bluuebunny/crossref_metadata_2025_split huggingface dataset:
An analysis of the temporal, age, and gender trends in human papillomavirus virus (HPV)-related versus non-HPV-related head and neck cancers (HNC) in Alberta, Canada.
Authors: Hao Desiree , Lau Harold Y. , Huang Longlong , Doll Corinne M. , Dort Joseph C. , Shack Lorraine 
Published: March 2020

e12505 Background: Recent epidemiologic studies have suggested that the incidence of HPV-associated HNC is increasing. This study assessed temporal, age-specific and gender specific changes in cancer incidence for HPV- versus non-HPV associated HNC compared with other HPV versus non-HPV associated malignancies in a population-based setting. Methods: We used the Alberta Cancer Registry, a population-based registry of all cancers diagnosed in the province of Alberta, Canada (population est. 3.6 million), to identify patients diagnosed with cancers of the oropharynx, cervix, vulva, vagina, anus, and penis (HPV-associated group) and compared this with non-oropharyngeal cancers of the head and neck and lung cancer (non-HPV associated, modifiable risk group) between January 1, 1975 and December 31, 2009. The age-standardized incidence rates (ASIR) for each cancer by gender and age-specific incidence was estimated with the annual percentage change (APC) assessed using Joinpoint regression. Results: The ASIR for oropharyngeal cancers (OPC) increased over time for both men (APC 3.5) and women (APC 1.5) with rapid increases seen in men under 35 (APC 27.3). Non-oropharyngeal squamous cell carcinomas of the head and neck had a higher ASIR overall with moderate temporal increases (APC 2.5) and age-specific increases highest in those aged 55 to 74. ASIR for anal canal cancers also increased over time, with greater increases amongst younger females, in contrast to OPC. By comparison, the ASIR of cervix cancer declined with more significant decreases in younger females; while the rates of other HPV-associated cancers (vulva, vagina, penile) showed little change. The ASIR for lung cancer decreased after 1987 (APC -1.5) for men and continued to moderately increase for women. Conclusions: Our findings suggest the greatest increases in OPC are occurring in younger men. Programs of HPV prevention such as vaccination should be explored to reduce the incidence of OPC in males.
Are there disparities in adjuvant treatment of HER2 positive breast cancer patients by age, race/ethnicity, and socioeconomic status?
Authors: Parise Carol , Caggiano Vincent 
Published: March 2020

e12512 Background: Standard adjuvant therapy for HER2-positive female breast cancer patients who are estrogen receptor (ER) positive is chemotherapy, trastuzumab, and endocrine therapy. Some studies report disparities in receipt of adjuvant treatment based on race/ethnicity, age, and socioeconomic status (SES). This study assessed the likelihood of receipt of adjuvant chemotherapy and endocrine therapy (C+E) versus endocrine therapy (E) alone by race/ethnicity, age, and SES in the ER+/PR+/HER- and ER+/PR+/HER+ subtypes. These subtypes differ only by HER2 status. Methods: We identified 86,666 cases of stages 1-3 ER+/PR+/HER- (n=74,422) and ER+/PR+/HER+ (n=12,244) breast cancer diagnosed between January, 2000 and December, 2010 from the California Cancer Registry. Logistic regression evaluating the odds of receipt of C+E versus E alone adjusting for age, race/ethnicity, SES, grade, and year of diagnosis was conducted separately for each stage and subtype. Odds Ratios (OR) and 95% confidence intervals were reported. Results: For both subtypes in all stages, patients over age 70 were less likely to receive C+E. Stage 1 ER+/PR+/HER-: Blacks were less likely to receive C+E (OR=0.77;0.59,0.99). The opposite was true for Hispanics (OR=1.31;1.15, 1.50) and Asians (API) (OR=1.25; 1.10;1.43). Stage 1 ER+/PR+/HER+:Hispanics were more likely (OR=1.67;1.24,2.24) to receive C+E while patients in the lowest SES category were less likely to receive C+E. Stage 2: ER+/PR+/HER-:Hispanics were more likely to receive C+E (OR=1.40;1.22,1.59) Stage 2: ER+/PR+/HER+:There were no treatment differences among race or SES. Stage 3: ER+/PR+/HER-:APIs were more likely (OR=1.87;1.19,2.94) to receive C+E. Stage 3: ER+/PR+/HER+:Patients in the lowest SES category were more likely to receive C+E (OR=2.97;1.29,6.87). Conclusions: Based on this investigation of a racially diverse population, there is no striking disparity in receipt of adjuvant treatment by race/ethnicity or SES. However there are some differences among the stages and subtypes. Patients over 70 are less likely to receive chemo and endocrine therapy for the subtypes studied.
U.S. Preventive Services Task Force (USPSTF) recommendations on PSA screening (PSAS) for prostate cancer (PC): Are they justified?
Authors: Strauss Gary M. 
Published: March 2020

