bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors for survival in patients with stage (stg) IV malignant melanoma (MM)
Authors: Seetharamu N. , Hamilton H. , Tu T. , Christos P. , Osman I. , Pavlick A. C. 
Published: August 2020

9072 Background: Prognosis for survival in MM is not uniform with some pts being long-term survivors. Identifying this subset of pts may have implications on surveillance and treatment (tx). Unfortunately, prognostic data available for MM and the utility of AJCC staging in predicting survival is limited. We analyzed prospectively collected data from the NYUCI Interdisciplinary Melanoma Cooperative Group program (IMCG) to identify clinicopathological variables predictive of MM survival. Methods: We identified 185 pts enrolled in the IMCG with MM diagnosed and treated at NYUCI. Demographic, clinical, and tx-related factors were included in the analysis. Kaplan-Meier (KM) survival analysis was used to identify univariate predictors of post-stage IV survival and their independent effect was assessed in a multivariate Cox proportional hazards regression model. Results: Median age at diagnosis (dx) of metastatic MM was 64 years (22–92). Median overall survival: 13.8 months(m) (128 deaths and a median follow up of 18.6 m (4–141) for survivors). Factors identified on univariate analysis at p<0.20 were evaluated in the multivariate model ( table ). Co-morbidities, site and histology of primary melanoma, initial staging, prior loco-regional recurrences, and adjuvant tx of primary melanoma were not associated with MM survival. Univariate analysis also showed significant survival advantage (p value 0.0011) for patients with AJCC stages M1a and M1b (21.6 m and 17.2 m respectively) over those with AJCC stage M1c (9 m). Conclusions: This cohort study of MM identified female gender, nl serum LDH, nl albumin, and solitary organ involvement as independent survival predictors. Patients who received systemic therapy± local measures had survival benefit over those that had surgery and/or radiation alone suggesting a role for systemic treatment in MM. Patients with personal history of another malignancy (n=37) showed a trend towards improved survival. This novel observation needs to be validated and studied further. [Table: see text] No significant financial relationships to disclose.
Effect of mebendazole on melanoma xenograft growth through targeting of bcl-2
Authors: Doudican N. A. , Pennell R. , Tu T. , Liebes L. , Pavlick A. , Berman R. , Shapiro R. , Goldberg J. D. , Osman I. , Orlow S. 
Published: August 2020

9075 Background: Defects in apoptosis are thought to contribute to melanoma chemoresistance, making the anti-apoptotic protein Bcl-2 an attractive therapeutic target. We identified mebendazole (MBZ), a microtubule binding agent, as an inducer of melanoma cytotoxicity via a Bcl-2 dependent mechanism in vitro (Mol Cancer Res, Aug 2008). In the present study, we assessed the effect of MBZ on human melanoma tumor growth and progression in a mouse xenograft model and compared the ability of MBZ to inhibit growth of cultured melanoma cells to that of oblimersen (OBL), an antisense drug targeting Bcl-2. Methods: Growth of human M-14 melanoma xenografts in mice administered MBZ orally at doses from 0.1 to 2 mg were compared to tumor growth in mice receiving 100mg/kg intraperitoneal temozolomide (TMZ) or vehicle alone. Tumor diameter, volume, histopathology, and immunohistochemical staining of caspase 3 and Ki67 were assessed. Bcl-2 phosphorylation was determined by immunoblotting. MBZ and OBL-induced melanoma growth inhibition was analyzed by MTT assay. Results: Anti-melanoma effects of MBZ were dose- dependent up to 1 mg which displayed a 72% reduction in tumor volume compared to vehicle treated mice. This reduction in volume was accompanied by a 46% decrease in proliferating cells and an 81% increase in apoptotic cells. Moreover, 1 mg MBZ inhibited tumor growth as effectively as high dose TMZ, the current melanoma standard of care. Orally administered MBZ treatment resulted in Bcl-2 phosphorylation in vivo, further confirming its mechanism of action. MBZ inhibited growth of melanoma cells in culture more effectively than OBL with GI50 values of 0.32 uM and 7.45 uM, respectively. Conclusions: MBZ safely and effectively inhibits melanoma growth and progression in a xenograft model. A phase II clinical trial investigating MBZ's utility as adjuvant therapy in patients with stage IV, resected melanoma is planned. No significant financial relationships to disclose.
Effect of celastrol on temozolomide cytotoxicity in melanoma cells and inhibition of NF-kB signaling
Authors: Chen M. , Osman I. , Orlow S. J. 
Published: August 2020

