bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human papillomavirus (HPV) in young patients with head and neck squamous cell carcinoma.
Authors: Ungtrakul Teerapat , Keelawat Somboon , Vinayanuwattikun Chanida , Sriuranpong Virote 
Published: March 2020

e17004 Background: HPV-associated head and neck squamous cell carcinoma (HNSCC) seems to increase during the last decades and has been commonly described to associate with younger patients. However the true prevalence of HPV in this specific population remains unclear. Methods: We collected archival 56 paraffin-embedded tumor tissue samples from HNSCC patients diagnosed and treated at King Chulalongkorn Memorial Hospital between 2000 and 2010. The major inclusion criterion was the age at diagnosis less than 45 year-old. HPV status was determined by HPV polymerase chain reaction (PCR) with degenerated primer covered over 37 HPV serotypes including high-risk HPV6, 11, 16, 18, 31 and 33. Additional immunohistochemical stain (IHC) of p16 was performed. The clinicopathological correlations with HPV status were analyzed. Results: Fourteen (25%) of the 56 HNSCC samples exhibited HPV DNA by PCR. Among cancer sites, 7 of 23 (30%) oral cavity, 3 of 11 (27%) oropharynx, and 4 of 22 (18%) hypopharynx and larynx primary organs displayed HPV DNA in tumor tissues. There was no major difference in the demographic data, tumor characteristics and treatment modalities between HPV DNA-negative and HPV DNA-positive samples. HPV DNA-positive tumors tended to have a better 2-year overall survival when compared with HPV DNA-negative tumors (66 and 40 percent, respectively) (p=0.10). After adjusted for independent prognostic variables of cigarette smoking, alcohol consumption, site of primary tumor and nodal status, only HPV DNA status was a predictor for a better survival (HR 0.16; 95%CI, 0.01-0.66). Additional IHC for p16 expression revealed 8 of 48 (16%) of p16 overexpression with twenty-two percent concordant rate with HPV PCR. Conclusions: Though HPV genome was moderately found in our young HNSCC patients, HPV DNA was not associated with a significant better survival in the primary analysis. Nevertheless, multivariate analysis adjusting for prognostic variables demonstrated a significant better prognosis in HPV DNA-positive tumors in this subset of HNSCC. Low concordant rate between HPV DNA and p16 overexpression in these young populations may caution the use of p16 overexpression as a surrogate marker of HPV.
Timing and severity of skin-related adverse events in a phase II trial of sorafenib (BAY43-9006) in patients with advanced thyroid cancer.
Authors: Terry Raya D. , Keefe Stephen Michael , Grande Carolyn Marie , Zifchak Larisa , Brose Marcia S. 
Published: March 2020

e17009 Background: We previously conducted a phase II study of sorafenib (BAY43-9006) in advanced thyroid cancer. Rash and Hand-Foot Skin Reaction (HFSR) were two of the most common adverse events (AEs). Because these skin-related AEs affect quality of life, we further explored their time course and management. Methods: Fifty-five patients were treated on UPCC 03305, a phase II study of sorafenib in patients with advanced thyroid cancer from 2006 to 2011. AEs were recorded using CTCAE v.3.0 and reported here if relation to the drug was deemed “possibly-related” or greater. Cycle length was four weeks. Results: No grade 4 or 5 skin toxicity was observed. Forty-nine patients (89%) experienced rash. Thirty-one patients had a maximum severity of grade 1 (56%), eight had grade 2 (15%), and nine had grade 3 (18%). Fifty patients (91%) had HFSR. Thirteen patients had a maximum severity of grade 1 (24%), 33 had grade 2 (60%), and four had grade 3 (7%). The severity of rash peaked at cycle 1 (19% grade 2,3) and declined by cycle 3 (4% grade 2,3). The severity of HFSR peaked at cycle 2 (39%, grade 2,3) and declined by cycle 6 (10% grade 2,3). The timing and severity of rash and HFSR by cycle are reported in the Table. Following cycle 12 the severity and prevalence of skin AEs reached a steady state. Of the 55 patients, 30 patients (55%) required dose-reduction, and nine of those patients (31%) resumed full dose by the end of study date. Nine patients (16%) were dose-reduced for rash, 17 patients (31%) were dose-reduced for HFSR, and three patients (5%) were dose-reduced for both rash and HFSR. Conclusions: The severity of skin toxicity peaked by cycle 1 for rash and cycle 2 for HFSR. The severity improved dramatically for rash by cycle 3 and for HFSR by cycle 6. Our data support the close supervision of skin-related AEs in the first six cycles of treatment with sorafenib. However, the sustained high prevalence of rash and HFSR requires all patients receive ongoing skin care for the duration of therapy. Clinical trial information: NCT00095693. [Table: see text]
Identification, characterization, and chemotherapy utilization in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) using real-world data: Retrospective U.S. claims database analysis.
Authors: Flaig Thomas W. , Mehra Maneesha , Stellhorn Robert , Ng Yvette , Todd Mary Beth 
Published: March 2020

