bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of Sprouty2 protein in human squamous cell carcinoma of the head and neck and suppression of cell proliferation in vitro.
Authors: Feng Yin-Hsun 
Published: March 2020

e17018 Background: Sprouty2 is known for its tumor-suppressing effect in various human malignant diseases. In head and neck squamous cell carcinoma (HNSCC), the role of sprouty2 in tumorigenesis and clinical implication is still unknown. Methods: Quantitative analysis of mRNA expression of sprouty2 was performed on frozen tumor samples from 42 patients with HNSCC and 19 oral verrucous hyperplasia (OVH). The expression of sprouty2 RNA was determined as the ratio of tested tumor sample and paired counterpart of normal mucosa , Sprouty2 expression and signaling in HNSCC cell lines were assessed by immunoblotting. In vitro proliferation was evaluated in HNSCC cell lines in response to enhanced expression of sprouty2 protein. Inhibition of cell proliferation by tyrosine kinase inhibitor, sorafenib, after modulation by expression of sprouty2 was measured by inhibition concentration. Results: Downregulation of sprouty2 expression was demonstrated in 79% of HNSCC samples compared with paired samples of normal mucosa, and in 58% of OVH samples compared with paired samples of normal mucosa. Low expression of sprouty2 was associated with invasiveness of huam HNSCC (p=0.03). Enhanced expression of sprouty2 protein suppressed the growth of HNSCC cells and signaling of the phosphorylated AKT pathway. After transfection of sprouty2 plasmid, HNSCC cells were more sensitive to sorafenib, a tyrosine kinase inhibitor of Raf and vascular endothelial growth factor receptor. Conclusions: Our data show that sprouty2 expression is down-regulated and behaves as a tumor suppressor in HNSCC. Sprouty2 expression in tumor cells enhances sensitivity to sorafenib.
Cetuximab, fluorouracil (5-FU), cisplatin, and docetaxel as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Interim results of a randomized phase II clinical trial (CeFCiD).
Authors: Knoedler Maren , Dietz Andreas , Gauler Thomas Christoph , Gruenwald Viktor , Stoehlmacher Jan , Knipping Stephan , Guntinas-Lichius Orlando , Frickhofen Norbert , Schroeder Michael , Maschmeyer Georg , Rethwisch Volker , Haxel Boris , Keilholz Ulrich 
Published: March 2020

e17021 Background: This study investigates efficacy and toxicity of docetaxel added to cetuximab, cisplatin and 5-FU for patients with R/M SCCHN. We here report a planned second interim analysis to compare response rates between arms in order to decide on continuing to full accrual. Methods: Inclusion criteria were: stage III/IV R/M SCCHN and ECOG 0-1. Patients were randomized to arm A: cetuximab (standard dose) plus a maximum of 6 cycles of docetaxel (40 mg/m², day 1+8), cisplatin (40 mg/m², day 1+8) and 5-FU (2000 mg/m², day 1+8) or to arm B: cetuximab (standard dose), cisplatin (100 mg/m², day 1) and 5-FU (1000 mg/m², day 1-4). Treatment was administered until progression or intolerability. The endpoint of this analysis was RR. Results: A first interim analysis for toxicity after treatment of 20 patients per arm revealed more hematologic and gastrointestinal grade III/IV toxicities in the experimental arm. Therefore dose reductions of cisplatin from 40 to 30 mg/m² and 5-FU from 2,000 to 1,000 mg/m² had been introduced. A secondary toxicity analysis with 40 patients per arm observed reduced treatment related toxicities. Currently 100 patients could be assessed for response: arm A: 82 % male, median age 58 years, arm B: 82 % male, median age 60 years. Best overall RR was 41 % (3 CR, 18 PR) in arm A compared to 45 % (4 CR, 19 PR) in arm B. The DCR was 75 % in arm A and 80 % in arm B. Conclusions: After introducing dose reductions toxicity is manageable. Comparable response rates were seen in both arms. CeFCiD continues per protocol for evaluation of the primary endpoint PFS. Enrollment is estimated to be completed in Aug 2013. Clinical trial information: CeFCiD-1108.
Comparitive study of quality of life in locally advanced head and neck cancers with concurrent chemoradiotherpy with three weekly cisplatin versus weekly cisplatin regimen.
Authors: Adavikolanu Kesava Ramgopal , Malik Monica , Lachi Pavankumar , Kothwal Syedakram , M Deepajoseph , Syed Fayaz ahmed , Pamidighantam Suresh , K.V Jagannathraonaidu 
Published: March 2020

