bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).
Authors: Bauman Julie E. , Saba Nabil F. , Roe Denise , Bauman Jessica R. , Kaczmar John M. , Bhatia Aarti K. , Muzaffar Jameel , Julian Ricklie Ann , Wang Steven , Bearelly Shethal , Baker Audrey , Steuer Conor Ernst , Giri Anshu , Burtness Barbara , Centuori Sara , Caulin Carlos , Saboda Kathylynn , Obara Stefanie , Chung Christine H. 
Published: June 2021

6015 Background: Cetuximab (C), an anti-EGFR monoclonal antibody (mAb), is approved for advanced HNSCC but benefits a minority. Crosstalk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways is a known resistance mechanism. HGF is also immunosuppressive within the tumor microenvironment. A Phase I study confirmed the safety of C and ficlatuzumab (F), an IgG1 anti-HGF mAb, with preliminary efficacy and biomarker data suggesting that dual pathway inhibition may overcome tumor-intrinsic or immune cetuximab resistance. Methods: The primary objective of this phase II randomized, non-comparative trial was to evaluate the efficacy of F (20 mg/kg every 2 wks), with or without C (500 mg/m2 every 2 wks), in pan-refractory, advanced HNSCC. Eligibility criteria included recurrent/metastatic HNSCC, performance status (PS) 0-1, C resistance (defined as progression on or within 6 months of exposure), and resistance to or ineligibility for platinum and anti-PD1 mAb. Randomization was stratified by HPV status and center. The primary endpoint was median progression-free survival (mPFS). An arm was deemed worthy of further study if the lower bound of the 90% 1-sided confidence interval (CI) excluded the historical control of 2 months. Secondary objectives included overall response rate (ORR) in the overall and HPV-stratified populations. A Bayesian continuous monitoring rule for futility was applied. Results: 60 patients were randomized and 58 treated between Jan 2018 and Dec 2020 (27 to F; 33 to FC). Baseline characteristics were balanced across major prognostic variables including age, PS, HPV status, platinum resistance, and PD1 mAb exposure. Median time since prior cetuximab was 3.5 months (range 0-48 months). Grade ≥3 adverse events attributed to F included: pneumonitis (2); edema (3); diarrhea (1); LFT elevation (1); rash (2); electrolyte abnormality (2). The Table presents efficacy data. The F arm stopped for futility after 26 evaluable subjects accrued. The FC arm completed accrual and met the primary endpoint; 32 evaluable subjects had mPFS of 3.6 months (lower bound 90% 1-sided CI: 2.3 months) and ORR of 19% (6/32). All responses were in HPV- subjects, including 2 complete (CR) and 4 partial responses (PR) to the FC combination and 1 PR to F monotherapy. The mPFS and ORR for the HPV- population (n = 16) on FC were 3.8 months and 38% (6/16). Mechanistic signaling and immune biomarkers are under analysis. Conclusions: The well-tolerated FC combination met the primary PFS endpoint in pan-refractory, advanced HNSCC with notable activity in HPV- HNSCC, warranting phase III investigation. Clinical trial information: NCT03422536. [Table: see text]
Expansion cohort validation of a clinical predictive model for head and neck cancer survival in patients treated with immune checkpoint inhibitors.
