bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Biomarker predictors of outcome from a randomized trial of nivolumab +/- stereotactic body radiotherapy (SBRT) in metastatic (M1) head and neck squamous cell carcinoma (HNSCC).
Authors: McBride Sean Matthew , Lee Nancy Y. , Pfister David G. , Sherman Eric Jeffrey , Tsai C. Jillian , Aghalar Jahan , Eng Juliana , Zhi Wanqing Iris , McFarland Daniel Curtis , Michel Loren S. , Dunn Lara , Ho Alan Loh , Riaz Nadeem
Published: May 2019

6063

Background: A minority of patients with M1 HNSCC respond to the anti-programmed death (PD-1) monoclonal antibody, Nivolumab (Nivo). We sought to determine biomarker predictors of outcome to Nivo in M1 HNSCC. Methods: Patients with M1 HNSCC were randomized (n = 60) with stratification by virus status (EBV/HPV+ vs not) to either Nivo alone or Nivo+SBRT to a single lesion. The primary end-point was objective response rate (ORR) in non-irradiated lesions with overall survival (OS) as a secondary end-point. PD-L1 staining in ≥ 1% of tumor cells was regarded as positive. Tumor mutation burden (TMB) was determined using a next generation sequencing assay (MSK IMPACT). Predictive model selection was done to minimize the Akaike Information Criterion (AIC). Results: There was no difference in ORR comparing the two treatment arms (p = 0.86). On univariate analysis, virus status trended towards predicting both ORR (Positive 41.9% vs Negative 20.7%, (p = 0.14)) and OS (1-yr OS for Positive, 65.9% vs 1-yr OS for Negative 40.6%, p = 0.08). In the sub-group of patients for whom PDL1 staining was available (n = 56), there was a trend towards association with ORR: PDL1+ 50% vs PDL1- 23.5% (p = 0.08). PDL1+ patients demonstrated significantly longer OS (1-yr OS 63% vs 47%, p = 0.02). There was no association between virus status and PDL1 staining. IMPACT data was available in 46 patients. TMB was significantly higher in virus negative (mean 8.1 mut/mB) vs. virus positive (mean 4.6 mut/mB) (p = 0.01); TMB was similar comparing PDL1+ to PDL1- (p = 0.47). TMB was higher in responders than non-responders (p = 0.02); TMB was significantly higher in virus positive responders (p = 0.01) and trended towards being higher in virus negative responders (p = 0.10). A model to predict ORR that included PDL1, virus status, and TMB minimized AIC with a C-index of 0.72. A model to predict OS that included PDL1 and virus status minimized AIC with a C-index of 0.62. Conclusions: A multi-variate model including viral status, PDL1 status, and TMB predicts well response to Nivolumab in M1 HNSCC. A model containing PDL1 and virus had moderate predictive value for OS. Clinical trial information: NCT02684253.
Induction chemotherapy with and without erlotinib in patients with oral cavity squamous cell carcinomas (OCSCCs) amenable for surgical resection.
Authors: Le Xiuning , Pickering Curtis R. , Rubin M. Laura , Netto Frederico , Kies Merrill S. , Johnson Faye M. , Lu Charles , Blumenschein George R. , Bell Diana , Ginsberg Lawrence E. , Wilson Kaye F , Lewis Jeff , Feng Lei , Wang Jing , Lee J. Jack , William William Nassib , Myers Jeffrey
Published: May 2019

