bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uroporphyrinogen decarboxylase gene expression in oral squamous cell carcinomas.
Authors: Kottayasamy Seenivasagam Rajkumar , Ganesan Arun Kumar , Ramamurthy Rajaraman , Kannan Munirajan Arasambattu , Rao Deva Magendhra 
Published: March 2020

e17002 Background: Oral cancer is one of the most common cancers in India. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, has recently been suggested as a novel tumor-selective radiosensitizing target against head and neck cancers. Further, a recent study has suggested that tumors with UROD expression may have poorer outcomes and higher rates of recurrence. We tested the expression of UROD splice variants in oral cancer patients who were treated in our hospital to study its expression and impact on the patients. Methods: The expression of both coding and noncoding splice variants of UROD gene was tested in 42 patients (31 male, 11 female) with oral cavity squamous cell carcinomas treated in 2011-12. Pretreatment tumor biopsies were collected and mRNA was extracted using Quiagen RNeasy kit method. cDNA was synthesized using Superscript III and subjected for UROD expression using specific primers. UROD expression and clinical data of patients were analyzed using IBM SPSS 20 Software. Results: The mean age of the patients was 52 years (range 32-70). Buccal mucosa (n=17) and tongue (n=13) were the most common subsites. Seventy six percent had locally advanced disease (T3/T4 and node-positive) and high-grade (70%) cancers. Chemoradiotherapy (CRT) (n =25) and chemotherapy (CT) (n = 10) was given in 35 patients of which 5 had progressive disease. The mean follow up was 11 months. Thirty seven patients were operated, 5 developed locoregional recurrence and 2 developed spine metastases and died during follow-up. UROD was expressed in 23 (54.8%) patients (coding variant = 52.8%, noncoding = 26%). There was no correlation between UROD expression and age, sex, subsite, stage, grade or node positivity. Patients with UROD expression had a slightly poorer response to CRT/CT (30.4% vs 24.1%; p =NS). Similarly, though they had a slightly higher incidence of recurrence, the difference was not significant. Both patients with spinal recurrence had UROD expression. Conclusions: UROD is highly expressed in oral cancer patients in India. Its proposed radiosensitizing and prognostic role in treatment and outcomes though promising needs further evaluation in a larger number of patients.
Chemotherapy with irradiation in salivary gland carcinomas (SGC): A Rare Cancer Network study (RCN).
Authors: Thariat Juliette , Aranguren Dawn , Gozde Yazici , Studer Gabriela , Krengli Marco , Ghadjar Pirus , Demiroz Candan , Cem Onal , Igdem Sefik , Ozkok Hale Basak , Akyurek Serap , Khanfir Kaouthar , Sun xu Shan , Miller Robert Clell 
Published: March 2020

e17019 Background: To report the role of combined chemotherapy in SGT. Methods: 251 patients with SGC treated in 2001-2011 were included in a collaborative IRB-approved retrospective RCN study. Chemotherapy is empirically administered based on extrapolation from conventional head and neck squamous cell carcinoma (Ca) (SCC) and data on systemic treatment in localized SGC are lacking. Results: Median age was 60 yo with 2/5 females/males. Tumor sites were the parotid 74.9%, submandibular 16%, sublingual 2.8% or minor gland 4%. Histologic findings were adenoid cystic (ACC) 17.3%, mucoepidermoid (MEC) 19.8%, adenoCa 15.6%, salivary duct (SDC) 10.3%, acinic cell (Aci) 6.2%, ex-pleomorphic 7.8%, undifferentiated 4.9%, myoepithelial 3.3%, epithelial myoepithelial 1.6%, basal cell 1.2%, lymphoepithelial 1.2%, others 4.0%. Surgery was performed in 95.1% (complete resection 38.1%). T stages 1, 2, 3 and 4 were 17.2%, 41.2%, 18.1% and 23.5% respectively. N stages were N0 61%, N1 13%, N2 24%, N3 2%. Perineural, vascular or lymphatic emboli were present in 47%, 24%, 27% respectively. Irradiation was performed postoperatively 96% or exclusively 4% (unilateral 84%, performed w/ photons only 78%, IMRT 41%). Chemotherapy was administered in 18%, dependent on grade, N stage, and emboli (p ≤ .05). None of 17 ex-pleomorphic, 25% of undifferentiated, 36% of SDC, and 66.7% of lymphoepithelial Ca received chemotherapy (p NS). With a median follow-up of 42 months for living patients, crude local, regional, metastatic relapse rates were 112% (in field 85%), 10%, 25%, respectively. Crude death rate was 28% including 77% from SGC. 5-year survival (5y OS) was 63%. The only prognostic factor was nodal involvement (p .002). However, 5y OS differed by histology: ACC 79%, MEC 84%, Aci 67%, SCC 43%, adenoCa NOS 40%, SDC 37%. Chemotherapy did not improve survival whatever histology. Conclusions: Further prospective studies are warranted to define the role of chemotherapy by histology in the setting of localized SGT. Also molecular profile-driven systemic treatments should be investigated.
Immunonutrition limits pro-inflammatory and pro-oxidant effects of radiochemotherapy in cancer patients.
Authors: Vasson Marie-Paule , Talvas Jeremie , Goncalves-Mendes Nicolas , Kwiatkowski Fabrice , Bienvenu Jacques , Bachmann Patrick , Bouteloup Corinne 
Published: March 2020

