bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab (pembro) for recurrent head and neck squamous cell carcinoma (HNSCC): Post hoc analyses of phase 3 KEYNOTE-040 prior radiation treatment (RT) and disease state.
Authors: Harrington Kevin J. , Cohen Ezra E.W. , Soulieres Denis , Dinis José , Licitra Lisa F. , Ahn Myung-Ju , Soria Ainara , Machiels Jean-Pascal H. , Mach Nicolas , Mehra Ranee , Burtness Barbara , Lin Jianxin , Cheng Jonathan D. , Swaby Ramona F. , Le Tourneau Christophe 
Published: May 2019

6026 Background: The open-label, randomized, phase 3 KEYNOTE-040 study (NCT02252042) showed that pembro vs standard of care (SOC) chemotherapy prolonged survival in patients (pts) with recurrent and/or metastatic HNSCC whose disease progressed during/after platinum-based therapy. Post hoc analyses were conducted to evaluate pembro vs SOC by prior RT and disease state (metastatic, locoregionally recurrent [referred to as recurrent herein], or recurrent and metastatic [R/M]). Methods: Pts (N = 495) were randomly assigned (1:1) to receive pembro (200 mg Q3W) or investigator choice of methotrexate (40 mg/m2 QW), docetaxel (75 mg/m2 Q3W), or cetuximab (400 mg/m2 loading dose, then 250 mg/m2 QW). Primary end point was OS; PFS and ORR were secondary end points. Results: 175, 97, and 195 pts had metastatic, recurrent, and R/M disease, respectively (28 pts had unknown disease state); 64 pts had no prior RT; 431 pts had prior RT. As in the ITT population, prolonged survival benefit and trend toward improved PFS and ORR was observed with pembro vs SOC in pts with prior RT (Table), and prolonged survival benefit was observed with pembro vs SOC in pts with metastatic and R/M, but not recurrent, disease. Conclusions: In this post hoc analysis, patients with prior RT benefited from treatment with pembro vs SOC. For patients without RT, sample sizes are too small to draw any definitive conclusions. Survival benefit of pembro vs SOC was observed in pts with metastatic and R/M disease. Clinical trial information: NCT02252042. [Table: see text]
Apatinib for locoregionally recurrent or metastatic nasopharyngeal carcinoma after failure of first-line chemotherapy: A multicenter, phase II trial.
Authors: Jiang Wei , Liang Jinghui , Pan Yufei , Ruan Xiaolan , Cai Rui , He Zhuokai , Chen Qiuqiu , Zhang Rongjun , Yang Xi , Liu Meilian , Zhao Bo , Liu Zhengchun , Niu Zhijie 
Published: May 2019

6030 Background: Concordant programs for patients with nasopharyngeal carcinoma (NPC) who failed to first-line chemotherapy after locoregional recurrence or metastasis are not yet available. Here, we investigated the efficacy and safety of apatinib as an second-line treatment in these patients. Methods: In this multicenter, phase II trial, patients of NPC with disease progression after failure of first-line chemotherapy were treated with apatinib (500mg/d).The primary endpoint of this study was objective response rate (ORR), secondary endpoints included progression free survival (PFS), overall survival (OS) and toxicity. Results: Between January and December 2017, 33 patients were finally enrolled onto the analysis from three centers in China. The baseline characteristics were summarized in Table. Of the 12 patients achieved a partial response and no complete responses were observed, yielding an ORR of 36.3%. Additionally, 6 patients (18.2%) experienced stable disease of at least 5 months in duration, and the disease control rate was 54.5%. At a median follow-up time of 14 months (range 1-22), median PFS was 5.0 months (95% CI, 2.3 to 7.7). The median OS had not reached, and the 1-year OS rate was 83.1%. The most common adverse events (grade 1 to 2) related to apatinib were hypetension (42.4%), hand-foot syndrome (54.5%), proteinuria (12.1%) and oral ulcer (24.2%). Conclusions: Apatinib showed a well therapeutic effect and a manageable safety profile for patients of advanced NPC after previous chemotherapy. Further study in combination with chemotherapy and other targeted agents in patients with NPC is warranted. Baseline demographic and disease characteristics. Clinical trial information: NCT03130270. [Table: see text]
A safety study of nivolumab in patients with recurrent and/or metastatic platinum-refractory squamous cell carcinoma of the head and neck (R/M SCCHN): Interim analysis on 199 patients—The TOPNIVO study on behalf of the GORTEC and the Unicancer Head & Neck Group.
