bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II, multicenter, open-label, single-arm trial of famitinib in patients with advanced recurrent and/or metastatic nasopharyngeal carcinoma (NPC) after two previous treatment regimens.
Authors: Huang Yan , Zhang Li , Pan Jian-ji , Hu Guoqing , Gang Wu , Xiong Jian ping , Hu Chaosu , Lin Lizhu , Yu Hao , Jiang Haoyuan 
Published: March 2020

6026 Background: Famitinib is an oral, small molecular multiple tyrosine-kinase inhibitor (TKI), targeting stem cell growth factor receptor (c-Kit), platelet derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR). So far, few target therapies show acceptable efficiency in advanced recurrent and/or metastatic nasopharyngeal carcinoma (RM-NPC) patients. The primary object of this study is to determine the safety and efficacy of famitinib in patients with RM-NPC. Methods: This study recruited histologically diagnosed RM-NPC patients who failed more than two lines of systemic chemotherapy. Other eligible criteria included ECOG PS≤2, adequate organ function and no prior exposure to other c-Kit, PDGFR or VEGFR TKIs. The patients received famitinib orally at a dose of 25 mg once daily until the disease progression or intolerable toxicity. Results: From May 2011 to Sep 2012, 58 patients (Simon’s two-stage design, 28+30) were recruited at 8 sites in China. The clinical benefit rate (partial response or stable disease maintained≥12 weeks, tumor response was evaluated every 4 weeks) is 32.8%, including 5 PR and 16 SD patients. Median PFS was 3.2 months. The most frequently observed hematologic toxicities included thrombocytopenia, leucopenia and neutropenia; non-hematologic AEs were hypertension, proteinuria, and hand-foot syndrome. All adverse events were generally mild-to-moderate (grade 1/2) and manageable with supportive treatment; grade 3/4 incidence was relatively low. Conclusions: This phase II study shows that famitinib demonstrates substantial clinical benefits in patients with advanced RM-NPC and the drug-related adverse reactions were most predictable and tolerable, no special toxicity was reported. Biomarker analysis for responder and non-responder is still ongoing and will be present at the meeting. Clinical trial information: NCT01392235.
Identification of a gene expression profile associated with progression-free survival (PFS) in relapsed or metastatic (RM) head and neck squamous cell cancer (HNSCC) patients (pts) treated with first-line cetuximab and platinum therapy.
Authors: Bossi Paolo , De Cecco Loris , Perrone Federica , Cortelazzi Barbara , Cossu Rocca Maria , Marco Siano , Sponghini Andrea , Bergamini Cristiana , Locati Laura D. , Mirabile Aurora , Granata Roberta , Resteghini Carlo , Pilotti Silvana , Canevari Silvana , Licitra Lisa F. 
Published: March 2020

6027 Background: First-line chemotherapy with platinum and cetuximab is usually offered to RM-HNSCC pts. In the Extreme trial a median PFS time of 5.6 months was reported. However, a small fraction of pts achieves a prolonged PFS (> than 12 months). Until now, no recognized predictive biological factor has been identified. Methods: A group of 14 pts treated with a first-line platinum and cetuximab with a PFS exceeding 12 months (long PFS) and a group of 26 pts with a PFS less than 5.6 months (short PFS) were selected. Tumor specimens of the recurrence (25 cases) or, if not available, of the primary tumor were collected. In order to identify molecular profiles deregulated between the 2 groups, a gene expression microarray analysis was performed using the Whole-Genome DASL assay and HumanHT-12_v4 BeadArray chips (lllumina). Results: The 2 groups were well balanced in regard to recognized prognostic factors (performance status, weight loss, prior radiotherapy, tumor grade, site of primary tumor, residual disease at primary tumor site). Mean PFS was 21 months in long (range 13-36) and 4 months in short PFS group (range 1-5). By class comparison analysis between the 2 groups, the expression pattern of 136 genes was found differentially expressed (FDR<0.05). In long PFS group, EGFR and genes associated to EGFR pathway including CDCP1 and EPGN were up regulated, as well as its ligand (EREG). Several members of the Kallikrein serine proteases gene family are present among the most upregulated genes in long PFS group, suggesting the involvement of extracellular-matrix remodelling. In addition to cellular morphology, pathways analysis showed an enriched modulation of genes belonging to cell-to-cell signalling, DNA replication/DNA repair and lipid metabolism. Conclusions: Our analysis suggests that a specific molecular signature may be associated with long and short PFS after platinum/cetuximab first line chemotherapy in RM-HNSCC pts. To our knowledge, it is the first study attempting to generate hypotheses in this field and further validation is required.
