bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective, open-label, randomized phase II trial to evaluate the changes of bone resorption marker after administration of zoledronic acid (ZOL) in nasopharyngeal cancer (NPC) patients with bone metastases (BM)
Authors: Zhao Y. , Liao H. , Hou X. , Sun J. , Guo Y. , Li S. , Zhang L. 
Published: August 2020

6063 Background: ZOL is the only bisphosphonate that has demonstrated efficacy for the prevention of skeletal-related events (SREs) in patients with BM in a wide range of tumor types. Recent retrospective analyses also showed that normalization of N-telopeptide of type I collagen (NTX) over 3 months by the treatment of ZOL provided a continuum of SRE risk reduction and survival benefit in patients with BM (Lipton et al. ASCO 2007). Therefore, we conducted the prospective open-label randomized phase II trial to evaluate the changes of NTX after administration of ZOL in NPC patients with BM. Methods: Newly diagnosed NPC patients with BM were randomized to receive chemotherapy of cisplatin (20mg/m2 IV, D1–5) plus FU (500mg/m2 IV, D1–5) (CF regimen, q3wks) and intravenous ZOL (4mg, q4wks, for 3months, CF+ZOL Group) or the same chemotherapy alone (CF Group). Urinary NTX was measured by ELISA method (Coleman et al. JCO 2005) at baseline and 1, 2, 3 months after administration of ZOL in all patients. Results: Sixty patients were enrolled into the study, 30 patients in each group. The median chemotherapy cycles was the same (4 and 4, respectively) in two groups. The median baseline NTX level had no difference between the two groups (75.4 vs. 95.6 nM BCE/mM creatinine, respectively p>0.05). The NTX decreased 65.9% within 1 month in CF+ZOL group, whereas NTX increased 2.61 % in CF group (p<0.01). The median NTX decrease percentage in 2,3 months after treatment were 70.8%, 86.5% in CF+ZOL Group and 15.9%, 34.5% in CF Group respectively (p<0.01, p<0.01). Conclusions: ZOL administered with chemotherapy (CF) consistently reduced NTX levels in NPC patients with BM, indicating potential benefit of ZOL may exist in this group of patients. The value of NTX reduction in NPC patients with BM need to be further studied in larger prospective randomized trials. [Table: see text] [Table: see text]
Synchronous and metachronous bilateral breast cancer: Are the risks greater in women with a history of radiation for Hodgkin lymphoma?
Authors: Elkin E. B. , Gonzales A. R. , Ishill N. M. , Klem M. L. , Hodgson D. , Ng A. K. , Marks L. B. , Weidhaas J. , Freedman G. M. , Miller R. C. , Yahalom J. 
Published: August 2020

607 Background: Women with a history of radiation therapy (RT) for Hodgkin lymphoma (HL) have an elevated risk of breast cancer (BC). The characteristics, treatment and outcomes of these cancers, compared with sporadic breast cancers, are not well described. In particular, rates of synchronous and metachronous bilateral BC may be greater in patients with a history of RT for HL. Methods: Women diagnosed with BC between 1980 and 2006 following RT for HL were identified retrospectively from 8 institutions in North America. Each patient in this cohort was matched with 3 BC patients with no history of HL, from the same institution, by age at BC diagnosis, year of BC diagnosis and race. Information on patient and tumor characteristics, disease recurrence and new contralateral tumors was obtained from medical records. Analysis of metachronous contralateral breast cancer (CBC) was limited to women with a breast at risk, and adjusted hazard ratios (HRs) for CBC were estimated using Cox proportional hazards regression. Results: 253 BC patients with a history of RT for HL were matched with 741 patients with sporadic BC. The median interval between HL and first BC diagnosis was 19 years. Median age at BC diagnosis was 44 years and median follow-up was 5 years from BC diagnosis. Synchronous bilateral BC was diagnosed in 6% of the HL survivors and 2% of the matched patients with sporadic BC. Among women with unilateral disease, 21% of HL survivors and 3% of sporadic BC patients had a bilateral mastectomy. Overall 64 women with a breast at risk developed metachronous CBC. BC patients with a history of RT for HL had a greater rate of metachronous CBC (adjusted hazard ratio 3.3, 95% CI 2.1–5.8), controlling for patient, tumor and treatment characteristics. In addition, those who received chemotherapy for BC were less likely to develop CBC (adjusted HR 0.51, 95% CI 0.31–0.85), and those with a family history of BC in a 1st degree relative were more likely to develop CBC (adjusted HR 1.8, 95% CI 1.1–3.0). Conclusions: Women who develop BC after RT for HL have more than 3 times the risk of CBC than similar women with sporadic BC. Our findings support close follow-up for CBC in BC patients with a history of RT for HL and may inform decisions about prophylactic mastectomy in this population. No significant financial relationships to disclose.
A pan-European survey to gauge public awareness and understanding of head and neck cancer and associated risk factors
Authors: Leemans C. R. , Lefebvre J. , Vermorken J. B. 
Published: August 2020

