bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant chemotherapy with S-1 after curative treatment in patients with head and neck cancer (ACTS-HNC).
Authors: Taguchi Takahide , Kubota Akira , Yoshino Kunitoshi , Tomita Kichinobu , Kohno Naoyuki , Kawabata Kazuyoshi , Fukushima Masaori , Tsukahara Kiyoaki , Takemura Hideki , Hasegawa Yasuhisa , Terada Tomonori , Nagahara Kunihiko , Nakatani Hiroaki , Higaki Yuichiro , Iwae Shigemichi , Beppu Takeshi , Hanamure Yutaka , Teramukai Satoshi , Fujii Masato ,   ACTS-HNC Study Group
Published: March 2020

6004 Background: To establish the efficacy of adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) after curative treatment in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), we conducted a randomized phase III study to investigate whether S-1 is superior to UFT (uracil/tegafur). Methods: Patients with SCCHN who had received curative treatment and were confirmed to be tumor-free were randomly assigned to receive UFT (300 or 400 mg/day for 1 year) or S-1 (80, 100, or 120 mg/day for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were overall survival (OS), relapse-free survival (RFS), and safety. We estimated that 500 patients were needed to establish the primary end point. Results: From April 2006 through November 2008, a total of 526 patients (262 assigned to UFT; 264 assigned to S-1) were enrolled. The 3-year DFS rate was 66.0% in the UFT group and 64.1% in the S-1 group (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.66 to 1.16; [log-rank], P = .34). The 3-year OS rate was 75% in the UFT group and 82.9% in the S-1 group (HR, 0.64; 95% CI, 0.44 to 0.94; [log-rank], P = .022). The 3-year RFS rate was 63.6% in the UFT group and 68.2% in the S-1 group (HR, 0.81; 95% CI, 0.60 to 1.09; [log-rank], P = .16). There were no significant differences in 3-year DFS or RFS; however, the 3-year OS was significantly better in the S-1 group. The incidence of the following grade 3 or 4 events was significantly higher in the S-1 group: oral mucositis/stomatitis (2.4%), leukopenia (5.2%), neutropenia (3.6%), and thrombocytopenia (5.0%). Conclusions: S-1 was not demonstrated to be superior to UFT in terms of 3-year DFS; however, 3-year OS was significantly better with S-1 than with UFT. Clinical trial information: NCT00336947.
Effect of PDL-1 expression on prognosis in head and neck squamous cell carcinoma.
Authors: Vasilakopoulou Maria , Velcheti Vamsidhar , Rampias Theodoros , Sasaki Clarence , Rimm David , Fountzilas George , Psyrri Amanda 
Published: March 2020

6012 Background: The recent demonstration that immunotherapeutic approaches may be clinically effective for cancer patients has renewed the interest for this therapeutic strategy. Engagement of programmed death-1 receptor (PD-1), expressed on activated T-cells, by its ligands, results in a negative regulatory effect, with inhibition of downstream cellular signaling events. Our aim was to investigate the expression and prognostic significance of immunoresistance molecule PDL-1 (the negative regulator programmed death-1-ligand 1) on an annotated HNSCC tissue microarray. Methods: A tissue array composed of 400 larynx cancers treated with surgery followed by radiotherapy was constructed. PDL-1 protein expression levels were assessed using automated quantitative protein analysis (AQUA). The objectives of this analysis were to determine the association of PDL-1 with efficacy outcomes ( overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) ). The univariate and multivariate Cox proportional hazards models were used to evaluate the relationship between PDL-1 and event-time distributions. Event-time distributions were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: Mean follow-up time for the entire cohort was 39.34 months. Two-hundred thirty eight of 400 cases had sufficient tissue for AQUA analysis. High tumor PDL-1 expression was associated with favorable outcome for OS (P=0.029) and trended towards improved DFS (P=0.06) at 5 years. In multivariable analysis, adjusting for well-characterized prognostic variables, PDL-1 expression status retained its prognostic significance for OS and there was again a trend for PFS (p=0.05). Conclusions: This paradoxical result is in accordance with reported studies in HPV-associated HNSCC where PD-1(+) T cells were associated with favorable clinical outcome. It is possible that PDL-1 detection may reflect a previous immune response against tumors. Further work will determine whether PD-1/PD-L1 blockade induces tumor regression in HNSCC.