9076 Background: Temozolomide (TMZ) exhibits clinical activity in the treatment of melanoma and glioblastoma, but response rates are low. Identification of agents that improve TMZ's efficacy and overcome resistance is of great interest. In this study, we have identified celastrol as a natural product that significantly enhances TMZ-induced cytotoxicity by testing a library of drugs and natural products for cytotoxic activity against glioma and melanoma cell lines and have examined its mechanism of action in melanoma cells. Methods: A preliminary screening of a library of 2000 drugs and natural products was performed and a short list of drugs was identified as able to enhance TMZ-induced cell killing in TMZ-resistant cancer cell lines. The effects of these compounds were further confirmed in five melanoma cell lines. A cell proliferation assay was used to compare growth inhibitory effects of single agent TMZ versus combination treatments. Synergy in inhibiting cell proliferation was assessed using combination-index methods. The expression of NF-kB, IkB, MAPK, and PARP were examined using Western blot analysis. The effect of treatments on the cell cycle was examined by flow cytometry. The localization of NF-kB in melanoma cells was evaluated through immunofluorescence microscopy. Results: Combining celastrol and TMZ synergistically inhibited cell proliferation, enhanced cell cycle arrest, and increased apoptosis in a series of melanoma cell lines, compared to treatment with TMZ alone. We further found that celastrol inhibited proteasome activity, TNF-α induced IkB phosphorylation and NF-kB translocation to the nucleus. Inhibition of NF-kB with siRNA mimicked the ability of celastrol to sensitize melanoma cells to TMZ-induced cell killing, suggesting inhibition of NF-kB was indeed involved in TMZ/celastrol-induced cytotoxicity. Furthermore, combination treatment induced phosphorylation of JNK. Conclusions: Our data suggest that combined use of TMZ with celastrol, a natural product derived from a vine extract that has been used orally in Chinese medicine for over a thousand years, may enhance the chemotherapeutic efficacy of TMZ in melanoma. No significant financial relationships to disclose.
Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma
Authors: Anderson W. F. , Pfeiffer R. M. , Tucker M. A. , Rosenberg P. S. 
Published: August 2020

9079 Background: Emerging data suggest that cutaneous malignant melanomas (CMM) may arise through divergent cancer pathways, linked to intermittent versus accumulated sun exposure. However, numerous questions remain regarding the timing and/or age of exposure. Methods: We, therefore, systematically examined the effect of aging upon CMM incidence in the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Standard descriptive epidemiology was supplemented with mathematical models. The impact of advancing age upon CMM incidence was assessed by gender, histopathological subtype (superficial spreading melanoma (SSM) or lentigo maligna melanoma [LMM]), and anatomic site (face, head, and neck [FHN] or lower extremity [LE]). Results: Gender, histopathological and anatomic site were age-specific effect modifiers for CMM, showing divergent (or bimodal) early- and late-onset cancer pathways. Early-onset melanomas were predominantly associated with female gender, SSM, and LE. Late- onset melanomas were correlated with male gender, LMM, and FHN. Early- and late-onset melanoma populations were confirmed with age-period-cohort models (adjusted for period and cohort effects) and two-component mixture models. Conclusions: These results are consistent with a divergent and age-dependent solar hypothesis for CMM. Early-onset melanomas may represent gene-sun exposure interactions occurring early (and/or intermittently) in life among susceptible individuals. Late-onset melanomas possibly reflect accumulated lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be adequately powered to account for this age-dependent effect modification for acknowledged (gender, histopathology, and anatomic site) as well as suspected melanoma risk factors such as constituent genetic variants. No significant financial relationships to disclose.
Identification of targetable cellular subsets within melanoma tumors
Authors: Sekulic A. , Miller A. , Barrett M. , Ejadi S. , Mengos A. , Pockaj B. , Markovic S. 
Published: August 2020