6067

Background: We have previously demonstrated activity of erlotinib in head and neck SCCs as monotherapy prior to surgical resection, or in combination with chemotherapy for recurrent/metastatic disease (William et al. ASCO 2011, 2017). The aim of this study was to evaluate the efficacy of induction chemotherapy with a platinum-taxane regimen and explore the potential benefit of erlotinib as part of induction therapy in patients with resectable OCSCCs. Methods: This was a randomized, placebo-controlled, phase II trial of induction chemotherapy (cisplatin 75 mg/m2 or carboplatin AUC 6 with docetaxel 75 mg/m2 every 3 weeks for 3 cycles) with erlotinib (150mg oral daily) or placebo in patients with OCSCCs stage III-IVB amenable for surgical resection. The primary endpoint was major pathological response (MPR, defined as < 10% viable tumor cells in the surgical specimen). Secondary endpoints included safety and long-term efficacy outcomes. Results: From April 1, 2014, to June 7, 2017, 52 patients were enrolled, of whom 47 underwent planned surgery. MPR was achieved in 7/23 (30%) in the erlotinib group and 10/24 (41%) in the placebo group. With a median follow up of 26.5 months, the 2-year long-term progression-fee survival (PFS) were estimated at 75% (95% CI: 59.5-94.5) in the erlotinib arm, and 58.6% (95% CI: 40.9-84.1) in the placebo arm, and 2-year overall survival at 73.5% (95% CI: 57.2-94.5) for the erlotinib group and 73.1% (95% CI: 55.9-95.6) for the placebo group. In patients who achieved MPR (n = 17), the 2-year PFS was 77.4% (95% CI: 57.3-100), compared to 64.5% (95% CI: 49.0-84.8) in patients who did not achieve MPR (n = 29, p = .16). All 7 patients in the erlotinib group who achieved MPR remained disease-free. The majority of patients (87%) completed all 3 cycles of induction chemotherapy. The common side effects were expected and distributed similarly between erlotinib and placebo groups. As expected, rash, diarrhea and dehydration were more common in the erlotinib group. Conclusions: Platinum and docetaxel-based induction chemotherapy induced major pathological response in 17/47 (36%) of resectable OCSSC patients. Two-year overall survival was 73%. Responders had improved long-term outcome. Addition of erlotinib did not improve the rate of MPR, but might have contributed to improved PFS. Clinical trial information: NCT01927744.
Impact of smoking cessation in locally advanced head and neck cancers undergoing radiation.
Authors: Sacks Ruth Lauren , Cui Yong , Karam-Hage Maher A.
Published: May 2019

6068

Background: Multiple studies have highlighted the negative outcomes associated with smoking during radiation (XRT) for locally advanced head and neck cancer. However, there has been little research investigating the potential benefit of smoking cessation prior to XRT and the effect on response rates, relapse, distant metastases, secondary malignancies, and overall survival. Methods: We reviewed 680 patients at the University of Texas MD Anderson Cancer Center from 2005-2012 with locally advanced head and neck cancer undergoing XRT. 127 were referred to the Tobacco Treatment Program (TTP) based on provider referrals, self-referrals, or screening. Of those referred and retrospectively reviewed, 89 were identified as current smokers and 41 of them participated in the TTP for smoking cessation. Among these 89 patients, 50 patients (18 participated in the TTP) quit smoking prior to XRT and 29 patients (19 participated in the TTP) continued to smoke, which are referred to as Quitters and Smokers, respectively. 10 patients (2 participated in the TTP) had incomplete data and were excluded from further analysis. Results: Quitters had 100% complete response (CR) on initial assessment following XRT. 7/50 (14%) developed relapsed disease with 4 local recurrences (LR) and 3 distant metastases (DM). 6/50 (12%) developed secondary malignancies. By contrast, Smokers had 96.5% CR on initial assessment following XRT. 8/29 (27.5%) developed relapsed disease with 6 LR and 2 DM. 6/29 (20.6%) developed secondary malignancies. The median follow ups for Quitters and Smokers were 57.5 and 54 months with overall survival rates of 82% and 79%, respectively. Conclusions: Current smokers that achieved smoking cessation prior to XRT demonstrated lower rates of relapse, DM, and secondary malignancies compared to those that continued to smoke. Thus, smoking cessation is an integral part of head and neck cancer treatment and needs to be further incorporated in cancer care to improve cancer treatment outcomes. As a future direction, a comparable group of patients who did not smoke from the same time range will be compared for response rates, LR, DM, secondary malignancies, and survival.
A phase II trial cohort of nivolumab plus ipilimumab in patients (Pts) with recurrent/metastatic adenoid cystic carcinoma (R/M ACC).
Authors: Tchekmedyian Vatche , Sherman Eric Jeffrey , Dunn Lara , Fetten James Vincent , Michel Loren S. , Kriplani Anuja , Morris Luc , Ostrovnaya Irina , Katabi Nora , Haque Sofia , Tran Crystal , Azar Julian , Pfister David G. , Ho Alan Loh
Published: May 2019