e12535 Background: PSAS has been debated since the Amer Can Soc recommended it in 1992 without data from randomized trials (RTs). Recent RT reports indicate that PSAS does not clearly reduce PC mortality (PCM). In Oct 2011, the USPSTF recommended against PSAS. Does the evidence support this position? Methods: Quebec Trial (QT) randomized 46,193 men 45-80 yrs 2:1 in 1988. Experimental group (EG) was invited for annual PSAS while control group (CG) was not invited. PLCO (Prostate-Lung-Colon-Ovary) randomized 76,693 men 55-74 yrs to annual PSAS or usual care starting in 1993. ERSPC (European study) randomized 162,243 men 55-69 yrs to EG invited to PSAS q4 yrs or CG not invited starting in 1994. Results: QT investigators reported in 1998 that PSAS reduced PCM. The problem was poor compliance with PSAS invitation in QT. Of 30,956 EG, 7,155 (23%) accepted. Of 15,237 CG, 982 (6%) underwent PSAS. Of 8,137 screened (SC), there were 5 PC deaths compared to 137 among 38,056 unSC (RR=0.17; 95% CI: 0.07-0.42). However, this analysis ignores the randomization. Intent to treat (ITT) analysis reveals no PCM reduction (RR=1.11; CI: 0.78-1.59). Selection bias did not account for lower PCM in SC vs unSC. In PLCO, there was no PCM advantage (RR=1.09; CI: 0.87-1.36). However, contamination was high; 72% of CG had PSAS. In ERSPC, there was a reduction in PCM (RR=0.79; CI: 0.69-0.92). Staging of SC detected PC was favorable. In PLCO & ERSPC, increased low/intermediate risk PCs in EGs reflect some overdiagnosis. However, there were significant reductions in high risk or metastatic PC, a hallmark of effective screening. In QT, no pt had distant metastases on repeat PSAS. In PLCO, 10-yr PC survival was ≈94% in both EG & CG. Conclusions: USPSTF recommendations against PSAS are not justified. While PCM comparisons by ITT do not show that PSAS clearly saves lives, ITT analyses are biased due to compliance or contamination. Conversely, RTs demonstrate that PSAS reduces high-risk and metastatic PC. From a population perspective, there has been a dramatic 42% reduction in PCM in US between 1991-2005, largely the result of our "national experiment" in which PSAS was widely introduced. If USPSTF guidelines are implemented, PCM will likely rise in US.
What would the experts do? Genetic testing, surveillance, and risk-reduction preferences for BRCA and Lynch syndrome.
Authors: Bonadies Danielle C. , Matloff Ellen T. , Brierley Karina L. , Moyer Anne 
Published: March 2020

e12542 Background: Extensive data and national guidelines are now available regarding surveillance and risk reduction options for BRCA and Lynch syndrome mutation carriers. However, most of these options are presented as choices to patients who will often ask their providers, “What would you do?” We surveyed providers from multiple specialties to learn what they would do if at 50% risk to carry a BRCA or Lynch syndrome mutation. Methods: In July of 2012 we surveyed providers from multiple specialties via internet- based surveys. Participants were obtained through the American Medical Association and the National Society of Genetic Counselors. All responses were anonymized. Results: 1,313 specialists completed the online questionnaire. Those providers who commonly treat breast, ovarian, colon and uterine cancers were grouped and compared to providers who are less likely to be the treating specialist. We found statistically significant differences in the percentage of cancer genetics specialists who would pursue BRCA and Lynch syndrome testing compared with providers in other specialties (p=0.000, 0.007, respectively). We found statistically significant differences in the percentage of providers who treat breast or ovarian cancer that would opt for prophylactic bilateral mastectomy or prophylactic oophorectomy if BRCA+ (p=0.000, p=0.004, respectively) compared to other providers. We found statistically significant differences in the percentage of providers who treat colon or uterine cancer that would have their colon or uterus removed if found to carry a Lynch syndrome mutation (p=0.000, p=0.04, respectively) compared to other specialists. Conclusions: Providers’ specialties and, possibly, disease-specific exposure to surveillance and treatment regimens impacted their personal choices with respect to cancer genetic testing, surveillance and prophylactic surgeries for BRCA and Lynch syndrome.
Florida's breast cancer deaths in the holidays.
Authors: Ana Sandoval , Hurley Judith , Koru-Sengul Tulay , Miao Feng , Tannenbaum Stacey , Lee David J , Byrne Margaret M 
Published: March 2020