6073 Background: Head and neck cancer is the sixth most frequently occurring cancer worldwide yet there appears to be little awareness of this disease amongst the general public in Europe. As part of an ongoing program to fully understand the patient perspective, the ‘About Face’ survey was planned and conducted in collaboration with the European Head and Neck Society to gauge current awareness and understanding of head and neck cancer and its associated risk factors. Methods: A total of 7,520 Omnibus internet interviews were conducted in 7 European countries (FR, DE, IT, NL, SP, SW, UK) in September 2008. Results: Only 23% of respondents overall were aware of the term ‘head and neck cancer.’ While most symptoms of head and neck cancer were recognized; the majority were cited correctly by fewer than half of respondents; 60% believed that ‘head and neck cancer’ includes tumors of the brain. Sixty-one percent of those surveyed underestimated the incidence of head and neck cancer in Europe by at least a factor of 10. While the majority recognized the link between head and neck cancer and smoking or high alcohol intake, far fewer were aware of the role of excessive sun exposure or HPV infection in disease etiology. One in four respondents felt that the consequences of surgery would cause the most distress to a person diagnosed with the disease. Conclusions: There is a general lack of knowledge amongst the general public in Europe of the risk factors and symptoms of head and neck cancer. This is a significant issue that should be addressed as these data suggest that patients may be more likely to delay consulting a physician and therefore be diagnosed with this difficult-to-treat disease at a late stage. Further education of the public on head and neck cancer is warranted. [Table: see text]
TPF versus PF as induction therapy in unresectable head and neck cancer: A pharmacoeconomic analysis
Authors: Liberato N. L. , Licitra L. , Bogaerts J. , Danese G. , Marchetti M. , Quaglini S. , Rognoni C. , Rubrichi S. , Vermorken J. B. 
Published: August 2020

6075 Background: Adding docetaxel to induction therapy with PF has been shown to improve overall survival of patients with head and neck cancer. On the basis of the raw data from the EORTC trial 24971/TAX 323 a pharmacoeconomic analysis has been performed. A National Healthcare System perspective and a 5-years temporal horizon have been adopted. Methods: A decision-analytic approach has been adopted, and a Markov model has been used to represent patient's weekly transitions among different health states, related to treatment (chemotherapy, radiotherapy, surgeries, palliative care) and disease status (complete/partial/no response, progression, recurrence). Constant or time-variant costs and quality of life adjustment factors have been assigned to each health state, together with transition probabilities to other states. A 3% discount factor has been used for costs sustained after the first year. The model allowed calculating expected life years (LYs), quality adjusted life years (QALYs) and costs. From these figures, incremental cost/effectiveness (ICER) and cost/utility (ICUR) ratios have been calculated. Robustness of results obtained with baseline values has been tested with probabilistic multivariate sensitivity analysis. Results: In the base case analysis, treatment with TPF yields an expectancy of 2.38 LYs and 1.53 QALYs at a cost of Euro (E) 23,018, which for PF were 1.93 LYs, 1.11 QALYs, and E 19,567, respectively. ICER and ICUR were E 7,669/LY and E 8,217/QALY, respectively. Sensitivity analyses were performed varying transition probabilities of 10%, costs of 30% and utility scores of 20% of their basal values. The analyses showed that 86% and 84% of the results lie below the threshold of E 50,000/LY and E 50,000/QALY, respectively. Conclusions: In our analysis TPF induction chemotherapy proved to be cost-effective with respect to PF, having an ICER and ICUR comparable to other widely accepted healthcare interventions. [Table: see text]
Role of mixed lineage kinase 3 in response of head and neck squamous cancer cell lines to epidermal growth factor receptor (EGFR) inhibition
Authors: Conley B. A. , Leece C. M. , Chandana S. , Dowlashati S. 
Published: August 2020