e17022 Background: Peri-operative immunonutrition improves digestive surgical outcomes of cancer patients reducing complications and length of stay. Radiochemotherapy (RCT) generates deleterious effects on nutritional and immune status limiting functional capacities of patients. This study aimed to evaluate if immunonutrition enriched in arginine, EPA & DHA and nucleotides could limit these side effects in Head&Neck (HN), and oesophageal cancer patients. Methods: A double-blind randomized clinical trial was driven with two groups receiving either an Immune Enteral Nutrition (IEN, n=13, Impact, Nestlé) or a Standardized Enteral Nutrition (SEN, n=15) during all RCT (5-7 weeks). Nutritional status, plasma antioxidant capacity (TEAC, FRAP) and functional capacities (WHO score, Karnofsky index) were assessed at the beginning (Db) and at the end (De) of RCT. Immune functions were assessed by leukocytes phenotyping, ex vivo PMN ROS production, and PBMC cytokines & eicosanoids (PGE2) secretion and gene expression. Results: At De vs Db, a significant improvement in total body weight (+2.1kg) was observed in IEN patients as well as albuminemia and NRI in IEN malnourished patients. TEAC and FRAP were increased (+100µM EqTrolox) in IEN patients and higher at De than for SEN patients. Functional capacities were maintained upper the autonomy threshold only in IEN patients. The PMN density of chemo-attractant receptors (CD62L, CD15) and ROS production (+30%) were significantly increased in IEN patients at De vs Db. PBMC PGE2 secretion was unchanged at De in IEN patients and lesser than for SEN patients (65.9±56.8 vs 106.8±59.3 ng/ml, p<0,05). Folding ratios (De/Db) of PBMC mRNA expression were strongly increased for antioxidant response genes (catalase, gpx1&4, sod1&2) and for bactericidal NOX system (cybA, rac1&2). Conclusions: Immunonutrition in adjunction to RCT contributes to maintain functional capacities of patients through improvement of nutritional, anti-oxidant and immune status. Immunonutrition could provide a higher bactericidal capacity and limit inflammatory and oxidative responses induced by RCT in immune cells of HN and oesophageal cancer patients. Clinical trial information: NCT00333099.
Comparison between the common neoadjuvant regimens in locally advanced squamous cell cancer of oral cavity.
Authors: Roy Rakesh , Chatterjee Indranil , Chatterjee Indranil 
Published: March 2020

