bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aldehyde dehydrogenase activity in serous ovarian carcinoma.
Authors: Bareiss Petra M. , Fehm Tanja N. , Fischer Anna , Grauer Matthias , Kokorsch Philipp , Buehring Hans-Joerg , Pham Deborah , Staebler Annette , Wallwiener Diethelm , Fend Falko , Kanz Lothar , Lengerke Claudia 
Published: March 2020

e15577 Background: Only specific subpopulations of tumor cells, so called cancer stem cells (CSC) may initiate and maintain tumors. The phenotype and molecular properties of ovarian CSC remain elusive. Aldehyde dehydrogenase (ALDH) activity characterizes (cancer) stem cells in different tissues and has been associated with ovarian CSC (Silva et al, 2011; Kryczek et al, 2012). Contradictory results have been reported on ALDH1 expression and prognosis in ovarian carcinoma. In this study, we explore the role of ALDH in serous ovarian carcinoma (SOC). Methods: Aldefluor-staining was used to assess ALDH activity in different ovarian carcinoma cell-lines and patient samples. ALDH+ and ALDH- cells isolated by FACS and ALDH1 versus control siRNA treated cells were analyzed in sphere forming, proliferation, BrdU and cell cycle assays. In vivo tumorigenicity assays including serial re-transplantations were performed in NOD/SCID/IL2Rγnull mice. ALDH1 and Ki67 expression were assessed immunohistochemically on a tissue microarray of 152 SOC samples. Results: ALDH+ cells formed more tumor spheres than ALDH- cells from the OVCAR-3 cell line and primary SOC and larger spheres (> 5.000 µm²) developed solely from ALDH+ cells. However, in vivo both cell fractions gave rise to tumors. Tumors contained both ALDH+ and ALDH- cells irrespective of the starting population. Notably, ALDH+ cells generated tumors more rapidly and induced larger tumors, suggesting a higher proliferative capacity. Immunohistochemical analysis of a larger cohort of SOC patients confirmed association of ALDH1 expression with the proliferation marker Ki67 (p=0.007). Surprisingly, co-stainings revealed that ALDH1 positive cells were mostly Ki67 negative and cell cycle synchronisation experiments using different agents showed ALDH induction in G0-enriched OVCAR-3 cells. However, inhibition of ALDH by treatment with three distinct siRNAs against ALDH1 did not alter cell cycle distribution. Conclusions: Our data suggest that ALDH is a correlative marker indicating, but not actively sustaining a quiescent stem-cell like state in SOC. Upon exit from G0, ALDH+ cells lose ALDH expression and induce a proliferative response.
Expression of vascular endothelial growth factor receptor (VEGF-R) and CD31 receptor (CD31-R) in high-grade neuroendocrine carcinoma of the uterine cervix (cNEC) and its association with prognosis.
Authors: Kuzman James A , Naraev Boris G. , Button Anna M , Samuelson Megan I , Goodheart Michael J , DeYoung Barry , O'Dorisio Thomas M. , Halfdanarson Thorvardur Ragnar 
Published: March 2020

e15580 Background: High-grade cNEC is uncommon cancer, and the optimal treatment is unclear. It is not known if cNEC expresses surface proteins related to angiogenesis. The aim of this study is to evaluate the expression of proteins involved in angiogenesis, as well as their possible association with clinical outcomes. Methods: Expression of VEGF-R and CD31-R was analyzed with standard immunohistochemical methods in tumor specimens from 16 patients with cNEC seen at our institution from 1977 to 2010. CD31-R expression was estimated by analyzing microvessel density using a CD31 specific antibody. Intensity and percentage of cells expressing VEGF-R was determined. Univariate survival analysis was performed using a Cox Proportional Hazard Model. Results: VEGF-R was expressed in 15 out of 16 specimens whereas CD31-R was expressed in all specimens. Increased VEGF-R expression correlated with shortened survival but the association was not statistically significant (p=0.0544, hazard ratio=1.514, CI=0.992-2.309). A one unit increase in VEGF-R expression correlated with increase in the risk of death by 51.4%. CD31-R expression showed no significant association with survival (p=0.9638,CI=0.865-1.165). Conclusions: VEGF-R and CD31-R are expressed by most cNECs. Increased VEGF-R, but not CD31-R, expression may be associated with worse survival. Further exploration of the role of angiogenesis in cervical NETs is warranted.