Authors: Even Caroline , Daste Amaury , Saada-Bouzid Esma , Lefebvre Gautier , Fayette Jerome , Zanetta Sylvie , Kaminsky Marie-Christine , Cupissol Didier , Prevost Alain , Vauleon Elodie , Johnson Alison Claire , Salas Sebastien , Rolland Frederic , Timar David Miruna , Jallut Isabelle , Delaye Jessy , Bourhis Jean , Guigay Joel , Texier Matthieu , Auperin Anne 
Published: May 2019

6032 Background: In the randomized phase III Study CA209141, Nivolumab (N) demonstrated significant overall survival (OS) benefit with favorable safety profile for platinum refractory R/M SCCHN and is now approved for these patients (pts). The objectives of the study are to provide additional insight into the frequency of high-grade AEs related to N and the efficacy of N in real life. Methods: Between August and December 2017, 203 pts were included in the multicenter, non-controlled phase II TOPNIVO. The main inclusion criteria were patients with platinum refractory R/M SCCHN with progressive disease, ECOG 0-2. Pts received N 3mg/kg every 2 weeks intravenously over 30 minutes. Four pts did not receive N. We report here the safety during the first 6 months (mo) after inclusion and OS results on the first 199 treated pts. Results: Median age was 62 yr, 83% were male, 84% were ECOG 0-1, 16% 2. The primary site of cancer was oral cavity 26%, oropharynx 38%, larynx 16%, hypopharynx 21%. 33% had loco regional relapse, 32% metastatic disease and 35% both. 49% had received one prior line of chemotherapy and 30% two prior lines. 157 (79%) pts ended their treatment within the first six mo: 5 for AE related to N (pneumonitis 3 pts, hepatitis 1 pt, diarrhea 1 pt), 107 for progression, 33 for death (24 related to progression, 9 to intercurrent disease), 12 other. 132 pts (66%) experienced at least 1 AE grade ≥3. On the 226 AEs grade 3-4, 21 (mainly pneumopathy, lipase increase and asthenia) were related to N and occurred in 18 pts. On the 51 AEs grade 5, 3 were considered related to N (2 pneumonitis, 1 cardiac arrest). The median OS was 7.7 mo (CI 95% [6.0; 9.5]) in the whole population; 9.2 mo [6.8; 12.1] in the 167 pts with ECOG 0-1, 3.0 mo [1.1; 6.0] in the 32 pts with ECOG 2; 12.1 mo [7.6; NR] in the 64 pts with metastatic disease, 7.7 mo [5.0; 9.6] in the 66 pts with locoregional disease and 4.6 mo [3.1; 7.9] in the 69 pts with both. OS was similar in pts older or younger 70 yr. Conclusions: The interim analysis of the TOPNIVO study shows no additional toxicities of N compared to what has been described previously, confirms the previous results of OS and provides new survival data in subgroups of pts. Clinical trial information: NCT03226756.
Efficacy and safety of immune checkpoint inhibitors in elderly patients (≥70 years) with squamous cell carcinoma of the head and neck.