e17510 Background: Limited data are available characterizing the progression of newly diagnosed PC to mCRPC and the use of different treatments in the mCRPC population. Real world longitudinal pt-level data were used to define, profile, and characterize treatment of pts with mCRPC. Methods: The PharMetrics database (2000-2011), a nationally representative, nonpayer–owned, integrated, commercial US claims database, was used to identify pts with an index PC diagnosis (dx) (ICD-9 codes 185.x or 233.4) and confirmation of ≥ 3 PSA test values in their claim history (n = 7402). An algorithm was developed to identify progression of PC from index dx to mCRPC by 1) evaluating the presence or absence of a secondary malignancy dx (ICD-9 codes 198.5, 199.1, and 198.82) to determine metastatic status, and 2) evaluating PSA increases with concurrent medical/surgical castration to determine castration-resistant status (Alemayehu et al, J Med Econ. 2010;13:351). Results: Mean follow-up duration was 50.7 ± 35.5 (SD) months. 271 pts (3.7%) had PC with metastases (mets) at dx. 2836 (38.3%) had medical/surgical/both castration during follow-up. 779 (11%) pts developed CRPC and 299 (4.0%) were defined as having mCRPC. Median age at PC dx and mCRPC dx was 73.5 and 76.7 years, respectively. Duration from initial PC dx to mCRPC was 28 ± 20.7 (SD) months. Prior to mCRPC dx (> 3 months), < 10% of pts were exposed to chemotherapy. Chemotherapy exposure (docetaxel, vinorelbine, estramustine, mitoxantrone) upon mCRPC dx (±3 mos) was 24%. Any docetaxel exposure after mCRPC dx was 42.8% (excluding pts with dx/follow-up pre-2004 docetaxel approval year). Other treatments in mCRPC pts at dx included opioids (n = 174, 58%) and bisphosphonates (n = 58, 19%). Conclusions: This effort identifies a methodology of using a retrospective US claims database to identify mCRPC, which accounts for less than 5% of pts with PC. 24% of pts presented with mets at initial PC dx while 76% developed mets over time. The moderate rate of opioid use and incomplete penetration of chemotherapy in mCRPC emphasizes the need for improved treatment alternatives.
Febrile neutropenia with adjuvant docetaxel and cyclophosphamide (TC) chemotherapy for breast cancer.
Authors: Yu Joanne Linda , Kurin Michael , Pasetka Mark , Sridhar Srikala S. , Warner Ellen 
Published: March 2020