9082 Background: Human tumors, including melanoma, are complex mixtures of individual, molecularly distinct subpopulations, or clones of cancer cells. Effective cancer therapy will likely require targeting of all tumor subsets within a given cancer. Understanding the tumor complexity and the ability to identify points of therapeutic vulnerability within the individual tumor subsets will be essential for development of effective personalized cancer therapies. Methods: We have developed an approach that combines identification of individual tumor subsets using a multiparameter nuclear flow cytometry coupled with a high-resolution genomic analysis using the array-based comparative genomic hybridization (aCGH). Melanoma nuclei were isolated from tumor tissues and subjected to flow cytomery using melanocyte-specific antibodies (to separate melanoma cells from stroma) and DNA content, to separate individual tumor subpopulations. DNA extracted from isolated nuclear subpopulations was extracted and analyzed by aCGH. This approach was adopted for both fresh-frozen and paraffin-embedded clinical specimens. Results: We initially demonstrate the feasibility of the outlined approach by successful separation of melanoma from stromal nuclei and separation of individual melanoma nuclear subpopulations by DNA content. aCGH analysis of the DNA derived from isolated tumor subpopulations allowed successful identification of potentially targetable molecular aberrations in individual subsets of tumor cells. Notably, such aberrations were often not detected in unsorted, bulk tumors analyzed by the same high-resolution aCGH approach. Conclusions: We demonstrate a feasible approach to in-depth molecular analysis of tumor subpopulations within a clinical cancer tissue. This approach allows identification of potentially targetable molecular aberrations within individual tumor subsets, thus opening a possibility for a broad tumor targeting through design of individually-tailored therapeutic approaches. No significant financial relationships to disclose.
Clinical trial participants’ strategies for coping with prescription drug costs: A companion study to CALGB 80405
Authors: Schrag D. , Naughton M. , Kesselheim A. , Archer L. , Niedzwiedcki D. , Romanus D. , Goldberg R. , Venook A. 
Published: August 2020

9503 Background: The strategies used by clinical trial participants to cope with the high costs of prescription drugs are poorly characterized. Methods: We identified a cohort of newly metastatic CRC patients participating in CALGB 80405, a phase III trial comparing first-line systemic chemotherapy with Bevacizumab, Cetuximab or both agents. We surveyed trial participants about their prescription drug insurance status and strategies they used to cope with out-of-pocket prescription drug costs. We surveyed patients before trial initiation and again 3 months later to assess the extent to which embarking on chemotherapy imposes additional financial burden requiring use of coping strategies. Results: Out of 1422 trial participants, 806 (57%) completed the baseline survey. The 515 enrolled before 09/01/2007 were asked to repeat the survey by phone at 3 months; 409/505 alive at 3 months (81%) did so. The 409 patients in the analytic cohort had similar clinical and demographic features to those not surveyed. 60/409 (15%) lacked prescription drug coverage and only 48/409 (12%) discussed prescription drug costs with their physicians. Conclusions: In the context of a trial in which costs of chemotherapy are covered and most participants had prescription drug insurance, patients rarely discuss prescription drug costs with their physicians. Although a considerable minority report having used coping strategies to lessen the cost burden, only a very small minority newly adopt such strategies after starting chemotherapy on trial. [Table: see text] [Table: see text]
An exploratory analysis of comprehensive geriatric assessment results and overall survival in 233 consecutive elderly cancer patients
Authors: Poon D. , Lee H. H. , Chan L. L. , Yap R. , Koo W. H. 
Published: August 2020

