bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.