bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of adjuvant chemotherapy and cumulative cisplatin dose in locally advanced nasopharyngeal carcinoma (LA-NPC) treated with definitive chemoradiotherapy.
Authors: Oliva Bernal Marc , Huang Shao Hui , Taylor Rachel , Su Jie , Xu Wei , Hansen Aaron Richard , Jang Raymond Woo-Jun , Bayley Andrew , Hosni Ali , Giuliani Meredith Elana , Ringash Jolie , Bratman Scott Victor , Cho John , Irish Jonathan Crawford , Waldron John , Weinreb Ilan , Kim John , O'Sullivan Brian , Siu Lillian L. , Spreafico Anna 
Published: May 2019

6046 Background: Total cumulative cisplatin dose (CDDP-D) (concurrent/induction/adjuvant) in multimodality therapy for LA-NPC has been associated with survival at centers in Asia. We evaluated the survival impact of adjuvant chemotherapy (adj chemo) and total CDDP-D in a large, single institution Canadian cohort of LA-NPC. Methods: Patients (Pts) withWHO type II and III LA-NPC treated with concurrent IMRT with high-dose CDDP and adj chemo with CDDP/Carboplatin and 5-FU (maximum total/adjuvant CDDP-D= 540/240 mg/m2) between 2003-2016 were analyzed. EBER status was tested by ISH. Staging was classified by UICC/AJCC7thedition TNM. Kaplan-Meier 5-year (5y) for overall survival (OS) and recurrence-free survival (RFS) were calculated and compared by log-rank test betweenstage, adj chemo (yes vs no) and total CDDP-D (>300 vs ≤300mg/m2). Multivariable analysis (MVA) identified survival predictors. Results: A total of 312 pts were evaluated: median age = 49.8 (range 17.4-75.9); EBER+/-/unknown=67%/1%/32%; stage II/III/IV=2%/51%/47%; T4=36%; N3=17%; adj chemo=83% (21% switched to carboplatin); median total/adjuvant CDDP-D=380/160 mg/m2; median follow-up 7.6 years (range 0.6-14.9). 5y OS differed by stage II-III vs IV (95% vs 80%, p<0.001) and total CDDP-D >300 vs ≤300mg/m2 (89% vs 83%, p=0.02). Adj chemo and total CDDP-D impacted 5y OS in stage IV (table). 5y RFS was higher in stage IV with total CDDP-D >300 vs ≤300mg/m2 (74% vs 59%, p=0.03), with a trend in locoregional control (LRC) (91% vs 80%, p=0.05) but not significant on distant control (DC) (78% vs 72%, p=0.36). Conclusions: Total CDDP-D >300 mg/m2 impacts OS in the overall cohort. The benefit of adj chemo and total CDDP-D on OS and RFS is significant in stage IV but not stage II-III LA-NPC, mainly due to higher LRC rather than DC. [Table: see text]
Pretreatment obesity prolongs survival in elderly patients (≥65 years) with head and neck cancer (HNC).
Authors: Desai Parth Anil , Kakarla Sushanth , Saksena Annapurna , Choi Byeongyeob , Goros Martin , Miller Frank R. , Karnad Anand B. , Cervantez Sherri Rauenzahn 
Published: May 2019

6052 Background: Pre-treatment Body mass Index (BMI) is an important prognostic factor in HNC with variable survival benefit reported till date. Despite increasing incidence of HNC in geriatric patients there is limited information on prognostic variables in this group. Methods: This is a single center, retrospective cohort study of patients with HNC≥65 years of age at their diagnosis from 2012 to 2016. Patients were stratified by BMI (Class 1- BMI<25 kg/m2 (underweight & normal), Class 2- BMI≥25-29.9 kg/m2 (overweight), Class 3- BMI≥30 kg/m2 (obese) ). Various variables were collected & appropriate statistical analysis was done. Results: 188 elderly HNC patients with non-metastatic disease were stratified into three BMI groups (Table) & found to have evenly distributed co-variates. The Median OS was significantly higher in class 3 patients (53 months) compared to class 1 (21 months) (p =0.02). In multivariate analysis, class 3 was an independent good prognostic indicator (Hazard ratio=0.44;Range-0.21-0.90, p=0.03). Stage, CCI score & gastrostomy tube were adverse prognostic factors in the study. Conclusions: Obese elderly HNC patients have survival benefit over normal/underweight patients. Predictive prognostic models incorporating BMI with other prognostic factors are needed to determine appropriate management in these patients. [Table: see text]
Immune signatures associated with response to neoadjuvant PD-1 blockade in oral cavity cancer.
