bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac safety in a phase II study of trastuzumab emtansine (T-DM1) following anthracycline-based chemotherapy as adjuvant or neoadjuvant therapy for early-stage HER2-positive breast cancer.
Authors: Dang Chau T. , Gianni Luca , Romieu Gilles , Dirix Luc , Campone Mario , Citron Marc L. , Zamagni Claudio , Krop Ian E. , Xu Na , Smitt Melanie , Suter Thomas 
Published: March 2020

532 Background: T-DM1 has demonstrated clinical activity as a single agent in patients (pts) with previously untreated MBC. In a previous phase II randomized trial of T-DM1 vs trastuzumab + docetaxel, T-DM1 had no clinically significant cardiac events, no cases of post-baseline left ventricular ejection fraction (LVEF) ≤40%, and fewer grade ≥3 adverse events (AEs; Hurvitz, ESMO 2011). This phase II study assessed the clinical safety and feasibility of T-DM1 following anthracycline-based chemotherapy in the adjuvant or neoadjuvant setting for early-stage HER2-positive breast cancer. Methods: TDM4874g (NCT01196052) is a phase II single-arm, open-label study of T-DM1 (3.6 mg/kg q3w IV; up to 17 cycles) following completion of doxorubicin/cyclophosphamide (AC; q2w or q3w for 4 cycles), or 5-fluorouracil/epirubicin (100 mg/m2)/cyclophosphamide (FEC; q3w for 3-4 cycles) chemotherapy in pts with early-stage HER2-positive breast cancer. Pre-chemotherapy LVEF by MUGA/ECHO ≥55% was required for enrollment. Co-primary endpoints are safety and rate of pre-specified cardiac events following initiation of T-DM1 treatment. An interim analysis was planned for the first 60 pts evaluable for cardiac safety (received ≥1 T-DM1 dose). Results: For pts in the interim analysis (20 received AC, 40 FEC), the most common all-grade T-DM1-related AEs were nausea (n=20), asthenia (n=17), and headache (n=17); 8 pts had grade 3/4 T-DM1-related AEs (including 3 with grade 3 increased aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]). No deaths occurred. Two pts had AEs leading to T-DM1 discontinuation (grade 3 AST and grade 2 ALT increase; grade 3 thrombocytopenia). No pre-specified cardiac events occurred; no pts delayed or discontinued T-DM1 due to cardiac AEs; there were no reports of grade ≥2 left ventricular systolic dysfunction, heart failure, or LVEF <50%. Results will be updated with data from all 153 enrolled pts. Conclusions: T-DM1 following anthracycline-based chemotherapy was not associated with cardiac toxicity in pts with early-stage HER2-positive breast cancer; this study continues without modification.
Adjuvant capecitabine for invasive lobular/mixed early breast cancer (EBC): USON 01062 exploratory analyses.
Authors: O'Shaughnessy Joyce , Pippen John E. , Paul Devchand , Stokoe Christopher T. , Blum Joanne Lorraine , Krekow Lea , Holmes Frankie Ann , Lopez-Diaz Christine , Vukelja Svetislava J. , Lindquist Deborah , Sedlacek Scot M. , Rivera Ragene Ruth , Brooks Robert J. , McIntyre Kristi , Wang Yunfei 
Published: March 2020

