bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma(NPC) patients treated between 2004 and 2016: Patient and treatment characteristics and long term outcome.
Authors: Altun Musa , Kaval Gizem , Ibis Kamuran , Ozkaya Kubra , Meral Rasim , Karadeniz Ahmet Nafiz , Sari Murat , Ekenel Meltem , Basaran Mert , Bavbek Sevil E. 
Published: May 2019

e17507 Background: Standard treatment of locoregionally advanced nasopharyngeal carcinoma (LRA-NPC) is CCRT with or without adjuvant chemotherapy (CT). The value of adding IC to CCRT in LRA-NPC is unclear. We aimed to retrospectively evaluate LRA-NPC patients treated with IC followed by CCRT and analyse patient, tumor, treatment characteristics and outcome. Methods: Between 2004 and 2016, 202 patients with nonmetastatic LRA-NPC (stage 3-4), 144 males and 58 females ranging from 17 to 75 (median 49) years old were treated with IC followed by CCRT. Eleven (%5.4) patients had keratinised (WHO I), and 191 (%94.6) had nonkeratinised or undiffrentiated (WHO II-III) carcinoma. Cumulative radiation dose to primary tumor ranged from 60 to 74 (median 70) Gy. Ninety-one (%45) of the patients received 2-dimensional and 111 (%55) received intensity modulated radiotherapy (IMRT). IC consisted of taxane (T)(75 mg/ m2) and platinum (P)(75 mg/m2) combination (199 patients) or P and fluoruracil or epirubicine (3 patients) combination and 188 of the patients received 3 cycles of IC. Concomittant P was used either weekly (40 mg/m2, 25 patients) or every 3-weekly (100 mg/m2, 177 patients) application. Follow-up ranged from 5 to 167 months (median, 72.5 months). Results: Treatment failure was observed in 52 (%25.7) of the patients (21 local, 13 regional and 27 distant failures). Distant failure rate of all the patients exceeds 13%. Five and 10 years disease free survival (DFS) rates are 75.2% and 70.4% and overall survival (OS) rates are 78.9% and 64% respectively. In univariate analysis patient age favoring those below 49 and stage of disease favoring WHO II-III were all significant predictors of DFS and OS. In addition pathology was a significant predictor of DFS. Conclusions: LRA-NPC patients treated with IC followed by CCRT have a high locoregional control rate. Despite the use of systemic (induction) chemotherapy distant control remains insufficient and continues to be a challenge in NPC treatment. Besides improving locoregional control more effective systemic therapy is needed. [Table: see text]
Synchronous esophageal cancer impact on survival of head and neck squamous cell carcinoma (HNSCC) patients.
Authors: Amor Divino Paulo Henrique , Matos Gustavo Duarte Ramos , Lima Karolina , Castro Gilberto , Nader Marta Gustavo , Takeda Flavio Roberto , Cecconello Ivan , Braghiroli Oddone Freitas Melro , Mak Milena Perez 
Published: May 2019

e17513 Background: Optimal treatment of synchronous tumors (ST) of the aerodigestive tract is debatable and care is often individualized. Our goal was to characterize patients with HNSCC and esophageal cancer (EC) ST and to establish prognostic factors that could aid therapeutic decision. Methods: In this retrospective observational study, we evaluated data from 1650 consecutive patients diagnosed with HNSCC from 2008 to 2016. Patients with ST of HNSCC and esophagus with an interval of ≤ 6 months between both diagnoses were included. Patients ≥ 6 months between both diagnoses, incomplete treatment information and presence of another tumor site were excluded. Results: 52 patients were eligible. Median age was 57 years (39-91). Most were male (98%), with smoking and drinking habits (98%) and ECOG 0-1 (73%). HNSCCs were mainly in oropharynx (54%) and locally advanced disease (LA, III-IVB) (88%). In contrast, EC was early stage (I-II, 62%), located in the thorax (94%) and squamous histology (96%). 14 (27%) had LA in both primaries. Most LA HNSCCs (85%) were treated with radiotherapy (RT) with a median dose of 70Gy (5-70Gy). 50% received platinum and taxane induction chemotherapy. 81% of initial EC received at least surgery, mucosectomy or RT (median 50.4Gy). Hospitalization due to toxicity occurred in 12 (23%) and 7 (14%) of HNSCC and EC treatments, respectively. 16 patients (31%) had no definitive treatment directed to EC, without apparent impact on survival. Median time to progression was 13.8 months, being HNSCC the most frequent site of progression/relapse (40%). Median survival was 23.9 months (IC 95% 9.2-38.6). Early HNSCC survival was comparable to LA HNSCC (17.3 vs. 23.9 mo, p = 0.98). In LA HNSCC, LA vs. initial EC carried a worse prognosis (16 vs. 36.3 mo, p = 0.008). Anemia, BMI, tobacco exposure had no impact on survival. Conclusions: The occurrence of EC and HNSCC ST leads to a dismal survival, even in patients with early stage HNSCC. The presentation of LA in both sites is particularly challenging and associated with worse prognosis. Given the rate of treatment-related toxicity in this population, cautious efforts should be employed when planning definitive treatment in ST pts.
Efficacy and safety of apatinib as second-line or beyond therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.
Authors: Qin You , Ding Qian , Xu Xinhua , Cao Fengjun , Ning Siqing , Zhou Haibo , Chen Guiming , Huang Jing , Peng Gang , Yang Kunyu 
Published: May 2019

