bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation of circulating DNA in melanoma patients
Authors: Hengge U. R. , Marini A. , Mirmohammadsadegh A. , Nambiar S. , Gustrau A. , Ruzicka T. 
Published: April 2020

8027 Background: DNA methylation is a well-known epigenetic phenomenon that occurs in higher order eukaryotes. Changes in the status of DNA methylation of tumor suppressor genes (TSG) is one of the common molecular alterations in many carcinomas. Methods: The purpose of this study was to investigate hypermethylation status of five different genes (TSG and cell cycle genes) involved in tumor suppression and DNA repair. Results: Serum before therapeutic intervention from 32 melanoma patients (stage I = 13; stage II = 9; stage III/IV = 10) was collected, cell-free DNA was isolated and sodium bisulfite conversion of genomic DNA was performed. The methylation status of CpG islands in the promotor region of SOCS1, SOCS2 (suppressors of cytokine signaling 1 and 2); RASSF1a (Ras-association domain family protein 1A); CDKN (D-type p16INK4a cyclin-dependent kinase inhibitor); and MGMT (O6-methylguanine DNA-methyltransferase) were analyzed using methylation specific-PCR (MSP). For comparison, sera from healthy controls (n = 20) and patients with other skin tumors (9 basal cell cancers, 5 Kaposi’s sarcoma) as well as different cancers (5 breast cancers, 5 colon cancers) were also analyzed. In addition, we examined if methylation was involved in silencing of these genes in 20 fresh melanoma specimens and we confirmed the hypermethylation status of SOCS2 using positional methylation analysis (pyrosequencing). Moreover, the expression of these genes was investigated cell lines (BLM, A375, MV3, and M13). Analysis of sera from cutaneous melanoma patients demonstrated circulating hypermethylated SOCS 1 in 59%, SOCS2 in 53%, RASSF1a in 53%, CDKN2a in 50%, while the MGMT did not show clear methylation pattern. Serum of healthy controls showed no methylation of any of the analyzed genes. The mRNA transcript of these genes showed a clear and significant downregulation, except for MGMT, for which an up regulation (7.3 times) was detected being consistent with the lack of promotor methylation. Detailed positional methylation analysis (pyrosequencing) has been performed for these genes and was found to correlate with mRNA expression in the tumor specimens in most cases. Conclusions: Analysis of positional methylation of circulating cell-free DNA seems to be a novel tool for molecular diagnosis in melanoma. No significant financial relationships to disclose.
Cognitive impairment associated with chemotherapy for breast cancer: An exploratory case-control study
Authors: Booth C. M. , Vardy J. , Crawley A. , Rourke S. , Pond G. , Wagner L. , Tannock I. F. 
Published: April 2020

8501 Background: There is evidence that some women suffer cognitive impairment after adjuvant chemotherapy (CT) for breast cancer and it may be sustained. We report a case-control study to explore underlying mechanisms with blood tests and functional imaging. Methods: Women diagnosed with breast cancer within 5 years were recruited to 3 groups of 20. Cases (group A) had received CT and self-reported cognitive dysfunction on a prototype FACT-COG questionnaire. There were 2 groups of controls: group B had received CT but did not report cognitive problems; group C had breast cancer but did not receive CT. Comprehensive tests of cognitive function (2.5 hr) were performed. Blood tests evaluated sex hormones, coagulation factors, 10 cytokines, and apolipoprotein genotype. Functional MRI (fMRI) scans were performed while subjects performed a mental task. Results: Currently, 60 women have completed FACT-COG, 39 have undergone neuropsychological assessment and 31 have completed fMRI; testing and analysis will be complete by May 2006. Median time from diagnosis was 2 years. There was increased self-report of cognitive impairment in CT vs non-CT patients (p<0.0001). Formal cognitive testing disclosed more impairment in group C (no CT) as compared to groups A and B: 29% vs 0% by classical tests (p=0.046), and 61% vs 47% and 25% (p=0.38) by computerized testing. This may be due to slight imbalance of demographic factors. Decreased activation in fMRI was seen in frontal areas and right parahippocampus of women who self-reported greater cognitive impairment (p<0.0005), while separate frontal areas show increased activity in women with greater objective cognitive impairment (p<0.0005). Patients who received CT reported more fatigue than non-CT patients (p=0.027). There was an association between fatigue and self-reported cognitive impairment (p=0.004) and anxiety and depression (General Health Questionnaire) (p=0.009), but not with objective cognitive testing. As yet there is no significant correlation between symptoms and cytokine levels. Conclusions: Self-reported cognitive impairment is associated with prior chemotherapy and changes in fMRI but not with formal cognitive testing. The larger sample size is required to confirm these changes and explore possible mechanisms. No significant financial relationships to disclose.
Self-reported cognitive impairment in cancer patients: A URCC CCOP longitudinal study of 595 patients
Authors: Kohli S. , Griggs J. J. , Jean-Pierre P. , Mustian K. M. , Roscoe J. A. , Wade J. L. , Kuebler J. , Fishkin E. , Morrow G. R. 
Published: April 2020