The results of first-line chemotherapy in 108 patients affected by recurrent or metastatic salivary gland malignacies (RMSGM).
Authors: Airoldi Mario , Garzaro Massimiliano , Raimondo Luca , Pedani Fulvia , Bellini Elisa , Ostellino Oliviero , Riva Giuseppe , Pecorari Giancarlo 
Published: March 2020

6038 Background: Recurrent/metastatic salivary gland malignancies (RMSGM) are not manageable by means of surgery and/or radiotherapy; chemotherapy (CT) represents a palliative strategy without any curative purposes. In this abstract we report the results of CT in 108 cases of RMSGM. Methods: We enrolled 108 patients with radiologically documented progression of RMSGM. Five pts received cisplatin (DDP) 100 mg/sm d 1, q 3wks; 8 pts doxorubicin (DOX) 75 mg/sm d1, q 3wks; 30 pts vinorelbine (VNB) 30 mg/sm d. 1 and 8, q 3 wks; 9 pts DDP 60 mg/ sm + epirubicin (EPI) 60 mg/sm + 5-FU 600 mg/sm d.1, q 3 wks; 42 pts DDP 80 mg/sm d.1 + VNB 25 mg/sm d. 1,8 , q 3 wks, and 14 pts carboplatin (CBDCA) AUC 5.5 + paclitaxel (Taxol; TAX) 175 mg/sm d.1, q 3 wks. The maximum number of CT cycles was 6. Results: Patients characteristics were as follows: 65 males (60%) and 43 females (40%); median age: 57 yrs (range 20-74); 42 pts (39%) had ECOG PS=0 and 66 pts(61%) PS 1-2 (0-2); histological evaluation was as follow: adenocarcinoma 28 pts (26%), adenoid cystic carcinoma 63pts (58%), undifferentiated carcinoma 12 pts (11%) and malignant mixed tumors 5 pts (5%); the disease was local in 40 pts (37%), local + distant metastases in 30 pts (28%) and only metastatic in 38 pts (35%). Conclusions: DDP is the probably the most effective single drug scheme; our data suggest that VNB has superimposeable results with a better gastroenteric and renal toxicity profile. Single drug CT seems less effective than multi drug CT with DDP-based schemes. DDP+EPI+5-FU is as effective as DDP+VNB; CBDCA+TAX seems to have worse clinical outcomes than DDP combinations. The impact of CT on symptoms is quite good while on survival needs further investigations, moreover our data confirm the need of new biological target agents to improve clinical outcomes in RMSGM. [Table: see text]
Evaluation of potential predictive markers of efficacy of dacomitinib in patients (pts) with recurrent/metastatic SCCHN from a phase II trial.