Authors: Knochelmann Hannah , Horton Joshua Dean , Meek Megan , Krieg Carsten , Timmers Cynthia Dawn , Romeo Martin , Wrangle John M. , Rubinstein Mark P. , Young M Rita I , Neskey David , Paulos Chrystal 
Published: May 2019

6055 Background: PD-1 inhibition therapy has revolutionized clinical medicine as it can mediate durable responses in a small cohort of patients. Yet, it remains incompletely understood why these patients respond. To address this question, we studied patients with oral cavity squamous cell carcinoma (OCSCC) to elucidate immune phenotypes associated with response to nivolumab. Methods: We defined the immune profile from the blood and tumor of patients on neoadjuvant nivolumab. We tested if tumor-infiltrating lymphocytes (TIL) could be preferentially expanded ex vivo from nivolumab-responsive patients versus those who were either non-responsive or had never received nivolumab. During the course of therapy, we comprehensively profiled a number of surface markers on patients’ T cells to define their activation status, cytotoxic capacity and memory phenotype. Moreover, the immune profile of the peripheral blood was assessed pre- and post-nivolumab using high dimensional mass cytometry. Results: Regardless of PD-1 therapy, TIL were successfully expanded from 11 of the 12 patients. TIL were comprised of both CD4+ and CD8+ T cells. Additional investigation revealed that the frequency of CD4+ T cells and effector memory T cells in TIL correlated with disease progression (CD4: p = 0.04, r = 0.74, effector memory: p = 0.046, r = 0.74). TILs from responders expressed higher CD26 (p = 0.007, r = -0.88) and Tim3 (p = 0.045, r = -0.74) while PD-1, Lag3, and Ox40 were not differentially expressed based on response. Spearman correlation and Mann Whitney U test were used to assess phenotypic differences. Conclusions: We demonstrate, for the first time, that TIL can be reliably expanded from OCSCC patients on neoadjuvant nivolumab. Moreover, individuals who were responsive to PD-1 blockade had TIL expressing high levels of CD26 and Tim3. Future studies will explore if these markers are predictive of responses and if they contribute to treatment outcome.
Safety and disease control achieved with the addition of nivolumab (Nivo) to chemoradiotherapy (CRT) for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG Foundation 3504.
Authors: Gillison Maura L. , Ferris Robert L. , Harris Jonathan , Colevas A. Dimitrios , Mell Loren K. , Kong Christina , Jordan Richard C. , Moore Kevin , Truong Minh Tam , Kirsch Claudia , Clump David Anthony , Ohr James , He Kai , Blakaj Dukagjin , Deeken John F. , Machtay Mitchell , Curran Walter John , Le Quynh-Thu 
Published: May 2019

6073 Background: Nivo, which inhibits the programmed death-1 (PD-1) receptor, improved survival for pts with platinum-refractory recurrent/metastatic HNSCC. A clinical trial evaluated the safety of adding nivo to 4 standard intensity modulated (chemo) radiotherapy (RT) regimens (see table) for pts with newly diagnosed IR/HR HNSCC. Primary endpoint was safety and feasibility. Methods: Eligibility included IR (p16+ oropharynx [op], T1-2N2b-N3/T3-4N0-3, >10 pack-years [pys], or T4N0-N3/T1-3N3, ≤10 pys) & HR HNSCC (oral cavity, larynx, hypopharynx, p16- op, T1-2N2a-N3/T3-4N0-3). 