bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of eribulin on skin metastases in breast cancer patients.
Authors: La Verde Nicla Maria , Moretti Anna , Gamucci Teresa , Borgonovo Karen , Botta Mario , Salesi Nello , Zuradelli Monica , Pavese Ida , Barbieri Elena , Cretella Elisabetta , Saladino Tiziana , Varese Paola , Addamo Gianfranco , Ciccarese Mariangela , Rispoli Anna Iolanda , Pellegrino Arianna , Mentuccia Lucia , Piva Sheila , Farina Gabriella , Di Maio Massimo
Published: March 2020

e12021

Background: Skin metastases (SM) occur in 20% of metastatic breast cancer (mBC). Clinical trials rarely describe them, even if they affect quality of life and self-perception of the disease. Eribulin (E) is a new drug, approved in mBC, after at least 2 lines of chemotherapy. The aim of this survey is to evaluate the activity of E treatment on SM compared to other metastatic sites, and on cutaneous symptoms (pain, infiltration, bleeding, smell, ulceration). Methods: This multicenter survey was conducted from November 2012 to January 2013 in 14 Italian Cancer Centers. Oncologists completed a database with patient (pts), tumor and treatment characteristics. Descriptive summary statistics were applied. Progression-free survival (PFS) was calculated according to Kaplan-Meier method. Results: 109 pts with mBC on E treatment were considered. 23/109 (21%) pts with SM were identified and analyzed. E was started between January 2012 and October 2012. Median age 63 (31-81). Prior chemotherapy lines: 4 (1-10). Prior hormonal lines: 1 (0-4). Basal Karnofski performance status 90 (50-100). 21/23 pts had other metastases, the remaining 2 had exclusively skin disease. SM were predominantly in the thorax (91%) and presented infiltration in 78%, ulceration in 70%, pain in 43%, bleeding in 43% and smell in 17% of cases. According to RECIST criteria, after E 43% of patients obtained a partial response (PR), 35% stable disease (SD), 22% progressive disease (PD). We evaluated skin response independently and found that 26% obtained a complete response (CR); 22% PR, 39% SD, 13% PD. Skin responses were in complete accordance with overall response in 16/23 (70%) pts, in partial accordance in 4 pts (skin CR, with an overall PR) and were discordant in 3 pts (1 skin SD despite overall PR, and 2 cutaneous CR despite overall PD). We found an improvement in SM symptoms: pain control was gained in 50% (5/10) of pts, as well as improvement in smell (50%, 2/4) and bleeding (50%, 5/10). Infiltration disappeared in 3/18 pts (17%). With a median follow up of 6 months, 21 (91%) pts had PD, median PFS was 4.3 months (95%CI 2.9–6). Conclusions: During E an improvement in skin metastases symptoms was observed; in the majority of cases, the response rate of SM was coherent with systemic responses.
Classification of subtype using IHC patterns for treatment decision of DCIS.
Authors: Date Yuko , Takimoto Masafumi , Morohoshi Toshio , Nakamura Seigo
Published: March 2020

e12035

Background: Ductal carcinoma in situ (DCIS) is a heterogenous group of breast lesion and demands a broad range of surgical management techniques. Previous studies reported the importance of receptor expression and referred to the risk of recurrence.We classified ductal carcinoma in situ (DCIS) into 4 subtypes using IHC staining (ER, PgR, HER2 and Ki-67) and investigated the frequency and their characteristics. Also we investigated whether this classification is related to the risk of recurrence. Methods: 117 women who underwent operation between 2010 and 2012 were included our study. We defined 4 subtypes as follows; luminal A (LA), ER and/or PgR (HR)(+) HER2(-) Ki-67(low), luminal B (LB), HR(+) HER2(-) Ki-67(high) or HR(+) HER2(+),HER2(H), HR(-) HER2(+), and basal-like(BL), HR(-) HER2(-).We also evaluated the risk of recurrence using Van Nuys Prognostic Index (VNPI), an algorithm based on DCIS size, nuclear grade (NG), necrosis, margin width and patient age. Results: The frequency of subtype was as follows; LA 77 cases (65.8%), LB 18 (15.3%), H 14 (12.0%) and BL 8 (6.8%). LA tended to smaller size (average: 3.2cm, range: 0.2-12), low NG (NG1 was 97.4%). In a contrary, H and BL were larger size (average: 3.7cm (H), 4.5cm (BL)) and high NG (these percentages of NG3 were 64.3% (H) and 50.0% (BL)). All of the BL had necrosis. About half of the LA was VNPI 6 and 7, but many of the other subtypes were more than VNPI 7 (p=0.02). Conclusions: Classification of subtypes using IHC patterns is simple, useful and, moreover, that are related to the risk of recurrence. Though it is important whether the woman is BRCA1/2 mutation carrier, we might be determined a treatment of DCIS by the subtype.
Prevalence of renal insufficiency (RI) in cancer (Ca) patients (pts) with bone metastases (BM).
Authors: Chen Kristina S , Hernandez Rohini Khorana , Quigley Jane M , Pirolli Melissa A. , Quach David , Liede Alexander , Arellano Jorge
Published: March 2020