e17523 Background: The combination of docetaxel and cyclophosphamide (TC) for adjuvant treatment of early stage breast cancer has been shown to improve overall survival compared with doxorubicin and cyclophosphamide (AC) (Jones et al., 2006). Although cardiotoxicity is avoided with TC, the risk of febrile neutropenia (FN) is higher. For TC, reported rates of FN without prophylactic G-CSF range from 5% in the phase III trial to as high as 50% in retrospective chart reviews. As G-CSF is not covered by our provincial cancer funding agency for primary prophylaxis of FN with TC chemotherapy, we sought to determine the incidence of FN with TC chemotherapy in two comprehensive cancer centres in Ontario, Canada. Methods: Patients who received adjuvant TC chemotherapy between January 1, 2008 and December 31, 2012 were identified through the pharmacy databases. Electronic charts were retrospectively reviewed to abstract patient characteristics, treatment details including G-CSF use, and incidence of FN. Results: Preliminary results from one institution demonstrate that 187 patients were treated with TC over the study period. Of the 74 (40%) patients who did not receive primary G-CSF prophylaxis, 23 (31%) developed FN requiring hospitalization and treatment with intravenous antibiotics. However, none of the 113 patients who received primary G-CSF prophylaxis (funded by the patient or a third party payer) developed FN. Putative risk factors for FN in the absence of G-CSF including age, BSA, BMI, and pre-treatment absolute neutrophil count were examined and will be reported. Conclusions: The FN rate associated with TC chemotherapy exceeds 30%, higher than that reported in the clinical trial. As per ASCO guidelines, primary G-CSF prophylaxis should be given with TC chemotherapy, and in Canada this should be covered by provincial cancer funding agencies.
The use of molecular profiling (MP) beyond standard panels in day-to-day practice: A multi-institutional multinational survey.
Authors: Lemech Charlotte Rose , Newmark Joshua , Arkenau Hendrik-Tobias 
Published: March 2020

e17532 Background: The complexity and associated cost of MP in cancer care is rapidly increasing and there are challenges as to its incorporation and utility in day-to-day oncological practice. Methods: A structured survey was sent to 42 institutions in Europe, USA and Asia-Pacific with well-established experience in basic oncology research and drug development. It aimed to gain insight into the frequency of MP beyond standard testing. The results from an 8 week snap-shot period were collated. Results: 42 medical oncologists, 5 radiation oncologists and 4 haematologists from 31 institutions responded; 41 from academic/teaching hospitals, 7 from the private sector and 3 from general hospitals. 26 respondents indicated that MP beyond standard panels was regularly performed. Testing was covered by public funding (38%), grants (35%) or private insurance/self pay (25%) and was performed for the purpose of research, diagnostics and other reasons (48, 47 & 5%, respectively). Gene analyses included DNA/RNA sequencing alone (11%) or in combination with IHC/FISH (38%), gene expression profiling (19%) and/or proteomics (8%). MP analysis was performed on state-of-the-art sequencing platforms (Sanger in 12%, a combination of Sanger and next generation sequencing (NGS) in 35% and NGS alone in 15%). Archived (60%) and fresh frozen biopsies (40%) were analyzed with a turnaround of <1 week (23%), between 1-3 weeks (66%) and >3 weeks (11%). 66% of results were discussed in a multidisciplinary meeting. Biobanking was available in 48% institutions with bioinformatics support available in 29%. The main challenges identified were funding and associated costs, incorporation of bioinformatics, data quality and staying abreast of new technologies. Conclusions: The use of MP beyond standard panels is increasing in both complexity and availability. Mastering clinical accessibility, data volume, and technical innovation will be key to incorporate MP in day–to-day practice.
The effects of multidisciplinary clinics on the variability in timeliness of care for lung cancer patients.
Authors: Blaseg Karyl , Schallenkamp John M , Stephens Catherine L , Needham Charles Scott , Nieva Jorge J. 
Published: March 2020

e17533 Background: Implementation of multi-disciplinary clinics (MDC) has the potential to improve the care of cancer patients. Little data presently exists on the impact of MDC based care on cancer patient populations. Methods: A multi-disciplinary lung cancer clinic was implemented at a large, rural, multispecialty medical center in 2009. A retrospective analysis of the impact of MDC implementation on patient care was accomplished from 2009-2010 and was compared to care of patients from a reference period consisting of all patients treated in 2007. Patient survival, time to first appointment, time to treatment, use of clinical trials, and selection of palliative therapy only were analyzed using descriptive statistics. Two sided students t-test was performed to compare results from each cohort. Results: A new diagnosis of lung cancer was identified in 290 patients from 2009-2010. A total of 175 patients received care within the MDC and 115 patients were treated outside of the MDC. One hundred and forty-two patients were analyzed from the pre-MDC period of 2007. Seventy-seven percent of patients had NSCLC in 2007 and 81% of patients had NSCLC in 2009-2010. The time from referral to first appointment, and diagnosis to treatment are shown in the Table. There was a significant improvement in the mean time to initiation of cancer therapy with the introduction of the MDC clinic with patients starting therapy at a mean of 22 days instead of 28 days, however, the median time to treatment increased to 17 days from 5 days. MDC was associated with improvement in clinical trial accrual to 15% from 10%. Conclusions: The implementation of MDC was associated with greater homogeneity in timeliness of care, with fewer patients being outliers with long delays in time to care, hence improvements in mean time to care, with a detriment in median time to care owning to the increased complexity of scheduling. MDC also resulted in improvements in clinical trial accrual. [Table: see text]
Hospital characteristics and breast cancer patients’ evaluation of care.
Authors: Pfaff Holger , Kowalski Christoph , Ansmann Lena , Ingendahl Julia 
Published: March 2020