8502 Background: Patients undergoing cancer treatment often report cognitive impairment, manifested as problems with concentration and memory. Such cognitive problems may be noticed only by the patient. The purpose of this multicenter longitudinal study was to investigate the frequency and severity of self-reported problems with memory and concentration over time. Methods: Patients undergoing treatment for solid tumors self-rated problems with memory and concentration using an 11-point Likert Scale (0 = Not present to 10 = “As bad as you can imagine”) at baseline before treatment began (T1), at their worst during treatment (T2), and at 6 months following treatment (T3). Any symptom level ≥ 7 was classified as “severe.” T-tests, paired or independent as appropriate, were used to examine differences in symptoms over time and between patients treated with and without chemotherapy. Results: Of 595 participants, 356 (60%) received chemotherapy, with or without radiation and 239 (40%) radiation alone. Concentration problems were reported by 48% of all participants at T1 (5% severe), 67% at T2 (18% severe) and 58% (8% severe) at T3 (p < .001). Memory loss was reported by 53% at T1 (4% severe), 67% (18% severe) at T2 and 68% (11% severe) at T3 (p < .001). The average frequency and severity of both symptoms in patients receiving chemotherapy increased significantly between T1 and T2 (p<.001). Both symptoms were less severe in patients receiving radiation alone at all three measurements (all ps<.001). Symptoms at T3 were significantly higher than T1 for both groups (p<.001). Conclusion: Self-reported problems with memory and concentration are experienced by the majority of cancer patients who receive chemotherapy and radiation. The cognitive problems get worse during treatment and persist at least 6 months following. Controlled studies of interventions for problems of memory loss and concentration are warranted. Supported in part by a supplement from the Division of Cancer Control and Population Sciences, NCI, to Public Health Service grant U10 CA37420 and by NCI grant 1R25CA102618. No significant financial relationships to disclose.
A randomized controlled pilot of home-based exercise (HBEX) versus standard care (SC) among breast (BC) and prostate cancer (PC) patients receiving radiation therapy (RTH)
Authors: Mustian K. M. , Morrow G. R. , Yates J. , Gillies L. , Boles C. 
Published: April 2020

8504 Background: Cancer-related fatigue (CRF) is reported in up to 97% of cancer patients during RTH. 60% rate it as moderate to severe. Fatigue can significantly reduce functional capacity (FC), treatment compliance, and QOL. Although there is no standard treatment for CRF, aerobic exercise has demonstrated a positive influence on CRF and FC during RTH, but the influence of combined resistance and aerobic exercise is not clear. We explored the efficacy of a low to moderate home-based exercise intervention, including resistance and aerobic training, to SC on CRF and domains of FC (aerobic capacity and strength), in a sample of BC and PC patients during RTH. Methods: BC and PC patients (N=38; ξ age=56; 71% BC), beginning at least 28 sessions of RTH were randomized to a 4wk HBEX (7 days/wk) or SC condition, with CRF (FACT subscale), aerobic capacity (6-min. walk), and strength (handgrip dynamometry) assessments pre and post-intervention. Results: Change scores indicated improvements in the HBEX group (N=19) in CRF (ξ=3.6, SE=2.1) and aerobic capacity (ξ=43.6, SE=52.3), while the SC group declined in CRF (ξ=-1.1, SE=1.1) and aerobic capacity (ξ=-28.5 SE=71.6). Change scores revealed declines in strength among both groups, however the HBEX group showed smaller declines in strength (ξ=-.05, SE=0.7) compared to the SC group (ξ=-.80, SE=.91). T-tests using intent-to-treat indicated statistically significant between group differences on changes in CRF (ES=.63; p=.05) from pre to post-intervention, as well as significantly higher aerobic capacity (ES=1.3; p<.001) with a statistical trend toward lower CRF (ES=.51; p=.09) between groups post-intervention. Conclusions: HBEX improved CRF and aerobic capacity, while SC resulted in declines. HBEX reduced declines in strength compared to SC. Future phase III randomized controlled trials are needed with larger samples to fully investigate the influence of this HBEX intervention on CRF, aerobic capacity and strength. Funded by NCI grant 1R25CA102618. No significant financial relationships to disclose.
Randomized trial of yoga in women with breast cancer undergoing radiation treatment
Authors: Cohen L. , Chandwani K. , Thornton B. , Perkins G. , Rivera E. , Arun B. , Raghuram N. , Nagendra H. 
Published: April 2020