e17517 Background: The aim of this study was to evaluate the efficacy and safety of apanitib in the treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who failed from one or more lines of therapy. Methods: Patients with recurrent and/or metastatic HNSCC after failure of at least one line of therapy were recruited in this open-label exploratory study. Subjects were initially given apatinib 250mg qd until disease progression or unacceptable toxicity. Dose reduction to 125 mg was allowed. Herein, we reported the preliminary results at the cut-of date of Jan 31, 2019. Results: Between Jul 2017 to Dec 2018, 17 patients were enrolled. The median age was 59 years; 94% were male; 88% had more than 2 lines of chemotherapy. The median PFS and OS were 5.71 and 7.86 months, respectively. Most treatment related adverse events (AEs) were in grade ½. The grade ¾ AEs were hypertension (1/17, 5.88%), fistula (2/17, 11.76%), mouth mucositis (2/17, 11.76%), proteinuria (2/17, 11.76%), and f bleeding (6/17, 35.29%). Conclusions: Apatinib showed promising efficiency with tolerable toxicity for recurrent and/or metastatic HNSCC patients who failed from one or more lines of therapy. Clinical trial information: ChiCTR1800015278.
Determining the biomarker landscape and its impact on outcomes in HPV+ head and neck cancer after primary resection.
Authors: Khanna Suchin Rajeev , Wise-Draper Trisha Michel 
Published: May 2019

e17520 Background: Human Papillomavirus (HPV) has emerged as a risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Despite the better prognosis, HPV OPSCC is managed the same as HPV-negative cancer with toxic multimodality therapy. Numerous clinical trials are ongoing in an attempt at de-escalation treatment strategies in this population. However, the population is heterogenous in that 25% of patients still do poorly despite aggressive therapy. Tools to accurately separate this subset with poorer prognosis remain elusive. Finding the molecular means of prognosticating and risk-stratifying HPV OPSCC patients is an area of emerging interest to help better identify suitable candidates for de-escalation. We conducted an exploratory analysis of biomarkers with this goal in mind, specifically looking at HPV OPSCC patients that underwent definitive resection as their primary treatment. Methods: Tumor specimens from 26 patients with HPV OPSCC that underwent primary definitive resection were clinically annotated with variables of interest including patient demographics, presence of adverse pathological features, and recurrence and survival outcomes. A tissue microarray (TMA) was generated and tissue was stained by immunohistochemistry (IHC) with highly specific antibodies for molecular markers with known involvement in the pathogenesis of OPSCC. Pathologists reviewed the slides and assessed both the percentage of positive cells and the intensity of immunoreactivity. Scores were given based on these values. Results: Decreased pAMPk IHC expression portended better progression free survival (PFS), with hazard ratio (HR) of 0.004 with p = 0.09 trending towards statistical significance. The HR for biomarker expression and outcomes for ERCC1, p4EBP1, pMTOR, PI3K, PTEN, pAkt, pS6 did not achieve statistical significance. Conclusions: Decreased expression of pAMPk appeared to signify better PFS with a trend towards statistical significance. This was an exploratory analysis and was not powered to detect a difference in expression in any particularly studied biomarker, and the sample size was a limitation. Further studies should be powered to specifically detect a meaningful difference of pAMPk expression as it relates to outcomes.
Nationwide treatment patterns of oropharyngeal cancer in the human papillomavirus era.
Authors: Yang Kailin , Ward Matthew C. , Reddy Chandana A. , Burkey Brian B. , Adelstein David J. , Koyfman Shlomo A. 
Published: May 2019

