bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of lapatinib and tegafur combination efficacy for the treatment of HER2+ metastatic breast cancer.
Authors: Manikhas Alexey , Sharvashidze Ineza O. , Kotkova Tatjana N. 
Published: March 2020

e11086 Background: One of effective ways to overcome resistance to trastusumab is to prescribe lapatinib, an inhibitor of ErbB1 and ErbB2 receptors, in combination with capecitabine, a fluopirimidine cytostatic agent. We examined the efficacy and safety of combination of lapatinib plus tegafur, another oral fluopirimidine, in patients with ErbB2-positive metastatic breast cancer (MBC). Methods: 13 patients with HER2+ MBC were enrolled into the study. 11 patients were analyzed, as 2 women had been included into the study too late to be assessed. Median age was 43.5 years. All patients had previously received trastuzumab for MBC, 92% of patients had been treated with taxanes, 77% - with anthracyclines, and 31% received capecitabine. 69% of patients were treated with more than 2 lines of chemotherapy for MBC. The study included 4 patients with CNS metastases. During the study, the patients received lapatinib 1250 mg/day and tegafur 1200 mg/day, days 1-21, with 3-week intervals. Results: 1 patient achieved and still is in partial response which has been lasting for 5 months, while disease stabilization was observed in 9 out of 10 cases. The clinical benefit rate in this trial was 90%. There was 1 case of the disease progression. At the time of analysis median TTP was 10.1 months (95%CI 6-13). The combination of lapatinib and tegafur was effective in 4 out of 5 patients with CNS metastases. There were no adverse events greater than grade I observed on lapatinib plus tegafur therapy. Diarrhea was the most common adverse event, but it did not compromise the patients' quality of life. Conclusions: The lapatinib plus tegafur combination is a promising option for treatment of patients with HER2+ MBC after progression on trastuzumab-containing therapy. This mode was acceptable for patients who had received 2 or more lines of previous therapy. The combination was well tolerated by the patients. Both agents being oral formulations, the treatment mode is quite suitable for outpatient use.
A randomized, open-label, phase II study of lapatinib / capecitabine, lapatinib / vinorelbine, or lapatinib / gemcitabine in patients with ErbB2-amplified metastatic breast cancer progressing after taxane treatment: Results of an interim analysis (GLICO-0801 / EGF111792).
Authors: Gomez Henry Leonidas , Neciosup Silvia P. , Tosello Celia , Xavier Patricia , Neron do Nascimento Yeni , Fanelli Marcelo , Ismael Gustavo , Bines Jose , Sampaio Carlos , Lerzo Guillermo Luis , Capo Adolfo Miguel , Mano Max S. , Fein Luis , Werutsky Gustavo , Barrios Carlos H. 
Published: March 2020

e11087 Background: Lapatinib-capecitabine is approved for the treatment of ErbB2-amplified metastatic breast cancer (MBC) after failure to anthracyclines, taxanes and trastuzumab. GLICO-0801 evaluates different lapatinib-based chemotherapy combinations as 1st/2nd line treatment for ErbB2 amplified MBC progressing after taxane treatment. We present the results of a planned safety interim analysis. Methods: This is an open-label, randomized, international, phase II trial exploring lapatinib (L) 1250mg qd in combination with capecitabine 2000mg/m2 d 1-14 (Arm A) or vinorelbine 25mg/m2 d 1 and 8 (Arm B) or gemcitabine 1000mg/m2 d 1 and 8 (Arm C). Primary objective is to determine the clinical benefit rate (defined as CR+PR+SD for ≥24 weeks). This trial is registered at www.clinicaltrials.gov number: NCT01050322 Results: The first83 randomized patients (pts) (Arm A=29, B=28 and C=26) were included in this analysis. Of them, 65 (78%) have discontinued therapy with mean number of cycles of 4.7, 6.2 and 7.5 in arms A, B and C respectively. Eighteen (21%) pts are still on treatment. Median age was 52y (29-84); 80 pts (96%) had PS 0-1; 51 (61%) were postmenopausal. Fifty-six pts (67%) had visceral metastasis, 52 (63%) were treated as 2nd line therapy and 36 (43%) had received prior trastuzumab. Most reported adverse events (AE) (87%) were grade 1-2. The most common AE (any grade) in arm A: diarrhea 72%, hand-foot syndrome 45%, vomiting 39%, anemia 36%; in arm B: diarrhea 75%, neutropenia 68%, nausea 43%, vomiting 39%; in arm C: diarrhea 72%, neutropenia 60%, anemia 44%, increase in ALT 44%. The most frequent serious AE reported in arm A: diarrhea in 3 pts (10%) and thrombocytopenia in 2 pts (7%); in arm B: febrile neutropenia in 2 pts (7%) and in arm C: sepsis in 1 pt (4%). There was one toxic death related to chemotherapy in arm C. Conclusions: There were no unexpected toxicities so far in this trial with most AEs being mild to moderate and manageable. This interim analysis supports the continuation of the study.
Breast cancer screening guidelines: Is it time to revisit? A survey.
Authors: Rao Archana C. , Gopaluni Srivalli , Lemke Sheila M. 
Published: March 2020