e12508

Background: Upon diagnosis of BM, cancer pts are at increased risk of serious debilitating bone complications. Of the U.S. approved bone-modifying agents (BMAs) [bisphosphonates (BPs), RANKL inhibitor] for the prevention of skeletal-related events (SREs) in these pts, BPs are nephrotoxic and may require dose adjustment or discontinuation. As low persistence to BMAs is associated with higher rates of SREs (Hatoum et al 2008), understanding the extent of RI in a real-world setting is warranted. K/DOQI guidelines recommend monitoring renal function using estimated glomerular filtration rate (eGFR) along with serum creatinine (SCr). Methods: Oncology Services Comprehensive Electronic Records (OSCER), a large electronic medical record database from U.S oncology clinics, was used. Cancer pts (age ≥ 18) with BM diagnosis in 2008 – 2012 were identified excluding acute renal failure, end-stage renal disease, and multiple myeloma. RI prevalence was examined using SCr and eGFR calculated with aMDRD and Cockroft-Gault formula. RI was defined as elevated SCr > 1.2 mg/dl or eGFR < 60 and < 90 ml/min/1.73m2. The analysis was also performed in the subgroup receiving BMAs. Results: The cohort included 15,623 pts (mean age 67.1±12.0, weight 76.5±18.5 kg; female; 56%). Using highest SCr during follow-up, 36% had elevated SCr, 87% eGFR < 90, and 47% eGFR < 60. Among pts with BM diagnosis in 2011 (n=3,839) and normal SCr (taken 1 month before or 3 months after diagnosis; n=3,192), almost 60% of the pts had mildly decreased renal function (eGFR < 90), and 8% had moderately decreased renal function (eGFR < 60) (table). Rates of RI based on eGFR estimated by both formulas were consistent. Conclusions: Nearly half of the cancer pts with BM had RI (eGFR < 60) during the course of their disease. As the risk of renal impairment is high in this population, assessment of renal function using eGFR and careful treatment consideration is imperative to achieve optimal therapeutic outcomes. [Table: see text]
Adverse changes in body composition of cancer surivors with BRCA mutations.
Authors: Caceres Aileen
Published: March 2020

e12514

Background: Post-diagnosis weight gain is a risk factor for cancer recurrence and many individuals diagnosed with breast and ovarian cancer gain weight during and after treatment. In the present study, we have measured the anthropometrics of cancer survivors with BRCA mutations and have studied the association between anthropometrics and post-diagnosis weight gain. Methods: The study population included 37 breast and ovarian cancer survivors with BRCA mutations, 45 BRCA previvors, and 26 controls. Anthropometric measurements included body mass index (BMI; kg weight/ m2 height) and body composition (% fat and lean tissue, assessed by using 4-lead bioelectric impedance). Post-diagnosis weight gain was determined via questionnaire. Potential effectors of anthropometrics included: diet (3-day food records), physical activity (General Practice Physical Activity Questionnaire), physical health (co-morbidities, Rand-36 Physical Health Quality of Life (QoL)), and psychological status (Beck Anxiety Inventory, Rand-36 Emotional Health QoL). Results: We found no significant differences in BMI between the survivors, previvors or controls (26+2 (SEM), 25+1, 25+1, respectively). However, the % lean body mass of the cancer survivors was significantly lower and their % body fat significantly higher than the previvors or controls (p=0.0005). Measures of body composition (% fat and lean mass) were independent predictors of post-diagnosis weight gain (r=0.86, p<0.001). No significant association was found between body composition measures and psychological status, energy intake or food composition. However, the adverse body composition measures of the survivors were associated significantly with physical inactivity (p<0.01), number of co-morbidities (p<0.0001), and physical health QoL (p<0.01). Conclusions: BRCA cancer survivors have adverse changes in body composition that increase their risk for weight gain and disease relapse. Based upon these findings, it is important for the survivorship care plan to include: 1) education regarding post-diagnosis weight gain, 2) a physical activity regimen, 3) health management, and 4) interval assessment of anthropometrics, including body composition, during and after treatment.
Clinicopathologic characteristics of pure papillary breast carcinoma.
Authors: Turkoz Fatma P. , Solak Mustafa , Keskin Özge , Arik Zafer , Arslan Cagatay , Kertmen Neyran , Aksoy Sercan , Altundag Kadri
Published: March 2020

e12521

Background: Pure papillary breast carcinoma (PPBC) is a very rare entity which usually occurs in older women with a favorable prognosis. The aim of this cohort study was to evaluate the demographic, clinicopathologic characteristics and survival rates of PPBC compared to invasive ductal carcinoma (IDC). Methods: A total of 2451 invasive breast cancer patients from a single center were analyzed retrospectively. Of these, 24 patients were PPBC (1%) and 1785 (73%) patients were pure IDC. Results: PPBC were significantly different from IDC with respect to the age at diagnosis, menopausal status, tumor size, grade and lymph node involvement (p<0.05) (Table 1). The median follow-up period was 26,5 months (4-400 months). Only one patient with PPBC had lung and bone metastasis, others were alive with no evidence of disease. PPBC was associated with a better 5-year overall survival (100 vs. 84%) and disease-free survival (75 vs. 54%) compared to IDC. Conclusions: Compared to IDC, PPBC is a small, low-grade tumor and less likely to involve the lymph nodes. Cases are usually older, postmenopausal women and have a better prognosis. [Table: see text]
Antibiotic exposure and risk of breast cancer: A causal association or a skyfall?
Authors: Koumarianou Anna , Manali Efrosyni D , Fragou Archontoula , Katsaounis Panagiotis , Bouga Georgia , Karageorgopoulou Sofia , Christodoulou Marianna , Pantazis Nikos , Athanasas George , Arkadopoulos Nikos , Tsionou Christina , Papiris Spyros , Xiros Nikolaos , Antoniadou Anastasia , Giamarellou Helen
Published: March 2020