Authors: Audet Marie-Lise , Allo Ghassan , Weng Xiaoduan , Kim Lucia , Gologan Olguta , Kamel-Reid Suzanne , Siu Lillian , Coutlee Francois , Laurie Scott Andrew , Hotte Sebastien J. , Singh Simron , Winquist Eric , Chia Stephen K. L. , Chen Eric Xueyu , Chan Kelvin K. , English Patricia A , Taylor Ian , Quinn Susan , Mormont Christine , Soulieres Denis 
Published: March 2020

6041 Background: Dacomitinib is an irreversible pan-HER TKI with preclinical (EGFRvIII+ cell lines, SCCHN xenografts) and clinical activity (phase II recurrent/metastatic SCCHN; Razak et al, Ann Oncol 2012). However, little is known about predictive markers of efficacy related to EGFR signalling in this setting. Methods: Of69 pts treated with 1st-line dacomitinib in a phase II trial for recurrent/metastatic SCCHN, 48 pts had archival tumor specimens obtained before treatment and 13 had paired biopsies (days 0 and 7 of therapy, FFPE and snap frozen). EGFRvIII and PTEN (IHC), HPV genotyping and human genomic mutations (Sequenom OncoCarta Panel – 19 genes, 238 mutations) were evaluated on archival tissue. IHC expression of AKT, CC3, EGFR, ERK, HER2, HER3, MET, Ki67, pAKT, pEGFR, pERK, pHER2 and pMET was evaluated in paired specimens. The presence/absence or expression level of these markers was correlated with response (RR)/clinical benefit (CB), PFS and OS. Results: In pts with archival tissue, no statistically significant difference was found in RR/CB or PFS based on HPV, EGFRvIII, PTEN or presence of mutation. There was a trend to increased OS in HPV+ pts (HR 0.47, 95% CI 0.21–1.07, P=0.068). In paired biopsies, some expression variation was seen for cytoplasm AKT, membrane EGFR, nuclear ERK and pAKT. There was no correlation between basal expression of these markers and RR/CB or PFS. Variations in ratio to baseline of EGFR, pAKT, pERK and MET were qualitatively associated with RR/CB. No statistically significant correlations could be established for PFS, but there were interesting qualitative variations in the levels of expression of some molecules, eg, EGFR, pAKT. Conclusions: No predictive efficacy marker was identified. It cannot be determined if increased OS in HPV+ cases is due to prognostic or predictive effects. Paired biopsies demonstrated that dacomitinib was associated with variation in expression of multiple elements in signalling pathways linked to EGFR. Given the small number of paired biopsies, and large amount of data generated, descriptive study of cases is required. Further data will be presented at the meeting. Clinical trial information: 00768664.
Health care-associated infections (HAIs) in head and neck carcinoma (HNC) patients treated with chemotherapy (CT) and/or radiotherapy (RT).
Authors: Mirabile Aurora , Vismara Chiara , Bossi Paolo , Locati Laura D. , Bergamini Cristiana , Granata Roberta , Resteghini Carlo , Morelli Daniele , Scarpellini Paolo , Licitra Lisa F. 
Published: March 2020

6046 Background: HAIs are dangerous complications of HNC treatment. In lack of data we collected own data in a high volume HNCMOU, comparing them with those observed in other departments. Methods: HAIs recorded retrospectively among 2,288 hospital admissions at our HNCMOU observed from 2005 to 2009 were compared with 427 recent (2010-2012) hospital admissions. In the same period HAIs observed in ENT Surgical, Medical Oncology (MO) and Bone Marrow Transplantation (BMT) dept were recorded. Results: Between 2005 and 2009, 140 HAIs were observed in the HNCMOU: 49% Gram-, 35% Gram+, 16% fungi; 88% of P. Aeruginosa and all Enterobacteriaceae were sensible to meropenem and piperacillin/tazobactam, methicillin-resistant S. aurei (MRSA) were 42% (Table). In the last 3 years infections and resistances rates increased with a similar pattern of bacteria: among 212 HAIs (43% Gram-, 32% Gram+, 24% fungi) the majority (39%) involved respiratory tract, 89% of P. aeruginosa and 92% of Enterobacteriacae were sensible to carbapenem and 89% and 51% were sensible to piperacillin/tazobactam. MRSA were 29%. We compared these data with HAIs occurred from 2005 to 2012 into other dept: most of HAIs in ENT Surgical dept were at surgical site (41%) due to Gram+ (45%), in BMT were sepsis (56%) due to Gram+ (51%) and in MO were urinary tract infections (39%) due to Gram – (70%). Conclusions: Gram- continue to represent the first cause of HAIs in HNC cancer patients treated with CT and/or RT, suggesting a peculiar pattern. This is paralleled by a rise in carbapenem resistance, while MRSA still represent a significant fraction. [Table: see text]
Induction chemotherapy (IC) with docetaxel/cisplatin/5-fluorouracil (TPF) followed by cisplatin-containing concomitant chemoradiotherapy (CRT) in fit patients with locally advanced head and neck cancer (LAHNC): The CONDOR study—A study of the Dutch Head and Neck Society.
