bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck.
Authors: Saloura Vassiliki , Cohen Ezra E.W. , Licitra Lisa F. , Billan Salem , Dinis Jose , Lisby Steen , Gauler Thomas Christoph 
Published: March 2020

6065 Background: Treatment for patients with platinum-refractory metastatic squamous cell carcinoma of the head and neck (SCCHN) is limited. Cetuximab has been approved in the US in this patient population based on a phase II trial that demonstrated 13% response rate (RR) and 5.9 months median OS. A recently conducted phase III trial of zalutumumab, a human monoclonal IgG1k antibody against EGFR, versus best supportive care showed significant increase in PFS. Here, we present the results of a companion phase II trial in the same patient population. Methods: Patients with platinum-refractory recurrent or metastatic SCCHN received weekly infusions of zalutumumab starting at a loading dose of 8mg/kg. The dose was then reduced to 4mg/kg and individually titrated by increments of 4mg/kg every 2 weeks based on skin rash evaluation up to a maximum of 16mg/kg aiming at a grade 2 skin rash. Primary objective was OS. The analysis was based on the intent-to-treat principle and OS was estimated using the Kaplan-Meier method. Results: Between January 2008 till August 2011 90 patients were enrolled in 57 centers in the United States, Europe and South America. 23% of patients had WHO PS 2 and 74% had distant relapse metastases. Grade 3-4 adverse events (AEs) related to zalutumumab were observed in 19% of the patients and included skin rash (5%), hypomagnesemia (4%) and pneumonitis (1%). Infusion-related reactions occurred in 33% of patients. The frequency of all-cause grade 3-4 AEs was 62% and included infections (14%), gastrointestinal disorders (12%), hypokalemia (6%), dyspnea (9%) and anemia (6%). Two deaths secondary to cardiac arrest in a patient with history of myocardial infarction, and respiratory acidosis in a patient with a pleural effusion and hypomagnesemia were deemed related to zalutumumab. CR was observed in one (1%) patient and PR in four (5%) patients. The median PFS was 8.6 weeks (95% CI [8.0, 10.4]) and the estimated median OS was 5.3 months (95% CI [4.1, 7.1]). Conclusions: Zalutumumab showed reasonable efficacy in platinum-refractory recurrent or metastatic SCCHN patients and dosing titration based on skin rash evaluation was feasible. Clinical trial information: NCT00542308.
The association between severe treatment-related lymphopenia and progression-free survival in patients with newly diagnosed squamous cell head and neck cancer.
Authors: Campian Jian Li , Sarai Guneet , Ye Xiaobu , Marur Shanthi , Grossman Stuart A. 
Published: March 2020

6068 Background: Severe treatment-related lymphopenia (TRL) occurs in 50% of glioblastoma and pancreatic cancer patients and is associated with early death from tumor progression. We sought to determine if similar findings were seen in head and neck squamous cell carcinoma (HNSCC). Methods: Eligible patients for this retrospective study had: 1) HNSCC cancer diagnosed in 2007-2009, 2) good performance status, 3) platinum-based chemoradiation, and 4) follow-up at Johns Hopkins. Serial total lymphocyte counts (TLC), overall survival (OS) and progression-free survival (PFS) were analyzed accounting for known prognostic factors. Results: Fifty-six adults met eligibility criteria: median age: 57 years, female: 21%, HPV+: 61%, surgery prior to chemoradiation: 16%, stage IVA-IVB: 77%, T stage 3-4: 40% and N stage 2b-3: 56%. Changes in TLC are shown below (Table). 14/56 patients (25%) had tumor recurrence and 9 (16%) died of their tumor. HPV+ patients had longer PFS (p=0.01) and OS (p=0.006) than HPV- patients. 10/22 HPV- patients had disease progression and 7 died. HPV- patients who developed grade III-IV TRL two months after beginning chemoradiation had a strikingly higher hazard rate for disease progression than those whose TLC remained higher (multivariate analysis HR 6.2, 95%CI: 1.1-35.2; p=0.039). Too few events occurred in the HPV+ cohort for analysis. Conclusions: TLCs were normal before chemoradiation. However, two months after chemoradiation ~60% of patients had severe TLC regardless of HPV status. HPV- patients with severe TRL were much more likely to have disease progression than those without TRL. Prospective studies are needed to confirm these findings which are similar to those reported in other cancers. Preservation of the immune system during chemoradiation may be important to improving PFS and OS. [Table: see text]
Evaluating the cost-effectiveness of low-level laser therapy (LLLT) in head and neck cancer patients submitted to concurrent chemoradiation.
Authors: Antunes Heliton Spindola , Herchenhorn Daniel , Small Isabele Avila , Araujo Carlos Manoel , Cabral Elida , Rampini Mariana Pereira , Rodrigues Pedro Carvalho , Silva Tereza Giannini Pereira da , Ferreira Elza Maria de Sa , Dias Fernando Luiz , Teich Nelson , Teich Vanessa , Schluckebier Luciene Fontes , Ferreira Carlos G. M. 
Published: March 2020

