bluuebunny/crossref_metadata_2025_split huggingface dataset:
The unique molecular signatures of nodular and superficial spreading melanoma
Authors: Rose A. E. , Wang J. , Pearlman A. , Doudican N. , Hernando E. , Orlow S. J. , Polsky D. , Ostrer H. , Osman I. 
Published: August 2020

9047 Background: Primary nodular melanoma (NM) patients have a relatively poor prognosis compared to superficial spreading melanoma (SSM) patients. The disparity is generally attributed solely to NM's advanced thickness at presentation. In this study we attempted to define molecular signatures of NM and SSM that may explain their clinical differences. Methods: We performed an in silico gene expression analysis of 2 public data sets consisting of 36NM and 54 SSM primary melanoma tissues (CCR 2007;13 and JNCI 2006;98). We then utilized DNA microarray to generate gene expression profiles of a panel of 22 melanoma cell lines (2SSM, 4 NM, 12 met, 4 melanocytes). Differentially expressed genes and over-represented pathways in NM and SSM were identified based on a pooled analysis of the 3 data sets. We then used SNP array to define genomic alterations unique to NM and SSM but not altered in normal melanocytes. Finally, we correlated SNP array with gene expression. Results: Genes significantly overexpressed (p<0.05) in NM showed over-representation of pathways related to MAPK signaling (p=0.05) and cytoskeleton organization (p=0.02), while SSM showed over-representation of cell communication (p=0.05) and primary metabolic processes (p=0.002). Notable correlations between gene expression and copy number alteration in NM include increased copy number/overexpression of SOX5 (transcription factor related to embryonic development and cell fate) and the downregulation/deletion of ST14 (suppression of tumorigenicity 14). SSM demonstrated concordance of increased copy number/overexpression of EZR (cell adhesion protein implicated in human cancer) as well as PALLD (a protein related to motility, adhesion, and extracellular matrix interactions). Notable SSM genes showing correlation between downregulation/deletion include BNIP3 (a pro-apoptotic protein) and MTAP (often co- deleted with tumor suppressor p16). Conclusions: Simultaneous integration of gene expression with SNP array revealed molecular signatures characteristic of NM and SSM. These results suggest that NM and SSM are distinct biologic entities and that molecularly targeted adjuvant therapy may be more effective if tailored to the molecular signatures of melanoma subtypes. Validation is necessary to draw further conclusions. No significant financial relationships to disclose.
A phase II study of gefitinib in patients with metastatic melanoma
Authors: Patel S. , Bedikian A. , Kim K. , Papadopoulos N. , Hwu P. , Vardeleon A. , Prieto V. , Bar Eli M. , Bronstein Y. , Bassett R. 
Published: August 2020

9057 Background: Gefitinib is an inhibitor of epidermal growth factor receptor (EGFR), which is frequently expressed on both choroidal and non-choroidal melanoma cells. We evaluated the clinical efficacy of gefitinib in patients (pts) with metastatic melanoma. Methods: Pts with stage IV or unresectable or recurrent stage III melanoma and Zubrod performance status of 0 to 2 were eligible. For non-choroidal melanoma, pts must have received systemic cytotoxic therapy, but no more than 2 regimens; for choroidal melanoma, pts could be either chemo-naïve or have received up to 2 systemic cytotoxic therapies. The dose of oral gefitinib was 250 mg daily, and tumor response was evaluated every 6 weeks per RECIST. Ten patients with cutaneous disease were also consented for paired biopsies and blood collection for correlative studies at baseline and after 3 weeks of treatment. Results: Fifty-two pts (46 non-choroidal; 6 choroidal primay) were treated and evaluated for toxicity, and 50 pts were evaluable for response. Median age of pts was 62.5 years, with median Zubrod PS Score of 1. The median number of prior systemic treatments was 1. Forty-one pts (79%) had stage M1c disease. There were no drug-related grade 4 or 5 adverse events (AEs), and fatigue was the only grade 3 AEs in >5% of the patients. There were 2 (4%) partial responses, including a pt with metastatic choroidal melanoma, and 13 pts (26%) had disease stabilization. A median duration of response was 9.5 months among the responders. Median time to progression was 6 weeks, and median overall survival was 4.6 months. Among 7 pts with sufficient tissue on paired biopsies, there were no notable trends in the changes of the expression of pERK1/2, pAKT, or pPAK1 with treatment. Additionally, no trends were identified in serum VEGF or IL-8 levels after treatment. Conclusions: Gefitinib was well tolerated, but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma of cutaneous origin. There were no consistent changes in the expressions of downstream kinase proteins with gefitinib treatment. No significant financial relationships to disclose.
Comparative survival analysis of melanoma patients with secondary papillary thyroid carcinoma using Surveillance, Epidemiology, and End Results (SEER) data
Authors: Whitman E. D. , Bustami R. T. 
Published: August 2020