e17521 Background: Human papillomavirus-mediated (HPV+) oropharyngeal cancer is now defined as a clinically distinct entity from HPV-unrelated (HPV-) disease in the 8th edition AJCC staging system, which more accurately informs prognosis for HPV+ patients. Treatment decisions are currently made according to the AJCC 7th ed staging. HPV+ patients are associated with favorable outcome. This study aims to analyze the national pattern of practice for HPV+ disease. Methods: Patients with oropharyngeal squamous cell carcinoma (OPSCC) diagnosed from 2010-2012 were identified from the National Cancer Database (NCDB). Patients were staged using the AJCC 7th system. Chemotherapy, radiotherapy and surgery were counted as treatment modalities. Fisher’s exact test and chi-squared test were used to assess treatment patterns over time. Overall survival (OS) was compared with Cox proportional hazards model. Results: 5,928 HPV+ OPSCC patients were identified. Single modality (surgery or radiation) was the most common treatment choice, used in 53.6% of stage I and 48.8% of stage II patients. For stage I, the use of dual modality therapy (70.8% received surgery with radiation) decreased from 36% in 2010 to 19% in 2012 (p = 0.05), though no significant difference in OS was seen between dual modality and single modality. Dual modality with chemoradiation was the main approach for stage III (58.6%) and stage IVA (67.5%) disease. Use of trimodality decreased from 2010 to 2012 in both stage III (p = 0.03) and stage IVA (p < 0.01). Conclusions: Using a national cohort of HPV+ patients from the NCDB, we showed that single modality was the most common for stages I/II and dual modality was the mainstay for stages III/IVA. Usage of aggressive approaches (dual modality for stages I/II and trimodality for stages III/IVA) decreased over time. Prospective studies would be needed to determine the optimized therapeutic choice for HPV+ patients given favorable outcome.
Osimertinib and dihydroartemisinin: A novel drug combination targeting head and neck squamous cell carcinoma.
Authors: Rosell Rafael , Chaib Imane , Cai Xueting , Llige David , Santarpia Mariacarmela , Jantus-Lewintre Eloisa , Filipska Martyna , Pedraz Carlos , Yang Jie , Miao Jing , Sun Rongwei , Bracht Jillian , Ito Masaoki , Aguilar Andrés , de Aguirre Itziar , Codony-Servat Jordi , Cardona Zorrilla Andres Felipe , Karachaliou Niki , Cao Peng 
Published: May 2019

e17526 Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored in vitro and in vivo the effect of the epidermal growth factor (EGFR) inhibitor, osimertinib, alone and in combination with dihydroartemisinin (DHA) in HNSCC. Methods: The combination of osimertinib with DHA was tested in the FaDu and CAL27 HNSCC cell lines. Tumor cell proliferation assays were conducted in cultured cells and mouse xenografts. Western blotting analysis of related signal pathways was performed to investigate the molecular mechanisms of the inhibitory effect of DHA and the combination. Other compounds, which inhibit signal transducer and activator of transcription 3 (STAT3), Src-family kinases (SFKs), sphingosine kinase 1 (SPHK1), or the receptor tyrosine kinase (RTK) AXL were also combined with osimertinib in vitro. Results: Osimertinib exerted synergistic cytotoxicity toward FaDu and CAL27 HNSCC cells when combined with DHA. DHA reversed the osimertinib-induced STAT3 and Src, phosphorylation. The double combination inhibited AXL expression. The anticancer potential of osimertinib plus DHA combination was validated in vivo on FaDu and CAL27 xenografts in mice without notable side effects. Conclusions: The results illustrate that the combinatory therapy of osimertinib and DHA, as a repurposing anticancer drug, could be a novel therapeutic strategy for recurrent and/or metastatic HNSCC patients. The findings indicate that a clinical trial is warranted to confirm the benefit of the combination.
Clinical prognostic factors in patients with recurrent or metastatic carcinoma of the head and neck treated with immune checkpoints therapies.
Authors: Resteghini Carlo , Cavalieri Stefano , Rametta Alessandro , Alfieri Salvatore , Galbiati Donata , Platini Francesca , Locati Laura Deborah , Bossi Paolo , Bergamini Cristiana , Granata Roberta , Orlandi Ester , Piazza Cesare , Mancinelli Moela , Licitra Lisa F. 
Published: May 2019