e11089 Background: Breast cancer is the most common non-skin cancer among women in US. In a 2012 report by CDCbreast cancer screening rates are falling short of government targets. At least 10 different societies have laid out screening guidelines, making it difficult to follow. We conducted a survey to better understand adherence to guidelines among health care providers. Methods: A questionnaire comprising of 15 questions was distributed to 120 providers within the Department of Medicine at a University Hospital. Results: 68% returned completed questionnaires: Residents (53%), Attendings/Fellows (36%) and Nurse Practioners/Medical students (11%). Despite 60% respondents claiming that screening guidelines were easy to comprehend and follow; the table suggests otherwise. 49% of the respondents follow United States Preventive Services Task Force guidelines (USPSTF) 28% of these commenced screening at age 40; against the recommendations to start at age 50 and to initiate discussions between the ages of 40-50. 16% of the respondents followed National Comprehensive Cancer Network (NCCN)/American Cancer Society guidelines. 46% of these commenced screening at age 50 or between ages 40-50 contrary to recommendations to begin screening at age 40. Similarly 42% of respondents chose to discontinue screening at the age of 75 in concordance to USPSTF guidelines. 5% chose to screen indefinitely and 1% said they would individualize. 52% did not conform to any guidelines. 69% advocated self breast examinations despite most societies not encouraging the same. Conclusions: While majority of providers follow USPSTF guidelines, there is a considerable discordance between guidelines respondents claim to follow and their practices. This could be attributed to the lack of uniformity in the guidelines across various societies making it harder to comprehend and recall. A unifying consensus would make it easier for providers to improve effective screening. [Table: see text]
Image-guided biopsy of non-palpable breast lesions: Experience of a university hospital in Mexico City.
Authors: Morales-Espinosa Daniela , Navarro-Garcia Lilian Monica , Green Dan , Motola Daniel , Alvarado-luna Gabriela , Cortes-Gonzalez Ruben 
Published: March 2020

e11098 Background: Breast cancer is the most common cancer in women in Mexico. It is mostly diagnosed at advanced stages. Objective: To describe the experience of image-guided biopsies of non-palpable breast tumors in a University Hospital in Mexico City. Methods: Medical records from the Radiology and Oncology Department (January 2007 - April 2011) were reviewed. Patients with incomplete medical records as well as those lacking imaging control and pathology report were excluded. Results: A total of 123 medical records were obtained,12 were excluded. The median age was 50 years (rank 21-88). Most patients were asymptomatic. Medical indications leading to biopsy: see table below. Of the studied population, 56% had a family history of any type of cancer; 40% had a family history of breast cancer. Nine patients had a past medical history positive for breast cancer, 8 patients had a past medical history of any type of cancer. 26 patients were nulligravid and 60 post-menopausal; of which 27 had received hormone replacement therapy. 24 patients had positive contraceptive use. Most patients were catalogued as BIRADs 4A. From all the imaged-marked lesions, only 18 were malignant; 72% of which were carcinoma in situ. Most procedures were ambulatory; only 15 patients had to be admitted. The complications rate was very low (6%), 1 procedure-related infection, 3 seromas and 3 hematomas. Conclusions: Imaging-guided biopsies are a safe, with very low morbidity, accessible procedure. It helps to prompt effective treatment; especially in patients with non-palpable lesions who would otherwise not be diagnosed until advanced stages. [Table: see text]
Feasibility, efficacy, and cosmetic effect of three-dimensional conformal external beam partial breast irradiation for the selected early-stage breast cancer patients after breast-conserving surgery in China.
Authors: Xu Min , Li Jianbin 
Published: March 2020