Authors: Driessen Chantal , De Boer J. P. , Gelderblom Hans , Rasch Coen R.N. , de Jong Martin , Verbist Berit M , Tesselaar Margot Et , Van Der Graaf Winette T.A. , Kaanders J. H. , Van Herpen Carla M.L.- 
Published: March 2020

6057 Background: Standard treatment for patients (pts) with LAHNC is concomitant CRT containing cisplatin. In general 70% of the pts receive all planned cisplatin cycles. TPF IC is associated with survival benefit, but has never been studied in combination with standard CRT. We aimed to determine if TPF followed by cisplatin-containing CRT, in 2 different schedules, was feasible. Methods: In this multicenter randomized phase II trial LAHNC pts, PS 0-1, were treated with maximal 4 TPF courses (T 75 mg/m2, P 75mg/m2 and F 750 mg/m2 day 1-5) and thereafter randomized between P 100 mg/m2 on days 1, 22, 43 combined with conventional RT (arm A) or P 40 mg/m2weekly, maximally 6, combined with accelerated RT (arm B). Primary endpoint was feasibility, defined as receiving ≥ 90% of the planned total radiation dose. Based on power analysis 70 pts were needed. Results: Following an interim-analysis, the study was early terminated after inclusion of 65 pts because only 32% of pts could be treated with the full cisplatin dose during CRT after TPF. 81,5% of pts was male, median age was 56 yrs and PS was 0 in 79% and 1 in 21%, primary site: oral cavity (23%), oropharynx (57%), hypopharynx (12%), larynx (8%). 3 pts did not start TPF; 6/62 pts were not randomized after TPF, due to death (1), toxicity (3) or severe PD (2). RR after TPF was CR 4%, PR 64% and SD 28% in the randomized pts. 27 pts were randomized in arm A and 29 in arm B. 97% of the pts received at least 90% of the planned total radiation dose. However, in arm A only 6 of the 27 pts (22%) and in arm B 12 of the 29 pts (41%) received the total planned chemotherapy part of the CRT. Most common grade 3-4 toxicity during TPF was febrile neutropenia (18%),and during CRT arm A vs arm B dehydration (26% vs 14% ), dysphagia (26% vs 24%), mucositis (22% vs 57%) and creatinin increase (19% vs 3%). After a median follow-up of 21 (7-42) months 66% of the pts was still alive. Conclusions: After TPF IC cisplatin-containing concomitant CRT is not feasible in LAHNC, because the total planned dose of cisplatin could only be administered in 32% of the pts due to severe toxicity. Clinical trial information: NCT00774319.
Acupuncture for dysphagia after chemoradiation therapy in head and neck cancer: A randomized sham-controlled study.
Authors: Lu Weidong , Lorch Jochen H. , Wayne Peter M , Davis Roger B , Tishler Roy B. , Posner Marshall R. , Goguen Laura A , Li Hailun , Macklin Eric , Burke Elaine , Jaffa Zachary , Dreyer Nicholas J , Haddad Tyler C , Buring Julie E , Rosenthal David S. , Haddad Robert I. 
