bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspirin use and mortality in men with localised prostate cancer: A cohort study.
Authors: Flahavan Evelyn M , Bennett Kathleen , Sharp Linda , Barron Thomas Ian 
Published: March 2020

5084 Background: Cyclooxygenase-2 (COX-2) expression in prostate cancer has been associated with high grade tumours and poorer prognosis. Use of aspirin, a COX-2 inhibitor, has been associated with reduced prostate cancer mortality in some studies. These studies have not, however, provided information on the dose and timing of aspirin use. Methods: National Cancer Registry Ireland data was used to identify men with stage I-III prostate cancer (ICD10 C61) diagnosed 2001-2006. Aspirin use in the year preceding prostate cancer diagnosis was identified from linked prescription refill data (General Medical Services) and stratified by dose (low ≤75mg, high >75mg) and dosing intensity (proportion of days in that year with aspirin supply available). Cox proportional hazards models, adjusted for age, smoking status, year of incidence, comorbidity score, Gleason score, tumour size, pre-diagnostic statin use, and receipt of radiation (time varying) were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between aspirin use and all-cause and prostate cancer-specific mortality. Interactions with tumour characteristics were examined. Results: 2,936 men with stage I-III prostate cancer were identified (aspirin users, N=1,131; 38.5%). Median patient follow-up was 5.5 years. In multivariate analyses, aspirin use was not associated with a significant reduction in prostate cancer-specific (HR 0.90, 95% CI 0.68-1.20) or all-cause mortality (HR 0.98, 95% CI 0.84-1.15). In dose response analyses aspirin use was associated with a significantly lower risk of prostate cancer-specific mortality in men receiving >75mg of aspirin (HR 0.59, 95% CI 0.35-1.00, p=0.048) but not ≤75mg aspirin (HR 1.01, 95% CI 0.75-1.37, p=0.938). Stronger associations were also observed in men with higher aspirin dosing intensity or a Gleason score >7. Conclusions: Pre-diagnostic aspirin use, measured using objective prescription refill data, was associated with a significant reduction in prostate cancer-specific mortality in men with stage I-III prostate cancer receiving >75mg of aspirin. These results confirm previous findings, and provide important new information regarding the dose of aspirin associated with survival benefit.
Vasectomy and risk of lethal prostate cancer: A 24-year prospective study.
Authors: Mucci Lorelei A. , Siddiqui Mohummad Minhaj , Wilson Kathryn M , Epstein Mara Meyer , Rider Jennifer R , Martin Neil E , Kantoff Philip W. , Stampfer Meir J. , Giovannucci Edward L. 
Published: March 2020

5086 Background: In the United States, 10 to 15 percent of adult men have undergone a vasectomy. There is conflicting evidence whether vasectomy is associated with increased prostate cancer risk. Methods: We undertook a prospective study among 49,432 men in the US Health Professionals Follow-up Study. The men were age 40 to 75 years at baseline in 1986 and were followed prospectively for cancer incidence and mortality through 2010; 6,398 incident cases of prostate cancer were diagnosed, including 734 with high grade (Gleason 8 – 10) and 813 with cancer causing death or bony metastasis (lethal). We used cox regression models to calculate hazard ratios (HR, 95% confidence intervals) of the association between vasectomy and incidence of high grade and lethal prostate cancer, adjusting for potential confounders. We examined associations in the total cohort, and in a subset of 12,371 men highly screened by PSA in order to disentangle potential diagnostic bias. Results: At baseline, 22 percent of men reported having had a vasectomy. Men who had undergone vasectomy were at increased risk of high-grade (HR 1.23, 95% CI: 1.04-1.47) and lethal (HR 1.20, 95% CI: 1.01-1.43) prostate cancer. In the highly screened cohort, the association was similar for high-grade cancer, and even stronger for lethal disease (HR 1.56, 1.03-2.36). The risk of lethal prostate cancer was higher among men who had a vasectomy before age 38 years compared to at older ages. The increased risks with vasectomy could not be explained by differences in hormone levels, prevalence of sexually transmitted infections, or cancer treatments. Conclusions: Data from this study support the hypothesis that vasectomy is associated with a small increased incidence of aggressive prostate cancer defined as high grade cancer and disease causing death or bony metastasis. Differences in diagnostic intensity or confounding bias do not explain this elevated risk.
