bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of radiotherapy, in addition to chemotherapy, on overall survival in the initial management of patients with newly diagnosed metastatic head and neck squamous cell carcinoma.
Authors: Baliga Sujith , Kabarriti Rafi , Ohri Nitin , Guha Chandan , Kalnicki Shalom , Garg Madhur 
Published: September 2018

6035 Background: The role of radiation therapy (RT) in the upfront management of patients with metastatic head and neck squamous cell carcinoma (HNSCC) is not clearly defined. In this study, we used the National Cancer Database (NCDB) to assess the association between RT use and overall survival (OS) for patients with metastatic HNSCC who received chemotherapy. Methods: We analyzed the NCDB to identify patients with newly diagnosed metastatic HNSCC from 2004-2013 who were treated with upfront chemotherapy. Associations between the use of RT and OS were evaluated using the Kaplan Meier method, univariate and multivariate cox regression, propensity score matching, and sequential landmark analysis. Survival outcomes were also compared for patients receiving a biologically effective dose (BED) ≥72 Gy10 and < 72 Gy10. Results: We identified 3,516 patients diagnosed with metastatic HNSCC who were treated with chemotherapy, of which 2,288 (65%) were also treated with RT. The median follow up was 11.9 months. The addition of RT to chemotherapy was associated with prolonged survival (median 13.6 v 11.3 months, logrank p < 0.001). On multivariate analysis, the use of RT remained associated with prolonged survival (HR = 0.71, 95% CI 0.61-0.82, p < 0.001). After propensity score matching, the addition of RT was associated with improved median survival (13.5 v 11.2 months) and 5-year (17% v 7%) OS compared to chemotherapy alone (log rank, p < 0·001). Landmark analyses limited to patients who survived at least 3, 6, and 12 months after diagnosis continued to demonstrate improved OS with the addition of RT. Among patients treated with RT, the use of RT schedules with a BED exceeding 72 Gy10 was associated with prolonged survival (median 18.0 versus 11.7 months, logrank p < 0.001). Conclusions: For patients with metastatic HNSCC, the addition of RT to chemotherapy was associated with improved OS in this population based study. These results provide rationale for prospective randomized trials to validate these findings and to determine the optimal radiation therapy dose/fractionation and treatment schedule for these patients.
A pilot study of the pan-class I PI3K inhibitor buparlisib in combination with cetuximab in patients with recurrent/metastatic head and neck cancer.
Authors: Brisson Ryan J. , Dekker Allison , De Souza Jonas A. , Saloura Vassiliki , Vokes Everett E. , Seiwert Tanguy Y. 
Published: September 2018

6039 Background: R/M HNC carries a poor prognosis with a median survival of 10-12 months. PI3K pathway aberrations are present in 30% of HNC. This pilot dose-escalation study assesses the safety and tolerability of the PI3K inhibitor buparlisib when given concurrently with cetuximab in R/M HNC, as well as assess efficacy in an expansion cohort. Methods: Patients (pts) with R/M HNC who were not amenable to curative intent therapy were enrolled. Pts were given oral buparlisib starting day -7 and daily thereafter. The dose of buparlisib was escalated in a 3+3 design (Level 1: 80mg daily, Level 2: 100 mg daily) followed by a dose expansion cohort. The maximum dose of buparlisib was 100 mg daily. Cetuximab (500mg/m2) was given intravenously every 14 days starting day 0. Pts continued on treatment until progression of disease. Prior cetuximab failure was allowed. Results: Of the 12 pts enrolled, 10 had at least 2 previous treatment regimens (11 with prior cetuximab). 5 pts were HPV+, 4 were HPV-, and 3 had unknown HPV status. 3 pts were treated at the 80 mg dose level while 9 were treated at the 100 mg dose level (3 + 6 patient expansion). Treatment was well tolerated with 2 pts experiencing grade 3 adverse events (AEs) (no grade 4 AEs). The most common AEs were fatigue (83.3%), maculopapular rash (50.0%), and anorexia (50.0%). 3 pts experienced grade 1 anxiety. There were no SAEs. Of the 10 pts who were evaluable for response one patient achieved a PR (10%), and 4 achieved stable disease (40%) per RECIST 1.1. Median overall survival was 280 days (HPV+: 370 days, HPV-:191 days). The study was closed early due to poor enrollment on the expansion cohort as patients opted for concurrently open immunotherapy trials. Conclusions: Based on this pilot study, buparlisib plus cetuximab proved to be well-tolerated and showed limited evidence of activity in a heavily pre-treated patient population. Further research is warranted to determine activity of buparlisib in a larger cohort of R/M HNC. Clinical trial information: NCT01816984.
Characterization of potential predictive biomarkers of response to nivolumab in CheckMate 141 in patients with squamous cell carcinoma of the head and neck (SCCHN).
Authors: Concha-Benavente Fernando , Gillison Maura L. , Blumenschein George R. , Harrington Kevin , Fayette Jérôme , Colevas A. Dimitrios , Licitra Lisa , Kasper Stefan , Even Caroline , Worden Francis P. , Saba Nabil F. , Haddad Robert I. , Tahara Makoto , Hasegawa Yasuhisa , Yen Chia-Jui , Lynch Mark John , Monga Manish , Geese William J. , Vokes Everett E. , Ferris Robert L. 
Published: September 2018

