bluuebunny/crossref_metadata_2025 huggingface dataset:
Pilot trial of chidamide, an oral histone deacetylase (HDAC) inhibitor, in combination with exemestane in hormone receptor-positive advanced breast cancer.
Authors: Zhang Qingyuan , Wang Tao , Geng Cuizhi , Zhang Yue , Zhang Jinwen , Ning Zhi-Qiang , Jiang Zefei
Published: September 2018

e12543

Background: Chidamide (CHI) is a novel benzamide type of subtype-selective histone deacetylase inhibitor approved in China for refractory and relapsed peripheral T-cell lymphoma with a dosage of 30 mg PO twice a week. A randomized, double blind and placebo-controlled phase 3 clinical trial of CHI plus exemestane (EXE) is currently ongoing in patients (pts) with hormone receptor-positive (HR+) advanced breast cancer (ABC). This abstract reports the results from the pilot study preceded the phase 3 trial. Methods: Eligible pts were postmenopausal women recurrent or progressed to at least one endocrine therapy. In the run-in period for pharmacokinetic (PK) analysis, pts received EXE 25 mg on day (D) 1 and CHI 30 mg on D 2. From D 5 pts started combination treatment having EXE 25 mg daily and CHI 30 mg twice a week until progression of disease (PD) or intolerable toxicities. A treatment cycle was defined as 28 days. Safety, PK parameters and preliminary efficacy were assessed. Results: 20 pts with HR+ and HER-2 negative were enrolled between Jul and Dec, 2015. Median duration of treatment was 5 cycles (range 0-16), with 4 pts still on treatment. 3 pts discontinued due to adverse events (AE). Drug-related AEs ≥ grade 3 in 2 or more pts were neutropenia (35%), thrombocytopenia (30%), and leucopenia (20%). Similar plasma exposure of EXE was observed in the absence and presence of CHI ( 73 ± 27 vs. 80 ± 29 ng·hr/mL). A potential increased plasma exposure of CHI was noted in the presence of EXE compared with CHI alone ( 2232 ± 973 vs 1787 ± 946 ng·hr/mL), apparently related to the inter-patient variations in CHI plasma concentrations. Best response in 18 pts was assessed by RECIST, including 3 pts with partial response, 12 pts with stable disease and 3 pts with PD. Median progression free survival was 7.6 months. Conclusions: The combination of CHI and EXE was generally well tolerated. Most AEs were related to the CHI single-agent treatment that are generally manageable. Encouraging antitumor activity was observed. The overall results from this pilot trial enabled the next-stage clinical development of this combination regimen in HR+ ABC pts. Clinical trial information: NCT02482753.
Review of next generation sequencing outcomes in patients with metastatic breast cancer.
Authors: Kang Irene , D'souza Anishka , Spicer Darcy V. , Russell Christy Ann , Lang Julie E. , Nelson Maria , Silberman Howard , Lu Janice M.
Published: September 2018