547 Background: Randomized phase III USON 01062 trial determining if patients with EBC would benefit from addition of capecitabine to docetaxel after AC (AC-T vs AC-XT). AC-T: docetaxel 100mg/M2 IV; AC-XT: docetaxel 75mg/M2 IV with capecitabine 825mg/M2 PO BID 14/7 days every 21days for 4 cycles. The primary endpoint, improvement in disease-free survival (DFS) at 5 years, was not met (HR=0.84, p=0.12) likely due to lower-than-expected event rate. The secondary endpoint, overall survival (OS), was improved with capecitabine (HR 0.68, p=0.01) (O’Shaughnessy, J. ASCO, 2011). Methods: Molecular analyses demonstrate that pleomorphic lobular (mixed lobular/ductal) carcinomas evolve from the same precursor and/or through the same genetic pathway as classical lobular cancers (Reis-Filho, J., J Path, 2005). We conducted exploratory analyses to evaluate the addition of adjuvant capecitabine in ductal vs lobular or lobular/ductal (mixed) EBC within USON 01062. Histology was classified according to local pathology assessment on patients’ primary cancers. Results: In ductal patients (n=2195), there was no difference in DFS (HR=0.92, p=0.48) and OS (HR=0.75, p=0.07) with AC-T vs AC-XT. In lobular/mixed patients (n=355), adding capecitabine improved DFS (HR=0.55, p=0.055) and OS (HR=0.38, p=0.04). There was no difference in DFS (HR=1.004, p=0.98) in the ER+ ductal patients (n=1258) with the addition of capecitabine. Conclusions: Ductal and lobular cancers have distinct histologic and molecular characteristics; lobular cancers are generally less sensitive to chemotherapy (Cristofanilli, M. JCO, 2005). This exploratory analysis suggests that patients with lobular/mixed EBC may benefit from adjuvant capecitabine. This hypothesis requires evaluation in other adjuvant capecitabine trials. [Table: see text]
Safety and efficacy of panitumumab (pmab) in HPV-positive (+) and HPV-negative (-) recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Analysis of the global phase III SPECTRUM trial.
Authors: Stoehlmacher-Williams Jan , Villanueva Cristian , Foa Paolo , Rottey Sylvie , Winquist Eric , Licitra Lisa F. , Davidenko Irina , Skladowski Krzysztof A. , Tahara Makoto , Faivre Sandrine J. , Oliner Kelly S. , Pan Zhiying , Bach Bruce A. , Vermorken Jan Baptist 
Published: March 2020

5504^ Background: SPECTRUM evaluated the safety and efficacy of pmab, a fully human monoclonal antibody against the epidermal growth factor receptor, with platinum‑based chemotherapy (CT) vs CT alone in patients (pts) with R/M SCCHN. This predefined analysis presents outcomes by tumor HPV status. Methods: All tumor samples were centrally reviewed. HPV status was determined using a validated immunohistochemistry assay to p16INK4A by an independent lab blinded to treatment assignments. Tumor samples were scored positive or negative according to prespecified criteria. Results: Of 657 enrolled pts (ITT), 443 (67%) had samples evaluable for HPV testing. Ninety‑nine (22%) tumors were HPV+ and 344 (78%) were HPV-. HPV+ rates varied by site (37% oropharynx, 19% larynx, 15% oral cavity, and 13% hypopharynx) and geographic region (44% N America, 22% W Europe, 21% Asia Pacific, 19% S America, and 18% E Europe). Demographics were generally balanced except pts with HPV+ vs HPV- tumors were more often non‑smokers (31% vs 14%), had oropharyngeal tumors (47% vs 23%), and had poorly differentiated tumors (30% vs 13%). Efficacy results are shown (Table). Adverse events were generally balanced between HPV+ and HPV- pts. Conclusions: Pts with HPV- R/M SCCHN administered pmab + CT had improved overall survival (OS) and progression‑free survival (PFS), whereas no improvement in OS or PFS was observed in pts with HPV+ tumors. [Table: see text]
A multicenter randomized controlled trial (RCT) of adjuvant chemotherapy (CT) in nasopharyngeal carcinoma (NPC) with residual plasma EBV DNA (EBV DNA) following primary radiotherapy (RT) or chemoradiotherapy (CRT).