Authors: Laliotis Georgios I. , Issa Majd , Klamer Brett , Karivedu Vidhya , Bhateja Priyanka , Dibs Khaled , Mladkova Nikol , Pan Xueliang Jeff , Old Matthew O. , Gamez Mauricio , Grecula John C. , Jhawar Sachin R , Mitchell Darrion L , Baliga Sujith , Carrau Ricardo , Rocco James William , Blakaj Dukagjin , Bonomi Marcelo Raul 
Published: June 2021

6030 Background: Immune checkpoint inhibitors (ICI) therapy is approved for patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The majority of pts will die within two years of diagnosis. We have shown that pretreatment clinical characteristics may predict overall survival (OS). Here, we expand our analysis to a total of 201 pts. Methods: Between January 15,2016 and April 9, 2020, 201 pts with R/M HNSCC were treated with ICI as first, second line and beyond. Data on p16 status, hemoglobin (Hb), albumin, lactate dehydrogenase (LDH), neutrophil, platelet and lymphocyte count was recorded initially. OS was defined from the start of ICI to death. Progression Free Survival (PFS) was defined from the start of ICI to disease progression (PD) or death. A nomogram was created using the rms package to generate individualized survival prediction. Results: 201 pts were analyzed, sex: 154 male (77%), 47 female (23%), median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), ipilimumab+nivolumab 10 (5%). Line of therapy: First: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), others 72 (36%). p16 status: negative 132 (66%), positive 69 (34%). Laboratory values: Median neutrophil count: 4.58 (IQR: 3.43-6.47), Median lymphocyte count: 0.69 (IQR: 0.47-1.08), Median Platelet count: 229 (IQR: 187-300), hemoglobin (Hb) normal/low 101/100 (50%/50%), albumin: normal/low 156/45 (78%/22%), LDH: normal/high 124/77 (62%/38%). Overall response rate: 36 (18%). Median OS: 12 months (CI: 9.4-14.8), median PFS: 4 months (CI: 3.5-5.7). The variables associated with OS were neutrophil count (high) [HR 1.28 (1.08 – 1.51), p=0.004], lymphocyte count (high) [HR 0.75 (0.60 – 0.95), p=0.015], albumin (low) [HR 2.06 (1.37 – 3.10), p<0.001], hemoglobin (low) [HR 1.64 (1.14 – 2.35), p=0.007], LDH (high) [HR 1.78 (1.23 – 2.56), p=0.002] and p16 status (positive) [HR 0.58 (0.39-0.87), p=0.009]. Using the prognostic index of the chosen model, we stratified patients into three risk groups at the 33rd and 66th percentile. Median OS in the good risk group was 24 months (CI: 18.5-NR), average risk group 13.8 months (CI: 11-20), poor risk group 2.3 months (CI: 1.7-4.4). The discrimination of the model after internal validation was c-index of 0.72. Conclusions: A small percentage of R/M HNSCC pts treated with ICI have good long-term survival outcomes. In a larger cohort, we internally validated the utilization of a simple, inexpensive and widely accessible nomogram based on clinical and laboratory variables which can predict OS in this patient population.
Outcomes and prediction of lethal recurrence after transoral robotic surgery for HPV+ head and neck cancer.
Authors: Basu Devraj , Shimunov David , Cohen Roger B. , Lin Alexander , Swisher-McClure Samuel , Lukens John Nicholas , Bauml Joshua , Hartner Lee P. , Aggarwal Charu , Duvvuri Umamaheswar , Rajasekaran Karthik , Chalian Ara , Rassekh Christopher , Cannady Steven , Newman Jason , O'Malley Bert W. , Weinstein Gregory S. , Gimotty Phyllis A. , Brody Robert 
Published: June 2021

6047 Background: Increasing use of transoral robotic surgery (TORS) for human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is likely to impact recurrence patterns and outcomes. Profiling HPV+ HNSCC recurrences after TORS and identifying features predictive of lethal outcome would facilitate tailoring adjuvant therapy and guide surveillance post-therapy. This study uses long term follow-up of patients at the first institution to bring TORS into clinical use to describe the recurrence patterns, distinguish outcomes associated with distinct patterns, and create a risk model for lethal recurrence. Methods: This retrospective cohort study at a single academic tertiary center analyzed 634 consecutive, treatment-naïve HPV+ HNSCC patients receiving TORS and neck dissection for clinical features at presentation and pathologic traits identified by surgical resection. The main outcomes were distant metastatic recurrence (DMR) and locoregional recurrence (LRR). Multivariate logistic regression with backward stepwise elimination was used to identify features associated with recurrence. Results: 6.5% of patients developed DMR at a median of 12.4 months after surgery and had a 5-year overall survival (OS) of 52.5% (95% CI, 33.9%-68.2%), whereas the 6.2% patients developing LRR alone had 5-year OS of 83.3% (95% CI, 66.2%-92.2%; P =.01). After recurrence, 5-year progression-free survival was 24.7% (95% CI, 11.4%-40.7%) for DMR cases and 85.7% (95% CI, 65.1-94.6%) for cases with LRR alone (P <.001). Comparing recurrent cases to recurrence-free controls showed DMR to be independently associated with positive surgical margins (AOR 5.7; 95% CI, 2.1-15.7) and advanced clinical stage at presentation (AOR 6.5; 95% CI, 1.9-23.0). Positive margins increased DMR risk by 4.2-fold and reduced 5-year disease-free survival (P <.001) in early-stage cases (Table), which comprised 95% of the cohort. By contrast, isolated LRR was associated with failure to receive indicated adjuvant therapy and was usually controllable by salvage therapy. Conclusions: Based on the largest single institution cohort reported to date, long term oncologic outcomes for HPV+ HNSCCs after TORS are excellent overall. While DMR is often fatal, LRR is salvageable with durable disease control. In addition to standard staging criteria, positive margins indicate substantially higher risk of DMR but not LRR. A risk model for DMR that incorporates margin status after TORS is relevant for guiding clinical trial design and whole-body surveillance.[Table: see text]
Endostar combined with intensity-modulated radiotherapy in low-risk local advanced nasopharyngeal carcinoma: A phase II, randomized, multicentric clinical trial.
