bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTEN and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC).
Authors: Da Costa Alexandre Andre B. A. , Costa Felipe D'Almeida , de Oliveira Andrea Cruz Ferraz , Stecca Carlos , Oliveira Audrey , Alves Ana Caroline Fonseca , Camandaroba Marcos Pedro Guedes , Araujo Daniel Vilarim , Machado Larissa , Cordeiro De Lima Vladmir Claudio 
Published: September 2018

6061 Background: Platinum-based chemotherapy in association to cetuximab is the standart first-line treatment for metastatic HNSCC. There is no established biomarker for cetuximab efficacy in HNSCC. We have previously shown that PTEN loss of expression is a bad prognostic factor for patients treated with platinum-based chemotherapy and cetuximab. The aim of the present study was evaluate the prognostic impact of PTEN loss of expression in patients treated with or without cetuximab and to evaluate its predictive value to cetuximab benefit. Methods: One hundred and nineteen patients with metastatic or locally recurrent HNSCC were included. Clinical data on treatment and outcomes was retroespectively colected from medical charts. Tissue micro-array was constructed to evaluate PTEN protein expression through immunohistochemistry. Citoplasmatic staining was evaluated using H-score. Tumors with H-score < 10 were considered to present PTEN loss of expression. Results: From the 119 patients 72 were treated with chemotherapy plus cetuximab while 47 were treated with chemotherapy alone. Median overall survival (mOS) was 9.2 months and median progression free survival (PFS) was 4.6 months. Patients treated with cetuximab compared to those who were not treated with cetuximab had a mOS of 11.4 vs 7.0 months (p = 0.770) and a median PFS of 6.2 vs 3.0 months (p = 0.249). Patients with PTEN loss of expression had a worse OS and PFS with mOS of 5.8 vs 10.5 months (p = 0.002) months and mPFS of 3.2 vs 5.2 (p = 0.015). On multivariate analysis including PTEN loss of expression and ECOG performance status both remained independently associated to survival with HR 2.25 (CI95% 1.28-3.97, p = 0.005) for PTEN loss of expression and a HR 1.63 (CI95% 1.07-2.50, p = 0.023) for ECOG. Negative prognostic impact of PTEN loss of expression was seen only in the cetuximab treated patients (mOS 7.3 vs 13.0 months; p = 0.002) but not in the chemotherapy only group (mOS 3.2 vs 7.5 months; p = 0.051). Interaction test for treatment group and PTEN loss of expression showed a p = 0.418. Conclusions: The present study confirms PTEN as a prognostic factor for metastatic HNSCC and suggests PTEN expression should be studied in larger cohorts to evaluate its predictive value to cetuximab response.
Disparities in supportive therapy for head and neck cancer and impact on missed radiation days and weight loss.
Authors: Ramey Stephen , Perlow Haley , Silver Ben , Jaffe Adam , Kwon Deukwoo , Chinea Felix , Samuels Stuart , Yechieli Raphael 
Published: September 2018

6077 Background: National guidelines emphasize the importance of speech and swallowing (SS) and nutrition services (NS) for head and neck cancer patients (pts). This study evaluates influences of demographic and treatment factors on receipt of SS and NS at a safety-net hospital (SH) and an adjacent private hospital (PH). It also examines associations between lack of these services and negative outcomes. Methods: This retrospective analysis included non-metastatic laryngeal or oropharyngeal cancer pts treated with radiotherapy (RT) at a PH or SH. Univariate (UVA) and multivariable (MVA) analyses utilized linear regression, logistic regression, and zero-inflated Poisson regression. Covariates included race, ethnicity, preferred language, insurance status, immigration status, gender, age, treating hospital, comorbidity score, primary treatment modalities, time to treatment initiation (TTI), and stage. Potential negative outcomes of not receiving SS and/or NS were analyzed only among pts treated with chemoradiation (CRT). Results: Of 239 pts (PH = 138 pts; SH = 56 pts), 28.6% of SH pts received SS pre-RT vs 54.1% at the PH (p < 0.001). Receipt of pre-RT NS did not differ significantly between SH (14.3%) and PH (19.7%) but was low at both. On MVA, SH care (OR 0.29; p = 0.029) and longer TTI (OR 0.99; p = 0.033) were associated with decreased pre-RT SS. In contrast, surgery before RT (OR 10.1; p = 0.002) and surgery before CRT (OR 10.7; p = 0.001) vs RT alone were associated with increased pre-RT SS. No covariates were significantly associated with receipt of NS on MVA. For pts receiving CRT, pre-RT SS was associated with less weight loss during RT (mean difference = 2%; p = 0.036). Receiving both pre-RT SS and NS was associated with fewer missed RT days (RR 0.49; p = 0.004). Receipt of SS and/or NS were not associated with gastric tube placement, emergency room visits, or non-chemotherapy admission days during or within 90 days of CRT. Conclusions: SS was received less often at a SH vs a PH. NS were delivered at a low level at both centers. Lack of supportive services was associated with increased missed RT days and increased weight loss during CRT. Quality metrics to establish supportive care benchmarks may help reduce disparities.
A phase 1 trial of NBTXR3 nanoparticles activated by intensity-modulated radiation therapy (IMRT) in the treatment of advanced-stage head and neck squamous cell carcinoma (HNSCC).
Authors: Le Tourneau Christophe , Calugaru Valentin , Jouffroy Thomas , Rodriguez Jose , Hoffmann Caroline , Dodger Bernard , Moreno Victor , Calvo Emiliano 
Published: September 2018