e11520 Background: To explore the feasibility, efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation after breast-conserving surgery for the selected Chinese early stage breast cancer patients Methods: Forty four early stage breast cancer patients undertaken EB-PBI after breast-conserving surgery. Twenty patients undertaken CT simulation scan in the state of moderate deep inspiration breathing hold (mDIBH), and twenty-four patients during free breathing (FB). The surgical cavity marked by silver clips was delineated and defined as gross tumor volume (GTV), and planning target volume (PTV) was defined as the area encompassed GTV with extended margin of 15 mm for the patients treated in the state of mDIBH or 20 mm for the patients treated in the state of FB. EB-PBI was planned and carried out by three-dimensional conformal radiotherapy (3DCRT) , the total prescribed dosage was 34 Gy delivered in 3.4 Gy per fractions in thirty nine patients and 38.5Gy delivered in 3.85 Gy per fractions in five patients, twice per day at intervals of at least six hours, in five consecutive days Results: Grade 1 of acute radiation-induced dermatitis was observed in 38.6% (17/44) of all the patients, no equal or more than grade 2 of radiation-induced dermatitis was observed, and no any grade of acute radiation-induced pneumonitis was observed. Cosmesis scored basing on Harris critieria was good or excellent in all cases at the time of six months after radiotherapy and in 94.9% cases at the time of two years after radiotherapy. The 2-, 3- and 5-year local control rates were 100% (39/39), 98.8% (30/31) and 93.8% (15/16), respectively. The 2-, 3-, and 5-year survival rates were all 100% and no metastases occurred Conclusions: EB-PBI delivered by 3DCRT is feasible for the selected Chinese early stage breast cancer patients after breast-conserving surgery, satisfactory cosmetic effect, local control rate and long-term survival rate are obtained, meanwhile, acute radiation response rate is lower.
Cost-effectiveness analysis of neoadjuvant chemotherapy with intensive dose of epirubicin and different cycles in patients with locally advanced breast cancer: 4 FE100C versus 6 FE100C.
Authors: Ramirez Nicolas , Herrera Jorge Eduardo , Chavez Jose Fortino , Astudillo Horacio 
Published: March 2020

e11565 Background: There are different combinations of neoadjuvant chemotherapy (NCT) to treat locally advanced breast cancer (LABC); treatment with cytostatics drugs make it a costly concern, by establishing economic differences in the consumption of healthcare resources. To compare the cost-effectiveness of two NCT strategies (4FE100C vs. 6FE100C). Methods: It was made a cost-effectiveness analysis (CEA) of two treatment schemes (4FE100C vs. 6FE100C) in patients with clinical stage III breast cancer, each cohort included 48 patients. Effectiveness parameter: pathologic complete response (pCR). Differential cost: incremental cost-effectiveness ratio (ICER) using a Markov’s model. Results are expressed in terms of incremental cost per extra unit of effectiveness. Costs were expressed in Mexican (MXN) pesos ($) as of 2005; these were calculated under the perspective of public healthcare system (SSP, for its acronym in Spanish) denominated IMSS, with a 3 to 4 years analytical horizon. In order to determine the robustness of the results, a sensitivity analysis was carried out by modifying only the medical direct costs with a 3% discount rate. Results: The use of 6FE100C offered greater effectiveness compared against 4FE100C; the medical direct cost of only the cytostatic drugs for NCT with 6 FE100C and 4 E100C generated a cost per case of $30,467.00 MXN (€ 2,343.61) and $18,004.00 MXN (€ 1,384.92), respectively. The greatest unit price was given by epirubicin. The CEA demonstrated that the cost-effectiveness (C/E) was greater with 6 FE100C and the incremental cost-effectiveness ratio (ICER) showed that it was necessary to pay $11,765,925.42 MXN (€ 905,071.20) because it tells us how much it is paid additionally for every extra unit of effectiveness (pCR) which assumes 6 FE100C in front of 4 FE100C. The sensitivity analysis performed shows the robustness of the results. Conclusions: The6 FE100C scheme is the chemotherapeutic strategy with better cost-effectiveness ratio and is the most efficient in the short run for treating LABC.
The predictive value of protein, glucose, and lactate for a diagnosis of neoplastic meningitis.
Authors: McClain Jonathan , Glantz Michael J. 
Published: March 2020