Authors: Chan Anthony T. C. , Ngan Roger K.C. , Hui Edwin Pun , Leung Sing Fai , Poon Patricia , Sin VC , Tung Stewart Yuk , Cheng Ashley Chi Kin , Yau Tsz Kok , Lee Victor , Ma Brigette , Cheng HC , Yuen Kwok Keung , Lee Conrad , Kam Michael K. , Yau Stephen , Ng Alice Wan-ying , Mo Frankie , Zee Benny C.Y. , Lo Dennis YM ,   Hong Kong NPC Study Group
Published: March 2020

5511 Background: The benefit of adjuvant CT in NPC is unclear. Administering CT after full-dose CRT presents challenges in treatment compliance and toxicity. Post-RT EBV DNA predicts poor survival and may be a biomarker of subclinical residual disease. We conducted a biomarker driven RCT using EBV DNA to select high risk NPC patients (pts) for adjuvant CT while sparing low risk pts from unnecessary toxicity. Methods: Biopsy proven NPC, AJCC stage IIB-IVB, detectable EBV DNA at 6-8 wks post-RT, no persistent locoregional disease or distant metastasis, ECOG 0 or 1, adequate organ function. Randomised with stratification for primary therapy (RT Vs CRT) and tumor stage (II/III Vs IV) to arm A (adjuvant cisplatin 40 mg/m2 and gemcitabine 1000mg/m2, both given on D1+8 q3w x 6 cycles) or arm B (clinical follow-up). EBV DNA and PET scan were performed before and 6 months after randomization. Primary endpoint was relapse free survival and secondary endpoints included toxicity of adjuvant CT. With a hazard ratio of 2, 100 pts were required with a power of 0.8 and an alpha at 0.05. This safety analysis was approved by DMSC. Results: From 9/2006 to 12/2011, 514 pts consented for EBV DNA screening, 95 with detectable EBV DNA consented for adjuvant study. After work-up, 74 were eligible for randomization (37 to arm A; 37 to arm B). The two arms were well balanced in baseline characteristics. 80% received prior neoadjuvant and/or concurrent CT. Staging: IIB (36.5%), III (29.7%), IVA (18.9%), IVB (14.8%). Five pts refused adjuvant CT after randomization. Overall 65% and 57% completed 5 and 6 cycles respectively. Mean dose intensity (DI): 84% for cisplatin (22.5 mg/m2/wk, range 0.0-26.7), 92% for gemcitabine (612.8 mg/m2/wk, range 333.3-777.8). Treatment related adverse events above CTC G2 were summarized in Table. Conclusions: Delivery of 6 cycles of adjuvant CT is feasible with acceptable toxicity after full dose RT or CRT. [Table: see text]
Exploratory pharmacodynamics (PD) trial to investigate the mechanism of action of RG7160 (GA201), a novel dual-acting, monoclonal antibody (mAb) designed to enhance antibody-dependent cellular cytotoxicity (ADCC), compared with cetuximab (C) in neoadjuvant head and neck squamous cell carcinoma (HNSCC).
Authors: Temam Stéphane , Spicer James F. , Gomez-Roca Carlos , Berge Yann , Jeannon Jean-Pierre , Soria Jean-Charles , Soehrman Brossard Sophia , Delmar Paul , Golding Sophie , Oppenheim David , Passioukov Alexandre , Manenti Luigi , Delord Jean-Pierre 
Published: March 2020

5522 Background: GA201 efficacy was superior to C in orthotopic xenograft models in terms of activity and PD. In a phase I study, objective responses and long lasting stable disease were observed in heavily pre-treated patients (pts). Methods: HNSCC pts (T2-4, any N, M0) received i.v. neo-adjuvant 700/1400 mg GA201 or C (as per SPC), on D1 and 8. Tumor biopsies were taken at baseline (BL) and pre-surgery. The primary objective was determination of changes in tumor immune cell infiltration after treatment. Peripheral CD3+, CD16+, CD56+ cells, plasma cytokines, tumor EGFR and 18F-FDG-PET avidity were also studied. Results: To date, 39 pts (15/10 vs 14 pts for 700/1400 GA201 vs C, respectively) were evaluable for the primary objective and 4 pts are on-going. Patient characteristics at BL were as follows: median age, 57/62 vs 62 years; gender, 11/10 vs 12 male; tumor size ≤ 4 cm, 7/3 vs 3 pts. A greater proportion of pts receiving GA201 compared to C had metabolic tumor reduction (> 25% of SUVmax) (10/15 at 700 mg [1 pathological CR], 7/10 at 1400 mg GA201 vs 7/14 C pts) and symptomatic relief (6/12 at 700 mg, 6/7 at 1,400 mg GA201 vs 2/10 C pts). Table shows changes in PD markers. Conclusions: GA201 treatment, compared to C, exhibited more extensive tumor immune cell infiltration and a greater metabolic response. Consistent with the proposed mechanism of action of GA201, peripheral NK cells dropped and a unique cytokine profile was observed. The data support the immunomodulatory superiority of GA201 - a mAb designed to enhance ADCC compared to C. [Table: see text]
Hearing evaluation of head and neck cancer patients (HNCP): Comparison of adverse event (AE) criteria.
