bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II randomized control trial of erlotinib in combination with celecoxib in patients with operable oral squamous cell carcinoma (OSCC): Erlo-Xib Study.
Authors: Nair Sudhir Vasudevan , Joshi Amit , Patil Vijay Maruti , Noronha Vanita , Sable Nilesh , Mahajan Abhishek , Dharavath Bhasker , Gardi Nilesh , Bal Munita , Nair Deepa , Gupta Tejpal , Laskar Sarbani , Agarwal Jaiprakash , Chaturvedi Pankaj , Dutt Amit , D'Cruz Anil , Gupta Sudeep , Prabhash Kumar 
Published: May 2019

6054 Background: When combined with COX-2 inhibitors, the EGFR tyrosine kinase inhibitor Erlotinib has shown a better antitumor response in preclinical studies. Since high volume hospitals in many countries usually have a longer waiting period for surgery, neoadjuvant targeted therapy may be helpful in reducing disease progression and downstaging oral squamous cell cancers. Methods: Sixty-four treatment-naïve operable oral cancer patients were randomized into a four-arm window of opportunity study consisting of treatment with erlotinib 150mg daily, celecoxib 200mg twice daily, the combination of both or observation alone (NCT02748707). Since the regular wait period for surgery at our hospital was four to five weeks, we planned a 21-day drug treatment versus observation followed by definitive surgery in the fourth week. MRI scans and biopsies were done before and after drug treatment. Post-operative adjuvant treatments were given as per the standard guidelines used for regular patients. Results: There were 10 females and 54 males with a mean and median age of 44 and 45 years respectively. Taking a 20% reduction in the maximum tumor dimension after drug treatment (assessed clinically and radiologically) as partial response, the combination arm had a 60% partial response and a 25% stable disease. Whereas, 60% in the control arm had disease progression. The ratio of the longest tumor dimension at day 21 versus day 0 (Clinical & MRI assessment) also showed a significant difference between the observation vs erlotinib arms (p < 0.001) using Mann-Whitney Test. Grade II/III rashes was the commonly observed toxicity predominantly in the combination arm. Though not powered for survival analysis, a significant difference (p = 0.048) was observed for two-year overall survival for celecoxib + control (60%) versus erlotinib + combination groups (86%) using Kaplan Meier estimator. Biomarker analysis (transcriptome sequencing and IHC) is being done on pre and post-treatment tumor specimens and the final results will be presented. Conclusion: Preoperative targeted therapy with erlotinib and celecoxib combination can arrest disease progression and downstage tumors with possible impact on survival. The identified biomarkers can further refine a future cohort for effective neoadjuvant targeted therapy in oral cancers. Clinical trial information: CTRI/2012/07/002828.
Prophylactic gabapentin decreases fatigue and swallowing difficulty in patients undergoing concurrent chemo-radiation (CCR) for head and neck cancer (HNC): Interim results from a randomized controlled trial.
Authors: Murphy Barbara A. , Ghiam Michael , Niermann Kenneth J. , Cmelak Anthony , Gibson Michael K. , Gilbert Jill , Smith Derek 
Published: May 2019

6059 Background: Preliminary data suggest that gabapentin (G) administered during HNC radiation may decrease treatment associated pain. To confirm this, we undertook a prospective, randomized trial in HNC patients undergoing CCR. Primary outcomes: pain severity (scale of 0-10) and opioid use. Exploratory outcomes: local and systemic symptoms measured by the Vanderbilt Head and Neck Symptom Survey version 2 plus the general symptom survey (VHNSSv2/GSS). We report results of the exploratory endpoints from the interim analysis. Methods: Measures: VHNSSv2 - 50 items, demonstrated reliability/validated, captures acute/chronic local HNC specific symptoms; GSS – 11 item checklist, demonstrated content validity, captures acute/chronic systemic symptoms. Population: HNC patients (≥ stage 2) undergoing primary or adjuvant CCR. Procedures: Randomized to standard pain management (SPM) or SPM + G dose escalated to 900mg tid. VHNSSv2/GSS completed weekly during treatment beginning week 1 and ending the last week of radiation therapy. Results were analyzed using a mixed-effects regression analysis adjusting for baseline levels of each symptom. Results: 71 patients completed a mean of 5.5 surveys. Patients on G experienced a reduction in overall systemic symptoms as measured by the GSS (11-items, p = 0.0073), fatigue (two-items, p = 0.013 ) sleep disturbance (five items, p < 0.0001) , neurosensory eating (3 items, p = 0.026), phlegm-related symptoms (4 items, p = 0.004), and trend to better smell (2 items, p = 0.055). No impact on swallow, xerostomia, voice, dental or musculoskeletal symptoms was noted. Conclusions: This exploratory analysis suggests that G may moderate neurological and neuropsychiatric toxicities in HNC patients undergoing CCR. Further studies are warranted.
Prognostic impact of baseline circulating tumor cells (CTCs) detected by the isolation by size of epithelial tumor cells (ISET) in locally advanced head and neck squamous cell carcinoma (LAHNSCC): Results of a prospective study.
Authors: Oliveira Thiago Bueno , Braun Alexcia Camila , Nicolau Ulisses Ribaldo , Abdallah Emne Ali , Alves Vanessa Silva , Jesus Victor Hugo Fonseca , Calsavara Vinicius Fernando , Kowalski Luiz Paulo , Chinen Ludmilla T.D. 
Published: May 2019