Authors: Even Caroline , Martin Nicolas , Borcoman Edith , Auperin Anne , Torossian Nouritza , Baste Neus , Guigay Joel , Le Tourneau Christophe , Saada Esma , Daste Amaury , Saleh Khalil 
Published: May 2019

6035 Background: Recent meta-analysis showed that immune checkpoint inhibitors (ICI) have comparable activity in younger vs older patients (pts) (≥65 years (y)). However little is known about efficacy and safety of ICI in elderly pts with relapsed/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The aim of this study is to compare efficacy and grade ≥3 immune-related adverse events (irAEs) of ICI in pts ≥70 y with R/M SCCHN to younger pts. Methods: A retrospective study was conducted at 4 French hospitals. Eligibility criteria were pts treated with ICI for R/M SCCHN between September 2014 and December 2018. Clinical and radiological data and outcome were collected from review of medical records. Results: Two hundred twenty six pts were enrolled including 67 pts ≥ 70 y. Median age of elderly pts was 75y (range 70-87). Elderly pts received ICI as first-line treatment in 21% of pts vs 17% in younger pts. In elderly pts, 9% had ECOG of 0, 72% had ECOG of 1 and 15% had ECOG of 2 at ICI initiation vs 34%, 62% and 4% respectively in younger pts (p = 0.0006). In elderly pts, 22% had only loco-regional relapse at ICI initiation, 30% only distant recurrence and 49% had both vs 42%, 32% and 26% respectively (p = 0.0014). Elderly pts received ICI as monotherapy in 73% of pts vs 52% (p = 0.0027). The ORR in elderly pts was 23% vs 13% in younger pts (p = 0.071). After a median follow-up of 16.8 months (m) (range 10.7-23.7), median OS was 9.7m in elderly pts vs 8.7m in younger pts (p = 0.87). Median PFS was 2.7 m in elderly pts vs 1.9 m (p = 0.2). After adjustment for ECOG, type of evolution, number of ICI drugs, time between initial diagnosis and ICI start and number of previous lines, age ≥70 years was significantly associated with a better PFS (HR = 0.66 (95%CI = 0.47;0.93), p = 0.02) but was not significantly associated with OS (HR = 0.91 (95%CI = 0.61;1.34), p = 0.62). Grade ≥3 irAEs occurred in 15% of elderly pts vs 8% of younger pts (p = 0.13). Patients with grade ≥3 irAEs had a significantly higher ORR than pts without Grade ≥3 irAEs (36% vs 14%, p = 0.007). Conclusions: Elderly pts treated with ICI had significantly higher PFS but not OS after adjustment. Grade ≥3 irAEs were associated with significantly higher ORR to ICI in the whole population.
Phase 1b/2, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Authors: Cohen Ezra E.W. , Nabell Lisle , Wong Deborah J.L. , Day Terry A , Daniels Gregory A. , Milhem Mohammed M. , Deva Sanjeev , Jameson Michael B. , Guntinas-Lichius Orlando , Almubarak Mohammed , Strother Robert Matthew , Whitman Eric D. , Chisamore Michael Jon , Obiozor Cynthia Chinedu , Bagulho Teresa , Candia Albert , Gamelin Erick , Janssen Robert , Algazi Alain Patrick 
Published: May 2019

6039 Background: SD-101, a synthetic CpG-ODN agonist of TLR9, stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells - activating T cell anti-tumor responses. Pembrolizumab has demonstrated activity in HNSCC. Study DV3-MEL-01 (NCT02521870) assesses safety and efficacy of SD-101 in combination with pembrolizumab in patients with recurrent/metastatic HNSCC. We have previously reported a 27.3% ORR in 22 patients receiving 8 mg SD-101/injection in the modified ITT after at least 2 CT scans due to late responses (Abstract 3560, ESMO 2018). Higher efficacy at a lower SD-101 dose, 2 mg/injection, has been reported in advanced melanoma patients (LBA 45, ESMO 2018). Consequently, this dose is now being assessed in HNSCC. We report preliminary data with the 2 mg/injection dose in 23 patients in mITT at the first CT scan. Methods: Anti-PD-1/PD-L1 naïve patients received 2 mg SD-101 intratumorally in 1 - 4 lesions (weekly x 4 doses then Q3W x 7 doses). Pembrolizumab is was administered IV at 200 mg Q3W. Responses were assessed per RECIST v1.1. Results: 28 patients enrolled: median age 63 y/o, male 68%; ECOG PS 0-1 (18%/82%); mean prior lines of systemic therapy 1 (0-3); mean treatment duration 70 days (1-253). Primary tumors: 19 (68%) oropharyngeal; 3 (10%) laryngeal; 2 (7%) hypopharyngeal; 4 (14%) unknown. Mean number of target lesions: 1.82 (1 to 5). HPV status: 7 (25%) +, 9 (32%) -, 12 (43%) unknown. 18 (64 %) discontinued treatment: 12 (42%) due to PD, 4 (16%) deaths, 1 (3%) consent withdrawn, 1 (3%) went to hospice. Mean follow up 2.70 months. Safety: 16 non-treatment-related SAEs in 9 patients. 2 treatment-related Grade ≥3 AEs: sepsis (4%) and lymphopenia (4% ). No treatment-related deaths. Efficacy: 23 patients in the mITT population with first CT scan at day 64: ORR: CR: 2, PR: 3 (22%); SD: 6 (26%), PD: 7 (30%), non-evaluable: 5 (22%). Disease control rate (48%). 5 patients on study have not had a CT scan. Conclusions: SD-101 with Pembrolizumab shows early promising data and is well tolerated. Additional follow-up scans from both dose cohorts are being evaluated and will be presented. Clinical trial information: NCT02521870.