6071 Background: Oralmucositis (OM) is a main factor for increasing treatment costs in head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of LLLT to prevent oral mucositis in HNSCC patients submitted to CRT. Methods: From June 2007 to Dec 2010, 94 patients with HNSCC of nasopharynx, oropharynx and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial (47 LLLT (LG) and 47 placebo (PG)). CRT consisted of conventional RT 70.2 Gy (1.8Gy/d, 5 times/wk) + concurrent cisplatin 100 mg/m2 every 3 wks. The LLLT used daily was a diode InGaAlP (660nm-100mW-4J/cm²). OM evaluation was done by WHO and OMAS scale. The resources used by patients in both groups were documented during the trial. Unit costs for procedures were obtained from a public reference list (SIGTAP / SUS) as of Jan 2012 and unit costs for drugs were based on ex-factory prices. The cost per laser session was US$ 34.00 (exchange rate from Brazilian currency to US dollar = 1.95) for the baseline analysis. Costs of RT, chemotherapy, fluconazole and chlorhexidine 0.12% were equivalent in both groups and therefore not included in the analysis. Hospitalization rates associated with the treatment of oropharyngeal or oral mucositis were not documented in the study and were estimated according to previously published data. Results: Under the perspective of the Brazilian public healthcare system (SUS), total costs were higher in PG than LG on opioide use (LG= US$ 29.45; PG= US$143.72, gastrostomy (LG= US$ 41.69; PG= US$107.22 ) and hospitalization (PG= US$ 63.59). In LG costs were higher with laser therapy (US$ 1,549.50). The total incremental cost associated with the use of LLLT was US$ 1,306.61 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 3,838.16 per case of grade 3 and 4 mucositis avoided when compared with no treatment. Conclusions: Our results indicate that laser group had a smaller morbidity during treatment and LLLT is cost-effective when compared to pacebo under a threshold of at least US$ 4,000 per avoided mucositis case. Clinical trial information: NCT01439724.
Clinical utility of CT and FDG PET/CT in assessing the neck in node-positive head and neck cancer after chemoradiotherapy.
Authors: Nakahara Susumu , Takenaka Yukinori , Yamamoto Yoshifumi , Yasui Toshimichi , Hanamoto Atsushi , Inohara Hidenori 
Published: March 2020

6082 Background: Concurrent chemoradiotherapy has been widely accepted to treat locoregional advanced head and neck cancer, but the need for subsequent neck dissection remains controversial. Our objective was to determine whether CT or fluorodeoxyglucose (FDG) PET/CT is superior in the evaluation of persistent nodal disease after chemoradiotherapy in patients with node-positive head and neck squamous cell carcinoma (HNSCC). Methods: Study entry criteria included node-positive HNSCC treated with concurrent chemoradiotherapy, a local complete response, and post-treatment CT and FDG PET/CT studies 11 weeks after chemoradiotherapy. Fifty-eight patients with 68 node-positive necks were eligible. Nodes larger than 1 cm (minor axis), or with central necrosis on CT, or any visually hypermetabolic nodes on FDG PET/CT were considered clinically positive. Regardless of PET/CT findings, necks with positive CT were subjected to neck dissection, whereas those with negative CT were observed without neck dissection. Results: Seventeen necks showed positive CT, 13 and 4 of which underwent neck dissection and fine needle aspiration cytology, respectively, resulting in pathologic evidence of persistent nodal disease in 5 necks. Four of 51 necks with negative CT developed regional recurrence. Diagnostic accuracy of CT and PET/CT is shown in table. In general, the negative predictive value (NPV) was equivalent between CT and FDG PET/CT, whereas FDG PET/CT was better than CT in the specificity and accuracy. Conclusions: In patients with HNSCC, both CT and FDG PET/CT after chemoradiotherapy have a high NPV for excluding residual regional disease and avoiding unnecessary neck dissection. Although the NPV is similarly high, PET/CT has superior utility compared with CT because the number of false positive findings is less in PET/CT than CT. [Table: see text]
miRNA analysis between malignant and benign tissue and circulating exosomes (CE) in patients (pts) with tongue squamous cell carcinoma.
Authors: Rabinowits Guilherme , Flores Ludmila , O'Neill Anne M. , Stevenson Kristen , Ghobrial Irene M. , Vergara Victoria , Jo Vickie Y , Verselis Sigitas Jonas , Chau Nicole Grace , Lorch Jochen H. , Haddad Robert I. 
Published: March 2020

