bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of cetuximab in high-risk premalignant lesions of the upper aerodigestive tract.
Authors: Califano Joseph A , Ferris Robert L. , Epstein Joel Brian , Gillespie Marion Boyd , Feldman Lawrence Eric , Gibson Michael K. , Pytynia Kristen B. , Khan Zubair 
Published: March 2020

5528 Background: High risk head and neck premalignancy includes patients with prior HNSCC and loss of heterozygosity (LOH). These patients demonstrate 30-60% rates of progression to malignancy despite conventional surgical excision. We performed a phase II trial using short term therapy with cetuximab, a humanized monoclonal antibody directed against EGFR, in the treatment of high risk premalignant lesions of the UADT. Methods: Inclusion criteria required; 1) presence of 3p, 9p21, or 17p LOH, and/or 2) surgically unresectable high grade premalignant lesions, and/or 3) high grade premalignancy after curative therapy for HNSCC. Patients received cetuximab 400 mg/m2 on week one followed by 250 mg/m2 on week 2-8 or observation, with the option for crossover to cetuximab for patients originally randomized to the observation arm. Histologic grade (1=benign, 2=mild dysplasia, 3=moderate dysplasia, 4=severe dysplasia/carcinoma in situ, 5=invasive cancer) and change in grade of dysplasia was evaluated. Results: 19 patients were enrolled. Two patients discontinued therapy due to toxicity. We noted a decrease in grade of dysplasia in the cetuximab treated group (-1.0) vs. the observation group (-0.2), (Wilcoxon test p value = 0.18). In the observation group, 0/5 patients (0%) underwent complete resolution of dysplasia; while 4/12 (33.3%) treated patients had no remaining dysplasia after therapy (p = 0.26), three of these patients had complete resolution of dysplastic changes after cetuximab therapy alone. Of these three patients, two have had no recurrence of leukoplakia or dysplasia at 1.5 and 2 years. One patient treated with oral cavity dysplasia has had no recurrence of dysplasia or lesions within the oral cavity, but developed a hypopharyngeal cancer at 1.5 years after trial completion. Of 5 patients randomized to observation, three underwent crossover to cetuximab therapy, and two of these three patients had complete resolution of dysplasia. Conclusions: EGFR blockade with cetuximab alone can result in significant, durable, and complete clinical and histological resolution of moderate to severe dysplasia in at least a subset of high risk patients.
Chemotherapy-induced amenorrhea in premenopausal breast cancer patients treated with adjuvant anthracycline and taxane based chemotherapy within the SUCCESS study.
Authors: Neugebauer Julia Katharina , Rack Brigitte Kathrin , Kupka Markus , Dinkel Carina , Jaeger Bernadette Anna Sophia , Ortmann Uta , Schneeweiss Andreas , Schrader Iris , Tesch Hans , Rezai Mahdi , Soeling Ulrike , Noeding Stefanie , Zabel Frauke , Sommer Harald Leo , Friese Klaus , Beckmann Matthias W. , Janni Wolfgang 
Published: March 2020

554 Background: Chemotherapy induced amenorrhea (CIA) is often used as a surrogate marker for cytotoxic gonadal damage. The aim of this analysis was to identify predicitve factors for CIA in premenopausal breast cancer patients treated with adjuvant chemotherapy. Methods: The German multicenter, phase III SUCCESS trial compared 3 cycles of FEC q3w followed by 3x docetaxel q3w vs. FEC followed by Doc+gemcitabine as adjuvant treatment in patients with node positive or high risk node negative primary breast cancer. Premenopausal patients with hormone receptor positive tumors underwent endocrine treatment with tamoxifen (Tam) for 5 years. Additional goserelin (GnRH) for 2 years was given in the following cases: Age <40 years at study entry, premenopausal hormone status or regular menses within 6 months after chemotherapy. We retrospectively investigated CIA rates of 1.189 initially premenopausal patients during disease-free follow-up. Results: Median age at diagnosis was 44 years (range 21-50). The median follow up time was 44 months (range 1-62). 791 patients (66.5%) received endocrine treatment. Tam intake was reported in 370 patients, GnRH in 29 patients, Tam+GnRH in 392 patients. In 963 patients (81.0%) CIA occurred for ≥3 months after chemotherapy. In 22.7% of initially amenorrheic patients CIA was temporary. 192 patients (16.2%) had continuous menstrual bleeding. In multivariate analysis the risk of CIA was significantly higher in older patients, increasing by factor 1.32 per life year (p<0.0001). Tam intake was also associated with increased CIA rates (p=0.0032). Patients with combined Tam+GnRH were more likely to resume menses compared to patients without endocrine therapy (p=0.0056). Factors like the cytotoxic regimen, tumor stage, grading, the patient`s BMI or the use of GnRH analogues as ovarian protectants during chemotherapy did not correlate with CIA rates. Conclusions: Age was the strongest predictor for CIA. Tam administered alone increased CIA rates. Opposite effects were observed for patients who received Tam+GnRH. The addition of gemcitabine to sequential anthracyline-taxane based chemotherapy did not influence CIA.
Feasibility and short-term efficacy of four facio-cervical fields’ conformal radiotherapy for nasopharyngeal carcinoma.
Authors: Zheng Wang fang , Zhenfu Fu 
Published: March 2020