Intraarterial high-dose cisplatinum (IAHDP) as a part of the treatment of relapsed or locally advanced tumors of the head and neck (H&N): A feasibility study.
Authors: Gonzalez Manuel Sureda , Moreno Antonio , Rebollo Joseba , Brugarolas A. , Cañon Rosa , Azinovic Ignacio , Crespo Aurora 
Published: March 2020

e16000 Background: IAHDP has been employed as a part of the treatment of relapsed or locally advanced H&N tumors with controversial results (RADPLAT protocol). We hypothesize that patients (pts) with relapsed or locally advanced tumors in several locations can be treated with IAHDP, in order to achieve a response, to be followed by a consolidation with radiotherapy, surgery or both. Methods: Pts with relapsed or locally advanced tumors of the H&N were treated with IAHDP (150 mg/m2/wk), after an initial supraselective angiography performed with the goal of mapping adequately the arterial supply. Prevention of toxicity with hyperhydration and simultaneous and delayed thiosulfate was done according to the previous schema of the RADPLAT protocol. Results: From June 2007 to September 2011, 11 patients – 8 M/ 3F; age 37-77 y, median 56 y- were treated (10 H&N epidermoid carcinomas, 1 orbitary mts of adenocarcinoma of unknown origin). A total of 50 cycles were administered (2-9 per pt, median 4). In 4 pts IAHDP was part of the primary treatment; 7 pts were treated in relapse. Three pts were retreated after relapse, one of them two times. Five pts received radiotherapy simultaneously with IAHDP. Toxicity was generally mild and reversible. Mucositis g4 was observed in 3 cycles, facial edema requiring extra dexametasone in 7, pain during infusion in 9, nausea and vomiting in 3, lasting ipsilateral hypoacusia in 1, persistent trismus in 1. No significant alterations of renal function were observed. One pt progressed after the first cycle; 7 pts presented partial response (duration 1-6 m, median 2 m; 2 of them were converted to a complete response with surgery); 2 pts presented complete response with IAHDP simultaneous to radiotherapy. Four pts remained with no evidence of disease at 3+, 15+, 16+ and 38+ m respectively. Conclusions: IAHDP constitutes a feasible and promising therapeutic option for selected pts and a consolidation with surgery and/or radiotherapy after IAHDP is possible. Further development of this approach is warranted.
Phase II/III randomized study of hyperfractionated radiotherapy with concomitant cetuximab versus concomitant chemotherapy in advanced nonmetastatic head and neck cancer: Preliminary report.