9068 Background: Malignant melanoma (MM) and papillary thyroid cancer (PTC) may share genetic mutations. The expected mortality of a patient with both MM and PTC should be predominantly influenced by MM and unchanged by the PTC diagnosis, unless shared genetic abnormalities or other factors alter the phenotype of either or both diseases. We hypothesize patients with both MM and PTC have altered mortality risk compared to patients with either cancer alone. Methods: The study population included patients identified in the SEER 1973–2004 database who were diagnosed with MM or PTC as a primary tumor. The population was divided into four groups: (1) patients with MM only (MEL); (2) patients with PTC only (PAP); (3) patients who developed MM as a second primary after PTC (2MEL); and (4) patients diagnosed with PTC after MM (2PAP). Time between diagnosis and death or last follow up (December 2005) and other demographic data was obtained from SEER. Comparisons between the group death rates were made using the Chi-Square Test. A Cox proportional hazards regression model, adjusted for patient characteristics, predicted the risk of death and survival by group. Results: 9575 SEER patient records were included: 6622 in MEL, 2778 in PAP, 113 in 2MEL and 62 in 2PAP. Overall, 2095 patients (22%) died. There was a significant difference in mortality rates between the groups: MEL 27%, PAP 9%, 2MEL 21% and 2PAP 18%, p<0.001 by Chi-Square. Controlling for other variables in a multivariate Cox model, patients in the 2MEL group were significantly less likely to die than MEL patients (HR 0.52, 95% CI 0.35–0.79, p=0.002). 2PAP patients, the smallest sample, also had a reduced likelihood of death that did not reach statistical significance (HR=0.75, 95% CI 0.42–1.37, p=.35). PAP patients had the best survival (HR=0.43, 95% CI 0.36–0.50,p<0.001). Other factors (age, race, gender and radiation therapy, data not shown) also significantly affected mortality. Conclusions: This study suggests that MM patients also diagnosed with PTC are more likely to survive than patients with MM alone. Identification of the causative factor(s) for this survival benefit will require additional epidemiologic and genetic studies. No significant financial relationships to disclose.
Progression-free and overall survival analysis in patients with metastatic melanoma undergoing first- versus second-line therapy
Authors: Allred J. B. , Suman V. 
Published: August 2020

9078 Background: A frequently discussed topic at meetings of oncologists is the question of expected clinical outcomes for patients with metastatic melanoma undergoing 1st vs 2nd line systemic therapy. Differing outcomes in these two patient populations could affect interpretation of non-randomized clinical trials involving both patient populations. Some have suggested superior clinical outcome in patients undergoing 2nd line therapy. As there is little data addressing this issue, we sought to answer the question by comparing the clinical outcomes of patients with metastatic melanoma treated on 1st vs 2nd line therapy across clinical trials conducted at our institution. Methods: Data were collected from 10 phase II clinical trials for patients with stage IV melanoma for which Mayo Clinic was the data center. The 10 trials included three categories of treatments: cytotoxic chemotherapy (4), cancer vaccines (4), and biologic agents (2). In all studies, eligibility criteria required: stage IV melanoma, life expectancy >3 months, reasonable hematology and serum chemistry laboratory results, and an ECOG performance status of ≤2. Cox proportional hazards models were fit to assess the relationship between patients' “therapy” status (1st vs 2nd line) and time to events, both overall survival (OS) and progression free survival (PFS), for each treatment category. Results: We identified 318 unique eligible patients across 10 trials. Removed from the analysis were 55 patients (ocular melanoma and/or metastases involving the central nervous system) leaving 263. Cox proportional hazards results demonstrated no differences in PFS or OS for 1st vs 2nd line patients for either “chemotherapy” or “vaccine” treatment regimens. However, patient treated on “biologic” trials as 1st line therapy appeared to demonstrate a PFS advantage over 2nd line treatments (HR=1.98, p-value=0.02). There was a suggestion of an OS benefit for 1st line patients in this category, however, the relationship was not significant (HR=1.77, p=0.07). Conclusions: The presented data suggest that there is no PFS/OS difference in stage IV melanoma patients receiving 1st vs 2nd line therapy (no PFS/OS advantage to patients treated in 2nd line vs. 1st line). No significant financial relationships to disclose.
Hospice utilization by men dying of prostate cancer
Authors: Bergman J. , Saigal C. S. , Miller D. C. , Hanley J. , Gore J. L. , Lorenz K. , Litwin M. S. 
Published: August 2020

