bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of molecular HLA typing and outcome in high-risk melanoma patients receiving adjuvant interferon
Authors: Gogas H. , Spyropoulou-Vlachou M. , Dafni U. , Tsoutsos D. , Markopoulos C. , Polyzos A. , Stratigos A. , Pectasides D. , Bafaloukos D. , Fountzilas G. 
Published: April 2020

8029 Background: Serological typing for both HLA class I and class II antigen expression, has previously shown association of specific HLA antigen expression with clinical response and survival in patients with metastatic melanoma treated with IL-2 (e.g. HLA-DQ1). Purpose: To evaluate the impact of HLA class I (low-resolution) and class II (high-resolution) expression, on the outcome of high-risk melanoma patients receiving adjuvant high-dose interferon. Methods: 181 stage IIB, IIC and III melanoma patients (88 female and 93 male), median age 52.1 years and 246 healthy controls were included in this study. DNA was used for the determination of HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 genotypes. Results: With a median follow-up of 37 months, 59 (group 1) patients have remained with no evidence of recurrence and 122 have recurred (group 2). Statistical significant differences between the two groups, were found in the following genotypes: HLA-A*02 (42% vs. 57.3%, p=0.08), HLA-A*33 (15.2% vs. 6.5%, p=0.05), HLA-B*51 (15.2% vs. 34.4%, p=0.01), HLA-B*57 (11.8% vs. 2.4%, p=0.02). Statistical significant differences between group 1 and healthy controls, were found in the following genotypes: HLA-A*33 (15.2% vs. 6.5%, p=0.05), HLA-B*51 (15.2% vs. 28.5%, p=0.05), HLA-B*57 (11.8% vs. 4.5%, p=0.05), HLA-Cw*03 (23.7% vs. 11%, p=0.01), HLA-Cw*06 (27.1% vs. 16.1%, p=0.06), HLA-DRB1*0701 (27.1% vs. 13.4%, p=0.01), HLA-DRB1*1601 (35.6% vs. 22.3%, p=0.01), HLA-DQB1*0202 (23.8% vs. 10.1%, p=0.09). Conclusions: Statistical significant differences were seen in HLA-A and HLA-B alleles between the patients with high-risk melanoma free of recurrence and those who recurred after treatment with adjuvant interferon. Additionally, differences were seen between healthy controls and melanoma patients free of recurrence. No significant financial relationships to disclose.
Antigen-specific T cell responses in patients with melanoma treated with the CTLA4 blocking mAb ticilimumab
Authors: Ribas A. , Comin-Anduix B. , Bozon V. , Camacho L. H. , Bulanhagui C. A. , Jalil J. , Seja E. , Gualberto A. , Economou J. S. , Glaspy J. A. , Gomez-Navarro J. 
Published: April 2020

8033 Background: We previously defined the magnitude of the minimum statistically significant change in value for the MHC tetramer and ELISPOT assays (Comin-Anduix, Clin Cancer Res 2006). We used those reference change values (RCV) to determine if the administration of ticilimumab to patients with melanoma expands the circulating populations of tumor antigen-specific T cells. Methods: HLA-A2.1+ pts with sIIIc or IV melanoma and baseline circulating MART-1-specific T cells above the low limit of detection by tetramer assay (LLD, 0.03% of CD8+ T cells) received ticilimumab at 10 mg/kg monthly. Two 40 ml blood samples were collected at baseline, and one at 1 and 2 weeks after each dose for 4 cycles. Primary endpoint was immune response for MART-1 by tetramer assay, for which the RCV is 80% (expressed as percent change from baseline). Results: Of 15 pts (2 sIIIc, 5 sIVa, 2 sIVb, 6 sIVc), 1 was not treated and 2 received only 1 dose due to rapid progression. The 12 remaining pts received 2–11 doses. Clinical immunologic response to ticilimumab was evidenced by immune-related toxicity (G3 diarrhea in 2 pts, G2 hypophysitis in 1 pt, G3 hepatitis in 2 pts) and by anti-tumor activity: CR in 1 pt (15+ mo), PR in 2 pts (9+, 8 mo), and SD in 3 pts (11, 8+ and 4 mo); the rest had PD at 4 mo or less. A mean of 2 baseline and 7 follow up (range 5–9) time points were tested by tetramer and ELISPOT assays. 4 pts had an increase in MART-1-specific T cells beyond the RCV on 1 or more occasions, but no pt had a consistent pattern of change over time. Indeed, there was no consistent pattern of change in any pt in circulating T cells specific for MART-1, gp100, tyrosinase, EBV, or CMV by tetramer or by ELISPOT assay. One pt had accessible regressing lesions which on biopsy showed heavy infiltration by CD8+/Granzyme B+ CTL and a 10-fold enrichment of gp100-specific T cells compared to his peripheral blood. Conclusion: Ticilimumab administered monthly induces immune-related phenomena and tumor responses in patients with melanoma without a demonstrable expansion of circulating melanoma antigen-specific T cells. Evaluation of melanoma antigen-specific T cells within the tumor may be a better way to study the mechanism of antitumor activity of CTLA4 blocking mAb. [Table: see text]
Transdermal testosterone in female cancer survivors with decreased libido
Authors: Barton D. L. , Loprinzi C. , Wender D. , Dalton R. , Balcueva E. , Atherton P. , Bernath A. , Dekrey W. , Larson T. , Bearden J. , Sloan J. 
Published: April 2020