e17024 Background: In locally advanced squamous cell carcinoma of the oral cavity, neoadjuvant chemotherapy induces a high response rate that may facilitate definitive surgery or radiotherapy. Patients have an acceptable long-term survival.A strategy was developed in a tertiary care cancer hospital in India to treat patients with locally advanced oral cancers with induction CT followed by surgery if possible.In our centre selection of neoadjuvant regimens were based on following criteria: age, performance status, financial status, accessibility, comorbid illness, and lab parameters. Methods: 32 patients with locally advanced cancers of the oral cavity and inoperable upfront were selected for neoadjuvant chemotherapy. All were male patients, age ranging from 32 – 65 years, with a performance status ECOG 0-1. All had been tobacco users in some form and hailed from east and northeast parts of India. HPV data were unavailable. 2 patients had controlled diabetes. No other comorbidity was found. 20 patients got DCF (docetaxel, 5FU, cisplatin), 8 patients received PCF (paclitaxel, 5FU, cisplatin), 4 patients received PC (paclitaxel, carboplatin). 20-hr infusional 5FU daily was given over a period of 3 days in both the DCF and PCF arms unlike the 5 day infusion. All received growth factors as primary prophylaxis. Results: Patients who received DCF showed the best response followed by PCF and finally PC. Complete response (CR) was found in 6 patients, all of whom received DCF. All underwent surgery. Amongst toxicity neutropenia was highest with DCF arm but none developed febrile neutropenia. Patients exposed to 5FU had grade 1-2 diarrhoea in 90 % cases. No grade 3-4 mucositis were recorded. Diabetic patients who received PC and PCF and did not experience additional neurotoxicity. Dose reduction or modification was required in one patient who received DCF. Conclusions: Neoadjuvant chemotherapy is an useful treatment option for locally advanced cancers of the oral cavity. DCF regimen is most effective and well tolerated in Indian patients. Judicious selection of patient is necessary.
Panobinostat, a novel histone deacetylase inhibitor, in advanced medullary and iodine-refractory differentiated thyroid cancer: A Wisconsin Oncology Network trial.
Authors: Traynor Anne M. , Leverson Glen E. , Elson Diane F , Hernan Hilary R , Larson Martha M. , Blank Jules Harris , Fareau Gilbert G , Wisinski Kari Braun , Mattison Ryan J. , Chen Herbert , Sippel Rebecca S 
Published: March 2020

e17025 Background: Histone deacetylase (HDAC) inhibitors suppress tumor cell proliferation in medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC) in vivo. We conducted a multicenter single arm phase II trial of panobinostat, a potent inhibitor of Class I, II, and IV HDAC enzymes, in MTC and radioactive iodine (RAI)-refractory DTC. Methods: We enrolled 13 patients (pts) with progressive metastatic MTC or RAI-refractory DTC. Panobinostat was given at 20 mg orally TIW until disease progression or intolerable toxicities. The primary objective was anti-tumor response rate; secondary objectives included overall survival (OS), progression-free survival (PFS), tolerability, and changes in serum thyroglobulin (Tg) concentration. Results: Mean age was 61±13 yrs; 7 pts were female. 11 pts had DTC; 2 had MTC. Median study follow-up was 11.8 months (mos). 9 pts required dose holds/reductions due to thrombocytopenia (n=7), hypocalcemia (n=3), neutropenia (n=2), diarrhea (n=1), bone pain (n=1), or asthenia (n=1). Due to protocol specified rules, 2 pts were withdrawn from therapy with thrombocytopenia or neutropenia, both asymptomatic. Of the 3 pts with ≥ grade 3 thrombocytopenia, 2 had no bleeding. The third pt continued to bleed from her chronically erosive tumor without exacerbation. Median duration of treatment was 2.1 mos (range, 0.8-11.8). Stable disease (SD) was seen in 7 pts, with a median duration of 5.8 mos (range,1.8-13.8). All 7 SD pts are currently alive, including 2 with SD 4.9 mo and 11.8 mo on treatment. Progressive disease (PD) occurred, and was the cause of death, in 6 pts.No anti-tumor responses were observed. Median PFS for the 13 pts was 3.6 mos (95% CI, 1.8-5.8), with 2 pts having a PFS longer than 6 mos.Median OS for the 13 pts was 18.4 mos (95% CI, 5.8-not estimable). 5 of 11 pts had reductions of their serum Tg on study; however, changes in serial Tg values did not distinguish PD from SD pts. Conclusions: 20 mg TIW was not tolerated by most pts. However, dose modified treatment yielded SD in half of our previously progressing pts. This promising disease stabilization warrants further evaluation, possibly in combination with a VEGFR TKI. Clinical trial information: NCT01013597.
EGFRv3 and PTEN as prognostic markers in head and neck squamous cell carcinoma patients treated with cetuximab.
Authors: da Costa Alexandre Andre Balieiro Anastacio , Ribeiro Adriana Regina G. , Guimaraes Andrea Paiva , Chinen Ludmilla Thome , Pinto Clovis , Lima Vladmir C. 
Published: March 2020