e12524

Background: Although it has long been hypothesized that the use of antibiotics may increase the risk of breast cancer, through effects on inflammation, immunity and gastrointestinal microflora that alter the metabolism of phytochemicals, clinical data on this association are sparse. Methods: Matched case-control study among 158 women with newly diagnosed primary invasive breast cancer from a single cancer unit and 158 age-matched controls (± 12 months) from healthy individuals accompanying patients to the outpatient clinics between January 1, 2006 and December 30, 2007. Clinical examination and a standard questionnaire for the collection of baseline characteristics and known aggravating factors, such as body mass index, smoking, age of menarche and menopause, parity, breastfeeding, history of respiratory, urinary or other infections and previous estrogen use, were carried out in all individuals. All antibiotic classes, such as β-lactams, amoxyl and clavulanic acid, cephalosporins, macrolides, quinolones, tetracyclines, trimethoprim, clindamycin and imidazoles, were recorded. Type of antibiotic and dose was ascertained from health insurance’s pharmacy records. Data were analyzed using multivariable conditional logistic regression models including adjustments for potential confounding factors. Results: The age matched groups of patients and controls were found to have statistically significant differences in the considered parameters such as delayed age of menopause, less parity and less smoking in the control group and more antibiotic intake in the patient population. The cumulative use for more than 21 days of any antibiotic classes were found to statistically significant correlate with increased risk of breast cancer [odds ratio(OR):3.5, 95%confidence interval(CI):1.7-7.3, p=0.001]. By subanalyses according to antibiotic class this increased risk was mainly associated with β-lactams (OR:11.4, 95%CI:3.8, 34.1, p<0.001) and less with macrolides (OR:2.8, 95%CI:1.1-7.5, p=0.039). Conclusions: Our study links β-lactam and macrolide consumption with increased breast cancer risk but further investigation of this association in large cohorts together with exploration of the underlying cause are needed.
Pancreas cancer: Influence of gender and other demographic and clinical parameters on survival.
Authors: Blank Patricia Renee , Szucs Thomas D.
Published: March 2020

e12529

Background: Research suggests that lower excess mortality risk for females compared to men do exist for several cancer types. The primary aim of this study was to investigate whether gender affects pancreatic cancer prognosis. In addition, the relationship of sex and survival adjusted for clinical and demographic factors was assessed. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (version 1973-2009) was used to identify patients with primary histological confirmed pancreas cancer (≥18 years, 80,689 males and 82,356 females). The analysis was stratified by five different stages (in situ, locally invasive, regional, distant, unstaged). The crude effect of gender was assessed in the total sample and in age-stratified Kaplan-Meier Curves (<55 years) in all five stages, respectively. Univariate and multivariate Cox proportional hazard models were run within the local stage. The predictors included in the models were demographic and clinical factors. P-values (2-sided) of 0.05 were assumed as statistical significant. Results: Between 1973 and 2009, 128,645 pancreas cancer-related deaths were reported. The median follow-up time of the censored patients was 13 months. The Kaplan-Meier curves showed a significant difference in survival among men and female in the locally invasive group (median survival in male and female: 7 months; 1-year survival: 35.5% and 35.1% among female and men, respectively; Log-Rank: p=0.0072). Of the remaining strata, all others had non-significant differences, except the unstaged group (Log-Rank: p= <.0001). The univariate Cox-regression indicated a 5.6% (95%CI: 1.4%, 9.9%, p=0.0081) higher rate of dying among men compared to female (local recurrence). Among the younger population (<55 years), the gender difference was significant across all disease stages, except the in situ group. Histology grade, age, race, and marital status was associated with survival from pancreatic cancer in the multivariate analysis. Conclusions: The present study indicates a gender difference in survival among pancreas cancer patients. The study findings are, however, preliminary and hypothesis generating and a matter for further investigation to give a distinct conclusion.
Interim decisions in oncology trials.
Authors: Yao Bin , Zhang Kathy , Jemiai Yannis , Chang David D.
Published: March 2020

e12530

Background: Interim analyses are commonly performed in oncology clinical trials. For a phase III trial, interim monitoring rules are in general pre-specified for an independent data monitoring committee (DMC) to allow for the possibility of early stopping. Challenges and controversies exist when interim monitoring and subsequent decisions alter the course of the trial. Methods: Abstracts and primary publications of ASCO plenary session presentations for the last 10 years (2003-2012) were reviewed. Interim analyses related to the study design, conduct, endpoints, DMC decision, and reporting were reviewed. Mid-trial adaptations not limited to interim results were also summarized. Results: Fifty-two presentations were identified. Forty-one were randomized controlled trials; almost all were phase III trials. Interim monitoring and analyses were discussed in the primary manuscripts of 31 trials. The objectives of these interim analyses were safety monitoring, inference for superior efficacy, or futility. Fourteen trials crossed interim boundaries and were declared by the DMCs to have met the study objectives on efficacy endpoints such as progression-free survival and overall survival (OS). Mid-trial adaptations included dropping an arm or selecting a dose based on interim safety results. Other trial adaptations, motivated by issues such as slower accrual rate, change in treatment paradigm, or unexpected longer trial duration, included modifications of trial objectives, primary endpoints, sample sizes, and unplanned analyses. Conclusions: Interim monitoring is an important component of clinical trials but is not consistently reported. Decisions made after the primary endpoint has crossed the interim boundary have an impact on subsequent inferences of other endpoints (e.g. OS). Greater transparency and practical guidelines are needed to ensure continued trial integrity and valid inferences post interim.
Breast cancer in male veterans: A retrospective chart review.
Authors: Aggarwal Anita , Liu Min-Ling L , Patel Nihar Kiritkumar , Evangelista Rebecca , Krasnow Steven
Published: March 2020