8507 Background: Problems with sexual functioning are an issue negatively affecting the quality of life of female cancer survivors. Testosterone has been implicated as an important hormone in sexual functioning such as libido. Studies of transdermal testosterone have shown benefit in enhancing libido in women who have been diagnosed with hypoactive sexual desire disorder after bilateral oophorectomy. This phase III placebo-controlled clinical trial evaluated whether transdermal testosterone would increase libido in female cancer survivors. Methods: Women with a history of cancer, currently without evidence of disease, were eligible if they reported a decrease in sexual desire and had a sexual partner. Women must have been postmenopausal. Eligible women were randomized to receive 2% testosterone in Vanicream (10 mg daily) versus placebo Vanicream for four weeks, then crossed over to the opposite treatment. The primary endpoint, libido, was measured via the desire subscales of the Changes in Sexual Functioning Questionnaire (CSFQ), which were completed at baseline and at the end of 4 and 8 weeks of treatment. The primary endpoint was the average intra-patient change from baseline to four weeks in the CSFQ subscales between the two arms. A total of 64 patients per group were needed to provide 80% power to detect a difference of 8 units between the treatment means. Two-sided alternative hypothesis testing and a 5% Type I error rate were used. Results: One hundred fifty women were enrolled onto this study. Complete data were available for 132 women. For those on active testosterone cream, serum bioavailable testosterone levels increased significantly over placebo, with a mean change from baseline of 12 and 10 ng/dl for the first and second period, respectively (p<.0001). The average intra-patient change from baseline to week 4 in libido was 5.5 on testosterone and 4.4 on placebo (p=0.58). No carryover effect was detected. The difference in average intra-patient changes from baseline for the entire crossover design between the two arms was only 1.1 points (95% confidence interval of -1.2 to 3.4, p=0.35). Conclusion: Testosterone is not a panacea for libido troubles in women with a history of cancer. Further studies are needed to determine whether there is a role for transdermal testosterone in this population. No significant financial relationships to disclose.
Double blind, placebo-controlled randomized study of chlorhexidine prophylaxis for chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy)
Authors: Sorensen J. , Skovsgaard T. , Bork E. , Damstrup L. , Ingeberg S. 
Published: April 2020

8508 Background: Oral mucositis is a frequent complication to many chemotherapy agents in conventional doses. Chlorhexidine prophylaxis has been beneficial in some studies and suggested detrimental in others, but never compared to cryotherapy. Methods: Previously untreatedpatients (pts) with colon or gastic cancer receiving the first course of bolus 5-FU 425 mg/m2 with leucovorine 20 mg/m2 daily in five days were randomized, pending informed consent, to either chlorhexidine 0.1% 15 ml mouthrinse one minut TID for 3 wks. (regimen A), or to doubble blind placebo (normal saline with same taste additive as in A) with same dose and frequency (reg. B), or to cryotherapy with crushed ice tips from 10 min. before to 35 min. after start of chemotherapy (reg. C). Pts self-reported on severity (CTC-grading, main end-point) and duration of oral mucositis and side effects on a questionnaire. 75 pts were planned in each arm to detect a 15% difference in grade 3–4 mucositis with a 5% type 1 error and a 20% power. Chi-square test and Mann-Whitney test were used. Results: Among 225 pts randomized, 206 answered the questionnaire (70, 64, and 63 pts in reg.A, reg.B, and reg.C) There were no differences between the regimens with respect to diagnoses, stage, age, gender, smoking habits, or performance status. Mucositis grade 3–4 (impaired oral nutrition/need of artificial nutrition) occurred in 13%, 33%, and 11% in regimens A, B, and C, respectively. Reg. B was significantly worse than A (p<0.01) and C (p<0.005). Median mucositis durations were A: 3 days (0–17), B: 5 (0–20), and C: 1 (0–20). Duration was significantly longer in B than in both A (p=0.035) and C (p=0.003). Pts <40 years had grade 3–4 mucositis in 36% compared to 18% among older pts (p=0.14). Conclusions: Oral mucositis is common with bolus 5-FU,but frequency and duration may be significantly improved by either prophylactic chlorhexidine or by cryotherapy, giving similar results. The latter is an easy and inexpensive treatment which however is drug- and schedule-dependent as it can not be used with infusional 5-FU or with chemotherapy with substantially longer half-lifes than 5-FU. No significant financial relationships to disclose.
Effectiveness of intrathecal ziconotide in malignant pain: A combined analysis of two controlled trials
Authors: Burton A. W. , Lemus B. , Fletcher R. , Chandler S. , Marmon T. 
Published: April 2020

