bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of androgen deprivation therapy on CD4/CD8 T cells in HIV-negative patients receiving definitive 3D radiation treatment for their prostate carcinoma: Final report of a prospective study
Authors: Elshaikh M. A. , Abdel Hafeez Z. , Lu M. , Ibrahim D. , El Masry T. , Yousef A. 
Published: August 2020

11056 Background: CD4 and CD8 T cells play critical roles in human immunity. The aim of this prospective study is to explore the correlation of the absolute CD4/CD8 T cell counts and total testosterone in patients receiving androgen deprivation therapy (ADT) with goserelin acetate and definitive radiation treatment (RT) for their prostate cancer. Methods: Thirty-four HIV-negative patients were included in this study between June 2006 and January 2007. All patients had a baseline total testosterone level (T), PSA, CD4 and CD8 T cell counts. CD4/8 T cells count was measured using flow cytometry. All patients received 6 months of ADT prior to (baseline) and during RT to the prostate. Subsequent blood samples were taken at 2, 8, 12 and 24 months. Blood samples were taken between 8–10 am to control for diurnal variations in CD4/CD8 T cell counts and T levels. To study the correlation of T with CD4/8 T cell changes, the Spearman correlation coefficient was calculated. The study was approved by the appropriate Ethics Committee. Results: Median age for the study patients was 68 years. At baseline, median testosterone level was 350 ng/dL, median CD4 T cell count was 1055 mm3, and median CD8 T cell count was 644 mm3. None of the patients received anti-androgens. At two months, testosterone was at the castrate and subnormal levels in 85% and 100% of the patients, respectively. The lower testosterone levels resulted in significant reduction of CD4 and CD8 T cell counts at 2, 8, 12 and 24 months compared to baseline counts. This effect was more pronounced for CD4 T cells at all time points (p=<0.02). At 24 months, when total testosterone levels were increasing, CD4 and CD8 T cell counts were also following these upward trends. The seen correlation between lower testosterone and decline in CD4 and CD8 T cells was only statistically significant in older patients (>65 years) and was not associated with significant decline in total white blood cell counts. Conclusions: CD4/CD8 T cell counts are sensitive to changes in total testosterone levels. Lower testosterone levels negatively affecting CD4/CD8 T cells counts at all study time points. Since CD4/CD8 T cells play major roles in cellular immunity, further studies are warranted No significant financial relationships to disclose.
Development of educational materials about inherited breast cancer in black women
Authors: Pal T. , Gjyshi A. , Rivers D. , Rocchio E. , Garcia A. , Quinn G. P. , Vadaparampil S. 
Published: August 2020

1536 Background: Current educational materials about inherited breast and ovarian cancer (HBOC) have not been culturally tailored for the Black community, which may contribute to lower levels of awareness about this topic. Through an academic and community partnership, realized through a Community Advisory Panel (CAP) comprised of breast cancer survivors, advocates, community leaders, and health care providers, this need was identified. Methods: Utilizing a phased approach implemented through this academic and community partnership, a culturally tailored brochure and booklet about HBOC for the Black community were developed and reviewed. To evaluate the brochure, three focus groups were conducted by race-concordant moderators. HBOC was discussed with Black women from diverse backgrounds, including those with and without breast cancer (n = 46). Summaries were created from audiotapes and handwritten notes and content was analyzed based on Grounded Theory, after which the brochure was revised. Similarly, revisions to the booklet were made based on feedback obtained about the brochure. Materials were then presented to the CAP for re-review. Results: From this iterative process, the key content identified as areas for improvement were: (1) Inclusion of breast cancer information specific to Black women; (2) Use of the term “Black”; (3) Inclusion of African American flag colors; (4) Clarification of the concept of genetic counseling; and (5) Enhancing relevance of information for young women. Conclusions: The CAP and study participants recognized the need for culturally relevant educational materials addressing HBOC in the Black community. Their feedback identified important areas for improvement which have been implemented in the design of a culturally tailored brochure that is available for widespread dissemination. Further evaluation of the booklet is currently in progress. No significant financial relationships to disclose.
Trends in screening for prostate cancer
Authors: Eisinger F. , Morere J. , Pivot X. , Blay J. , Coscas Y. , Calazel Benque A. , Roussel C. , Viguier J. 
Published: August 2020