Authors: Kang Min , Lin Shaomin , Zhu Haisheng , Liao Sihui , Huang Haixin , Yu Bin , Wang Hongqian , Liu Meilian , Zhu Jinxian , Huang Guang , Zhang Tingting , Yang Zhendong , Zhou Pingting , Zhou Ziyan , Qin Yutao , Wei Zhuxin , Du Qinghua , Zhao Changhong , Shen Mingjun , Wang Rensheng 
Published: June 2021

6050 Background: A Phase II, randomized, prospective, multicentric trial was conducted to evaluate the efficacy and safety of Endostar plus radiotherapy in patients with low-risk local advanced nasopharyngeal carcinoma (NPC). This study reported the preliminary results of NCT02237924. Methods: From 09/2014 to 08/2016, patients with low-risk local advanced NPC were randomly treated with Endostar plus radiotherapy (ERT group, n=60) and concurrent chemoradiotherapy (CCRT group, n=60). Primary endpoint was the 5-year overall survival (OS) rate. The secondary endpoints were 3-year OS rate, progression free survival (PFS) rate, loco-regional recurrence free survival (LRRFS) rate and distance metastasis free survival (DMFS) rate. Results: After a median follow-up of 47 months, 3-year OS rate were 93.2% and 79.3% (p=0.032), 3-year PFS rate were 89.8% and 70.6% (p=0.011), 3-year DMFS rate were 93.2% and 80.7%, in two groups, respectively (P=0.042). 3-year LRRFS rate were 96.6% and 92.0% in two groups, respectively (but P=0.565). For short-term curative effects, CR rate were 71.2% and 60.0% for primary tumor, 74.6％and 63.3％for cervical lymph nodes, in two groups, respectively (P < 0.05). Moreover, the incidences of adverse events were significantly lower in ERT group compared with in CCRT group. The grade 3/4 Hyponatraemia (0 [0%] vs 3 [5%], p=0·04), the grade 1/2 vomiting (10 [16.7%] vs 52 [86.7%], p=0.000), dry mouth (45 [75.0%] vs 56 [93.3%], p=0.012), leukopenia (22 [36.7%] vs 42 [70.0%], p=0.000) and weight loss (30 [50.0%] vs 45 [75.0%], p=0.005). No patients died of treatment-related causes. Conclusions: OS, PFS, and DMFS rates can be improved, adverse events be reduced, with better tolerability, by Endostar plus radiotherapy, when compared to concurrent chemoradiotherapy for local advanced low-risk NPC. Clinical trial information: NCT02237924. [Table: see text]
Randomized phase II study of sorafenib with or without everolimus in patients with radioactive iodine refractory Hürthle cell thyroid cancer (HCC) (Alliance A091302/ ITOG 1706).
Authors: Sherman Eric Jeffrey , Foster Nathan R. , Su Yungpo Bernard , Shergill Ardaman , Ho Alan Loh , Konda Bhavana , Ghossein Ronald A , Ganly Ian , Schwartz Gary K. 
Published: June 2021

6076 Background: HCC is a rare subtype of follicular cell thyroid cancer that has been poorly studied in the past. Recent genomic studies have shown the PI3K/Akt/mTOR pathway is frequently altered in HCC. In addition, a phase II study of sorafenib (S) and everolimus (E) showed promising data in HCC. A study to evaluate this was initiated through Alliance and the International Thyroid Oncology Group. Methods: Patients (pts) were randomized to either sorafenib and everolimus (SE) vs. sorafenib alone (S). Inclusion criteria included; (1) diagnosis of HCC (confirmed through central review), no prior S or E, refractory to radioactive iodine, progressive disease by RECIST over prior 14 months. Primary endpoint was a comparison of progression-free survival (PFS) between SE and S using a stratified 1-sided log-rank test with 0.20 significance level and a power of 80%. 28 events were needed at final analysis. Secondary endpoints consisted of overall survival (OS), confirmed response rate (RR), and adverse events. Results: 35 pts were randomized from 10/2014 to 9/2019, 34 of which were evaluable for analysis (17-SE; 17-S) because 1 patient cancelled prior to receiving treatment. Median age was 66.5 years and 74% were male. ECOG performance status (PS) was 0 (47%) and PS 1 (53%). 41% had prior systemic treatment for HCC. No significant differences in baseline characteristics were observed between treatment arms. Median follow-up in 22 alive patients was 39.2 months (range: 15.1-64.9). Seven (21%) patients remain on treatment. PFS was significantly improved in the SE arm as compared to the S arm (HR=0.65 (95% CI: 0.26, 1.57); median PFS: SE=24.7 months (95% CI: 6.1-no upper), S=10.9 months (95% CI: 5.5-no upper); stratified 1-sided p=0.1662). OS was similar between the arms (2-sided p=0.4138). Confirmed response rate was similar between arms as well (SE: 18% (3 partial response (PR) vs. S: 24% (3 PR, 1 complete response)); Fisher’s exact p=1.00). Grade 3 adverse event (AE) rates (regardless of attribution) were similar between arms (SE: 77% vs. S: 77%; p=1.00). Each arm had 1 patient with at least one grade 4 AE (SE patient: cardiac arrest, tracheal obstruction, encephalopathy; S patient: mucositis oral) and no grade 5 AEs. Conclusions: PFS was improved with the addition of E to S in this small randomized multi-institutional phase II study done. Accrual was difficult, but these promising results suggest that this combination should be further studied. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org ; Novartis/GSK; ClinicalTrials.gov Identifier: NCT02143726. Clinical trial information: NCT02143726.