e17550 Background: There is a large body of research on patient evaluations of care and its associations with patient characteristics, such as the sociodemographics or the severity of diseases. A number of studies have recently been published that consider the characteristics of various hospitals in order to explain the differences in patient evaluations between hospitals in non-oncological patient populations. This study investigates the relationship between13 dimensions of satisfaction and breast center hospital characteristics which account for the patient case mix. Methods: The cross-sectional survey data of 3,601 newly-diagnosed breast cancer patients (response rate: 88% of consenting patients) who were treated in 85 out of 91 breast center hospitals in the German state of North Rhine-Westphalia in 2010 were combined with structural data from a key informant survey from the same hospitals. Multilevel linear regression models were calculated in order to investigate patients’ evaluations of the care differences between hospitals and their associations with hospital characteristics (i.e. teaching status, volume, network size, clinical studies, case manager employed) accounting for patient characteristics (self-rated health, mother language, insurance status, age, education, cancer stage, type of surgery). Results: Patients evaluated non-teaching hospitals as being statistically significantly better in 8 out of 13 satisfaction dimensions. None of the other hospital characteristics were significantly associated with any of the satisfaction dimensions. Overall, the differences between hospitals were small to moderate, with null model ICCs ranging from 0.02 to 0.09 for the different dimensions. Conclusions: Teaching breast cancer hospitals face substantial difficulties in achieving patient evaluations that are as good as those from non-teaching hospitals in Germany. The question of extra staffing for the additional teaching tasks needs to be discussed.
Targeted agents (TA) for advanced solid tumors (AST): What is the likelihood of being helped or harmed (LHH)? Assessing the clinical impact of therapies with FDA/EMEA approval.
Authors: Bria Emilio , Pilotto Sara , Bonomi Maria , Milella Michele , Massari Francesco , Fojo Antonio Tito , Sperduti Isabella , Giannarelli Diana , Tortora Giampaolo 
Published: March 2020

e17555 Background: Health care agencies adopt systems to inform patients and health care providers about relative risks and benefits using Evidence Based Medicine (EBM) measures, such as the number of patients needed to be treated/harmed (NNT/NNH), and LHH. This analysis was undertaken to provide an overview of the LHH provided by TA for AST. Methods: Randomized clinical trials (RCTs) supporting FDA/EMEA approval for TA (tyrosine kinase inhibitors, TKI, and monoclonal antibodies, MoAb) were evaluated provided efficacy (PFS, OS), and safety (grade 3-4 specific toxicities) data were available. NNT/NNH were calculated from absolute differences determined for PFS/OS rates (reported/extracted from Kaplan-Meier (K-M) curves and for the worst drug-specific toxicities. LHH was calculated for PFS or OS. A sensitivity analysis according to the randomized comparison (placebo controlled [P] or accepted standard [STD] vs add-on) was performed. Results: Thirty-five separate approvals were identified (23/12 for PFS/OS advantage, respectively). Results are shown in the Table. Hypertension and rash were most frequent drug specific toxicities. LHH >1 may be interpreted as "number of times drug is more likely to provide a benefit than to harm." Conclusions: Despite limitations (estimation from K-M curves and differences in drug toxicities) the data demonstrate the greatest benefit as measured by LHH was achieved with TKI against P or STD with PFS as the endpoint. Marginal benefits were achieved in the majority of OS analyses, and with add-on design. The latter may reflect difficulty of the OS endpoint, marginal benefits of the TA added (bevacizumab and cetuximab) or may indicate TAs combine only poorly with conventional regimens. These data should be complemented with a cost-analysis and put in the context of the general health care system. [Table: see text]
Oncology phase II clinical trials in 2011: Summary description and comparison to phase II trials in other subspecialties.
Authors: Chia Yee Hong 
Published: March 2020