e12558

Background: Among patients with newly diagnosed breast cancer in the US, 6-10% will have metastatic disease. With many treatment options to choose from, Next Generation Sequencing (NGS) is a technology that can potentially guide treatment. However studies on the clinical use of NGS are currently limited. Methods: We identified patients with metastatic breast cancer treated at Norris Comprehensive Cancer Center and Los Angeles County Medical Center who underwent NGS with FoundationOne, a clinical-grade NGS tool. Medical records were reviewed for genetic findings, tumor type, treatment outcomes and impact of NGS testing. Results: NGS data derived from FoundationOne testing were analyzed in 27 patients tested between 2013 and 2017. The most commonly occurring mutations were TP53 and PIK3 occurring in 29% of tested patients; followed by MYC, CDH1 and CCND1 (26% each). Clinical data were available for 26 patients:18 patients were hormone receptor (HR) positive Her2 negative, 6 were triple negative, one had HR positive Her2 positive disease, and one had adenoid cystic pathology. A median of 4 mutations per patient (range 0-13) were detected by NGS testing. Twenty-one of 27 patients (78%) were found to have clinically actionable mutations with a median of 1 clinically actionable mutation (range 0-3) per patient. Of these patients, 10 (47%) received treatment directed at their mutation. Five patients were treated on clinical trial as a result of AKT, PTEN or ERBB2 mutations. An additional two patients had received targeted treatments empirically before the time of NGS and three cases are intended for future use. Patients had received on average 5 lines of therapy (range 0-13) at time of study. Conclusions: In patients with metastatic breast cancer, NGS provides data that may drive clinical care. Potential benefits include more precise selection of treatment regimens as well as identifying benefit from drugs that are not yet standard of care in breast cancer. Here we report that clinically actionable mutations are found in a majority of patients tested. Further study is necessary to determine the utility of NGS in this population.
Multicenter study of the evaluation of eribulin (E) use in Sicily in metastatic breast cancer (MBC): A prospective registry (VESPRY trial).
Authors: Adamo Vincenzo , Ricciardi Giuseppina , Giuffrida Dario , Scandurra Giuseppa , Russo Antonio , Blasi Livio , Spadaro Pietro , Lucenti Antonio , Soto Parra Hector J. , Savarino Antonino , Ferraú Francesco , Zerilli Filippo , Verderame Francesco , Butera Alfredo , Franchina Veronica , Cottini Lorenzo , Fedele Guido , Caruso Michele
Published: September 2018

e12565

Background: Eribulin Mesylate is a non taxane microtubule dynamics inhibitor, approved for heavily-pretreated MBC patients (pts). Methods: This is a multicenter, prospective, single arm study for E-treatment of third line in pretreated MBC pts, conducted in 14 oncology centers in Sicily. All pts had received two previous chemotherapy regimens for MBC. Pts received E at 1.23 mg/m2 on days 1,8 every 3 weeks until progression. Primary Endpoints: overall response rate (ORR) according to the site of metastases and safety. Secondary objectives: Progression-free survival (PFS) and ORR according to different subtypes. PFS curve was estimated using the Kaplan-Meier method. Multivariable logistic regression model were used to evaluate the associations of each variables with tumor response. ORR was assessed according to RECIST 1.1 and safety with CTCAE v4.0. Results: 122 pts were enrolled and received at least 1 dose of E. Median age was 58 (range 29-79). All received previously anthracycline and taxane based-therapies. Subtypes: Luminal A 69%, Luminal B 7%, HER2 enriched 4% and Triple Negative 20%. The most common metastatic sites were bone and liver; 67% had metastatic disease involving two or more organs. A median of 5 cycles of E (range 1-26) was administrated. 106/122 pts were evaluable for efficacy, all for safety. ORR was 48%. Exploratory subset analysis showed significantly higher ORR in the lung, liver and bone lesions compared to other site of metastases and in HER2 negative pts. Multivariable regression model showed that HER2 positive subtype was correlated with a poor response (odd ratio 6.7, 95% CI 1.2-36.5). The median PFS was 14.7 months (mos) (95% CI 7.2–25.7). Among pts with < 65 and ≥ 65 years, the median PFS was 14.7 and 25.7 mos, respectively. Most common toxicities: G2 diarrhea 1%, asthenia G1 4%, G2 neutropenia 6%, G1 neurotoxicity 5%, QT prolongation 1%, G4 mucositis in only one case. Conclusions: This study showed a significant improved of PFS with E in third line setting and a favorable safety profile compared with results reported in the pivotal trial. Our findings suggest that E has substantial antitumor activity when used early for the treatment for MBC with acceptable safety.
Do the efficacy of BP-C1 correlate to receptor status in patients suffering from metastatic breast cancer stage IV?
Authors: Larsen Stig Einride , Butthongkomvong Kritiya , Sorraritchingchai Sirikul , Sangsaikae Isaraporn , Manikas Alexey , Trishkina Ekaterina , Matrosova Marina , Poddubuskaya Elena
Published: September 2018

