bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel anticancer agent, benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride, activates multiple immunologic mechanisms of an antitumor response.
Authors: Kirkin Alexei , Dzhandzhugazyan Karina , Fang Jens , Lindkair-Jensen Steen , Guldberg Per
Published: March 2020

e12024

Background: BP-C1 (a combination of a benzene polycarboxylic acids complex (BP-Cx-1) with cis-diamineplatinum in a very low concentration) was demonstrated to be safe and effective in the treatment of stage IV breast cancer. Methods: In order to investigate whether the immune system mediates some of the clinical activity of BP-C1, we conducted an in vitro study of the immune modulating properties of this compound. The study was done using peripheral blood mononuclear cells from healthy donors. Results: It was demonstrated that the production of a number of cytokines was significantly increased by BP-C1, first of all IL-1beta, TNF-alpha, GM-CSF, IFN-gamma, and IL-25. The carrier molecule, BP-Cx-1, alone also stimulated IL-6 production. Experiments with isolated cultures of monocytes and lymphocytes indicated that the primary targets for these reagents are monocytes. Activation of monocytes leads to two major effects: a) the production of cytokines that are able to increase the anti-tumor activity of lymphocytes, and b) the acquired ability of monocytes to inhibit tumor cell growth. In addition, direct effects on lymphocytes were also demonstrated, exemplified by the induction of IL-25 production. Conclusions: In conclusion, it was demonstrated that BP-C1 and the related compounds are able to activate multiple immunological mechanisms of anti-tumor response.
Neoadjuvant chemotherapy with metronomic doxorubicin, cyclophosphamide, and capecitabine in patients with locally advanced (LA) triple-negative breast cancer (TNBC).
Authors: Frolova Mona , Skrypnikova Marina , Ignatova Ekaterina , Petrovsky Alexander , Stenina Marina , Ivankina Oxana , Vishnevskaja Yana , Tjulandin Sergei
Published: March 2020

e12027

Background: TNBC is associated with aggressive behavior and poor prognosis. It has been shown that patients (pts) with TNBC with pathological complete regression (pCR) after neoadjuvant chemotherapy have a higher survival. Rates of pCR with standard antracycline- and taxanebased chemotherapy regimens don’t exceed 20-27%. Dose-dense and metronomic schedules may be more effective in these highly proliferative tumors. We performed a prospective pilot trial to evaluate efficacy of metronomic schedule of doxorubicin, cyclophosphamide and capecitabine in pts with LA TNBC. Methods: Pts with LA TNBC (cT2-4N1-3M0) were treated with doxorubicin 25 mg/m2 iv weekly, cyclophosphamide 50 mg po daily and capecitabine 1500 mg po daily for planned 16-19 weeks followed by surgery. Pathological response was evaluated according to the Chevallier classification. Results: Twenty pts was included in the study in 2009-2010. Median agewas 47 years (33-70), 63% of pts had tumor grade 3, Ki67 was >20% in all cases. Nineteen pts completed chemotherapy (median treatment duration 17.1 weeks) and underwent surgery. One pt had a disease progression during chemotherapy and was switched to 2nd-line chemotherapy. Seven pts (36,8%) achieved a pCR (6 pts class 1 and 1 pt class 2). With median follow-up of 33 months, 3-year DFS and OS were 60%. All but one pt with pCR, who developed brain mts shortly after surgery, are currently alive without relapse. In contrast 50% of pts with residual tumor relapsed. Pts with pCR had significantly higher median cumulative dose of doxorubicin (420 mg/m2) than pts with residual disease (300 mg/m2, p=0.046). The dose-limiting toxicities were hand-foot syndrome (26.3% grade 3), mucositis (31.6% grade 3), and neutropenia (31.6% grade 3-4), which resulted in permanent discontinuation of doxorubicin in 4 pts. Conclusions: Despiterelatively hightoxicity metronomic doxorubicin, cyclophosphamide and capecitabine regimen shows promising activity as neoadjuvant treatment of LA TNBC. Achievement of pCR and higher cumulative dose of doxorubicin were strongly associated with improvement of survival.
Access to medical treatments in relation to the social status of the cancer patient cured at the Veneto Oncology Institute of Padua (IOV).
Authors: Imbevaro Silvia , Bortolami Alberto , Mazurek Magdalena , Rescigno Paola , Jirillo Antonio , Giacobbo Maria
Published: March 2020