e17568 Background: Phase II clinical trials in oncology have previously been reported to differ significantly in design compared to trials in other subspecialties. The purpose of this study is to provide a summary description of Phase II oncology clinical trials published in 2011, and to identify persistent major cross-specialty differences in clinical trial design. Methods: Records identified through a computerized literature search on PUBMED were reviewed manually using pre-defined criteria to identify abstracts of Phase II clinical trials published in 2011. The abstracts were classified according to variables including subspecialty, use of control group (active and/or placebo), randomization, blinding, and study conclusions. Trials with positive outcomes were defined as those in which the conclusion indicated that the intervention was safe and effective/worthy of further investigation. Statistical analysis was performed using the chi-squared test. Results: A total of 1,500 abstracts of Phase II clinical trials were identified, of which the majority (75%) describe trials on interventions for neoplastic diseases. Among oncology trials, the largest proportion of abstracts described trials evaluating intervention for hematologic neoplasms (16%), followed by upper and lower gastrointestinal (15%), lung (13%) and breast (11%) cancers. Compared to trials in other subspecialties, oncology trials are significantly less likely to include the use of randomization (17% vs 66%, p < 0.0001), blinding (3% vs 44%, p < 0.0001), and control (13% vs 70%, p < 0.0001). The majority of the abstracts reported positive outcomes (66% for oncology; 74% for the other subspecialties). Among oncology trials, trials utilizing a control group are less likely to report positive outcomes than those without a control group (53% vs 67%, p = 0.002). Conclusions: Major differences in design still exist between Phase II trials in oncology and other subspecialties. Only a minority of oncology trials report the use of randomization, blinding, or control groups. Whether the growing interest in randomized Phase II oncology trials will translate into a larger proportion of such trials in the future remains to be seen.
Factors affecting the offering and enrollment of patients on clinical trials in radiation oncology.
Authors: Rich Shayna Eliana , Mendenhall Nancy Price 
Published: March 2020

e17571 Background: Improvements in cancer treatment require significant patient involvement in research, which may be particularly limited for new technologies such as proton radiation therapy. Studies with biased referrals or enrollment may not be generalizable to a general population. This study examines the reasons why patients were not offered or refused enrollment in clinical trials at the University of Florida Proton Therapy Institute (UFPTI). Methods: All patients seen at UFPTI between April-October 2012 for proton therapy for tumor sites with a clinical trial available (N=463) had information collected prospectively regarding whether they were offered enrollment and consented for clinical trials, and the reasons for each decision. The majority of patients had already secured funding for proton therapy. Results: Seven percent (34/463) of patients were ineligible for an available clinical trial, due to study exclusion criteria, concerns for patient safety based on comorbidity, or concerns for data integrity (e.g., other non-skin cancer within five years). Only 3% (9/275) of eligible patients were not offered a clinical trial. Forty-four percent (99/226) of patients offered a clinical trial refused. The most common reasons for refusal included: discomfort with lack of mature data, dislike of protocol, fear that protocol is not best option for disease control, and fear of side effects. Although UFPTI treats a variety of malignancies, the overwhelming majority of those who refused consent were prostate adenocarcinoma patients, who often self-referred for proton therapy. Conclusions: Despite near universal availability of clinical trials at UFPTI, less than half of patients enroll in clinical trials. The greatest factor for non-enrollment appears to be patient acceptance. Despite the availability of non-randomized trials with fairly standard treatment approaches, 44% refused to enroll on clinical trials, suggesting discomfort for less well documented treatment approaches. Further studies should examine whether findings are similar among all US cancer patients, as patients seeking proton therapy may not resemble the general population.