e12581

Background: Cis-coordinated complexes of platinum(II) with polymer of benzene polycarboxylic is currently evaluated in clinical trials for treatment of metastatic breast cancer (MBC) patients. The RECIST was used for evaluation of the target lesions and the sum diameter of the five largest target lesions was measured. BP-C1 inhibits tumor growth, improves quality of life with only few mild to moderate adverse events. The aim was to investigate the correlation between the efficacy of BP-C1 and the receptor status of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (HER-2) Methods: The material consists of prospectively collected results from 30 Thai and 30 Russian MBC patients included in two randomized and double-blinded controlled clinical trial with stratified semi-cross-over design. The patients received daily IM injections of 0.035mg/ml bw BP-C1 for 32 days. The results from Russia available by March 2017, and will be included in the final presentation Results: Negative ER recorded in 13 patients and positive in 15. During 32 days of BP-C1 treatment, the sum lesion diameters reduces with 1.9 % in the negative receptor group, but increases with 8.0 % among the positive. Similar pattern also detected regarding the PR. Negative PR detected in 17 patients and positive in 12. No changes (0.1%) in the sum lesion diameter found in the group with negative PR, but an increase of 8.8% in the positive group. Negative HER-2 receptor recorded in 13 patients and positive in 13. The sum lesion diameter increases with 7% in the negative group and 6.0% in the positive. In five patients, all the three receptors were positive, 10 patients had one negative receptor, 12 had two negative and three were triple negative. During the 32 days of BP-C1 treatment, the sum lesions increases by 20.7% in the triple positive group and by 7.6% in the group with one negative receptor. In the patients with two or three negative receptors, the sum lesion diameter was unchanged; -0.6% and 0.5%, respectively. The reduction sum lesion diameter seem to increase with increasing number of negative receptors. Conclusions: These findings indicate that BP-C1 may be an important treatment of stage IV MBC with negative ER, PR or HER-2 receptor.
Triple negative breast cancer: An Indian problem— Experience from a tertiary care oncology centre.
Authors: Gupta Sameer , Paryani Jeetendra , Chaturvedi Arun , Kumar Vijay , Akhtar Naseem
Published: September 2018

e12583

Background: Breast cancer is a heterogeneous disease with distinct biological subtypes as determined by gene expression profiling studies. Breast cancer is most common cancer in Indian females and is believed to be biologically different from west, notably in terms of high prevalence of Triple negative subtype (TNBC). Reliable data on clinical and epidemiological profile of TNBC in Indian population is scarce. Aim of this study was to analyze the epidemiological and clinical profile of TNBCs Methods: Data of 355 patients of breast cancer registered in our department between 2013 and 2015 and followed up until December 2016 was collected and reviewed for epidemiological and clinical features Results: Of total 355 patients analysed, TNBC group was most common (n = 152) (43%) followed by Luminal A (25%). Median age at disease presentation in TNBC was 42.4 years compared to overall age of 45.3 years (24–73 years). In TNBC subgroup, 48% patients presented in locally advanced and 15% in metastatic stage, more commonly in pre-menopausal patients. Overall 268 (76%) patients underwent surgery with Modified radical mastectomy being preferred surgical option (86%), followed by adjuvant chemotherapy. TNBC subgroup demonstrated low response rate to neoadjuvant chemotherapy with only 9% of patients having complete response and 25% patients having progressive disease. Median followup was 34 months (6 50 months). Of the total recurrences (n = 19), nearly 2/3rd (n = 13) were documented in TNBC subgroup. Disease free survival (DFS) of TNBC subgroup was lower than of other luminal subtypes (p = .043) Conclusions: TNBC was the most common breast cancer subtype (43%) in Indian population which is nearly twice the rate reported in Western countries. This finding has significant clinical relevance as it may contribute to poor outcomes in Indian patients. Our study also corraborated this fact with higher prevalence of premenopausal breast cancer, poor response to neoadjuvant chemotherapy, high recurrence rates and decreased disease free survival. Additional research is needed to understand the determinants of TNBC in India as it is a prognostic group with aggressive behaviour that commonly lack the benefit of any specific targeted therapy
Triple-NOTE (Triple Negative Outcome in ESME): Large recent real-world prognostic data on triple negative metastatic breast cancers (mTNBC).
Authors: Sablin Marie-Paule , Tchokothe Corinne , Loirat Delphine , Bachelot Thomas Denis , Fourme Emmanuelle , Carton Matthieu , Mokdad-Adi Meriem , Berchery Delphine , Levy Christelle , Jacot William , Penault-Llorca Frederique Madeleine , Goncalves Anthony , Vanlemmens Laurence , Eymard Jean-Christophe , Campone Mario , Simon Gaetane , Robain Mathieu , Cailliot Christian , Le Tourneau Christophe , Ricci Francesco
Published: September 2018