1542 Background: Screening for prostate cancer is still in debate. In France, there is no financial barrier for individuals to be screened with the prostate-specific antigen (PSA) test, and there is no recommendation for mass screening. Methods: Two nationwide observational studies were carried out in France. The first one, EDIFICE 1, was conducted in 2005 among a representative sample of 1504 subjects aged between 40 and 75 years and a representative sample of 600 general practitioners (GPs). The second one, EDIFICE 2, was conducted in 2008 with the same methodology. Results: General population: In 2005, 36% of the interviewed male population aged between 50 and 75 years declared having undergone a screening test, compared to 49% in 2008 (OR = 1.63 CI95% 1.25; 2.12). Prostate cancer screening increased in all age groups, however, the most significant increase can be observed in the population aged between 50 and 54 years: 18% in 2005 versus 35% in 2008 (OR = 2.43 CI95% 1.31; 4.52). This trend for increasing testing will probably be confirmed in the future since 57% of males never screened plan to undergo a test, and only 16% of those who did screening plan to stop. The expected participation in the future will be close to 70%. Physicians: In 2005, 58% of GPs systematically recommended prostate cancer screening for their male consultants ages 50 to 74, in 2008 the figure is 65% (OR = 1.32 CI95%1.04; 1.66). For prostate cancer screening, a GP's gender has no significant impact. Systematic recommendation for both breast and colorectal cancer screening has an impact on recommending prostate cancer screening as well; OR = 2.9 (CI95% 2.0–4.4) and OR = 2.0 (CI95% 1.3–3.2) respectively. The GP's age is not associated with a higher rate of systematic recommendation. Conclusions: We have observed in France a significant growth in prostate cancer screening: more persons screened, more often, at a younger age. Despite the lack of consistent evidence, persons and GPs exposed to mass communication and campaign for breast and colorectal cancer screening might infer that screening is valuable for other conditions. No significant financial relationships to disclose.
Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM
Authors: Heimberger A. B. , Archer G. E. , Mitchell D. A. , Bigner D. D. , Schmittling R. J. , Herndon J. E. , Davis T. , Friedman H. S. , Keler T. , Reardon D. A. , Sampson J. H. 
Published: August 2020

2021 Background: Unlike conventional therapies for GBM, immunologic targeting of tumor-specific gene mutations allows precise eradication of neoplastic cells with reduced toxicity. EGFRvIII is a constitutively activated and immunogenic mutation not expressed in normal tissues, but widely expressed in GBM and other neoplasms. The cancer vaccine CDX-110 is comprised of an EGFRvIII-specific peptide sequence linked to keyhole limpet hemocyanin (KLH). Methods: A phase II multi-center trial assessed the immunogenicity and efficacy of CDX-110 in patients with newly-diagnosed, EGFRvIII+ GBM. After resection and radiation / TMZ, patients received CDX-110 vaccinations biweekly x 3, then monthly until tumor progression. Sequential cohorts received CDX-110 alone [ACTIVATE (n = 18)] or in combination with TMZ (200 mg/m2 x 5/28 days [ACT II A (n = 13)]) or (100 mg/m2 x 21/28 days [ACT II B (n=10)]). Results: Reversible systemic drug hypersensitivity reactions were seen in 1 ACTIVATE and 4 ACT II patients. Two patients had non-specific changes on MRI which were possibly due to the vaccine but which resolved. Despite grade 2 or 3 lymphopenia in all ACT II patients, EGFRvIII-specific immune responses were generated in all patients, and all immune responses were sustained or enhanced during subsequent TMZ cycles. Although ACT II B patients had more severe TMZ-induced lymphopenia, they developed greater EGFRvIII-specific immune responses (p = 0.028) when compared to ACT II A. EGFRvIII-specific IgG1 also increased in avidity with vaccination (Ka>>2x109M-1) in a randomly selected subset of 4 patients (p = 0.000068). Of the 23 recurrent tumors studied, 18 lost EGFRvIII expression (p = 0.001). There are no significant differences between ACT II A and B in estimated median TTP (18.5 vs. 14.9 months, p = 0.31) and OS (23.6 vs. 19.9 months, p = 0.75). ACTIVATE TTP (14.2 months) and OS (26.0 months) and ACT II TTP (15.2 months) and OS (23.6 months) compare favorably to a TMZ-treated, matched historical control group (TTP: 6.3 months; OS: 15.0 months). Conclusions: CDX-110 vaccination in patients with GBM appears very promising. TMZ enhances immune responses despite lymphodepletion. CDX-110 with simultaneous TMZ is under further investigation in a larger phase II trial. [Table: see text]
Effect of granulocyte-macrophage colony stimulating factor (GM-CSF) administered with a multipeptide vaccine on circulating CD8+ and CD4+ T-cell responses: Outcome of a multicenter randomized trial
Authors: Slingluff C. L. , Petroni G. R. , Olson W. C. , Smolkin M. E. , Ross M. I. , Haas N. B. , Grosh W. W. , Boisvert M. E. , Kirkwood J. M. , Chianese-Bullock K. A. 
Published: August 2020

