bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cetuximab/radiotherapy (CET+RT) versus concomitant chemoradiotherapy (cCHT+RT) with or without induction docetaxel/cisplatin/5-fluorouracil (TPF) in locally advanced head and neck squamous cell carcinoma (LASCCHN): Preliminary results on toxicity of a randomized, 2x2 factorial, phase II-III study (NCT01086826).
Authors: Ghi Maria Grazia , Paccagnella Adriano , Ferrari Daris , Foa Paolo , Nole Franco , Morelli Franco , Azzarello Giuseppe , D'Ambrosio Consuelo , Casanova Claudia , Guaraldi Monica , Mantovani Giovanni , Rossetto Ciro , Bonetti Andrea , Siena Salvatore , Crino Lucio , Buffoli Alberto , Koussis Haralabos , Pieri Gabriella , Gava Alessandro , Floriani Irene ,   for the GSTTC Italian Study Group
Published: March 2020

5513 Background: The standard treatment options for LASCCHN are cCHT+RT or CET+RT. Strategies to improve the efficacy with the integration of induction chemotherapy are being investigated. Primary endpoints of this study were to compare: 1) the overall survival (OS) of induction vs. no induction arms; 2) the Grade(G)3-4 in-field toxicity of cCHT+RT vs. CET+RT. Methods: Patients (pts) with unresectable LASCCHN, stage III-IV, ECOG PS 0–1 were randomized to a 2x2 factorial design: Arm A1: cCHT+RT (2 cycles of ciplatin/5fluorouracil); Arm A2: CET+RTX; Arm B1: 3 cycles of TPF followed by the same cCHT+RT; Arm B2: 3 cycles of TPF followed by CET+RT. A total of 204 deaths over 420 pts ( including the 101 randomized in the phase II part of the study comparing cCHT+RT with or w/o induction TPF) were required to detect a HR of death of 0.675 (A1+A2 vs. B1+B2; 2-sided a=0.05; b=0.20) and a 10% difference in G3-4 in-field mucosal toxicity (A1+B1 vs. A2+B2). Results: By February 2012, 387 pts over 413 pts were evaluable for toxicity. 82% of pts were male; median age was 60y; PS: 0=77.8% and 1=22.2%. Disease stage was III (31%) or IV (69%). Sites of disease were oral cavity (21.7%), oropharynx (54.8%), hypopharynx (23.5%). At a median follow-up of 21 months, 126 deaths occurred. Data on G3-4 in-field toxicity (primary endpoint) and compliance to cCHT+RT vs CET+RT are shown in the table. Conclusions: No advantage for CET+RT over cCHT+RT was observed regarding G3-4 in-field toxicities and feasibility. Pts are still being followed-up to assess OS. [Table: see text]
Prospective comparison of recurrence score and independent central pathology assessment of prognostic tools in early breast cancer (BC): Focus on HER2, ER, PR, Ki-67 results from the phase III WSG-Plan B trial.
Authors: Gluz Oleg , Kreipe Hans Heinrich , Christgen Matthias , Degenhardt Tom , Kates Ronald E. , Liedtke Cornelia , Shak Steven , Clemens Michael R. , Salem Marwa , Markmann Susanne , Liedtke Bernd , Aktas Bahriye , Henschen Stephan , Pollmanns Anke , Krabisch Petra , Uleer Christoph , Augustin Doris , Thomssen Christoph , Nitz Ulrike , Harbeck Nadia ,   West German Study Group
Published: March 2020

