an impaired immune system and not uncommonly develop secondary MM. We hypothesized that MM pts with pre-existing CLL are more likely to die than MM pts without a second malignancy. Methods: Pts were identified in the updated Surveillance Epidemiology and End Results (SEER) (1973-2008) database with MM only (MEL) or with primary CLL and secondary MM (MELpCLL). Time between diagnosis and death or last follow up and other demographic SEER data were recorded. The Chi-Square Test was used to make unadjusted comparisons between group death rates. A Cox proportional hazards regression model, adjusted for patient characteristics, predicted the risk of death by group. Results: 8,294 SEER pts were included (8,115 in MEL, 179 in MELpCLL). With a median follow-up time of 7 years, 2,454 pts (30%) died. There was a significant difference in mortality rates between the groups: MEL 29% / MELpCLL 71%; p<0.001 by Chi-Square. In the multivariate Cox model (Table), MELpCLL pts were significantly more likely to die than MEL pts (HR = 1.22, 95% CI = 1.02-1.46, p = 0.034). Higher risk of death was also significantly associated with older age and male gender (p<0.001) but not MM location (data not shown). MM data like thickness and ulceration were only available in more recent SEER records, precluding survival analysis. Conclusions: MELpCLL pts had a 22% increased risk of death compared to MEL pts in multivariate analysis, consistent with the hypothesis. [Table: see text]
Evaluation of cognitive function and quality of life in breast cancer patients receiving adjuvant dose dense chemotherapy.
Authors: Dabrow Michael B. , Szarka Christine E. , Moore Joanne , Chernick Michael R 
Published: March 2020

e19519 Background: Breast cancer therapy related neurocognitive dysfunction, such as memory impairment and “chemo-brain”, has been reported by many women during and after receiving adjuvant chemotherapy. Studies evaluating this effect have had mixed results regarding its validity. No study has evaluated a specific regimen and none have examined dose dense therapy. We have serially evaluated the cognitive and quality of life changes in patients receiving dose dense adjuvant adriamycin/cyclophosphamide followed by pactitaxel (DD AT-P) chemotherapy. Methods: Patients with early stage breast cancer (Stages I, II) who were treated at a single community hospital cancer center and were given dose dense AC-P adjuvant chemotherapy were asked to participate in this trial. 45 patients were enrolled and 43 were eligible for evaluation with the following instruments: FACT-F, FAS test, MMSE, MNA and BDI. Tests were administered at the start of chemotherapy, at the completion of chemotherapy, at 6 months and 12 months after completing chemotherapy. The tests were administered by oncology nurses. Scores were evaluated using repeated measures analysis of variance testing whether or not the change from baseline test scores had a trend over time. Results: 43 patients were evaluated. Age range was 34-72 years with a median age of 52. 34 patients completed 4 evaluations, 6 completed 3 evaluations, 3 completed 2 evaluations. The only measures demonstrating significant trends were the FAS test (p=0.022) and the Functional Well-Being (p=0.002) and Physical Well-Being (p<0.0001) portions of the FACT-F. The changes over time for these measures all indicated improved performance over baseline at the completion of the trial. The remainder of the tests showed no significant change over time. Conclusions: Dose dense adjuvant chemotherapy with AC-P for breast cancer does not result in decreased cognitive or quality of life measures over time. Patients can be reassured that this specific program of therapy will not lead to long term decreases in mental function and quality of life.
Clinical signs of dying in cancer patients: A prospective longitudinal observational study.
Authors: Hui David , dos Santos Renata , Kilgore Kelly L. , Buosi Silva Thiago , Chisholm Gary B. , Perez-Cruz Pedro Emilio , Souza Crovador Camila , de Almeida Leite Raphael , Del Fabbro Egidio , de Angelis Nascimento Maria Salete , Zhukovsky Donna S. , GonÃƒÂµaves de Freitas Seriaco Fabiola de Lourdes , Reddy Suresh K. , Machado Frascari Luciana , Yennurajalingam Sriram , Paiva Carlos Eduardo , Dev Rony , Hall Stacy , Fajardo Julieta , Bruera Eduardo 
Published: March 2020