6080 Background: Functionalized hafnium oxide nanoparticles (NBTXR3) have been developed as selective radioenhancers, which may represent a breakthrough approach for the local treatment of solid tumors. The high electron density of the nanoparticles, when exposed to radiotherapy (RT), allow the absorption/deposition of a high radiation dose within the tumor cells, to physically kill the cells and possibly improve outcome. A phase I trial was implemented for the treatment of locally advanced HNSCC in patients (pts) older than 65 years who cannot receive cisplatin. Methods: Pts received a single intratumor (IT) injection of NBTXR3, volume dose levels escalated at 5%, 10%, 15% and 22% of baseline tumor volume, followed by RT (IMRT, 70Gy/ 35 fractions / 7 weeks). Primary endpoints included feasibility of the IT implantation and safety. Secondary endpoints included IT residency of NBTXR3 using CT scan and RECIST 1.1 response. Results: Enrollment was completed for volume 5%, 10%, and 15% (11 pts) and 1 patient at volume dose level 22%. Feasibility of the IT injection was confirmed. The treatment was easily administered, was safe with no SAE, or early DLT, which allowed the pts for completion of the planned RT schedule. Adverse events related to the injection procedure included grade 1-2 injection pain (1 pt), and tumor hemorrhage (1 pt). Results demonstrated that a single injection of NBTXR3 provides adequate bioavailability of NBTXR3 IT over seven weeks of RT. No leakage of NBTXR3 to the adjoining healthy tissues was observed. Preliminary results of antitumor activity according to RECIST 1.1 are presented below: 11 evaluable pts, 10 showed complete or partial response (RECIST 1.1) including, 1/5 complete response at dose levels ≤ 10% and 3/6 complete responses at dose levels > 10% Follow up results with duration of response and tolerance will be disclosed. Conclusions: Injection of NBTXR3 was safe and well tolerated. All pts received the planned RT. Clinical trial information: NCT01946867.
RNAseq analysis of the sorafenib phase III DECISION trial in differentiated thyroid cancer (DTC): Correlation with clinical outcome.
Authors: Capdevila Jaume , Matos Garcia Ignacio , Mancuso Francesco M , Iglesias Carmela , Nuciforo Paolo , Zafon Carles , Palmer Hector G. , Ogbah Zighereda , Muiños Laura , Pena Carol Elaine , Brose Marcia S. , Schlumberger Martin , Vivancos Ana 
Published: September 2018