552 Background: Use of multi-gene real-time PCR (RT-PCR) based assays e.g. Recurrence Score (RS) and single markers (grade, uPA/PAI-1, ER/PR, HER2, KI-67) is currently controversially discussed in early BC. Here, we present the final WSG-planB trial correlation analysis of risk assessment tools and first prospective comparison of independent central pathology IHC/FISH assessment and RT-PCR for single markers. Methods: Plan B trial (n=2,448 randomized for 6xTC vs. 4xEC-4xDOC in locally HER2- BC). RS has been used as selection criterion for cht omission in HR+ BC (if RS<11 in pN0 or pN1). uPA/PAI-1 was optionally obtained. Grade, ER/PR, HER2 (IHC/FISH), Ki-67 were evaluated by the independent trial pathologist in all tumors. Results: From 04/09 to 11/11, 3196 patients have been recruited and 2448 randomized. RS distribution in 2551 HR+ tumors: 0-11 (18%), 12-25 (60%), >25 (22%). In 354 pN0-1 patients, cht was omitted based on low risk RS (88% compliance). Central grade for n=3038 and IHC/FISH results are currently available in n=1476. Moderately significant correlations were only found between RS and both central grade (rs=0.313; p<0.001) as well as Ki-67 (rs=0.374; p<0.001) and a weak one for uPA/PAI-1, particularly due to poor correlations within the RS group <26. In 1476 locally HER2- cases, n=9 were found as 3+ and/or FISH+ by central analysis. In 6 HR+/HER2+ cases, RS revealed 2 positive, 2 equivocal and 2 negative results. In 7 cases positive for HER2 by RT-PCR central pathology revealed 4 negative results. 24 locally HR+ cases are assessed as HR- in central pathology (2%). Among these, 6 were ER positive by RT-PCR. Final correlation analyses will be presented at the meeting. Conclusions: These first prospective data demonstrate that high-risk status according to RS is predictive of high risk by other factors, but the converse is not true. Regarding controversial HER2 and HR status by RT-PCR and IHC/FISH, we found few cases with false-negative or positive RT-PCR results in HER2- BC by local pathology. However, these discrepancies could potentially have a substantial impact on clinical patient management.
Differences in biomarker expression in HNSCC according to p53 status.
Authors: Feldman-Moreno Rebecca Anne , Kemkes Ariane C. , Xiu Joanne , Blevins Richard , Esmay Paula , Battaglia Leslie , Radebach Katrina , Rose Inga , Johnston Curtis , Gatalica Zoran 
Published: March 2020

5523 Background: Patients with p53 wildtype head and neck squamous cell carcinoma (HNSCC) tend to be HPV-positive, which associates with better prognosis. The purpose of this study was to explore biomarker expression profiles for insight into molecular differences in HNSCC patients based on p53 status. Methods: TP53 gene sequencing using the AmpliChip p53 microarray (Roche Molecular Systems, Inc.) was attempted on 61 HNSCC patients previously tested with Caris Target Now tumor profiling service. DNA was extracted from a FFPE sample, amplified and processed on the AmpliChip p53 microarray to detect single base pair substitution and deletion mutations in exons 2 - 11 and their flanking splice sites in the TP53 gene (GenBank X54156). EGFR FISH , HER2 IHC and 22 other predictive biomarkers, e.g. TS, TOPO2A, MGMT, etc., were assayed and retrospectively analyzed. All tests were performed in a CLIA-certified lab and interpreted by board-certified pathologists or cytogeneticists. Statistical analysis was performed using SPSS (PASW statistics17) for parametric and non-parametric tests of independence. Results: 52 cases provided sufficient quality DNA for p53 analysis and results revealed a mutation rate of 25% in HNSCC patients. Interestingly, only EGFR FISH and HER2 IHC (p=.002 and p=.004, respectively) were differentially expressed in wildtype vs. mutated p53. Matched-pair analysis in the p53 mutated subgroup (n=13) showed no significant trend regarding EGFR status (p=.763) but a slight trend towards HER-2 negativity (p=.020). In the p53 wildtype subgroup (n=39), a strong association with EGFR FISH non-amplification (n=28, 71.8%, p<.001) as well as HER-2 negativity (n=38, 97.4%, p<.001) was shown. Conclusions: To our knowledge, this is the first analysis of differential biomarker expression profiles in HNSCC based on p53 status. We hypothesize that the absence of EGFR amplification in the p53 wildtype cancers may be a contributing factor to the improved prognosis observed in HPV-positive HNSCC. Additionally, the strong association between p53 wildtype HNSCC patients and EGFR non-amplification suggests EGFR-targeted therapies like cetuximab would likely fail in p53 wildtype patients.
Influence of extracapsular extension on lymph node staging for patients with squamous cell carcinoma of the head and neck.
Authors: Baumgart Megan Ann , Acevedo-Gadea Carlos Rodrigo , Wang Zuoheng , Buta Eugenia , Davies Marianne , Deshpande Hari Anant , Decker Roy H. , Sasaki Clarence , Judson Benjamin , Herbst Roy S. , Morgensztern Daniel 
Published: March 2020