e17530 Background: Immunotherapy (IT) provides advantages in a small proportion of recurrent / metastatic head and neck squamous cell carcinoma (RM HNSCC) patients (pts). Predictive biomarkers are still an unmet need. We aimed to determine if known prognostic clinical factors in RM HNSCC as well as new variables hold prognostic value in the IT era. Methods: We conducted a retrospective analysis of a cohort of 106 RM HNSCC pts enrolled into IT trials at National Cancer Institute of Milan-Italy between Oct 2014 - Jul 2018. Using Log Rank test and Cox proportional hazard model we computed univariate and multivariate analysis (UVA; MVA) of demographics, clinical and biological data to assess their prognostic value for progression free survival (PFS) and overall survival (OS). Results: Ninety-three pts (M 75; F: 18) were included in the final analysis with a median follow up of 20.8 months. The majority (96%) were treated in platinum-refractory setting. Approximately half of pts received anti-PD-1 or anti-PDL-1 monotherapy while the remaining 52% received them in combination with other IT agents. Median OS and PFS were 6.5 (CI 95%: 4.6-10.4) and 2.1 months (CI 95%: 1.8-2.2), respectively. Statistically significant factors at UVA for PFS were smoking history - both pos vs neg and < vs ≥ 30 PY, disease subsite, weight loss > 5%, Karnosfky performance status (PSK), occurrence of any and G3-G4 drug related (DR) toxicities, neutrophil to lymphocytes ratio (NLR). Without stratification for disease subsite, MVA showed independent predictive value of prolonged PFS for positive smoking history (HR 0.5, p 0.02) and any DR toxicities (HR 0.43, p < 0.01). Several factors reached significance for OS in UVA (smoking history and PY, weight loss > 5%, ECOG PS, PSK, occurrence of any toxicities, CRP, baseline C-reactive protein, antibiotic use, steroid use in the 30 days before IT). Of these, PSK (HR 0.95, p 0.01) and any DR toxicities (HR 0.3, p < 0.01) resulted to be predictive in the MVA. Conclusions: Clinical parameters, especially pretreatment PSK, smoking history and occurrence of any DR toxicities, appear to be strong predictors of outcome in RM HNSCC pts treated with IT. These results should be validated in an independent cohort.
A novel mechanism of miRNA-mediated CBX8 associated with tumorigenesis in head and neck squamous cell carcinoma.
Authors: Shiah Shine-Gwo , Chou Sung-Tau , Kuo Ching-Chuan , Chi Ya-Hui 
Published: May 2019

e17534 Background: Polycomb group (PcG) proteins influence the development and progression of cancer. However, the mechanism that contributes to tumorigenesis have not been fully understood in head and neck squamous cell carcinoma (HNSCC). Methods: The expression of chromobox 8 (CBX8), a member of the polycomb group (PcG) of proteins, on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-410-3p and CBX8 were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Results: Here we found that CBX8 is upregulated in HNSCC tissues and cell lines. Using CBX8 knockdown cDNA microarray, we identify a CBX8-mediated target gene MIPOL1 which is inversely correlated with CBX8 expression in HNSCC tissues. Ectopic expression of MIPOL1 could inhibit tumor invasion and migration, whereas MIPOL1 silencing suppressed these effects in CBX8-knockdown HNSCC cells. Otherwise, depletion of CBX8 also induced p53 activity and increased the expression level of p21 and p27 through MIPOL1-independent manner, which result in cell cycle arrest in G2M phase. Silencing of p53 could inhibit p21 and p27 accumulation in CBX8 knockdown cells. Furthermore, we demonstrated that down-regulation of miR-410-3p promoted HNSCC cells migration and invasion through directly targeting CBX8. Overexpression of miR-410-3p decreased CBX8 expression and reduced migration and invasion, while ectopic expression of CBX8 rescued the miR-410-3p-reduced migration and invasion. In clinical samples, miR-410-3p level closely inversely correlated with CBX8 and positively correlated with MIPOL1. Conclusions: Collectively, our findings indicate that miR-410-3p may act as a tumor suppressor via negatively regulating CBX8. The newly identified miR-410-3p/CBX8/MIPOL1 and miR-410-3p/CBX8/p53 signaling axes may suggest new therapeutic strategies against HNSCC.
Retrospective analysis of baseline clinical factors associated to CDDP-nephrotoxicity in locally advanced head and neck cancer (LAHNC) patients.
Authors: Platini Francesca , Barretta Francesco , Alfieri Salvatore , Cavalieri Stefano , Resteghini Carlo , Galbiati Donata , Locati Laura Deborah , Bergamini Cristiana , Granata Roberta , Calareso Giuseppina , Iacovelli Nicola Alessandro , Quattrone Pasquale , Incandela Fabiola , Bossi Paolo , Licitra Lisa F. 
Published: May 2019