e17028 Background: Concurrent chemoradiotherapy with three weekly cisplatin is the standard of care for organ preservation in locally advanced head and neck cancers. Quality of life (QoL) is vital in this strategy and this study aims to compare QoL in patients of locally advanced head and neck cancers treated with concurrent chemoradiation with either three weekly or weekly cisplatin regimen. Methods: Between January 2011 and May 2012, 30 patients of locally advanced head and neck cancer were divided into two arms each consisting of 15 patients. All patients received conformal radiotherapy (RT) on linear accelerator to a total dose of 70 Gy, 2 Gy per fraction over 35 fractions. Patients in Arm A received concurrent chemotherapy with Cisplatin 100mg/m2 given on day1,22,43. Patients in Arm B received concurrent chemotherapy with Cisplatin 40 mg/m2given weekly for seven weeks. QoL was assessed using EORTC QLQ-C30 and QLQ-H&N35 questionnaires at baseline, completion of RT and at one and two months following completion of treatment. The collected data was analyzed using standard statistical software package (SPSS version 20.0). Results: Median age in Arm A and Arm B were 45 years (range 23-67years) and 48 years (range 36-71) respectively. All patients completed the planned RT, 73% of patients in Arm A and 93% of patients in Arm B received the planned dose of chemotherapy. Compliance with completion of QoL questionnaires was high in both arms. QoL scores decreased during chemoradiotherapy in both arms, and the scores were better in Arm B without statistical significance. The QoL scores reached baseline earlier in the Arm B compared to Arm A for most of the function scales and symptom scales at second month follow up. There was no statistical difference between the two arms for most of the parameters, except for symptom scales of pain (p=0.029) at 1st month follow-up and swallowing (p=0.023) at 2ndmonth follow-up favouring Arm B. Conclusions: Chemoradiotherapy with weekly cisplatin 40mg/m2 with its better compliance and favourable quality of life can serve as an alternative for the conventional three weekly cisplatin regimen.
Induction chemotherapy (ICh) followed by concurrent chemoradiotherapy (ChR) in locally advanced squamous cell carcinoma of head and neck (SCCHN): Experience in a Mexican institute.
Authors: Avitia Miguel Angel Alvarez , Ponce Jose Luis Aguilar , Lara Gisell Anaid , Molina Violeta Moreno , De La Garza Jaime G. , Granados-Garcia Martin , M Juan Cruz , Mendoza Andres Moran , Ruiz Abraham 
Published: March 2020

e17031 Background: ICh has taken an important role in the treatment of locally advanced disease, but it has not been recognized in which patients (pts) may be the best option ICh followed by ChR or just ChR. We present our experience with ICh followed by ChR regimen in the National Cancer Institute of Mexico (INCan). Methods: We identified 69 patients (pts) diagnosed with locally and/or regionally advanced non-metastatic squamous cell cancer of head and neck, who were attended at the INCan from 2008-2012, in whom, the original treatment was ICh with two cycles of Paclitaxel (P), cisplatin (C) and 5Fluorouracil (5FU) scheme, followed by concurrent ChR with C. But only 35 pts of the original group accomplished the treatment. Results: 13 pts were women (37%) and 22 were men (63%).The median age at diagnosis was 59 years old. In stages III (28%), IVa (46%), and IVb (26%); AJCC, 2002. The subsites per pts. studied were: oral cavity 9 (25.7%), larynx 9 (25.7%), hypopharynx 7 (20%), paranasal sinuses 7 (20%) and oropharynx 3 (8.6%). The rate response was observed in 83%: complete objective rate response (CR) in13 pts (37%), partial response rate in 16 pts (46%) and progression rate in 6 pts. (17%). The mean survival was of 18.3 months (mth) (CI-95: 0.32-0.68).Median survival was not achieved in pts with CR with a median follow up of 2 yrs, pts with PR had a median survival of 15 mth (CI-95: 0.27-0.75) and the median progression was 11 mth (CI-95: 0.11-0.80). We have not got any CR with ICh only, but 13 patients obtained CR at the end of the ChR. Neither age, sex nor subsites were crucial to the clinical response. Conclusions: Our results cannot distinguish patients who might benefit from ICH. In the intention-to-treat population, more than a half of pts did not complete the proposed scheme. Recently, we reported a study using an alternative scheme: Cisplatin and gemcitabine concurrent with radiotherapy to treat pts with advanced SCCHN, and we found that this scheme of treatment is effective and well tolerated, with a 5 yr progression-free survival rate of 27.8 (CI-95: 0–61.5). Yet further studies are needed to compare ICh followed by RCh vs RCh to assess what the best treatment may be.
Methotrexate and cetuximab for metastatic advanced head and neck squamous cell carcinoma.
Authors: Atassi Bassel , Yoo George H. , Robinette Natasha , Sibai Khaled , Sukari Ammar 
Published: March 2020