e12028

Background: The NHS in Italy is a public system of universal nature that guarantees health care to all citizens. Few Italian studies relate the therapy received by a cancer patients with their socio-economic status, so we decided to analyze the situation of the IOV. Methods: It is an observational monoinstitutional study conducted on 886 patients (pts) treated at the IOV from May 2006 to December 2011. They were selected from the Onco-AIFA registry which is a national tool used to monitor anticancer high-cost therapies. The socio-demographic data were obtained from medical records.We verified if there are differences in access to treatments (number of diagnostic tests, chemotherapy treatments, specialist and follow visits) in association with the socioeconomic determinants. We analyzed the survival differences in connection with demographic and clinical characteristics.The statistical analysis was performed using the Kruskal-Wallis test and the Cox model. Results: There are 520 pts evaluable of the 886 pts selected: 42% suffering from colorectal cancer, 28% lung cancer and 30% breast cancer. The median age is 63 years (41% male). With regard to the profession the sample is divided as follows: 34% traders/artisans/workers, 25% technical professions/office workers, 14% highly specialized occupations, 25% retired/housewives. The statistical analysis shows no significant differences in the number of exams and medical services in relation to the profession, except one that regards the mean number of chemotherapy infusions (25 manual professions vs. 20 other professions, p = 0.007). The socioeconomic variables do not affect survival, unlike the age (hazard ratio [HR], 1.42, p <.001) and the type of cancer (HR, 0.72, p <.001). The average cost of benefits per pt is about 4.600,00 euro/year, there is a major expense for traders/artisans /workers compared to other professions (+19%). Conclusions: The analysis of the sample of cancer pts did not reveal significant differences if it comes to access to care, so the system does not seem discriminatory. Probably these differences are homogenized by the state of economic well-being enjoyed so far by pts of the IOV.
Quality of life (QoL) and symptoms evaluation in metastatic breast cancer (MBC) patients (pts) treated with eribulin: Preliminary results of a prospective observational study.
Authors: Gamucci Teresa , Mentuccia Lucia , Quadrini Silvia , Moscetti Luca I. , Vici Patrizia , Sperduti Isabella , Pizzuti Laura , Franco Daniela , Giampaolo Maria Anna , Fabbri Maria Agnese
Published: March 2020

e12031

Background: Eribulin (E) is a nontaxane microtubule inhibitor currently indicated for third-line chemotherapy (CHT) of MBC. To evaluate its tolerability and impact on QoL and symptoms improvement in MBC pts, from April 2012, we conducted a prospective observational study. Methods: Pts pretreated with anthracycline (A) and taxane (T) who has received 2 CHT lines for MBC, scheduled to be treated with E were considered eligible. Pts complete the Edmonton Symptoms Assessment Scale (ESAS) at each cycle and the Functional Assessment of Cancer Therapy-Breast (FACT-B) every 2 cycles. Outcome of QoL included the FACT-B total score, FACT-General (FACT-G) score and the Trial Outcome Index (TOI) score. Groups of data were analyzed using ANOVA and the Friedman test. Kaplan-Meier method was used for survival calculation. Overall Survival was calculated by the Kaplan-Meier product-limit method. Results: 25 consecutive MBC pts entered the study. Median age 65 (range 31-77), PS (ECOG) 0-1 96%, 24% had triple-negative MBC, 70% ER/PgR positive and 5% HER2 positive. All pts were pretreated with A and T, 19 (76%) also with capecitabine. Median cycles 6 (range 3-13), 36% received more than 6 cycles. Five pts are to early for evaluation. Of the 20 evaluable pts main toxicity were: alopecia G1 58% and G2 42%, asthenia G2 40% peripheral neuropathy G2 25% neutropenia G2 0% and G3-G4 10%.At a median follow-up of 6 months 16% of pts achieved partial response (PR) 44% stable disease (SD) and 20% progressive disease; disease control rate (PR+SD ≥ 6 m) occurred in 40% of pts. Median PFS is 5 m (95% CI, 4-6) currently 70% of pts are alive. Data of ESAS and QoL are reported in table. Conclusions: Our preliminary results shows that treatment with E is associated with a significant improvement of ESAS scores (p=0.03) mainly in responders pts (p=0.02) and with a good maintenance of QoL with expected and manageable toxicities. Data collection is ongoing and update results will be presented. [Table: see text]
Taxanes-based neoadjuvant chemotherapy in advanced nonmetastatic breast cancer.
Authors: Mehmood Tahir , Ali Muhammad , Saeed Kamran , Munawar Atif , Usman Sadaf , Rashid Asma , Irfan Nabia , Ghaffar Abdul , Shah Mazhar Ali , Syed Aamir Ali , Jamshed Arif
Published: March 2020

e12033

Background: Pakistan has the highest rate of breast cancer for any South Asian population and majority of the patients present with locally advanced or metastatic disease. We report on response and survival of primary locally advanced non-metastatic breast cancer in women treated with neoadjuvant Adriamycin/Taxanes (AT) based regimens at our institute. Methods: Between 1995 to 2009 the hospital information system identified 517 women with pathologically confirmed locally advanced breast cancer. All patients received neoadjuvant chemotherapy with AT based regimen followed by surgery. Median age was 43 years (range 17-71 years). AJCC stage; stage II 54% and stage III 46% of the patients. Axillary nodes were palpable in 72% of the patients at presentation. Histological sub-types; infiltrating ductal carcinoma 95%, infiltrating lobular carcinoma 3% and others 2% respectively. Pathological grade was I/II in 44% and grade III 56% of the patients. ER, PR, and Her2-neu receptors were positive in 44%, 40% and 24% of the patients respectively. Twenty one percent of the patients had triple negative breast cancer. Post operative radiotherapy was delivered to 94% of the patients. Patients with positive ER/PR receptors also received hormonal manipulation. Results: Following neo-adjuvant chemotherapy, pathological response was; complete response (CR) 13.5%, partial response 21%, stable disease 52% and progressive disease in 13% of the patients respectively. Breast conservation was possible in 36% of the patients. The 5 year disease free survival in patients with and without CR was 81% and 36% respectively. On multivariate analysis, T stage (p = 0.001) and response to neo-adjuvant chemotherapy (p = 0.001) were found to be independent predictors for disease free survival. Conclusions: Pathological response to neoadjuvant chemotherapy is a predictor of long term survival. Chemotherapy regimens with high response rates merit evaluation in randomized trials to improve outcome in locally advanced breast cancer.
The discordance of the ER, PR, and HER2 status after neoadjuvant chemotherapy in breast cancer.
Authors: Oven Ustaalioglu Basak , Bilici Ahmet , Aker Fugen Vardar , Erkol Burcak , Aliustaoglu Mehmet , Gurleyik Gunay
Published: March 2020

