bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized study comparing high-dose (HD) influenza vaccine to standard-dose (SD) influenza vaccine in patients with breast cancer age < 65 receiving chemotherapy.
Authors: Jamshed Saad , Falsey Ann R , Thushara Paul , Walker Jennifer , Walsh Edward E 
Published: September 2018

e21695 Background: Patients on chemotherapy often fail to develop a robust response to influenza vaccine. We had previously demonstrated that HD vaccine improved immunogenicity in cancer patients receiving chemotherapy. The present subgroup analysis evaluates immunogenicity & tolerability of HD to SD vaccine specifically in breast cancer pts <65 yrs receiving chemotherapy. Methods: 35 breast cancer pts were randomized to receive either SD or HD (17 vs 18) vaccine on day1 of chemotherapy during 2 influenza seasons. HAI titers were measured prior to & 4-wks after vaccination. HAI were summarized as geometric mean titer (GMT) and seroconversion (>4-fold titer rise) & seroprotection (GMT ≥40) rates calculated. t-test was used to compare log2-transformed GMT titers between groups and χ2 for comparison of seroconversion and seroprotection rates. Results: 2 pts were included only once (yr 1) as they received study vaccine both yrs. Mean age (50.4 vs 51.3 yrs) and baseline HAI titers were equivalent; 81 vs 88% were receiving therapy with curative intent in SD vs HD arms, respectively. Both vaccines were well tolerated with no SAEs. Post vaccination GMT were greater after HD vaccine, but was statistically significant only for H3N2 virus. Seroconversion rates for B strain was significantly improved with HD vaccine while seroprotection was excellent for all antigens in both arms. Conclusions: Trivalent HD influenza vaccine can be safely administered with increased seroconversion over SD vaccine. Most patients with breast cancer should be offered vaccination even if they are receiving chemotherapy, as they demonstrate robust response to either influenza vaccine. A larger study is needed to show clinical benefits with HD vaccine. Clinical trial information: NCT01666782. [Table: see text]
Clinical observation of yizhongshengxue capsule on the treatment of advanced gastric cancer-related anemia.
Authors: Hou Li , Wang Jia , Wang Jing , Li Ya , Chen Xinyi 
Published: September 2018

e21696 Background: Cancer-related anemia is an important factor that affects the clinical efficacy and quality of life for patients with advanced gastric cancer. This study is to observe the clinical efficacy of Yizhongshengxue Capsule, which is an herbal formula, on advanced gastric cancer-related anemia. Methods: A total of 96 eligible patients were randomized into three arms: 46 patients in the experimental arm, 26 patients in the positive control arm, and 24 patients in the negative control arm. All three arms received basic treatment of conventional medicine. Meanwhile, the experimental arm received Yizhongshengxue Capsule at the dosage of 3 capsules, 3 times daily. The positive control arm received Fufangejiao Syrup at the dosage of 20 ml, 3 times daily. The negative control arm received only basic treatment of western medicine. The course of treatment was 5 weeks. Results: After the 5-week-treatment, there was a statistically significant rise ( p<0.05) of hemoglobin(HGB) in both experimental arm and positive control arm. The negative control arm had no statistically difference of HGB ( p>0.05) before and after the treatment. Symptoms of dizziness, fatigue, loss of appetite, palpitation and insomnia in experimental arm were improved after the treatment ( p<0.05). Symptoms of fatigue and loss of appetite in positive control arm were alleviated after the treatment ( p<0.05). The negative control arm had no statistically difference in the above symptoms ( p>0.05) before and after the treatment. Furthermore, there was a significant improvement of dizziness, loss of appetite, palpitation and insomnia in the experimental arm compared to the negative control arm ( p<0.05). Finally, an improvement of the Karnofsky Performance Score(KPS) was seen only in the experimental arm after the treatment compared to that before the treatment ( p<0.05). Conclusions: Our study shows that Yizhongshengxue Capsule can not only improve the clinical symptoms and quality of life in patients with advanced gastric cancer-related anemia, but also reduce or even reverse the trend of HGB decrease. Therefore, it is very promising in treating cancer-related anemia. Clinical trial information: ChiCTR-TRC-13003604.
Association of Met-BDNF allele with pre-existing peripheral neuropathy in breast cancer patients.
Authors: Azoulay David , Leibovici Anca , Sharoni Rivka , Goldberg Hadassah 
Published: September 2018