e12531

Background: Male breast cancer (BCA) is rare and makes up < 1% of all of breast cancer cases. Treatment is mainly based on what is known from female BCA and survival is similar between genders. Objectives: To investigate the clinicopathologic characteristics of BCA and overall survival in male veterans. Methods: Medical records of male patients diagnosed with breast cancer at the Veterans Affairs Medical Centers of Washington DC, Baltimore and Martinsburg from 1992-2012 were reviewed after Institutional Review Board approval. Results: From 1995-2012, 51 male patients with BCA were identified from cancer registry. 29/51(57%) were African American (AA), 41% Caucasian (WM), and 2% other race. Median age was 70 years (44-86years). Palpable mass was presenting symptom in 41/51(80%) and 8(16%) had gynecomastia or bloody nipple discharge. Family history of breast cancer was positive in 11 patients without mention of BRCA genes except pt #24 who was BRCA2+. 3 patients were exposed to Agent Orange. ER/PR was positive in 36(71%), ER+/PR- in 1(2%), ER+/PR+/HER2+ in 2(4%), ER-/PR-/HER- in 2(4%). 41% & 57% had right and left BCA, respectively. 40 (80%) underwent mastectomy. 18(36%) had lymph node involvement (1-13 LN). 90% had invasive ductal carcinoma (IDC), 8% DCIS, and 2% sarcoma. Cancer in 26% was stage I, 38% stage II, 18% stage III and 8% stage IV. 12(24%) received combination chemotherapy. 33(66%) were given tamoxifen. 4(8%) patients had relapsed/recurrent disease in 1-5 years of their diagnosis and died within 2-12 years after the relapse. At median follow up of 174m (4m-19years), 28(56%) patients died (cause of death not known in all), 21(42%) alive and 3(6%) lost to follow up. Conclusions: Median age at diagnosis of BCA seems to be higher in males (70 years) as compared to historical female age (60 years). IDC is the main pathology and 73% tumors were ER +. Survival rate is approximately 40% at >10years of follow up. Survival by stage revealed no difference.
Cancer in pregnancy: To treat or not?
Authors: Walsh Elaine , O'Kane Grainne , Cadoo Karen Anne , Graham Donna M. , Korpanty Grzegorz , Power Derek Gerard , Carney Desmond
Published: March 2020

e12533

Background: Cancer in pregnancy accounts for ~1 in 1,000 pregnancies. Studies show that cytotoxic agents are safe from the second trimester. Long-term follow up has not shown increased malformations or malignancies in children exposed to chemotherapy in utero. There is no evidence of worse outcomes among women diagnosed in pregnancy. Methods: We retrospectively identified women diagnosed with cancer in pregnancy over a 25-year period. Medical records were reviewed for demographics, diagnosis, gestation, timing of treatment and outcomes. We assessed if all cancers need to be treated in pregnancy or if treatment could be safely deferred to allow normal delivery. Results: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology. Of 25 women, 16 (64%) received chemotherapy during pregnancy. These included 13 cases of breast cancer, one Ewing’s sarcoma, one ovarian cancer, and one small cell of cervix. All 16 women received doxorubicin and cyclophosphamide. There were 15 live births and no abnormalities seen in children who received chemotherapy in utero. At a median follow-up of 6 years 11 mothers (69%) are disease free and 4 (25%) have recurrent disease. Of nine mothers who did not receive chemotherapy in pregnancy, seven received chemotherapy immediately post-partum. Six (86%) were diagnosed in early pregnancy (median gestation 13 weeks). There were three cases of Hodgkin lymphoma, two breast cancers, and one ovarian cancer. At a median follow-up of 12 years, all mothers remain disease free. There were no abnormalities seen in these children. Conclusions: We did not identify any adverse outcomes in mothers or infants exposed to chemotherapy during pregnancy. We identified a cohort of patients that do not need immediate treatment during pregnancy. In selected cases, it is safe and appropriate to delay chemotherapy until delivery of the baby. There were no adverse outcomes to mothers due to delayed treatment and no adverse outcomes to babies not exposed to chemotherapy in utero. A multi-disciplinary team is essential to individualize treatment planning. [Table: see text]
Potential risk of residential asbestos exposure: Japanese general screening study for asbestos-related diseases (JGSARD).
Authors: Seki Nobuhiko , Yamaguchi Takuhiro , Eguchi Kenji , Kaneko Masahiro , Kusumoto Masahiko ,   JGSARD Study Group
Published: March 2020

e12541

Background: Currently, an argument about health risks by residential asbestos exposure as well as occupational asbestos exposure has been closed up in Japan. Therefore, the latest large-scale CT screening study reflective of a country's general situation of asbestos exposure will help citizens understand significant information about asbestos-related diseases. Methods: JGSARD is a prospective cohort study for the general population representative of Japan designed to evaluate the actual situation of asbestos exposure and the prevalence of asbestos-related diseases through chest radiography and low-dose CT (LDCT) at baseline and after 2 years of follow-up. From 2006 to 2008, 9810 subjects (mean age, 57 years; 54% male and 50% smokers) underwent baseline screening at 26 institutions in Japan. Lifetime self-reported history of asbestos exposure (SHAE) was obtained. Results: Occupational SHAE was definite and possible in 1103 (11.2%) and 1702 (17.3%) subjects, respectively, whereas residential SHAE was definite and possible in 262 (2.7%) and 931 (9.5%) subjects, respectively, although asbestos factory in their residential areas actually existed in 2870 (29.3%) subjects. The false negative rates of residential SHAE in all participants of this study (n=9810), those with pleural plaque on LDCT (n=264), and those with pleural plaque without occupational SHAE (n=83) were calculated as high value of 85.6%, 76.0%, and 87.9%, respectively. Presence of pleural plaque was significantly correlated with male (odds ratio [OR], 2.32), age 60 years and older (OR, 1.75), smoking (OR, 1.60), occupational or residential SHAE (OR, 3.92), residential period in asbestos factory area (OR every 10 years, 1.13), and asbestos-related work period (7 works identified). Lung cancer was identified in 29 (0.3%) subjects. Presence of lung cancer was significantly correlated with age 60 years and older (OR, 2.67) and presence of pleural plaque (OR, 4.17) regardless of occupational and residential SHAE. Conclusions: Our results indicate the potential risk of residential asbestos exposure and thus the importance of public relations and enlightenment for them among Japanese general population.
Breast cancer incidence in a large cohort of Peruvian women affiliated to a pre-paid system.
Authors: Suazo Juan F. , Valdiviezo Priscila I. , Flores Claudio J. , Iberico Jorge , Pinto Joseph A. , Aguilar Alfredo , Vigil Carlos Enrique , Gomez Henry , Vallejos Carlos S.
Published: March 2020