Serum mass spectrometry analysis in primary ovarian cancer (OC) treated with surgery and adjuvant chemotherapy (CT).
Authors: Roder Heinrich , Kasimir-Bauer Sabine , Kimmig Rainer , Wimberger Pauline , Zeillinger Robert , Castillo-Tong Dan Cacsire , Sehouli Jalid , Vergote Ignace , Mahner Sven , Roder Joanna , Grigorieva Julia , Meyer Krista , Aktas Bahriye 
Published: March 2020

5575 Background: To address the unmet need for non-invasive tests to predict outcomes in OC we investigated the effect of the serum test, VeriStrat (VS), in independent cohorts of OC patients (pts) who were treated with platinum based chemotherapy following surgery. VS assigns “Good” (VSG) and “Poor” (VSP) classifications and has been shown to be prognostic in various tumor types and predictive for certain treatments. Methods: Samples from primary OC pts from the University Hospital, Essen (ESSEN), N= 108, and from OVCAD consortium (Berlin, Leuven, Hamburg, Vienna), N = 138, were obtained within 1 week before surgery that was followed by platinum-based CT. VS testing was done blinded to clinical data. Overall survival (OS) was analyzed by Kaplan-Meier method and compared using log-rank p-values. Cox models were used in multivariate analysis. Associations with categorical variables were analyzed by Fisher’s exact test. Results: The cohorts had similar distribution of VSG/VSP classification: 73% VSG (ESSEN), 71% VSG (OVCAD). The distribution by histology (non-serous/serous), and nodal status were different (p = 0.003 and p = 0.049). The results for OS in all pts (ALL), in pts with tumor (and/or metastases) present post-surgery (TPPS-pos), and in pts with complete resection and no metastases (TPPS-neg) are presented in the Table. VS was not associated with circulating tumor cells (ESSEN, p=0.736). In a Cox model analysis for TPPS-pos groups VS was independently significant (p= 0.016, ESSEN) or trended to significance (p=0.063, OVCAD). Conclusions: VS demonstrated similar results in two independent cohorts; in ALL and TPPS-pos populations it significantly correlated with OS in ESSEN, showed same trends in OVCAD, and was not correlated with OS in TTPS-neg pts. While requiring further investigation, VS may provide useful prognostic information. [Table: see text]
Expression of glucose-regulated protein 78 (GRP78) and its regulator microrna-181 during the development and progression of ovarian cancer.