e12005 Background: Neoplastic Meningitis (NM) is a complication of many common cancers that occurs with an incidence as high as 15% in some cancer types. Diagnosis remains elusive with poor screening tools and insensitive diagnostic options. Methods: A retrospective analysis of 341 consecutive patients with suspected NM was undertaken. Clinical presentation, demographic, cytologic and MRI data were recorded. Using cytology as the diagnostic gold standard, sensitivity, specificity, ROC curves and likelihood ratios were calculated. Results: 210 patients met inclusion criteria, 87 with primary brain tumors (PBT), 72 with non-CNS solid tumors, and 44 with lymphomas. 111 patients were male; 123 (58.6%) ultimately had a positive cytology. Only 59% of patients with positive cytology presented with symptoms concerning for NM. 32.9% of patients with PBTs and positive CSF cytology exhibited neurologic symptoms suggestive of NM. Patients with non-CNS solid tumors and positive CSF cytology presented with symptoms concerning for NM 80% of the time. Patients with cytology-positive, MRI-positive and symptom-positive NM had very different survivals. Potentially informative CSF values are in table below. Conclusions: A definitive diagnosis for patients with suspected NM remains elusive without a positive cytology, but some clinical, radiographic, and CSF findings are useful for raising diagnostic concern, and for screening in at-risk populations. Symptom-positive or MRI-positive NM may represent different diseases than cytology-positive NM. [Table: see text]
Gene polymorphisms of folate metabolizing enzymes and susceptibility to lung adenocarcinoma in Serbia.
Authors: Jankovic Radmila , Cavic Milena , Krivokuca Ana , Jakovljevic Ksenija , Malisic Emina , Spasic Jelena , Radosavljevic Davorin , Radulovic Sinisa 
Published: March 2020

e12020 Background: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are important enzymes of the folate metabolism and are suggested as new prognostic factors for lung cancer. Cytosine to thymine transition at nucleotide 677 (C677T) leads to reduced MTHFR activity. The TS promoter has a tandem repeat polymorphism (2R, 3R) and a guanine to cytosine transition in the 3R allele related to TS protein expression. The aim of this study was to analyze the association of MTHFR and TS polymorphisms with lung adenocarcinoma in Serbia. Methods: A case-control study including 55 late-stage lung adenocarcinoma patients and 53 healthy subjects was performed. Restriction fragment length polymorphism analysis was used for MTHFR and TS genotyping. Depending on the presence of high (3RG) or low (2R, 3RC) expression alleles, TS functional groups were subclassified into HH (3RG/3RG), HL (2R/3RG, 3RG/3RC) and LL (2R/2R, 2R/3RC, 3RC/3RC) groups. Descriptive analyses included genotype and allelic frequencies; the odds ratio (OR) and 95 % confidence interval (CI) were calculated as an estimate of relative risk. Significance was considered for p < 0.05. Results: The distribution of the MTHFR variants in patients vs. controls was 61.8 % vs. 24.5 % for CC, 32.7 % vs. 62.3 % for CT and 5.5 % vs. 13.2 % for TT. A significant difference in CC vs. TT+CT MTHFR genotype distribution was observed between patients and controls (χ2 = 13.79; OR = 4.98; 95 % CI, 2.14 – 11.61). There was no significant association between the TS polymorphisms and the risk of lung adenocarcinoma occurrence, but in the CT+TT MTHFR subgroup, a nonsignificant difference in LL vs. HL+HH TS genotype distribution was observed between patients and controls (χ2 = 0.04; OR = 1.07; 95% CI, 0.31 – 3.67). Conclusions: A significant corelation between the CC MTHFR genotype and lung adenocarcinoma occurence in Serbia was found. Also, there was no significant correlation with lung adenocarcinoma occurence in the CT+TT MTHFR subgroup for carriers of the LL TS genotype. As this study was performed on a relatively small sample size further large case-control studies including analysis of gene-gene interactions with genes coding for other folate metabolism enzymes is needed.
Investigating parent of origin effects (POE) and anticipation in Irish Lynch Syndrome kindreds.
Authors: Farrell Michael P. , Hughes David J. , Schmid Jasmin , Boonstra Philip S , Mukherjee Bhramar , Walshe Margaret B. , Mac Mathuna Padraic M. , Gallagher David J 
Published: March 2020