e12037

Background: Neoadjuvant chemotherapy(NAC) is the accepted approach for women with locally advanced breast cancer with technically inoperable disease. Systemic treatment is mainly based on the presence of the Estrogen (ER) receptor, Progesterone (PR) receptor and HER2 status on the core needle biopsy prior to treatment. Previously, discordance of the hormone receptor (HR) status was reported as 8-33% in the breast cancer patients after NAC. In here, we evaluated the HR and HER2 discordance after NAC in locally advanced breast cancer patients. Methods: We reviewed the data of 849 breast cancer patients retrospectively. The pathological specimens of core needle biopsy and operation specimens were re-evaluated for HR and HER2 status in 38 patients who had been treated with NAC. The changing of HR and HER2 status after chemotherapy was defined as discordance. The relationship between clinicopathological parameters and discordance and significance of them for disease-free survival (DFS) was analyzed by chi-square and univariaty test. Results: Over 80% of patients were clinically stage III breast cancer. Out of 24 patients were premenapouse and median age was 44.5(30-94). The patients were received median 4(1-6) cycles of NAC as 2 of them were only hormonotherapy, 8 were only antracycline and others were both antracycline and taxanes. Nearly 80% of patients were performed modified radical mastectomy(MRM).Postoperatively median tumor size was 1.6cm(0-10) and median dissected lymph nodes was 14(0-28). After operation, 4(10.5%), 8(21.1%) and 8(21.1%) discordance were detected for ER, PR and HER2 respectively. While HER2 discordance were related with recurrence(p=0.01) and PR discordance(p=0.04), ER discordance was related with only patological stage(p=0.03). At the median follow-up of 15.7 months, 5 year DFS rate and time were 30% and 30.4 months(18.7-42.2), respectively. Operation type, stage, lymphovascular invasion, perineural invasion were found to be significant for DFS, HR and HER2 discordance was not related with DFS. Conclusions: Until more definitive results will be obtained from future studies, receptor status of the residual tumor after NAC should be retested.
Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer (TNBC) in a Peruvian institute.
Authors: Rojas Katerin Ingrid
Published: March 2020

e12038

Background: TNBC is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expressions (HER-2). This molecular classification is an excellent prognostic and predictive method in breast cancer (BC). This is an aggressive malignancy with a poor prognosis despite the high rates of response to chemotherapy. Methods: Observational descriptive. We included 165 patients with TNBC stage I-III who received neoadjuvant chemotherapy at National Cancer Institute of Peru from 2000 to 2010. Clinical and pathologic complete response rates, survival measurements, and organ-specific rates of relapse were evaluated. Overall survival (OS) and disease free survival (DFS). Results: The mean age at diagnosis was 48.6 years (range, 24-74 years). The mean size tumor before treatment was 7.7 cm (range, 1-25 cm). One hundred and fifty seven patients (95.2%) had ductal carcinoma. One hundred twenty nine cases (78.2%) were histological grade III. According to T stage, 65 (39.4%) T3 and 83 (50.3%) T4. Thirty four cases (20.6%) were N0. Seventy three patients (44.2%) received AC-Paclitaxel schedule. Thirty four patients (20.6%) had CR to neoadjuvant chemotherapy. There is a significant difference about tumor size before and after neoadjuvant treatment (7.7 vs. 3.6, p<0.05).OS at 5 years for patients with residual disease was 83.5%. In patients with complete response the DFS at 5 years was 55.1%. Locoregional and lung were the most frequent site of recurrence (15.8%) and (13.9%) respectively. According Miller and Paine to grade tumor response, 17 patients(10.3%) I ,33 (20.0%) II, 33 (20.0%) III, 20 (12.1%) IV and 27 (16.4%) V. Node response, 20 patients (12.1%) had type A, 51 (30.9%) type B, 23 (13.9%) type C and 34 (20.6%) type D. Conclusions:These results suggest that most TNBC are in accordance with literature data, especially concerning young age at diagnosis, high grade tumors, advances locally stage at diagnosis, and short time to relapse, high response rate to chemotherapy and excellent OS and DFS. We know it is a heterogeneous disease; however the clinical characteristics still play an important role to predict treatment response and survival.
Inequities in Pap smear screening for cervical cancer between Brazilian urban and rural populations.
Authors: Martínez-Mesa Jeovany , Werutsky Gustavo , Sampaio-Filho Carlos Alberto , Calabrich Aknar , Barrios Carlos H.
Published: March 2020