e21702 Background: We previously published preliminary results suggesting an association between the met-BDNF allele and vulnerability to paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients. Here we present updated data obtained from our extended study. Methods: 35 patients; 34 women (33 with breast cancer and 1 with ovarian cancer) and one man (breast cancer) completed their follow-up. Peripheral neuropathy (PN) was assessed at diagnosis and along the treatment protocol, using the reduced version of Total Neuropathy Score (TNSr). Patients with TNSr≥2 at diagnosis were determined with pre-existing PN (Pre-PN). Allelic discrimination of BDNF polymorphism (rs6265) was determined by Sanger sequencing. Results: BDNF genotype Val/Val was found in 20 patients (57.14%), Val/Met in 15 patients (42.86%). No patient had the Met/Met genotype. 10 patients (28.57%) were diagnosed with Pre-PN, 3 of them with diabetic-related neuropathy. A higher incidences of the Met-BDNF allele was found in patients with Pre-PN as compared to patients with no Pre-PN (7/10 (70%) vs. 8/25 (32%) Val/Met in Pre-PN and no Pre-PN respectively, prob > ChiSq < 0.05). The three patients with diabetic related Pre-PN were genotyped Met-BDNF. The maximal TNSr scores developed by each patient during follow-up were higher in Met-BDNF patients compare to Val/Val patients. (Maximal TNSr mean ± SEM in Val/Val 4.80±0.62 vs. 7.73±1.34 in Val/Met BDNF, prob < t 0.04). No difference in the maximal TNSr scores between Met-BDNF and Val/Val patients were shown after excluding the patients with Pre-PN (Maximal TNSr mean ± SEM in Val/Val 5.05±0.78 vs. 5.25±0.62 in Val/Met BDNF, prob < t 0.44). Conclusions: Our data demonstrate an association between met-BDNF and Pre-PN. Higher maximal TNSr scores in our met-BDNF patients is generally the consequence of their higher Pre-PN.
Race-specific genetic aberrations in B-acute lymphoblastic leukemia in children.
Authors: Reddy Amit , Espinoza Ingrid , Johnson Dana , Schallheim Jason , Bhanat Eldrin , Zhou Yunyun , Zabaleta Jovanny , Megason Gail , Gomez Christian 
Published: September 2018

e22000 Background: B-Acute Lymphoblastic Leukemia (B-ALL) is the most common childhood cancer and the leading cause of death in children. Studies have shown that African-American (AA) children have significantly lower survival rates compared to European-American (EA) children. This disparity is not related to socioeconomic variables, suggesting a molecular basis for the lower survival. Here we present a study showing genetic aberrations (GA) involved in race-specific leukemogenesis and contribute to health disparities in B-ALL in AA and EA children. Methods: A total of 20 newly diagnosed pediatric patients were studied (5 AA and 15 EA) at University of Mississippi Medical Center. Ages range between 1 and 18 years with a median age of 4 years. None of the patients in our study had a relapse. Frozen bone marrow (BM) aspirates were used to extract DNA and whole-exome DNA sequencing was performed, focusing on race and B-ALL specific germ-line mutations. Results: Most GA were shared between AA and EA, for example those present in the Anaplastic Lymphoma Receptor Tyrosine Kinase (ALK) gene. Some genes with GA were specific to AA and others to EA. Genetic non-synonymous germ-line aberrations were identified such as, Lipoma Preferred Partner Gene, in AA and Leukemia Inhibitory Factor Receptor, in EA. Ingenuity pathway analysis revealed these genes clustered in race-specific canonical pathways. In AA, the pathways were related to telomerase signaling and cancer signaling. While in EA, it was related to stem cell pluripotency and hereditary cancer. Conclusions: The prevalence of GA in B-ALL may contribute to differences in outcomes between AA and EA children. Aberrant biological networks revealed by our study, will provide information on distinguishing signaling networks involved in race-specific leukemogenesis. Our study provides a strong basis to develop a race-specific prognostic assay for B-ALL in BM aspirates. In the future, this can help guide risk stratification and treatments based on race and advance the prognostication of B-ALL in AA children. Funding: Hyundai Hope on Wheels Scholar Grant, UMMC Division of Pediatric Hematology Oncology.
Patterns of care in treating childhood neuroblastoma: Evidence from a population level study (SEER) in the United States.
Authors: Coughlan Diarmuid , Lynch Charles , Gianferante Matthew , Stevens Jennifer , Harlan Linda C 
Published: September 2018