8552 Background: Ziconotide is a nonopioid, N-type calcium channel blocker that inhibits neuronal calcium influx, thereby reducing neurotransmitter release at primary pain afferents. Clinical trials have shown ziconotide is useful in managing severe chronic pain, including nociceptive and neuropathic pain of malignant etiology. We reviewed the effectiveness of ziconotide using the Visual Analog Scale of Pain Intensity (VASPI: 100 mm=worst possible pain, 0 mm=no pain). Methods: Cancer patients from two double-blind, placebo-controlled trials (Studies 95–001 and 301) were analyzed. Study 95–001 used a fast titration scheme over 5 to 6 days, enrolling only patients with malignant pain due to cancer or AIDS. In Study 95–001, the initial dosing regimen was based on a pilot trial and was later modified due to the frequency of adverse events (AEs). The final slower titration, lower dosing regimen resulted in a reduced AE rate. Only patients from the final dosing regimen of Study 95–001 were included in this analysis. Study 301 used a slower titration scheme over 21 days, enrolling patients with malignant or nonmalignant pain. A two-sided, two-sample t-test was used to evaluate the null hypothesis that the mean percent change in VASPI score from baseline to end of titration for the ziconotide group was not significantly different from that of the placebo group (intent-to-treat population). Results: A total of 67 patients with malignant pain were treated in the trials; 51 (35 ziconotide, 16 placebo) had both baseline and end of titration VASPI scores. The ziconotide and placebo groups had similar mean baseline VASPI scores (75.5 and 75.8 mm, respectively). The mean percent improvement in VASPI score was 36.5% in the ziconotide group and 8.6% in the placebo group (p=0.0230). Conclusions: These results indicated that ziconotide was effective in relieving malignant pain. [Table: see text]
Anticoagulation vs. vena caval filters in cancer patients with venous thromboembolism: Improved survival with anticoagulation
Authors: Barginear M. F. , Lesser M. L. , Strakhan M. , Khetarpal P. , Bradley T. , Budman D. R. , Shapira I. 
Published: April 2020

8553 Background: Cancer patients (pts) have an increased incidence of venous thromboembolism (VTE). Inferior vena caval (IVC) filters are used extensively in the US; over 40,000 are inserted annually. The impact on survival of cancer pts receiving IVC filters has not been studied. Methods: A retrospective study examined 154 consecutive cancer pts with VTE in order to compare the effects of IVC filter placement with anticoagulation (AC) therapy on overall survival (OS), as measured from the time of VTE. Pts were classified into three treatment groups: AC (n=58), IVC filter (73), or combination IVC filter+AC (23). OS was analyzed using survival analysis methods (e.g., Kaplan-Meier Product-Limit Method, logrank test). Multivariate Cox regression was used to account for the possible confounders: ECOG performance status (PS) and type of thrombus. Results: Treatment groups did not differ with respect to age, gender, or albumin levels. Groups did differ for PS (P<0.033 chi-square test, better PS was associated with AC only) and for type of thrombus (P<0.007 chi-square, DVT was associated with AC, PE with IVC, and DVT/PE with AC+IVC). Median OS was significantly greater in pts treated with AC (11 mos) compared to IVC filters (3 mos) or IVC+AC (3.5 mos) (p<0.0046). IVC pts were 1.73 times more at risk of death than AC only (hazard ratio; 95%CI 1.18–2.52). Multivariate analysis revealed that PS and type of thrombus were not confounders and had no effect on OS. Conclusion: AC should be considered primary therapy for cancer pts with VTE. IVC filters should be considered a therapeutic option only when AC is strictly contraindicated. Prospective randomized trials are needed to address this issue. No significant financial relationships to disclose.
Prospective validation of a risk model for first cycle neutropenic complications in patients receiving cancer chemotherapy
Authors: Lyman G. H. , Kuderer N. M. , Crawford J. , Wolff D. A. , Culakova E. , Poniewierski M. S. 
Published: April 2020