e12592

Background: During last decade, therapeutic arsenal has expanded for metastatic breast cancer (mBC), but few data are available about mTNBC, a poor prognosis subtype. In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data. This base represents a great opportunity to update the outcomes and the treatment practice patterns of this population. Methods: The ESME-mBC database was built from information systems, treatment databases and patients’ electronic files including quality control processes. All pts who initiated treatment for mBC between 01-Jan-2008 and 31-Dec-2014 were selected. The primary objective of this study was to assess overall survival (OS) of mTNBC pts. TNBC status was defined as ER and PR < 10% in both primary and metastatic disease, as well as the absence of overexpression or amplification of HER2. The secondary objectives were to describe the characteristics of this population, clinical management (duration and sequence of treatments) and to evaluate the prognostic value of several clinical factors (age, distant disease free interval, location and number of metastatic sites) Results: Among 16703 pts in the ESME-mBC database, 2368 (14%) had mTNBC. Median OS over this time period was 14.8 months (95% CI 14-15.6). Median age at diagnosis of mBC was 57 years. For the pts who relapsed, median metastasis free interval was 24 months, while 25.5% of the pts were de novo metastatic. 61% of the pts presented visceral metastasis and 12% had cerebral metastasis as first metastatic site. The pattern of metastatic involvement (visceral and cerebral) and a short metastasis free interval ( < 24 months) were the most important prognostic factors in multivariate analysis. The description of treatment sequences (duration, prognostic value) will be presented. Conclusions: In this real-life setting database, mTNBC remain of poor prognosis despite a trend for a better OS than the historical data available (12-13 ms). This TNBC ESME cohort is one of the largest available and offers an updated assessment of the outcomes of this population.
Genetic counseling to outpatient cancer population.
Authors: Ce Coelho Juliano , Trasel Henrique de Araujo Vianna , Koech Bruno Lopes , Oliveita Netto Cristina , Azevedo Sergio J , Ashton-Prolla Patricia
Published: September 2018

e13009

Background: Recent advances in genetics and molecular biology have made possible to define the hereditary risk of certain diseases. About 10% of cancer are due to a hereditary syndrome and increasing access to genetic testing allows us to identify people or families at risk. Methods: A multidisciplinary team composed of clinical oncologists and geneticists retrospectively evaluated all cancer patients referred to the outpatient clinics of the Hospital de Clínicas de Porto Alegre Cancer Center between October 1st, 2014 and July 31st, 2015. Epidemiological data, pathological examination and family history of cancer recorded in the electronic database at the first visit to the oncologist were analyzed. Results: A total of 708 patients were analyzed. 44 (6.21%) patients were identified and referred for genetic evaluation by the clinical oncologist. Another 85 (12.0%) patients were identified by the multidisciplinary team, completing a total of 129 (18.22%), patients that should be evaluated to the presence of a hereditary syndrome. 164 (23.16%) patients could not be evaluated by the multidisciplinary team because insufficient data were recorded especially those related to family history of cancer. The main diagnosis that indicated genetic evaluation were colorectal cancer (47 cases - 36.43%), breast cancer (36 cases - 27.90%) and ovarian cancer (8 cases - 6.20%). Conclusions: A multidisciplinary evaluation of the oncologic patient is mandatory. Few patients are referred to a genetic counseling and 1 out of 4 patient could not be evaluated because there was missing data in the medical records. A precise genetic evaluation can identify patient / families at risk to develop cancer, allowing the development of cancer prevention strategies in this high-risk population.
Prevalence of BRCA1/2 mutations among an Irish cohort unrestricted by testing eligibility thresholds.
Authors: Conroy Michael , Gallagher David James , Farrell Michael P.
Published: September 2018