3008 Background: GM-CSF administered locally with vaccines can augment T-cell responses in animal models. Human experience with GM-CSF has mostly occurred in uncontrolled or nonrandomized trials. Thus, a multicenter prospective randomized phase II trial was performed to determine whether local administration of GM-CSF augments immunogenicity of a multipeptide vaccine administered in an emulsion with an incomplete Freund's adjuvant (IFA). A second component of the trial was designed to assess whether the vaccine administered in two sites is more immunogenic than in a single site. Methods: 121 eligible and evaluable patients with resected stage IIB-IV melanoma were administered a sequence of multipeptide vaccines, each consisting of 12 MHC Class I-restricted melanoma peptides (12MP) to stimulate CD8+ T cells, plus an HLA-DR restricted tetanus helper peptide to stimulate CD4+ T cells. Peptides were emulsified with IFA, with or without GM-CSF. T cell responses were assessed by IFN-gamma ELIspot assay and tetramer analysis, weekly x 8. Clinical outcome was evaluated for all patients. Results: Vaccination was well-tolerated, and each peptide was immunogenic. Overall CD8+ T-cell response rates to the 12MP (days 1–50), for patients vaccinated with or without GM-CSF were 43% and 75%, respectively (p < 0.001), and response magnitude was almost twice as high in patients without GM-CSF. Class I MHC tetramer analyses corroborated the functional data. There was also a greater CD4+ T-cell response to the tetanus helper peptide without GM-CSF than with it (95% and 77%, respectively, p = 0.005). There was no significant difference in immune response rates by the number of vaccine sites. For the entire patient group, 3-year overall and disease-free survival estimates [95% CI] were 76% [67, 83%] and 52% [43, 61%], respectively. There have been too few events to assess differences in clinical outcome by study arm. Conclusions: High immune response rates were achieved with this multipeptide vaccine, but CD8+ and CD4+ T-cell responses appear to be partially suppressed with addition of GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans. [Table: see text]
Association of plasminogen-activator inhibitor 1 (PAI-1) 4G/5G gene polymorphism with survival and chemotherapy-related vascular toxicity in non-seminomatous testicular cancer (TC)
Authors: de Haas E. C. , Zwart N. , Meijer C. , Boezen H. M. , Suurmeijer A. J. , van der Meer J. , Hoekstra H. J. , van Leeuwen F. E. , Sleijffer D. T. , Gietema J. A. 
Published: August 2020