8561 Background: A nationwide, prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications (NC) in cancer patients receiving chemotherapy. Methods: 3,596 patients initiating a new chemotherapy regimen with solid tumors or lymphoma were registered at 115 randomly selected sites. Data on at least 1 cycle of chemotherapy were available on 3,468. A logistic regression model for cycle 1 NC was derived and then validated using a split sample random selection process. Results: The risk of cycle 1 NC ranged from 5.5%-30.2%, averaging 18.5% across tumor types. No significant differences in distribution of NC or predictive factors were observed between the derivation dataset (n=2,592) or the validation dataset (n=876). Major independent baseline clinical risk factors for cycle 1 NC in the derivation model include: prior chemotherapy (P=.044), number of myelosuppressive agents (P<.0001), anthracycline-based regimens (P<.0001), planned delivery >85% of standard (P<.0001), cancer type (P<.0001), concurrent antibiotics (P=.023) or phenothiazines (P=.006), abnormal alkaline phosphatase (P=.002), elevated bilirubin (P=.031), low platelets (P=.004), elevated glucose (P=.023) and reduced glomerular filtration rate (P=.013). Reduced risk of cycle 1 NC was associated with primary prophylaxis with a myeloid growth factor (P<.0001). Model R2 was 0.273 and c-statistic 0.80 [95% CI: 0.78–0.82; P<.0001]. At the median predicted risk of cycle 1 NC of 11%, model test performance consisted of: sensitivity 84%; specificity 57% and diagnostic odds ratio (DOR) 7.2 while cycle 1 NC risk was 31% and 6% among high risk and low risk half, respectively. The model performed well in the smaller validation dataset with a model R2 of 0.354 and c-statistic of 0.84 [95% CI: 0.81–0.87, P<.0001]. Test performance of the model in the validation sample included: sensitivity 90%; specificity 62%; DOR 14.1 and risks of 35% and 4% in high risk and low risk patients, respectively. Conclusions: Validation in a randomly selected patient sample suggests that this model has general applicability in identifying patients at increased risk for NC. Further validation in other independent cancer patient populations receiving chemotherapy is planned. [Table: see text]
Predictors of fatigue and quality of life in a prospective palliative care cohort
Authors: Martin M. G. , Currow D. C. , Abernethy A. P. 
Published: April 2020

8571 Background: Palliative care seeks to minimize distress at the end of life. Fatigue significantly diminishes quality of life (QOL) in this population. Are there potentially modifiable factors that influence fatigue and QOL? Methods: This analysis focuses on a subset of 198 patients from a larger 2×2×2 factorial randomized trial of pain education and care coordination conducted in South Australia. Selected participants were adults referred to a community palliative care service with pain in the preceding 3 months and a hemoglobin assessment within 14 days of enrollment. Pain, other symptoms, and Australia-modified Karnofsky Performance Status (AKPS) were recorded at enrollment. Predictors considered were anxiety, depression, dyspnea, constipation, pain, AKPS, hemoglobin, age, and gender. Dependent variables were global QOL from the McGill QOL Questionnaire and fatigue. Using forward stepwise linear regression, multivariate models predicting fatigue and QOL were constructed from significant univariate variables. Results: Mean age was 69 (standard deviation (SD) 13); 97% had cancer. Most frequent diagnoses were lung (18%), hematological (15%), and colorectal (15%) malignancies. Mean hemoglobin was 11.4 gm/dL (SD 1.9); median AKPS 60%; mean worst pain 4.0 (SD 3.4; 0–10 scale). Distressing symptoms (3–4 on 0–4 scales) included dyspnea (22%), constipation (13%), anxiety (11%), and depression (6%). Mean QOL was 5.9 (SD 2.0) on a 0–10 scale; mean fatigue was 2.3 (SD 1.0) on a 0–4 scale. The final multivariate model predicting fatigue included AKPS (p<0.01), constipation (p=0.02), and dyspnea (p=0.06). Hemoglobin was not predictive of fatigue (univariate p=0.7069). QOL was significantly influenced by fatigue (p=0.03), anxiety (p< 0.01), and AKPS (p= 0.01). Conclusions: Fatigue was driven by performance status, constipation, and dyspnea. In contrast to an oncology population, hemoglobin was not a significant contributor to fatigue in this population, consistent with other palliative care cohorts. QOL was driven by fatigue, anxiety, and performance status. This analysis of a prospectively collected population suggests that performance status, constipation, dyspnea, and anxiety are potentially modifiable variables impacting fatigue and QOL in the palliative care setting. No significant financial relationships to disclose.
Prospective neurocognitive effects and quality of life (QOL) in patients with multiple brain metastases receiving whole brain radiation (WBRT) ± thalidomide on radiation therapy oncology group (RTOG) trial 0118
Authors: Fox S. , Berkey B. , Knisely J. , Chakravarti A. , Yung W. A. , Curran W. , Robins H. , Brachmen D. , Henderson R. , Mehta M. , Movas B. 
Published: April 2020