Authors: Colevas A. Dimitrios , Lira Ruth R , Colevas Electra A , Lavori Philip W. , Chang Kay W 
Published: March 2020

5525 Background: The incidence and severity of baseline hearing abnormality in HNCP is poorly characterized, as is the subsequent CDDP associated hearing loss. While formal behavioral audiograms can characterize CDDP associated hearing loss in great detail, most oncologists either rely on subjective evaluation of hearing loss or grade hearing impairment using the CTCAE. Two new grading systems for grading cisplatin ototoxicity have been developed for use in pediatrics, the Brock and Chang systems. This report is the first evaluation of these 3 hearing loss criteria in an adult cancer patient population. Methods: We conducted an electronic medical records (EMR) search for all HNCP between 2004 and 2010 treated at the Stanford Cancer Institute (SCI) and identified which patients had audiograms in the EMR, and who had received CDDP. Three investigators (RL, ADC, KC) independently graded these audiograms using the CTCAE v3 and v4, Brock and Chang criteria. Baseline distributions, changes following CDDP dosing, and inter-observer variability were calculated for hearing impairment grading using all four criteria. Results: We evaluated 460 audiograms in 111 patients. Because 282/460 of the audiograms did not have threshold shifts measured at 1,2,3,4,6 and 8 kHz, CTCAE v4 could not be applied to them . We therefore limited all further comparisons to CTCv3, Brock and Chang criteria. The table below summarizes the analysis. Conclusions: The Brock and Chang ototoxity criteria scales deliver a distribution of hearing AE grades at baseline more compatible than the CTCAE v3 with respect to the expectation that most HNCP do not have severe baseline hearing loss. Both the Brock and Chang scales are more sensitive than the CTCv3 to CDDP associated hearing changes. The Brock scale, followed by the Chang scale, demonstrated highest inter-rater agreement. Additional data concerning performance characteristics and utility of these three grading systems will be presented. Replacement of the present hearing impairment criteria in the CTCAE with either the Brock or Chang scales should be considered. [Table: see text]
Prognostic significance of the AJCC staging in patients with squamous cell carcinoma of the oropharynx.
Authors: Acevedo-Gadea Carlos Rodrigo , Baumgart Megan Ann , Wang Zuoheng , Deshpande Hari Anant , Davies Marianne , Decker Roy H. , Sasaki Clarence , Judson Benjamin , Herbst Roy S. , Morgensztern Daniel 
Published: March 2020

5529 Background: There have been significant changes in the epidemiology of head and neck squamous cell carcinomas (HNSCC), with an increase in the incidence of oropharyngeal (OP) cancer and opposite effect in other sites. Since the rise in OP cancer incidence is attributed to human papillomavirus (HPV), which is associated with a different biology and clinical behavior, we evaluated whether the current AJCC system retained its prognostic impact in this patient population. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with HNSCC diagnosed between 2004 and 2007. Overall survival (OS) was estimated by the Kaplan-Meier method and the Cox model was used to compare the survival curves for each AJCC stage. Patients were grouped into three anatomical locations: oral cavity (OC), larynx (L) and OP. Results: There were 26,520 patients meeting eligibility criteria, including 8622 OP, 7332 OC, and 10566 L. The AJCC staging retained its prognostic significance across all stages for patients with HNSCC of the OC and L. Patients with OP cancer, however, had similar 4-year survival for stages I through IVA, whereas stage IVB and IVC had a significantly decrease survival compared to IVA and IVB respectively (Table). Conclusions: The OS for stages III and IVA OP cancer is similar to those with stages I and II, in an effect that may be attributed to the increased frequency of HPV in this population, rendering the tumors more sensitive to chemotherapy and radiation. Therefore, the AJCC stage in OP cancer may be more useful in guiding the therapy than as a prognostic factor. [Table: see text]
Phase II trial of chemoradiotherapy concurrent with S-1 plus cisplatin in patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN): Results of the Japan Clinical Oncology Group study, JCOG 0706.