Predictors of early immunotherapy response in head and neck cancer: Per lesion analysis of a prospective randomized trial with nivolumab.
Authors: Yu Yao , Chen Linda , Riaz Nadeem , Kang Jung , Tsai C. Jillian , Sherman Eric Jeffrey , Lee Nancy Y. , McBride Sean Matthew 
Published: May 2019

6041 Background: The capacity for radiation and checkpoint inhibitors to elicit clinical responses is impacted by tumor immunogenicity and the immune microenvironment. We sought to determine whether head and neck primary site and metastatic tumor location was associated with initial response in non-irradiated lesions. Methods: We evaluated response in 144 non-irradiated lesions from 59 patients with metastatic head and neck cancer enrolled on a phase II randomized controlled trial of nivolumab with stereotactic body radiotherapy (n=30) vs. nivolumab alone (n=29). Nivolumab was administered 3 mg/kg intravenously every 2 weeks. Radiated lesions were treated with 27 Gy / 3 fractions to a single lesion within 14 days of the first dose of nivolumab. Non-target lesion progression was defined ≥30% increase in the greatest axial diameter 8 weeks after enrollment. Fisher’s exact test with nested bootstrap resampling was used for univariate analysis. Logistic regression with a mixed random effects term was used for multivariate analysis. Results: Primary tumor site, metastatic tumor organ sites, and the unadjusted likelihood of progressive disease by site are listed in the table. On multivariate logistic regression controlling for PD-L1 status (p=0.66) and viral status (p=0.29), lymph node metastases (OR 0.79, p=0.0064) were associated with decreased risk of progression, while liver metastases (OR 1.39, p=0.014) and oral cavity primaries (OR 1.56, p=0.018) were associated with increased risk of progression at 8 weeks, using lung metastases and larynx/hypopharynx primaries as reference. Conclusions: Primary tumor subsite and metastasis location were predictors of response or stable disease following treatment with nivolumab. Metastases from oral cavity primaries and metastases to the liver were at increased risk of early progression. Clinical trial information: NCT02684253. [Table: see text]
Association between human papillomavirus (HPV) status and duration of response of anti-programmed cell death protein-1 (PD-1) inhibitors in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Authors: Kirtane Kedar , Muzaffar Jameel , Slebos Robbert , Chung Christine H. 