e12570

Background: Breast cancer (BC) is the second most common malignancy and the leading cause of death by cancer in Peruvian women (age-standarized rate [ASR] of 34 new cases/100,000 women estimated by GLOBOCAN 2008). The purpose of this study was to assess the incidence of BCin acohort ofwomenat Oncosalud, an oncologic pre-paid system that currently has 600,000 affiliates. Methods: We evaluated a dynamic cohort (period 1989 to 2011) of women affiliatedat Oncosalud – AUNA, an oncologic prepaid system.The crude incidence rate per year (number of new cases/women 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 BC incidence rate per year was 175.6 and the ASR incidence was 111.9 per 100,000 affiliates respectively. In our cohort of affiliates there were no BC cases before 1993 (with 907 women at risk for that year). The highest incidence rate was 177.6 registered in 1997 (11,822 women at risk). Incidence rates started decreasing in 2003 (169.2 with a population at risk of 39,593 women). The lowest incidence was 71.5, registered in 2011 (279,680 women at risk).According to age-groups, there were no BC cases under20 years old. Specificincidence ratesper age-group increases from the 30 year old-group (55.8). The peak of BC incidence was between 70 to 74 years old (407.4). In the same way, the cumulative risk increases after 30 years old. Conclusions: In our cohort of affiliates, the incidence of BC is greater than the general population, it could be due to the process of negative selection; however, specific incidence rates per age-group and cumulative risk are increased after 30 years, as seen in the general population.
Breast cancer: First results of an institutional cancer registry 2007-2011 in Colombia.
Authors: Yepes Andres , Gonzalez Luis , Durango Isabel Cristina , Pineda Beatriz , Figueroa Juan D. , Triana Jaime
Published: March 2020

e12571

Background: The aim of this retrospective study was to describe the clinical characteristics of patients with breast cancer (BC) treated at the Oncology Unit of the Hospital Pablo Tobon Uribe in Medellin, Colombia, an institution's 10-year experience. Methods: All cases were Identified from our institution's cancer registry from 2007-2011. Results: During the study period 1224 BC were cases identified. Men: 12 (1%). Median age at diagnosis was 56 years (range 23-88). Stage at diagnosis was stage 0 (6.1%), stage I (30%), stage IIA (24.5%), stage IIB (10.8%), stage IIIA (6.8%), stage IIIB ( 6.1%), stage IIIC (9.5%), stage IV (3.4%) and unknown (2.8%). Primary right breast (50.2%). Most common histology was invasive ductal carcinoma (71%) and histologic grade 2 (34.6%). Estrogen and progesterone receptor status assessed at diagnosis was positive in 74,7% and 69% of cases tested respectively. HER2/neu status was positive in 14.2% (with hormone receptor positive 8,1% and hormone receptor negative 6.1%). Triple-negative BC 12.2%. Median tumor size was 2.3 cm (range 0.4-14.0 cm). Procedure performed was mastectomy in 59% and lumpectomy in 35%. Nodal staging was performed by axillary dissection (AD) (81%) and sentinel node biopsy (SN) alone (19%). Neoadjuvant chemotherapy was given to 39%, adjuvant chemotherapy to 69%, adjuvant hormonal therapy to 62% and adjuvant radiation therapy was used in 40,6%. The preferred adjuvant regimens was AC (doxorubicin / cyclophosphamide) followed by weekly paclitaxel in 51%. The average time from diagnosis to entry into consultation with specialist breast surgery 12 days. Time from diagnosis and staging complete and the beginning of the treatment: 16 days. Conclusions: The patient profile inquiry to our hospital with breast cancer is a woman of 56 years, with commitment right breast, invasive ductal carcinoma, grade 2, luminal A (estrogen receptor positive and / or progesterone receptor positive, HER2 negative), stage I and most commonly treated with mastectomy and chemotherapy with AC and paclitaxel.
MRI-based maps differentiating tumor from nontumor tissues for improved clinical management of brain tumor patients.
Authors: Mardor Yael , Guez David , Last David , Daniels Dianne , Grober Yuval , Nissim Ouzi , Hoffmann Chen , Nass Dvora , Talianski Alisa , Spiegelmann Roberto , Cohen Zvi R , Zach Leor
Published: March 2020