5083 Background: High PAI-1 expression by tumor has been associated with poor prognosis in different cancer types, while high systemic PAI-1 levels may increase the risk of vascular thrombosis. We investigated whether the 4G/5G del/ins polymorphism in the PAI-1 promoter (rs1799889; 4G might lead to higher transcription), is associated with differences in survival and prevalence of cardiovascular events in TC. Methods: Data were collected on survival and cardiovascular events (venous thromboembolism [VTE] and coronary heart disease [CHD]) of TC patients treated with standard platinum based chemotherapy from 1977–2004. PAI-1 genotype was determined from non-tumor genomic DNA by a Taqman SNP assay. Genotypes were compared for survival (Kaplan-Meier curves + log-rank and Cox-regression analysis), disease outcome (logistic regression) and prevalence of VTE and CHD (χ2-test). Results: Data are available for 324 patients with median follow-up of 10 yrs (range 0–28). The 3 genotypes 4G/4G (n = 84), 4G/5G (n = 164), and 5G/5G (n = 76) do not differ in age and initial chemotherapy regime. However, the 4G/4G variant shows a higher prevalence of International Germ Cell Cancer Classification (IGCCC) poor prognosis compared to 4G/5G + 5G/5G (24% vs 10%; p = 0.003), as well as a decreased TC related survival compared to 4G/5G + 5G/5G (83% vs 94%; p = 0.001) with a hazard ratio of 2.68 for TC related death (95%CI 1.26–5.72; adjusted for IGCCC p = 0.011). In addition, the 4G/4G variant shows an odds ratio of 3.35 for refractory TC and early relapses (<2 yrs) (95% CI 1.48–7.58; p = 0.004). The 3 genotypes do not differ significantly in prevalence of VTE (4G/4G 11.9%, 4G/5G 8.5%, 5G/5G 7.9%; p = 0.616) and CHD during/after chemotherapy (4G/4G 6.0%; 4G/5G 4.9%; 5G/5G 2.6%; p = 0.594). Conclusions: The 4G/4G variant of the PAI-1 4G/5G gene polymorphism is associated with IGCCC poor prognosis, reduced survival and higher prevalence of refractory disease and early relapses. No effect on vascular toxicity was found. The 4G/4G variant of the PAI-1 gene may be an unfavorable prognostic factor as well as an unfavorable predictive factor for response to chemotherapy in patients with TC. No significant financial relationships to disclose.
Short-term (ST) versus long-term (LT) hormone treatment (HT) in combination with radiotherapy (RT) for locally advanced prostate cancer (LAPC): Meta-analysis of randomized trials (RCTs)
Authors: Cuppone F. , Bria E. , Giannarelli D. , Milella M. , Ruggeri E. M. , Sperduti I. , Nisticò C. , Terzoli E. , Cognetti F. , Carlini P. 
Published: August 2020

5128 Background: Hormone suppression plus RT is able to significantly decrease the recurrences and the mortality of patients (pts) affected by LAPC. In order to determine if difference exists between ST-HT (HT ≤6 months), and LT-HT (HT ≥8 months) in combination with RT for LAPC, a literature-based meta-analysis was conducted. Methods: Event-based relative risks (RR) with 95% confidence intervals (CI) were derived through a random-effect model. Differences in primary (biochemical failure, BF, and cancer-specific survival, CSS), and secondary outcomes (overall survival, OS, and pattern of recurrence, local or distant, LR/DM) were explored. Absolute differences (AD) and the number of patients needed to treat (NNT) were calculated. Heterogeneity test, a meta-regression analysis with clinico-pathological predictors for outcomes and a correlation analysis for surrogate end-points were conducted as well. Results: Four trials (3,148 patients) were gathered. Data were available for all RCTs only for BF; patient population ranged from 297 to 1,521 pts. Three predictors were identified: median PSA (range 9.5–20.35), Gleason score 7–10 (27–55% pts/trial) and T3–4 (13–77% pts/trial). None of the selected predictors did significantly affect any outcomes. A significant correlation and trend between the log of the BF-RR and DM and OS were found (p=0.029 and p=0.07, respectively). Conclusions: Although with significant heterogeneity (reflecting different patient’ risk stratifications), LT-HT seems to significantly decrease biochemical, local and distant recurrences, and increase cancer specific survival in comparison with ST-HT. Balancing these advantages with toxicities and costs represents the next step of the current analysis. [Table: see text] No significant financial relationships to disclose.
Postrandomization analysis assessing survival following radiation therapy (RT) with or without 6 months of androgen suppression therapy (AST) for localized prostate cancer (PCa)
Authors: Nguyen P. L. , Chen M. H. , Beard C. J. , Loffredo M. , Renshaw A. A. , Suh W. W. , Kantoff P. W. , D'Amico A. V. 
Published: August 2020