6083 Background: In DECISION, sorafenib significantly impacted progression-free survival (PFS) and response rate (RR) in radioactive-iodine refractory DTC. The aim of this biomarker study was to identify RNA expression profiles related with PFS, overall survival (OS) and RR and to describe the expression profiles of DTC histologies. Methods: Of the 417 patients in the trial, 247 had sufficient formalin fixed paraffin embedded archival tumor material for RNAseq. We generated on average 77 million paired-end reads for each sample on HiSeq2000 (Illumina). RNAseq reads were mapped against the human reference genome (GRCh38) with STAR (v2.5.1b) using ENCODE parameters. 125 samples had sufficient quality to be included in the analysis. Results: The analysis subset included 68 sorafenib and 57 placebo patients (PFS 10.3 vs 7.4 months, HR: 0.62 CI 95% 0.38-0.99, p = 0.046). Unsupervised clustering using the 100 most variable genes identified 3 groups: BRAF-like (included most of the BRAF-mutated tumors), RAS-like (included most of the RAS mutated tumors) and non-BRAF-non-RAS-like group (included most wild-type tumors). These groups, based on the mutational profile, can be correlated with tumor type: the papillary BRAF-mutant, the follicular wild-type, and a third group with papillary, follicular and poorly differentiated with predominant RAS mutations. A Student t-test comparing papillary and follicular histologies revealed a signature of 283 genes with significantly different expression that, within the papillary tumors, identifies a subset with an expression profile more similar to follicular. No RNA signatures correlating with benefit from sorafenib were identified. Conclusions: While papillary and follicular thyroid cancers have significantly different RNA expression profiles, a subset of papillary has been identified with an expression profile more similar to follicular. In addition, a unified RAS-like expression profile spans subsets of papillary, follicular, and poorly differentiated thyroid cancers, suggesting that tumor biology can be similar across histologies. Clinical trial information: NCT00984282.
Do the American Society of Clinical Oncology (ASCO) Value Framework and the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale measure the same construct of clinical benefit?
Authors: Cheng Sierra , McDonald Erica , Cheung Matthew C. , Arciero Vanessa Sarah , Qureshi Mahin Iqbal , Jiang Di Maria , Ezeife Doreen Anuli , Sabharwal Mona , Chambers Alexandra , Han Dolly , Leighl Natasha B. , Sabarre Kelley-Anne , Chan Kelvin K. 
Published: September 2018

6509 Background: Whether the American Society of Clinical Oncology (ASCO) Value Framework and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) measure similar constructs of clinical benefit is unclear. It is also unclear how they relate to quality-adjusted life-years (QALYs) and funding recommendations in the UK and Canada. Methods: Randomized clinical trials (RCTs) of oncology drug approvals by the Food and Drug Administration, European Medicines Agency and Health Canada between January 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework (August 10, 2015), ASCO version 2 (v2) framework (May 31, 2016) and ESMO-MCBS (May 30, 2015) by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against incremental QALYs from the National Institute of Clinical Excellence (NICE) and the pan-Canadian Oncology Drug Review (pCODR)). Associations between scores and NICE/pCODR recommendations were examined by logistic regression models. Inter-rater reliability was assessed using intra-class correlation coefficients. Results: From 109 included RCTs, 108 ASCOv1, 111 ASCOv2 and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 vs. ESMO, ASCOv2 vs. ESMO, and ASCOv1 vs. ASCOv2 were 0.36 (95% CI 0.15-0.54), 0.17 (95% CI -0.06-0.37) and 0.50 (95% CI 0.35-0.63), respectively. Compared with NICE QALYs, correlation coefficients were 0.45 (ASCOv1), 0.53 (ASCOv2) and 0.46 (ESMO); with pCODR QALYs, coefficients were 0.19 (ASCOv1), 0.20 (ASCOv2) and 0.36 (ESMO). None of the frameworks were significantly associated with NICE/pCODR recommendations. Inter-rater reliability was good for all frameworks. Conclusions: The weak-to-moderate correlations between the ASCO frameworks and ESMO-MCBS, with QALYs, and with NICE/pCODR funding recommendations suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS in fact did not increase with the updated ASCO framework.
Trends in the geographic distribution of cancer clinical trials in the US: 2008-2015.
Authors: Bennette Caroline Savage , Wang Wei-Jhih , Ramsey Scott David , McDougall Jean A. 
Published: September 2018