Authors: Al Saleh Khalid , Safwat Reham , Bedair Ahmed , AL Basmy Amany , Hooda H.S. , Shete Jitendra 
Published: March 2020

e16002 Background: This is a randomized study to compare the use of cetuximab versus platinum based chemotherapy with concurrent hyperfractionated radiation therapy (HRT). Acute and late morbidity, locoregional control (LC) and disease free survival (DFS) were set as primary end points, while overall survival (OS) was set as secondary end point. Methods: Between December 2009 and May 2011, 24 patients were randomly assigned to HRT consisting of 120 cGy twice daily, for a total of 69.6 Gys in 58 fractions over 6 weeks, plus either cisplatin chemotherapy at weeks 1, 4, 6 (Arm A: 14 patients) or weekly cetuximab (Arm B: 10 patients). The overall radiation dose was the same for the two groups. The median follow up time of the whole group was 14.07 months (IQR: 5.8- 25.0 ms). Results: Overall treatment time was 72 days in arm A and 63 days in arm B (p= 0.64). Grade 3 skin toxicity was experienced in 42.9% of patients in arm A and 9.1% in arm B (p= 0.09). Grade 3 mucositis was 64.3% in arm A and 45.5% in arm B (p= 0.43). Hematologic toxicity of G3-4 occurred in 21.4% and 18% of the cases respectively (p= 0.06). The mean percent of weight loss was (13 % +/- 0.1%) in group A, and (10.75 % +/- 0.1%) in group B respectively (p=0.56). Complete response was observed in 12 (85.7%) and 100% of patients of arm A and B respectively. Partial response was achieved in the remaining 2 (14.2%) patients in arm A. Loco-regional recurrence occurred in 2 (14.2%) of the patients in arm A after partial response, and one of them died eventually due to progressive disease. Two patients developed distant metastasis, one patient in arm A and another one in arm B. As the sample size was small and events were limited, survival analysis could not be computed at this stage of the study Conclusions: Hyperfractionated radiotherapy and concurrent cetuximab seems to have less side effects compared to concurrent platinum. There's a trend of less skin, mucosal and haematological toxicity with cetuximab that might become significant as the number of patients increase. We will be able to evaluate the outcomes of the patients regarding LC, DFS and OS within 2 years.
Gender associations in head and neck squamous cell carcinoma (HNSCC).
Authors: Hoang Tien , Zhang Chong , Geye Heather M , Speer Tod , Yu Menggang , Wiederholt Peggy A , Kakuske Jennifer C , Traynor Anne M. , Cleary James F. , Dailey Seth H , Ford Charles N , McCulloch Timothy M , Hartig Gregory K , Harari Paul M. 
Published: March 2020

e16010 Background: The primary objective of this analysis was to examine the association of gender with various presentation and outcome parameters in HNSCC. Methods: We queried the head and neck cancer (HNC) database at the University of Wisconsinand examined selected clinical, treatment and outcome data for all patients (pts) treated consecutively during the 10-year period (1/01-12/10). Results: From a total of 1,108 HNC pts, we identified 965 with SCC histology, including 252 women (26.1%) and 713 men (73.9%). Women were slightly older at presentation (mean age 62 vs. 60, p = 0.03); 29.6% of women vs. 19.6% of men were 70 years or older. There were no differences in race distribution. Smoking and drinking habits were frequently reported in both sexes, although seen more frequently in men. 74.1% of women vs. 83.1% of men had smoked cigarettes (p=0.003), while 74.9% and 90.6% respectively had consumed alcohol (p<0.0001). 16.3% women never smoked or drank in comparison to 4.6% in men (p<0.0001). There was a difference in primary tumor site distribution between genders (p=0.0003). Oral cavity (41.3%) and larynx (23%) were the most common sites in women vs. oropharynx (31.1%) and larynx (24.8%) in men. There appeared to be no difference in tumor T stage. However, more men presented with N2/3 (51.7% vs. 39.9%, p=0.01) and stage IV (63.1% vs. 53.2%, p=0.04). For initial treatment, more men received multi-modality therapy (56.2% vs. 48.4%, p=0.009) while more women received surgery as sole therapy (37.3% vs. 27.1%). Overall, 72.7% of men vs. 62.3% of women received radiation (XRT); 36.5% and 26.2% respectively received concurrent chemoradiation. There were no differences in baseline performance status, total XRT dose (mean 65.8 Gy), fractionation (mean 33), XRT technique (3D conformal, linac-based IMRT or tomotherapy), or chemotherapy delivered. Recurrence free outcome was achieved equally in both genders at the primary tumor site (~80%), neck (~84%) and distant sites (~88%). Median survival was 89.5 months in women and 84.2 months in men (p=0.65). Conclusions: Although there were no differences in overall survival,our analysis suggests that some gender differences may exist in risk factors and clinical presentation for HNSCC pts. Further study is warranted.