e13002

Background: We have recently demonstrated delayed contrast extravasation MRI for calculating maps providing clear, high resolution depiction of tumor/non-tumor tissues. >100 brain tumor patients have been recruited in 3 clinical studies. In all cases increased tumor volumes (TVs) on our maps were followed by progression while stable/decreased TVs did not require treatment changes. Following histological validation the maps are being used for clinical decisions. Methods: Our maps were applied for improved patient management in 23 patients post treatment in which consensus regarding tumor progression vs. treatment effects (TEs) has not been reached. In all cases increased enhancement was shown on T1-MRI and rCBV was low/inconclusive. Results: In 5 GBM patients 1-3 months post surgery our maps showed significant TVs, therefore 2 were started on Avastin and 3 were re-operated. One of the latter showed increased enhancement on T1-MRI after the second operation. The maps showed no TV consistent with later clinical improvement. Two GBM patients 3-4.5 months post chemoRT showed increased TEs and stable TVs consistent with pseudoprogression. Adjuvant TMZ was continued followed by decreased lesion volumes. 2 patients (GBM/AA) showed increased TVs 5 months/years post chemoRT and were referred to Avastin/surgery. One patient was scanned 2 wks post chemoRT with clinical deterioration and rescanned 3 wks later when stabilized showing significantly increased TVs with no change on standard MRI. The patient was re-operated. Brain mets patients were recruited 1-21 months post SRS. Four showed significant TVs and were referred to treatment (surgery, WBRT, Xeloda). Two were followed for 3-6 months and upon increase in TV were referred to surgery. In 6 patients 73-100% of the enhancing lesion consisted of TEs thus are currently stable under FU. In 3 the lesion has resolved within 2-4 months. Active tumor was confirmed histologically in all above resected lesions. Conclusions: Following validation of our easily interpreted color code maps patients are now referred from 4 major Israeli hospitals with a question of progression vs TEs. Our data suggests that the maps may be used for improved patient management when standard MRI is inconclusive.
Analysis of long-term survival in patients with glioblastoma.
Authors: Melegari Elisabetta , Dall'Agata Monia , Guiducci Graziano , Cremonini Anna Maria , Cerasoli Serenella , Ibrahim Toni , Sintini Michele , Cenni Patrizia , Bomprezzi Chiara , Faedi Marina
Published: March 2020

e13007

Background: Adult glioblastoma (GBM) is the most common type of malignant primary brain tumor. Despite advances made in treatment, median survival is between 12 and 15 months. Standard care is concomitant radiotherapy (RT)/temozolomide (TMZ) and adjuvant TMZ for 6 cycles (EORTC/NCIC trial 2005). At progression, subsequent treatments are left to the discretion of the treating physician. Methods: We evaluated retrospective data of GBM patients (pts) treated from 2003 to 2010, focusing on the treatment of patients with longer survival (over 24 months). Results: 139 pts with GBM were treated during the period. Thirty of these showed survival > 24 months: 20 were subjected to macroscopically radical neurosurgery, 9 to non-radical surgery and 1 to biopsy. All pts had a KPS 100%. 11 pts were treated in the period pre-EORTC/NCIC trial (Stupp et all) and 19 in the period “post-Stupp”. In the former group 10 pts underwent RT followed by TMZ ( 2-12cycles) and 1 patient received only RT. All pts in the latter group were treated with concomitant radio-chemotherapy followed by TMZ. 3 pts are currently disease stable. After the first documented evidence of disease progression (PD) 21 pts were treated, one with neurosurgery, 4 with neurosurgery plus chemotherapy (CT), 15 with only CT and 1 with CT and tomotherapy. With regard to chemotherapy, 14 pts received TMZ ( 2-21cycles), 3 fotemustine (4-16 cycles), 1 carboplatin and VP16 (2 cycles) and 1 irinotecan plus bevacizumab (2 cycles). Further progression was treated with another line of CT in only 8 pts, fotemustine in 5 (1-3 cycles), TMZ in 2 (2 cycles) and carboplatin plus VP16 In 1 (5 cycles). Median overall survival (mOS) of our long-term survivors was 36.18 months (CI 95% 28.32 – 42.01). Considering the two groups separately (pre- and post- Stupp), we observed a mOS of 36.18 months (CI 95% 26.45 – 42.01) (1 pt alive) for the first group and of 36.15 months (CI 95% 28.26 – 48.52) (7 pts alive) for the second. Conclusions: Our long-term survivors, independently of treatment, showed an mOS of 36.18 months (CI 95% 28.32 – 42.01). There was no significant difference in mOS between the 2 groups (p=0.6963). Further research is needed to identify the biomolecular and genetic pattern that is responsible for the long survival of some patients.
Multimodality treatment for intracranial germ cell tumors: Experience from an Asian tertiary hospital.
Authors: Chong Dawn QQ , Tan Iain BeeHuat , Tan Daniel HY , Chua Eu Tiong , Tham Chee Kian
Published: March 2020

e13027

Background: Intracranial germ cell tumors (GCTs) represent up to 11 percent of pediatric central nervous system (CNS) tumors in Asia. We compared the efficacy of radiotherapy alone (RT) with platinum-based chemotherapy (CT) in combination with dose-attenuated RT. Methods: We identified 61 patients treated at National Cancer Centre Singapore from 1995 to 2011. Patient’s demographics, histopathologic characteristics and survival data were collected. Median follow up was 39 months. Results: Forty-eight (79%) patients were male; mean age at diagnosis was 17 years. Most (87%) patients had pineal or suprasellar tumors. The distribution of pure germinomas, non-germinomatous tumors and mixed tumors was 54 (89%), 5 (8%) and 2 (3%) patients, respectively. Twenty patients had RT alone, 2 had CT alone, and 31 received a combination of CT and attenuated RT. There was no difference in overall survival (OS) between unifocal or multifocal disease (p = 0.81). Amongst the germinomas, there was no difference in OS between patients given RT alone and CT combined with attenuated RT (median OS not reached vs 145 months, respectively, p = 0.668). Conclusions: Treatment with CT followed by dose attenuated RT is an alternative to conventional craniospinal RT and did not compromise survival in patients with germinomas. This may represent a therapeutic modality with a more favorable long term toxicity profile in these patients who have excellent long term outcomes.
Patient-specific mathematical modeling as a precision-medicine approach to evaluating therapeutic gains of a novel chemoprotection treatment in newly diagnosed glioblastoma.
Authors: Johnston Sandra K. , Adair Jennifer E. , Bridge Carly , Guyman Laura , Hawkins-Daarud Andrea , Rockne Russell , Baldock Anne , Rockhill Jason K. , Mrugala Maciej M. , Beard Brian C. , Kiem Hans-Peter , Swanson Kristin
Published: March 2020