6050 Background: Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, demonstrated longer median overall survival (7.5 vs 5.1 months) and improved response (13.3% vs 5.8%) versus investigator choice chemotherapy (ICC) in patients with recurrent SCCHN after platinum failure in CheckMate 141 (NCT02105636), a randomized, open-label Phase 3 trial. We screened peripheral blood lymphocytes (PBL) to identify biomarkers which may predict response to nivolumab. Methods: Paired baseline (day 1) and on treatment (day 43) PBL samples (n = 36; 24 nivolumab; 12 ICC) were analyzed using multicolor flow cytometry and a non-competing anti-PD-1 antibody. Results were correlated with clinical outcome: responders (complete/partial response) and non-responders (stable or progressive disease). Results: Levels of CD8+ T cells at baseline and on treatment were higher in nivolumab responders compared to non-responders (23% vs 13%; P< 0.05). Interestingly, PD-1+ CD8+ and PD-1+ CTLA-4+ CD8+ effector T cells (likely exhausted T cells) decreased about 2-fold following nivolumab in both responders and non-responders ( P< 0.05), whereas, the decrease in CTLA-4+ CD8+ effector T cells following nivolumab was significant in responders only (8% vs 5%; P< 0.05). Levels of PD-1+ TIM-3+ CD8+ effector cells decreased following nivolumab in non-responders only (11% vs 7%; P< 0.05), a similar non-significant reduction was observed in responders. Levels of PD-1+ Tregs were lower in responders than non-responders at baseline (19% vs 33%; P< 0.01), and following nivolumab (12% vs 20%; P< 0.001). As in T-effector cell populations, PD-1+ Tregs decreased about 1.6-fold after nivolumab in both responders and non-responders ( P< 0.01). Interestingly, baseline Ki67+ Treg levels were lower in non-responders (28% vs 17%; P< 0.05). Conclusions: Response to nivolumab may be associated with higher levels of CD8+ T cells and CTLA-4+ CD8+ effector T cells, and lower PD-1+ CD8+ effector T cells and PD-1+ Tregs at baseline. Targeting both PD-1 and CTLA-4 axes is warranted in SCCHN to overcome suppressive signals in CD8+ effector T cells and in Treg cells expressing both checkpoint receptors. Clinical trial information: NCT02105636.
A phase II randomized, multicentric clinical trail comparing recombinant human endostatin plus intensity-modulated radiotherapy versus concurrent chemoradiotherapy in locally advanced low-risk nasopharyngeal carcinoma.
Authors: Kang Min , Lin Shaomin , Zhu Haisheng , Liao Sihui , Huang Haixin , Yu Bin , Wang Hongqian , Liu Meilian , Zhu Jinxian , Huang Guang , Qin Yutao , Wei Zhuxin , Du Qinghua , Hu Kai , Zhang Tingting , Zhou Pingting , Liao Xueyin , Wang Rensheng 
Published: September 2018