6515 Background: Access to and patient enrollment in cancer clinical trials is likely strongly impacted by where trial enrollment sites are located. Our objective was to evaluate temporal trends in the geographic location of cancer clinical trials launched in the US. Methods: We obtained the recruiting location(s) of all public- and privately-funded phase II/ III cancer clinical trials launched in the US between 2008 and 2015 from the ClinicalTrials.gov database. We linked the recruiting location(s) of each trial to the relevant hospital service area (HSA), which are defined by ZIP codes as local health care markets for hospital care (n = 3436). We estimated the number of cancer clinical trial sites in each HSA each year between 2008 and 2015. We also calculated a statistical measure of inequality, the Gini coefficient. The Gini coefficient would be 0 if all hospital service areas launched the same number of cancer clinical trials, and would be 1 if all cancer clinical trials were launched in only a single hospital service area. Results: 62% of HSAs (n = 2133) did not launch a single cancer clinical trial between 2008 and 2015. There was a small and non-statistically significant decline in the overall number of cancer clinical trial sites in the United States between 2008 and 2015 (-1.6% per year [95% CI: -4.0, 0.9]). During this same period of time, however, inequality in the geographic distribution of cancer clinical trial sites considerably deepened. For example, in 2008-09, no trials were launched in 68% of HSAs while 19% of trial sites were in only 1% of HSAs. Trials launched in 2014-15 were even more concentrated: no new trials were launched in 74% of HSAs while 25% of trial sites were in the top 1% of HSAs. The Gini coefficient increased significantly from 0.683 (95% CI: 0.666, 0.700) for trials launched in 2008-09 to 0.726 (95% CI: 0.706, 0.746) for those launched in 2014-15. Conclusions: Our findings indicate increased inequality in the geographic distribution of cancer clinical trials launched in the United States since 2008. The underlying causes and consequences of such increasing concentration warrant further analysis given the importance in ensuring equitable geographic access to cancer clinical trials in the US.
A multicenter analysis of patient reported risk factors for not working during cancer therapy.
Authors: Blinder Victoria Susana , Eberle Carolyn E. , Aviki Emeline , Schleicher Stephen Matthew , Patil Sujata , Basch Ethan M. , Sloan Jeff A. , Bennett Antonia Vickery 
Published: September 2018

6523 Background: Treatment for most types of cancer results in work disruptions. The aim of this study is to identify risk factors for not working during cancer therapy using a patient-reported outcome tool. Methods: Patients of all cancer types, who were undergoing treatment with curative or palliative intent, were enrolled in a survey-based study at Memorial Sloan Kettering Cancer Center and the North Carolina Cancer Hospital from 1/2014 to 7/2015. All patients working full- or part- time at the time of cancer diagnosis were included in this analysis. Patient reported outcomes were collected using a survey tool at any time during active cancer treatment. The primary outcome of this analysis was self-reported work status at the time of survey completion. Results: Of 119 patients who were working before their cancer diagnosis, 68% were working at the time of survey completion. The mean age was 52.9 (range 20-80). Younger age was associated with working: 82% of patients age < 40 were working during treatment vs. 31% of patients age > 65 (p=0.01). The number of days patients reported being completely unable to work in the past month was significantly associated with work status; only 26% of patients who missed > 10 days continued to work compared to 69% who missed ≤ 10 days (p<0.01). Patients who report having a flexible work schedule were 23% more likely to continue to work during treatment (69% vs. 46%, p=0.01). In a multivariable model controlling for having an employer contingent health plan, and household income > 200% of the federal poverty level (fpl), only age, having a flexible work schedule, and inability to work > 10 days were independently associated with work status during treatment (Table). Conclusions: Having a flexible work schedule allowed for more work interruptions without job loss. Patients who are likely to miss more than 10 days of work and who have inflexible work schedules are at high risk of unemployment and should be targeted for employment retention initiatives. [Table: see text]
Disparities in access to breast cancer treatment: An observational study based on insurance status.
Authors: Kailasam Karthik , Omaira Mohammad , Ravichandar Marie , Sivsammye Suceil 
Published: September 2018

6534 Background: Breast cancer is the second leading cause of cancer death in Caucasians and African-Americans, and the most common cause of cancer death in Hispanic women. Methods: A retrospective analysis was done with data obtained from 1473 hospitals by National cancer database (NCDB) for the years 2004-2014. Patients with breast cancer were analyzed for differences in treatment offered based on their insurance status. Patients in the insurance group were enrolled under either Private, Medicare, Medicaid or other government insurance. Treatments offered were surgery, chemotherapy, radiation therapy or a combination of the above. Patients with unspecified insurance status and those who were on active surveillance were excluded from the analysis. Results: A total of 2,245,259 patients with breast cancer from all age groups were identified from the registry. 47,294 patients did not have insurance; among which 3275 (7.4%) were not offered any treatment. Among 2,093,809 patients with insurance, 58,726 (2.8%) patients were not offered any treatment. Hence, patients without insurance were twice (OR 2.65; CI 2.55-2.75 p < 0.0001) more likely to not receive any first course treatment. Sub-group analysis for different stages of breast cancer showed; carcinoma in-situ (OR 2.44; CI 2.20-2.71 p < 0.0001), stage1 (OR 2.68; CI 2.43-2.96 p < 0.0001), stage2 (OR 2.86; CI 2.61-3.12 p < 0.0001), and stage 3 (OR 2.56; CI 2.25-2.92 p < 0.0001) have similar odds for not being offered any treatment. However, the odds of receiving treatment were better for stage 4 breast cancer (OR 1.44; CI 1.32-1.55 p < 0.0001). Uninsured Caucasians (OR 2.70; CI 2.56-2.85 p < 0.0001) were less likely to receive any treatment compared to uninsured African-Americans (OR 2.16; CI 2.00-2.33 p < 0.0001) and uninsured Hispanics (OR 1.66; CI 1.52-1.82 p < 0.0001) Conclusions: With the recent suggested changes in health care policy, we can expect the number of uninsured patients to rise and therefore more patients might not have access to breast cancer treatment.
Exploring the time delay between regulatory approval and health techonology assessments (HTAs) of oncology therapies in France, Germany, England, Scotland, Canada, and Australia.
Authors: Jaksa Ashley , Pontynen Anson , Bastian Alexander 
Published: September 2018