Authors: Barua Animesh , Yellapa Aparna , Grasso Salvatore A , Abramowicz Jacques S , Sharma Sameer , Guirguis Alfred S , Basu Sanjib , Bitterman Pincas 
Published: March 2020

5579 Background: Ovarian cancer (OVCA) is a lethal malignancy of women with a distinct pattern of metastasis through peritoneal dissemination. Sustained exposure of the ovaries to oxidative stress due to inflammatory processes including ovulatory genotoxicity, makes the ovarian microenvironment conducive to malignant cell proliferation. GRP78 is a stress-inducible protein which resides in the endoplasmic reticulum of the cell. Thus GRP78 may be a marker of ovarian tumor associated stress and could represent a therapeutic target for OVCA. The goal of this study was to examine if GRP78 expression increases in association with OVCA development and determine the molecular mechanism of its increase in ovarian tumors. Methods: All tissues were collected from patients who underwent surgery and processed for immunohistochemistry (IHC), proteomic study (2D-WB) and miRNA expression. Expression of GRP78 was examined in paraffin sections of normal ovaries (n = 20), benign (serous cystadenoma, n = 15 and cystadenofibroma, n = 5) and ovaries with papillary serous carcinoma at early stage (n= 20 at stages I and II) and late stage (n = 20, stages III and IV) by IHC and confirmed by 2D-WB (representative samples). Changes in miRNA-181 (post-translation regulator of GRP78) expression were examined by qRT-PCR. Results: GRP78 expression by normal ovarian surface epithelium and epithelium of benign tumors was very weak. In contrast, the intensity of GRP78 expression was significantly (p<0.05) high in early stage OVCA and increased further in late stage OVCA. An immunoreactive band of 78kDa detected by 2D-WB confirmed IHC observations. In contrast, expression of miRNA-181 by malignant tumors significantly (p<0.05) decreased as the tumor progressed to late stages. Conclusions: The results of the present study suggest that GRP78 expression is associated with the development and progression of malignant ovarian tumors. Increase in GRP78 expression was associated with the down-regulation of miRNA-181. Expression of GRP78 by malignant ovarian epithelium represents a potential marker with usefulness for targeted drug delivery. Support: Elmer and Sylvia Sramek Foundation.
Changes in renal function following treatment for ovarian cancer.
Authors: Butler Matthew James , Stark Azadeh , Kirchner Lester , Gogoi Radhika , Leader Joseph B , Lewis Meredith W , Muggia Franco 
Published: March 2020

5581 Background: Among women treated for Epithelial Ovarian Cancer (EOC), new or worsening renal dysfunction has been observed but not systematically studied. We conducted a retrospective cohort study to estimate the rate of decline in renal function following a diagnosis of EOC, compared with the rate of decline among the same patients prior to diagnosis. Methods: We study a historical cohort of women diagnosed with EOC between 1/1/2000 and 12/31/2011, who received health care services within a large community medical center. Data were retrieved from institutional electronic records. We develop a Generalized Estimating Equations (GEE) model to quantify changes in estimated glomerular filtration rate (eGFR) over time, with the date of EOC diagnosis as the reference point (time zero). All analyses were conducted using SAS version 9.2 (SAS Institute Inc., Carey, NC). Results: The cohort is comprised of of 323 women. At diagnosis, the mean age was 63.4 (± 13.5) years and the mean eGFR was 81.0 (± 22.7). There were 74 (22.9%) patients carrying a diagnosis of hypertension, 25 (7.7%) with diabetes, and 73 (22.6%) who were clinical obese. Prior to EOC diagnosis the decline in mean monthly eGFR was not significant (- 0.052, 95% CI -0.11-0.009, p = 0.092), after controlling for age, obesity, hypertension, and diabetes. This monthly decline increased by almost 4-fold (p = 0.0007) subsequent to EOC diagnosis. To discern the potential effect of chemotherapy on renal function, we conducted a secondary analysis on the 120 women for whom detailed chemotherapeutic data is available. For women who received standard first-line chemotherapy (paclitaxel and carboplatin) the rate of eGFR decline increased 10-fold (-0.025 vs. -0.25, p = .0066) relative to their baseline rate of decline. For those who received other regimens, the increase was 11.4 times (-0.025 vs. -0.286, p =.0011); this was not significantly higher than those receiving the standard regimen (p = 0.72). Conclusions: This ongoing study suggests that women treated for EOC suffer an accelerated rate of renal function decline, independent of major comorbid conditions, that is therefore attributable to the disease and/or its treatment.
Eribulin mesylate (Erib) plus capecitabine (X) for adjuvant treatment in post-menopausal estrogen receptor–positive (ER+) early-stage breast cancer: Phase II, multicenter, single-arm study.