e12510

Background: Cervical cancer (CC) represents an important public health problem in Brazil being the second most common cancer in women. The expected incidence rate in 2012 was 17.5 per 100,000 women while the age-standardized mortality rate in 2010 was 4.04 per 100,000 women. Inequities in access to health preventive programs contribute to this figure. The goal of this analysis is to identify inequities in Pap smear screening in women from urban and rural populations from Brazil. Methods: Using the Health Supplement of the National Household Sample Survey 2008 (PNAD) with 102,108 Brazilian women aged 25-64 years Pap smear screening was analyzed dichotomously as women having ever or never been screened. Residence area was categorized as urban or rural. Age-adjusted prevalence of never-screened was analyzed using chi-squared test. Poisson regression modeling, crude and full adjusted for age, income, number of children, education, skin color, having visited a physician in the previous 12 months and healthcare insurance were performed for Brazil in general and for Brazilian major regions. Results: The prevalence of never-screened women for CC was 12.9% in Brazil, 11.5% in urban and 22.2% in rural areas. The poorest Brazilian major-regions showed the highest prevalence of never-screened women: North (17.4% in general, 14.7% in urban and 27.3% in rural areas) and Northeast (14.7% in general, 12.8% in urban and 23.7% in rural areas). After full-adjustment, the rural population showed a higher relative risk for never-screened as compared to those living in urban areas [PR=1.23 (95%CI 1.14; 1.31); p<0,001]. The highest risk was also found in the North [PR=1.39 (1.13; 1.31); p=0.002]. However, South and Central-west regions showed no association between never-screened and area [PR=1.06 (0.88; 1.28); p=0.541; PR=1.18 (0.87; 1.58); p=0.270, respectively]. Conclusions: Our findings point out inequities in Pap smear screening between Brazilian urban and rural population. These inequities possibly contribute to the high incidence and mortality rate of CC in Brazil.
The role of chemotherapy in hormone receptor-positive and HER2-positive breast cancer patients over age 70.
Authors: Caggiano Vincent , Parise Carol
Published: March 2020

e12511

Background: Standard adjuvant therapy for HER2 positive female breast cancer patients that are estrogen receptor (ER) positive is chemotherapy, trastuzumab, and endocrine therapy. For patients older than 70 years of age, the combination of chemotherapy and trastuzumab may increase the toxicity profile. The purpose of this study was to evaluate the role of chemotherapy in for the ER+/PR+/HER- and ER+/PR+/HER+ subtypes in patients over age 70. These subtypes differ only by HER2 status. Methods: We identified 13,167 cases of patients over age 70 with stages 1-3 first primary invasive breast cancer from the California Cancer Registry diagnosed between January 1, 2000 and December 31, 2010. Of these, 9,710 were ER+/PR+/HER- and 988 were ER+/PR+/HER+. Cox regression analysis adjusted for race/ethnicity, socioeconomic status, grade, and year of diagnosis was used to compare risk of mortality for combination endocrine and chemotherapy versus endocrine therapy alone. Analyses were conducted separately for each stage. Results: For the ER+/PR+/HER- subtype, there was no difference in the risk of mortality for patients given endocrine and chemotherapy versus endocrine therapy alone for stages 1 and 2. For stage 3, there was a 57% reduced risk of mortality (HR = 0.43; 95%CI: 0.27-0.69) for patients given combination chemo and endocrine therapy. For the ER+/PR+/HER+ subtype, there were no differences in risk of mortality in any stage due to treatment. Conclusions: With the exception of stage 3 patients with the ER+/PR+/HER- subtype, chemotherapy appears to add little or no benefit to risk of mortality for patients over 70 years of age. These results support the use of endocrine therapy and anti-HER2 therapy without chemotherapy in elderly patients with early stage, estrogen receptor positive, HER2 positive breast cancer.
Association of cigarette smoking and glutathione S-transferase M1 polymorphism with risk for uterine cervical cancer.
Authors: Nishino Koji
Published: March 2020

e12540

Background: To elucidate the role of tobacco smoking and polymorphisms of carcinogen metabolism genes in cervical carcinogenesis. Methods: We analyzed genotypes of nine genes, 11 polymorphisms encoding carcinogen metabolizing enzymes, information on smoking, and the presence of human papillomavirus in 124 Japanese cervical cancer patients and 125 healthy controls. Results: The incidence of human papillomavirus infection (95.5% vs 9.9%; P < 0.001; odds ratio (OR), 231.98; 95% confidence interval [CI], 57.17-941.22), and smoking (41.1% vs 18.4%; P < 0.001; OR, 3.40; 95% CI, 1.88-6.17) were both significantly higher in patients than in controls. The genotype distributions of CYP1A1, CYP2E1, CYP2A6, NQO1, NAT2, mEH, MPO and GSTT1 genes were not statistically different; however, the ratio of the GSTM1 null genotype was significantly higher in patients than in controls (62.1% vs 47.2%; P = 0.019; OR, 1.83; 95% CI, 1.11-3.04). The incidence of GSTM1 null was significantly higher in the non-smoking group (63.0% vs 47.1%; P = 0.038; OR, 1.92; 95% CI, 1.04-3.54), and not in the smoking group (60.8% vs 47.8%; P = 0.300; OR, 1.69; 95% CI, 0.63-4.56). Conclusions: In the current study, risk factors for developing cervical cancer were tobacco smoking and GSTM1 null; however, no association was observed between these two factors. We could not prove that smoking-GSTM1 null interaction was responsible for the increase in cervical cancer among young Japanese, and further studies with more detailed smoking status, not only active but passive smoking, will be required.
The sensitivity and specificity of screening mammography in primary care setting in Saudi Arabia.
Authors: Alkhenizan Abdullah , Hussain Aneela , Alsayed Adher
Published: March 2020