e17032 Background: Cetuximab (CTx) is used in treatment of locally advanced (LAD) head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy (RT) or in metastatic disease (MD). There is no comparison between CTx plus RT and cisplatin plus RT. Patients treated with CTx in daily clinical practice are frequently different from the selected population treated in clinical trials. There are no biomarkers for efficacy of CTx in HNSCC. EGFR variant 3 mutation (EGFRv3), an extracellular domain mutation of EGFR, has been reported in different frequencies in HNSCC in the last years and its association with prognosis and CTx efficacy is still unknown. Methods: Retrospective review of data from patients with HNSCC treated with CTx at a single institution from 2007 to 2010. We evaluated CTx efficacy and expression of EGFRv3, EGFR, PTEN, CD44 and CD44v6 and their impact in objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Biomarkers were analyzed by immunohistochemistry in tissue microarray. Results: For a median follow-up time of 13 months, 61 patients with LAD treated with RT plus CTx had a median OS of 22.7 months, and a median PFS of 8.0 months. Age adjusted Charlson Comorbidity Index (AA-CCI) and ECOG performance status were the most important predictors of poor prognosis in this population. For a median follow-up time of 10.9 months, 44 patients with MD had a median OS of 13.0 months and a median PFS of 7.0 months, for an ORR of 53.7%. EGFRv3 was expressed in 27.1% of tumor samples and was not associated with any clinical outcome. EGFR positivity was associated to higher ORR in LAD and PTEN negativity was associated with shorter OS in the MD setting. Conclusions: In a non selected population with LAD treatment results with CTx in combination with radiotherapy were worse than expected by the phase III study, median OS 22.7 months vs 49.0 months. This difference may be attributed to different population characteristics with higher ECOG and AA-CCI in our study and warrants an adequate proof of efficacy of CTx in this population. EGFRv3 is present in HNSCC but does not impact prognosis. PTEN and EGFR expression emerged as potential biomarkers in HNSCC patients treated with CTx.
The effect of gaps in chemotherapy in patients with stage IV colorectal cancer.
Authors: Sada Yvonne , Davila Jessica , El-Serag Hashem , Duan Zhigang 
Published: March 2020

e17501 Background: Chemotherapy (CT) utilization in patients with stage IV colorectal cancer (CRC) has not been well documented in community practice settings. Further, clinical trial data indicate that time gaps during CT for stage IV CRC patients are associated with worse survival. However, the prevalence of CT gaps and their effect on survival in the general population is unclear. Methods: Using national Surveillance, Epidemiology, and End Results-Medicare linked data, stage IV CRC patients diagnosed during 2000-07 were identified. Those who received CT (based on ICD-9 codes) within 3 months after CRC diagnosis were identified. CT duration during the 2 years following CRC diagnosis and frequency of gaps were calculated. A CT gap was defined as >30 days between 2 CT claims. Data on demographics and clinical factors were collected. Multivariable regression was used to identify determinants of CT gaps. Cox proportional hazard models were used to examine the effect of gaps on mortality. Results: 4015 patients with stage IV CRC were identified. Median age was 74 (IQR: 70-79); 51% were male. A CT gap occurred in 2123 patients (53%). Most patients received <3 months of CT (37%), followed by 7-12 months (26%), 3-6 months (21%), >12 months (16%). Nearly 70% of patients who had >3 months of CT had a gap. Among these patients, 41% had 1 gap, 27% had 2 gaps, and 32% had ≥3 gaps. Median number of days per gap was 42 (IQR: 35-75). Multivariate analysis showed that patients who were Asian (OR 1.8, 95% CI: 1.2-2.70), had >12 months CT (5.1, 4.0-6.5), hospitalized during CT (3.9, 3.3-4.6), or had toxicity (1.5, 1.3-1.8) were more likely to have a gap, while patients with comorbidity index ≥2 (0.7, 0.6-0.9) were less likely to have a gap. 1-yr survival was higher in patients with gaps compared to no gaps (89% vs. 60%) after excluding patients who had <3 months of CT. Cox proportional hazard models showed that patients with gaps had a lower risk of mortality (HR 0.58, 0.52-0.64), adjusting for patient and clinical factors. Conclusions: Over half of patients with stage IV CRC had a gap during CT. Contrary to clinical trial data, CT gaps were associated with a survival benefit. Further studies are needed to confirm these findings and to explore patient and provider reasons for stopping CT.
Utilization of subspecialty care by Hispanic pediatric oncology patients, California 1983-2010.
Authors: Alvarez Elysia , Chamberlain Lisa J. , Marina Neyssa , Saynina Olga , Wise Paul 
Published: March 2020