e17033 Background: After the failure of first-line palliative chemotherapy in recurrent non-resectable or metastatic head and neck squamous-cell carcinoma (HNSCC), there is no standard of care second-line treatment that is proven to improve quality of life or prolong survival. Both methotrexate and cetuximab has shown a single-agent activity in advanced HNSCC. We are presenting our institutional experience in using unique combination chemotherapy with methotrexate plus cetuximab (MC). Methods: Retrospectively, single institution’s charts were reviewed from 2004-2010, all patients have documented recurrent non-resectable or metastatic HNSCC. After failing at least one line of palliative chemotherapy, patients received weekly IV methotrexate 25 mg/m2 plus IV cetuximab 400 mg/m2 loading dose at week one followed by 250 mg/m2 maintenance dose weekly. Each cycle is 4 weeks treatments. Patients who completed at least 2 cycles were included in the study. Patients can receive MC as first line if they have poor performance status. Treatment was continued until progression. Results: Total of 34 patients were included in the study, 26 male and 8 female, 18 African American and 16 Caucasian. Median patient age was 60 years old. 18, 6 and 6 patients received MC as second, third and fourth line therapy, respectively. 4 patients received MC as first line because there were not candidates for more aggressive chemotherapeutic regimens. The average received number of weekly treatments was 25 (8-69) and average number of cycles was 6 (2-17). Prior chemotherapy regimens include taxanes, platinum, 5-flurouracil, and gemcitabin. Median progression free survival was 4.9 months and overall survival was 10.7 months. Overall survival based on race was 9.9 months for Caucasians and 10.7 months for African Americans (P=0.0391). Grade I and II skin rash was observed in 41% of patients, no grade III/IV toxicities were noticed. Conclusions: Methotrexate plus cetuximab is a well tolerated regimen with a significant survival benefit. Prospective studies are warranted in order to evaluate this regimen as a second line palliative therapy for patients with advanced non-curable head and neck squamous cell carcinoma.
“Stop smoking!”: Do we say it enough?
Authors: Reifer Hildebrand Jessica Ann , Sastry Sangeeta , Adams Ashley 
Published: March 2020

e17500 Background: There are clear benefits of smoking cessation after the diagnosis of Bronchogenic Carcinoma (BC). Patients who quit smoking after the diagnosis of BC report lower levels of pain and are less likely to develop a second primary tumor when compared to patients who continue to smoke after they are diagnosed. Persistent smoking is also associated with poor performance status and survival outcomes. Evidence suggests that smokers are more likely to quit if they are counseled by their physicians. Yet, there may be a prevailing belief among physicians that treating tobacco dependence is futile in this population. The purpose of this study was to investigate whether physicians addressed smoking cessation with patients who were diagnosed with BC. Methods: A retrospective chart review of patients who were diagnosed with BC was conducted at a community medical center between 2008 and 2010, using the hospital’s cancer registry. Demographic information including age, race, sex, AJCC stage, and smoking status at the time of diagnosis was collected. Evidence of tobacco cessation counseling was sought through billing codes, physician notes, and orders surrounding the time of diagnosis. Results: A total of 948 patients were diagnosed with lung cancer between 2008 and 2010. 438 were current smokers at diagnosis, 422 were former smokers, and 88 had never smoked. Of the 438 smokers, only 36% were counseled on smoking cessation. On average, each patient encountered 3 different physicians in both the inpatient and outpatient settings. Of note, Stage I patients were 1.7 times more likely to be counseled than those with Stage IV disease (p=0.017). There was no significant difference between the counseled group and the non counseled group in regards to age, race, or sex. Conclusions: In spite of evidence that smoking cessation is beneficial even after the diagnosis of BC, physicians are not counseling their patients sufficiently. Reasons physicians may fail to counsel include: an inability to effectively assess tobacco dependence, competing concerns during patient encounters, and reduced awareness of current quality measures. With the implementation of quality improvement programs, we suspect that smoking cessation counseling for patients with BC will improve in the community setting.
Cost comparison and economic implications of commonly used originator and generic chemotherapy drugs in India.
Authors: Lopes Gilberto , Kulkarni Hrishikesh , Bele Vivek 
Published: March 2020