5532 Background: Although extracapsular extension (ECE) is a known poor prognostic factor in head and neck squamous cell carcinoma (HNSCC) and recommended to be collected by the current AJCC manual, it currently does not influence the final stage. We evaluated the prognostic impact of ECE in 4 primary sites. Methods: The Surveillance Epidemiology and End Results (SEER) was queried for patients with squamous cell cancers of the oral cavity (OC), oropharynx (OP), hypopharynx (H) and larynx (L), known ECE status, M0, and diagnosed between 2004 and 2007. Survival curves were estimated by the Kaplan-Meier and compared by Cox proportional hazards models. Results: There were 23,384 patients meeting eligibility criteria, including 14,664 (62.7%) N0, 6483 (27.7%) N+ without ECE (NECE), and 2237 (9.6%) with ECE. ECE was associated with decreased 3-year overall survival (OS), compared to NECE, for all lymph node stages including N1 (52% vs 61%, HR 1.32, p = 0.001), N2a (60% vs 76%, HR 1.82, p<0.001), N2b (44% vs 62%, HR 1.62, p<0.001), N2c (34% vs 47%, HR 1.43, p<0.001), N3 (31% vs 44%, HR 1.38, p=0.012). ECE was also an independent poor prognostic factor for cancer in the OC (HR 1.43, p < 0.001), OP (HR 1.44, p < 0.001), H (HR 1.58, p = 0.01), and L (HR 1.28, p = 0.01). The comparison between ECE and NECE with one additional N degree showed no significant OS difference, except OP N1 and H N2a ECE, where survival was inferior to OP N2a and H N2b NECE respectively (Table). Conclusions: ECE is a significant predictor for poor outcomes in HNSCC, with survival equivalent to one additional degree of N involvement. [Table: see text]
Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN): Analysis of African American patients.
Authors: Hayes David N. , Peng Guangbin , Pennella Eduardo , Cuyun Carter Gebra , Muehlenbein Catherine E. , Covello Kelly L. , Corral Mitra , Obasaju Coleman 
Published: March 2020

5533 Background: Previous retrospective analyses show poor outcomes for African American (AA) patients with head and neck carcinoma (HNC). Such racial disparities are not well understood, but patient (pt) demographics, comorbidities, tumor site, and human papillomavirus (HPV) status are suggested to play a role. Methods: The LORHAN registry was used to identify pts ≥18 yrs of age with de novo, non-metastatic HNC, and a record of survival time. This study evaluated pt and treatment characteristics by race, and conducted adjusted Cox regression analyses of overall survival (OS) and progression-free survival (PFS) to identify prognostic factors and interactions, and estimate hazard ratios (HRs) of AA vs. non-Hispanic white (NHW). Results: Baseline pt characteristics (see table below). The median OS/3-yr rate was 41.7 mo/51% in AA vs. 52.9 mo/70% in NHW, (age-adjusted HR: 1.73 [95% CI: 1.45, 2.08]). The median PFS/3-yr rate was 29.6 mo/43% in AA and 49.9 mo/62% in NHW, (age-adjusted HR: 1.64 [95%CI: 1.40, 1.93]). Multivariate analysis of OS and PFS showed that AA race, stage III and IV, PS 2, and smoking were significantly associated with a worse HR, while OP demonstrated a favorable HR over other sites. Significant interaction tests led to subgroup analyses for OS showing an elevated risk in AA with OP (HR: 2.62 [95%CI: 1.95, 3.52]) and similar risk elevations in male AA as well as in AA with PS 0-1 when compared to NHW in the corresponding subgroups. Conclusions: Controlling for other factors like PS and smoking, a worse prognosis was seen in AA males with OP localized SCCHN. Further investigation to improve the outcomes in this population is warranted. [Table: see text]
Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma.
Authors: Sukari Ammar , Kafri Zyad , Heilbrun Lance K. , Yoo George H. , Mulrenan Heather a , Smith Daryn , Kim Harold , Jacobs John Robert , Kucuk Omer , Salem Mohamed E. 
Published: March 2020