e22011 Background: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors. This heterogeneity is reflected in the sequence and variety of treatment modalities administered. We describe the treatment pattern and survival of childhood neuroblastoma patients using population-based data in the United States. Methods: Using the National Cancer Institute’s (NCI) Patterns of Care data, we examined treatment provided to childhood neuroblastoma patients newly diagnosed in 2010 and 2011 and registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Data were re-abstracted from hospital records and treating physicians were contacted to verify the treatment given. Stratifying by the Children’s Oncology Group (COG)’s 3-level (low, intermediate and high) neuroblastoma risk classification system for therapeutic decision-making, gave a snapshot of community-based treatment patterns. Kaplan-Meier survival analyses were also performed. Results: The majority of 250 patients (76%) were enrolled on an open/active clinical trial. All low-risk patients received surgery with/without chemotherapy. The majority of intermediate-risk patients (77%) received chemotherapy regimen that included carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received extensive, multimodal treatment consisting of chemotherapy, surgery, high dose chemotherapy with stem cell rescue (transplant), radiation, immunotherapy (dinutuximab), and isotretinoin therapy. Cyclophosphamide was the most utilized chemotherapy agent (94%) in high-risk patients. Survival with a maximum follow-up of 48 months, was lowest (68%) for patients diagnosed with high-risk disease. Conclusions: The majority of childhood neuroblastoma patients are registered on a risk-based open/active clinical trial. Variation in modality, systemic agents and sequence of treatment reflects the heterogeneity of therapy for childhood neuroblastoma patients.
Lack of micro-RNA 128A expression as a novel prognostic marker in neuroblastoma patients and combination with TERT hyperexpression to define patient outcomes.
Authors: Druy Alexander , Tsaur Grigory , Shorikov Egor , Zaychikov Artem , Olshanskaya Yulia , Saveliev Leonid , Fechina Larisa 
Published: September 2018

e22014 Background: Rearrangements of TERT gene with its correspondent hyperexpression were identified as adverse prognostic markers in neuroblastoma (NB) patients, while significance of microRNAs expression is undiscovered. Methods: RNA from 103 fresh-frozen NB tissues was subjected to reverse transcription qPCR for miR128A and TERT expression evaluation. Copy number variations were determined by MLPA and FISH. Correspondence of miR128A and TERT expression levels to event-free survival (EFS) was proved by ROC-analysis and established threshold levels (TL) were utilized for group separation in subsequent survival analysis. Median of follow-up time achieved 5.8 years. Results: Abundant TERT expression and lack of miR128A expression resulted in superior frequency of adverse events (p = 0.027, TL = 4,7E-3 and p = 0.004, TL = 4.6E-2 respectively). EFS in group of patients with TERT expression above 4,7E-3 (group TERT) was 0.66SE0.07, in patients with miR128A expression below 4.6E-2 (group miR128A) was 0.64SE0.15, patients harboring both TERT overexpression and lack of miR128A expression (group miR128/TERT) had dismal outcome: EFS 0.29SE0.11, comparing to patients without these abnormalities (group "neither"): EFS 0.92SE0.06, p < 0.001. Analogously, cumulative incidence of progression differed significantly between all these groups, p < 0.001. MYCN amplified (MNA) samples were accumulated in the groups TERT and miR128/TERT (p = 0.061), while chromosome 17 gain, 9p and 14q deletions prevailed in the group "neither" (p = 0.014, 0.043 and 0.017 accordingly). MNA and 14q deletion had prognostic significance in the correspondent groups (p < 0.001, p = 0.022). The classifier was proposed for distinguishing patients with unequal outcome: MNA EFS = 0.25SE0.11, MYCN single copy patients divided into groups miR128A/TERT (0.40SE0.15), miR128A (0.60SE0.15) and TERT (0.74SE0.08). Group "neither" was separated basing on presence (0.71SE0.17) and absence (EFS = 1.00) of 14q deletion, p < 0.001. Conclusions: Levels of miR128A and TERT expression together with cytogenetic data allow discriminating patients into groups with significantly different outcome.
Human chorionic gonadotropin (HCG) as a biomarker in sarcoma: A systematic review.
Authors: Schoen Martin W. , Al-Taee Ahmad , Jallad Bassel 
Published: September 2018