Published: May 2019

6044 Background: Human papillomavirus status is known to be prognostic for patients with HNSCC. Current data suggests that HPV-positive HNSCC tumors exhibit increased infiltration of immune cells and higher levels of T-cell exhaustion markers compared with HPV-negative tumors, possibly suggesting a difference in response patterns to immunotherapy. We evaluated whether HPV status is associated with duration of response in patients receiving anti-PD-1 inhibitors. Methods: We performed a retrospective chart review of 54 patients at Moffitt Cancer Center who received either pembrolizumab (N = 32) or nivolumab (N = 22) from February 2016 to July 2018 for R/M HNSCC. We collected the following data for our patient population: primary site of disease, stage, smoking status, duration of treatment, and overall survival (OS). Overall survival time was defined as the date of starting anti-PD-1 inhibitors to death. Primary disease site was oropharynx (N = 25), oral cavity (N = 13), larynx (N = 11), nasopharynx (N = 3) and unknown primary (N = 2). HPV status was available for 37 patients. Analysis of survival and time on treatment was done using log-rank test. Results: Overall survival was not different with respect to primary site of disease, smoking, ECOG status, or type of anti-PD-1 inhibitor, but was significantly longer for patients with HPV-positive vs HPV-negative HNSCCs (17 months vs 4.5 months; log rank p < 0.001). Time on anti-PD-1 inhibitor was also significantly longer for patients with HPV-positive HNSCCs (7 months vs 3 months; log rank p < 0.001). Conclusions: Our data suggests patients with HPV-positive R/M HNSCCs have longer duration of response and OS on anti-PD-1 inhibitors compared to HPV-negative patients.
Association of single nucleotide polymorphisms within genes in NF-κB, TGF-β, and JNK signaling pathways with the risks of nasopharyngeal carcinoma in Chinese Han.
Authors: Zhang Hanyi , Lu Shun , Lang Jinyi 
Published: May 2019

6053 Background: Nasopharyngeal Carcinoma(NPC) is an Epstein-Barr virus(EBV) associated malignancy with remarkable ethnic and geographical distribution. The EBV oncoprotein latent membrane protein 1 (LMP1) is the primary oncogene of EBV infection through the its signaling cascade and its connections to other pathways including NF-κB, TGF-β and JNK signaling, which plays an important role in the pathogenesis of NPC. In GWASs(Genome-wide association studies) associations these pathways were also identified. Single nucleotide polymorphisms (SNPs) in the regulatory regions may regulate the expression of genes in these pathways, or affect the function of the coded protein. Methods: Altogether 149 SNPs were covered by the 15 SNPs in the TRAF2, TRAF3, NFKBIA, MAP2K4, and CHUK genes were genotyped in a hospital-based case-control study of 350 NPC cases and 587 healthy controls from the Chinese Han. The observed genotype frequencies in the controls were tested for Hardy–Weinberg equilibrium (HWE) using the chi-square test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between genotypes and NPC risk and tumor characteristics were calculated by logistic regression, and they were adjusted for multiple testing using the SNP spectral deposition (SNPSpD) approach for multilocus analyses. Results: We found one NFKBIA SNP was associated with NPC risk after adjustment for multiple comparisons. Minor allele carriers of the NFKBIA had an increased risk of NPC (P < 0.05). The analyses were adjusted for age and gender. For a polymorphism with a variant allele frequency between 10 %and 50%, the study had greater than 90% power to detect an OR of 1.50 at a significance level of 0.05 (PS—software for power and sample size calculation, http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize). The other genotyped SNPs were not associated with NPC risk. Conclusions: Our data suggests that genetic variation especially in the NFKBIA maybe a useful biomarker for NPC screening and further studies are warranted.
Risk of mortality varies by type of fat consumed in a longitudinal cohort of head and neck cancer patients.