6088 Background: The identification of a specific miRNA pattern in HNSCC is challenging given the heterogeneity of this disease and different methodologies used in prior studies. Here we chose to group pts according to primary tumor location and used Nanostring as a larger miRNA platform. Methods: CE-miRNA was isolated from 500ul of plasma collected in Heparin/EDTA tubes. Samples were pretreated with Pacific Hemostasis Thromboplastin D. Supernatant was treated with ExoQuick. Exosomal pellet was resuspended in 1ml of QIAzol Lysis Reagent. Formalin fixed paraffin embedded (FFPE) samples were deparaffinized and digested with proteinase K. miRNA from plasma and FFPE were isolated with miRNeasy Mini Kit. Samples were processed by Nanostring Technology. In this analysis, only tongue cancer pts were selected due to availability of paired tumor and benign tissue miRNA in conjunction with CE from the same pts and others with tongue cancer. Results: 21 HNSCC pts and 32 age-matched controls have enrolled to date. For homogeneity we analyzed only patients with tongue cancer (n=9): 8 males, median age 55.5 years (range 24-64), all had stage IVA tongue cancer (6 base of tongue), 6 HPV/p16 positive. Nine pts received chemoradiation; 4 also had surgery; 8 had clinical and radiological complete response. Of the 800 miRNAs tested 62 were overexpressed and 15 were suppressed in the tumor compared to benign tissue in the same pts. Of those overexpressed and suppressed in tumor tissue, 4 (miR23a-3p; miR150-5p; miR199a-5p; miR203) had a post/pre treatment average ratio (PPTAR) less than 1, while 4 (miR720; miR1253; miR145-5p; miR1283) had PPTAR greater than 1, respectively on CE of pts. miR150-5p was suppressed and miR1283, miR145-5p and miR1253 were overexpressed on CE of control samples compared to pre treatment samples of pts. Conclusions: Of the 800 miRNAs, 8 appear to correlate with treatment response. The average levels of 4 of those miRNA mirror the average levels of tumor tissue miRNA and is in an inverse relationship with benign tissue and control blood samples, suggesting this may be a unique signature for tongue cancer. This observation needs to be validated in larger studies.
Survival in patients with HPV-positive oropharynx squamous cell carcinoma with distant metastases.
Authors: Price Katharine Andress Rowe , Okuno Scott H. , Garcia Joaquin J. , Molina Julian R. , Olsen Kerry D. , Kasperbauer Jan C. , Price Daniel L. , Garces Yolanda I. , Ma Daniel , Neben-Wittich Michelle A. , Shull Shastin E. , Foote Robert Leonard , Moore Eric J. 
Published: March 2020