6084

Background: R/M ACC is a malignant neoplasm most commonly of salivary gland origin with no standard treatment. The impact of combined PD-1/CTLA-4 checkpoint blockade in R/M ACC is unknown. Methods: In a two-stage minimax phase II trial, pts with progressive R/M ACC (non-salivary primaries allowed) were enrolled and treated with nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (1 cycle = 6 weeks). Imaging, using RECIST v1.1 response assessment, was scheduled to be performed approximately every 12 weeks. The primary endpoint was overall response rate (ORR = complete response [CR]+partial response [PR]) per RECIST v1.1. To detect a difference between an unacceptable ORR of 5% and a desirable ORR of 20% (one-sided type I error of 10%, power of 90%), at least 1 in the first 18 pts required an observed response. At least 4 responses of 32 total pts were needed to meet the primary endpoint. Treatment beyond progression of disease (PD) was allowed at the discretion of the investigator. A second cohort of pts with non-ACC salivary cancer is still accruing for separate analysis. Results: From 6/12/2017-6/20/2018, 32 pts were enrolled and evaluable for the primary endpoint. There was 1 confirmed PR in the first 18 pts, therefore enrollment of the second stage continued. ORR was 6% (2/32). One additional pt had an unconfirmed PR (-31% regression before CNS PD). For best overall response, there were 2 PRs, 15 SD, and 11 PD. Four pts never reached a first disease assessment: 3 due to death from clinical PD and 1 was removed for toxicity. Six pts discontinued the trial for toxicities (Grade 4 (G4) neutropenia/sepsis and G3 adrenal insufficiency (1), G2 hypophysitis (2), G3 arthritis > 7 days (1), G3 colitis (1), and G3 hepatitis/G4 creatinine kinase (CK) elevation (1)). The 2 confirmed PRs consisted of -73.1% and -58.4% regressions, with a duration of therapy of 18.4 and 7.8 months, respectively (treatment ongoing for both). Conclusions: The study did not meet its primary endpoint, though the responses observed were dramatic. Paired biopsy and peripheral blood samples will be analyzed to elucidate insights into mechanisms of response and resistance to dual checkpoint blockade. Clinical trial information: NCT03172624.
Pilot study combining PD-L1 antibody durvalumab (D) with CTLA-4 antibody tremelimumab (T) and stereotactic body radiotherapy (SBRT) to treat metastatic anaplastic thyroid cancer (ATC).
Authors: Sherman Eric Jeffrey , Tsai C. Jillian , Zhi Wanqing Iris , Fetten James Vincent , Wu Vanessa , Ho Alan Loh , Riaz Nadeem , Pfister David G. , Lee Nancy Y.
Published: May 2019

6088

Background: ATC is a rare and aggressive cancer with very limited treatment options. The thyroid is one of the most immunogenic organs in the body and PD-L1 is commonly expressed on ATC tumor cells and PD-1 in the inflammatory cells in the ATC microenvironment. However, antibodies to PD-1 as single agents have a poor record in this disease. Methods: This study evaluated the addition of T (75 mg every 4 weeks up to 4 doses) to D (1500 mg every 4 weeks). SBRT 9Gy x 3 fractions was given within the first 2 weeks of treatment to produce an “abscopal” effect. Major inclusion criteria: Metastatic ATC; ECOG PS 0-2; No prior immunotherapy; Last anti-cancer treatment > 7 days prior to starting study. Primary objective 1-year overall survival with target of ≥ 2 out of 12 patients. Results: 12 patients were accrued. Male – 50%; Median PS 1; Median Age – 71 (49-82); Prior radiation to neck (75%); Prior chemotherapy (75%). MSI-High was noted in 2/11 subjects. BRAFV600E mutation in 3/12 subjects. There were 0 confirmed responses and only 1 subject with SD for 4 cycles or longer. Median time on treatment was 11 weeks (1-28+ weeks). MSI status did not affect treatment response. MSI-High patients were on treatment before progression for 8-14 weeks. Median overall survival was 14.5 weeks with only one person alive past 1 year. Neither the presence of a BRAF or p53 mutation appeared to affect either outcome. Conclusions: T/D with SBRT was not active in metastatic ATC. Future studies looking at other novel immunotherapy combinations in ATC should be evaluated. Biopsies done on study are being analyzed. Clinical trial information: NCT03122496.
Effect of montelukast and rupatadine on rituximab infusion time, rate, severity of reactions, and cost of administration.
Authors: Kotchetkov Rouslan , McLean Jesse , Gerard Lauren , Nay Derek , Hopkins Sean P.
Published: May 2019