e12031 Background: Genetic diseases associated with dynamic mutations often display parent-of-origin effects (POEs) in which the risk of disease depends on the sex of the parent from whom the disease allele was inherited. Genetic anticipation describes the progressively earlier onset and increased severity of disease in successive generations of a family. We sought evidence for a specific POE effect in Lynch syndrome families by studying the ages at diagnosis in the offspring of affected parent-child pairs. In addition, a paired t-test and a specifically developed bivariate statistical approach were used to assess a possible role of anticipation. Methods: Affected parent-child pairs (APCPs) (N = 53) were evaluated from kindreds (N = 20) with known germline MMR mutations. Differences in the mean age of LS associated cancer diagnosis were compared between various groups via t-tests: all p-values were 2-sided. Different group comparisons include: (1) unique parental ages (mothers vs. fathers) (2) affected offspring ages (mothers vs. fathers (3) age of affected female offspring (mothers vs. fathers (4) age of affected male offspring (mothers vs. fathers. Results: There were no statistically significant differences in diagnosis of offspring or parents. Sons of affected mothers were more likely to be affected than daughters of affected mothers. However, the affected cohort/study number is small and while affected sons of affected mothers were diagnosed with cancer almost 3 years younger than female offspring (39.7 vs 42.5), this finding failed to reach clinical significance. Comparison in age at diagnosis in 53 affected parent-child pairs with Lynch syndrome associated malignancies Conclusions: These data demonstrate a similar age at diagnosis among all offspring of affected mothers that was indistinguishable from affected fathers. This study will be expanded to recruit more eligible affected parent child pairs to increase the power of this evaluation. The Veiland & Huang algorithm will be used to compare mean ages of affected parents and children.
Using primary patient data to identify the symptoms of brain metastases to develop a patient-reported outcome measure.
Authors: Lasch Kathryn Eilene , Fitzgerald Kristina , Ganguli Arijit , Bonthapally Vijayveer , Pompilus Farrah , Delbecque Laure , Ray Saurabh 
Published: March 2020

e12515 Background: Increasingly, there has been a public call for direct patient input into the development of patient reported outcome (PRO) measures of treatment benefit in adult oncology clinical trials. Patient involvement is especially important in conditions where there is poor prognosis and comparative treatment benefit is minimal with standard outcome measures such as overall or progression free survival. To develop a PRO instrument specifically for patients with brain metastases (BM), this study interviewed patients in this population and also reviewed the clinical literature to identify the signs and symptoms relevant to BM. Methods: A literature search was performed inMEDLINE for articles published between 2000 and 2010. Individual in-depth interviews were conducted with 19 patients with BM using open-ended questions to elicit the most frequent and the most bothersome symptoms. Patient inclusion criteria included a diagnosis of BM and being eligible for whole brain radiotherapy. Results: The literature review identified the following symptoms as important: intracranial pressure symptoms (e.g., headache, nausea, vomiting), seizures, and focal neurological symptoms (e.g., paralysis, mental status changes, memory, motor loss/weakness, visual loss/changes). The most frequent symptoms reported by patients in the interviews were: headache (74%), memory loss (63%), vision problems (58%), loss of balance (53%), and physical weakness (53%). Also, the patient interviews identified the following as most bothersome: headache (32%) and vision problems (21%). The patients reported additional concepts not identified in the literature review, including pain, fear, falling, fainting, and difficulty reading. Some symptoms or signs identified in the literature were not mentioned by patients during the interviews such as intracranial hypertension and hemorrhage. Conclusions: Although there was considerable overlap among patient and literature reports, including patient input broadened the comprehensiveness of potential symptoms. The results suggest the added value of collecting direct, primary patient data when developing measures to assess benefits of treatment in BM patients.