Differences in sexual practices and their role in gender, age, and racial disparities in HPV-positive HNSCC.
Authors: Fakhry Carole , Cullen Kevin J. , Bowie Janice , Thorpe Roland , D'Souza Gypsyamber 
Published: March 2020

6032 Background: Human papillomavirus associated head and neck cancers (HPV-HNC) have been steadily rising in the U.S., while HPV-unassociated HNCs have declined due to reductions in tobacco use. The trend of increasing HPV-HNC has been attributed to the sexual revolution, but not well explored. Individuals with HPV-HNC tend to be younger, white, and male and HPV-HNC is strongly associated with sexual behaviors. Methods: This analysis included 2270 men and 2261 womenfrom the 2009-10 National Health and Nutrition Examination Survey (NHANES) who answered a survey on demographic and behavioral risk factors. Participants also provided an oral rinse and gargle sample for HPV DNA analysis. Prevalence of sexual behaviors and oral HPV infection were calculated by gender, age cohort (18-29, 30-44, 45-59, 60-69), and race using NHANES samples weights to provide unbiasedestimates for the US population. Results: Men (85%) and women (83%) were similarly likely to have ever performed oral sex, but men had more lifetime oral and vaginal sexual partners and higher oral HPV16 prevalence (each p<0.001).Ever having performed oral sex was less common among 60-69 than 30-44 year old men (74% vs. 92%, p<0.001) and women (71% vs. 91%, p<0.001). Older individuals also had less lifetime sexual partners, but marginally higher oral HPV16 prevalence. Whites were more likely than blacks (90%vs69%, p<0.001) to have ever performed oral sex, to have more lifetime oral sex partners and higheroral HPV16 prevalence(each p<0.001). Prevalence ratios of ever performing oral sex for men vs. women (PR=1.03), 45-59 vs 60-69 year olds(PR=1.25), and whites compared to blacks (PR=1.32) were modest relative to more striking prevalence ratios for oral HPV infection andHPV-HNC(each PR>1.5). Conclusions: There are significant gender, age-cohort, and racial differences in oral sexual practices in a representative sample of the U.S population. Although men, younger age-cohorts, and whites have higher exposures to sexual behaviors of interest, the magnitude of these behavioral differences does not appear large enough to explain the observed disparities in oral HPV infection and HPV-HNC.
CAPRA: Safety, efficacy, and translational biomarkers of weekly everolimus, carboplatin, and paclitaxel as induction therapy for locally advanced head and neck squamous cell carcinoma (HNSCC).
Authors: Raymond Eric , Le Tourneau Christophe , Gatineau Michel , Delord Jean-Pierre , Fayette Jérôme , Dreyer Chantal , Tijeras-Raballand Annemilai , Albert Sebastien , Granier Muriel , Chibaudel Benoist , Hadengue Alexandra , Aissat Nasredine , Slimane Khemaies , Faivre Sandrine J. 