6061 Background: The prognostic impact of CTCs in LAHNSCC is yet to be determined, with conflicting results in previous trials, the majority utilizing cytokeratin dependent techniques for identification and counting of CTCs. The primary objective of this study is to determine the detection rates using the ISET method, and the prognostic role of CTCs in LAHNSCC patients (pts) treated with a curative intent. Methods: In this prospective study, peripheral blood samples of pts with non-metastatic LAHNSCC, stages III/IV, were analyzed for CTCs using the ISET method, in two scenarios: curative surgical resection and adjuvant radiotherapy (CTCs before RT) and candidates for a non-surgical strategy (unresectable or organ preservation) either with upfront RT concurrent with chemotherapy (CT) or cetuximab (CTCs before RT), or preceded by induction CT (CTCs before ICT). Results: Eighty-three pts were included, the majority males (83%), with oropharynx primary (50%) and submitted to ICT (40%). The detection rate of baseline CTCs was 94% (78/83), and CTCs counts were significantly correlated with survival. For each increase of 1 CTC at baseline there was a relative increase of 18% in the risk of death (HR = 1.18; 95%CI: 1.06-1.31; p < 0.001), 16% in the risk of progression (HR = 1.16; 95%CI: 1.04-1.28; p = 0.004) and a reduction of 26% in the odds of complete response to treatment (non-surgical group only - OR = 0.74; 95%CI: 0.58-0.95; p = 0.022). Using the maximum of the standardized log-rank statistic proposed by Lausen and Schumacher we establish cut off points for overall survival (OS) and progression-free survival (PFS). Pts with CTCs < 6.5/ml had an estimated 2y OS of 85.6% versus 22.9% for CTCs ≥ 6.5/ml (HR = 0.18; 95%CI: 0.06-0.49; P < 0.0001) and pts with CTCs ≤ 3.8/ml had an estimated 2y PFS of 71.8% versus 37% for CTCs > 3.8/ml (HR = 0.32; 95%CI:0.15-0.67; p = 0.001). Conclusions: The detection rate of baseline CTCs using the ISET method was very high in LAHNSCC and the counts of CTCs were strongly correlated with survival and response to treatment.
Impact of antiviral prophylaxis in HSV positive patients treated with concurrent chemoradiotherapy for head and neck cancer.
Authors: Letarte Nathalie , Taillefer Vincent-T. , Marty Céline , Lambert Louise , Aubin Francine , Soulieres Denis , Jamal Rahima , Adam Jean-Philippe 
Published: May 2019