10 pts/arm (8 evaluable; 0-2/8 DLTs acceptable). Nivo (dose & schedule varied per arm) started 2 wks pre-RT & continued 3 months post-RT. Feasibility of adjuvant nivo months 3-12 post-RT defined as ≥4 of 8 pts/arm received 7 doses. Arm 4 limited to age ≥70, Zubrod performance status (PS) 2, CrCl <50 ml/min, grade ≥2 hearing loss or ≥ grade 3 neuropathy. Results: Characteristics of 39/40 treated pts: median age 62, 79% male, 49% PS0, 38% HR, 67% >10 pys, 62% p16+ op, 72% T3-4, 85% N2-3. Grade ≥3 nivo-related AEs: adrenal insufficiency, diarrhea-3, anemia, fatigue-2, mucositis-3, nausea, vomiting, lipase increase-6, amylase increase-2, lymphocyte/neutrophil/WBC decrease-4, hyponatremia-3, anorexia, maculo-papular rash. SAE in 4/10, 4/9, 5/10 & 4/10. DLTs, adjuvant chemo feasibility, median follow-up (mo), progression or death events per arm shown in table. Conclusions: Nivo concomitant with all (chemo)RT regimens was safe for patients with newly diagnosed IR/HR HNSCC but adjuvant nivo was infeasible after high-dose cisplatin or in cisplatin-ineligible patients ( NCT02764593 ). Preliminary data on progression/death is provided. Acknowledgements: Support for this study was provided by Bristol-Myers Squibb Company. Clinical trial information: NCT02764593. [Table: see text]
Cost-effectiveness analysis of chemoradiation compared to radiation alone in the treatment of nonmetastatic oropharyngeal cancer.
Authors: Albarmawi Husam , Onukwugha Ebere , Cullen Kevin J. , Goloubeva Olga G. 
Published: May 2019

6075 Background: Using concurrent chemoradiation (CRT) to treat oropharyngeal cancer (OPC) has increased since 2000. However, there is limited information regarding the cost-effectiveness of CRT compared to radiation alone (RT) especially given the approval of cetuximab (cetux) in 2006. We conducted a cost-effectiveness analysis of 1) platinum-based CRT compared to RT and 2) cetuximab plus RT (cetux+RT) compared to RT to determine the value of CRT over time. Methods: In this retrospective cohort study, we identified non-metastatic OPC patients aged 66 years or older diagnosed between 2000-2011 using the linked Surveillance, Epidemiology and End Results -Medicare dataset. We defined two cohorts based on the diagnosis period: 2000-2005 (Cohort I) and 2006-2011 (Cohort II). Cetux+RT was identified in Cohort II only. We matched the platinum-based CRT and cetux+RT groups to the RT groups using propensity score models that included age, race, marital status, income, Charlson Comorbidity Index and stage at diagnosis. The outcomes were incremental cost, incremental life-year gained (LYG) and incremental cost-effectiveness ratio (ICER) during the 3 years after diagnosis. Costs were estimated from the Medicare perspective and using 2017 USD. Results: 2,646 OPC patients were eligible for the study. The estimated parameters with the corresponding 95% confidence intervals (CI) are shown in the table. Conclusions: From 2000-2005, platinum-based CRT was a cost-effective option compared to RT. From 2006-2011 and compared to RT, platinum-based CRT provided a survival benefit at higher costs while cetux+RT patients incurred higher costs with no survival benefit. [Table: see text]
Randomized phase II study with or without induction chemotherapy combined with accelerated high dose radiotherapy and cetuximab in locally advanced unresectable HPV positive squamous cell carcinoma of the head and neck.