Authors: Smith John W. , Rege Jessicca , Maniar Hina , Song James , Cox David , O'Shaughnessy Joyce 
Published: March 2020

563 Background: Erib and X have both shown single agent activity in MBC; and X also has activity in ER+ adjuvant tx. This study was designed to evaluate the feasibility of the combination in the adjuvant setting. Methods: Female pts stage I-II, HER2 negative, ER+ BC received Erib at 1.4 mg/m2 iv D1 and D8 and X at 900 mg/m2 po bid on days 1-14 of 21 day cycle, for 4 cycles. The study was considered feasible if 80% of pts are able to achieve the target relative dose intensity (RDI) of at least 85% of the regimen and lower 95% confidence boundary (LCI) is above 70%. Results: Final results of 67pts enrolled are reported here. 88% pts completed 4 cycles of tx. Pt characteristics: Median age 62 yrs (range 28-80), ECOG 0(90%), stage 2(52%). 64/67 pts were evaluable for feasibility. The study met its primary endpoint demonstrating feasibility rate of 81%(95% LCI:71%) with average RDI of 91%. Results were mainly affected by X dose adjustments (Erib RDI-93%, X RDI-88%). X related dose reductions(24, (36%)), missed doses (57,(85%)) and discontinuations due to AE (11(16%)) were higher compared to that with Erib(14(21%), 5(8%) and 7(10%)), respectively. Most common AEs with dose reductions were gr 3/4 hand foot syndrome (HFS) (12%), neutropenia(8%), neuropathy(8%), and GI disorders(6%); and drug discontinuation were HFS(8%), neutropenia(3%), neuropathy(2%), and GI disorders(3%). Tx related AEs and SAE are reported in the Table. 14(21%) pts had an SAE with 12(18%) requiring hospitalization. Conclusions: Adjuvant tx with the Erib-X combination can be given safely with the majority of the patients able to achieve full dosing regimen. We plan to explore an alternative schedule of X(7wk on/off) with this regimen to see if it will further improve tolerability and the RDI. Clinical trial information: NCT01439282. [Table: see text]
Psychophysical functioning and quality of life in 94 patients affected by oropharyngeal cancer and treated with different therapeutic approaches.
Authors: Pedani Fulvia , Airoldi Mario , Garzaro Massimiliano , Torta Riccardo , Raimondo Luca , Riva Giuseppe , Varetto Antonella , Bellini Elisa , Salonia Laura , Pecorari Giancarlo 
Published: March 2020

6039 Background: The treatment of oropharyngeal squamous cell carcinomas (OSCC) may heavily affect patient’s quality of life (QoL). Aim of our study was the evaluation of the impact of different treatments on physical and psychological functioning and on QoL of patients affected by stage III-IV disease. Methods: The enrolled sample was composed by 94 OSCC patients divided into 3 subgroups based on treatment modalities: surgery + adjuvant radiotherapy (S + RT: 30 patients), exclusive concomitant chemo-radiotherapy (CT + RT: 30 patients) and exclusive chemotherapy (CT) in 34 patients not suitable for surgery and/or radiotherapy. Psycho-oncological assessment included: Hospital Anxiety Depression Scale (HADS), Montgomery-Asberg Depression Scale (MADRS), Mini-Mental Adjustment to Cancer scale (MINI-MAC), EORTC QLQ C-30 questionnaire with the specific module Head and Neck 35 (H&N35). Results: The 60 patients primarily treated with S + RT or CT + RT presented superimposeable clinical and tumour characteristics while those treated with exclusive CT were affected by stage IV disease and in the 90% of cases underwent to previous treatment exclusive or combined treatment such as surgery, radiotherapy and chemotherapy. In the following table, data about physical and psychological functioning and on QoL of the 3 subgroups of patients are summarized. Conclusions: In stage III-IV OSCC treatments have a strong influence on QoL and coping styles. Patients treated with CT + RT were characterized by a lower percentage of self-reported anxiety and depression and higher EORTC Global QoL score. More than one third of patients treated with S + RT had overt symptoms of anxiety and depression. Stage IV patients treated with palliative CT had elevated level of anxiety, depression and low quality of life. Auto-evaluation is less effective in depression assessment. The role of concomitant psychological supportive care should be evaluated in these patients treated with different approaches. [Table: see text]
Hospital variation in bronchoscopy and esophagoscopy rates during head and neck cancer diagnostic evaluation.
