bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety/efficacy of a phase I/II study of SNS-301 added to pembrolizumab in patients with ASPH+ locally advanced unresectable or metastatic/recurrent squamous cell carcinoma of the head and neck (SCCHN).
Authors: Smith William , Celebi John , Pierce Robert , Drumheller Alice , Csiki Ildiko , Algazi Alain Patrick 
Published: May 2020

e18510 Background: SNS-301 is a first-in-class immune activating agent targeting human aspartyl (asparaginyl) β-hydroxylase (ASPH). ASPH is overexpressed in +20 tumor types. SNS-301 is an inactivated λ-bacteriophage, engineered to express a highly immunogenic fragment of ASPH fused to the phage gpD coat protein, previously shown to safely and effectively generate CD4, CD8 and B cell responses in a Phase I study (NCT04034225). Anti-PD-1 antibodies such as pembrolizumab and nivolumab can induce durable clinical responses in 13-16% SCCHN patients. While ASPH is frequently expressed in SCCHN, effective de novo responses to this tumor-specific antigen may be limited due to immune tolerance. Our hypothesis is that SNS-301 will break tolerance and trigger a significant anti-ASPH T-cell immune response, which in combination with anti-PD-1 blockade, will result in improved anti-tumor responses in this difficult-to-treat patient population. Methods: This is a Phase I/II study of SNS-301 delivered intradermally in combination with pembrolizumab. The population consists of 30 patients with ASPH+ locally advanced unresectable or metastatic/recurrent SCCHN who are actively receiving pembrolizumab or nivolumab for ≥12 weeks and have a best response of stable disease (SD) or first evidence of progressive disease (PD). A safety run-in will be performed for safety and any dose limiting toxicities (DLT) using a modified rolling six design prior to proceeding to full enrollment. Patients will provide a pre-SNS-301 tumor sample, an on-treatment tumor biopsy and an optional biopsy at PD to characterize the tumor microenvironment and correlate with clinical outcomes. SNS-301 in combination with pembrolizumab is given until confirmed PD or unacceptable toxicity. Study Objectives: Safety, tolerability and anti-tumor activity such as objective response rate, duration of response, progression-free and overall survival, immune responses, tumor/immune biomarkers and their associated treatment outcome. Results: Three patients have been enrolled. There have been no DLTs. Emerging safety data includes G1 adverse events with one G1 injection site pain. Patient status includes 1 PD and 2 patients with SD of at least six weeks duration. Immunological analyses will be presented. Conclusions: Early safety/efficacy warrant further evaluation of this combination therapy. Trial will be proceeding to full enrollment after the safety run-in is completed. Clinical trial information: NCT04034225.
Capecitabine therapy in recurrent/metastatic nasopharyngeal cancers.
Authors: Alshamsan Bader I , Alata Maaz Kamal , Gad Ahmed , Alzahrani Mashari J , Elhassan Tusneem , Atallah Jean Paul 
Published: May 2020

e18515 Background: A wide range of chemotherapeutic agents have demonstrated antitumor activity in patients with recurrent or metastatic Nasopharyngeal Cancers (NPC). These therapeutic agents have different efficacy and toxicity profile. Capecitabine monotherapy had activity in recurrent/metastatic NPC based on small previous retrospective studies. The primary objective is to evaluate the overall response rate and tolerability of capecitabine in recurrent/metastatic NPC. Methods: A retrospective electronic chart review performed for 51 cases of recurrent/metastatic NPC patients who received capecitabine 1000-1,250 mg/m² twice daily two weeks on, one week off between 2011 to 2019 at King Faisal Specialist Hospital & Research Center (KFSH&RC). The Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 was used. Results: The median age at diagnosis was 42 years. 98% had a non-keratinized undifferentiated squamous cell carcinoma (Grade III). The most common sites for metastases were Bone (58.3%), Lung (50.0%), and liver (45.8%). 95% of patients received platinum-based chemotherapy and radiation therapy as the primary treatment. Capecitabine was used as the second or third line of treatment in the metastatic setting 45.1% and 43.1%, respectively. The patients tolerated the standard dose for a median of 6 cycles; only 20.0% of patients required a 25% dose reduction. The best response for capecitabine was complete response in 8 patients (15.7%), partial response in 14 patients (27.5%), stable disease in 10 patients, (19.6%), with a clinical benefit achieved in 32 patients (62.7%), and progressive disease in 16 patients (31.4%). The overall response rate to capecitabine was 43.2%, which was consistent regardless of the site of metastasis. The median progression-free survival was seven months (95%.CI: 5.3 -8.8). The one and three-year survival rates were 79% and 53%, respectively. Capecitabine was generally tolerated, the most common grade I & II adverse events were hand-foot syndrome (HFS) in 9 patients (20.5%), fatigue in 8 patients (15.7%), Diarrhea in 6 patients (11.7%), anemia in 5 patients (9.8 %), thrombocytopenia in 4 patients (7.8%) and neutropenia in 2 patients (4.0%). The most common grade III & IV was HFS in 3 patients (6%) and fatigue in one patient (2%) that led to treatment discontinuation after the first cycle. Conclusions: Capecitabine in Recurrent/Metastatic NPC is an effective and well-tolerated oral agent; however, a randomized prospective trial to evaluate capecitabine efficacy in this setting still recommended.
Incidence trends of squamous cell carcinoma of the head and neck (SCCHN) in the aging population: A SEER based analysis from 2000-2016.
Authors: Taylor Melissa , Patel Mihir , Switchenko Jeffrey M. , McDonald Mark William , Steuer Conor Ernst , Beitler Jonathan Jay , Shin Dong Moon , Saba Nabil F. 
Published: May 2020