e12547 Background: Several studies have been done to determine if there is an increase in the death rate associated with the holiday season or important events. Data has shown that there is an increase in death due to cardiovascular causes but the evidence for cancer related death is non-conclusive. Anecdotal information suggests that women with breast cancer expire more frequently during the Thanksgiving to Christmas holiday season compared with the rest of the year. It is unclear if this constitutes a real finding or if the circumstances connected with the patient’s death makes the dates more memorable. We evaluate if death occurs more frequently during the holiday season (11/15-01/07) for female breast cancer patients. Methods: Data on deaths from female breast cancer patients (n= 34,664) were obtained from linkage of the 1996-2009 Florida Cancer Data System, a population-based cancer registry, to the Florida Agency for Health Care Administration database providing procedure and diagnoses codes. Holiday season was defined as from 11/15-01/07 to create a dichotomous outcome measurement. Clustered logistic regression models were used to predict death during holidays; demographic, clinical, treatment factors and comorbidities were included in adjusted models with race, ethnicity, SES, marital status and presence of depression as the main factors. Results: Deaths (16%) occurred significantly more during the weekends, January-March and November-December. We found a temporal cluster of deaths during the holiday season defined from 11/15-01/07. Overall deaths were significantly more than expected during Thanksgiving and New Year. In the adjusted model, uninsured (OR: 1.24: 95% CI: 1.04-1.47) and been married (OR:1.13; 95%CI:1.03-1.23) were significant predictors of dying during the holiday season. Conclusions: Our results show that there is a seasonal effect on the time of death for Florida breast cancer patients. Marital status and non-insurance were significant predictors of dying during the holiday season.
Outcomes of HER2-positive nonmetastatic breast cancer patients with or without deleterious BRCA mutations after trastuzumab treatment.
Authors: Afrough Aimaz , Lin Heather , Gutierrez-Barrera Angelica M. , Litton Jennifer Keating , Valero Vicente , Arun Banu 
Published: March 2020

e12550 Background: Human epidermal growth factor receptor (HER2) overexpression or amplification occurs in 20–25% of all breast cancers and is associated with an aggressive form of the disease with reduced disease-free survival (DFS) and overall survival (OS). However, the outcome of patients with HER2+ tumor and BRCA mutation is poorly described. The purpose of this analysis was to analyze the clinical and pathological features and outcomes of patients with HER2+ breast cancer regards to their BRCA status. Methods: Patients who were referred for genetic counseling between 2004-2012 and who had a HER2+ breast cancer treated with trastuzumab were included in our analysis. Patients were considered Her2+ if immunohistochemistry was 3+ or had a ratio of ≥2 by FISH. Patients with metastatic breast cancer at diagnosis were excluded. Clinical and pathological and outcome data was extracted from a prospectively maintained research data base after IRB approval was obtained. Results: Ninety-four patients were identified. The median age at diagnosis was 39 years (range 21 – 58). The majority of the patients were White (76%). Tumors were invasive ductal carcinoma in 89% and had nuclear grading of 3 in 76% of patients. Hormone receptors were positive in 66% and BRCA 1 or 2 mutations were positive in 16% (N=15). The majority of the patients were treated with a combination of Anthracyclines plus Taxanes (76%). All patients received trastuzumab in the neoadjuvant or adjuvant setting. After a median follow-up of 4.4 years, OS and DFS in all patients were 97% and 88%, respectively. Three HER2-positive breast cancer patients had died (3.2 %). Recurrence had occurred in 11 patients; all of these patients were BRCA negative. OS and DFS of patients with BRCA mutations were then compared with OS and DFS of patients without BRCA mutation (both 100% vs. 96% and 81.9%, respectively). There was no statistically significant survival difference in BRCA mutation carriers compared with non-carriers (p=0.362). Conclusions: The presence of a BRCA mutation does not seem to offer prognostic information in this population. Further investigation with larger cohort are needed for confirmation.
Prevalence and outcomes of cancers in Ekiti State, southwest Nigeria.
Authors: Babatunde Oluwole Adeyemi , Elegbede Olusegun Elijah , Ayodele Majekodunmi Lawrence , Abidoye Sunday David 
Published: March 2020