e19528 Background: The fundamental process of dying has not been well characterized. We determined the frequency, onset, accuracy and likelihood ratio (LR) for various clinical signs in dying cancer patients. Methods: We systematically documented 100 signs/symptoms on consecutive advanced cancer patients admitted to palliative care units at MD Anderson Cancer Center (MDA) in the United States and Barretos Cancer Hospital (BCH) in Brazil every 12 hours from admission to death/discharge in 2010/2011. We analyzed the serial data from death backwards using generalized estimating equations for decedents, and calculated the accuracy and LRs for all patients. Results: 203/357 (MDA 52, BCH 151) patients died, and had the following characteristics: average age 58 (range 18-88), female 49%, Caucasian 76%, median admission length 6(Q1-Q3 4-9) days. The average palliative performance scale decreased from 50% to 20% (P<0.001). The frequency of pulselessness of radial artery (PRA), decreased urine output, respiration with mandibular movement (RMM), inability to close eye lids (EL), death rattle, vocal cord grunting, Cheyne Stokes and nasolabial drooping increased as death approached (P<0.001 for all), with high LR+ for impending death (Table 1). Presence of PRA, RMM and EL had a high specificity (100%), positive predictive value (99.4%) and LR+ (13) for death in 3 days. Conclusions: We identified highly specific cardiovascular, respiratory and neuromuscular signs associated with imminent death. [Table: see text]
The estimation of life-time for the patients who acquired resistance to standard chemotherapies.
Authors: Taniyama Tomoko , Hashimoto Kenji , Hirakawa Akihiro , Katsumata Noriyuki , Kodaira Makoto , Yonemori Kan , Yunokawa Mayu , Shimizu Chikako , Tamura Kenji , Ando Masashi , Fujiwara Yasuhiro 
Published: March 2020

e19535 Background: Prognostication is important for the advanced cancer patients to make the most for the rest of their life. We examined the accuracy of oncologists’ clinical predictions of survival (CPS) and the factors that oncologists referred to in cancer patients who acquired resistance to standard chemotherapies. We also examined how oncologists share the information about the survival with patients and their family. Methods: Fourteen oncologists treating major adult solid malignancies (breast, lung, gastrointestinal, pancreatic, gynecologic cancer and sarcoma) participated in this observational prospective cohort study between Oct 2010 and Oct 2011. The oncologists were asked to fill in the questionnaire about CPS when patients acquired resistance to standard chemotherapies. Results: The data of 52 patients were available for analysis. The median CPS was 92 days (Interquartile range [IQR], 61 - 168), and the median actual survival (AS) was 80 days (IQR, 35 to 148). The median difference between CPS and AS (|CPS-AS|) was 21 (IQR, -26 to 50) days. According to Pearson correlation between CPS and AS (r = 0.55, p < 0.001), log(CPS) and log(AS) (r = 0.69, p < 0.001) and spearman correlation between CPS and AS (r = 0.66, p < 0.001), it was statistically considered CPS corresponded to AS. The proportion of patients with |CPS-AS| were as follows; within a week, 6%; within 2 weeks, 14%; and within 4weeks, 42%. Concordance rate between CPS and AS was more accurate in gastric and ovarian cancer while it depended on the oncologists. Although, age, oral intake, the number of chemotherapy regimens and the prognostic factors that oncologists referred to were not related with |CPS-AS|. Eighteen patients (35 %) were informed about the prognosis and thirty-seven patients (71 %) were provided with information about palliative care unit. Thirty-three patients (64 %) received best supportive care alone and eighteen patients (35 %) received further chemotherapies. Conclusions: Oncologists’ predictions generally correlated with AS. As long as the prediction of survival is based on the prognostic factors that oncologists referred to, CPS can be correct to within as least 4 weeks.
Effect of dose escalation with single opioid, fentanyl matrix, for current cancer pain management: Multicenter, prospective, observational study.
Authors: Koh Sung Ae , Kim Min Kyoung , Lee Kyung Hee , Lee Kyu Taek , Park Seung Woo , Nam Seung-Hyun , Han Hye-Suk , Ryoo Hun-Mo 
Published: March 2020