e18522 Background: SCCHN is more prevalent in the elderly. As the United States population ages, it is increasingly important to evaluate the change in the incidence of SCCHN in this population. Methods: This was a retrospective study using data from a population-based cancer registry (Surveillance, Epidemiology, and End Results) to identify patients ≥65 years old with the diagnosis of SCCHN between the years 2000-2016. The subgroups of oral cavity (OCC)and oropharynx cancer (OPC) were also analyzed independently. The incidence per year was calculated and joinpoint detection was used to identity significant changes in incidence trends. Annual percent change (APC) was detected to determine if the incidence trend was statistically significant. The study population was further stratified by sex. Results: For all sites, a joinpoint was found in 2003 with a statistically significant decrease in APC in incidence for males from 2000-2003 of -2.45%. For OCC, there was a joinpoint in 2005 with a statistically significant increase in APC in incidence for male patients of 1.41%. For (OPC), no joinpoint was found, but there was a statistically significant increase in APC in incidence for males of 3.41%. For females no joinpoint was found, but for OCC there was a statistically significant decrease in APC in incidence of -0.40%. Conclusions: In patients ≥ 65 years old the trend in incidence rate for all SCCHN sites stratified by sex has decreased between 2000-2016. However, for males the annual percent change in incidence has increased for OCC from 2005-2016 and for OPC from 2000-2016. [Table: see text]
Second malignancy post-chemoradiation in head and neck cancer patients.
Authors: Singh Gunjesh Kumar , Swami Rohit , Patil Vijay Maruti , Noronha Vanita , Joshi Amit , Menon Nandini Sharrel , Prabhash Kumar 
Published: May 2020

e18525 Background: There is limited data available in the literature regarding incidence and treatment of second malignancy post-chemo-radiation (CTRT) in head and neck cancer patients. Hence we planned this analysis to address this lacuna in the current literature. Methods: We have already published a randomized study of 536 head and neck cancer patients, comparing radical CTRT with weekly cisplatin with or without nimotuzumab. The database of this study was used for the current analysis. Data regarding occurrence, site, stage, treatment details and outcomes were extracted from the database. Continuous variables were expressed in terms of the median with range, while non-continuous variables were reported in percentage. Kaplan Meier method was used for estimating the overall survival (OS). Results: Out of 536 patients, 18 (3.35%) patients developed second malignancy. The most common site was head and neck (44.44%) followed by lung (27.77%), prostate, ovary, breast, gallbladder and thyroid. 16/18 (88.88%) patients developed metachronous, while 2/18 (11.11%) had synchronous second malignancy. Most of the patients (55.55%) presented with locally advanced and metastatic disease, while 44.44% of patients had early-stage disease. 8/18 (44.44%) patients received palliative treatment. Of these, 6/18 (33.33%) patients received best supportive care and 2/18 (11.11%) patients were given palliative chemotherapy and palliative radiotherapy. 10/18 (55.55%) patients received radical treatment in the form of radical surgery (22.22%), CTRT (11.11%) and radical radiotherapy (5.55%), while 16.66% patients were kept under observation only. The median OS after the diagnosis of second malignancy was 451 days (95% CI, 301.45-600.59). It was seen that median OS the diagnosis of second malignancy in the aerodigestive and non-aerodigestive system was 446 days (95% CI, 39.10 - 852.89) and 840 days (95% CI, 278.46 - 1401.53), log-rank test P-value = 0.24. Conclusions: Second malignancy is not an uncommon phenomenon in head and neck cancer patients after CTRT and if properly taken care of, the improved outcome can be expected.
The incidence of NTRK fusion in Chinese head and neck cancer and response to crizotinib treatment.
Authors: Liu Lianke , He Yuange , Xu Jiali , Wang Rong , Chen Rongrong , Xia Xuefeng 
Published: May 2020