e12553 Background: There is an increase in the prevalence of cancer in Nigeria with a change in disease pattern from predominantly infectious to one with both communicable and non-communicable diseases. This study was carried out to determine the prevalence and outcomes of cancers in Ekiti State, Nigeria. Methods: This was a review of the data on patients diagnosed with cancers in Ekiti State as recorded in the database of the Cancer Registry of the Federal Medical Centre, Ido Ekiti between 2007 and 2012. The data was obtained from the cancer registry of the hospital and analysed with SPSS version 15 using descriptive statistics. Results: There were 612 diagnosed cancer patients on record in the cancer registry within the five-year period under review. Most (67.6%) were females, 97.1% belonged to the Yoruba ethnic group, 93.5% were Christians, and 86.6% were married while 13.2% were single and 0.2% were separated. The site most commonly affected was the breast (14.6%) followed by the prostate gland (14.1%), cervix (6.9%), ovary (6.8%), uterus (3.1%) and the stomach (1%). Also, the commonest morphological type of cancer seen was adenocarcinoma (8.5%). The highest levels of education were tertiary, secondary and primary education for 47.4%, 30.2% and 15.2% of the patients respectively while 7.2% had no formal education. Of all the patients seen, 85.3% were symptomatic and 14.7% were not while 79.7% were alive, 2.1% dead and the outcome for 7.6% of the patients was unknown at the time of this survey. Conclusions: The prevalence of cancer is increasing with many of the patients not being able to afford the drugs for treatment. More needs to be done by all stakeholders to encourage early screening and diagnostic measures, reduce exposure to risk factors for cancers and subsidize or waive treatment costs for patients.
Using ANG4043, a brain-penetrant anti-HER2 mab, to increase survival in a murine intracranial breast tumor model.
Authors: Lachowicz Jean E , Demeule Michel , Regina Anthony , Tripathy Sasmita , Che Christian , Currie Jean-Christophe , Lord-Dufour Simon , Houle Emilie , Castaigne Jean-Paul 
Published: March 2020

e13013 Background: Treatments for metastatic brain tumors originating from HER2-positive breast disease are limited due to the inability of most anti-tumor agents to enter the brain. While the selectively permeable blood-brain barrier (BBB) restricts access of therapeutics such as mAbs to the brain, transcytosis of hormones, nutrients, and other homeostatic modulators is mediated by endogenous receptors such as LRP1, low density lipoprotein receptor-related protein 1. We have created a family of peptides (Angiopeps) that are recognized by LRP1 and enter the brain via transcytosis. Using these proprietary Angiopeps, we have created novel, brain-penetrant Peptide-Drug Conjugates. An iterative process of linker selection and reaction condition optimization led to the discovery of ANG4043, consisting of the Angiopep An2 attached to a trastuzimab biosimilar. This brain-penetrant peptide-mAb conjugate, which displays HER2 binding affinity and in vitro anti-proliferative properties similar to that of the native mAb, was tested in a murine model of breast tumor brain metastases. Methods: Athymic nude mice were stereotactically implanted 1.5 mm anterior and 2.5 mm lateral to bregma with 1X106 BT-474 cells twelve days prior to initiation of drug treatment. Body weight and morbidity/mortality were monitored daily. Results: Median survival in the control group was 45 days, compared with 68 days and 80 days for the 5 mg/kg (p = 0.0005) and 15 mg/kg (p = 0.0003) groups, respectively, demonstrating a 52% and 78% improvement over the control group. Conclusions: These data demonstrate that ANG4043 increases survival in a mouse HER2-positive intracranial tumor model. These results extend the validation of An2 conjugation beyond small molecules and peptides to include larger molecules such as therapeutic mAbs for development of new brain-penetrant anti-tumor therapeutics.
A 10-year review of primary CNS lymphoma treatments and outcome: The Irish experience.
Authors: Alken Scheryll Paula , Teo MinYuen , Bambury Richard Martin , Mohd Sharial Mohd Syahizul Nuhairy , Jayaram Anuradha , Brett Francesca , Keohane Catherine , Farrell Michael Anthony , Keane Maccon M. , Power Derek Gerard , Moylan Eugene J. , Grogan William , O'Reilly Seamus , Breathnach Oscar S. 
Published: March 2020