8505 Background: Yoga, an ancient Indian science, incorporates stress-reduction techniques that include regulated breathing, visual imagery, and meditation, as well as various postures that may be useful for cancer patients. Methods: A yoga program was developed that including loosening and breathing exercises, postures, alternate nostril breathing, a deep relaxation technique, and meditation for patients with breast cancer who were undergoing radiotherapy. Women participated in bi-weekly classes during their 6 weeks of radiation treatment. Sixty-one women with breast cancer were randomly assigned to either the yoga program or to a waitlist control group. Patients completed measures of intrusive thoughts and avoidance behaviors (Impact of Events Scale: IES), depressive symptoms (CES-D), sleep disturbances (Pittsburgh Sleep Quality Index), fatigue (BFI), and quality of life (SF-36) at baseline, 1 week, and 1 and 3 months after the last radiation therapy. We report on the outcomes 1 week after the end of radiotherapy. Results: The average age of the women was 52, 3% stage 0, 28% stage I, 43% stage II, and 26% stage III, 48% had undergone breast-conserving surgery, and 75% had received chemotherapy prior to starting radiotherapy. Analysis of covariance, controlling for baseline, revealed that the yoga group had significantly better SF-36 physical function scores (adjusted means: yoga 81.8 vs. control 68.6, P < 0.01), significantly higher SF-36 general health scores (adjusted means: yoga 78.3 vs. control 67.9, P < 0.03), marginally better SF-36 social functioning scores (adjusted means: yoga 85.3 vs. control 76.0, P > 0.1), significantly lower levels of sleep-related daytime dysfunction (adjusted means: yoga 0.5 vs. control 1.2, P < 0.04), and marginally lower levels of fatigue (adjusted means: yoga 1.9 vs. control 3.1, P < 0.06) than the control group. There were no other group differences on the SF-36 subscales or for the CES-D or IES scores. Conclusions: The results indicated that the yoga program was associated with statistically and clinical significant improvements in aspects of quality of life. No significant financial relationships to disclose.
Osteonecrosis of the jaw in patients receiving intravenous bisphosphonate therapy
Authors: Hoff A. O. , Toth B. B. , Altundag K. , Guarneri V. , Adamus A. , Nooka A. K. , Sayegh G. G. , Johnson M. M. , Gagel R. F. , Hortobagyi G. N. 
Published: April 2020