e18532 Background: Previous studies have been reported that the frequency of NTRK ( NTRK1 NTRK2 NTRK3) fusion varies from up to 1% in solid or hematological cancers but more common in rare tumor types, such as mammary-analog secretory carcinoma of the salivary gland (more than 90%), thyroid cancer (up to 25%) and gastrointestinal stromal tumour (up to 25%). The specific TRK inhibitor Larotrectinib and multiple TRK inhibitor Entrectinib have been approved by FDA for advanced solid tumors. Here we report the incidence of NTRK alteration in Chinsese Head and Neck cancer and a patient harboring ETV6- NTRK3 fusion acquired durable clinical response to multiple TRK inhibitor Crizotinib. Methods: We retrospectively analyzed the genetic aberrations in 127 patients of Chinese Head and neck cancer. All the patients were detected by hybridization capture-based NGS 1021-gene panel (including NTRK1 NTRK2 NTRK3) sequencing with tumor tissue and peripheral blood control samples. A parotid cancer patient with lung metastasis harboring ETV6-NTRK3 fusion underwent Crizotinib treatment after disease progressed with chemotherapy. Results: A parotid cancer patient with lung metastasis harboring ETV6-NTRK3 fusion was diagnosed on Mar. 2016. Five months after first-line chemotherapy, the disease progressed. Crizotinib was administered from Aug. 2017 to Sep. 2019 with regular CT examination. The latest CT on Sep. 2019 showed mixed response, some of the lesions shrunk but one of them enlarged. Then the patient received third line chemotherapy. In brief, the patient reached a progression-free survival (PFS) of 2 years. Then we reviewed 127 cases of Head and Neck cancer in our database, the most common histology type was HNSCC (87.4%), the incidence of NTRK genetic aberrations was 7.9% (10/127) including NTRK fusion (n = 4, 3.1%) and NTRK mutation (n = 6, 4.7%). The most common fusion was ETV6-NTRK3 (n = 3, 2.4%). Conclusions: In conclusion, we reported the incidence of NTRK genetic aberrations in Chinese Head and Neck cancer and an ETV6-NTRK3 fusion patient reached long-term response (2 years) with Crizotinib, indicating alternative therapy insights to Head and Neck Cancer patients.
Phase II study: Induction chemotherapy & transoral surgery as definitive treatment (Tx) for locally advanced oropharyngeal squamous cell carcinoma (OPSCC): An update and retrospective review of non-study patients.
Authors: Siegel Robert S. , Thakkar Punam , Sadeghi Nader , Goodman Joseph , Joshi Arjun , Vongpachith Anonglack 
Published: May 2020