6076 Background: More efficacious treatments of head and neck squamous cancers (HNSCC) are urgently needed. HNSCC overexpress EGFR, yet the efficacy of EGFR inhibitors is marginal, with minimal effect on patient survival. Mixed lineage kinases (MLKs) are members of a large family of mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs) that activate MAPK pathways, involving JNK, ERK 1/2 and p38 cell signaling pathways. (Gallo KA, Johnson GL, Nat Rev Mol Cell Biol. 2002;3:663–72) We explored the role of MLK3 in HNSCC as a possible therapeutic target. Methods: The requirement of MLK3 for cell proliferation and survival of HNSCC cell lines UM-SCC-38 and -47 (HPV+) (obtained from TE Carey, U Michigan) was investigated using RNA interference (siRNA) and MLK3 inhibitor K252a to inhibit the expression and activity of MLK3. Cells were also exposed to EGFR inhibitor Compound 56 at various concentrations. Proliferation was assessed with MTT after 72 h exposure. The effect of MLK3 inhibition on relevant cell signaling pathways was assessed by immunoblotting with activation-specific phosphoantibodies directed against MAPKs, the prosurvival kinase Akt and apoptotic proteins. Results: MLK3 is overexpressed in malignant HNSCC cell lines compared to normal tonsil lysate, and its expression can be inhibited by siRNA or K 252a. Inhibition of MLK3 expression is associated with downregulation of phospho-Akt and with decreased proliferation. Compound 56 inhibits proliferation at lower concentrations in HPV+ cell line UM-SCC-47 (10 microM) compared with UM-SCC-38 (25 microM), inhibits expression of pErk, and decreases expression of pAkt. Combining siRNA or K252a and compound 56 showed less pAkt expression and increased apoptosis (caspase 3 or PARP cleavage) compared with compound 56 alone. Conclusions: MLK3 may have a role in avoiding apoptosis in HNSCC cells. Its inhibition may enhance the effects of EGFR inhibition in HNSCC. No significant financial relationships to disclose.
Effect of insulin-like growth factor 1 receptor inhibitor on sensitization of head and neck cancer cells to cetuximab and methotrexate
Authors: Hatakeyama H. , Parker J. , Wheeler D. , Harari P. , Levy S. , Chung C. H. 
Published: August 2020

6079 Background: Insulin-like growth factor 1 receptor (IGF1R) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and IGF1R inhibitors have been shown to modulate sensitivity to selected chemotherapeutic agents and radiation. The combination effects of an IGF1R inhibitor, MK-0646, with cetuximab or cytotoxic agents that are commonly used in the treatment of recurrent and/or metastatic HNSCC were examined in cetuximab resistant and sensitive HNSCC cell lines. Methods: The cell lines, SCC1 and its cetuximab-resistant clone 1Cc8, were treated with MK-0646, cetuximab or methotrexate, and a combination of MK-0646 and each anti-cancer drug (MK-0646 was supplied by Merck & Co., Inc.). The effect of treatments on cell proliferation and anti-tumor activity was determined using MTS assay in vitro and in vivo using mouse xenografts generated from the cell lines. Overall changes in the gene and protein expressions with the treatments were determined by DNA microarrays and western blots. Results: The IGF1R inhibitor, MK-0646, showed high-sensitivity in vitro xenograft model in SCC1 as monotherapy and increased sensitivity to cetuximab in SCC1 and to methotrexate in 1Cc8 in combination. However, MK-0646 did not inhibit cell proliferation in vitro and in vivo in 1Cc8. The gene expression array and western blot analyses showed that MK-0646 decreased expression of AKT and dihydrofolate reductase (DHFR), a target of methotrexate. Increased expressions of AKT and DHFR have been shown to associate with cetuximab and methotrexate resistance as well as radiation resistance. Conclusions: The development of tolerance in response to the IGF1R inhibitor and cetuximab is common. Whereas IGF1R inhibitors may have little therapeutic impact in cetuximab resistant, the IGF1R inhibitor may modulate response to selected chemotherapeutic agents and to radiation. The IGF1R inhibitor appears to enhance cetuximab and methotrexate response, and modulates genes associated with radiation resistance thereby providing alternative regimens for recurrent and refractory HNSCC patients who have developed resistance to initial therapies. No significant financial relationships to disclose.
Meta-analysis of the impact of human papillomavirus on cancer risk and overall survival in head and neck squamous cell carcinoma
Authors: Dayyani F. , Etzel C. , Liu M. , Ho C. , Lippman S. M. , Tsao A. S. 
Published: August 2020