Authors: Tahara Makoto , Kiyota Naomi , Mizusawa Junki , Nakamura Kenichi , Hayashi Ryuichi , Akimoto Tetsuo , Hasegawa Yasuhisa , Iwae Shigemichi , Monden Nobuya , Matsuura Kazuto , Fujii Hirofumi , Onozawa Yusuke , Homma Akihiro , Kubota Akira , Fukuda Haruhiko , Fujii Masato 
Published: March 2020

5542 Background: To evaluate the efficacy and safety of chemoradiotherapy (CRT) concurrent with S-1 plus cisplatin in patients with unresectable locally advanced SCCHN. Methods: Eligibility criteria included histologically proven SCCHN with unresectable locally advanced lesions, PS 0-1, aged 20 to 75 years old, adequate organ function, and no prior treatment. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at 60 mg/m2/day, and cisplatin at 20 mg/m2/day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently startingon day 1. For patients achieving an objective response after CRT, two additional cycles of chemotherapy wereadministered. The primary endpoint was clinical complete response rate (%CR), which was the proportion of complete response (CR) and good partial response (good PR). Good PR was defined as remaining tissue with tumor shrinkage, which was not regarded as residual tumor but rather as scar material.The planned sample size was 45 patients, which was calculated by SWOG's two-stage attained design based on an expected %CR of 60% and a threshold of 45%, with a one-sided alpha of 0.1 and a power of 0.9. Results: From July 2008 to July 2010, 45 eligible subjects were accrued, including 43 males, with median age 63 years, ECOG PS 0/1 (36/9), oropharynx/ hypopharynx/larynx (26/15/4), T1/T2/T3/T4a/T4b (1/11/7/17/9) and N0/N2a/N2b/N2c/N3 (2/3/10/24/6). %CR was 64.4% (8 CR, 21 good PR) on central review. After a median follow-up of 1.56 years, 1-year local progression-free survival was 77.8%, with 1-year progression-free survival of 70.9%, 1-year overall survival of 93.3% and 1-year time to treatment failure of 57.6%. Grade 3 or 4 toxicity included mucositis (46.7%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis (26.7%), neutropenia (26.7%) and febrile neutropenia (4.4%). No treatment-related deaths were observed. Conclusions: This combination showed promising efficacy with acceptable toxicities. Further investigation in a phase III trial is planned.
Validation for a novel diagnostic standard in HPV-positive oropharyngeal squamous cell carcinoma.