Published: March 2020

6036 Background: ThePI3K/mTOR pathway is activated in >50% of HNSCC with preclinical synergism between everolimus and carboplatin/paclitaxel. Methods: Patients (pts) with untreated locally advanced HNSCC with ECOG PS<2 received 9 consecutive weekly (w) cycles (cy) of CAPRA combining everolimus (30 mg/w at dose-level 1 then 50 mg/w at dose-level 2) with carboplatin (AUC2) and paclitaxel (60 mg/m2) followed by chemoradiotherapy. Endpoints were safety (CTCv3.0), antitumor activity (RECIST1.1), pharmacodynamic biomarkers on tumor biopsy. Results: A total of 50 pts with stage IV HNSCC (41 males, 9 females, median age 61) were enrolled. Among 7 patients included in the phase I, no dose-limiting toxicity was reported and the recommended dose (RD) of everolimus was 50 mg/w. Safety evaluation in 46 pts treated at RD for 325 cy and a mean number cy/pt of 7.1 (95%CI: 6.3-7.8) showed grade (Gr) 1-2 adverse events consisting of asthenia (50%), nausea/vomiting (28%), alopecia (26%), mucositis (24%), and constipation (20%). Hematological toxicities (Gr1-2/3-4) were neutropenia (35%/39%), anemia (61%/17%), and thrombocytopenia (54%/13%). Everolimus-related Gr3 toxicities were rashes (1pt), pruritus (1pt), dyspnea (1pt), hyperglycemia (2pts), and Gr1-2 hypercholesterolemia (23pts). There was no toxic death. Among 38 pts evaluable for antitumor activity, one pt experienced a complete response (2.6%), 29 pts a partial response (76.3%), and 8 pts a stable disease (21%) for an overall response rate of 79% (no progression reported). Interestingly, 20 major responses (>50% reduction tumor volume) were observed in large necrotic primary tumors/N3 involvement. Efficacy was not correlated to KRAS/BRAF/PI3KCA/EGFR mutations. Significant decreases of Ki67/p-S6K activities were observed in post CAPRA biopsies compared to baseline. Conclusions: Weekly everolimus with carboplatin/paclitaxel as induction regimen was well tolerated with 11% grade 3 and no grade 4/5 toxicity. Translational data showed direct effects of everolimus in tumors. CAPRA yields high rate of objective responses in patients with locally advanced HNSCC. Clinical trial information: NCT01333085.
Quantitative measurements of p95HER2 (p95) protein expression in tumors from patients with metastatic breast cancer (MBC) treated with trastuzumab: Independent confirmation of the p95 clinical cutoff.
Authors: Duchnowska Renata , Sperinde Jeff , Haddad Mojgan , Chenna Ahmed , Paquet Agnes , Lie Yolanda , Weidler Jodi , Huang Weidong , Winslow John William , Jankowski Tomasz , Czartoryska-Arlukowicz Bogumila , Wysocki Piotr Jan , Foszczynska-Kloda Malgorzata , Radecka Barbara , Litwiniuk Maria Malgorzata , Zok Jolanta , Wisniewski Michal , Zuziak Dorota , Biernat Wojciech , Jassem Jacek 
Published: March 2020

604 Background: Expression of p95 in HER2-positive breast cancer is potentially a major determinant of trastuzumab resistance because p95 lacks the trastuzumab binding site while retaining kinase activity. Previously, an optimal clinical cutoff for a continuous measurement of p95 expression was defined in a training set of trastuzumab-treated MBC patients (Clin Cancer Res, 16:4226, 2010). Methods: Quantitative H2T (HERmark HER2-total) and p95 assays (VeraTag, Monogram Biosciences) were retrospectively performed on formalin-fixed, paraffin-embedded tumors from an independent series of 240 trastuzumab-treated MBC patients. The pre-specified cutoff for p95 was tested to determine whether p95 above the cutoff in the HER2-positive subset correlated with worse progression-free survival (PFS) and overall survival (OS), as was observed in the training set. P95 expression was also assessed by immunohistochemistry (IHC) using the same antibody as the p95 VeraTag assay. Results: In the subset of tumors assessed as H2T-positive (N=190), p95 VeraTag values above the pre-defined cutoff correlated with shorter PFS (HR=1.41; p=0.043) and shorter OS (HR=1.72; p=0.021) where both outcomes were stratified by hormone receptor status and tumor grade. The hormone receptor positive patients (N=78) primarily drove the shorter PFS (HR=2.08, p=0.0026) and OS (HR=2.28, p=0.0099) observed in the p95-high subset. In contrast to the quantitative p95 VeraTag measurements, p95 IHC was not significantly correlated with outcomes. Conclusions: A clinical p95 cutoff (VeraTag assay) predictive of clinical outcomes derived from a previous training dataset was confirmed in a second independent clinical series. In contrast, p95 IHC did not correlate with outcomes. The observed consistency in the p95 VeraTag cutoff across different cohorts of MBC patients treated with trastuzumab justifies additional studies employing blinded analyses in larger series of patients. Clinical relevance of p95 protein expression remains to be established in a controlled clinical trial.