9504 Background: Performance status (PS) is the main clinical parameter used by most oncologists to assess the ability of elderly cancer patients to tolerate chemotherapy and estimate prognosis. The results of comprehensive geriatric assessment (CGA) for elderly cancer patients were analyzed to investigate the impact of each CGA functional, physical, cognitive, and affective domain on overall survival in relation to performance status. Methods: CGA was used for 233 consecutive elderly cancer patients aged 70 and above. CGA tools included the Katz index of daily activities independence (ADL), instrumental activities of daily living (IADL), mini-mental state examination (MMSE), geriatric depression scale (GDS), Charlson comorbidity risk index, get up and go test, and mini-nutritional assessment. Geriatric syndrome is defined as any high risk of falls, depression, dementia, increased functional dependence, or malnutrition. Eastern Cooperative Oncology Group (ECOG) scale was used to grade PS. Cancer type and stage were also analyzed. Log rank test was used to compare overall survival and hazard ratio (HR) derived using Cox regression method. Univariate and multivariate analyses were done to assess impact of ECOG status, presence of geriatric syndrome, stage of disease and cancer type on overall survival. Results: All 233 patients were included in the analysis, median age 77 (70 - 93), all had solid tumors and predominant tumors comprising 79% of diagnoses were colorectal, lung and breast, 50% had advanced metastatic disease. ECOG grades 2,3,4 (HR 0.28, 95% CI 0.14 - 0.55), dependent IADL status (HR 0.30, 95% CI 0.11 - 0.83), presence of geriatric syndrome (HR 0.42 95% CI 0.26 - 0.69), poor cognition (HR 0.53 95% CI 0.36 - 0.77), or advanced disease (HR 0.30 95% CI 0.14 - 0.65) was associated with inferior overall survival in univariate analysis. Only poor ECOG status, presence of a geriatric syndrome and advanced disease predicted adversely for overall survival in multivariate analysis. Poor cognition (MMSE score <24) in those with borderline ECOG 2 status was associated with poorer survival (HR 0.38 95% CI 0.33 - 0.90). Conclusions: Utility of CGA will improve the assessment of the elderly cancer patient. No significant financial relationships to disclose.
Illness understanding in patients with advanced lung cancer
Authors: Temel J. S. , Greer J. A. , Admane S. , Jackson V. A. , Billings J. A. , Dahlin C. M. , Jacobsen J. C. , Blinderman C. D. , Lynch T. J. , Pirl W. F. 
Published: August 2020

9515 Background: Accurate understanding of prognosis among terminally-ill patients impacts decision-making at the end of life. The goal of this study was to explore illness understanding in patients with advanced non-small cell lung cancer (NSCLC). Methods: As part of a larger randomized study of integrated versus standard palliative care in an ambulatory thoracic oncology clinic, we recruited 120 patients within eight weeks of diagnosis of incurable NSCLC with a performance status of 0–2. Prior to randomization, patients completed questionnaires on quality of life (FACT-L) and mood (HADS), as well as the following items regarding illness understanding: 1) “My cancer is curable” (yes/no); “The goals of my therapy are: to help me live longer” (yes/no), “try to make me feel better” (yes/no), “to get rid of all my cancer” (yes/no); and 3) “My current health status is: relatively healthy, seriously but not terminally ill, or seriously and terminally ill”). Results: Approximately one third of patients (n=39/116, 33.6%) believed their cancer to be curable. While most patients felt that the goals of therapy were to help them live longer (n=110/113, 97.3%) and feel better (n=102/102, 100%), 66.0% (n=64/97) also believed that getting rid of all of the cancer was a treatment goal. Only 13.9% (n=16/115) of patients believed that their current health status was seriously and terminally ill. Patients who reported greater depression and anxiety symptoms on the HADS were more likely than those without such distress to believe that their cancer was curable (OR=2.47, p=.03) and that one of the goals of treatment was to get rid of all of their cancer (OR=3.83, p=.02). Conclusions: Despite having an incurable illness, the majority of patients with advanced NSCLC do not view themselves as terminally ill or have an accurate understanding of the goals of anti-cancer therapy. Given that patients often make treatment decisions based on their prognostic awareness, many of these individuals, particularly those with comorbid mood symptoms, may be at risk of pursuing unsuitable choices for their care. Interventions are needed to promote greater understanding of prognosis and goals of therapy in this population. No significant financial relationships to disclose.
Cognitive function (CF) and prognostic information understanding in advanced cancer patients (ACP)
Authors: Hlubocky F. J. , Larson E. , Ratain M. J. , Sachs G. , Daugherty C. K. 
Published: August 2020