6080 Background: Human papillomavirus (HPV) is an important etiologic factor in HNSCC and its prevalence has been reported in several independent studies. We conducted a meta-analysis to determine the prevalence of HPV, its impact on risk of developing HNSCC and overall survival (OS). Methods: Pubmed search terms “HPV” and “HNSCC” were used to identify 40 clinical and translational studies between the years 1980–2008 that reported the prevalence of HPV in HNSCC. Statistical software STATA 10.0 was used in the meta-analyses to identify the association of HPV and HNSCC risk and OS. Pooled adjusted odds ratio (OR) or hazard ratio (HR) were obtained using a random-effects model. The amount of heterogeneity between studies was estimated with both the Chi-squared based Q test and the I2 statistic model. Potential sources of publication bias were detected using funnel plots. OS between the trials was compared in forest plot. Results: A total of 6,794 patients (pts) were included. The prevalence of HPV among HNSCC pts was 24.2%; and 86.8% of all HPV(+) tumors were HPV16. Thirteen studies (n = 1933 pts) determined HPV status by serology and the remainder detected HPV DNA in tumor tissue by PCR. Overall, HPV positivity conferred an increased risk for HNSCC (OR = 1.43; 95% CI 1.04–1.82). Risk for HNSCC among HPV16(+) pts was 4.47 times that of HPV16(-) pts. The OS was improved in HPV(+) pts compared to HPV(-) pts (HR = 0.40; 0.27–0.53). In HPV16(+) pts the HR for OS was 0.41 and the survival benefit was even more pronounced in the subgroup of HPV16(+) oropharyngeal cancers (HR = 0.38;0.17–0.58). Conclusions: This meta-analysis provides further evidence supporting the role of HPV as an important causative agent in HNSCC and supports HPV(+) HNSCC as a separate biologic entity which likely should be treated differently than HPV(-) HNSCC. Additional analysis on treatment outcomes to systemic and local therapy is ongoing. No significant financial relationships to disclose.
Prognostic significance of metabolic adaptation for hypoxic environment in oral squamous cell carcinoma
Authors: Hong S. , Roh S. , Koh Y. , Won H. , Shim B. , Byun J. , Lee M. , Woo I. , Kang J. , Hong Y. 
Published: August 2020

6082 Background: During tumor growth, tumor adapts the hypoxic environment and increases glycolysis. This metabolic switch is related to the aggressive malignant behavior. We investigated the connection between the biomarkers related to the glycolytic metabolism (HIF-1α, PDK-1, LDH-5) and clinicopathologic characteristics in oral cavity and oropharynx squamous cell carcinoma (SCC). Methods: Eligibility criteria was the patients diagnosed oral SCC, received curative radical resection and had available tissue samples. Immunohistochemical stain of the HIF-1α, PDK-1, and LDH-5 was done. Statistical analysis was performed to compare biomarkers between patients and time point. Results: Overall 74 patients were enrolled and stage grouping of the patients was as follows: stage I, 25 (33.8%) patients; stage II 17 (23.0%); stage III 8 (10.8%); stage IV 24 (32.4%). 25 patients were relapsed and 5-year disease-free survival (DFS) rate was 61.4%. High expression of HIF-1α was related to the advanced T stage (p = 0.029), more invasive tumor (p = 0.003) and tumor recurrence (p = 0.037). High expression of PDK-1 was related to the advanced N stage (p = 0.026) and high expression of LDH-5 was related to the lymphatics invasion (p = 0.028), advanced N stage (p = 0.020) and more invasive tumor (p = 0.015). The high expression of HIF-1α, PDK-1, and LDH-5 showed a significant correlation to each other. 16 (21.6%) patients were highly expressed all three markers. High expression of all three markers correlated with more invasive tumor (p = 0.004) and tumor recurrence (p = 0.017). In survival analysis, high expression of HIF-1α and LDH-5 associated with shorter DFS in log rank test (p = 0.002 and p = 0.016, respectively). High expression of all three markers was also associated with shorter DFS (p = 0.002). In multivariate Cox regression analysis, high expression of all three markers was strong independent prognostic factor for DFS (p = 0.021). Conclusions: The oral SCC which glycolytic metabolism was changed showed a more invasive and aggressive phenotype. Taken together, biomarkers related tumor metabolism may be independent prognostic markers for the DFS in the patients with oral SCC. No significant financial relationships to disclose.
Clinicopathologic predictors of distant metastasis in head and neck cancer
Authors: Holsinger F. C. , Dong W. , Bekele N. , Weber R. S. , Kies M. S. , Glisson B. S. 
Published: August 2020