Role of adjuvant radiation in patients with squamous cell carcinomas of the oral cavity.
Authors: Maron Steven Brad , Gould Rothberg Bonnie , Otremba Michael , Judson Benjamin , Morgensztern Daniel 
Published: March 2020

6042 Background: Although surgery is the initial treatment of choice for patients with stage III squamous cell carcinoma (SCC) of the oral cavity (OC), the role of adjuvant radiotherapy (RT) remains undefined. We evaluated the differences in outcome according to stage subsets and use of adjuvant RT. Methods: The Surveillance Epidemiology and End Results (SEER) database was queried for patients with SCCOC, treated with surgery (S), RT, or both (SRT); older than 21 years; and diagnosed between 2004 and 2009. Patients with extracapsular lymph node extension or multiple primary cancers were excluded. Overall Survival (OS) rates were estimated by the Kaplan-Meier method and compared using log-rank testing as well as Cox proportional hazards. Results: Among the 1,051 patients meeting eligibility criteria, the most common treatment was SRT (49.1%), followed by S alone (28.9%), and RT alone (22.0%). The 5-year OS ranged from 33.3% in T3N1 to 52.8% in T1N1. Compared to S alone, the addition of RT improved 5-year OS in the entire cohort from 39.5% to 51.1% (HR 0.69, 95% CI 0.54-0.87, p = 0.002). This benefit, however, was significant only for stage T3N0 with a trend towards improvement in the T3N1 group. No significant benefit was observed in T1N1 or T2N1 disease (Table). Conclusions: Stage III SCC of the oral cavity is a heterogeneous disease with significant differences in survival according to its subsets. Adjuvant RT was associated with improved survival for patients with stage T3N0 disease but not T1N1 or T2N1. The benefit of RT in T3N1 cases did not reach statistical significance likely due to the small number of patients. If confirmed in prospective studies, further subdivision of stage III SCC of OC may be necessary, and the indication for RT may be restricted to patients with T3 disease. [Table: see text]
Phase (Ph) I/II study of investigational Aurora A kinase (AAK) inhibitor MLN8237 (alisertib): Updated ph II results in patients (pts) with small cell lung cancer (SCLC), non-SCLC (NSCLC), breast cancer (BrC), head and neck squamous cell carcinoma (HNSCC), and gastroesophageal cancer (GE).
Authors: Melichar Bohuslav , Adenis Antoine , Havel Libor , Lockhart Albert C. , Bennouna Jaafar , Schusterbauer Claudia , Dansky Ullmann Claudio , Zhang Bin , Benaim Ely , Dees Elizabeth Claire 
Published: March 2020

605 Background: MLN8237 is an investigational oral AAK inhibitor being evaluated in pts with hematologic (Ph III) and non-hematologic malignancies. We report here Ph II results from a, 5-arm study of single agent MLN8237 in pts with advanced, predominantly refractory, solid tumors (NCT01045421; closed for enrolment). Methods: Pts ≥18 years with relapsed/refractory disease measurable by RECIST, ECOG PS 0–1, and ≤2 prior (≤4 for BrC pts) cytotoxic chemotherapy regimens were enrolled. Pts with stable brain metastases were eligible. Pts were treated at the recommended Ph II dose; 50 mg BID for 7 d in 21-d cycles. For each cohort, a Simon’s 2-stage design was employed for Ph II, with ≥2 responses required in the first 20 response-evaluable pts to proceed to stage 2. The primary endpoint was overall response rate (ORR) by RECIST v1.1; safety and progression-free survival (PFS) were key secondary endpoints. Results: As of Dec 2012, 47 SCLC, 23 NSCLC, 49 BrC, 45 HNSCC and 47 GE pts in Ph II were response-evaluable (median age, 61 yrs [range 30–88]). NSCLC did not proceed to stage 2. ORR was 9%, 6%, and 4% in HNSCC, GE, and NSCLC pts, respectively; median PFS was 2.7, 1.5 and 3.1 months. BrC and SCLC data are shown in the Table. 92% of pts had a drug-related adverse event (DRAE). 57% of pts had Gr ≥3 DRAEs; including neutropenia (38%), anemia (10%), stomatitis (8%), and thrombocytopenia (6%). 22 pts died during the study; none were study-drug related. Conclusions: Single-agent activity of MLN8237 was evaluated across a range of solid tumors with a manageable toxicity profile. Encouraging Ph2 data in BrC and SCLC pts suggest that MLN8237 warrants further evaluation in these tumor types. Clinical trial information: NCT01045421. [Table: see text]
Squamous cell carcinoma of the oral cavity (SCCOC) in young patients: The Dana Farber Cancer Institute experience.