e13041

Background: Glioblastoma (GBM) is the most common and lethal of all brain tumors (median overall survival (OS)14.6 months), yet the incidence is low posing difficulty in creating statistically powered clinical trials, delaying advances in treatment. A patient-specific mathematical model for disease progression coupled with clinical imaging data may provide a tool for quantifying each individual tumor’s response relative to its inherent growth kinetics rather than a universal approach, and, potentially, predicting treatment efficacy. Methods: An exploratory analysis with a patient-specific mathematical model of GBM was used to evaluate therapeutic effect of a novel treatment for newly diagnosed GBM compared to standard care treatment. A cohort of 3 patients from a novel-chemoprotective stem cell gene therapy treatment study (CSCGT) received RT only, followed by dose-intense BCNU and infusion of autologous gene-modified hematopoietic stem cells. Patients then received TMZ combined with O6-benzylguanine (O6BG). Tumor volumes were calculated using T1 weighted gadolinium -enhanced and T2-weighted pretreatment MRI images to estimate patient-specific net rates of proliferation and invasion for predicting untreated tumor growth. Control patients were selected based on matching model-based rates of net proliferation and invasion and standard prognostic variables (age, performance, extent of resection). Deflection of tumor growth, days gained (DG), was determined by finding the time point on the untreated growth curve that corresponded to the post-treatment tumor size and calculating the amount of time treatment gained for the patient. DG per mg of TMZ dosed is used to compare treatment effects of TMZ with differing dose regimens. Results: CSCGT patients experienced higher DG per mg of TMZ dosed compared to their matched controls treated with standard care regimens. Conclusions: Patient-specific mathematical modeling can be used to evaluate treatment gains in small clinical trial design. The addition of O6BG to TMZ in the post RT milieu can provide greater treatment gains per mg of TMZ dose than TMZ alone. Clinical trial information: NCT 00669669.
A model-based approach to optimize detection of treatment effects in early oncology trials.
Authors: Retout Sylvie , Phipps Alex , Geho David , Tessier Jean , Nichols Gwen L. , Bottino Dean
Published: March 2020

e13508

Background: Tumor size change from baseline (RECIST) is often used to assess antitumor activity of investigational agents in phase 1 trials, but this measure does not take into account the tumor growth rate (TGR) prior to treatment. TGR could be highly variable in a phase 1 ‘all-comers’ patient population, with a high TGR potentially masking a meaningful treatment effect (TE). Assessing the change in TGR (Mehrara et al, BJC 2011) using historical tumor burden assessments (Gomez-Roca et al, Eur J Cancer 2011) may provide higher sensitivity to true TE (TTE). The objectives of the current study are to formalize a Growth Rate Based Method (GRBM) and to compare, using simulated patients, the ability of GRBM and RECIST assessments to detect and quantify TTE. Methods: The exponential tumor growth model (Claret et al, J Clin Oncol. 2009) was used to simulate the sum of the longest diameters (SLD) individual time courses of 2000 virtual patients under different TGR scenarios: slow, medium, fast and ‘all comers’ (highly variable TGR as often encountered in phase 1). Different sampling designs were simulated wherein tumor assessments with measurement errors were obtained, ranging from 16 to 4 weeks prior to treatment initiation (TI), immediately before TI, and 8 and 16 weeks after TI. TTE was defined as the difference between the simulated SLDs at 16 weeks with and without treatment. GRBM response was defined as the model-predicted difference between the SLDs with and without treatment, as estimated from the simulated samples. Sensitivity (Se) of RECIST or GRBM was defined as the probability of classifying a patient as a RECIST or GRBM >30% reduction when the TTE >30%, and specificity (Sp) as the probability of RECIST or GRBM reduction <30% when TTE <30%. Results: RECIST Se was consistently inferior to GRBM, notably in the all-comers TGR (37% vs 74-89%) scenario. GRBM maintained Se (71-89%) irrespective of TGR whereas RECIST Se degraded significantly with increasing TGR. RECIST Sp was high (97-100%) while GRBM Sp was lower (55-80%) depending on sampling design and TGR. Conclusions: Incorporation of an additional pretreatment tumor assessment by GRBM may augment RECIST by increasing sensitivity to TTE, particularly in a heterogeneous TGR phase 1 setting.
Effect of short course, high-dose valproic acid on proliferation in breast adenocarcinomas.
Authors: Cohen Adam Louis , Factor Rachel , Schabel Matthias , Bild Andrea , Werner Theresa Louise
Published: March 2020