e22503 Background: Human chorionic gonadotropin (HCG) has been reported in soft tissue sarcoma and osteosarcoma. In some patients, the ectopic production of HCG can lead to delays in diagnosis due to concern for pregnancy or germ cell tumors. Methods: We performed a systematic review of the scientific literature in English using PubMed to categorize cases of sarcoma search terms were HCG, sarcoma, human chorionic gonadotropin and osteosarcoma. Cases of sarcoma associated with HCG production were identified and further categorized by type and grade of tumor. Initial HCG, Peak HCG, response to therapy and case outcome were collected when available. We also included a case seen at our institution of osteosarcoma with ectopic HCG production. Results: We identified 21 manuscripts and 23 cases of patients with both sarcoma and elevated serum HCG. 10/23 patients were male (43%).The most frequent type of sarcoma was osteosarcoma with 9/23 (39%) of cases, leiomyosarcoma was identified in 7/23 (30%) and liposarcoma in 3/23 (13%) of cases. When described, all tumors were high grade or poorly differentiated. 20/23 tumors (87%) had HCG expression of the tumor by immunohistochemistry. Mean initial HCG was 3607 with a peak value of 6188. In 19 cases, HCG was used to monitor disease after treatment and 14/19 (74%) responded with a decrease in HCG after treatment. Of responders, 3 patients were considered cured and 2 were put into remission, while none of the patients without response survived. Overall, outcomes were poor with 16/23 (70%) deaths within one year. Conclusions: Sarcomas that secrete HCG tend to be high grade, poorly differentiated and appear to portend a poor prognosis. When expressed, HCG can be used as a marker of disease and response to therapy. Oncologists should consider checking HCG as a potentially low-cost marker of prognosis and response to treatment in patients with sarcoma. [Table: see text]
Safety and efficacy of trabectedin when administered in the inpatient vs. outpatient setting in a subset analysis of a phase III randomized clinical trial.
Authors: Jones Robin Lewis , Maki Robert G , Patel Shreyaskumar , Wang George C. , Shin Chu Ri , Knoblauch Roland Elmar , Parekh Trilok V. , von Mehren Margaret , Demetri George D. 
Published: September 2018

e22516 Background: Trabectedin (T) has been shown to improve progression free survival (PFS) (4.2 vs 1.5 months, HR 0.55, p < 0.0001) in comparison to dacarbazine (D) in patients (pts) with advanced leiomyosarcoma or liposarcoma following failure of prior chemotherapy. Pts randomized to T in this phase III trial (ET743-SAR 3007) received T as a 24 hr IV infusion in either an inpatient (InP) or outpatient (OP) setting, based upon site preference. Here we report the safety, efficacy, and patient reported outcomes (PROs) of pts based on first infusion site of care. Methods: Pts were randomized 2:1 to receive T (1.5 mg/m2) or D (1 g/m2 over 20-120 min). Site of T infusion was based on institutional preference/standard of care. The site of T administration (InP vs OP) was collected for the first infusion with the assumption that site of care was unchanged for subsequent doses. Results: Of 378 pts treated with T, 100 (27%) and 277 (73%) pts received T as InP or OP, respectively. No differences were observed in PFS or overall survival (OS) by site of care (InP vs OP): Median PFS of 4.1 vs 4.2 months; HR 0.90, p = 0.49 and median OS of 14.3 vs 13.7 months; HR 0.89, p = 0.40. No difference in other efficacy endpoints between InP vs OP were observed: disease control rate (CR+PR+(SD≥18wks)) (38% vs 33%; Odds Ratio [OR] 1.22; p = 0.44) and Overall Response Rate (14% vs 8%; OR 1.76; p = 0.15)). Grade 3-4 adverse events (AEs) occurred in 87% InP vs 79% OP pts and grade 3-4 SAEs occurred in 43% InP vs 33% OP. The most common grade 3-4 AEs in both groups were increased ALT/AST, hematologic toxicity, nausea and fatigue. The incidence of grade 3-4 febrile neutropenia was similar in both groups at 5.0% InP vs 4.7% OP, as was increased blood creatine phosphokinase at 5.0% InP vs 6.1% OP, and catheter related complications of any grade at 16% InP vs 15% OP. No clinically meaningful differences were observed in PROs measured by MD Anderson Symptom Inventory scores. Conclusions: The majority of patients randomized to the trabectedin arm of the ET743-SAR-3007 Phase III study received trabectedin in the OP setting. Treatment outcomes with trabectedin suggest equivalent efficacy and safety when administered in the InP or OP setting. Clinical trial information: NCT01343277.
BMI as a risk factor for toxicities in patients with advanced soft tissue sarcoma treated with trabectedin.
Authors: Silletta Marianna , Armento Grazia , Badalamenti Giuseppe , spalato Ceruso Mariella , Catania Giovanna , Incorvaia Lorena , Santini Daniele , Tonini Giuseppe , Vincenzi Bruno 
Published: September 2018