Authors: Hanna Glenn J. , Haddad Robert I. , Barletta Justine A. , Posner Marshall R. , Lorch Jochen H. 
Published: March 2020

6054 Background: Young patients (≤ age 45) with SCCOC and limited tobacco and alcohol exposure represent a distinct clinical entity with a poor prognosis. These patients are poorly characterized. We report our institution’s experience treating these patients over the past decade. Methods: Patients ≤ 45 years with SCCOC treated between 2001 and 2012 were identified retrospectively. Patient characteristics and treatment were recorded. Results: A total of 99 patients were identified (34 F and 65 M). Median age at diagnosis was 34 and 38 years, respectively (range 14 to 45 years). Thirty one (91.2%) women were never or former smokers with fewer than 10 pack-years, as compared with 50 (76.9%) men (p = 0.07). In women, 33 (97.1%) reported minimal to no alcohol use, compared with 52 (80%) men (p = 0.02). Oral tongue was the primary site in the majority of patients (30 F, 58 M). Surgical resection was the primary treatment modality (30, 88.2% F vs. 44, 68% M). Post-op radiation or chemoradiation was applied depending on stage and pathological findings. Stage: 53/99 (53.5%) presented with stage I or II disease and 46/99 (46.5%) had stage III or IV disease. Males on average had more advanced stage disease at presentation (33/65, 50.8%). Four of 7 women and 4 out of 18 men tested positive for human papilloma virus (HPV). Seven women (20.6%) and 13 (20%) men demonstrated evidence of local or locoregional recurrence with a median time to recurrence of 5 years and 0.67 years (range 1-10 and 0.08-11), respectively. Second primaries were rare (2, 5.88% F vs. 0, 0% M). Two women (5.9%) and 9 men (13.9%) died from recurrent disease. Overall, 4 (30.8%) women with stage III, IV disease demonstrated recurrence vs. 6 (18.2%) men (p = 0.35). Conclusions: In our experience, young patients with SCCOC have high cure rates that do not appear to be inferior to other sites in the head and neck area. Men and women are equally affected. Further clinical and genomic characterization for this group of patients is warranted.
A randomized, multicenter, open phase II study of cetuximab with docetaxel, cisplatin as induction chemotherapy in unresectable, locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Authors: Koh Youngil , Lee Keun-Wook , Kim Sung-Bae , Park Kyong Hwa , Shin Sang Won , Kang Jin Hyoung , Keam Bhumsuk , Lee Se-Hoon , Heo Dae Seog 
Published: March 2020

6069 Background: In this randomized phase II trial, we investigated the efficacy and safety of cetuximab in induction chemotherapy and followed by concurrent chemoradiotherapy (CCRT) in LA-HNSCC. Methods: Patients were randomized to receive 3 cycles of docetaxel (75 mg/m2) and cisplatin (75 mg/mg2) every 3 weeks with or without cetuximab (CDP vs. DP). CCRT was given as a definitive treatment. Patients in CDP arm received CCRT with weekly cetuximab (250 mg/m2) and cisplatin (30 mg/m2), while patients in DP arm received CCRT with weekly cisplatin. Primary endpoint was objective response rate (ORR) after induction chemotherapy. Results: 92 patients were randomized to receive either CDP (48) or DP (44). The median age was 59 years (range 29 – 73 years). The location of primary disease included oropharynx (41), hypopharynx (24), larynx (13) and oral cavity (14). 40 of the 48 patients in CDP arm and 40 of the 44 patients in DP arm completed 3 cycles of chemotherapy. Reason for incompletion in CDP arm included hypersensitivity (1), septic shock (1), skin rash (1), seizure (1), arterial thrombosis (1), unexplained death (1), unsatisfactory response (1), and withdrawal of informed consent (1). ORR to chemotherapy in CDP arm and DP arm was 81% (4 CR and 35 PR) and 82% (4 CR and 32 PR), respectively. 