e17505 Background: Generic substitution may lead to increased access to cancer drugs. Little data have been published on cost savings in emerging markets. Methods: Estimate of cost and savings per cycle, per patient, and for India with generic drugs. Cost of paclitaxel, docetaxel, gemcitabine, irinotecan and oxaliplatin was obtained for originator branded and generic versions from a distributor in India. Costs are depicted in 2012 Rupees. Utilization was based on a BSA of 1.7, standard doses, expected lenght of treatment for common oncology indications and incidence data from GLOBOCAN. Results: Generic drugs cost from 8.9% to 36% of their equivalent branded originator drug, resulting in cost-savings of approximately INR 11,000 to 90,000 [US$ 200-1,600] per each drug per cycle; and approximately INR 50,000 to 240,000 [US$ 900-4,300] per patient treated. Overall, potential yearly savings for health systems in India were nearly INR 47 billion [US$ 843 million]. Conclusions: Generic substitution for commonly used chemotherapy agents has an enormous potential to generate significant cost-savings and increase access to cancer treatments in India and other low and middle income countries. [Table: see text]
Patients with schizophrenia and breast cancer: Adjuvant radiation treatment.
Authors: Davies Lauren , Abdullah Kashif , Janardhan Radhakrishna , Hwang Mark , Farasatpour Michael , Margenthaler Julie A. , Virgo Katherine S. , Johnson Frank E. 
Published: March 2020

e17506 Background: Schizophrenia affects about 1% of subjects in all populations studied so far. It impairs medical care delivery. We sought to evaluate how patients with schizophrenia who are later diagnosed with breast carcinoma fare when adjuvant radiation therapy (ART) is indicated. Methods: We searched the Patient Treatment File (PTF) of the Department of Veterans Affairs (DVA) to identify subjects with schizophrenia who later developed breast carcinoma and were treated in DVA Medical Centers (DVAMCs) from 1999 - 2005. Chart-based clinical data from the DVAMCs where the subjects had been treated supplemented PTF data. Results: 42 patients had preexisting schizophrenia, later developed breast carcinoma, and were candidates for ART. There were 31 women (74%) and 11 men (26%). 27 of the 42 study subjects had records specifying TNM stage; 18 of the 27 (67%) had TNM stages III-IV. 31 subjects had records about compliance with indicated medical therapies; 24 (77%) had previously been non-compliant. 39 subjects had records regarding therapy delay; 20 (51%) had previously delayed medically indicated therapy. Of the 42 subjects who were candidates for ART based on TNM stage, we found data about the decision to recommend ART in 37; only 23 (26%) were offered ART and 3 of those 23 (26%) refused it. Of the 6 subjects who refused ART, 4 had been non-compliant with previous medically indicated care, 3 had delayed initial cancer treatment, 4 had documented suicidal ideation, and 2 had documented homicidal ideation before being offered ART. Conclusions: Subjects with schizophrenia and breast carcinoma often do not understand their illnesses well. They often do not comply with recommended standard therapies such as ART. Treatments that rely on ART are likely to be met with non-compliance. A history of non-compliance appears to be a predictor of non-compliance with ART. Our results should be of interest to caregivers because we describe ways to avoid suboptimal ART in patients with breast carcinoma. Breast-conserving multi-modality treatment with ART is frequently not appropriate; radical surgery is often preferable.
Characteristics of clinical trials for adolescent and young adult (AYA) cancer patients (pts) in Ontario.
Authors: Kwong Wilson , Fraser Graeme A , Barr Ronald , Tu Dongsheng , Meyer Ralph M. 
Published: March 2020