6078 Background: Chemoradiotherapy used for the treatment of locally advanced head and neck cancer (HNC) causes a high incidence of mucositis that may be accentuated by a reactivation of herpes simplex virus (HSV). To date, no study has evaluated the impact of antivirals used as prophylaxis to prevent mucositis or their severity. Methods: This is a retrospective observational study including patients who received at least one cycle of concurrent chemoradiotherapy for the treatment of head and neck cancer between January 2014 and June 2017 at the Centre hospitalier de l’Université de Montréal (CHUM). HSV negative patients were excluded. After approval by the IRB, we compared the incidence and severity of mucositis in HSV positive patients who started an antiviral prophylaxis before cycle 1 or 2 (prophylaxis group) to HSV+/unknown HSV patients who did not receive antiviral prophylaxis (control group). Emergency visits and hospitalizations related to mucositis were collected. Mucositis were assessed regularly by radiation oncologists during the treatment. Results: Of 482 patients who received concurrent chemoradiotherapy for HNC, 75 were HSV negative and 407 were included in this study. In the group with (n = 94) and without prophylaxis (n = 313), patients received carboplatin and 5-FU (77% vs 62%) and cisplatin (23% vs 38%) with concurrent radiation respectively. The rate of all grade mucositis in patients with and without prophylaxis (99% vs 96%; p = 0.19) was not statistically significant. The rate of grade 3 and 4 mucositis (42% vs 49%; p = 0.29), the rate of emergency visit (29% vs 28%; p = 0.91) and hospitalization (9% vs 8%; p = 0.80) were not statistically significant between each group. However, in a subgroup of patient receiving carboplatin and 5-FU, antiviral prophylaxis seems to decrease significantly the rate of grade 3 (49% vs 63%; p = 0.04). Conclusions: The addition of antiviral prophylaxis in HSV positive in patients undergoing concurrent chemoradiotherapy for locally advanced HNC didn’t decrease the rate of all grade mucositis. In the subgroup of patients receiving carboplatin and 5-FU mainly of oropharynx origin, HSV prophylaxis decreased the severity of mucositis.
Outcomes of postoperative treatment with concurrent chemoradiotherapy (CRT) in high risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.
Authors: Geiger Jessica Lyn , Woody Neil McIver , Tsai C. Jillian , Ghanem Ahmed I. , Dunlap Neal , Liu Howard , Burkey Brian B. , Lamarre Eric , Ku Jamie , Scharpf Joseph , Joshi Nikhil Purushottam , Caudell Jimmy J. , Siddiqui Farzan , Porceddu Sandro , Lee Nancy Y. , Koyfman Shlomo A. , Adelstein David J. 
Published: May 2019

6080 Background: Adjuvant CRT with high-dose cisplatin remains standard treatment for OCSCC with high risk pathologic features of positive surgical margins (SM+) and/or extranodal extension (ENE). High-dose cisplatin is associated with significant toxicities, and alternative dosing schedules or treatments are used. We evaluated outcomes associated with different systemic therapies concurrent with RT and the effect of cumulative dosing of cisplatin. Methods: An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by systemic therapy received, and resultant groups compared for demographic data, pathologic features, and outcomes by t-test and Chi-squared tests. Kaplan-Meier curves, log-rank p-values, and multivariate analysis (MVA) for disease free survival (DFS) and freedom from metastatic disease (DM). Results: From a total sample size of 1282 pts, 196 pts were identified with high risk features (SM+, ENE) who were treated with adjuvant CRT. Median age was 56 years, 63.3% of pts were men, 81.1% were Caucasian, 70.9% had significant tobacco history. 35.7% of pts had SM+, 82.7% ENE, 65.3% with perineural invasion (PNI), 49% had lymphovascular space invasion (LVSI). There was a trend associating higher cisplatin dose delivered with improved locoregional control, DM, and overall survival (OS) (p-values 0.131, 0.084, and 0.187, respectively). DFS was significantly better with higher cisplatin dose (HR = 0.95 per 100 mg/m2 increase in cisplatin). Administration schedule of cisplatin (weekly versus high-dose) was not significantly associated with DFS. On MVA, PNI and higher cisplatin dose remained statistically significant for DFS (p < 0.001 and 0.007). Median OS by cisplatin dose was 10.5 ( < 200 mg/m2) vs. 20.8 months ( > / = 200 mg/m2). Conclusions: This multi-institutional analysis demonstrated cumulative cisplatin dose > / = 200 mg/m2 was associated with improved DFS in high risk resected OCSCC pts. It remains unclear by this analysis if cisplatin administration schedule has any prognostic implication. Further study is warranted to elucidate the optimal cisplatin schedule for this population.
PROSPERO: A study to determine the utility of focused genomic profiling to guide selection of drug therapy in salivary gland cancer.
Authors: Rack Samuel , Li Yonghan , McKay Craig , Wallace Andrew , Metcalf Robert 
Published: May 2019