6500

Background: Rituximab is associated with frequent infusion reactions which carry significant burden to patients and health care practitioners. Standard pre-medications (SP) do not prevent reactions sufficiently. Rupatidine (R) and Montelukast (M) are used for symptomatic treatment of urticaria and allergic rhinitis. We assessed addition of R, M and their combination on Rituximab infusion, rate, severity of reactions and cost of administration. Methods: Adult patients with lymphoproliferative disorders treated at our cancer center between Jan 2018 to Jan 2019 were evaluated with Rituximab-containing regiments. Since the majority of reactions occur during the first infusion, our study was limited to the initial Rituximab treatment. Patients received either SP with diphenhydramine/acetaminophen and additional R, M or R+M combination. Comparative analysis of infusion time/rate, severity of infusion reactions, number of rescue medications and cost of Rituximab infusions among groups was performed using one-way ANOVA with Tukey post-hoc or chi-square. The study was approved by our institutional IRB. Results: Patients received either: 1) SP; 2) SP + Rupatadine (R) 10 mg; 3) SP + Montelukast (M) 10 mg; or 4) both (SP+R+M). Patient demographics are shown in the table. Compared to SP, the R, M and R+M groups had greater improvement in Rituximab delivery. Mean infusion time was 306 [range 235-441] min. in SP, 254 [105-390] in M, 265 [193-350] in R and 248 [196-342] in R+M groups, (p=0.0001). Infusion reactions occurred in 92% in SP vs. 38, 45, 33% in M, R and R+M groups (p=0.0001). Median reaction grade was 2 in SP, 1 (M), 0 (R and R+M). Median number of rescue medications was 3 [0-10] in SP vs 0 [0-7] in M, R and R+M groups. Cost of rescue medications (US$) was 38 [0-63] (SP), 11 [0-50] (M), 17 [0-63] (R), 12 [0-58] (R+M) groups (p<0.0001). Mean nursing cost (US$) per patient infusion was calculated as 269 [207-388] in SP vs 222 [92-343] (M), 233 [170-308] (R), 218 [174-301] (R+M) group. Conclusions: Addition of R, M and particularly R+M significantly improved Rituximab delivery, lowered the rate and severity of infusion reactions, and lowered the cost of Rituximab administration. [Table: see text]
Quality of end-of-life cancer care at minority-serving US cancer centers: A retrospective study of Medicare claims data.
Authors: Wasp Garrett , Alam Shama S , Brooks Gabriel A. , Khayal Inas S , Kapadia Nirav S. , Carmicheal Donald Q , Austin Andrea M , Barnato Amber
Published: May 2019