8589 Background: RTOG 0118 was a randomized trial of WBRT (37.5 Gy/15 fractions) ± thalidomide in patients (pts) with brain metastases, which showed no effect on survival (Knisely et al, ASCO, 2005). This analysis examined the relationship between neurocognitive progression (NCP) and QOL in patients on both arms. Methods: NCP was assessed with the Folstein Mini-Mental Status Exam (MMSE) and QOL with the Spitzer QOL Index (SQLI). Pts with MMSE scores below age/education adjusted cutoff levels were considered to have NCP. T-test and Chi-Square statistics were used to determine significant differences in NCP and QOL between the two treatment arms over time. Results: Of 176 pts, 88 and 92% had SQLI and MMSE scores at baseline (43% were below the MMSE cutoff). Baseline SQLI (but not MMSE) was a significant predictor for OS (p=0.034). From baseline, SQLI and MMSE compliance rates were 74 and 60% at 1–2 months (mo), 37 and 29% at 4 mo, and 21 and 19% at 6 months, respectively. While QOL was stable, those who failed to meet MMSE cutoffs increased by 60% by 6 mo, on both study arms. Although a weak correlation (r=.23) existed at baseline between QOL and MMSE for both the WBRT (0.04) and WBRT/thalidomide (0.058) arms, there was no correlation beyond baseline. Conclusions: Baseline QOL is a significant predictor of OS. While QOL remained essentially stable, the degree of neurocognitive decline (60%) over time is concerning. These findings suggest the importance of these outcome measures in pts with brain metastases and the need for interventions to conserve cognitive status. RTOG is developing a trial to study the role of preventive strategies for NCP in brain metastases. No significant financial relationships to disclose.
Symptom distress, quality of life and challenges of illness according to race and income in women with metastatic breast cancer
Authors: Rosenzweig M. , Wiehagen T. , Brufsky A. M. , Arnold R. M. 
Published: April 2020

8609 Background: Response to a diagnosis of metastatic breast cancer (MBC) may vary according to race and income. The aims of this study were: 1) to identify quality of life, symptom distress and challenges of illness during MBC treatment and 2) to determine if these variables differ according to race and income. Methods: The study was a 2×2 prospective design conducted at an urban breast cancer center. Women with MBC were categorized into four groups based on race and income: white low (WL), white high (WH), African American high (AAH) and African American low (AAL). Instruments were 1) Symptom Distress Scale (SDS), (higher scores /worse distress) 2) Functional Assessment of Cancer Therapy (FACT), (higher scores/better QOL) and a 3) semi structured interview assessing patient perspectives of MBC. Interview analysis utilized grounded theory. Results: Preliminary results are for 51 women. Mean age was 58.2 years, with mean 24 months since MBC diagnosis. Quantitative data indicated worse quality of life in AA than white women. (P=0.06), with AALI women exhibiting worse symptom distress (P=0.03) as compared to white women. Qualitative data (n=48) corroborated quantitative data. The most prevalent themes among all sociodemographic groups were of hope (33/48 - 69%), faith (28/48 - 58%) and progressive loss (29/48, 60%). Each racial/economic delineation expressed unique themes: AALI talked about physical (7/7,100%)and social distress (6/7, 86%) as well as uncertainty regarding “whether treatment was worth it” (6/7 - 86%). WLI women verbalized an overall optimism, describing themselves as “lucky” (6/14 - 43%), with minimization of symptoms (10/14 - 71%). WHI women articulated a sense of betrayal at their progressive illness (9/20 - 45%) and fear of physical and economic dependence. Conclusion: Race and economic delineation brings unique symptom experience, quality of life and patient perspective to the metastatic breast cancer experience. These findings will advise tailored intervention. [Table: see text] No significant financial relationships to disclose.