6063 Background: A prospective, randomized, and multicentric phase II study was performed to evaluate the short-term efficacy and safety of Endostar plus intensity-modulated radiotherapy (IMRT) versus concurrent chemoradiotherapy(CCRT) in locally advanced low-risk nasopharyngeal carcinoma(NPC). Methods: From September 2014 to August 2016, 120 patients with low-risk NPC at stages III-IVa from 9 centers were randomly divided into experimental group (Endostar plus radiotherapy (ERT); n = 60) and control group (CCRT; n = 60). ERT patients were given Endostar (7.5 mg/m2/day) by continuous intravenous infusion (CIV) from 5 days before radiotherapy for consecutive 10 days for 2 cycles with an interval of 14 days. Then, ERT patients received 2 cycles of 10 days of maintenance treatment with Endostar after radiotherapy. The CCRT patients were given cisplatin (100 mg/m2) on days 1, 22, and 43 for 3 cycles. Immediate and 3-month efficacy and adverse effects were evaluated between the two groups. ClinicalTrials registration number was NCT02237924. Results: All patients were eligible for toxicity and response analysis. Regarding immediate efficacy, the complete response(CR) rates were 45.0% for ERT arm and 33.3% for CCRT arm in nasopharynx (P = 0.190), and 43.3% for ERT arm and 36.7% for CCRT arm in regional nodes (P = 0.456). Three months after RT, the CR rates were 71.2% for ERT arm and 60.0% for CCRT arm in nasopharynx (P = 0.151), and 74.6% for ERT arm and 63.3% for CCRT arm in regional nodes (P = 0.172). The rate and severity of leukopenia, hemoglobin reduction and thrombocytopenia in ERT arm were significantly lower than CCRT arm (P < 0.01). The occurrence rates of Xerostomia, oral mucositis, nausea / vomiting, constipation and weight loss in ERT arm were significantly lower than those in CCRT arm (P < 0.01). Conclusions: The present study demonstrates that ERT has similar short-term efficacy on locally advanced low-risk NPC compared with CCRT, but the acute adverse effects of ERT are fewer, and the compliance and tolerability of patients are better. Clinical trial information: NCT02237924.
LIHNCS: Lugol’s Iodine in Head and Neck Cancer Surgery—A multi-centre, randomised, controlled trial assessing the effectiveness of Lugol’s Iodine to assist excision of moderate dysplasia, severe dysplasia and carcinoma in-situ at mucosal resection margin of oral and oropharyngeal squamous cell carcinoma.
Authors: McCaul James Anthony , McMahon Jeremy McMahon , Quantrill Jacqueline , Gilbert Kayleigh , Mehanna Hisham Mohamed , Shaw Richard , McConkey Christopher C , Gouldesbrough David , Robinson Max , Dunn Janet 
Published: September 2018

6065 Background: Oral cavity and oropharynx cancer are increasing worldwide but survival has not significantly improved over the last thirty years. Presence of dysplasia or carcinoma in-situ at surgical margins following resection of squamous carcinoma (SCC) of the head and neck is associated with increased local recurrence and reduced survival. While carcinoma can usually be distinguished from normal mucosa, dysplasia is less readily distinguished at operation. We describe outcomes of LIHNCS, a RCT assessing effectiveness of Lugol’s iodine staining for visualization and excision of margin dysplasia at primary surgery. Methods: Patients planned for curative surgical resection of oral cavity/ oropharynx SCC were recruited. Participants were randomised 1:1 into either a standard surgical treatment arm or surgical treatment including Lugol’s iodine staining according to defined SOP. Randomisation was stratified by centre and surgeon using computer-generated random permuted blocks. Data monitors, pathologists and external reviewers were blinded to treatment allocations. Chief investigator, surgeons and other health care professionals were blinded to results. Primary endpoint is presence of carcinoma or dysplasia at mucosal margins. Results: Sixty-five surgeons in 24 centres recruited and LIHNCS was powered for 300 cases. Following successful recruitment, extension was granted for progression to 409, including 300 T1 and T2 cases. Patient acceptance was 89%. Median follow up is 36.5 months and 118 patients have died to date. Significantly fewer patients in the Lugols arm required further mucosal resection after primary surgery (p = 0.005). In as treated analysis dysplasia is reduced at resection margins for T1 and T2 tumours (p = 0.04). Conclusions: Lugol's iodine visualisation of dysplasia at curative surgical resection of oral and oropharynx SCC is associated with reduced requitement for further mucosal resection and appears to result in reduced dysplasia at mucosal resection margins. Clinical trial information: ISRCTN03712770.
Treatment outcomes of 257 patients with locally advanced nasopharyngeal carcinoma treated with nimotuzumab plus intensity-modulated radiotherapy with or without chemotherapy: A single institution experience.
Authors: Zheng Wang Fang , Jiang Chuner 
Published: September 2018