Benefits of pembrolizumab in progressive radioactive iodine refractory thyroid cancer: Results of the AcSé Pembrolizumab Study from Unicancer.
Authors: Leboulleux Sophie , Godbert Yann , Penel Nicolas , Hescot Segolene , De La Fouchardiere Christelle , Blonski Marie , Lamartina Livia , Cousin Sophie , Do Cao Christine , Hadoux Julien , Simon Clotilde , Hoog Labouret Natalie , Chevret Sylvie , Massard Christophe 
Published: June 2021

6082 Background: AcSé Pembrolizumab is a Phase II, non-randomized parallel arm, open-label, multicentric study from Unicancer investigating the efficacy and safety of pembrolizumab monotherapy in different cohorts of patients with rare cancers (NCT03012620). Here we report the first results of pembrolizumab in the radioactive iodine refractory thyroid cancer cohort. Methods: Main inclusion criteria were progressive radioactive iodine refractory (RAIR) thyroid cancer (TC) resistant to standard treatment, age > 18, ECOG PS≤1. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycle for a maximum of 2 years. The primary endpoint was the confirmed objective response (OR) rate according to RECIST v1.1 by investigator. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Results: 43 patients (21 female, mean age 64.8 years; range 40-86) with TC (27 patients with differentiated TC (DTC) [papillary: 7; follicular: 14: oncocytic: 5 poorly differentiated: 1] and 16 patients with anaplastic TC (ATC)) were included from September 2017 to December 2020. The median number of previous systemic treatment lines was 2 (range, 0-7) in DTC and 2.5 (range, 1-4) in ATC. The median number of pembrolizumab cycles was 4 (range, 1-35). The median follow-up was 5.9 months (range: 22 days-22.9 months) for DTC and 2.7 months (range: 3 days- 24.4 months) for anaplastic TC. For DTC the best tumor response was partial response (PR) in 3 (11.1%) patients and stable disease (SD) in 5 (18.5%). Median duration of response was 2.5 months (range: 5 days-7.2 months). The median PFS was 2.6 months, the 6-month PFS was 16.9 %. The median OS was 12.7 months with a 6-month OS of 73.3%. For ATC the best tumor response was PR in 3 cases (18.8 %) and SD in 1 case (6.2 %). Median duration of response was 1.6 months (range: 2 days-7.2 months). The median PFS was 2.3 months, the 6-month PFS was 33.8 %. The median OS was 3.6 months with a 6-month OS of 32.9%. Treatment emergent adverse event included 9 Grade 1-2, 20 Grade 3 (3 being considered as related and 17 as not related) and 1 Grade 4 (sepsis, unrelated). Overall, the toxicity profile was similar to that observed in other cancers. Conclusions: The response rates observed under pembrolizumab is low in DTC and not negligible in ATC, but with a short duration of response. Clinical trial information: NCT03012620.
Medicaid patients more likely to die at home without hospice during the pandemic versus before, exacerbating disparities with commercially insured patients.