e13013

Background: Diagnostic criteria for BRCA1/2 genetic testing vary worldwide. Different eligibility thresholds for testing are used in different healthcare systems. In the public system in Ireland, this threshold is based on the Manchester Score (MS), with a score of ≥16 (approximately 10% likelihood of BRCA1/2 mutation) required for testing. Individuals unaffected by cancer are not eligible for diagnostic testing. Testing is also available privately by self-paying. We reviewed all self-pay patients in Ireland who were unrestricted by national guidelines. Methods: We performed a retrospective chart review of results from BRCA1/2 genetic testing in the Mater Private Hospital genetics clinic. Outcomes were recorded as ‘positive’, ‘wild type’ or ‘variant of uncertain significance’ (VUS). Results: 276 patients underwent testing between 2011 and 2016. 203 were affected with a median age of diagnosis of 48 (range 14-76), and 73 were unaffected individuals with a median age of 45 (range 30-74) at testing. 103 affected patients had a MS of ≥ 16: 7(6.8%) tested positive for BRCA1 mutation and 11(10.7%) tested positive for a BRCA2 mutation. Seven (6.8%) had a VUS characterised. 100 affected patients had an MS of <16: 3(3%) tested positive for a BRCA1 mutation and 5(5%)tested positive for a BRCA2 mutation. Eight (8%) had a VUS identified. 39 unaffected individuals had a MS ≥ 16: 6(15.4%) tested positive for a BRCA1 mutation, and 1(2.6%) for a BRCA2 mutation. 5(12.8%) had a VUS. 34 unaffected patients had an MS of <16: 2 (5.8%) tested positive for a BRCA2 mutation and 1 (2.9%) had a VUS. A total of 134 patients had a MS<16, and the prevalence of BRCA1/2 mutation in this group was 7% (n=10). Conclusions: The mutation detection rate was higher than expected in unaffected individuals and individuals belonging to families with MS < 16. Scoring systems such as the MS help to prioritise resources but miss many BRCA1/2 mutation carriers. [Table: see text]
Clinical actionability of germline testing in patients with limited colorectal polyps.
Authors: Rohanizadegan Mersedeh , Aldubayan Saud H , Giannakis Marios , Mu Xinmeng Jasmine , Nishihara Reiko , Qian Zhi Rong , Nowak Jonathan , Cao Yin , Liu Li , Song Mingyang , Chan Andrew T. , Garraway Levi A. , Ogino Shuji , Fuchs Charles S. , Van Allen Eliezer Mendel
Published: September 2018

e13027

Background: As classic adenoma-carcinoma sequence is the main process underlying most colorectal cancer (CRC), early detection and removal of colorectal adenomas is crucial in preventing CRC. Although adenomatous polyps are usually sporadic, several inherited CRC syndromes such as Familial adenomatous polyposis, MUTYH-associated polyposis and Lynch syndrome can present initially with colon polyps. The identification of germline defects in patients with colon polyps is thus critical for proper cancer risk counseling and CRC prevention. Current guidelines recommend germline testing for patients with more than 20 polyps or those with more than 10 polyps and a family history of CRC. However, the diagnostic yield of germline testing on otherwise healthy individuals with 10 or fewer colon polyps has not been well studied. Here, we performed a pilot study to evaluate the clinical actionability of germline genetic testing on these patients. Methods: A total of 13 cancer-free adults, who presented with colon polyps (n < 10) and who otherwise were not selected based on age of onset or family history underwent germline Exome Sequencing. Variants in 13 well-established CRC risk genes ( APC, CHEK2, MYH, MLH1, MSH2, MSH6, PMS2, NTHL1, BMPR1A, SMAD4, PTEN, STK11, TP53) were evaluated for pathogenicity. Results: A total of 13 patients (12 male, 1 female) were evaluated. The median age of presentation was 69 (range 49 to 88). The median number of adenomatous colon polyps was 1 (range 1 to 8). Two (15.4%, 95% CI = 1.9 - 45.4, Binomial Exact) patients had at least one disruptive mutation in the examined genes. One of these patients had a truncating mutation in APC (p.Arg216*) and presented with two tubulovillous adenomas at age 49. The second patient had 8 adenomas in distal colon and rectum at age 64, and harbored a known pathogenic mutation in MSH6(p.Arg1035*). Conclusions: This pilot study provides evidence that a relatively high percentage of patients presenting with a few colon polyps may have inherited defects in highly actionable genes. If validated in larger cohorts with appropriate population controls, these findings may influence the clinical care of such patients and their families and suggest germline molecular testing in those patients.
Family history of breast cancer in non-BRCA male breast cancer: A case-control study.
Authors: Calip Gregory Sampang , Exten Katherine Rebecca , Rauscher Garth H , Brown Krystal , Bernhisel Ryan , Kidd John , Saam Jennifer , Lancaster Johnathan , Hoskins Kent
Published: September 2018