6086 Background: For most patients with recurrent or metastatic salivary gland cancer (RM-SGC), there are no standard therapies. Many patients undergo genomic profiling to guide selection of targeted therapy. The MSK-IMPACT study applied a 468 gene next generation sequencing (NGS) panel, identifying actionable mutations in 34/114 patients (30%) with RM-SGC. Minimising cost will facilitate application within publically funded healthcare systems. We therefore sought to determine the utility of genomic profiling using a focused 24 gene targeted NGS panel to identify actionable mutations in RM-SGC with a sub-group analysis in adenoid cystic carcinoma (ACC) and non-ACC sub-types. Methods: From January 2017 to 2018, 125 patients with RM-SGC provided informed consent to an ethically approved study. Clinical and demographic characteristics were collected. DNA was extracted from FFPE samples and analysed using Qiagen GeneRead DNAseq Targeted Panel V2 in the Manchester Centre for Genomic Medicine Diagnostic Laboratory, an NHS clinically accredited lab. A custom bioinformatic pipeline was validated to detect single nucleotide variants and indels ( < 40bp) to 5% mutant allele frequency. Alterations were categorised following American College of Medical Genetics guidelines and Association for Molecular Pathology tiering. Results: DNA from 101 tumours (69 major, 32 minor salivary gland) was sequenced with 95% coverage at > 350x read depth over the target enrichment. 65 patients had adenoid cystic carcinoma (ACC) and 36 had non-ACC SGC. Median age was 55 years (range 18-80). 43 actionable alterations were identified in 33 patients within the following genes: TP53 (21%), PIK3CA (8%), ERBB2 (6%), PTEN (3%), BRAF (2%), EGFR (T790M) (1%), and AKT1 (1%). Targeted therapy was selected based on genomic findings in 12% of these patients. In ACC patients, actionable alterations were seen in 25% compared with 55% of non-ACC patients (9 adenocarcinoma, 5 salivary duct carcinoma, 3 carcinoma ex pleomorphic adenoma, 2 mucoepidermoid carcinoma and 1 myoepithelial carcinoma). Conclusions: This study identified actionable alterations in 33% of SGC patients using focused genomic profiling, demonstrating comparable utility to larger research panels. This focussed panel is being expanded to include emerging biomarkers such as NOTCH gene mutations, with NOTCH inhibitors currently in trials in ACC. Greater access to basket studies incorporating therapies matched to genomic alterations will maximise the clinical utility of this approach.
Preventing excess narcotic prescriptions in MIS urologic oncology discharges (PENN): A prospective cohort quality improvement initiative.
Authors: Talwar Ruchika , Xia Leilei , Serna Juan , Lee Daniel , Ziemba Justin , Guzzo Thomas J. 
Published: May 2019

6502 Background: In the setting of the national opioid crisis, there is increasing interest in non-narcotic pain strategies, particularly for oncology patients. Robotic urologic surgeries for cancer have been shown to result in less pain than open approaches. We hypothesized that the majority of these patients could be safely discharged with adequate analgesia without opioids. Methods: This prospective cohort study aimed to reduce narcotics prescribed at discharge after robotic radical prostatectomy (RARP), robotic radical nephrectomy (RARN) and robotic partial nephrectomy (RAPN). Prior to 9/2018, 100% of patients were discharged on varying amounts of oxycodone (range: 75-337.5 oral morphine milligram equivalents [MME]). We implemented a standard non-opioid analgesia pathway with escalation options across the continuum of care. Patients received gabapentin 300 mg and acetaminophen 975 mg once PO pre-operatively, as well as gabapentin 300 mg every 8 hours, acetaminophen 975 mg every 8 hours PO, and ketorolac 15 mg every 6 hours IV post-operatively. If complaining of persistent pain despite the standing regimen, patients were given 50 mg or 100 mg of tramadol every 6 hours as needed for pain level 5-7 or 8-10 on the visual analog scale, respectively. If requiring further escalation, patients were given 5 or 10 mg of oxycodone every 6 hours as needed on the aforementioned scale. Regardless of escalation status, all patients were discharged on the standing non-narcotic protocol. If escalated, ten pills of tramadol 50 mg or oxycodone 5 mg were prescribed accordingly. Results: Our cohort (n = 170) consisted of patients undergoing RARP (n = 87), RARN (n = 25), RAPN (n = 58) between 9/1/2018-1/9/2019. Overall, 67.7% were discharged without opioids, 24.4% with ten pills of tramadol 50 mg (50 MME) and 8.2% with ten pills of oxycodone 5 mg (75 MME). On multivariate analysis, older age (OR: 0.961, 95% CI: 0.923-0.995, p = 0.026) was associated with lower odds of needing opioids at discharge. There was no difference in postoperative telephone encounters between those discharged with or without opioids. Conclusions: The majority of robotic surgery patients do not require opioids upon discharge. An escalation protocol allows for a patient centered approach to reduce narcotic prescribing while still addressing cancer and surgical pain.
Clinical benefit of breakthrough cancer drugs approved by the United States Food and Drug Administration.
Authors: Molto Consolacion , Hwang Thomas J. , Andres Marta , Borrell Maria , Gich Saladich Ignasi J. , Barnadas Agust , Amir Eitan , Kesselheim Aaron S. , Tibau Martorell Ariadna 
Published: May 2019