e19538 Background: It is clinical experience that end-of-dose failure was commonly observed and many cancer patients increase the frequency of opioid administration because of that. Another treatment option could be to increase the dose of the opioid administered. High-dose fentanyl matrix use is known to be effective in controlling pain in cancer patients. To measure effectiveness of increase in single dose of fentanyl matrix in patients whose pain was not controlled sufficiently with the analgesic use in real practice at the investigator’s discretion, we perform the study. Methods: A multi-center, open-label, prospective, observational study was conducted in 30 hospitals in Korea between August and December 2008. Results: 452 patients were enrolled. A total 404 patients completed the study. Mean pain intensity decresed from 5.27 on the second to 3.37 at the end of the trial. There was significant difference in pain intensity (p < 0.001) between first and last visit. The percentage of pain intensity difference was 30.1%. The prevalence of end-of-dose-failure (EOD) at visit 1 was 73% of the enrolled 452 patients. After the use of the fentanyl patch EOD decreased from 73% to 56%. Pain intensity of patients experiencing EOD was 5.64 at baseline compared to 4.27 in patients without EOD. On Visit 2, pain intensity in patienst with and without EOD was 4.02 and 2.54. Of enrolled 404 patients, mean of increasing dose of fentanyl matrix was 55.6mcg/day. Satisfaction rate of investigator’s global assessment was 66.0%, and that of the patients’ global assessment was 63%. The rate of pain improvement was 33.7% by Clinical Global Improvement- Improvement after the use of the fentanyl patch. The observed adverse events were mainly nausea, asthenia, constipation and diarrhea. Conclusions: This study demonstrated that increasing dose of fentanyl patch decreased pain intensity, and decreased the rate of patients experiencing EOD. Also satisfaction rate was increasing after use fentanyl patch. Thus, fentanyl patch may be effective in cancer patients whose pain was previously not controlled sufficiently or who experienced EOD, the side effects were as could be expected with an opioid.
Cancer cachexia syndrome (CS): A symptom complex associated with yet distinct from fatigue in ambulatory cancer patients.
Authors: Mertens Wilson C. , Emmons Gregory Scott , Katz Deborah , Barham Ruth , Cassells Lucinda Jane , Dahiya Saurabh , Howard Leslie M. 
Published: March 2020

e19543 Background: Fatigue and CS (Lancet Oncol 2011;12:489) are common, multifactorial symptoms in ambulatory cancer patients. Clinical and laboratory correlates require further evaluation, although erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), nausea and weight loss have been associated with both CS and fatigue. A practical classification of cancer-associated fatigue is lacking. Methods: Patients with cancer—newly diagnosed, receiving treatment, as well as those undergoing post-treatment surveillance and recurrent/persistent disease—were consented and screened with a visual aid. Those reporting moderate fatigue were asked to participate in a study assessing the degree and impact of fatigue using the FACT-G and study-specific questionnaires, followed by focused laboratory testing. Results: 102 patients were accrued. Mean age 60.2 years (95%CI: 58.0, 62.5); 80% female; no evidence of disease 55.9%; disease present/initial presentation 18.6%, persistent/recurrent disease 25.5%; >5% weight loss 35%; CS 39%; anorexia-CS 18%; increased ESR 49% and CRP 32%; currently receiving chemotherapy 16%. Patients currently receiving chemotherapy had more fatigue (p=.011); none of CS, >5% weight loss, disease presence/recurrence, histologic diagnosis, gender, age, pain, appetite, nausea, depression, exercise, blood pressure (BP), hemoglobin level, ESR or CRP were statistically associated with fatigue. CS was associated with increased ESR and reduced BP and appetite (all p<.001), and increased nausea and CRP (both p<.05) as well as disease presence/recurrence (p=.003). FACT-G total and physical scale scores did not differ between CS and other fatigued patients. Conclusions: CS affects a substantial proportion of ambulatory cancer patients screened for moderate fatigue; however, CS patients did not exhibit increased fatigue or poorer FACT-G scores despite differences in weight, disease extent, weight loss, or laboratory markers of inflammation when compared to other sampled patients. CS patients may represent a distinct subset of cancer fatigue, or this symptom complex may be distinct from fatigue even though present in the same patient.