Authors: Taha Hania M. , Rozek Laura S. , Chen Yi Tang , Slade Alexander N , Wolf Gregory T. , Arthur Anna 
Published: May 2019

6056 Background: Dietary interventions have promise for improving cancer outcomes, but remain an understudied area of cancer care. The relationship between head and neck squamous cell carcinoma (HNSCC) mortality and dietary fat intake has not yet been examined. The objective of this study was to determine how pre- and post-treatment intake of various types of fat are associated with disease-specific and all-cause mortality in adults diagnosed with HNSCC. Methods: Our sample included 472 newly diagnosed HNSCC patients recruited into the University of Michigan Head and Neck Specialized Program of Research Excellence (HN-SPORE) between 2008 and 2012. Participants completed pre-treatment and post-treatment Food Frequency Questionnaires (FFQs) and health surveys. Multivariable Cox Proportional Hazards models were used to test the associations between both the type and quantity of fat intake (categorized into tertiles: low, medium and high intake) and time to mortality, after adjusting for relevant covariates. Fat types included animal, vegetable, medium-chain-fatty-acids (MCFA), long-chain-fatty-acids (LCFA), unsaturated, saturated, and trans. Results: During the study period, there were 144 total deaths and 97 cancer-specific deaths. In considering pre-treatment dietary intake, compared to low intake levels of LCFA, high intake was associated with a reduced risk of all-cause mortality (HR: 0.57; 95% CI: 0.34–0.94). High intakes of unsaturated-fats were associated with a reduced risk of HNSCC-specific mortality compared to low intake (HR 0.52; 95% CI: 0.29–0.93). Considering post-treatment dietary variables, medium (HR: 0.21; 95% CI: 0.08–0.49) and high (HR: 0.41; 95% CI: 0.21–0.78) total fat intakes were associated with reduced risk of all-cause mortality compared to low intake. Medium (HR: 0.25; 95% CI: 0.08–0.67) and high (HR: 0.26; 95% CI: 0.09–0.67) total fat intakes were associated with reduced risk of HNSCC-specific mortality compared to low intake. Conclusions: Our data suggest that HNSCC prognosis may vary depending on both the type and quantity of fats consumed, specifically total fat and long chain fatty acids. Clinical intervention trials are needed to further examine this hypothesis.
Tumor volume, circulating tumor cells, and cfDNA changes during radiotherapy in patients with head and neck cancer.
Authors: Ng Sweet Ping , Hall Carolyn S. , Meas Salyna , Sarli Vanessa Nicole , Cardenas Carlos , Bahig Houda , Elgohari Baher , Moreno Amy Catherine , Skinner Heath Devin , Garden Adam S. , Rosenthal David Ira , Morrison William H. , Phan Jack , Gunn Gary Brandon , Frank Steven J. , Fuller Clifton David , Lucci Anthony 
Published: May 2019

6062 Background: Head and neck (HN) cancer treatment response relies heavily on macroscopic clinical findings. Monitoring of circulating markers during treatment may improve detection of responders versus non-responders during radiotherapy (RT). Our work prospectively describes the changes in gross tumor volume (GTV), circulating tumor cell (CTC), and cell-free DNA (cfDNA) enumeration during RT. Methods: Patients with intact HN squamous cell carcinoma were enrolled in a prospective IRB-approved study. Pre-, after first RT, weekly in-, and post-RT blood samples were collected. Serial pre-, weekly in-, and post-RT magnetic resonance imaging (MRI) was obtained. Serial GTV measurements were recorded. CTC was enumerated using the FDA-approved CellSearch (Menarini Silicon Biosystems) system. Plasma were collected and cfNA from pre-, mid- and post-RT timepoints were isolated using the MagMAX Nucleic Acid Isolation Kit (Thermo Fisher Scientific), and cfDNA were quantified with Qubit high sensitivity dsDNA assay (Invitrogen). Results: 40 patients were eligible for analysis. Median age was 60 years and 36 were males. The median pre-RT GTV was 14.1cc (range 1.3 – 44.9cc). There was a median reduction of 81% in GTV by week 4 (p < 0.0001). Of the 341 samples analyzed for CTC, 146 (43%) had detectable CTC. 7 patients had detectable pre-RT CTCs (1-3/7.5ml blood). There was no correlation between cancer stage, nodal status, and GTV with detection of CTC. After 1 fraction of RT, 14 patients had CTCs detected, including 11 who had no CTC detected prior. All patients had CTC detected at some point during RT except for 2 patients who had none. In week 4, with significant reduction in GTV, 25 (63%) had detectable CTC. 16 and 11 patients had detectable CTC in final week and post-RT timepoints. The cfDNA levels increased during RT, with its highest level in the final week of RT and lowest at post-RT time-point, inversely correlated with GTV. Conclusions: Our study showed that CTCs can be detected during RT, suggesting mobilization into peripheral circulation during RT with unknown viability. cfDNA kinetics during RT correlated with CTC release, and may indicate apoptotic change during RT. Combined cfDNA-CTC as an early marker of treatment response should be investigated further.