e13522

Background: Our in vitro and in vivo studies showed that single agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is effective in a subset of breast cancers. Whether VPA is effective as a single agent and what the optimal dosing would be are unknown. Methods: In an ongoing IRB-approved, window-of-opportunity study testing a genomic predictor of sensitivity to VPA (NCT01007695), we performed biopsies and DCE-MRI on women before and after seven days of escalating doses of VPA on untreated women with breast adenocarcinoma with an intact breast tumor. Within patient dose-escalation was done with a goal dose of 50 mg/kg. Proliferation was assessed with MIB-1 immunohistochemistry. Only correlative secondary endpoints are presented here. Results: Sixteen women have completed treatment and are evaluable. Total and free VPA levels on the last day of treatment averaged 136 µg/ml (range 15-242) and 30 µg/ml (range 1-90), respectively. Proliferation rate by MIB-1 decreased by and average of -7.25% (range +4% to -45%, p=0.04). The change in proliferation did not correlated with VPA levels, although only one of four women with VPA levels less than 100 µg/ml had a decrease in proliferation, compared to five of twelve women with VPA levels greater than 100 µg/ml. Four women had MIB-1 decreases of 10% or greater. Two women have had post-treatment biopsies with fibrosis similar to that seen with chemotherapy treatment effect. DCE-MRI parameters, including ktrans, vp, and kep, did not change significantly with VPA treatment or correlate with VPA levels. Conclusions: VPA as a single agent can reduce proliferation in a subset of women with breast cancers. Higher VPA levels are needed than those achieved at standard dose levels, but VPA levels by themselves do not predict effect. Other monitoring parameters, such as peripheral blood histone acetylation changes, or other predictors of benefit are needed. Clinical trial information: NCT01007695.
Use of combination treatment with the investigational RAF kinase inhibitor MLN2480 and the investigational MEK kinase inhibitor TAK-733 on the growth of BRAF-mutant and RAS-mutant preclinical models of melanoma and CRC.
Authors: Cunniff Elizabeth Grace Carideo , Zhang Julie , Chouitar Jouhara , Mettetal Jerome , Nakamura Kazuhide , Arita Takeo , Nakamura Akito , Okaniwa Masanori , Ishikawa Tomoyasu , Yoshida Sei , Fabrey Robyn , Vincent Patrick , Eng Kurt , Garcia Khristofer , Borrelli Deanna , Vagrhese Teena , Stroud Steve , Menon Saurabh , Kuranda Mike , Galvin Katherine
Published: March 2020

e13529

Background: RAS mutant melanoma and colorectal cancer represent areas of significant unmet medical need. MLN2480 is an investigational class II RAF kinase inhibitor and TAK-733 is an investigational allosteric MEK kinase inhibitor; each of which is the subject of a single agent phase I clinical trial. The present studies have characterized the combination activity of these agents in BRAF mutant and RAS mutant preclinical models of melanoma and colorectal cancer. Methods: Combination effects of MLN2480 and TAK-733 on cell viability were studied using an ATP-based cell viability assay across a panel of BRAF and RAS mutant melanoma and CRC cell lines. Western blot analysis was used to compare effects on MAPK pathway signaling and response markers in cell lines showing a range of sensitivity to this combination. Pharmacodynamic responses and growth inhibitory effects of the combination were studied in xenografts of the same cell lines, as well as in primary human tumor xenografts, of RAS mutant melanoma and CRC. Results: MLN2480 inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preclinical cancer models at concentrations that are tolerated in vivo. MLN2480 is most potent in BRAF mutant melanoma models but also has single agent activity in some RAS mutant models. The combination of MLN2480 with TAK-733 inhibits the growth of a broader range of RAS mutant tumor models than single agent MLN2480, including primary human tumor xenograft models of melanoma and CRC. In vitroanalysis of this drug combination in cell proliferation assays demonstrates synergistic activity. Western blot analysis demonstrated the effect of MLN2480 in reversing feedback activation of MEK in response to TAK-733, leading to more concerted MAPK pathway inhibition. Conclusions: The activity of the RAF kinase inhibitor MLN2480 in preclinical models of BRAF and RAS mutant melanoma and CRC provides a rationale for clinical testing. The combination of MLN2480 with the MEK inhibitor TAK-733 represents an additional strategy for clinical research within these tumor types.
Evaluation of the toxicity and efficacy of paclitaxel nanoencapsulated with polyethyloxazoline polymers.
Authors: Yin Ray , Pan Jing , Zhou Bingsen , Zhang Yubei , Dougherty Jeffrey , Liu Joanna , Riesenberger Tracy A , Qin Dujie , Vallejo Yli Remo
Published: March 2020

e13538

Background: Paclitaxel’s antineoplastic activity is limited by its solubility and toxicity. Encapsulation with polyethyloxazoline (PEOX) branched polymers can increase its solubility, decrease toxicity and enhance its antitumor efficacy. Methods: Paclitaxel was mixed with PEOX-based branched polymers at drug loading percentages of 11 - 17% to form nanoparticles (< 90 nm in diameter). The product was purified and lyophilized as a white powder, designated FID-007. Its cytotoxicity was tested on normal human fibroblast cells and cell lines for human lung (A549), triple negative breast (MDA-MB-231) and ovarian (OV-90) cancers. Commercial paclitaxel drugs, Taxol and Abraxane, were similarly tested. Maximum tolerated dose (MTD) of the three drugs were determined in CD-1 mice. FID-007’s efficacy in controlling tumor growth was compared to the other drugs in vivo using xenograft tumor models in Scid mice with the three human cancer cell lines (20 mice per cancer). Saline and polymer were used as negative control treatments. Results: FID-007, Taxol and Abraxane showed similar cytotoxicity to all cancers.FID-007 was > 10-fold less active in normal fibroblasts. The single dose MTD in CD-1 mice was < 30 mg/kg for Taxol, 175 mg/kg for FID-007 and >180 mg/kg for Abraxane. FID-007 exhibited the best efficacy in controlling tumor growth in mice compared to Taxol and Abraxane with the three human cancers. Results from the lung tumor study are presented in the Table. Conclusions: Encapsulation with PEOX-based polymers reduced the toxicity and significantly improved the efficacy of paclitaxel in controlling tumor growth in vitro and in vivo. [Table: see text]