5568 Background: Conventional bilateral facio-cervical fields increased the local control and overall rates for nasopharyngeal carcinoma, and generated severe late complications, while intensity-modulated radiation therapy (IMRT) may take up a lot of labor power and material resources.This study was to explore feasibility and short-term efficacy of four facio-cervical fields’ conformal radiotherapy (4F-CRT) for nasopharyngeal carcinoma. Methods: Between November 2007 and June 2009, 101 patients with histology-proven nonmetastatic NPC were rolled into this study and received 4F-CRT. 90 of all patients received four cycles chemotherapy. Results: The treatment was completed for all patients within 7 weeks. The complete response (CR) rate was 95.0% (96/101) and the partial response (PR) rate 5.0% (5/101). Overall response was 100% for nasopharyngeal lesions. The CR rate was 90.0% (91/101) and the PR rate 7.0% (7/101) in lymph node lesions. One year local control, regional control, overall survival (OS) rate, metastasis-free survival (MFS) and disease-free survival (DFS) rate are 100%, 100%, 100%, 97%, 97%, respectively. The major toxicities observed were grades 1-2 leukocytopenia. Conclusions: 4F-CRT can generate desirable dose distribution of tumor volume for nasopharyngeal carcinoma. The short-term efficacy of 4F-CRT is satisfactory and its acute toxicities are tolerable.
Effects of vandetanib on body composition in patients with advanced medullary thyroid carcinomas: Results from a placebo-controlled study.
Authors: Massicotte Marie-Helene , Borget Isabelle , Leboulleux Sophie , Baudin Eric , Baracos Vickie E. , Mansouriah Merad , Schlumberger Martin , Antoun Sami 
Published: March 2020

5569 Background: Muscle (MT) and adipose tissue (AT) share common intra cellular pathways with tumor, thus it is not surprising to observe metabolic consequences with targeted therapies. The aim of the study was to assess the effects of vandetanib, a tyrosine kinase inhibitor (TKI) which demonstrated efficacy for the treatment of advanced medullary thyroid carcinoma (MTC), on MT and AT. Methods: 33 patients (25 men and 8 women, mean age of 54 years) with metastatic MTC received vandetanib 300 mg/d (n=23) or placebo (n=10) in the setting of the ZETA study. Cross-sectional areas (cm2) of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and MT were assessed by computed tomography imaging at 3rd lumbar vertebra and were indexed for height (cm2/m2). Comparisons between treatment and placebo were made at 3 months, and long-term evolution was evaluated over 12 months. Results: At 3 months, compared to baseline, patients treated with vandetanib gained 1.5 kg, 1.3 cm2/m2 of MT, 5.1 cm2/m2 of VAT and 4.5 cm2/m2 of SAT. In contrast, patients under placebo lost 1.5 kg (p=0.02), 1.0 cm2/m2 of MT (p=0.009), 5.5 cm2/m2 of SAT (p=0.004) and gained significantly less VAT (0.6 cm2/m2) (p=0.02). At 12 months, compared to baseline, patients treated with vandetanib gained 2 kg (NS), lost 0.3 cm2/m2 MT (NS), gained 3.4 cm2/m2 of VAT (NS) and 8.7 cm2/m2 of SAT (95% CI, 1.1 to 16.2). A significant decrease of calcitonin (defined as ≤50% compared to baseline) was associated with higher weight (p=0.01), VAT (p=0.01), and total adipose tissue (p=0.02). Conclusions: Beyond its proved efficacy in MTC treatment, and despite common intracellular pathways, vandetanib is the only studied TKI to preserve MT and to restore AT. Further research is needed to explore whether the relationship between changes of VAT and vandetanib treatment results from a direct metabolic action of vandetanib or is a consequence of biochemical tumor control.
Correlation of microbiomic profiles with disease status and MDR1 methylation in head and neck squamous cell carcinoma (HNSCC).
Authors: Funchain Pauline , Bebek Gurkan , Bennett Kristi L , Burkey Brian , Eng Charis 
Published: March 2020