9501 Background: The 25,000 American men who die of prostate cancer each year often suffer from fatigue, bone pain, and weight loss. Enrollment in hospice programs improves both the quality of life and the quality of death for this cohort. However, previous data suggest that hospice is often used inappropriately, either through underuse or through improperly timed referral. We sought to characterize sociodemographic and clinical factors that affect appropriate and inappropriate utilization of hospice services by men with metastatic prostate cancer in a population-based dataset. Methods: We used linked data from Surveillance, Epidemiology, and End Results and Medicare data to identify a cohort of beneficiaries who died of prostate cancer between 1992 and 2005. We then evaluated the bivariate association between sociodemographic and clinical data and any hospice enrollment. Hospice referrals within 7 days of death or more than 180 days before dying were considered inappropriate. Results: Of the 14,521 men dying of prostate cancer, 7,646 (53%) utilized hospice resources. Enrollment within 7 days of death was noted in 1699 subjects (22% of hospice users), and enrollment more than 180 days prior to death was seen in 717 participants (9% of hospice users). Subjects who utilized hospice within the appropriate time frame were enrolled for a mean of 47 days (S.D. 41, range 7–180 days) prior to death, with a median of 31 days. In our bivariate analysis, white ethnicity, partnered status, and achieving at least a high school diploma were significantly associated with hospice use ( Table ). Conclusions: Hospice utilization rates in our cohort compared favorably with previous analyses, but the frequency of improperly timed hospice referrals was similar to prior reports and provides an opportunity for improvement. [Table: see text] No significant financial relationships to disclose.
A survey of U.S. and Canadian oncologists’ attitudes toward the cost, cost-effectiveness (CE), and reimbursement of cancer drugs
Authors: Neumann P. , Berry S. R. , Nadler E. , Evans W. C. , Palmer J. , Bell C. , Strevel E. , Fang H. , Ubel P. A. 
Published: August 2020

9502 Background: Drug costs and reimbursement issues offer significant challenges to U.S. and Canadian oncologists even though they practice in substantially different health care systems. However, little is known about the attitudes of American and Canadian oncologists towards these issues. Methods: We surveyed 1,379 U.S. and 356 Cdn oncologists to assess their attitudes to cancer drug costs, CE and reimbursement policies. Results: Response rate was 57% in the U.S. and 48% in Canada. Oncologists in both countries stated that patients' “out-of-pocket” drug costs influenced their treatment recommendations (84% U.S., 80% Cdn respondents). Most respondents felt that every patient should have access to effective cancer treatments regardless of cost (66% US; 54% Cdn), while 59% of U.S. and 72% of Cdn and respondents believed that patients should only have access to effective cancer treatments that provided “good value for money.” 70% of U.S. and 64% Cdn respondents felt that <$100,000 per life year gained was a reasonable definition of “good value for money” but less than half of respondents (42% US, 49% Cdn) felt well prepared to interpret and use CE information in their treatment decisions. A majority of respondents (57% US, 69% Cdn) felt government price controls for cancer drugs are needed while a minority felt that more cost-sharing by patients was needed (29% US, 37% Cdn). Most oncologists felt that evaluating whether a drug provides “good value” should be overseen by an independent non-profit agency (57% US, 71% Cdn) or physicians (61% US and Cdn); in contrast, few believed that government (21% US, 33% Cdn), patients (36% US, 37% Cdn) or insurance companies (6% US, 10% Cdn) should determine “good value”. 79% of U.S. and 69% of Cdn respondents felt more use of CE data in coverage and reimbursement decisions is needed. Conclusions: Oncologists in the U.S. and Canada share many similar attitudes to cancer drug costs, CE, and reimbursement policies despite differences in their health care systems. In both countries, oncologists favor more use of CE information. No significant financial relationships to disclose.
Pregabalin for hot flashes in women: NCCTG trial N07C1
Authors: Loprinzi C. L. , Qin R. , Stella P. J. , Rowland K. M. , Graham D. L. , Erwin N. , Dakhil S. R. , Jurgens D. J. , Burger K. N. 
Published: August 2020