e12551

Background: Breast cancer is the leading cancer diagnosed in women in Saudi Arabia, accounting for 25% of all cancers diagnosed in women. The mammogram screening program at King Faisal Specialist Hospital and Research Center (KFSHRC) is the only structured screening program in the country. KFSHRC provides primary care services for a catchment population of 30,000 patients. This program covers all women above the age of 40 within this catchment population. Methods: A retrospective review of electronic and paper records were reviewed for mammograms done between January 2002- January 2012. Summary statistics were used to describe patient and examination characteristics. Results from mammograms were reported using the Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology. The stage of diagnosis was reported using the American Joint Committee on Cancer (AJCC) system using stages one through four. ACR BIRADS classification and cancer status definitions mammograms were linked with cancer outcomes to identify true-positive, true-negative, false-positive, and false-negative examinations. On the basis of these classifications, sensitivity, specificity, positive predictive value, and negative predictive value were estimated. All mammograms and tissue biopsies were read by board certified specialists. Results: During the first round of screening 1694 mammograms were analyzed, and 12 cases of cancer were diagnosed. Cancer detection rate (per 1000 examination) was 7.1. Biopsy rate was 3.7 per 100 mammograms. Follow up ultrasounds rate was 2.7 per 100 mammograms. Sensitivity of mammogram screening was 80%, and specificity was 76%. Conclusions: The yield of a structured mammogram screening program in Saudi Arabia is high. There is a need to implement a national program for breast cancer screening in Arabian world in general and within Saudi Arabia in particular.
Gastric malignancy presenting after elective Roux-en-Y gastric bypass for treatment of morbid obesity.
Authors: Nau Peter N , Meireles Ozanan
Published: March 2020

e12559

Background: Obesity has become a significant public health problem in westernized societies. Medical attempts at weight loss are fraught with failures and recidivism. Bariatiric surgery provides for reliable and durable weight loss. The rate of gastrointestinal pathology in this population is significantly higher than in the non-obese. Gastric malignancy following Roux-en-Y gastric bypass (RYGB) is an uncommon presentation. Symptoms occur late secondary to the properties of the RYGB complicating a curative approach. Methods: A retrospective review of the Massachusetts General Hospital bariatric surgical history and PubMed literature search were performed. Data points recorded include the patient age and risk factors for cancer, use of preoperative screening, presenting symptoms, and outcomes of gastric malignancy following RYGB. Statistical analysis was performed using SPSS 20.0. Results: Including the one case treated at Massachusetts General Hospital, that are 11 reported cases of gastric malignancies following RYGB in the literature. The average patient age was 53 years. In four cases preoperative risk factors for gastric cancer were identified. No reports identified pre-bypass evaluation of the stomach. Seventy percent of the cases involved malignancies arising from the gastric remnant. The median time between operation and presentation was 8 years (range 1 – 26). The most common chief complaint was pain (70%). Additional symptoms included nausea and vomiting (50%), and dysphagia (30%). At the time of diagnosis 4 patients had advanced disease rendering surgical resection impossible. Conclusions: Surgical management of obesity provides for durable weight loss and improvement in obesity-associated medical comorbidities. This population is at a higher risk for harboring asymptomatic gastrointestinal pathology. There are 11 cases of gastric malignancies following RYGB in the literature. In four cases the diagnosis of advanced cancer dictated palliative measures only. Diagnosis of this disease is complicated by its subtle presentation and the inability to access the remnant stomach. Given this, it is reasonable to screen all patients prior to exclusion of the gastric remnant.
Prostate cancer incidence in a large cohort of Peruvian men affiliated to a prepaid system.
Authors: Aguilar Alfredo , Iberico Jorge , Neciosup Silvia P , Flores Claudio J. , Valdiviezo Priscila I. , Pinto Joseph A. , Suazo Juan F. , Aguilar Marin Ivan Carlos , Vallejos Carlos S.
Published: March 2020

e12566

Background: Prostate cancer (PC) is the most common malignancy and the leading cause of death by cancer in Peruvian men (age-standardized rate [ASR] of 37 new cases/100,000 men estimated by GLOBOCAN 2008). The purpose of this study was to assess the incidence of PC in a cohort of men at Oncosalud, an oncologic pre-paid system that currently has 600,000 affiliates. Methods: We evaluated a dynamic cohort (period 1989 to 2011) of men affiliated to Oncosalud – Auna, an oncologic prepaid system.The crude incidence rate per year (number of new cases/men at risk), the specific rate according to age (number of new cases / persons-year), and cumulative risk were calculated. Results: Overall, during the assessment period, the PC incidence rate per year was 183.7 and the ASR incidence was 145 per 100,000 affiliates respectively. In our cohort of affiliates there were no PC cases before 1995 (with 3061 men at risk for that year). The highest incidence rate was 160.5 registered in 1999 (12,461men at risk). Incidence rates showed a decreasing tendency since 2008 (159.7 with a population at risk of 86,408 men), reaching its lowest value in 2011(92.3 with 213,531men at risk). According to age-groups, there were no PC cases under 35 years old except for the 20-24 year old group (incidence rate 2.3). Specific incidence rates per age-group increases from the 40 year old-group (38.5). The peak of PC incidence was between 75 to 79 years old (1506.05). In the same way, the cumulative risk increases after 40 years old. Conclusions: In our cohort of affiliates, the incidence of PC is greater than the general population, it could be due to the process of negative selection; on the other hand, specific incidence rates per age-group and cumulative risk are increased after 40 years, as seen in the general population.
Obesity as a prognostic factor for incidence and survival in female patients diagnosed with breast cancer.
Authors: Ramadan Islam Elsayed
Published: March 2020