5573 Background: Recent studies of the aerodigestive tract have uncovered the functional importance of the microbiome, the total collection of microorganisms that reside within the human host. Furthermore, specific bacterial species have been shown to be etiologic agents or show potential as a screening biomarker in cancers including gastric, colon and pancreas. Here, we hypothesize that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Methods: Matched tumor and adjacent normal fresh frozen tissue specimens were collected from 55 prospectively enrolled HNSCC patients. Microbiomic profiles were obtained using Sanger sequencing of 16S rDNA PCR products. Methylation status of four genes previously linked to HNSCC or inflammation (MDR1, IL8, RARB, TGFBR2) was assessed in 49 samples by combined bisulfite restriction analysis and by Illumina HumanMethylation27 chip. Principle component analysis and multivariate analysis of covariance (MANCOVA) were used to identify bacterial subpopulations significantly associated with HNSCC and relevant clinical variables. Results: In this cohort, median age is 62, male:female ratio is 3:2, 16% are HPV+. Specific bacterial subpopulations associate with HNSCC over normal tissue and correlate with larger tumor size and higher nodal stage (p<0.05). Furthermore, microbial populations can separate tumors by tobacco (p<0.005) but not alcohol (p>0.7) status. Bacterial profiles are independent of HPV status. MDR1 promoter methylation is seen in tumor samples but not in normal oral mucosa (22/49 vs 0/49), and associates with specific microbiomic subpopulations in the order Enterobacteriales and phylum Tenericutes (p<0.001). Additionally, MDR1 methylation correlates with regional nodal metastases. Conclusions: Specific bacterial subpopulations differ between normal and tumor tissue and show association to specific clinicopathologic features, suggesting a role for microbial profiling in HNSCC as a novel area of investigation for diagnosis, prognostication, and therapeutic targeting.
Identification of head and neck cancers (SCCHN) that may respond to dual inhibition of EGFR and HER3 signaling.
Authors: Shames David S. , Stern Howard , Walter Kim , Jiang Brittany , Fu Ling , Do An , Raja Rajiv , Wilson Tim , Settleman Jeff , Sliwkowski Mark X. , Pirzkall Andrea , Amler Lukas C. 
Published: March 2020

5575 Background: Oncogenic signaling through the epidermal growth factor receptor family is one of the most frequent alterations found in human epithelial cancers. These receptor tyrosine kinases mediate their effects via high-level co-expression and homo- and heterodimerization events that drive tumor growth, metastasis, and survival. Extensive preclinical studies suggested that some cell lines depend on oncogenic autocrine signaling through HER3 (Wilson et al.). This phenotype was particularly prominent in cell lines derived from SCCHN and was strongly correlated with high HRG expression. Interestingly, two patients with SCCHN tumors that expressed high levels of HRG in our phase Ia trial (abstract #95245) of MEHD7954A, a dual-action human IgG1 antibody that blocks ligand binding to EGFR and HER3 (Schaefer et al.) had partial responses. To further explore the hypothesis that high-level HRG expression defines a sub-population of SCCHN that may be sensitive to agents targeting HER3, and to identify other potential target indications for the development of MEHD7954A, we evaluated the expression of HRG in large cohorts of multiple solid tumor indications. Methods: HER3 and HRG expression was analyzed by qRT-PCR in 648 formalin-fixed paraffin embedded primary tumor samples from patients with NSCLC, SCCHN, melanoma, CRC and triple-negative breast cancer. Results: SCCHN-derived tumor samples had the highest levels of HRG expression, exhibiting a bimodal distribution in SCCHN – a pattern that is clearly distinct when compared to other tumor types. These data suggest that high HRG levels and potentially HER3-dependent autocrine signaling occur more frequently in SCCHN than in other tumors. Further we investigated whether overexpression of HRG in SCCHN correlated with stage and disease outcome. Updated results from these extended studies will be presented. Conclusions: SCCHN tumors exhibit bimodal expression of HRG, suggesting that HRG expression levels may be useful in identifying a subset of patients most likely to benefit from inhibition of HER3 activity. Antitumor activity in such patients has been observed in a phase I study of MEHD7954A (abstract #95245).
Aromatase inhibitors and cardiac outcomes in women undergoing cardiac angiography after early breast cancer.
Authors: Seruga Bostjan , Zadnik Vesna , Grasic Kuhar Cvetka , Marinko Tanja , Zorman Darko , Cufer Tanja , Zakotnik Branko , Ocana Alberto , Amir Eitan 
Published: March 2020