Authors: Panattoni Laura Elizabeth , Li Li , Sun Qin , Fedorenko Catherine R. , Sanchez Hayley , Kreizenbeck Karma L. , Shankaran Veena , Ramsey Scott David 
Published: June 2021

6502 Background: The COVID-19 pandemic dramatically reduced family access to hospitals and created new barriers to home hospice care, raising concerns about how the pandemic has impacted cancer patients’ place of death and end of life home hospice support. Hypothesizing that Medicaid-enrolled cancer patients may be at greater risk of disruptions in end-of-life care compared to commercially insured patients, we examined changes in place of death and home hospice support for Medicaid and Commercial enrollees following the pandemic. Methods: We linked WA State cancer registry records with claims from Medicaid and approximately 75% of commercially insured cancer patients in the state. Patients ages 18-64 with solid-tumor malignancies who died March-June 2020 (COVID) were compared to those who died March-June 2017-2019 (Pre-COVID). Place of death was categorized as hospital, home with hospice, and home without hospice; nursing home deaths were excluded. Given our sample size, we examined differences in the likelihood of place of death with Fisher’s exact tests and multinomial logistic regressions stratified by payer and by COVID period, controlling for age, gender, race, stage, cancer type, and census tract-level neighborhood deprivation. We report marginal effects. Results: In Fisher’s exact analyses, Medicaid but not commercial patients were significantly less like to die in hospital and more likely to die at home without hospice during COVID (Table). In pre-post adjusted analysis of Medicaid patients, the probability of dying in the hospital was 12.3% (p=0.03) percentage points lower during the pandemic versus before, while the probability of dying at home without hospice was 11.1% (p=0.04) greater. Place of death did not change significantly pre-post for commercial patients. In addition, Pre-COVID, the probability of dying in the hospital was 10.7% (p=0.03) greater for Medicaid than commercial patients. During COVID, the probability of dying at home without hospice was 15.8% (p=0.04) greater for Medicaid versus commercial patients but lower for women (ME=20.2%; p=0.01) and colorectal versus breast cancer patients (ME=39.2%; p=0.01). Conclusions: Following COVID, Medicaid patients place of death shifted from hospital to homes, but without an increase in the use of home hospice services. In contrast, place of death and hospice use among commercial patients did not significantly change. This widening disparity in home deaths without hospice services raises concerns that the pandemic disproportionately worsened end of life experience for low income patients with cancer.[Table: see text]
Association between perceptions of prognosis and end-of-life outcomes for patients with advanced lung and gastrointestinal cancer.
Authors: Topping Carlisle E. W. , Elyze Madeleine , Plotke Rachel , Heuer Lauren , Vyas Charu , Greer Joseph A. , Nipp Ryan David , Temel Jennifer S. , El-Jawahri Areej 
Published: June 2021

6503 Background: Many patients with advanced cancer maintain misperceptions of their prognosis and are thus unprepared to make difficult decisions regarding their end-of-life (EOL) care. However, studies examining the associations between patients’ perceptions of their prognosis and their EOL outcomes are limited. Methods: We conducted a secondary analysis using longitudinal data from a randomized controlled trial of a palliative care intervention for patients with newly diagnosed incurable lung and non-colorectal gastrointestinal cancer. We administered the Prognosis and Treatment Perceptions Questionnaire to assess patients’ perceptions of their prognosis at baseline, week-12, and week-24, using the final assessment closest to death. We used multivariate logistic and linear regression models, adjusting for age, gender, marital status, cancer type, and randomization to the palliative care intervention, to examine the associations among patients’ perceptions of their prognosis with the following EOL care outcomes abstracted from the electronic health record: 1) hospice utilization and length-of-stay (LOS); 2) hospitalizations in the last 30 days of life; 3) receipt of chemotherapy in the last 30 days of life; and 4) location of death. Results: We enrolled 350 patients in the parent trial, of which 80.5% (281/350) died during the study period and were included in this analysis. Overall, 59.4% (164/276) of patients reported that they were terminally ill, and 66.1% (154/233) reported that their cancer was likely curable at the assessment closest to death. In multivariate analyses, patients who reported that their cancer was likely curable were less likely to utilize hospice (OR = 0.25, 95%CI 0.10-0.61, P = 0.002) or die at home (OR = 0.56, 95%CI 0.32-0.98, P = 0.043), and more likely to be hospitalized in the last 30 days of life (OR = 2.28, 95%CI 1.20-4.32, P = 0.011). In contrast, patients’ report that they were terminally ill was only associated with lower likelihood of hospitalizations in the last 30 days of life (OR = 0.52, 95%CI 0.29-0.92, P = 0.025). Patients’ perceptions of their prognosis were not associated with hospice LOS or chemotherapy administration in the last 30 days of life. Conclusions: Patients’ perceptions of their prognosis are associated with important EOL outcomes including hospice utilization, hospitalizations at the EOL, and death at home. Interventions are needed to enhance patients’ perceptions of their prognosis in order to optimize their EOL care.