6545 Background: Drugs in the USA become available from the moment of FDA approval. Access to oncology therapies outside of the USA may be delayed by regulatory and additional payer HTA processes. This study aimed to examine the time from regulatory approval to an HTA reimbursement decision in countries with mandatory HTA. Methods: Oncology HTAs (N=569) for medicines approved by the EMA, Health Canada, and the Therapeutic Goods Administration (Australia) were matched on indication with HTAs from France, Germany, Canada, England, Scotland, and Australia. Resubmissions were excluded. The date of the first reimbursement decision was subtracted from the date of the regulatory approval to determine the time taken to complete HTA and to issue reimbursement decision. Trends by country were examined. Results: Time between regulatory approval and HTA reimbursement required a mean of 321 days (Median=214 days; Std.Dev. 330 days). Access in England took the longest, on average, (547 days) to issue a decision compared to the other countries. This time was two to three times longer than any other country. Australia had the shortest time to issue a reimbursement decision, which was approximately 6 months. Conclusions: Approximately one additional year is required after regulatory approval for oncology medicines to complete HTA and receive a reimbursement decision, potentially delaying patient access to oncology medicines outside the USA. The large variability in time to a reimbursement decision by country is likely due to varying processes. Additional research is needed to clarify the impact of these delays on access to care and patient outcomes. [Table: see text]
Asian representation in clinical trials of new drugs for the treatment of cancer.
Authors: Fashoyin-Aje Lola A. , Fernandes Laura L. , Lemery Steven , Keegan Patricia , Sridhara Rajeshwari , Bull Jonca C. , Pazdur Richard 
Published: September 2018

6564 Background: In the US, statistics for Asians are often aggregated with other racial groups. This poses challenges in estimating the cancer burden and in defining cancer clinical trial enrollment targets in this demographic subgroup. ‘Asian‘ refers to persons with origins in the Far East, Southeast Asia, or the Indian sub-continent. Asians comprise 6% of the US population and the largest Asian subgroups in the US are of Chinese (22%), Filipino (19%), Asian Indian (19%), Vietnamese (10%), Korean (9%), and Japanese (7%) descent. The representation of Asian patients in global clinical trials may not be reflective of the Asian subgroups in the US. FDA conducted an analysis to describe patients categorized as ‘Asian’ in clinical trials supporting the approval of new drugs. Methods: We reviewed the marketing applications of 33 new molecular entities approved for the treatment of solid tumor malignancies between 2011- 2016 to identify trials that provided the primary evidence of safety and efficacy. Results: A total of 29,941 patients were enrolled; 17 % were Asian. Most Asian patients were enrolled in Korea (20%), Taiwan (20%), mainland China (20%), Japan (16%), and US (5%). Few patients were enrolled in India (3%); the Philippines (1%); Vietnam (0). In the US, Asian patients comprised 3% of the total number of patients enrolled. Conclusions: Asian patients represented a heterogeneous mix. A large proportion was enrolled in Taiwan (20%) and Korea (20%), whereas the largest proportion of US Asians have origins in mainland China (22%), the Philippines (19%), India (19%), and Vietnam (10%). Nevertheless, although Asians share a common ancestry, it is not clear whether data from global clinical trials are generalizable to Asian patients in the US. Therefore, strategies to improve the enrollment of US Asian patients in clinical trials are needed. Among patients enrolled in the US, 3% were Asians, a proportion that is below US Asian population estimates (6%). While most site-specific cancer incidence and death rates are lower in US Asians compared to Whites, the rates of some cancers (e. g., stomach and liver) are higher in this group. Therefore, studies are needed to determine adequate enrollment targets in this demographic subgroup.