Authors: Ma Xiao-Jun , Schache Andrew , Liloglou Triantafilos , Risk Janet , Jones Terence , Wang Hongwei , Bui Son , Luo Yuling , Sloan Philip , Shaw Richard , Robinson Max 
Published: March 2020

5543 Background: HPV testing is now widely advocated in the work up of oropharyngeal squamous cell carcinoma (OPSCC). The "gold standard" for oncogenic HPV detection is the demonstration of transcriptionally active high-risk HPV in fresh tumour tissue. For clinical utility, testing strategies have necessarily focused on formalin-fixed paraffin-embedded (FFPE) tissue, but this has been at the expense of reduced sensitivity and specificity for oncogenic HPV. This study evaluates a novel RNA-based in situ hybridisation test against the analytical gold standard; detection of high-risk HPV mRNA, derived from fresh frozen tissue samples, by quantitative reverse transcriptase polymerase chain reaction (qPCR). Methods: A tissue-microarray comprising FFPE cores from 79 OPSCC was tested using High Risk HPV RNAscope (Advanced Cell Diagnostics, USA) for HPV16, 18, 31, 33, 35, 52, and 58. Analytical accuracy and capacity for prognostic discrimination was determined by comparison with HPV RNA qPCR for HPV16, 18 and 33. Demographic and tumour parameters were compared by Chi-squared and Kruskal-Wallis tests. Test sensitivity and specificity were calculated against the standard. Kaplan–Meier survival estimates were constructed to assess prognostication. Results: High risk HPV RNAscope had sensitivity and specificity of 97% and 93% respectively (PPV 91%, NPV 98%) by comparison to the gold standard. Kaplan-Meier estimates of disease specific survival (DSS, p=0.002) and overall survival (OS, p<0.001) by RNAscope were similar to the gold standard (DSS, p=0.006, OS, p=0.002) and superior to p16 immunohistochemistry (IHC) or the combination of p16 IHC and DNA qPCR. Conclusions: We demonstrated that High Risk HPV RNAscope can be used to detect oncogenic HPV in FFPE OPSCC samples and has both excellent analytical and prognostic performance against the gold standard test for oncogenic HPV. These results raise the possibility that High Risk HPV RNAscope could be adopted as an ‘international standard’ test for OPSCC in clinical practice. As the oncology community approaches therapeutic de-escalation based on HPV status, such a reliable and efficacious test may have immediate application.
The role of family caregiver in the head and neck cancer: Psychological distress and quality of life evaluation.
Authors: Airoldi Mario , Garzaro Massimiliano , Raimondo Luca , Bartoli Claudia , Carnio Simona , Fora Gianluca , Giordano Carlo , Pecorari Giancarlo 
Published: March 2020

5546 Background: The family caregiver (FCG) has become a hot topic. This figure among head and neck cancer patients is still largely un-investigated; aim of our study was: 1) to describe in a more detailed way the role of FCG, 2) to evaluate quality of life (QoL) and psychological distress of FCGs and patients 3) to investigate relationships between FCG’s wellbeing and patient’s QoL and emotional pattern. Methods: Sixty couples of patients and their caregivers were enrolled in this observational cross-sectional study between April 2007 and May 2011 at 1st ENT Division, 2th Medical Oncology Division and 2th Radiotherapy Division of San Giovanni Battista Hospital of Turin. Inclusion criteria were: diagnosis of SCC, advanced stage (III-IV), completion of curative treatment and no evidence of disease at the enrolment. Psycho-oncological assessment was performed using: Distress Thermometer (DT), Stay-Trait Anxiety Inventory Manual in Y1 and Y2 form (STAI Y1-Y2), Beck Depression Inventory (BDI) and Montgomery-Asberg Depression Rating Scale (MDRS), EORTC-QLQ-C30 and Head and Neck-35 module and Caregiver Quality of Life Index-Cancer (CQOLC). Results: Patients: state and trait anxiety are 46,7% (STAI Y1 mean value 40,2±10,2; cut-off 40) and 36,7% (STAI Y2 mean value 36,7±8,2; cut off 40) respectively; self reported and clinician rated depression are 31,6% (BDI mean value 8,2±5,3; cut-off 9) and 48,3% (MDRS mean value 7,9±5,9; cut-off 6) respectively.CGs: state and trait anxiety are 50% (STAI Y1 mean value 42,5±9,9; cut-off 40) and 41,7% (STAI Y2 mean value 39,1±8,7; cut off 40) respectively; self reported and clinician rated depression are 28.3% (BDI mean value 7,3±4,7; cut-off 9) and 41.7% (MDRS mean value 7,6±5,8; cut-off 6) respectively.Data analysis underlined a positive association among emotional scales of patients and caregivers. Patients’ psychological aspects are negatively associated with caregivers’ QoL and vice versa. Conclusions: Anxiety and depression are often present in FCGs and cured HNC patients. Long term patient's QoL is the result of a frail balance between FCG and patiet emotional and psychological distress. A psychological support for FCG could improve patient well-being.