Published: March 2020

6058 Background: Dysphagia is a common side effect following chemoradiation (CRT) in pts with head and neck cancer (HNC). The purpose of this pilot trial was to assess the feasibility of recruiting HNC pts and to collect preliminary data on the efficacy and safety of acupuncture on dysphagia-related QOL. Methods: Pts were eligible if diagnosed with stage III-IV HNC, without evidence of distance metastasis, receiving curative-intent CRT. Pts were randomized to 12 sessions of either active or sham acupuncture, once every two weeks, over 24 weeks from during CRT to 20-week post-CRT. All study personnel and the pts were blinded; the treating acupuncturists were not. MDADI and other questionnaires were measured at baseline (end of CRT), end of acupuncture, and at six months follow-up (12-month post-CRT). Data were analyzed by repeated-measures ANOVA adjusting for baseline. Results: Accrual was completed in December 2011. Among 42 pts enrolled, 35 (83%) received at least 8 sessions of acupuncture, and 28 (67%) received all 12. Six pts withdrew due to time constraints. No serious side effects were observed. The mean MDADI total scores improved from baseline in both treatment arms [64.5 (SE+2.4) vs. 71.4 (SE±3.1), p = 0.048; 64.5 (SE±2.4) vs. 77.8 (SE±3.0), p< 0.001]; the difference in improvement was not significant (p = 0.12). The median feeding tube duration did not differ between active and sham treatments (n = 39, median 125 days vs. 147 days, p = 0.93). Conclusions: Acupuncture is a safe and feasible treatment for HNC pts. There were improvements in QOL parameters from end of CRT to the time points examined that did not differ between the two arms. Efficacy of acupuncture to improve swallowing-related QOL in HNC pts may require more frequent or longer duration of treatment. Clinical trial information: NCT00797732.
Phase II trial of concomitant hyperfractionated-accelerated radiotherapy (HART) with cisplatin (Cis) plus cetuximab (Cet) for locoregionally advanced inoperable squamous cell carcinoma of the head and neck (LA SCCHN): Feasibility and 2-year OS.
Authors: Kuhnt Thomas , Schreiber Andreas , Pirnasch Anett , Hautmann Matthias , Hass Peter , Sieker Frank , Engenhart- Cabilic Rita , Richter Michael , Dellas Kathrin , Dunst Juergen 
Published: March 2020

6077 Background: To report the mature data of a prospective phase II-trial to investigate the feasibility, efficacy and safety of combination therapy with Cis, Cet and HART in LA SCCHN. Methods: Patients (pts) with stage III or IV, M0 SCCHN were enrolled and treated with an initial dose of Cet (400 mg/m2), followed by weekly dose of 250 mg/m² before HART, which started with a prescribed dosage of 2.0 Gy per day for three weeks followed by 1.4 Gy twice daily to a total dosage of 70.6 Gy to the gross tumor volume. Cis 40 mg/m² was administered weekly for 6 weeks. Results: From February 2007 through November 2010, 74 pts were enrolled, 68 pts with a median age of 56 years (range 37 to 69 years) were evaluable. 50% had oropharyngeal SCC. Of these, 65 pts (96%) received > 90% RT dosage, 50 pts (74%) > 90% Cet dosage and 56 pts (82%) > 4 cycles Cis 40 mg/m². 3D-CRT was used in 72% and 28 patients are currently still being followed up. The most common grade >3 toxicities were mucositis (59%) and dysphagia (52%). Cet-related grade >2- toxicities included dermatitis (15%) within the radiotherapy portals. Nine (14%) pts were missing for response evaluation (e.g. withdrawal of consent). Complete remission rate [(p)CR] was observed in 23/68 (34%) including with 16 pts (24%) who reached a CR of the primary tumor but a selective lymph node dissection was performed 6-8 weeks after end of radiation treatment for residual neck disease. Furthermore, partial remission (PR) was achieved in 29/68 (43%), so an overall response (OR) of 52/68 (77%) was reached. No change/stable disease occurred in 3/68 pts (4%), progressive disease (PD) occurred in 1 pt (1%) and 3 pts (4%) have died due to disease progression. The 2-year overall survival and disease-free survival were 64.2% and 45.3%, respectively. Conclusions: Combination therapy of LA SCCHN consisting of HART-Cis-Cet is an highly active regimen. The addition of Cet to weekly Cis and daily RT was well tolerated and resulted in encouraging local disease control and survival rates. Clinical trial information: 2005-000355-15.
Proton beam therapy combined with selective intra-arterial infusion chemotherapy for locally advanced tongue cancer.