e12567

Background: The incidence of obesity in females ≥15 years of age in Egypt is one of the highest all over the world (33%)we investigated the impact of increased BMI on breast cancer incidence and survival. Methods: we reviewed files for 1873 female patients with breast cancer, presented at ACOD, from Jan. 1996 to Dec. 2005. , only 907 were eligible BMI of every patient was calculated and four groups were formed.The duration of follow-up was calculated from the date of registration to the date of death or last follow-up. The locoregional control period was between the end of treatment and failure of local control at 5 years or death or last follow-up OS was measured as the interval between the beginning of treatment and death or last follow-up evaluation. Results: patients were classified into 4 groups, the first group included 100 patients of BMI less than 18.5, the second group including 299 patients of BMI more than or equal to 18.5 and less than 25, the third group including 336 patients of BMI more than or equal to 25 and less than 30, and the fourth group including 172 patients of BMI more than 30. the highest peak of breast cancer incidence was in the age group 55-65 years (32.4%), while the lowest incidence was in the age group more than 65 (8.6%). Obese patients had the tendency to have breast cancer in younger age than normal weight patients with a mean of 38.6 years vs. 58.6 years. results showed that over weight patients constituted more than 37% while obese patients only constituted 19 %, normal weight 33% and underweight 11%. In our study, the majority of cases were staged as stage II and III (42.6 and 45.9 % respectively). Only 10.2% of patients in our series were recorded with stage IV; most of them were obese.Patients with increased BMI, in our study, had a significantly lower DFS ( p < 0.013).there was a statistically significant correlation between overall survival and BMI of patients (p=0.0015); there was an increase in mortality with increasing BMI. Conclusions: Our results report an increase in the incidence of breast cancer in overweight and obese patients in our population. Patients with high BMI were diagnosed at younger age, had more advanced stage and a statistically significant lower DFS & OS as compared to normal weight patients.
Genetic polymorphisms of EGF 5'-UTR in patients with glioma: A possible predictive marker of outcome.
Authors: Vattemi Emanuela , Cipollini Giovanna , Dealis Cristina , Rossi Lorena , Baier Susanne , Cretella Elisabetta , Di Meglio Giovanni , Sini Valentina , Lusso Maria Rita , Ruda Roberta , Petric Marija , Graiff Claudio
Published: March 2020

e13009

Background: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer otucome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. Methods: EGF 61A/G polymorphism (rs4444903) was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method (GenBank reference sequence-accession no. AC005509) from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. Results: We investigated EGF +61G/A polymorphism in 24 glioma patients . EGF +61G allele has been found in 67% of glioma patients (25% G/G genotype and 42% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 71% and 50%. In WHO IV gliomas, the EGF +61G allele represents a 63% frequency, (27% G/G and 36% A/G ), in WHO III gliomas a 77% frequency (33% G/G and 44% A/G ) and in WHO II gliomas a 50% frequency (100% A/G ). Median PFS of glioblastoma patients was 9 months. 83% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. Conclusions: Our data conferm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.
Patient-specific biomathematical model to predict benefit of resection in human gliomas.
Authors: Baldock Anne , Rockne Russell , Ahn Sunyoung , Neal Maxwell , Corwin David , Clark-Swanson Kamala , Sterin Greg , Trister Andrew Daniel , Malone Hani , Sonabend Adam , Mrugala Maciej M. , Rockhill Jason K. , Silbergeld Daniel L. , Lai Albert , Cloughesy Timothy Francis , McKhann Guy , Bruce Jeffrey N. , Rostomily Robert , Canoll Peter , Swanson Kristin
Published: March 2020

e13017

Background: Gliomas are incurable, primary brain tumors noted for their invasion of brain parenchyma. Our goal was to apply a biomathematical model to estimate the overall tumor invasiveness on an individual basis and determine whether the estimated number of residual glioma cells after resection of any extent is predictive of survival. Methods: Estimates of net rates of proliferation (ρ) and diffusion (D) of glioma cells, based on a biomathematical model of cell density, yield a ratio describing relative invasiveness (ρ/D). This metric was derived for 185 contrast enhancing gliomas from pretreatment MRIs. The residual MRI-detectable volume was combined with the ρ/D tuned to each patient's tumor to allow estimation of the number of glioma cells remaining post-resection. The patients were split into three cohorts by ρ/D values. Within each cohort, all possible cut-off values were considered as a possible threshold between low and high residual patient groups. Log-rank tests were performed for each possible threshold to determine if the Kaplan-Meyer curves were significantly different. Results: We demonstrate that for low ρ/D tumors there was no threshold of residual tumor cell population observed that could yield a significant survival benefit. Both the mid ρ/D and high ρ/D had robust thresholds of residual tumor cell population, below which patients saw significantly higher survival than patients with similar invasiveness and more residual tumor. Conclusions: These results suggest that our patient-specific biomathematical model-based estimates of tumor invasiveness and residual tumor cells have clinical utility in driving neurosurgical decision making. Given the physicians understanding of patient-specific risk factors such as tumor location, age, and physical health, an understanding of the differential surgical benefit allows for more informed cost-benefit analysis and improved quality of life. This metric enables physicians to identify a subset of patients who do not see a survival benefit from resection, making the operation potentially not worth the risks.
Single-agent bevacizumab for recurrent high-grade glioma.
Authors: Greally Megan , Cadoo Karen Anne , Coleman Niamh , O'Brien Michelle , O'Riordan Lynda M. , Grogan William , Breathnach Oscar S.
Published: March 2020