Authors: Sun Gordon H. , Aliu Oluseyi , Moloci Nicholas M. , Mondschein Joshua Keith , Burke James F. , Hayward Rodney A. 
Published: March 2020

6044 Background: Hospital variation in bronchoscopy and esophagoscopy rates while diagnosing head and neck cancer may reflect professional uncertainty about the effectiveness of these procedures and a lack of clinical guidelines on best practices. Furthermore, high-volume hospitals have demonstrated better outcomes for select oncologic procedures. We examined the association between hospital case volume and diagnostic bronchoscopy and esophagoscopy rates. Methods: This retrospective cohort study used the 2006-2010 Michigan State Ambulatory Surgery Databases, capturing all outpatient surgical cases in Michigan. Eligible cases included head and neck cancer patients who underwent laryngoscopy, bronchoscopy, and/or esophagoscopy. The primary outcome measure was the likelihood that a patient who underwent laryngoscopy during head and neck cancer diagnostic workup also underwent either bronchoscopy or esophagoscopy. We used hierarchical, mixed-effect logistic regression to measure the association between the primary outcome and hospital case volume (<100, 100-999, or ≥1,000 cases/hospital) while adjusting for patient-level variables such as age, sex, race, insurance status, and household income. Results: Of 17,828 head and neck cancer patients, 9,218 underwent diagnostic laryngoscopy. The 50 low-volume and 40 medium-volume hospitals performed significantly more concurrent bronchoscopies and esophagoscopies compared to the 2 high-volume hospitals (both p<0.001). After adjusting for patient characteristics, medium-volume and low-volume hospitals respectively had 9.3-fold and 7.8-fold higher odds of performing esophagoscopy relative to high-volume hospitals (p=0.003), although the association with bronchoscopy was no longer statistically significant. Conclusions: The proportion of head and neck cancer patients undergoing diagnostic laryngoscopy with concurrent esophagoscopy, but not bronchoscopy, varies significantly by hospital volume. A robust discussion of the comparative effectiveness of comprehensive and selective endoscopy will require further research into whether endoscopic volume correlates with tumor staging, survival, and other outcomes data.
Cetuximab with or without sorafenib in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).
Authors: Gilbert Jill , Schell Michael J. , Zhao Xiuhua , Murphy Barbara A. , Tanvetyanon Tawee , Hayes David N. , Haigentz Missak , Saba Nabil F. , Nieva Jorge J. , Perez Jimena , Bishop Justin A. , Chung Christine H. 