e17525 Background: Outcomes of pediatric and adult cancer pts have improved more than outcomes of AYA pts. Reduced access of AYA pts to clinical trials may partially account for this. Methods: The 10 cancers of highest annual incidence for pts ages 15-29 were identified using the 2005-09 SEER data base and searched on ClinicalTrials.gov (2012/OCT/27) using restriction terms “recruiting”, “intervention studies”, “Canada-Ontario”, and “Adult (18-65)”. Among trials identified, variables compared were sponsor (industry; not industry), intent (curative; palliative; other), endpoints (survival; disease control-adverse event; other), previous therapy (none; other), age (max < 29; max>29 but <50; max>50), intervention (drug; RT+/-drug; other) and randomized design (yes; no). Comparisons used a 2-tailed Fisher’s exact test. Results: We identified 139 trials, including (incidence rank order in bracket): breast-41 (8), non Hodgkin’s lymphoma-36 (4), CNS-30 (6) and acute lymphoblastic leukemia (ALL)-21[10]. There were 45 trials available for the other 6 indications; some trials permitted multiple indications. Most common features were non-industry sponsorship (58%), palliative intent (65%), disease control-adverse event primary endpoint (82%), not restricted to 1st line therapy (76%), max age>50 (69%), drug-only intervention (78%) and non-randomized design (56%). Among all trials, those with an age restriction did not significantly differ from trials with an age maximum of >50. Industry sponsorship was associated with fewer non-drug-only trials (2% vs. 36%; p<0.0001), curative trials (12% vs. 41%; p=0.0002) and age-restricted trials (10% vs. 48%; p<0.0001). CNS and ALL trials were more likely to restrict age eligibility (60% vs. 13%; p<0.0001 for CNS; 52% vs. 18%; p<0.0001 for ALL) and have non-industry sponsorship (90% vs. 49%; p<0.0001 for CNS; 76% vs. 24%; p=0.09 for ALL). Conclusions: Availability of clinical trials for Ontario AYA pts is very heterogeneous and no correlation is seen between AYA cancer-type incidence and number of trials. While CNS cancers and ALL appear unique, access and characteristics of trials for other AYA pts appear to relate to determinants associated with older patients.
Cancer Care Ontario’s lung disease pathway initiative: Building resources for lung cancer quality care.
Authors: Evans William K. , Ung Yee , Chyjek Anna , Gollnow Angelika , Sawka Carol Anne 
Published: March 2020

e17531 Background: Cancer Care Ontario (CCO) is the provincial agency mandated to improve the quality of cancer care in Ontario. CCO has driven quality improvement (QI) on a programmatic basis but in 2008, introduced Disease Pathway Management (DPM) as an additional QI approach. The lung cancer (LC DPM) began in 2009 as a two-year, phased initiative. Methods: The LC DPM team, consisting of clinicians, patients and system stakeholders, was organized into five groups and focused on aspects of the patient journey from diagnosis to end-of-life care, guided by draft pathway maps of the ideal state. 17 improvement concepts were identified of which 8 were selected for detailed development at a provincial consensus conference and validated as LC DPM’s Priorities for Action. 14 regional road shows presented region-specific performance and quality data to practitioners involved in LC patient care to promote ideas for improvement. Funding was provided to support both provincial and regional initiatives that addressed identified gaps. Results: Key outputs of the LC DPM initiative were: establishment of lung diagnostic assessment programs in 14 regions; completion of diagnostic and treatment pathways for NSCLC and SCLC which were grounded in evidence; 10 improvement projects on various stages of the cancer continuum; and 6 one-year Dyspnea Management Pilot Projects. For the dyspnea projects, each funded centre used different approaches and evaluated impacts on patient symptom burden, measured by Edmonton Symptom Assessment System (ESAS), patient satisfaction and quality of life. The learnings from each project have been summarized and will be shared with all regional cancer programs to facilitate knowledge transfer. Tools to support the patient experience include a LC Patient Pathway Map (PPM) and a document, Understanding Lung Cancer. The physician and patient pathways and related materials are available on CCO's website at https://www.cancercare.on.ca Conclusions: LC DPM has proven an effective strategy to accomplish system changes across a large geography that impact the quality of LC care, processes and patient experience. Indicator development and performance management will be used to sustain the gains achieved.