e17537 Background: CDDP is the standard of care for HNC. We performed a retrospective analysis related to baseline clinical characteristics and CDDP-nephrotoxicity in LAHNC patients (pts) treated in a curative setting with CDDP and concomitant RT (CRT) or with CDDP as part of induction chemotherapy. Methods: We collected data of LAHNC pts treated between 2008 and 2018 at the National Cancer Institute of Milan. CDDP was administered 100 mg/sm every 3 weeks or 50 mg/sm once a week during CRT, or 75 mg/sm during induction. Nephrotoxicity was assessed using creatinine increase (CreaIncr) recorded at day 6-20 post CDDP, graded according to CTCAE v4.0 and analyzed as a dichotomous variable (Grade>0 vs Grade = 0). We used univariable logistic regression to investigate associations between CreaIncr and clinical variables. Continuous variables were modeled using 3-knots restricted cubic splines. Results: Overall, 204 pts were considered. Male: 74%; median age: 56 yrs [IQR 51-63]. CRT was performed in 179 pts (88%). Three-weekly schedule was performed in 75% of pts. The median CDDP dose was 250 mg [IQR 200-300]. One fourth had history of hypertension and 9% were on diuretics. At baseline, median [IQR] creatinine was 0.80 mg/dL [0.69-0.89], creatinine clearance 109 mL/min [98-129] and uricaemia 4.90 mg/dL [4.11-5.74]. In total, 44% pts suffered from CreaIncr (G1: 46 pts; G2: 39 pts; G3-G4: 5 pts) all of them occurred within the first 2 cycles. CreaIncr was observed in 92% of pts treated with CRT, 84% received 3-weekly CDDP. Baseline creatinine clearance, azotaemia and hypertension were not significantly associated with CreaIncr. Loop diuretics alone appeared a potential relevant factor [OR 4.72;95%CI 0.96-23.32;p = 0.057]. Concomitant drugs (ACE inhibitors, Sartans, Ca-blockers) [OR 1.48;95%CI 1.00-2.18;p = 0.050] and uricaemia [OR 1.95;95%CI 1.27-3.0;p = 0.006] were statistically significantly associated to CreaIncr. Conclusions: In our selected population we found that concomitant medications and uricaemia were significantly related to CreaIncr. A better understanding of clinical baseline factors may improve decision making in a setting where CDDP has a curative significance.
Association of low neutrophil-to-lymphocyte ratios (NLR) and high lymphocyte-to-monocyte ratios (LMR) with overall survival and response to induction chemotherapy (IC) when used to select patients (pts) with locally advanced squamous cell of the larynx (LSCC) for combined chemoradiation (CRT).
Authors: Risch Zachary , Bellile Emily , Townsend Ryan , Swiecicki Paul , Casper Keith , Malloy Kelly M , Hogikyan Norman D , Spector Matthew E , Shuman Andrew , Stucken Chaz , Chinn Steven Bennett , Chepeha Douglas Brian , Jolly Shruti , Mierzwa Michelle Lynn , Bradford Carol Rossier , Eisbruch Avraham , Carey Thomas E. , Prince Mark E , Wolf Gregory T. , Worden Francis P. 
Published: May 2019

e17539 Background: University of Michigan Cancer Center (UMCC) protocol 9520 treated pts with stage III/IV LSCC with 1 cycle of cisplatin & 5-FU (PF) to select pts for definitive therapy. Pts whose tumors attained a ≥ 50% response after 1 cycle of PF underwent CRT. Those who had a < 50% response to IC were treated with total laryngectomy + RT. Correlative science from UMCC 9520 demonstrated that an increased percentage of CD4+ cells predicted response to PF & suggested improved survival. Published retrospective data also has demonstrated that lower NLR & higher LMR are associated with improved prognosis in p16- SCC of the oropharynx & pyriform sinus, while cancers with higher NLR & lower LMR have a worse prognosis. Similar to our previous correlative analysis, this study is also a secondary analysis of the predictive value of NLR & LMR in a prospective trial of bio-selective IC. Methods: NLR & LMR were calculated from pre-treatment CBC for all pts (N = 87) enrolled onto UMCC 9520. Results: All 87 pts received IC with PF. 65/87 (75%) responded to IC & received CRT. Results of response to IC compared the NLR & LMR ratios by logistic regression analysis & was used to create NLR & LMR cut points. Among pts with LMR ≥ 3, the response rate (RR) was 89% while the RR was 64% with LMR < 3 (p = 0.008). Among pts with NLR < 4.7, the RR was 79% while the RR of pts with > 4.7 was 58% (p = 0.06). Overall & disease specific survivals were greater in pts with LMR ≥ 3, (log rank p = 0.04, p = 0.03, respectively). Conclusions: Higher LMR & lower NLR are associated with favorable responses to IC & LMR ≥ 3 is associated with improved survival. This data correlates strongly with our published results from UMCC 9520, whereby elevated circulating CD4+ lymphocytes predict response to IC & survival. This important information may help direct the design of future laryngeal preservation protocols.