e18549 Background: The standard of care for OPSCC includes chemoradiation (CRT) or surgery with adjuvant radiation (RT). However, RT is associated with significant life long morbidity. We assessed the efficacy of a two-drug induction regimen, followed by transoral robotic assisted surgery (TORS) & neck dissection for locally advanced OPSCC. Methods: This is an IRB approved single-arm phase II study for untreated stage III or IVA (AJCC 7th edition) OPSCC patients (pts) with an ECOG < 2 and GFR > 50 cc. Induction cisplatin 75 mg/m2 and docetaxel 75 mg/m2 was administered every 21 days for 3 cycles. Patients then underwent TORS and neck dissection(s). At post-op visits, flexible laryngoscopy, blood tests, and imaging with PET/CT and/or MRI were done. Short and long term toxicity, progression-free survival, overall survival, and quality of life (QOL) were evaluated in all pts. Results: Twenty oropharyngeal pts were treated, 19 were male, 17 were Caucasian, and 19 were HPV+. Median age at dx was 57. Three pts were stage III, and 17 were stage IVA. Pathologic CR at the primary site occurred in 15 pts and CR among LN neck dissections occurred in 13 pts. Four pts were given dose-reduced chemo and 1 pt was changed to carboplatin per protocol because of renal dysfunction. Pre vs post tx QOL scores did not change. At a mean follow-up of 40.7 months (range 13 to 55), 18 pts are alive and NED. Three pts recurred a mean of 2.2 mos after surgery, and were treated with salvage CRT. Two pts died of metastatic disease, the third is alive and well. All 3 pts had positive LN (9 LN, 3 LN and 1 LN) at surgery. A fourth pt had 12 pos LN and received radiation. He has not recurred. A retrospective review of an additional 20 twenty pts treated in the same way, were also reviewed for efficacy. Mean age was 61.5. Two pts died of metastatic disease. Twenty pts have been followed for > 13 mos (17 are alive and well, 2 died, and 1 LFU), and their mean follow-up is 43.5 mos. Conclusions: Cisplatin + docetaxel followed by TORS & neck dissection(s) appears to be an effective model for the definitive treatment for OPSCC, while avoiding the adverse effects of RT. Clinical trial information: NCT02760667.
VEGF-A and TGF-β in bioptates of oral squamous cell carcinoma reflect tumor response to chemotherapy and monoclonal antibodies (cetuximab).
Authors: Vladimirova Liubov Yu , Frantsiyants Elena M. , Neskubina Irina V. , Lyanova Aza A. , Shalashnaya Elena V. , Kit Oleg I. , Engibaryan Marina A. , Abramova Natalia A. , Popova Irina L. , Ryadinskaya Ludmila A. , Tikhanovskaya Natalia M. , Teplyakova Maria A. , Novoselova Kristina A. , Myagkova Valeriya S , Sergeeva Marina M. , Fomenko Yuriy A. 
Published: May 2020

e18563 Background: Cetuximab is a monoclonal antibody directed against the EGFR receptor, able to block the EGFR signaling pathway and also indirectly affect the secretion of some growth factors. The search for biomarkers responsible for cetuximab resistance is an urgent task. The purpose of the study was to analyze VEGF-A and TGF-β levels in tumor tissue bioptates in patients with squamous cell carcinoma of the oral cavity receiving chemotherapy (CT) and cetuximab. Methods: The study included 30 patients with HNSCC St III-IV, T3-4N0-1M0. All patients received 2 cycles: cisplatin 100 mg/m2, intravenously, day 1, 5-fluorouracil 1000 mg/m2/day, intravenously, 96-hour continuous infusion, in combination with targeted therapy cetuximab 400 mg/m2 on day 1 in a loading dose, then 250 mg/m2 on days 8 and 15). Patients were divided into two groups: with response to cetuximab and CT (partial regression and stabilization) n = 17 and progression considered (resistance to the treatment) n = 13. Levels of VEGF-A and TGF-β were determined in tumor tissue bioptates by ELISA using standard test systems (Bender Med System, Austria). Statistical processing of results was performed using the Statistica 6.0 program (Stat-Soft, 2001). Results: CT and cetuximab in patients with resistance did not result in statistically significant changes in levels of VEGF-A, TGF-β and the VEGF-A/TGF-β ratio in tumor tissue bioptates, compared to the initial values. The studied markers in tumor tissue bioptates in patients with response to CT were statistically significantly different from the initial values: VEGF-A was decreased by 1.46 times, TGF-β by 2.96 times, while the VEGF-A/TGF-β ratio was twice elevated (p < 0.05). Conclusions: The results on levels of VEGF-A and TGF-β and the VEGF-A/TGF-β ratio are of a prognostic value and can be used for evaluating the efficacy of cetuximab and CT in patients with HNSCC.
Patterns of thyroid dysfunctions during treatment with immune checkpoint inhibitors (ICI) in 59 solid cancer patients.
Authors: Jiang Yong , Yang Li , Han Yin , Zhang Yongshen , Kong Feng-Ming 
Published: May 2020