8528 There have been reports of osteonecrosis of the jaw (ONJ) in patients (pts) with metastatic bone disease (MBD) treated with IV bisphosphonates (IVBP). To estimate the frequency and identify risk factors for ONJ we performed a retrospective analysis of pts treated with IVBP. The cohort included 4019 patients identified through the MDACC pharmacy database (PD) treated with IVBP from 9/1996 to 2/2004, and 6 patients diagnosed with ONJ at the MDACC Dental Clinic. ONJ was defined as exposed non-healing bone of at least 3 months duration. Preliminary statistical analysis included 4000 patients. The most common diagnoses were breast cancer [BRCA] (1340), MM (550) and lung cancer (380).The indications for IVBP therapy included MBD (60%), hypercalcemia (25%), MM (14%) and osteoporosis (7%). We identified 34 patients with ONJ: 18 BRCA, 14 MM, 1 prostate cancer and 1 thyroid cancer. The frequency of ONJ was calculated by including patients from the PD only: 16/1338 (1.2 %) in BRCA and 14/448 (3.1%) in MM. Patients with ONJ received pamidronate [P] (6), zoledronate [Z] (10), combination of P and Z (15). The mean cumulative dose (MCD) of P was 2182 mg (720–4410) in MM and 2745mg (1980–3510) in BRCA. MCD of Z was 61 mg (24–152) in MM and 62 mg (28–110) in BRCA. The total doses of P and Z were significantly higher in the ONJ group VS NON-ONJ group (P<0.0001). Pts with ONJ had longer duration of disease and longer follow-up than NON-ONJ cases (P<0.0001). Univariate and multivariate logistic regression analyses (MLRA) revealed dental extractions (DE), ER positive tumors, and treatments with P and Z as significant factors associated with ONJ in BRCA pts. In MM, DE, periodontal disease and osteoporosis were significant factors. Further statistical analysis, including Cox regression analysis, is under way. ONJ pts were treated with aggressive oral hygiene, oral rinses, debridement of necrotic bone and antibiotics. 15 pts were followed at the dental clinic longer than 6 months. ONJ healed in 1, improved in 1, stable in 4 and progressed in 9 pts. In conclusion, ONJ is a significant but uncommon event. Higher doses of IVBP, longer treatment duration, DE, and periodontal disease are associated with a greater risk to develop ONJ. Good dental care and avoidance of dental interventions should be recommended to all patients treated with IVBP. [Table: see text]
A placebo-controlled trial of etanercept, a tumor necrosis factor (TNF) inhibitor, in patients with the cancer anorexia/weight loss syndrome. North Central Cancer Treatment Group (NCCTG) trial N00C1
Authors: Jatoi A. , Dakhil S. R. , Kugler J. W. , Rowland K. M. , Keit J. , Verdirame J. D. , Novotny P. J. , Sloan J. A. , Nguyen P. L. , Loprinzi C. L. 
Published: April 2020

8534 Purpose: Tumor necrosis factor (TNF) is a putative mediator of the cancer anorexia/weight loss syndrome. This study was designed to determine if etanercept (a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton TNF receptor linked to the Fc portion of human IgG1) could palliate this syndrome. Methods: 63 evaluable patients were randomly assigned to etanercept 25 mg SQ twice/week versus a comparably-administered placebo, both of which were to be given for at least 12 weeks. All patients had an incurable malignancy, acknowledged loss of weight and/or appetite as a concern, and reported weight loss of > 5 pounds over 2 months and/or a daily intake of < 20 calories/kg body weight. The above sample size provided 81% power to detect a 24% difference in the percentage of patients who gained >/= 10% of baseline weight. Results: At baseline, groups were comparable on age, gender, tumor type, and degree of weight loss. Over time, weight gain was minimal in both groups; no patient gained >/= 10% baseline weight. Appetite questionnaires (the NCCTG Anorexia/Cachexia Questionnaire and FACT-AN) revealed negligible improvements in both groups. Median survival was comparable: 175 days versus 148 in etanercept-treated and placebo-exposed patients, respectively (p=0.82). Finally, preliminary data on adverse events showed that etanercept-treated patients had higher rates of neurotoxicity (29% versus 0%) but lower rates of anemia (0% versus 19%) and thrombocytopenia (0% versus 14%). Infection rates were negligible in both groups. Clinical correlative data on TNF genotyping will be available at the time of the meeting. Conclusion: This TNF inhibitor does not appear to palliate the cancer anorexia/weight loss syndrome. The study was supported by CA37404, the American Institute for Cancer Research, and Amgen. No significant financial relationships to disclose.
Finding an appropriate dose of fentanyl effervescent buccal tablets for relief of cancer-related breakthrough pain
Authors: Weick J. K. , Tremmel L. , Messina J. , Portenoy R. K. 
Published: April 2020

8564 Background: The recommended dose of a short-acting oral opioid used to treat cancer-related breakthrough pain (BTP) is 5%-15% of the equianalgesic around-the-clock (ATC) opioid dose used to control persistent pain; however, this dosing strategy may not be successful when oral transmucosal fentanyl citrate is used. The applicability of this strategy to fentanyl effervescent buccal tablets (FEBT) use was assessed as part of a multicenter study in opioid-treated patients with cancer BTP. Methods: This double-blind, randomized, placebo-controlled, crossover study required 63 evaluable patients for adequate statistical power. Eligible adults were to receive ≥60 mg/day morphine or equivalent for chronic cancer pain and to have experienced 1–4 BTP episodes daily. After open-label titration to an effective FEBT dose, patients were randomized to 1 of 18 predefined sequences of 10 tablets (7 FEBT, 3 placebo). Pain was assessed repeatedly after each dose; the primary efficacy variable was the sum of pain intensity differences at 30 minutes postdose (SPID30). Results: Of 123 enrolled patients, 77 found an effective FEBT dose (100–800 μg) and continued in the double-blind period; 72 were evaluable for efficacy. The SPID30 was 3.0±0.12 (mean±SE) for FEBT vs 1.8±0.18 for placebo (P<.0001). Ratios of the effective FEBT dose to ATC opioid or prior supplemental opioid dose showed no consistent trend (table). An effective FEBT dose showed no meaningful correlation with prior supplemental dose (r2=.094; Pearson’s coefficient=.3066), with ATC dose in patients using oral opioids (r2=.0609; Pearson’s coefficient=.2468), or with ATC dose in patients using transdermal fentanyl or combinations (r2=.1842; Pearson’s coefficient=.4292). Conclusions: There was no relationship between the effective FEBT dose and either ATC opioids or prior supplemental drugs. Therefore, titration, rather than use of a percentage of the ATC dose, is likely to be important in establishing an effective FEBT dose for each patient. [Table: see text] [Table: see text]
Academic oncologists’ attitudes and practices regarding the care of cancer patients at the end of life
Authors: Dias L. , Lamont E. 
Published: April 2020