9513 Background: Hot flashes are a major problem in many women for which better treatment options are needed. Given the known efficacy of gabapentin for decreasing hot flashes, it was decided to evaluate pregabalin, with hopes that it would work better and/or with fewer toxicities. Methods: A three-arm, double-blinded, placebo-controlled randomized trial was developed. Women with bothersome hot flashes (at least 28/week) were randomized to receive either a placebo or target pregabalin oral doses of 75 mg bid or 150 mg bid (starting at 50 mg/d and then increasing the dose at weekly intervals to 50 mg bid, then 75 mg bid, and then, in the higher dose arm, 150 mg bid); patients were treated for 6 weeks. Hot flash numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flash diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intra-patient difference in hot flash score between baseline and week six, comparing the higher dose pregabalin arm and the placebo arm. With the planned sample size of 55 patients per arm, there was an 80% power and two-sided 5% Type I error rate to detect a difference of 0.54 standard deviations, or 1.08 hot flashes per day, or 2.7 units of hot flash score per day. Results: 207 patients were randomized between 6/20/2008 and 8/21/2008. The study arms were well balanced. Mean/median daily hot flash scores and frequencies for all pts at baseline were 15.7/13.4 and 8.3/7.7, respectively. The table shows the decreases in hot flashes from the baseline to the sixth treatment week. Larger numbers illustrate greater hot flash reductions. Toxicity information, quality of life information, and information regarding the effects of hot flashes on subjective symptoms will be available at the meeting time. Conclusions: Pregabalin reduces hot flashes in women. There appears to be similar effects with both studied doses. [Table: see text] No significant financial relationships to disclose.
Declines in physical function from androgen deprivation therapy (ADT) in men with nonmetastatic prostate cancer: A matched cohort study
Authors: Breunis H. , Timilshina N. , Tomlinson G. , Naglie G. , Tannock I. , Fleshner N. , Krahn M. , Duff Canning S. , Warde P. , Alibhai S. 
Published: August 2020

9526 Background: Although prolonged use of ADT is hypothesized to adversely affect physical function, few studies have examined this relationship longitudinally using objective measures of physical function. Methods: Men age 50+ with non-metastatic prostate cancer (PC) starting continuous ADT were enrolled in this prospective longitudinal matched cohort study. Physical function was assessed with the six-minute walk test (6MWT), grip strength, and the Timed Up and Go (TUG) test, representing endurance, upper extremity strength, and lower extremity strength, respectively. Self-reported physical function was measured with the Medical Outcomes Study SF-36. Assessments were done at baseline, 3 months, 6 months, and 12 months. Two control groups, matched on age, education, and baseline function were also enrolled. One control group had PC but did not receive ADT, and the other group did not have PC. Linear mixed effects regression models were fitted adjusting for baseline covariates. Results: 85 patients on ADT, 86 PC controls, and 86 healthy controls were enrolled. All 3 groups were similar in age (mean age 69.1 y, range 50–87) and physical function (all ANOVA p>0.05). The 6MWT distance improved in both control groups (p=0.05 and 0.05 for PC and healthy controls, respectively) but remained stable in the ADT group (p=0.96)). Grip strength declined in the ADT group (p=0.04), remained stable in the PC control group (p=0.31), and improved in the healthy control group (p=0.008). TUG scores remained stable over time and across groups (p>0.10). SF-36 physical function declined in the ADT group (p<0.001) but increased in both control groups (p<0.001). Negative effects on outcomes were noted within 3–6 months of starting ADT and were larger with older age. Conclusions: Endurance, upper extremity strength, and self-reported physical function are affected within 3–6 months of starting ADT, particularly in older men. Declines persist at 12 months after adjustment for baseline function and covariates. Exercise intervention studies to counteract these losses are warranted. No significant financial relationships to disclose.
Efficacy of venlafaxine for the prevention and relief of acute neurotoxicity of oxaliplatin: Results of EFFOX, a randomized, double-blinded, placebo-controlled prospective study
Authors: Durand J. P. , Deplanque G. , Gorent J. , Montheil V. , Raymond E. , Scotte F. , Mitry E. , Goldwasser F. 
Published: August 2020