5534 Notice of Retraction: "Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma." ASCO's Confidentiality Policy requires that abstracts be considered confidential and embargoed from the time of submission until the findings have been publicly released in conjunction with the ASCO Annual Meeting. Abstract 5534, published in the 2012 Annual Meeting Proceedings Part I, a supplement to the Journal of Clinical Oncology, violated this policy and has been retracted from publication and presentation at the 2012 ASCO Annual Meeting. Background: Patients with metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, limited treatment options, and median survival of 6 to 9 months. Docetaxel and gemcitabine have both shown activity in HNSCC. The optimal combination, dosing, and scheduling of both drugs is, however, unknown. Thus, we investigated the efficacy and safety of biweekly dose intense GEM/DOC in patients with recurrent locoregional or metastatic HNSCC. Methods: An open-label, single-institution, single-arm, phase II study was conducted for patients who were previously treated with no more than two cytotoxic regimens. The patients received docetaxel (60 mg/m2IV) and gemcitabine (3000 mg/m2 IV) on day 1. The treatments were repeated every 14 days (one cycle), until disease progression or unacceptable toxicity. The primary end point was response rate. RECIST-defined response was evaluated every 4 cycles and toxicities were evaluated at each cycle. Results: A total of 36 patients were enrolled (M:F 26:10; median age (range), 60 years (46-79); performance status 0-1) , 29 of whom were response-evaluable. The patients received a median of 4 cycles (range 0-24). Of these 29 patients, none achieved complete response (CR) and 6 demonstrated a partial response (PR). Thus, the overall response rate was 21% (95% confidence interval [CI], 0.10 – 0.38). Ten patients had stable disease (SD), resulting in tumor control (CR or PR or SD) in 16 of 29 patients (55%), whereas 13 patients (45%) had disease progression. The median response duration was 3.2 months (80% CI: 2.0 – 6.1 months). For all 36 patients, the median overall survival was 4.2 months (95% CI: 2.4 – 7.0 months). Myelosuppression was the most common adverse event. Grade 3-4 neutropenia and anemia were observed in 10 (30%) and 13 (39%) patients, respectively. None of these patients, however, had febrile neutropenia or bleeding events, and there were no treatment-related deaths. Conclusions: The combination of biweekly dose intense GEM/DOC was tolerable and active regimen in patients with recurrent locoregional or metastatic HNSCC. Our findings warrant further investigation in a larger patient population.
An open-labeled, multicentric clinical study of cetuximab combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy in locoregionally advanced (LA) nasopharyngeal carcinoma (NPC): A 2-year follow-up report.
Authors: Chen Chun-yan , Zhao Chong , Gao Li , Lang Jin-yi , Pan Jian-ji , Hu Chao-su , Jin Feng , Wang Ren-sheng , Xie Conghua , Lin Tongyu , Lu Tai-xiang 
Published: March 2020

5535 Background: To evaluate the safety and efficacy outcomes of concurrent cetuximab plus IMRT and cisplatin in Chinese patients with LA NPC. Methods: Patients with primary stage III-IVb (UICC/AJCC 2002 staging system) and non-keratinizing NPC were enrolled in this prospective, multicentric, phase II study. Cisplatin (80mg/m2,q3week) and cetuximab (400mg/m2 one w before radiation, and then 250mg/m2/w) were given concurrently. The prescription dose of IMRT to GTVnx (primary tumor in nasopharynx) was 66 Gy - 75.9 Gy, GTVnd (positive cervical lymph nodes) was 60 Gy - 70Gy, The response rate was evaluated according to RECIST 1.0 criteria, and adverse events (AEs) were graded according to NCI CTCAE V3.0 criteria. Results: From July 2008 to April 2009, 100 patients were enrolled (74 male), with median age of 43 years. The proportion of stage III, IVa and IVb patients were 71%, 22% and 7% respectively. 99% of enrolled patients completed the planned treatment. AEs were within the expected range and manageable. No toxic death occurred during the treatment. Acneiform skin eruptions, mucositis, in-field dermatitis, xerostomia and neucopenia were the most common seen AEs, with 64% grade 2/3 acneiform eruptions, 26% grade 2/3 in-field dermatitis, 90% ≥ grade 2 mucositis (2 cases of grade 4 mucositis with spontaneous bleeding), 40% ≥ grade 2 xerostomia and 8% grade 2/3 neucopenia. With a median follow-up time of 23.5 months, the 2 year overall survival (OS), disease-free survival (DFS), local recurrence-free survival, regional (cervical lymph node) recurrence free survival and distant metastasis-free survival rates for the ITT population were 91%, 89%, 90%, 90% and 89%, respectively Multivariate analysis showed that N stage was the only prognostic factor for OS (p=0.0392, HR=2.946) and DFS (p=0.0062, HR=4.246) in these patients. Conclusions: Cetuximab combined with IMRT plus concurrent cisplatin in patients with LA NPC shows satisfactory 2-year locoregional control rate and 2-year overall survival. The combination seems to be well tolerated with a manageable side-effect profile.
A phase II study of sorafenib in combination with cisplatin and 5-fluorouracil in the treatment of recurrent or metastatic nasopharyngeal carcinoma.
Authors: Xue Cong , Yu Qitao , Pan Jian-ji , Sun Yuanlu , Zhang Li 
Published: March 2020