Authors: Friesland Signe , Mercke Clas , Sjödin Helena , von Dobeln Gabriella , Carstens Hanna , Margolin Gregory , Bjorgvinsson Einar , Lax Ingmar , Gubanski Michael , Embring Anna , Farrajota Neves Da Silva Pedro , Nilsson Josef , Wickart-Johansson Gun 
Published: May 2019

6077 Background: Concomitant chemoradiotherapy (CT/RT) is the standard treatment for locally advanced non- resectable squamous cell carcinoma of the head and neck. Acute side effects can be serious and late effects important. Patients with HPV+ tumors carry a better prognosis than other patients. De-escalation studies are explored with respect to RT, dose, fractionation, target volumes, adjuvant pharmacotherapy, with encouraging results. However, several patients still recur locoregionally, also in high dose RT volumes. Some patients have distant metastases, often with massive tumor burden and late during follow up (FU). Purpose of the study: 1.To evaluate the effect of induction chemotherapy (IC) on (a) progression free survival (b) distant metastases as first site of failure (c) locoregional failure (d) pattern of tumor response, spatial and timely, exploring the possibility to reduce RT dose and/or target volume(s) in future protocols. 2. to address the impact of high dose RT for bulky disease, T3/T4 given concurrent with cetuximab (E). Methods: Patients had previously untreated stage III/IV (>80 % st IV; TNM 7th), M0 disease, WHO 0-1, unresectable squamous cell carcinoma of the head and neck, HPV positive as evaluated with p16 and/or PCR. Pts were randomised between 2 arms. Pts in arm A were scheduled for 2 cycles of TPF : T (docetaxel) 75 mg/m2 day 1, P (cisplatin) 75 mg/m2 day 1 and F (fluorouracil) 1000 mg/m2 over 24 hours day 1-4. RT was delivered with IMRT to all pts : 68 Gy in 6 weeks for T1/T2 tumors, 76 Gy in 6.5 weeks for T3/T4 tumors with E given one week before and weekly during RT. Tumor response was evaluated according to RECIST with CT, MRI or PET/CT after IC, at 6-8 weeks, 1 and 2 years FU. Results: From january 2011 to february 2016, 152 consecutive pts were enrolled, 77 in arm A. All pts had oropharyngeal cancer. In arm A, 7 pts had CR after TPF, 19 had PR out of 36 evaluable pts. At 2 years FU 70/77 pts (91%) were alive in arm A, 69/75 (92%) in arm B. Distant metastases as first site of failure was 3 (3.9%) in arm A and 7 (9.3%) in arm B. Adverse events grade 3-4, ever registered, were seen in 71 pts in arm A and 63 in arm B, were transient, most often related to RT. Conclusions: Survival and locoregional control at 2 years was high and similar in both arms. Distant metastases as first site of failure was more than doubled in arm B, not having induction chemotherapy (IC). Clinical trial information: EudraCT number: 2009-013438-26.
Influence of tumor size and Eastern Cooperative Oncology Group performance status (ECOG PS) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (RR-DTC).
Authors: Wirth Lori J. , Leboulleux Sophie , Kiyota Naomi , Tahara Makoto , Muro Kei , Ahn Myung-Ju , Ando Yuichi , Taylor Matthew H. , Takahashi Shunji , Kim Sung-Bae , Misir Soamnauth , Dutcus Corina E. , Xie Ran , Joshi Prashant Ramesh , Hughes Brett Gordon Maxwell , Aller Javier , Krzyzanowska Monika K. , Capdevila Jaume 
Published: May 2019

6081 Background: In SELECT, lenvatinib significantly improved progression-free survival (PFS) of pts with RR-DTC versus placebo (18.3 v 3.6 months; hazard ratio [HR]: 0.21 [99% CI: 0.14, 0.31]; P<0.001). Here we examine the treatment of RR-DTC with lenvatinib in relation to tumor size (sum of all targeted lesions) and ECOG PS. Methods: In this post hoc analysis of SELECT with pts randomized to receive lenvatinib, Kaplan-Meier estimates of time to ECOG PS ≥2 were calculated for subgroups of pts according to baseline ECOG PS or tumor size. Objective response rate (ORR) and Kaplan-Meier estimates of overall survival (OS) and PFS according to ECOG PS (0 or 1) at baseline were calculated. Correlations between ECOG PS at baseline (0 or 1) and maximum tumor shrinkage were calculated using one-way analysis of variance. Results: Pts with ECOG PS 0 or 1 at baseline had similar demographic and disease characteristics. ORR was 78.5% and 51.0% for pts with ECOG PS 0 and 1 at baseline, respectively (odds ratio [95% CI]: 3.508 [2.018, 6.097]). Mean maximum percent decrease in tumor size was significantly greater in pts with baseline ECOG PS 0 (-46.13%) versus pts with ECOG PS 1 (-37.16%; P=0.0017). For pts with ECOG PS 1 at baseline, time to ECOG PS ≥2 was numerically shorter with tumor size >60 mm versus tumor size ≤60 mm (HR [95% CI]: 1.450 [0.708, 2.967]). Additional results are summarized in the table. Conclusions: Among pts with RR-DTC, PFS, OS, ORR, and time to ECOG ≥2 were generally better for patients with lower ECOG PS or smaller tumor size at baseline. These results may indicate that it is beneficial to start lenvatinib in pts with RR-DTC early, before ECOG PS worsens and tumor size increases. Clinical trial information: NCT01321554. [Table: see text]
A randomized phase II study of pembrolizumab with or without radiation in patients with recurrent or metastatic adenoid cystic carcinoma.