6095 Background: Prognosis for patients (pts) with locally-advanced, HPV-positive oropharynx squamous cell carcinoma (HPV+OPSCC) is significantly better than for pts with HPV-negative head and neck squamous cell carcinoma (HNSCC). Historic survival of pts with metastatic HNSCC is 6-9 months with palliative therapy. However, the prognosis and survival of pts with HPV+OPSCC with distant metastases is not known. Methods: Pts with HPV+OPSCC with distant metastatic disease were identified from databases from the departments of surgery, radiation, and medical oncology. Demographic and clinical data was abstracted from the medical record. All pts had confirmed HPV/p16+ disease. Results: Fifteen pts with metastatic HPV+ OPSCC were identified. The median age was 57 years (range 42-78, 15 male). The median pack-year smoking was 0 (range 0-120). Primary site included 10 tonsil and 5 tongue base. At diagnosis, one pt had stage III and 14 had stage IV disease (IVA: 9, IVB: 2, IVC: 3). T- and N-stage included T1 (1), T2 (10), T3 (3), T4 (1) and N1 (1), N2a (1), N2b (9), N2c (3), N3 (1). Extracapsular extension was seen in 8 pts, absent in 2, and unknown in 5. Seven pts had lymph node (LN) involvement at level IV/V. Initial therapy for locally-advanced disease included surgery followed by adjuvant radiation (RT) in 1 pt and chemoRT in 8, and definitive chemoRT in 3 pts. Three pts were metastatic at initial diagnosis. Of 6 pts with an isolated metastatic site, 3 pts are alive > 2 years from diagnosis of metastasis (median 1.97 years, range 0.49-2.29). Palliative therapy included surgery (3), RT (9), platinum chemo +/- cetuximab (8), cetuximab alone (2) or with a taxane (2). The most common sites of metastasis included bone (6), lung (5), and LNs (5). The 1-year survival rate after diagnosis of metastatic disease was 92%. The median time to diagnosis of metastatic disease after definitive therapy was 0.47 years (95% CI 0.19-1.29); 75% of pts who developed metastatic disease did so within 1 year of definitive therapy. Of note, 2 of the 15 pts developed a secondary immune-mediated malignancy (melanoma and non-HIV associated Kaposi’s sarcoma). Conclusions: The survival of pts with metastatic HPV+OPSCC is significantly better than that of historic controls.
A phase I pharmacokinetics trial comparing PF-05280014 (a potential biosimilar) and trastuzumab in healthy volunteers (REFLECTIONS B327-01).
Authors: Yin Donghua , Barker Kerry B , Li Ruifeng , Meng Xu , Reich Steven D , Ricart Alejandro D , Rudin Dan , Taylor Carrie T , Zacharchuk Charles M. , Hansson Arne G 
Published: March 2020

612 Background: PF-05280014, a proposed biosimilar to trastuzumab, has an identical amino acid sequence and similar physicochemical and in vitro functional properties to trastuzumab. This study was designed to demonstrate PK similarity of PF-05280014 to trastuzumab from the US (trastuzumab-US) and EU (trastuzumab-EU), and between the licensed drugs. Safety and immunogenicity were also evaluated. Methods: In this double-blind trial (NCT01603264), 105 healthy male volunteers, 18-55 years old were randomized 1:1:1 to receive a single 6 mg/kg IV dose of PF-05280014, trastuzumab-US or trastuzumab-EU. All subjects provided informed consent. PK, safety, and immunogenicity assessments were conducted for 70 days. PK similarity for a given test-to-reference comparison was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to the last time point (AUCT) and maximum concentration (Cmax) were within 80% – 125%. Results: The baseline demographics for the 101 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar characteristics of target-mediated disposition and similar PK parameters (Table). The 90% CI for the ratios of Cmax, AUCT, and AUC0-∞were within 80% – 125% for the comparisons of PF-05280014 to trastuzumab-EU or trastuzumab-US, and trastuzumab-EU to trastuzumab-US. Adverse events (AE) were similar for the 3 arms with treatment-related AEs reported by 71.4%, 68.6%, and 65.7% subjects in the PF-05280014, trastuzumab-EU and trastuzumab-US, respectively. No serious AEs were reported. Only 4 subjects had treatment interruptions; 2 discontinued. Only 1 subject (trastuzumab-EU) developed anti-drug antibodies after dosing. Conclusions: This study demonstrates PK similarity of PF-05280014 to both trastuzumab-US and trastuzumab-EU and of trastuzumab-EU to trastuzumab-US. The three study drugs also showed similar safety profiles. Clinical trial information: NCT01603264. [Table: see text]
Correlation between poly (ADP-ribose) polymerase (PARP) and phospho-p65 expression in human breast cancer.
Authors: Klepczyk Lisa Caroline , Wei Shi , Brazelton Jason D. , Keene Kimberly Sue , Bonner James A. , LoBuglio Albert F. , Forero Andres , Grizzle William E. , Yang Eddy Shih-Hsin 
Published: March 2020