e13019

Background: High grade gliomas(HGG) are aggressive primary brain tumors. Most patients relapse following adjuvant therapy and treatment options are limited. Novel therapies have impacted little on overall survival (OS). Bevacizumab is approved for use following recurrence. We aimed to evaluate the extent of clinical benefit derived from this treatment, as defined by decreased steroid usage and median OS. Methods: We retrospectively reviewed medical records of consecutive patients with recurrent HGG treated with single agent Bevacizumab from May 2009 to Dec 2012 at our institution. We recorded patient demographics, histological features, therapeutic interventions, OS, steroid use and radiological response. Results: 29 patients with recurrent glioma were identified, 19 male and 10 female, with a median age at diagnosis of 47 years (16-72). All patients developed tumour recurrence following various combinations of multimodal therapies including 1-3 partial debulking surgeries, radiotherapy and chemotherapy. The median time from diagnosis of HGG to commencement of bevacizumab was 15 months (6-42). Patients received a median of 7 cycles (1-22) of therapy on a variable dosing schedule. 4 patients are alive, 2 continue on Bevacizumab. 19 patients were on steroid therapy when commencing therapy. There was a significant reduction in mean daily steroid use during therapy (7.65mg vs 3.97mg, p = 0.012). However, daily steroid use ultimately increased in some patients following treatment failure. Interval imaging appearances improved in 6 cases, deteriorated in 15, were stable in 4 and 1 patient had a mixed response. 1 patient was not re-imaged due to deterioration in performance status on therapy. The median OS was 5.5 months (0.5-16 months) from commencement of bevacizumab. Conclusions: The management of patients with recurrent HGG is challenging and prognosis remains dismal. In our unselected cohort, Bevacizumab therapy resulted in temporary or sustained steroid reduction in a majority. However, only a small number of patients demonstrated an objective radiological response and median OS was poor. Tumour response was variable and the addition of a predictive biomarker to establish which patients are likely to benefit from treatment may be helpful.
Neurotrophin signaling and melanoma brain metastases.
Authors: Fortenbery Nicole , Kenchappa Rajappa , Forsyth Peter A. J.
Published: March 2020

e13024

Background: Adult metastatic brain tumors occur more frequently than primary intracranial neoplasms. Melanoma is the third most common tumor type that metastasizes to the brain. Therefore, elucidating the underlying biological mechanisms of melanoma metastases is critical. Melanocytes and neurons share a neural ectodermal origin, and thus, melanoma may preferentially travel to the brain due to the expression of common neurotrophin receptors, namely p75 neurotrophin receptor (p75NTR) and Trks. Further, high concentrations of neurotrophic factors present in the brain may recruit metastatic melanoma. We hypothesize that neurotrophin signaling through p75NTR is required for the malignant phenotype of melanoma and melanoma brain metastases (MBM). Methods: We investigated the expression of several neutrophin receptors, signaling molecules, and neurotrophins that we hypothesize to be important in the process of MBM. Using 14 malignant melanoma cell lines and two primary MBMs grown under neurosphere conditions, we investigated the expression of these molecules using standard western blotting, flow cytometry, and RT-PCR. We also performed an in depth microarray using of 14 primary MBM patients from Moffitt’s Total Cancer Care project. Results: All melanoma lines examined have robust expression of p75NTR, Trks, and neurotrophins. We find melanoma cell lines resistant to the BRAF inhibitor, vemurafenib, have elevated expression of neurotrophins and neurotrophin receptors when compared to lines sensitive to vemurafenib. We also detect high levels of p75NTR in patient MBM, at both mRNA and protein levels. Finally, we find a significant level of expression of all 11 genes tested by microarray. Conclusions: Previous studies have demonstrated that p75NTR has a role in melanoma cell survival in vitro. Here we demonstrate p75NTR and Trk receptors have high expression in melanoma cell lines and importantly, primary MBM. These data suggest that signaling through neurotophin receptors may be important for melanoma metastases and survival in the brain. Moreover, increased expression by vemurafenib resistant lines may suggest that these cells upregulate the expression of neurotrophin signaling as a means of treatment resistant.
Chemotherapy for adult medulloblastoma: Is it necessary for all?
Authors: El-Haddad Mostafa S. , Hawety Amr , Farag Ahmad , Badawy Abd Al-Rahman , Kaled Karim , El-Haddad Shawky
Published: March 2020