Authors: Schoenfeld Jonathan Daniel , Mahmood Umair , Chen Yu-Hui , Mak Raymond H. , Lorch Jochen H. , Hanna Glenn J. , Sridharan Vishwajith , Bang Andrew , Busse Paul Martin , Willers Henning , Mamon Harvey J. , Yoo Hyung-Jin , Pai Sara I. , Wirth Lori J. , Haddad Robert I. , Chau Nicole Grace 
Published: May 2019

6082 Background: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy characterized by a high rate of distant recurrence. Systemic therapy has generally failed to produce durable benefit. Radiation (RT) is used for localized disease and as directed treatment for metastases. Here, we report the safety and efficacy of pembrolizumab (pembro) administered with or without hypofractionated RT in a phase II randomized study. Methods: Eligible patients (pts) had recurrent or metastatic ACC with evidence of progressive disease (PD) within the last 12 mos and >=1 measurable non-CNS lesion, along with 1-5 additional lesions deemed appropriate for RT to 30 Gy in 5 fractions. Pts were randomized to pembro alone (200 mg IV q3 weeks) or in combination with RT given within 7 days of cycle 1, day 1. The primary endpoint was objective response rate (ORR) outside the RT field by RECIST 1.1. Using a parallel two-stage design, if >=1 response out of 10 was observed in either arm, 10 more pts would be enrolled to that arm. If >=3 responded, the null hypothesis (ORR=5%) would be rejected in favor of a 25% ORR. Predefined secondary endpoints included progression free survival (PFS) and toxicity. Analyses of tumor growth rate (TGR) excluding RT lesions and immune biomarkers were exploratory. Results: Ten pts per arm were randomized into the trial’s first stage with median age 65 (45-79). No objective responses were seen. Stable disease (SD) was observed in 13 pts; 6 had PD as best response, 1 was unevaluable. Median PFS was 7 mos 95% CI (3 - 13 mos), with 9 pts without progression at 6 mos. 3 pts remain on study treatment (range 8-11 mos). In pts with SD, TGR decreased by >25% in 7 of 12 pts and by >75% in 4 pts. There was no difference in likelihood of SD or PFS between arms. Treatment related AEs (TRAEs) occurred in 18 pts but there were no G3-5 TRAEs. Among 8 biopsies analyzed, PD-L1+ tumor/immune cells ranged from 12-52%. Conclusions: Pembro alone or with hypofractionated RT was well tolerated. We observed no objective responses, but 65% of pts with PD prior to study entry achieved SD, the majority with decreased TGR, and 15% had prolonged SD. Additional strategies are needed to further delay progression and effect response. Clinical trial information: NCT03087019.
Economic analysis of alternative pembrolizumab and nivolumab dosing strategies at an academic cancer center.
Authors: Hall Evan Thomas , Zhang Jenny , Kim Eun-Jeong , Hwang Grace , Bhatia Shailender , Reddy Sunil A. 