6079 Background: To report the long-term outcome and toxicitie of locally advanced nasopharyngeal carcinoma (NPC) treated with nimotuzumab plus intensity- modulated radiotherapy (IMRT) with or without chemotherapy. Methods: From October 2009 to March 2014, 257 newly histology-proven, non-metastatic NPC patients were retrospectively enrolled. They are aged 10-76 years. The distribution of disease was stage III in 150 (58.4%), stage IV A in 88 (34.2%), and stage IV B in 19 (7.4%). All the patients received the treatment of nimotuzumab plus IMRT, and 239 cases were used for cisplatin-based chemotherapy. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival was calculated according to the Kaplan-Meier method. Log-rank test was used to compare the survival difference. Multivariate analysis was performed using Cox’s proportional hazard model. Results: All patients had completed the combined treatment. With a median follow-up of 48 months (range, 13–94 months), the estimated 3-year and 5-year overall survival rates were 92.6% and 86.2%, respectively. Univariate analysis showed that age, T stage, clinical stage and neoadjvant chemotherapy were related with OS. Multivariate analysis indicated that age and clinical stage were independent prognosticators. The median cycle for nimotuzumab addition was 12 weeks. The incidence of grade 3–4 acute mucositis and leukocytopenia were 10.9% and 9.3%, respectively, with no cases of skin rash and infusion reaction. Xerostomia was the most common late complication, and the degree of dry mouth in most survivors was mild-to-moderate at the last follow-up time. Conclusions: Nimotuzumab plus IMRT with or without chemotherapy showed promising outcomes in terms of loco-regional control and survival, without increasing the incidence of radiation-related toxicities for patients.
Phase Ib study of cetuximab + BYL719 + IMRT in stage III-IVB head and neck squamous cell carcinoma (HNSCC).
Authors: Dunn Lara , Riaz Nadeem , Baxi Shrujal S. , McBride Sean Matthew , Sherman Eric Jeffrey , Michel Loren , Haque Sofia , Katabi Nora , Wong Richard J. , Xiao Han , Lee Nancy Y. , Fury Matthew G. , Ho Alan Loh , Pfister David G. 
Published: September 2018

6081 Background: Activation of the PI3K/mTOR signaling pathway is common in HNSCC. PI3K inhibitors have been shown to enhance radiosensitivity. BYL719 is an α-specific PI3K inhibitor that is synergistic and efficacious when combined with cetuximab, an FDA-approved radiosensitizing agent in HNSCC. This study evaluates the addition of BYL719 to cetuximab and radiation in the treatment of locally advanced HNSCC. Methods: This is a single-institution, phase I study. Patients with Stage III-IVB HNSCC received cetuximab 400 mg/m2 IV loading dose prior to intensity modulated radiation therapy (IMRT), followed by 250 mg/m2 weekly infusions during IMRT. BYL719 was given orally during IMRT in 3 dose levels (DLs): 1) 200 mg, 2) 250 mg, and 3) 300 mg per day in a standard 3 + 3 dose escalation design. Results: 11 patients are evaluable; median age-60 years (36-73); Stage III-1, IVA-9, IVB-1; oropharynx primary-9, unknown primary-2; HPV-positive -10. 8 patients completed treatment. 3 patients were treated on DL 1 and 2 without a dose limiting toxicity (DLT). Both patients on DL 3 experienced a DLT of grade 3 mucositis. Related adverse events (AEs) of any grade experienced by all 8 patients include: mucositis, weight loss, and hyperglycemia. Related grade 3 and 4 AEs in at least 2 patients include: mucositis (4), dysphagia (4), and decreased lymphocyte count (2). An additional 3 patients have been enrolled onto DL 2 and are undergoing treatment. All other patients had a complete response (CR) on post-treatment PET (from 6/2015 - 9/2016) and remain free of disease. Of 6 patients with mutational analysis, 1 had an activating PIK3CA mutation associated with a rapid response on serial intra-treatment MRIs. Conclusions: BYL719 administered at DLs 200 mg or 250 mg oral daily with cetuximab and IMRT resulted in expected AEs of radiation-based treatment with cetuximab and tolerable class-related AEs of PI3K inhibitors. BYL719 300 mg oral daily exceeds the maximum tolerated dose; the phase II recommended dose is pending completion of expansion of DL 2. All patients who completed treatment had a CR. Further evaluation of the addition of BYL719 to the platinum-sparing regimen of cetuximab + IMRT in the treatment of locally advanced HNSCC is warranted. Clinical trial information: NCT02282371.
Post-discharge transitions of care for hospitalized patients with advanced cancer.
Authors: Lage Daniel E , Nipp Ryan David , D'Arpino Sara , Moran Samantha M.C. , Hochberg Ephraim P. , Traeger Lara , Jackson Vicki A. , Cashavelly Barbara J. , Martinson Holly S , Ryan David P. , Greer Joseph A. , Temel Jennifer S. , El-Jawahri Areej 
Published: September 2018