9533 Background: Neurosensory toxicity of oxaliplatin is dose-limiting and presents as two distinct clinical syndromes: acute symptoms and cumulative peripheral neuropathy. Methods: From October 2005 to May 2008, patients (pts) presenting oxaliplatin-induced acute neurotoxicity were randomized in a double-blinded study, to receive either arm A: venlafaxine hydrochloride (Effexor, Wyeth Pharmaceuticals Inc.) 50 mg 1 hour prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d. from day 2 to day 11, either arm B : placebo. The primary endpoint was percentage of pts without acute neuropathy. The study was designed to detect, with 54 pts, a difference of 25%. The neurotoxicity was evaluated using a numeric rating scale of symptoms relief and the Neuropathic Pain Symptom Inventory (Pain 2004;108(3):248–57). Results: 45 pts were included (male : 24; median age : 67.5). Most pts had colo-rectal cancer (75.6%). The two most used chemotherapy regimens were FOLFOX (82.2%) and GEMOX (11.1%). Median number of cycles administered at inclusion was 5. In January 2009, 16 pts out of 22 in arm A (venlafaxine) and 21 pts out of 23 in arm B (placebo) were evaluable. Venlafaxine reduced the incidence of neurosensory acute symptoms : 35.3 % in arm A vs 76.2% in arm B (p=.023, Fisher's exact test). Side effects were emesis (4 pts) and somnolence (3 pts). Conclusions: Venlafaxine is effective for prevention and relief of oxaliplatin-induced acute neurotoxicity. No significant financial relationships to disclose.
The efficacy, tolerability, and speed of onset of fentanyl pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain (BTCP): A multicenter, placebo-controlled, double-blind, two-phase crossover study
Authors: Gabrail N. Y. , Burton A. W. , Reyes E. , Nguyen A. , Taylor D. R. 
Published: August 2020

9535 Background: Breakthrough cancer pain (BTCP) affects up to 95% of patients with cancer pain but oral fentanyl formulations do not consistently match the typical time course of BTCP, which is rapid in onset and lasts for 30–60 min. To tailor fentanyl delivery for the treatment of BTCP, a new nasal formulation of fentanyl (fentanyl pectin nasal spray [FPNS]) has been developed to provide both rapid and controlled nasal delivery of fentanyl. Methods: A randomised, placebo-controlled, double-blind (DB) study assessing the efficacy and tolerability of FPNS was conducted in 114 cancer patients experiencing 1–4 BTCP episodes/day while taking ≥60 mg/day of oral morphine (or equivalent) for cancer pain. Patients who completed a titration phase (N=83) continued to a DB phase where 10 episodes of BTCP were treated with the effective dose identified during titration (7) or placebo (3). Pain intensity (PI) was measured using an 11-point categorical scale and pain relief (PR) using a 5-point scale, both PI and PR were measured at 5, 10, 15, 45 and 60 min post-dose. The primary endpoint was the Summed Pain Intensity Difference at 30 min (SPID30min). Secondary efficacy endpoints included Pain Intensity Difference (PID) from baseline, PI and PR. Safety was assessed by adverse events (AEs) and both objective and subjective nasal assessments. Results: Compared with placebo, FPNS significantly improved mean SPID30min scores (P<0.0001) and significantly improved SPID scores as early as 10 min (P<0.05) and up to 60 min (P<0.0001). Significant differences in favour of FPNS were found in PI as early as 5 min (P<0.05). Similar benefits were also seen with PID, with a trend at 5 min (P=0.07) that was significant from 10 min onward (P<0.01). PR was significant from 10 min (P<0.001) and at all time points to 60 min (P<0.001). Only 5.3% of patients withdrew from titration due to AEs; no significant nasal effects were reported. Conclusions: FPNS provided rapid and effective analgesia in BTCP and was generally safe and well tolerated. [Table: see text]