6507

Background: Higher EOL treatment intensity is burdensome and has been defined as low-quality care. We explored cancer centers’ EOL quality outcomes among minority and white patients and evaluated whether minority-serving cancer centers had systematically lower EOL quality. Methods: We conducted a retrospective cohort study of Medicare beneficiaries with poor-prognosis cancers who died between April 1, 2016 and December 31 2016. We attributed patients’ EOL treatment to the cancer center where they received the preponderance of inpatient services during the last 6 months of life. We then compared age-sex-comorbidity adjusted center-level measures of EOL care (EOL chemotherapy, emergency department (ED) use, intensive care unit (ICU) admission, hospice use, life-sustaining treatment use, palliative care, and advance care planning) between minority (black, Hispanic, Asian, other) and non-Hispanic white (white) patients within the same center and across centers, grouped by concentration of minorities served (low: < 15%, medium 15-30%, and high > 30%). Results: Among 126,434 patients, 10,006 (21.4% minority) received treatment at one of 53 National Cancer Institute-designated and/or National Comprehensive Cancer Network-affiliated cancer centers. Only 4/8 quality measures had sufficient sample size to calculate a minority-specific rate for ≥10 centers. Those measures showed high within-center correlation for minority and white patients (ICU admission: r = 0.79,p < 0.001; no hospice referral: r = 0.70,p < 0.0001; life sustaining treatment: r = 0.73,p = 0.004; and palliative care: r = 0.78,p < 0.0001), but the mean adjusted rate for minority versus white patients was significantly worse for two measures: no hospice referral (40.2% v. 37.2%; p < 0.02) and life-sustaining treatments (21.8% v. 19.4%; p < 0.02). When grouped by concentration of minorities served (low/medium/high), 5/8 measures showed systematically lower quality as the concentration of minorities increased: more than 1 ED visit (6.0/8.5/7.7%; p = 0.002), ICU admission (29.1/29.7/35.1%; p = 0.0004), no hospice referral (34.3/38.7/36.8% (p = 0.005), and life sustaining treatments (14.8/16.7/17.9%; p = 0.005). Conclusions: There were systematic differences in end-of-life quality measures across US cancer centers. For many measures, quality was lower at centers that served a greater concentration of minorities. However, EOL care quality for minority and white patients was similar for most but not all measures within any given center.
The impact of routine ESAS use on overall survival: Results of a population-based retrospective matched cohort analysis.
Authors: Barbera Lisa Catherine , Sutradhar Rinku , Earle Craig , Mittmann Nicole , Seow Hsien , Howell Doris , Li Qing , Deva Thiruchelvam
Published: May 2019

6509

Background: The study objective was to examine the impact of routine Edmonton Symptom Assessment System (ESAS) use on overall survival among adult cancer patients. We hypothesized that patients exposed to ESAS would have better overall survival rates than those who didn’t have ESAS. Methods: The effect of ESAS screening on survival was evaluated in a retrospective matched cohort study. The cohort included all Ontario patients aged 18 or older who were diagnosed with cancer between 2007 and 2015. Patients completing at least one ESAS assessment during the study were considered exposed. The index date was the day of their first ESAS assessment. Follow up time for each patient was segmented into one of three phases: initial, continuing, or palliative care. Exposed and unexposed patients were matched 1:1 using hard (birth year ± 2 years, cancer diagnosis date ± 1 year, cancer type and sex) and propensity-score matching (14 measures including cancer stage, treatments received, and comorbidity). Matched patients were followed until death or the end of study at Dec 31, 2015. Kaplan-Meier curves and multivariable Cox regression were used to evaluate the impact of ESAS on survival. Results: There were 128,893 pairs well matched on all baseline characteristics (standardized difference < 0.1). The probability of survival within the first 5 years was higher among those exposed to ESAS compared to those who were not (73.8% vs. 72.0%, P-value < 0.0001). In the multivariable Cox regression model, ESAS assessment was significantly associated with a decreased mortality risk (HR: 0.49, 95% CI: 0.48-0.49) and this protective effect was seen across all phases. Conclusions: ESAS exposure is associated with improved survival in cancer patients, in all phases of care. To the extent possible, extensive matching methods have mitigated biases inherent to observational data. This provides real world evidence of the impact of routine symptom assessment in cancer care.
Phase III non-randomized controlled trial of PROMPT-Care, an eHealth intervention utilizing patient reported outcomes in routine clinical care: Impact on emergency department presentations.
Authors: Girgis Afaf , Durcinoska Ivana , Arnold Anthony , Kaadan Nasreen , Miller Andrew Alexis , Descallar Joseph , Delaney Geoff ,   PROMPT-Care Program Group
Published: May 2019