6086 Background: Despite advances in achieving improved locoregional control for patients with head and neck cancer (HNC), overall survival has not improved in the last 30 years. Several studies have implicated distant metastasis as a potential cause, hindering progress in the treatment of HNC. However, little is known about which patients fail systemically. We therefore sought to identify clinico-pathological factors that are associated with distant metastasis as the only cite of failure. Methods: We retrospectively studied 389 patients with head neck squamous cell carcinomas with distant metastases as the primary site of failure excluding all patients with locoregional recurrence and those receiving chemotherapy at primary presentation. The median follow up period was 5.3 years. An estimate of the risk of DM and DM free survival by prognostic factors was calculated using multivariate analysis and Cox proportional modeling. Results: Overall, 11% (43/389) of the patients developed DM. With univariate analysis, site of the tumor arising within the laryngopharynx, T stage (T3–4), N stage>2, and metastasis to level IV were significantly associated with DM. However, using Cox proportional hazards regression modeling, two clinicopathologic variables, N classification >N2b and diminishing degree of histologic differenention, were found to be most significantly associated with the development of systemic, distant metastasis. For patients staged as N2b or N2c, there was a relative risk (RR) of 6.13 (95% CI: 2.61 - 14.38; p < 0.0001) for developing DM. For patients staged as N3, the RR was 8.23 (95% CI: 2.39 - 28.38; p < 0.001). For patients with poorly differently HNSCC, RR was 11.01 (95% CI: 1.42 - 85.15; p = 0.022) Conclusions: Recognizing patients at primary presentation with tumors with the highest risk for the development of DM might le us to selectively treat them aggressively with systemic therapy to eradicate the tumor, thus improving overall survival rates. No significant financial relationships to disclose.
Optimal timing of radioactive tracer for sentinel node biopsy in breast cancer patients
Authors: Reuter N. P. , Bower M. R. , Scoggins C. R. , Martin R. C. , McMasters K. M. , Chagpar A. B. 
Published: August 2020

611 Background: While sentinel node biopsy (SNB) is well established as a minimally invasive means of staging the axilla in breast cancer patients, the optimal timing of injection of technetium 99m sulfur colloid (Tm) for SNB remains unclear. Methods: In a prospective multicenter study of 4131 patients who had a SNB for breast cancer followed by axillary node dissection, 3305 patients had a SNB using Tm with the elapsed time from injection to SNB being recorded. These 3305 patients formed the cohort of interest for this study. The dose of Tm remaining at the time of SNB was calculated with the formula mCiremaining=mCiinjected*0.5^(elapsed hours/6). Patients with injection of Tm ≤12h and >12h were compared using SPSS. Results: The mean age of the 3305 patients in this study was 60 years, with a mean tumor size of 1.8 cm. A sentinel node (SN) was identified in 95% of patients. SN identification (ID) was not affected by mCi injected (p=0.88), mCi remaining at time of SNB (p=0.13), or type of Tm (filtered vs. unfiltered, p=0.37). There was a statistically non-significant trend of more SN's removed in the ≤12h group (3.2 vs. 2.5, p=0.06). False negative rate was not affected by mCi injected (p=0.39), mCi remaining at time of SNB (p=0.24), or type of Tm (filtered vs. unfiltered, p=1.00). The overall false negative (FN) rate was 8.0%. Of the 3305 patients in this study, 3221 were injected ≤12h prior to SNB and 84 were injected >12h prior to SNB. For the patients injected ≤12h compared to >12h, there was no difference in SN ID rate, FN rate, counts of the hottest node, or background counts despite more mCi injected and less mCi remaining at SNB in the >12h cohort (see Table). Conclusions: Injecting Tm >12h prior to SNB has an acceptable SN identification rate, and the FN rate was not significantly different than injecting Tm ≤12h prior to SNB. [Table: see text] No significant financial relationships to disclose.