558 Background: Data show that in post-menopausal women with early breast cancer, longer use of aromatase inhibitor (AI) is associated with increased odds of ischemic heart disease. Here we explore the association between adjuvant AI use and cardiac disease in women undergoing cardiac angiography after a diagnosis of early breast cancer. Methods: We linked a database of 7,681 women who underwent cardiac angiography at the University Clinical Center of Ljubljana between December 2004 and November 2010 with the Cancer Registry for Slovenia. Women with early breast cancer that subsequently underwent cardiac angiography were identified. Information on cardiovascular risk factors was retrieved from the patients’ charts and from discharge letters after cardiac angiography. The endpoint of interest was a diagnosis of ischemic heart disease or left ventricular dysfunction (IHD-LVD) without evidence of valvular heart disease at the time of angiography. Conditional, logistic regression was used to test for associations between variables. Results: Among 117 eligible women 75% (n=88) were postmenopausal and 62% (n=73) had hormonal receptor positive (HR+) disease. Of these 42% (n=31) were treated with AI. Overall, 48% (n=56) of women were found to have IHD-LVD. In patients with HR+ breast cancer, use of AIs was significantly associated with IHD-LVD as compared to tamoxifen alone (HR 2.50, 95% CI 1.01-6.29, p=0.046). For each year of AI therapy, there was a trend for higher odds of IHD-LVD (OR: 1.25, 95% CI 0.95-1.67, p=0.116). This effect appeared independent of age, body mass index, baseline hypertension, hypercholesterolemia, diabetes and heart disease or prior anthracyclines exposure. Among all patients, use of anthracyclines and left-sided irradiation was associated with non-significant increases in IHD-LVD (HR 2.37, 95% CI 0.89-6.09, p=0.45 and HR 1.28, 95% CI 0.69-2.40, p=0.44 respectively). Conclusions: Compared to tamoxifen, AIs are associated with a time dependent increase in IHD-LVD. This risk appears independent of other risk factors for heart disease. Anthracycline exposure and left breast or chest wall radiation showed non-significant associations with IHD-LVD in this small cohort.
Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced carcinoma maxillary sinus.
Authors: Patil Vijay , Prabhash Kumar , Noronha Vanita , Joshi Amit , Muddu Vamshi , Chauhan Bharat , Juvekar S , Chaukar D. , Chaturvedi Pankaj , Pai P. S. , Dcruz A. K. 
Published: March 2020

5585 Background: Locally advanced carcinoma of maxillary sinus has been historically reported to have poor prognosis. We evaluated the role of neoadjuvant chemotherapy in improving the outcome in these patients. Methods: 41 patients with locally advanced borderline resectable (stage IVa) or unresectable maxillary carcinoma (stage IVb) were treated with induction chemotherapy between 2008 and 2011. The protocol included 2 cycles of chemotherapy, response assessment and multidisciplinary clinic review for definitive local treatment. The demographic profile, response to induction therapy, toxicity of chemotherapy, definitive treatment received, time to treatment failure (TTF) and overall survival (OS) were analysed. Univariate and multivariate analysis was performed to determine factors associated with response, TTF and OS. Results: The cohort of 41 patients had a median age of 48 years (22-71) with male preponderance (80.5%). The chemotherapy included two drugs (platinum and taxane) in 34 patients (82.9%) and three drugs (platinum, taxane and 5 FU) in 7(17.1%) The taxane utilized was docetaxel in 22 patients (53.7%) and paclitaxel in 19 patients (46.3%). There was no complete response, stable disease in 18 (43.9%), partial response in 16 (39%), and progression in 7 (17.1%) patients. All patients competed two cycles of chemotherapy, adequate dose intensity was maintained in 33 patients (78%) and there were no deaths. Post-induction, the treatment planned included surgery in 12 (29.3%), CT-RT in 24 (58.5%), radical RT in 1 (2.4%), palliative RT in 1 (2.4%) and palliative chemotherapy in 3 ( 7.3%) patients. Overall, the median TTF was 10.2 months. With 16 deaths, the median OS was not reached. Only response post-induction was significantly associated with better TTF (p=0.02). Grade 3 tumor (p=0.04) and baseline serum albumin more than 4 mg/dl (p=0.02) were associated with better OS. Grade 3-4 neutropenia, febrile neutropenia and loose motions were seen in 21.1%, 23.8% and 15.8% respectively. Conclusions: In unresectable maxillary carcinoma, induction chemotherapy has clinically significant benefit with acceptable toxicity. Response to induction was the only significant factor for improved TTF.
Pattern of symptoms in head and neck cancer (HNC) survivors treated with radiation therapy (RT): Association with systemic therapy.
Authors: Rosenthal David Ira , Gunn Gary Brandon , Garden Adam S. , Lu Charles , Mendoza Tito R. , Morrison William H. , Frank Steven J. , Beadle Beth Michelle , Phan Jack , Fuller Clifton David , Hanna Ehab Y. , Ang K. Kian , Cleeland Charles S. 
Published: March 2020