6510

Background: The significant impact of routine assessment and clinical utilization of patient-reported outcomes (PRO) on patient and survival outcomes and reduced emergency department (ED) presentations has been demonstrated in specific patient populations (e.g. advanced cancer). This controlled trial evaluated the impact of an eHealth system, PROMPT-Care, on ED presentations in a diverse population of cancer patients from four oncology treatments centers. Methods: All adult patients receiving cancer care (including adjuvant therapy and follow-up) were eligible, excepting those with a diagnosis of a hematological malignancy, insufficient English literacy or no internet access outside of the clinic. Intervention (PROMPT-Care) patients completed monthly online assessments comprising 61 items of distress, common symptoms and unmet needs, with PRO results electronically transferred into the electronic medical record (EMR). In “real-time”, the care team accessed patients’ PRO summary reports to guide their care, an email alert notified nurses of ongoing unresolved issues between visits, and patients received links to support self-management. Control group patients (n = 2,288) comprised the general cancer patient population receiving usual care at the participating cancer therapy centers. Multivariable negative binomial regression was used to compare between-group differences. Results: From April 2016 to March 2018, 345 eligible patients (mean age 62, 58% female, 27% stage IV) participated and were sent at least four assessments within the first six months on trial. On average, control patients had 30 ED presentations and PROMPT-Care patients had 21 ED presentations per 10,000 patient days. After adjusting for age, sex and stage of disease, PROMPT-Care patients had 26% (95% CI 0.2%, 57%) fewer ED presentations compared to the control group (p = 0.0483). Conclusions: The PROMPT-Care intervention resulted in significantly fewer ED presentations in a broad population of cancer patients, including those currently undergoing cancer treatment or are in follow-up, and patients with a wide range of tumor types. The results support its utility as an improved model for ongoing supportive care for a diverse population, with potential healthcare cost savings. Clinical trial information: ACTRN12616000615482.
Enhancing community capacity to improve cancer care delivery and the effect on patient-reported outcomes, healthcare utilization and total costs of care.
Authors: Patel Manali I. , Ramirez David , Agajanian Richy , Agajanian Hilda H. , Bhattacharya Jay , Coker Tumaini
Published: May 2019

6522

Background: To curb rising expenditures and improve patient-reported outcomes (PROs), we designed an intervention with patient, caregiver, provider, and payer input. The intervention is based on prior work using a lay health worker (LHW) to assess advanced cancer patients' symptoms. In this study, we trained the LHW to refer patients to palliative care and/or behavioral health services in response to positive assessments and expanded the intervention to all cancer stages. We implemented the intervention with a health plan and a community oncology group serving elderly racially/ethnically diverse patients to test the effect on symptoms, healthcare use, and total costs. Methods: We enrolled all newly diagnosed health plan beneficiaries with solid and hematologic malignancies from 10/2016 to 11/2017 and compared outcomes to all cancer patients diagnosed in the year prior to the intervention (control arm). Our primary outcome was change in patient-reported symptoms using the Edmonton Symptom Assessment Scale and Personal Health Questionnaire-9 at baseline, 6 and 12 months post-enrollment. Secondarily, we compared 12 month healthcare use and costs. All generalized linear regression models were adjusted for age, stage, comorbidities, diagnosis, and follow-up. Results: 425 patients were in the intervention; 407 in the control. In both groups, mean age was 79 years; 48% were non-Hispanic White, 43% Hispanic, 3% Black, 6% Asian/Pacific Islander; 60% had advanced stages; 28% had breast, 28% had gastrointestinal, and 10% had thoracic cancers. Intervention patients had significantly decreased symptom burden over time as compared with the control (Mean Difference: intervention (-0.77 +/- 0.28 p = 0.01) vs. control: (0.45 +/- 0.25 p = 0.06)); difference in difference: (-0.68 +/- 0.25 p = 0.007)). Depression scores also significantly decreased over time among intervention patients as compared with the control (Mean Difference: intervention (-1.10 +/- 0.38 p = 0.04)) vs control: (1.21 +/- 0.34 p = 0.01); (difference in difference: -2.03 +/- 0.3 p < 0.001)). As compared to the control arm, intervention patients had lower inpatient admissions (0.7 vs. 0.5 p = 0.01) and emergency department visits per thousand patients per year (0.6 vs. 0.42 p = 0.02), and lower median total healthcare costs ($32,270 versus $25,512 p = 0.01). Conclusions: An LHW intervention significantly improved patient-reported outcomes and the value of cancer care delivery and may be a solution to improve burdensome and costly care for patients.