e22517 Background: Since the first steps of its clinical development, trabectedin was noticed to be extremely active against myxoid liposarcoma (MLS), whose pathogenesis seems to be associated to the presence of the t(12;16)(q13;p11) translocation, resulting in the expression of FUS-DDIT3 fusion genes. Therefore, the drug seems to induce a maturation of MLS lipoblasts, with transition of the residual spindle non-lipogenic cells into mature vacuolated lipoblasts. This effect could be prevented by the increase of leptin circulating levels in obese patients. For these reasons we designed this retrospective analysis in order to evaluate the BMI status (measure of total adipose content) as a predictors or efficacy of trabectedin in MLS patients. Methods: Patients were treated in cancer centers with trabectedin at the approved dose of 1.5 mg/m2, given as a 24-hour infusion every 3 weeks. This retrospective analysis was preformed on the basis of clinical charts or databases. For the purpose of this analysis only patient with a BMI > 18.5 were included and an the population divided into two categories: normal weight if BMI < 25, overweight > 25. An analysis of the correlation between BMI and objective response (OR) rate, tumor control (TC) rate (OR+stable disease lasting ≥3 months), progression-free survival (PFS) and overall survival (OS) was performed. Results: 62 adult patients with recurrent MLS were enrolled (M/F: 33/29; median age: 53 ys). All patients were doxorubicin-pretreated. The median BMI in the whole population was 22.5 (range: 1.85 – 29.8). No statistically significant differences were identified in terms of OR or TC. On the contrary, PFS (6.8 vs. 3.7 months; p< 0.026, log rank test) and OS (14.9 vs. 8.3 months; p< 0.0001, log rank test) were significantly prolonged in normal weighted patients vs over weighted patients. Six and 12-months Kaplan-Meier PFS estimates and survival rates at 12, 24 and 36 months were also better in those patients. Conclusions: these results seem confirm a role o adipose content as a predictor of resistance to trabectedin in MLS patients. Further studies are warranted to confirm this preliminary observation and understand the biological mechanisms of this relationship.
Efficacy of bevacizumab and temozolomide in locally advanced and metastatic hemangiopericytoma (HPC) and malignant solitary fibrous tumor (SFT).
Authors: De Lemos Mario , Kang Isabell , Markarian Adeline , Badry Nadine 
Published: September 2018

e22535 Background: Patients with locally advanced, recurrent or metastatic HPC/SFT are often treated with a combination of BEV/TEM based on the clinical efficacy reported in a cases series of 14 patients (Park MS, et al. Cancer 2011). BEV is costly and this regimen should ideally be supported with further data. Given the rarity of HPC/SFT, large trials are not feasible. We report the efficacy of this regimen based on population-based analysis. Methods: This was a population-based retrospective, multi-centre analysis using patient data from the BC Cancer Agency, a government funded, integrated care organization which delivers cancer drug therapy through a network of cancer centres in the province of British Columbia, Canada. Cases from June 2006 through October 2016 were identified from the provincial registry and systemic therapy drug database for patients receiving at least one treatment of BEV/TEM for histologically diagnosed locally advanced, recurrent or metastatic HPC/SFT. The primary outcome was overall response rate (ORR) based on changes of lesion size in computerized tomography scan and clinical assessment through chart review. Secondary outcomes included time to response, progression free survival (PFS) and overall survival (OS), estimated using the Kaplan-Meir method. Results: Fourteen patients were identified: median age 59 (range 44-70), male 78.6%. Diagnoses were HPC 4 (28.6%) and SFT 10 (71.4%), with metastatic disease in 10 (72.7%) patients. Primary sites were: meninges 4 (28.6%), lung/pleura 2 (14.3%), pelvis 3 (21.4%), abdominal wall 2 (14.3%), gluteal regional 1 (7.1%), others 2 (14.3%). Eleven (78.6%) patients had no prior drug therapy. The median follow-up was 15.5 months, with median treatment of 4 months. ORR was 21.4% with median time to response of 4 months (3 [21.4%] partial response, 10 [71.4%] stable disease, 1 [7.1%] progressive disease). Median PFS, 6-month PFS and OS were 17 months, 65.0%, and 45 months, respectively. Conclusions: Efficacy of BEV/TEM in HPC/SFT appeared to be similar to that previously reported. PFS and OS were longer in our patients, probably reflected by having most patients with SFT and less heavily pretreated.