e17504 Background: Previous analysis has shown that Hispanic pediatric oncology patients in California have decreased utilization of pediatric cancer specialty centers (PCSC). The purpose of this study was to examine the clinical and non-clinical factors associated with decreased inpatient utilization of PCSCs by Hispanic pediatric oncology patients. Methods: Using the California Office of Statewide Health Planning and Development private database we performed a retrospective population based analysis of Hispanic patient discharges 0-18 years of age to explore the influence of age, gender, payer, income, distance to admission site, tumor type and diagnosis of fever and neutropenia on the utilization of PCSCs by Hispanic patients. Results: Analysis of 82,832 Hispanic pediatric oncology discharges showed concentration of hospitalization in PCSCs increasing from 64% in 1983 to 94% in 2010. In addition, an increased percentage of acute lymphoblastic leukemia discharges was seen for Hispanics (28.3%) compared to all discharges (22.4%). The adjusted regression analysis revealed decreased utilization of PCSCs for patients ages 15-18 (OR 0.466; CI 0.441-0.493) and for those residing 6 - 10 miles from a PCSC (OR 0.927; CI 0.883 - 0.974). Increased utilization of PCSCs was seen for Hispanic patients living in zip codes where household income was >4 times the Federal Poverty Level. Payer status was not significantly associated with discharge from a PCSC. None of these findings changed when Los Angeles County was removed from the analysis. A separate analysis was done on Hispanic pediatric oncology patients with a discharge diagnosis of fever and neutropenia. For this subset decreased utilization was seen for those with private insurance (OR 0.84; CI 0.81-0.887), age <1 (OR 0.719; CI 0.64-0.808), ages 15-18 (OR 0.596; CI 0.558-0.636) and those residing >40 miles from a PCSC (OR 0.913; CI 0.854-0.975). Conclusions: Utilization of inpatient pediatric oncology care by Hispanic patients in California has become regionalized in PCSCs since 1983 and is influenced by age, and geography, with payer status not being a significant contributor. Clinical outcomes as they relate to access to PCSCs for Hispanic patients should be examined.
Clinical impact of an online tool to guide choice of therapy (Tx) for patients (Pts) with advanced renal cell carcinoma (RCC).
Authors: Quill Timothy A , Rini Brian I. , Jonasch Eric , Bowser Andrew , Mortimer Jim A. , Motzer Robert John 
Published: March 2020

e17530 Background: Clinical practice guidelines outline multiple treatment options for pts with advanced RCC, but provide little to no guidance on the best Tx for an individual pt. We have previously reported that online interactive decision support tools may help practicing community oncologists identify optimal treatment approaches in breast and lung cancers and CML (ASCO 2011 [abstr 6063]; ASTRO 2012 [abstr 162]; ASH 2012 [abstr 4279]). Here, we assess the impact of a tool on the decisions of clinicians treating pts with advanced RCC. Methods: An online tool was developed based on asurvey of experts who were asked what Tx they would choose for 76 pt case variations. Experts considered patient- and tumor-specific characteristics including histology (clear cell vs nonclear cell), extent of metastases, previous systemic therapy received, MSKCC risk status (good/intermediate vs poor), and ECOG performance score (0 vs 1 vs ≥ 2). The tool was built based on their responses and posted online July 12, 2012. After tool users input specific pt characteristics and indicate their intended Tx plan, a table of expert Tx choices are displayed for that pt scenario. To determine the impact of viewing the expert choices, users are then asked if the expert feedback has confirmed or changed their original Tx plan. Results: Three experts completed the survey. Key factors in the experts’ Tx choices were MSKCC risk status for first-line therapy and previous systemic therapy. Preliminary data of 419 cases entered by participants in the online tool show that expert insight changed or confirmed Tx choice for 81% of participants (changed: 22%; confirmed: 59%). An analysis of expert vs user treatment selections in specific subpopulations will be presented. Conclusions: An online tool designed to provide customized, patient-specific expert advice may increase the number of clinicians who make optimal treatment decisions for patients with advanced RCC. Data indicate that the expert choices influenced clinicians’ Tx decisions and, therefore, may facilitate improvements in pt care and outcomes. The tool was developed through an unrestricted educational grant from Pfizer.