A phase II study of nimotuzumab and CDDP concurrent with radiation in locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: Lim Wan-Teck , Ang Mei-Kim , Ng Quan Sing , Wang Lan-Ying , Chau Noan-Minh , Tan Daniel S. W. , Chay Wen Yee , Leong Swan , Tan Eng-Huat 
Published: March 2020

e16024 Background: Nimotuzumab is a humanized monoclonal antibody (MAb) to EGFR. Concurrent cisplatin with radical radiotherapy (RT) is standard treatment for locally advanced SCCHN where it is unresectable or for organ-preservation. We explored the combination of nimotuzumab with concurrent CDDP and RT in these patients (pts). Methods: Pts with locally advanced stage III/IV SCCHN were eligible for study if: age > 18, ECOG 0-1, SCC, normal organ function. Analysis was by intention-to-treat (ITT). CDDP 100 mg/m2 on days 1, 22, and 43 was given with RT (70 Gy over 35 fractions). Nimotuzumab was given as a flat dose of 200 mg weekly on weeks 1 to 8 of treatment. Pts were followed up for RECIST response, progression free survival and toxicity. Results: Twenty-eight pts were available for analysis at the time of report. The median age was 58 (30-69). Most were Chinese (90%) and all ECOG 0-1. Twelve pts had oropharynx Ca, 16 had non-oropharyx Ca. Twenty-five pts were evaluable for response, 2 pts withdrew consent after 2 weeks, 1 pt died of undiagnosed Fanconi anemia. By ITT, the best overall response rate (CR/PR) was 78.6% (12 CR/10 PR), SD 3.6% (1), PD 7.2% (2). Pts with oropharynx Ca had higher PFS rate at 1 year than non-oropharynx (80% vs 48%). Major grade 3/4 toxicities were limited to mucositis, dysphagia, and fatigue. Grade 5 toxicity due to febrile pancytopenia occurred in 1 pt with undiagnosed Fanconi’s. Acneiform rash typical of EGFR inhibitors occurred in 1 pt. Conclusions: Nimotuzumab with concurrent CDDP/RT is feasible and there was minimal additional toxicity encountered. Final results will be updated at the meeting.
A phase I/II study of radiation therapy, paclitaxel poliglumex, and cetuximab in locally advanced head and neck cancer.
Authors: Hahn Seung Shin , Bogart Jeffrey , Chung Chung Taik , Hsu Jack , Kellman Robert , Kim Jung-AH , Graziano Steve , Martin Dena , Gajra Ajeet 
Published: March 2020

e16047 Background: In patients with locally advanced head and neck cancer (LA-HNC), radiotherapy (RT) + cisplatin showed survival benefit over RT alone, but with significant toxicity. The addition of cetuximab to RT demonstrated survival benefit without increased RT-related toxicity. Paclitaxel poliglumex (PPX) is a novel conjugate consisting of paclitaxel linked to a biodegradable, water-soluble polymer of glutamic acid. PPX has a radiation enhancement factor of ≈8 and improved curability in a murine carcinoma model. In a phase I study of PPX + RT in esophageal cancer, no dose-limiting toxicities (DLTs) occurred at PPX doses up to 70 mg/m2/week and an encouraging rate of pathological CRs was observed. This phase I/II study addresses the combined use of intensity modulated RT (IMRT), PPX, and cetuximab in patients with LA-HNC. Methods: Eligible patients had untreated stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx; ECOG PS 0-1; and adequate bone marrow function. In the phase I portion, patients received cetuximab 400 mg/m2 day 1 and 250 mg/m2 days 8, 15, 22, 29, 36, 43, and 50. PPX was administered at 40 mg/m2 days 8, 15, 22, 29, 36, 43, and 50 for Cohort 1 (n = 3) then escalated or decreased for Cohorts 2-5 (3 patients each) until the maximum tolerated dose (MTD) was established. IMRT began on day 8 and consisted of 69.96 Gy delivered in 2.12 Gy daily fractions. In the phase II portion, patients received PPX at the MTD + cetuximab and IMRT at the phase I dose and schedule. Results: In total, 14 patients were treated (9 phase I, 5 phase II). The PPX MTD was determined to be 40 mg/m2. The majority of adverse events (AEs) were grade 1/2 and consistent with known toxicities of individual agents. The most common grade 3 AEs were mucositis (n = 8), radiation dermatitis (n = 4), and cetuximab rash (n = 3). Of 13 patients evaluable for response, 9 had CR and 4 had PR. After a median 17-month follow up, the local control rate was 11/11 and the median survival was 20 months. Two patients with stage IVC disease were excluded for local control and survival analysis. Conclusions: The combination of IMRT, PPX, and cetuximab is tolerable and shows promising clinical activity in patients with LA-HNC.