e13032

Background: Approximately 85% of male breast cancer (MBC) patients test negative for a BRCA mutation, and the role of genetic predisposition is unclear. Cancer risk counseling for unaffected relatives of BRCA-negative MBC patients relies on accurate cancer risk estimates, but there is limited data on the risk of breast cancer (BC) for relatives of these men. We characterized the association between MBC and family history of BC in patients who test negative for BRCA mutations in order to facilitate cancer risk counseling and to explore the possibility of unidentified MBC susceptibility alleles. Methods: We performed a case-control study of patients who had full length sequencing and large-rearrangement analysis for germline mutations in BRCA1/2 or the mismatch repair (MMR) genes at a commercial laboratory from 2006-2012. Cases were MBC patients who tested negative for a BRCA1/2 mutation (n = 3,647); controls were male colon cancer patients who tested negative for mutations in MMR genes (n = 4,269). Information on family history of BC was ascertained from test request forms completed by the ordering healthcare provider at the time of testing. Unconditional multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between family history of BC in first- (FDR) and second-degree relatives (SDR) and MBC with adjustment for potential confounders (age, ethnicity, year of testing). Results: Compared to controls, MBC cases had higher odds of BC in a FDR or SDR (OR = 4.7; 95% CI 4.1, 5.3). Associations were strongest for family history of BC in 1 female FDR (OR = 3.9; 95% CI: 3.3, 4.6), ≥2 female FDR (OR = 7.5; 95% CI 5.0, 11.4), BC in a FDR < 45 years old (for cases diagnosed < 45, OR = 6.9; 95% CI 3.9, 12.4), a male FDR or SDR with BC (OR = 17.9; 95% CI 7.6, 42.1), and both a male and female FDR or SDR with BC (OR = 15.7; 95%CI 4.4, 55.3). Conclusions: MBC patients who test negative for a BRCA mutation have significantly higher odds of reporting family members affected by breast cancer, particularly with affected FDR < 45 years old, multiple affected relatives, and male relatives with BC. This data can guide risk counseling in MBC families, and suggests the existence of unidentified MBC susceptibility alleles.
Ultrasound-guided mammotome for diagnosis and minimally invasive excision of mammary clustered calcifications.
Authors: Hu Wei
Published: September 2018

e13034

Background: To validate the ultrasound-guided vacuum-assisted breast biopsy system (Mammotome) for diagnosis and minimally invasive excision of calcification in breast. Methods: In 20 patients, breast calcification lesions diagnosed by mammography were excised by ultrasound-guided Mammotome system with 8-gauge probe. The samples were taken mammography and followed by pathological examination. Results: All lesions were removed accurately and thoroughly with satisfactory cosmetic outcomes. No clinically significant hematoma developed. Each mass was resected through 9.15±2.70 cores on average over a mean of 11.65±3.88 minutes. Two cases of them were histologically diagnosed as ductal carcinoma in situ and 8 cases were fibroadenoma and 10 cases were adenosis. Conclusions: Ultrasound-guided Mammotome system can profit to diagnose and treat breast calcification lesions which is ultrasound positive. Ultrasound detection rate of microcalcifications is up to the instrument resolution and the operator's experience and patience.
Influence of insulin therapy for type 2 diabetes mellitus on cancer incidence.
Authors: Cho Oyeon , Oh Young-Taek , Chun Mison , Noh O Kyu , Heo Jaesung
Published: September 2018