5129 Background: 6 months of AST+RT was shown to improve survival vs. RT alone in men with unfavorable-risk localized PCa, but it is unknown if this benefit applied to all risk subgroups. Methods: Among 206 men with clinical T1b-T2b PCa and at least 1 unfavorable feature (PSA>10 or Gleason >=7 or MRI evidence of T3 disease) randomized to 70Gy of RT with or without 6 months of AST, we performed post-randomization subgroup analyses within four subgroups defined by both risk group (high risk [Gleason 8–10 or PSA >20] or intermediate risk [all others]), and by ACE-27 comorbidity level (no/limited comorbidity or moderate/severe comorbidity). Within the 4 subgroups a log-rank test was used to compare Kaplan Meier estimates of survival (requiring p < 0.05/4 or p < 0.0125 to adjust for multiple comparisons) and within the 2 risk groups we used Cox multivariable analysis (MVA) to assess the association of treatment with the risk of death after adjusting for known prognostic factors. Results: After a median follow-up 8.2 yrs, 74 men died. In men with no or minimal comorbidity, estimates of survival were significantly higher among those who received AST+RT vs. RT alone, regardless of whether they had intermediate risk disease (90.9 vs. 85.8% at 7yrs, p = 0.009) or high-risk disease (88.9% vs. 51.2% at 7yrs, p = 0.007). In men with moderate or severe comorbidity, no difference in survival was observed after AST+RT vs. RT in intermediate risk (p = 0.2) or high risk (p = 0.5). After adjusting for known prognostic factors, treatment with RT as compared to AST+RT was associated with an increased risk of death in men with intermediate (AHR: 3.0 [95% CI: 1.3 to 7.2]; p = 0.01) and high risk disease (AHR: 3.3 [95% CI: 0.94 to 11.3]; p = 0.06) in a model that adjusted for the interaction between treatment and comorbidity. Conclusions: Among men with T1b-T2b prostate cancer who have no or minimal comorbidity, the addition of 6 months of AST to RT was associated with improved survival in men with both intermediate risk and high-risk disease. Among men with moderate to severe comorbidity, neither risk group appeared to benefit from the addition of AST. No significant financial relationships to disclose.
Use of pain at baseline and pain progression to predict overall survival (OS) in patients (pts) with docetaxel pretreated metastatic castration-refractory prostate cancer (CRPC): Results from the SPARC trial
Authors: Sartor A. O. , Petrylak D. , Sternberg C. , Witjes F. , Halabi S. , Berry W. , Petrone M. , McKearn T. , Noursalehi M. , George M. 
Published: August 2020

5148 Background: First-line chemotherapy trials have reported that pain predicts OS in CRPC. We report relationships between OS and baseline pain –a major component of CRPC patient reported outcomes (PRO) –and pain at progression, for docetaxel pre-treated patients in a second-line chemotherapy trial in CRPC. Methods: Docetaxel pre-treated pts (N = 488) were analyzed from the multi-national, randomized, double-blind SPARC trial, comparing second-line satraplatin + prednisone vs placebo + prednisone in 950 metastatic CRPC pts. Daily pain intensity and narcotic analgesic use were recorded as a PRO from one week prior to randomization until end-of-study. Pain was measured by the 6-point Present Pain Intensity (PPI) component of the McGill-Melzack Pain Questionnaire. After randomization, weekly PPI scores were calculated as the mean of the daily PPI scores (using ≥3 daily measurements/week). Baseline pain was the mean of ≥5 daily PPI scores recorded during 7 days preceding randomization. An independent blinded review committee (IRC) determined pain progression (defined as an increase in weekly PPI score ≥1 point from baseline or ≥2 points from nadir, or a >25% increase from baseline in weekly average analgesic score for ≥2 consecutive weeks). To examine the effects of pain on OS, pts were categorized as “no pain” (PPI ≤1) or pain (PPI ≥2) by baseline assessment; and, as either pain progressors or pain non-progressors. Results: Shortened OS was observed in pts with baseline pain; median survival of 178 pts with pain was 44 weeks vs 72 weeks for 287 pts without pain (Strat. Log-rank p < 0.0001, Strat. HR 0.59; 95% CI: 0.48–0.74). IRC found disease progression in 414 (84.4%) of the docetaxel pre-treated pts with 196 of these pts showing pain progression. Pain progression was strongly linked to OS with 196 pain progressors having median OS of 47 weeks compared to 71 weeks for 292 pain non-progressors (Strat. Log-Rank p = 0.0022; Strat. HR 0.71; 95% CI: 0.57–0.87). Conclusions: Both pain at baseline and pain at progression are important prognostic indicators of OS in metastatic CRPC pts failing first-line docetaxel. [Table: see text]