Authors: Takayama Kanako , Nakamura Tatsuya , Takada Akinori , Makita Chiyoko , Suzuki Motohisa , Ishikawa Youjirou , Azami Yusuke , Kikuchi Yasuhiro , Tsukiyama Iwao , Kato Takahiro , Tohnai Iwai , Fuwa Nobukazu 
Published: March 2020

6086 Background: The standard treatment for locally advanced tongue cancer is surgery. However, the patient’s quality of life is lost. As a newly non-operative treatment, we report the efficacy and toxicity of proton beam therapy combined with selective intra-arterial infusion chemotherapy (PBT-IACT) for locally advanced tongue cancer. Methods: Between February 2009 and August 2012, 45 cases of stage III-IV(M0) squamous cell carcinoma of the tongue (28 men and 17 women) were treated by PBT-IACT at Southern TOHOKU Proton Therapy Center. Median age was 58 years (range:24-83 years), and clinical stage III/IVA/IVB were 11/32/2 respectively. In case of surgery, the patients required subtotal or total resection of the tongue. Initially, 2 courses of systemic chemotherapy and prophyractic whole neck irradiation (36Gy/20fr.) were performed. Subsequently, for gross tumor targets, PBT (33Gy/15fr.) and IACT were administered via the superficial temporal artery by continuous infusion of cisplatin with sodium thiosulphate. For PBT, 1 or 2 portals of 210 MeV proton beam were arranged in optimal angles to avoid overdosing the risk organ. Systemic chemotherapy was performed only for age of 70 years or younger. Results: The median follow-up was 27 months (range:8-48 months). Over all survival (OS), disease-free survival (DFS), and local control (LC) rates at 2 years were 88%,78%, 80%, respectively. LC of cervical lymph node metastases at 2 years was 86%. As the early toxic event, grade 3 mucositis (32/45) and blood/bone marrow toxicity (22/45) were observed. Within 6 months after this therapy, mandibular osteomyelitis occurred in 1 case. Conclusions: PBT-IACT appeared to be safe and has a good LC rate for locally advanced tongue cancer. Furthermore, it is not inferior to surgery and can be one of the new effective treatment options for locally advanced tongue cancer.
Coexpression of HER3 as a predictor of survival in HER2-positve breast cancer patients.
Authors: Bartsch Rupert , Berghoff Anna Sophie , Bago-Horvath Zsuzsanna , Preusser Matthias , Steger Guenther G. , Rudas Margareta , Birner Peter , Zielinski Christoph 
Published: March 2020

611 Background: Improved understanding of the pathobiology of the metastatic cascade as well as the identification of new prognostic markers may lead the path to the development of novel targeted agents in breast cancer patients (BC pts). Recently, HER3-expression was postulated as independent risk factor for metastatic spread. Methods: Pts of different BC subtypes (luminal, HER2-amplified, triple-negative) with metastatic disease were identified from a breast cancer data base. Tissue of the primary tumor was retrieved from the local pathology institute. Immunohistochemical staining of estrogen-receptor, progesterone-receptor, and HER2 and HER3 was performed. In HER2 equivocal cases, subsequent FISH analysis was performed. Results: Specimens of 110 pts (36/110 luminal, 35/110 HER2-amplified, 40/110 triple-negative) were available for this analysis. 23/110 (21%) specimens showed strong, complete, membranous staining for HER3 of at least 10% of all tumor cells. HER2/HER3 co-expression was observed in 12/110 (11%) specimens. HER3 showed a statistically significant association with HER2-expression (p=0.02; Chi square test). No correlation was observed for HER3-expression and overall survival (OS), incidence of brain metastases, or time to diagnosis of brain metastases in the entire patient cohort (p>0.05; log rank). In the HER2-amplified subgroup, however, HER3-expression was significantly associated with shorter OS (median 30 vs. 63 months; p=0.02; log rank test) and remained significant when entered into a multivariate model (p=0.02; Cox regression). Conclusions: HER2/HER3 co-expression is significantly associated with impaired OS in pts with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or inhibition of HER2/HER3 hetero-dimerization could improve prognosis of this patient population.