e18567 Background: Immune checkpoint inhibitors (ICI) have now become the mainstay treatment in patients with many kinds of cancers. Thyroid dysfunction as the most common endocrine toxicity is poorly understood. This study aimed to report hypothyroidism and exam its changing dynamtic in our first series of patients treated with ICI. Methods: This is a retrospective study. Patients received nivolumab or pembrolizumab between July 2018 and December 2019 were considered. Patient must have euthyroidism within the 3 months before immunotherapy and those had previous use of levothyroxine were excluded. They were monitored by thyroid function tests every cycle until stopping ICI. Patients must have received at least 3 cycles of antibody treatment. Results: Among 89 patients treated, 59 met the inclusion criteria. There were 33 males, 26 females, including 26 (44.1%) nivolumab, and 33 (55.9%) pembrolizumab. Median age was 62 years [range: 27-88]). Cancer diagnoses observed were non small cell lung cancer 17(28.8%), small cell lung cancer 4 (6.8%),liver cancer 9 (15.3%), head and neck cancer 5 (8.5%), esophageal cancer4 (6.8%) colon cancer 3 (5.1%), nasopharygeal carcinoma 3 (5.1%) melanoma 3 (5.1%) and other cancers 11(18.6%). There were 9 patients (15.3%) developed a thyroid dysfunction, including 5 females. Four patients had thyrotoxicosis (median onset: 8 weeks) followed by hypothyroidism. There were three types of thyroid dysfunctions: the first type patients 3 (33.3%) had a brief time period of TSH flair (peak 17.4-57.8) after the first cycle of ICI, followed by TSH dramatic drop companied with rising fT4, which usually returned to normal level during 3-4 cycles of . The other 4 patients (44.4%) with thyroid dysfunction presented with remarkably elevated TSH (15.43-125.2) after 3.5-10 months’ treatment, followed by hypothyroidism development with a need of levothyroxine. The remaining 1 patient had a third type of thyroid dysfunction with elevated TSH, elavated more while the treatment continue, the patient should be given levothyroxine as soon as possible. Additionally, 1 patient developed hypopituitarism presented with both low level of TSH and fT4 after 10 month treatment. There was no significant difference in patient characteristics between patients with hypothyroidism and those without. Conclusions: There are heterogeneity in thyroid function and hypothyroidism after ICI. Before more experience is gained, frequent monitoring of thyroid function during ICI is warranted for prompt management of the hypothyroidism.
Analysis of race and gender disparities in incidence-based mortality in patients diagnosed with thyroid cancer from 2000 to 2014.
Authors: Cintron-Garcia Juan , Pappoppula Lakshmi Priyanka , Shahbandi Ashkan , Komiya Takefumi , Guddati Achuta 
Published: May 2020

e18570 Background: Well-differentiated thyroid cancer has better outcomes compared to anaplastic thyroid cancer. The incidence of well-differentiated thyroid cancer is higher in women whereas it is approximately the same in both genders for anaplastic thyroid cancer. The variability of incidence-based mortality across gender in the context of race has not been studied. This study analyzes the rates of incidence-based mortality among both the genders in four racial groups. Methods: The Surveillance, Epidemiology, and End Results Database was queried to conduct a nation-wide analysis for the years 2000 to 2016. Incidence-based mortality for all stages of well-differentiated and undifferentiated thyroid cancer was queried and the results were grouped by race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander) and gender. All stages and ages were included in the analysis. T-test was used to determine statistically significant difference between various subgroups. Results: Incidence-based mortality rates (per 100000) for well-differentiated and undifferentiated thyroid cancer for all races and both the genders are shown in the table below. The incidence-based mortality rates for both genders is approximately the same despite a 2-3:1 difference in incidence. Anaplastic thyroid cancer has a higher mortality rate in Caucasian and Asian/pacific Islander women compared to men despite an equal ratio of incidence. As expected, the mortality rates of anaplastic thyroid cancer were significantly higher compared to well-differentiated cancer across all races and genders. Also, Asian/Pacific Islander women have a higher rate of mortality compared to both the genders of Caucasian and African American races. Conclusions: Incidence-based mortality for anaplastic thyroid cancer is higher in women in all races whereas there is no difference in mortality between men and women for well-differentiated thyroid cancer. This is divergent from the incidence ratios noted in these malignancies. In the context of increasing incidence of thyroid cancer for the past few decades, this data suggests that additional resources may be devoted to decreasing the disparity of mortality in this gender. [Table: see text]