6504 Background: Patients with advanced cancer experience frequent hospitalizations and burdensome transitions of care post-discharge. We examined predictors of discharge location for patients with advanced cancer. Methods: We prospectively enrolled patients with advanced cancer with unplanned hospitalizations from 9/14 to 3/16. Upon admission, we used the Edmonton Symptom Assessment Scale and Patient Health Questionnaire-4 to assess physical and psychological symptoms, respectively. We used logistic regression models to identify predictors of discharge to location other than home, including post-acute care (PAC) [skilled nursing facility or long term acute care hospital] or hospice [any setting]. We used Cox regression models adjusted for clinical variables to assess the relationship between discharge location and survival. Results: Out of 932 patients, 726 (77.9%) were discharged home, 118 (12.7%) to PAC and 88 (9.4%) to hospice. Compared with patients discharged home, those discharged to PAC or hospice had higher symptom burden, including dyspnea, constipation, low appetite, drowsiness, fatigue, depression, and anxiety (all p < 0.05). Patients discharged to PAC or hospice vs. home were more likely to be older (OR 1.03, p < 0.0001), live alone (OR 1.95, 95% CI: 1.25-3.02, p < 0.003), have impaired mobility (OR 5.08, 95% CI: 3.46-7.45, p < 0.0001), longer length of stay (OR 1.15, 95% CI: 1.11-1.20, p < 0.0001), higher ESAS physical symptoms (OR 1.02, 95% CI: 1.003-1.032, p < 0.017), and higher PHQ-2 depression symptoms (OR 1.13, 95% CI: 1.01-1.25, p < 0.027). Patients discharged to hospice vs. PAC were more likely to receive palliative care consultation (OR 4.44, 95% CI: 2.12 to 9.29, p < 0.0001) and have shorter length of stay (OR 0.84, 95% CI: 0.77 to 0.91, p < 0.0001). Compared with patients discharged home, those discharged to PAC had lower survival (HR 1.53, 95% CI 1.22-1.93, p < 0.0001). Conclusions: Patients with advanced cancer discharged to PAC or hospice have substantial physical and psychological symptom burden and poor physical function. Patients discharged to PAC also have inferior survival compared with those discharged home. They may benefit from targeted interventions to improve their quality of life and care.
Utilization of consultative molecular tumor board in community setting.
Authors: Farhangfar Carol J. , Morgan Oshuna , Concepcion Charlene , Hwang Jimmy J. , Mileham Kathryn Finch , Carrizosa Daniel R. , Dellinger Beth , Farhangfar Farhang , Kim Edward S. 
Published: September 2018

6508 Background: Physicians in the community have a broad range of experience using genomics data to inform treatment decisions. They typically have a heavier patient load than found in academic centers and treat a variety of tumor types. Genomic data has been reportedly used less than anticipated, even when results were actionable. Monthly didactic molecular tumor boards have been implemented in a number of cancer centers to try to fill gaps in knowledge. Methods: A weekly virtual consultative molecular tumor board (MTB) was implemented (Mar 2016) at an academic hybrid, multi-site community-based cancer institute to provide rapid molecularly-driven treatment guidance to physicians, augment genomics education, provide supporting documents for off-label use and clinical trials. A baseline survey was performed prior to first MTB. MTB assessments were summarized and provided to treating physician. Data was abstracted from the electronic medical records and clinical trials management system. Descriptive statistics were utilized to summarize utilization of MTB and treatment recommendations. Results: Genomics testing with a large panel (~600 genes) was requested for 809 patients (Jun 2015-Feb 2017). The MTB received 81 requests for review from 32 physicians from 14 locations. Most commonly reviewed disease sites were lung, ovary, pancreatic, colon, breast and head and neck cancers; 37% of reviews requested were for rare tumors. Median time to review request was 15 days from receipt of results. MTB recommendations were followed in 70% of cases, 16% continued current/other therapy, 11% declined rapidly (hospice/died), and 3% of patients decided against recommendations. Forty-four (44) percent were screened for recommended clinical trials; 26% went on study. Conclusions: Implementation of a weekly virtual consultative MTB facilitates molecularly-driven treatment decisions in community setting, especially in rare tumor types and enhances clinical trial accruals.