9516 Background: The role of advanced cancer patients' (ACP) cognitive function (CF) and its relationship to understanding of a terminal prognosis has never been formally evaluated. Methods: ACP CF was evaluated among a population of terminally-ill patients enrolling in phase I trials at our institution using a neuropsychological battery designed to assess several domains of decisional capacity: Memory (Hopkins Verbal Learning HVLT); Executive Functioning (Verbal Fluency and Trail-making A/B); Language (Boston Naming-short); Attention (Digit Span); Comprehension (Auditory Comprehension & WAIS comprehension). Semi-structured interviews of ACPs also evaluated md-pt communication regarding prognosis, and included the Hospital Anxiety and Depression Scale (HADS), BDI-II, and the FACT-COG. Results: To date, 110 ACP enrolling in phase I trials have been interviewed: median age 60 (23–83); 66% male; 88% Ca; 62% married; 71% >high school education; 52% GI dx. 59% of ACPs reported having a discussion regarding life expectancy, and 55% stated that the physician gave them a prognostic timeframe regarding the amount of time left to live. ACP who stated the physician did not provide them a timeframe had measurable deficits in CF as indicated by Z scores for HVLT immediate recall (-1.3 ± .84 v -.74 ± 1.1, p=.03); total recall (-1.9 ± 1.2 v -1.2 ±1.5, p=.02); delayed recall (-1.7 ± 1.6 v -1.1 ±1.6, p=.04); language (.26 ± 1.3 v .78 ± .68, p=.03); Trails B (-1.6 ± 2.5 v -.61 ± 2.2, p=.04) and WAIS comprehension ss scores (14 ± 2.9 v 16 ± 3.0, p=.06). These ACP tended to exhibit more depressive symptoms (12 ± 10 v 6 ± 3, p=.04) and had lower scores for perceived cognitive impairment (96 ± 25 v 105 ±16, p=.04); impact on quality of life (26 ± 7 v 28 ± 5, p=.03); and FACT-COG total (152 ± 31 v 164 ± 22, p=.05). Conclusions: ACP enrolling in phase I trials who could not recall specific prognostic information had measurable cognitive impairment as compared to those ACP who could recall such information. Our data indicate that CF may play a role in ACP communication and/or understanding of prognostic information. [Table: see text]
Efficacy of electroacupuncture for bone metastatic cancer patients with neuropathic pain: A randomized controlled trial
Authors: Sima L. , Yin C. 
Published: August 2020

9534 Background: Bone metastatic lung cancer or breast cancer pts often have neuropathic pain which has poor reaction to opioids. A clinical trial is to investigate efficacy of electroacupuncture (EA) in cancer pts with neuropathic pain. Methods: Inclusion criteria were: bone metastatic lung cancer or breast cancer pts at least one of the symptoms as burning pain, shooting pain, dysesthesias, or allodynia; numerical rating scale (NRS) of pain intensity >=4.0; stable dose of opioids for at least 72 hours. Exclusion criteria were: chemotherapy or radiotherapy from 15 days before or during the study. Hormone or adjuvant therapy could be started before the study, but the dose could not be changed afterwards. Opioids could be increased step by step according to the pain. EA was manipulated with low-frequency (2 Hz) and high-frequency (100 Hz) dense-disperse waves alternatively, 30 minutes per day, 5-day therapy with 2-day interval, 3 weeks continuously. Acupoints were selected as ST36, SJ3, SJ5, LI3, LI4 bilateral. Controlled group accepted non-acupoint treatment close the right acupoint. Results: Ninety pts with neuropathic pain participated in a randomized, controlled design trial from 2006 to 2008. Overall, 45 pts accepted EA treatment and 34 completed the study. 45 pts accepted controlled and 32 completed. There was no difference of initial NRS which was 6.3±2.1 in EA group and 7.2±1.8 in controlled, p = 0.0669. Analysis showed a significant difference of NRS between EA group (3.2±1.7) and controlled (5.4±2.2) at the end of survey, p < 0.0001. The decrease in NRS was significantly higher in the EA group compared to the controlled (3.2±1.7 vs. baseline, p < 0.0001; 5.4±2.2 vs. baseline, p = 0.0007). Mean analgesics consumption variety in EA group was as follows: transdermal fentanyl increased by 51.2% (16 pts) and 77.3% (21 pts) in EA and controlled, p = 0.0005. Oxycodone increased by 85.5% (18 pts) and 115.6% (11 pts) in EA and controlled, p = 0.0183. Functional Assessment of Cancer Therapy-General (FACT-G) scale had no difference at the beginning, while it were 102±18 and 85±12 in EA group and controlled at the end of survey, p < 0.0001. Conclusions: EA can alleviate neuropathic pain of bone metastatic cancer pts, decrease the analgesics consumption, and promoting quality of life. No significant financial relationships to disclose.