e13020 Background: PCNSL is a rare variant of diffuse large B cell lymphoma. Optimum treatment strategies are yet to be defined. We report the Irish experience. Methods: We examined the Irish National Cancer Registry to assess the incidence of PCNSL. Patients diagnosed between 2001 and 2011 were cross referenced and identified from medical oncology, neuropathology and pharmacy database in the 3 cancer centres. Progression-free survival (PFS) and overall survival (OS) were estimated via Kaplan-Meier methods, and Cox proportional hazard model was used to identify risk factors. Results: 74 patients were treated in the 3 centres over the time period, representing 57% of all cases diagnosed in Ireland (ranging from 12.5% in 2001 to over 90% from 2008 onwards). 39 (52.7%) were male, with a median age of 60 years (range 17 – 78). 64% had an ECOG PS of 0 – 1 at presentation. Involvement of the deep structures occurred in 37.5% (n=24), with 29.7% (n = 19) having multifocal disease. 20.3% presented with hemiparesis with 18.6% presenting with symptoms suggestive of raised intracranial pressure. 80% were treated with the DeAngelis regimen and 14% with the Ferreri regimen. 35.7% received whole brain radiotherapy. The median PFS was 22.4 months, (95% CI, 14.2 – 32.1), and median OS was 33.3 months, (95% CI, 22.3 – 68.8). ECOG PS and presence of hemiparesis at diagnosis were independent poor prognostic factors for PFS but not for OS. Age, tumour site, multi-focality, chemotherapy regimen and delivery of radiotherapy did not significantly affect PFS or OS. Conclusions: Our data compares favourably with published series. Increased understanding of the molecular biology of PCNSL is urgently needed in order to define optimum therapies. PCNSL should be treated in specialist centres to facilitate increased casemix, enrolment in clinical trials and banking of tumor tissue.
Relationship of the p75 neurotrophin receptor (p75NTR) and hypoxic response and treatment resistance in malignant gliomas.
Authors: Kenchappa Rajappa , Forsyth Peter A. J. 
Published: March 2020

e13026 Background: Malignant gliomas (MGs) are resistant to Radiotherapy (RT). The molecular pathways that produce resistance to therapy and ability to tolerate hypoxia are poorly understood. We previously found that the p75NTR causes invasion & proliferation of MGs/Brain Tumor Initiating Cells (BTICs). We think MGs use the neurotrophin-rich brain environment as a survival advantage to resist treatment by expressing the p75NTR. We hypothesize that hypoxia cause p75NTR proteolysis which produces HIF-1α stabilization and activation of hypoxic responses. This repertoire of hypoxic responses leads to resistance to both hypoxia & radiotherapy (RT) and account for MG recurrence. Methods: We used glioma cells and BTICs they express very low or and high levels of p75NTR and manipulated the expression of p75NTR by shRNAs and activation by mutant receptors and pharmacological inhibitors. We exposed these cells to hypoxia and radiation treatment and performed biochemical and functional assays. We have also used paired pre and post-RT frozen patient specimens. Gene expression profiles were analyzed for patients using microarray expression data for 516 primary GBM patients from the TCGA and 239 patients from Moffitt’s Total Cancer Care (TCC) project. Results: We found that inhibiting p75NTR pharmacologically significantly reduced invasion/proliferation of MGs/BTICs in vitro & in vivo. We have also found that p75NTR is required for HIF-1α stabilization and VEGF expression in MGs/BTICs in vitro & in vivo, that p75NTR expressing MGs/BTICs are very resistant to hypoxia & RT in vitro, and these effects are reversed with inhibition of p75NTR signaling. In addition, p75NTR expression and its cleavage are associated with treatment resistance in patient specimens. We also found using TCGA and Moffitt patient specimen data that the p75NTR/Siah2/PHD axis is expressed in MG patients and associated with RT resistance/poor prognosis. Conclusions: These results suggest that p75NTR expression/cleavage are required for HIF-1α pathway activation and hence the phenotype of MGs/BTICs and their treatment resistance. Targeting the p75NTR signaling axis therefore will provide novel therapeutic approaches.