e13036

Background: This study aimed to investigate the influence of insulin therapy for type 2 diabetes mellitus (T2D) on cancer development. Methods: We evaluated 4780 patients with T2D, treated at our institution, from 1994-2006, after excluding patients with 1) preexisting cancer or cancer within 1 year after T2D registration, 2) renal transplantation, and 3) follow-up period of < 5 years. The following information was collected from the patients’ electronic medical records: age; sex; registered date of T2D and cancer; last visit; use of metformin, insulin, and medications for microvascular complications; and start date of using insulin in the first year after cohort entrance. Insulin users were stratified according to insulin start date and complication as follows: < 3 months with (462 patients) or without complications (526 patients), ≥3 months with complications (852 patients) or without complications (1249 patients). The standardized incidence ratio (SIR) was calculated using the expected age-standardized incidence rate in Korea. The adjusted hazard ratio (AHR) of insulin was estimated for evaluation of all-year cancer risk and time interval of 3 years from cohort entrance. Results: SIR was > 1 in all cancer types except laryngeal and esophageal cancers. The median follow-up was 12 years (interquartile range: 9–15 years), and 679 events occurred. Insulin users had a significantly higher risk of all-time cancer. The patients with insulin use for ≥3 months without complications had a continuously increasing cancer risk 2–3, 4–6, 7–9, 10–12, and 13–15 years from cohort start (AHR [95% confidence interval {CI}]: 2.2 [0.91–5.3], P= 0.081; 2.39 [1.07–5.32], P= 0.0335; 1.98 [1.35–2.9], P= 0.0005; 2.41 [1.52–3.81], P= 0.0002; and 1.6 [0.6–2.83], P= 0.1077, respectively), while the rest did not. This was significantly associated with stomach, colorectal, lung, liver, pancreatic, and bladder cancers (AHR [95% CI]: 6.09 [2.58–14.4], P= 00001; 2.49 [1.22–5.07], P= 01188; 3.36 [1.18–9.51], P= 0.02265; 14.8 [1.97–110], P= 0.0088; 14.6 [1.88–113], P= 0.0103; and 10.4 [2.38–45.6], P= 0.00186, respectively). Conclusions: Incidences of gastrointestinal, lung, and bladder cancers could be increased in new insulin users without complications.
Risk factors associated with mortality among women with breast cancer in Haiti.
Authors: Bernard Joseph , Pascal Garvey Rama , Raymond Sarah Cassandra , DeGennaro Vincent
Published: September 2018