The impact of interventions on provider and treatment delays in head and neck cancer patients.
Authors: Lai Dominic W. , Kim June , Marciscano Ariel , Buckley Sarah A , Schmidt Brian L. , Cohen Richard F. , Nierodzik Mary Lynn R. , Myssiorek David , DeLacure Mark D. , Sanfilippo Nicholas , Seetharamu Nagashree 
Published: March 2020

e16052 Background: Diagnosis and management of squamous cell carcinoma of head and neck (SCCHN) involves a multidisciplinary approach. Navigation at a public hospital can be difficult and lead to delays. In a previous study, we reported English-speaking and employed patients having longer provider delays (Lai 2011). In July 2010, we instituted the use of patient navigators, bimonthly management conferences, and improved inter-disciplinary communication in order to improve the patient experience. Aims: 1. Study differences in “provider delay” (time between first contact with health care provider and positive biopsy) between patients in cohort A (diagnosed between 1/2007 and 6/2010) and cohort “B” (diagnosed between 7/2010 and 6/ 2011). 2. Study differences in “treatment delay” (time between biopsy and initiation of treatment) between the two cohorts. 3. Determine what factors influence delays in both cohorts. Methods: The delays of the two cohorts were compared using the student t-test. Independent t-test and chi-square tests were used to examine associations between delays and the following characteristics: language, employment, presence of partner, gender, ethnicity, age, cancer sub-site, staging, number of co-morbidities, tobacco use, and alcohol use. The likelihood ratio test was used for multivariate analysis. Results: 133 patients in cohort A and 20 patients in cohort B were evaluable. Both provider and treatment delays in cohort B (50.5 and 39.3 days, respectively) were shorter than cohort A (60.2 and 41.6 days), but this was not statistically significant. The standard deviations of both delays were lower in cohort B, pointing towards a greater consistency in this group. In cohort A, provider delay was significantly shorter (p-value=0.003) for non-English speakers than English speakers on univariate and multivariate analysis. Other trends were not observed. Conclusions: Simple interventions can reduce provider and treatment delays. Our observations suggest that these interventions can mitigate the effect of patient factors on provider and treatment delay. However, our results may be affected by small sample size and demographic shifts. With time, we will accrue more patients to address these issues.
A prospective, multicentric clinical study of intensity modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC): A 4-year follow-up report.