623 Background: Despite the efficacy of targeted agents in patients with HER2+ breast cancer, resistance often develops necessitating novel treatment strategies. Poly (ADP-ribose) polymerase inhibitors (PARPi) are known to target tumors with aberrant DNA repair. We previously reported sensitivity of HER2+ breast cancer cells to PARPi independent of a DNA repair deficiency but rather due to attenuation of NF-kB signaling. In this study, we investigated the expression of PARP and the active NF-kB subunit phospho-p65, indicators of activity for these pathways, in human HER2+ breast tumors and compared to HER2- tumors. Methods: Patients with breast cancer treated at the University of Alabama at Birmingham between the years 1999 and 2012 were identified. Formalin-fixed, paraffin-embedded tissue blocks were stained for PARP and phospho-p65 and evaluated independently by two blinded physicians, including a board-certified pathologist. An H-score was calculated by multiplying the percent of tumor cells with staining intensity of 0, 1, 2, and 3 and subsequently adding these together for a final score of 0-300. Nuclear and cystosolic staining were scored separately for both proteins. Results: Forty-six HER2+ and 38 HER2- patients with available tissue were identified; however, only 41 HER2+ and 32 HER2- cases had tumoral tissue at the time of analysis. PARP and phospho-p65 were found to be almost exclusively nuclear in both groups. The mean nuclear PARP score was 122.3 in HER2+ cases compared to 61.6 in HER2- cases (p value <0.0001). Mean nuclear phospho-p65 scores were 89.0 and 59.4 in HER2+ and HER2- groups, respectively (p value 0.0008). Additionally, a significantly positive correlation was observed between PARP and phospho-p65 levels. Conclusions: Our study suggests that HER2+ breast cancers have elevated PARP and NF-kB activity compared to HER2- cancers. Furthermore, a direct correlation between PARP and phospho-p65 levels was found. When combined with our previously published preclinical findings, the current research supports the potential clinical utility of PARPi in patients with this aggressive form of breast cancer.
Predictive factors for pathologic complete response (pCR) to trastuzumab (T)-based neoadjuvant chemotherapy in HER2+ breast cancer (BC) women treated in the National Cancer Institute (NCI) of Mexico.
Authors: Sifuentes Erika , Chavarri Guerra Yanin , Baez-Revueltas F. Berenice , Soto-Perez-de-Celis Enrique , Lara-Medina Fernando , Ruano Santiago , Villarreal-Garza Cynthia Mayte 
Published: March 2020

634 Background: Neoadjuvant treatment identifies subgroups of patients (pts) with different prognosis. In HER2+ BC, some tumors have been reported to be more sensitive to anti-HER2 therapy than others. We conducted an exploratory analysis in HER2+ BC women who received T-based neoadjuvant chemotherapy. Methods: Clinico-pathologic data from HER2+ BC pts who received neoadjuvant chemotherapy and T between January 2007 and May 2012 at the NCI were identified. Estrogen receptor (ER), progesterone receptor (PR) and HER2 expression were determined by immunohistochemistry and/or FISH. pCR was defined as complete absence of invasive tumor in breast and axillary nodes. Proportion differences were tested using the Chi-square test. A generalized linear model was used for multivariate analysis. Results: 243 pts received T-based neoadjuvant chemotherapy for localized HER2+ BC tumors. Median age was 49 (26-72) years. 96% had positive axillary nodes at diagnosis and median tumor size was 5.5 (1.5-20) cm. 49.4% had hormone receptor (HR) + (ER+ and/or PR+) and 50.6% HR negative (ER- and PR-) tumors. 63.4% pts achieved pCR. HR negative tumors reached significantly higher pCR rates than HR + tumors (69.9% vs. 56.7%, p=0.034). Pts with inflammatory BC (n=27) had a trend to achieve pCR less frequently than the non-inflammatory tumors (48.1% vs. 65.3%). Those who received taxane-anthracyline sequence chemotherapy (n=20) achieved pCR in 70% of the cases vs. 62.8% with anthracycline-taxane sequence. Differences among other variables (age, tumor size, nodes and HER2 positivity ++/+++) were not significant. Variables that positively influenced pCR were HR negative status (p=0.015), non-inflammatory BC (p=0.082) and chemotherapy sequence (p=0.086). Conclusions: HR negative HER2+ BC tumors were associated with higher pCR, consistent with neoadjuvant trial reports. Preclinical data suggest bi-directional crosstalk between HER2 and ER pathways, which might influence anti-HER2 agents and chemotherapy sensitivity for tumors co-expressing both receptors. New strategies are needed to overcome resistance for HER2+ HR+ BC tumors.