5538 Background: Nasopharyngeal carcinoma (NPC) is a disease with distinctive epidemiology and clinical behavior compared with Head and neck cancer (HNC) and more common in South-East Asia. Sorafenib monotherapy has been shown modest anticancer activity in HNC and NPC (C Elser et al; JCO 2007). This study was to evaluate the efficacy and tolerability of sorafenib combined with cisplatin and 5-fluorouracil (5-FU) for patients with recurrent or metastatic NPC. Methods: A phase II, single arm clinical trial was conducted in three centers in China. Chemotherapy-naive histologically confirmed NPC patients with recurrent or metastatic disease were enrolled. Patients received oral sorafenib 400mg bid continuously until disease progression or unacceptable toxicity, cisplatin 80mg/m2 intravenously (iv) on day 1-5, and 5-FU 400mg/m2 iv infusion for 96 hours on day 1. Treatment was repeated every 21 days for a maximum of 6 cycles. Results: 54 patients were enrolled. Most patients were with bone metastases (70.0%), followed by liver (56%) and lung metastases (56%). The median chemotherapy administrated was 4.0 cycles (range, 2 - 6 cycles). The disease control rate (DCR) reached 90.7%, including one complete response (CR), 41 partial responses (PR) and 7 stable diseases (SD). Median PFS was 7.2 months (95% CI 6.8-8.4 months) and median OS was 11.8 months (95% CI 10.6-18.7 months). Tumor cavitation after treatment was observed in 32.1% of patients with lung metastases. Decreased percentage of contrast update in responder patients (PR and CR) with liver metastases was also observed by Contrast-Enhanced Doppler ultrasound. The major toxicities include hand foot syndrome (HFS), myelo-suppression and gastrointestinal reaction.Dose reduction of sorafenib was required in 22 patients (40.7%) and dose interruption in 14 patients (25.9%) because of toxicity. Conclusions: Sorafenib combined with cisplatin and 5-FU has an encouraging efficacy profile with tolerable toxicity. Further randomized studies are needed to confirm the clinical benefit of sorafenib combined with chemotherapy in recurrent or metastatic NPC.
Patterns of care in elderly patients with squamous cell carcinoma of the head and neck: A SEER-Medicare analysis.
Authors: VanderWalde Noam Avraham , Meyer Anne-Marie , Tyree Seth D , Zullig Leah L. , Carpenter William Ruffin , Weissler Mark C , Shores Carol G. , Hayes David N. , Chera Bhishamjit S. 
Published: March 2020

5539 Background: Head and neck squamous cell carcinoma (HNSCC) is predominantly a disease of the elderly, however age and co-morbidity may affect therapy decisions. The purpose of this study was to assess the patterns of care of elderly HNSCC patients and identify factors associated with non-receipt of surgery and chemoradiation (CRT). Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2007) we identified a retrospective cohort of non-metastatic HNSCC patients and categorized them into treatment cohorts. Comparisons were made between surgery vs. non-surgery, and CRT vs. non-CRT cohorts. Multivariate logistic regression models examined factors associated with non-receipt of treatment. Variables included tumor location, stage, year of diagnosis, age, gender, marital status, race, comorbidity, race-comorbidity interaction, SEER region, socioeconomic variables, and hospital affiliations. Results: The final cohort of 11,336 were 63% male and 83% white. 52% had no co-morbidities, 44% had oral cavity HNSCC, 52% were diagnosed between 2002 and 2007, 58% had surgery, and 21% received CRT. For the CRT vs. non-CRT model, increasing age (OR = 0.93; 95% CI 0.92 -0.94) and non-whites with co-morbidity (OR = 0.71; 95% CI 0.55 – 0.92) were associated with decreased likelihood of receiving CRT. More advanced staged disease, oropharyngeal tumor location, and diagnosis after 2002 were associated with increased likelihood of receiving CRT. For the surgery versus non-surgery model, age was not associated with receipt of surgery (OR 0.99; 95% CI 0.99-1.00), nor was existence of comorbidity in white patients (OR 0.97; 95% CI 0.88-1.05). However, recent year of diagnosis, non-oral cavity tumor location, and advanced stage were all associated with reduced likelihood of receiving surgery. During the 15 year surveillance period, patients were less likely to receive surgery, and CRT was used more often. Conclusions: Age may influence the non-receipt of CRT in this elderly cohort but does not appear to be significantly associated with the non-receipt of surgery. There has been an increasing trend in the receipt of CRT with a decrease in surgery over the past 15 years.