Published: March 2020

6047 Background: For patients with R/M SCCHN, cetuximab, a monoclonal antibody against EGFR, is approved as a single agent and has a survival benefit when combined with chemotherapy. We hypothesized that addition of sorafenib, a multi-kinase inhibitor of targets including VEGFR, to cetuximab may have greater clinical benefit than cetuximab alone. Methods: This trial was designed as a blinded, randomized phase II, placebo-controlled study of cetuximab at 400 mg/m2 IV on day 1 followed by 250 mg/m2 IV weekly plus placebo bid (Arm A) or cetuximab at the same dose and schedule plus sorafenib 400 mg po bid (Arm B), each in 21 day cycles. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility. Target sample size was 84 patients with 83% power to detect a 2-month increase in PFS, the primary study endpoint. Interim analysis was planned at midpoint, requiring hazard ratio < 1 to proceed to the second stage of study. Serum cytokine and tumor HPV ISH and p16 analyses were performed. Results: Of 56 patients (ages 26-74, 80% male) enrolled, 53 patients received treatment and 41 were evaluable for response. Of the patients who received therapy, 26 received cetuximab only (Arm A). For Arm A, the mean number of cycles delivered was 4.3 (range 1-16) and the mean for Arm B was 3.3 (range 1-11). The most common grade 3/4 AEs were fatigue (2 A, 1 B), hypertension (3 B), infusion reaction (both arms), and diarrhea (2 B). Arm A had 2 PRs and Arm B had 4 PRs. Median OS was 7 mo and 5.9 mo respectively. Median PFS was 3.1 mo for both arms. 24 patients had pre-treatment cytokine measurements. Of the 12 measured cytokines, high TGFB1 level was significantly correlated with inferior PFS (4.6 mo vs 1.6 mo), regardless of arm (p=0.015). 38 patients had tumors available for p16 staining (31 neg and 7 pos). 3 of 7 p16 pos were also HPV ISH pos. The p16 neg patients had significantly improved PFS (3.5 mo vs 1.6 mo) regardless of arm (p=0.032) but no difference in OS (p=1.0). Conclusions: Both arms demonstrated clinical activity although no significant difference was observed. However, a subset of patients with p16 neg tumors or low serum TGFB1 may have a greater benefit with cetuximab-based therapy. Clinical trial information: NCI-2012-02847.
Phase II trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma.
Authors: Massarelli Erminia , Ginsberg Lawrence E. , Lin Heather , Tran Hai T. , Lee J. Jack , Williams Michelle D. , Blumenschein George R. , Lu Charles , Kies Merrill S. , Papadimitrakopoulou Vassiliki 
Published: March 2020

6067 Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression but treatments targeting EGFR have met with limited clinical success. We hypothesized that everolimus (EV), an mTOR inhibitor, potentiates the activity of erlotinib (ER), an EGFR tyrosine kinase inhibitor, in platinum-resistant recurrent and/or metastatic HNSCC. Methods: This single-arm two-stage phase II clinical trial evaluated EV 5 mg and ER 150 mg orally daily in patients (pts) with platinum-resistant recurrent and/or metastatic HNSCC. Primary endpoints were response rate and 12-week progression-free survival (PFS). Plasma biomarkers by multianalyte profiling (Luminex Corp) and ELISA at baseline (20 pts), 4 weeks (18 pts) and 12 weeks (16 pts) as well as p16 expression in baseline tumor tissue (29 pts) were assessed in correlation with clinical results. Results: Of the 36 evaluable pts (median age 61 years, 29 males, 19 with oropharynx primaries, 15 with ≥2 lines of chemotherapy, 17 with prior cetuximab), 3 (8%) achieved partial response at 4 weeks, one of which was confirmed at 12 weeks, while 27 (75%) pts achieved disease stabilization at 4 weeks, 11 of which were confirmed at 12 weeks. The 12-week PFS was 49%, median PFS was 11.9 weeks and median overall survival (OS) was 10.25 months. Grade 3 toxicities included mucositis (17%), fatigue (14%), skin (8%), diarrhea (8%), and 5 pts withdrew from trial secondary to toxicity. High neutrophil gelatinase-associated lipocalin(NGAL) levels at baseline were associated with worse OS (HR 4.59; 95%CI 1.36, 15.46; p=0.014) and at 4 weeks with worse PFS (HR=12.29; 95% CI 1.26, 119.87; p=0.03) and OS (HR=6.21; 95% CI 0.95, 40.62; p=0.057). High carbonic anhydrase-9 (CA-9) levels at 4 weeks were associated with worse OS (HR=1.18; 95% CI 1.001, 1.41; p=0.049), while decreased CA-9 levels at 4 weeks were associated with better PFS (p=0.77). Conclusions: Efficacy for the combination ofEV and ER is reasonable however plasma markers of tumor invasion and hypoxia are associated with worse outcomes, and further biomarker analysis may define subsets of pts with significant therapeutic benefit. Clinical trial information: NCT00942734.