Authors: Wu Fang , Wang Ren-sheng , Feng Guosheng , Li Guisheng , Liu Meilian , Yan Haolin , Zhu Jinxian , Hu Kai , Zhang Yong 
Published: March 2020

e16054 Background: To evaluate the treatment efficacy, toxicity and prognostic factors of patients with NPC treated with IMRT. Methods: Between January 2006 and August 2008, 300 patients with pathologically diagnosed NPC from 6 medical center received IMRT. The number of patients with stage I, II, III, IVa-b disease (UICC/AJCC 2002 staging system) was 6, 45,141, and 108, respectively. The prescription doses were as follows: 70~74Gy/30 fraction to GTVnx, 68~70Gy/30 fraction to GTVnd, 60~64Gy/30 fraction to CTV1,50~54Gy /30 fraction to CTV2. Patients with stage III, IVa-b disease also received cisplatin-based chemotherapy. Results: The median follow-up time was 47.1 months (range,11-68 months). There were 18,15 and 42 patients who had developed local, regional recurrence and distant metastasis, respectively. There were 45 patients died. 34 patients died of distant metastasis,6 died of local and regional recurrence, 2 died of re-treatment, one died of hemorrhage complications of nasopharynx,one died of second primary tumor, and the other one died of unknown cause.The 4-year rate of local control (LC), regional control(RC), metastasis-free survival(DMFS),disease-free survival(DFS) and overall survival(OS) was 94.0%, 95.5%, 87.4%, 80.8%, 86.1%, respectively. Multivariate analysis showed that N stage was the only prognostic factor for OS (x2=3.912, p=0.048, HR=14.565), DMFS (x2=5.195, p=0.023, HR=8.737)and DFS (x2=7.613,p=0.006, HR=7.628), in these patients. Mucositis was the most severe acute toxicity, with 18.1% grade 1, 48.6% grade 2, 33.3% grade 3 . No patient suffered from grade 4 mucositis. Xerostomia was the most common seen late toxicity, with 8% grade 0, 50.5% grade 1, 4.6% grade 2. No grade 3-4 xerostomia was observed. Conclusions: IMRT can improve the treatment efficacy of patients with NPC. The acute and late toxicities were tolerated. Distant metastasis becomes the main treatment failure. N stage is a significant prognostic factors.
Global survey on barriers to clinical cancer research.
Authors: Cufer Tanja , Cazap Eduardo L. , Delgado Lucia Beatriz , Digumarti Raghunadharao , Leighl Natasha B. , Meshref Mohamed M. , Minami Hironobu , Robinson Eliezer , Yamaguchi Nise Hitomi , Sadikov Aleksander , Seruga Bostjan , Pyle Doug 
Published: March 2020

e16505 Background: Many authorities, including ASCO, have raised concerns about growing barriers to clinical cancer research. We believe this is the first global survey of perceived barriers to clinical cancer research from the investigator perspective. Methods: The ASCO International Affairs Committee invited 300 oncologists in 19 countries to complete a web-based survey. Eighty responded, with 41 from high-income countries (HIC) and 39 from low- and middle-income countries (LMIC). Most responders were medical oncologists (62%), at academic hospitals (90%). Barriers were ranked from 1 (most) to 8 (least) important. Results: Most responders reported participating in academia-driven (ADCT) (92%) and industry-driven clinical trials (IDCT) (89%) in the last 5 years, with a significantly higher proportion from HIC compared to LMIC involved in more than 10 ADCT (71% vs. 29%; p=0.008) and IDCT (71% vs. 29%; p=0.017) in that time. Most of the responders (45% from HIC vs. 55% from LMIC; p=NS) reported “no change” in the last 5 years in the proportion of their trials that were IDCT. Of those who said it has become more difficult to conduct ADCT (40/80) and IDCT (27/80), a significantly higher share came from HIC than from LMIC in the case of both ADCT (29/40; 73% vs. 11/40; 28%; p=0.001) and IDCT (19/27; 70% vs. 8/27; 30%; p=0.009). Average time reported from regulatory initiation to the first-patient-in was up to 90 days for 39% of responders, 90-120 days for 26% and more than 120 days for 30%, with extremes reported most frequently by LMIC responders. A lack of funding was ranked the most important barrier to ADCT by both HIC (3.15) and by LMIC (3.18) responders, and a lack of patients the least important by both HIC (5.27) and LMIC (5.59) responders. LMIC responders considered competent authorities (regulatory) procedures a more important barrier than HIC responders (3.87 vs. 4.67). Conclusions: Though investigators from HIC are involved in more ADCT and IDCT than LMIC counterparts, they are more likely to perceive the barriers to conducting trials as worsening. Of note, no major shift towards greater IDCT was reported in our survey. With regards to ADCT, the main barrier that should be improved globally is financing, with an additional focus in LMIC on regulatory procedures optimization.