6513 Background: The Breakthrough Therapy program was established in July 2012 to expedite drug development and approval by the FDA. We compared the characteristics of clinical trials leading to FDA approval as well as the magnitude of clinical benefit and value framework scores of breakthrough-designated and non-breakthrough-designated cancer drugs. Methods: We searched the Drugs@FDA website for cancer drug approvals from July 2012 and December 2017. For each indication, we applied the value frameworks and used thresholds of high clinical benefit developed by American Society of Clinical Oncology Value Framework version 2 (ASCO VF v2; scores ≥45), the ASCO Cancer Research Committee (OS gains ≥2.5 months PFS gains ≥3 months), the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1; grade of A or B for trials of curative intent and 4 or 5 for those of non-curative intent), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks (scores of 4 and 5). Trial characteristics and value framework scores were compared using Chi squared or Mann Whitney U tests. Results: We identified 106 pivotal trials supporting the approval of 52 individual drugs for 96 indications. Of these indications, 38 (40%) received breakthrough designation. Compared with trials for non-breakthrough drugs (n = 62), trials for breakthrough drugs (n = 44) had smaller sample size (median 373 vs 612, P= .03), were less often randomized (57% vs 86%; P= .001) and more likely to be open-label (84% vs 53%, P= .001). Trials for breakthrough drugs were more likely to demonstrate high clinical benefit using ASCO VF (68% vs 31%, P= .002) and NCCN Evidence Blocks (86% vs 56%, P= .002). A similar proportion of trials supporting breakthrough and non-breakthrough drugs demonstrated high clinical benefit using the ASCO Cancer Research Committee (82% vs 68%, P= .25) and ESMO-MCBS (35% vs 33%; P= .87) frameworks. Conclusions: In patients with advanced solid tumors, cancer drugs approved under breakthrough therapy designation were more likely to demonstrate high clinical benefit as defined by the ASCO VF and NCCN value frameworks. A similar proportion of approved breakthrough and non-breakthrough therapy drugs met the high benefit thresholds using the ASCO Cancer Research Committee and ESMO-MCBS frameworks.
Quantification of the financial burden of antineoplastic agent price increases.
Authors: Alevizakos Michail , Gaitanidis Apostolos , Appleman Leonard Joseph 
Published: May 2019

6519 Background: Antineoplastic medication prices are overall increasing yet this phenomenon is not limited to new medications but can also be observed in already established medications. Methods: We accessed the yearly payment files from Medicare Part B for injectable antineoplastic agents (codes J8501-J9999) for the years 2010-2017 and all costs were adjusted to 2017 USD to adjust for inflation. We then calculated the price-per-dose for every medication and compared that price with the price-per-dose that the medication would have if its initial price was only affected by inflation. We subsequently multiplied the difference with the total doses of the medication administered in order to calculate the additional cost accrued by Medicare from medications whose price had increased more than the inflation rates. Only medications with total annual payments >10 million USD/yr were included in the analysis. Notably, Medicare provides reimbursement based on average U.S. market prices. Results: Price increases were noted on average in 64.5% of already established medications (median 69.6%, range 45.4-74.1%), leading to an average additional extra cost of 243 million USD per year (range 140-330 million USD), for a total of 1.7 billion USD over the 7 years of observation. Rituximab (539 million USD), trastuzumab (221 million USD), and bevacizumab (178 million USD) accrued the highest extra costs. This extra cost represented 4.6-8.9% of the annual total Medicare Part B spending for antineoplastic medications (Table). Conclusions: The majority of already established injectable chemotherapeutics demonstrate price increases that lead to substantial additional financial cost to Medicare and likely other U.S. markets as well. Price increases of Medicare Part B antineoplastic medications with cost >10 million USD/yr. [Table: see text]