Published: May 2019

6504 Background: Pembrolizumab (P) and nivolumab (N) were initially investigated and FDA-approved with weight-based dosing strategies, but later the approval label was amended to a fixed dose administration. Given increasing concerns about financial toxicity of cancer therapies, we hypothesize that weight-based dosing of P and N and allowing vial sharing among patients will result in substantial cost savings. Methods: We obtained IRB approval to retrospectively examine all outpatient doses of P and N given at three Stanford Medicine infusion centers between July 1, 2018 and Oct 31, 2018 using the Stanford Medicine Research Data Repository (STARR) database. We performed cost-minimization analysis modeling the impact of dosing strategies based upon patient weight versus fixed dosing (2 mg/kg vs 200 mg q3wks for P; 3 mg/kg vs 240 mg q2wks or 6 mg/kg vs 480 q4wks for N). “Dose-minimization” (DM) was defined as whichever dose was lower (weight-based or fixed dose). The impact of allowing vial sharing (considering commercially available vial sizes) between patients treated at the same site and on the same date was assessed. Average sales price (ASP) from Center for Medicare and Medicaid Services for Part B drugs was used for cost estimates. Results: A total of 1,029 doses of P or N were administered across a variety of cancer types. For most doses (N = 789, 77%), the calculated weight-based dose was less than the fixed dose. DM resulted in decreased usage and expenditures of both P and N, and a further decrease was observed with vial sharing. Total savings estimated with DM and vial sharing strategy were > $1.4 million (Table). This amounted to savings of > 22,000 mg of P (112 fixed doses) and > 11000 mg of N (47 fixed doses). Savings were greatest at the highest volume infusion center. Conclusions: Alternative dosing strategies of P and N would result in significantly less drug utilization and pharmaceutical expenditure without anticipated impact on efficacy. Potential barriers to this approach include existing policies regarding vial sharing and drug vial sizes. [Table: see text]
Deployment and integration of a cognitive technology in China: Experiences and lessons learned.
Authors: Li Tianle , Chen Cheng , Zhang Shan-shan , Dankwa-Mullan Irene , Chen Alan , Preininger Anita , Jackson Gretchen Purcell , Liang Jun 
Published: May 2019

6538 Background: Cognitive technologies are rapidly being introduced in oncology for decision-support, prescribing therapy, predicting risk, reducing medical errors and for care management. Few studies have reported on successful approaches for clinical adoption. We report the early adopter experience of BahealIntelligenceTechnologyCo., Ltd. (Baheal), across China within a 2-year period (April 2017-January 2019). We also describe lessons and experiences of oncology users. Methods: Baheal developed collaborative agreements for use of IBM Watson for Oncology (WFO) in 96 hospitals across 8 provinces. Key opinion leaders who saw the potential for AI were recruited as champion advocates. A 29-item survey conducted included usability and integration within clinical workflow. 85 questionnaires were distributed to oncologists who were major WfO users; 51 were completed. All questionnaires were completed anonymously and de-identified prior to analysis. Results: As of January 31, 2019, 866 physicians have entered a total of 52,537 cancer cases into WfO. Most users approved of both the quality (44/51, 86.3%) and comprehensibility (45/51, 88.2%) of treatment options, rationales, and literature references. WfO was most frequently applied in the context of inpatient cases reviewed by a multidisciplinary tumor board (MDT) (44/51, 86.3%). A lack of locally available treatments in WfO was cited as an area for improvement by two-thirds of users (34/51, 66.7%). CDS was rated from 0 (lowest) to 10 (highest) for each of the following uses: EBM medical education (8.1); assistance with literature (7.7); medical care quality control (7.3); second opinion consultations (7.0); case review with tumor board (6.9); and decision support (6.4). Overall, users were willing to recommend CDS to patients and other clinicians (7.3). Conclusions: WfO CDS, employed in a variety of settings, was viewed positively by more than 86% of users, with perceived benefits differing by context. Future incorporation of locally available treatments and understanding reasons for their omission in CDS may increase perceived value, improve standardization, quality of cancer care and equity of care in China.