e13025

Background: Medulloblastome is rare in adults and treatment is usually extrapolated from the pediatric age group, the aim of our study is to highlight the importance of chemotherapy both in the concurrent and adjuvant setting in adult medulloblastoma. Methods: Fourty patients between 1995 and 2011 with diagnosis of medulloblastoma were treated at both the department of clinical oncology Cairo University or Nasser Institute Cancer Center, files reviewed for demographic characteristics, radiographic findings, extent of resection, staging, computerized tomography (CT) scans or magnetic resonance (MR), histopathology, treatment received, pattern of recurrence and treament received. All patients treated with craniospinal irradiation with total dose of 36Gy followed by a boost to the posterior fossa till 54Gy. Results: Fourty patient were identified from our medical records 24 (60%) male and 16 (40%) female, mean age 25 year (range = 18 - 45), 2 patients had residual tumor more than 2cm, one patient had leptomeningeal deposits, 13 patients had weekly vincristin 2 mg weekly followed by cisplatin vepside, 27 patients didn’t receive any form of chemotherapy. Five year overall and disease free survival for the whole group was 92% (95% CI: 88-142) , 66% (95% CI: 73-135) respectively, for patients received chemotherapy OAS and DFS was 80% (CI:71-138), and 68% (48-162) for patients didn‘t receive chemotherapy OAS and DFS was 90% (CI:81-161), and 67% (C: 58-101), No statistical significance difference of survival between the two groups. univariate analysis didnt show any statistical significance correlation with chemotherapy.G3 neutropenia was more in the chemotherapy group 6 patients vs. 1 patient in the chemotherapy group. Conclusions: Chemotherapy for adult medulloblastoma should be further investigated as good survival time can be achieved with radiotherapy alone. And recurrence can be still salvage with chemotherapy
Early recurrence in glioblastoma.
Authors: New Pamela Z. , Teh Bin S. , Paulino Arnold
Published: March 2020

e13032

Background: Current standard treatment for glioblastoma (GBM) consists of surgical resection, radiotherapy of 6000 cGy to the tumor bed and concomitant then adjuvant temozolomide (TMZ). Median survival on this regimen is 14 months. Early recurrence on imaging studies can be conflicted with treatment effect. Six patients are presented who recurred locally within 7 months of diagnosis despite optimal treatment, in an effort to determine molecular characteristics of patients with early progression. Methods: Three patients underwent gross total tumor resection, 3 underwent subtotal resection. All received IMRT totaling 6000 cGy with concomitant TMZ, followed by adjuvant TMZ. Ages ranged from 23 to 71, median 56. Time to radiographic recurrence was 3 to 7 months, median 4.8 months. There are 5 males and one female. Tumor methylation status and other markers are presented. Results: Three of the 6 patients were re-operated and pathology consistent with recurrent GBM. The remaining 3 progressed neurologically and by MRI scan. The O-6-methylguanine-DNA methyltransferase (MGMT) promoter gene of one tumor was unmethylated. This tumor specimen also expressed topoisomerase II; EGFR and EGFR VIII were negative. One tumor specimen expressed the BRAF V600e mutation. Both of these latter specimens expressed high levels of ERCC1, a DNA repair enzyme which would render these tumors unresponsive to platinum compounds. Conclusions: MGMT promoter methylation status may not be the only predicter of early recurrence. Exploring other biomarkers in more patients with glioblastoma at the time of surgery may assist in predicting true early progression verses pseudoprogression, an imaging challenge, in patients who may respond to different agents.
A phase II trial of lithium, bevacizumab, temozolomide, and radiation for newly diagnosed glioblastomas (GBM).
Authors: Narayana Ashwatha , Tam Moses M , Gruber Deborah Beth , Golfinos John , Parker Erik , Zagzag David , Gruber Michael L.
Published: March 2020

e13033

Background: Invasion is a dominant escape mechanism following angiogenic blockade in glioblastomas (GBM). Lithium has shown anti-invasive activity in glioma cells by inhibiting Glycogen Synthetase Kinase -3. This phase II study evaluated the safety and efficacy of using lithium and bevacizumab (BEV) in newly diagnosed GBM. Methods: From 2010 through 2012, 20 GBM patients with residual disease after surgery were treated with involved-field radiation therapy to 5940 cGy and concomitant temozolomide (TMZ) (75 mg/m2 daily for 42 days) along with BEV (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by six 28-day cycles of TMZ (150 mg/m2 on days 1-7, BEV (10 mg/kg) on days 8 and 22, and lithium 300 mg BID. Lithium was increased every 7 days up to 600 mg BID with a serum lithium goal level of 0.8 to 1.2 mEq/L. Results: The median follow-up was 9.9 months (range 1.9-24.5). Fourteen patients (70.0%) received at least one dose of lithium and three patients completed the entire course of therapy. The median number of BEV infusion was 9 (range 2-19). Five patients discontinued trial due to skin sensitivity (n = 2), pulmonary embolism (n = 1), infection (n = 1), and hematological toxicity (n=1). Two patients experienced dose limiting lithium toxicity which included drowsiness (n = 1) and tremor (n = 1). No patients experienced grade 3/4 intra-cranial hemorrhage. The median progression free survival (PFS) was 9.3 months. The 12-month PFS and OS were 31.9% and 59.3% respectively. For the 14 patients who received lithium, the 12-month PFS and OS were 42.9% and 69.2% respectively. Conclusions: The strategy of targeting angiogenesis and invasion simultaneously in newly diagnosed GBM is effective and feasible. Clinical trial information: NCT01105702.