3 patients were not evaluable for response in CDP arm due to unexplained early death (1), septic shock (1), and hypersensitivity reaction after the first dose of cetuximab (1). CCRT completion rate after the completion of CDP and DP was 80% and 85%, respectively. Median PFS and OS were not reached in either arm, with a median follow-up time of 33 months. CDP arm showed 70% and 88% of PFS and OS rate, while DP arm showed 56% and 74% of PFS and OS at 3 years, when intend-to-treat analysis was performed. If we limited to the patients who received 3 cycles of CDP or DP, we saw 78% and 59% of 3-year PFS rate, respectively and 94% and 73% of 3-year OS rate, respectively. Conclusions: Addition of cetuximab during induction and CCRT phase may compromise completion rate of 3 cycles of induction chemotherapy but does not compromise completion of CCRT and shows promising survival data. Clinical trial information: NCT00623558.
Phase I/II trial of crolibulin and cisplatin in solid tumors with a focus on anaplastic thyroid cancer: Phase I results.
Authors: Gramza Ann Wild , Balasubramaniam Sanjeeve , Fojo Antonio Tito , Ward Jean , Wells Samuel A. 
Published: March 2020

6074 Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive of all solid tumors, with a median survival of 3-5 months. Chemotherapy has not impacted local control or survival. Crolibulin (CRO) is a microtubule destabilizing agent that disrupts vascular endothelial cells, and in turn, blood flow to the tumor. Preclinical studies showed synergism with cisplatin (CIS). The phase I portion of this phase I/II study, designed to assess the safety and tolerance of CRO and CIS in patients with solid tumors, has completed accrual. Methods: Patients with advanced solid tumors, ECOG ≤ 1, and adequate organ function were treated on a dose escalation schema with CIS (75-100 mg/m2) IV day 1 and CRO (13-20 mg/m2) IV days 1, 2, 3 (21-day cycles). CIS and CRO were continued until unacceptable toxicity or progressive disease (PD), with an option to continue CRO alone if toxicity was CIS-related. Results: Between Jan 2011 and Jan 2013, 21 patients were enrolled and assigned CIS/CRO (mg/m2) at 75/13 (6), 75/20 (3), and 100/20 (12). Diagnoses were as follows: ATC (16), urothelial carcinoma (2), prostate carcinoma (2) and mesothelioma (1). Patients received a median of 2 cycles of CIS/CRO (range: 1-6). Presently, four remain on CIS/CRO and one on CRO alone. The most common grade (G) 3 toxicities were: lymphopenia (33%), hyponatremia (29%), anemia (19%), hypertension during infusion (14%), and hypophosphatemia (9%). There were two G4 toxicities: elevated lipase and thrombocytopenia; and one G5 toxicity of laryngeal hemorrhage related to tumor erosion. There were two dose-limiting toxicities: G3 pancreatitis at dose level (DL) 1 and laryngeal hemorrhage at DL3. Eight ATC patients were treated at DL3. Of these, one (13%) had RECIST 1.1 complete response (CR) and one (13%) had stable disease (SD). Three (38%) had PD, and three are not yet evaluable. The CR has been on study for > 12 months and remains on CRO alone. Conclusions: CIS plus CRO deserves further evaluation as a regimen for ATC. The MTD of CIS/CRO is 100 mg/m2 IV day 1 and 20mg/m2 IV days 1, 2, 3 every 21 days. This combination is well tolerated, with toxicity primarily related to CIS. The phase II portion of this trial will compare CIS/CRO versus CIS in ATC patients. Clinical trial information: NCT01240590.