5589 Background: We sought, in a large, long-term follow-up cohort, to determine benchmark cross-sectional analysis of HNC patient (pt) symptom profiles as a function of chemotherapy (CT)/RT strategy. Methods: Pts treated with RT with or without CT in remission > 18 mos. were surveyed with the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN). Clinical data were extracted. Data were tabulated, and group comparison performed using non-parametric analyses. Results: 250 pts participated; 81% were male. Median age at RT was 54 years. 87% had oropharynx HNC. Most were T1/X (41%), 37% T2 and, 22% T3/4. For N-category, most were N2 (55%), <5% N3, and 40% NX-1. 18% had induction CT, 26% concurrent, 5% both, and 50% had none. At a median follow-up time of 5.9 years (range 2-15), 11% of pts were entirely symptom free, 31% reported ≤mild symptom severity, 20% ≤moderate, and 38% reported ≥1 symptom as severe. 16% of pts receiving RT alone and 11% sequential CT followed by RT were symptom free, vs. 1% of those receiving concurrent CT (chi-square p<0.01), and the symptom distribution profile was distinct (p<0.03). The proportion of pts who received concurrent CT reporting any severe symptom item was 44%, vs. 36% of those not receiving concurrent CT (p=n.s.). No difference was seen in the moderate to severe (M/S) symptom report by treatment group. For all MDASI-HN items, most pts rated “0” or “not present”, except dry mouth and difficulty swallowing items, where mild symptoms were most likely (36% and 33%). The most common symptoms rated M/S were dry mouth, swallowing, choking, fatigue, and mouth and throat mucus reported by 42%, 23%, 18%, 16%, and 16%. MVA demonstrated T-stage and primary site, but not CT cohort correlated with M/S symptom report. Conclusions: Cumulatively, most pts had no more that mild symptom severity, but a substantial group of pts experience M/S levels. The symptom severity profile was highest with concurrent CT, though this effect appears mediated by disease specific factors. The addition of sequential CT to RT did not to appear to alter M/S symptom report substantially; however, concurrent pts were almost never symptom free, in contrast to induction and no CT cohorts.
The impact of the Oncotype Dx breast cancer assay in clinical practice: Systematic review and meta-analysis.
Authors: Carlson Josh John , Roth Joshua A. 
Published: March 2020

560 Background: Many studies have evaluated the Oncotype Dx Breast Cancer Assay (ODX) and its impact on adjuvant chemotherapy (ACT) treatment decisions. However, it can be difficult for clinicians and other stakeholders to interpret the collective findings of these studies, as they were conducted in diverse settings and have limited sample sizes. To address this issue, we conducted a systematic review and meta-analysis to synthesize ODX results and provide insights about the utility of ODX in actual clinical practice. Methods: We performed a systematic review of ODX studies using PubMed, Embase, ASCO, and SABCS. Studies were included if patients had ER +, node -, early stage breast cancer, reported use of ODX to inform actual ACT decisions, and reported outcomes of interest, including: 1) distribution of ODX recurrence scores (RS); 2) impact of ODX on ACT recommendations; 3) impact of ODX on ACT use; and 4) proportion of patients following the treatment suggested by the ODX RS. Results: A total of 28 studies met inclusion criteria. The distribution of RS categories was 48.8% low, 39.0% intermediate, and 12.2% high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4% of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT was: 28.2% overall, 5.8% low, 37.4% intermediate, and 83.4% high. High RS patients were significantly more likely to follow the treatment suggested by ODX vs. low RS patients RR: 1.07 (1.01–1.14). Conclusions: The pooled results for the impact of ODX on ACT recommendations are consistent with most individual studies to date. However, the proportion of intermediate RS results is nearly 2-fold higher than reported in the ODX development studies by Paik et al., which may have implications for the clinical utility and cost impacts of testing. Also, high RS vs. low RS patients were more likely to follow the ODX results, suggesting a tendency toward aggressive treatment despite a low ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use vs. standard approaches, suggesting additional studies are warranted. [Table: see text]