8572 Background: Despite the fact that cancer is the second leading cause of death in the US and represents the most frequent diagnosis among hospice patients, little is known about the factors that influence oncologists in their decision making around end of life care. Methods: We surveyed all clinically active medical oncology attending and fellow physicians at two affiliated academic medical centers eliciting oncologists’ attitudes and practices regarding care of cancer patients at the end of life. Included in the survey were a series of randomized vignettes describing patients with advanced solid tumors. Oncologists were asked to describe their next treatment recommendations. Results: Of the 181 oncologists contacted for survey participation, 116 (64%) returned completed questionnaires. Sixty six percent (77/116) of respondents were attending physicians and 34% (39/116) were fellows. Sixty-five percent favored concurrent treatment with third-line chemotherapy and hospice if insurance would allow. Eighty percent (93/116) agreed that patients with advanced cancer should be able to receive hospice care even if they are receiving anti-tumor therapies. Results of randomized scenarios suggest that advanced patient age was positively associated with earlier referral to hospice care and that prior treatment on a clinical trial, although not statistically significant, was modestly associated with delayed referral to hospice (1.49, 95% CI 0.71–3.11). Conclusions: Among oncologists at two academic centers, chemotherapy is an important modality for management of advanced cancer patients at the end of life. Therefore, insurance policies that prohibit chemotherapy for hospice patients may constrain oncologists in their management of such patients. No significant financial relationships to disclose.
Factors associated with fatigue in children with cancer at the end of life
Authors: Ullrich C. K. , Hilden J. M. , Sheaffer J. W. , Moore C. L. , Berde C. B. , Weeks J. C. , Wolfe J. 
Published: April 2020

8574 Background: Fatigue is prevalent in children with cancer but is poorly understood. Improved understanding of this symptom will inform development of interventions aimed at alleviating it. Methods: Cross-sectional survey conducted between 1997–2001 of 144 parents of children who died of cancer cared for at Dana-Farber Cancer Institute/Children’s Hospital Boston and Children’s Hospital and Clinics, St Paul and Minneapolis (response rate 65%). Parents reported the child’s experience of symptoms in the last month of life and associated suffering, and patient characteristics. Determinants of suffering from, and treatment of fatigue were explored with univariate analyses adjusting for physician and time since death. A logistic regression model was built to determine factors associated with suffering from fatigue, with a threshold for entry of P<.05, and accounting for physician clustering. Results: Almost all children experienced fatigue and 50% suffered significantly from it (a great deal/a lot versus some/a little/none at all). Only 15% received treatment, and of them, 79% were not successfully treated. Univariate analyses revealed significant associations between suffering from fatigue and suffering from pain, dyspnea, anorexia, diarrhea, and nausea/vomiting, as well sadness, anemia and successful treatment of pain (P<.05). Treatment of fatigue was associated with side effects from treatment of pain (OR 3.9, P=.008) and treatment of dyspnea (OR 3.9, P=.02). In the multivariate analysis of suffering from fatigue, successful treatment of pain remained significant (OR 4.2, P=.009). Conclusions: Suffering from fatigue is common in children with cancer at the end of life and efforts to palliate it are limited. Significant fatigue is highly associated with other symptoms and their treatments. Increased attention to treatment-related fatigue and evaluation of interventions such as stimulants may be effective in ameliorating fatigue in children with advanced cancer. No significant financial relationships to disclose.