e13069

Background: According to recent estimations of GLOBOCAN 2012, breast cancer is the 2ndmost common cancer among Haitian women. This study aims to describe the epidemiology of breast cancer at a Haitian hospital and to determine the factors associated with mortality. Methods: A retrospective chart review was conducted on women treated for breast cancer at the Innovating Health International Cancer Center, in Port-au-Prince, Haiti. All charts with complete information from 2014 and 2015 were included. Charts were reviewed to collect key variables related to breast cancer. Odds ratios were calculated and Mantel-Haenszel Chi-square test was used to identify the factors associated with mortality. Results: Among the 289 charts reviewed, 275 were selected for this study. The mean age is 51.82 years-old [20 - 100]. 81.1% of the patients had stage III or IV breast cancer at their first consultation. 92% of the women were diagnosed with invasive ductal carcinoma. Of the 165 cases tested for hormone receptor status, 54.5% were ER-positive, 31.5% were triple negative and 12.1% were HER2-enriched. The mortality rate is 24.4%. The odds of dying from breast cancer was significantly higher among women who had their menarche before 15 years old [Odds Ratio (OR) = 4.2; P = 0.02], stage III or IV breast cancer (OR = 3.7; P = 0.01), triple-negative or HER2-positive breast cancer (OR = 2.5; P = 0.01). Mortality was significantly lower among women who benefited from hormone therapy (OR = 0.22; P < 0.01). Conclusions: Breast cancer is often diagnosed at late stages in Haiti, which increases mortality. Women with ER-positive breast cancer survive significantly more than those with HER2-positive or triple-negative breast cancer, mainly due to the availability of hormone therapy and the absence of trastuzumab. A national awareness and screening program has to be implemented to educate Haitian women on breast cancer and increase early diagnosis. As an essential medicine in oncology according to the World Health Organization (WHO), biosimilar trastuzumab needs to be available to increase the survival of patients with HER2-positive breast cancer.
Association of body mass index (BMI) and stage in patients with non-small cell lung cancer harboring KRAS mutations.
Authors: Bhatt Ananta , Mueller Catherine , Gui Jiang , Dragnev Konstantin H. , Tafe Laura J.
Published: September 2018

e13071

Background: Body mass index (BMI) is inversely associated with lung cancer risk, particularly in former or current smokers. KRAS mutant non-small cell lung cancer (NSCLC) has been shown to be highly associated with smoking status. Therefore, we sought to investigate the association of BMI and stage in a cohort of patients with KRAS mutant NSCLC. Methods: Patients with KRAS mutant lung cancer who underwent tumor genotyping using next generation sequencing testing were identified. BMI( kg/m2 ) was categorized as: Underweight ( < 18.5), normal weight (18.5 – 24.9), overweight (25-29.9) and obese (≥30). Chi-square and t-tests were performed to test association between stage (I vs. II+) and BMI (4 categories), and stage and BMI as a continuous variable, respectively. Results: From 5/2013 to 9/2016, 201 patients with KRAS mutant NSLC were identified. Of these, 178 (88.6%) were current or former/ever smokers (SM) and 23 (11.4%) were never smokers (NS). In the SM group, 114 were female and 64 male with a median age at diagnosis of 66.5 years (range 45-93). In the NS group, 15 were female and 8 male with a median age at diagnosis of 71.5 years (range 51-92) (age for NS vs. SM p = 0.0439). Fifty-two (25.9%) patients presented with stage I disease, 149 (74.1%) presented with advanced (stage II-IV) disease. There was no significance in the BMI at diagnosis of SM vs. NS or by sex. There was a difference (p = 0.0430) in the BMI between patients with stage I disease (mean 28.6) and patients with stage II or greater disease (mean 26.6). This was also seen in SM with stage I vs. II+ disease (p = 0.0417); however, this was no longer significant in SM when broken out by sex or in NS alone. Conclusions: We identified a significant difference in BMI in patients with KRAS mutant NSCLC with stage I vs. advance stage disease, with a higher BMI associated with early stage disease at diagnosis. The lower BMI in patients with more advanced stage may be a confounding variable explained by comorbidities, and the lung cancer itself. It is unlikely that treatment effects were a factor as the KRAS testing was done prior to initiating therapy. Further studies looking at BMI and survival analysis in patients with mutant KRAS NSCLC are warranted.
Complementary and alternative medicine use and hormonal therapy initiation in women with hormone receptor-positive breast cancer: The BQUAL study.
Authors: Greenlee Heather , Neugut Alfred I. , Shi Zaixing , Hillyer Grace , Buono Donna , Mandelblatt Jeanne S. , Roh Janise M. , Ergas Isaac J. , Kwan Marilyn L. , Lee Marion , Tsai Wei-Yann , Lamerato Lois E. , Kushi Lawrence H. , Hershman Dawn L.
Published: September 2018

e13097

Background: Use of complementary and alternative medicine (CAM) has been associated with initiation of breast cancer chemotherapy.We examined the association of CAM use with initiation of hormonal therapy in women with hormone receptor-positive (HR+) breast cancer. Methods: In aprospective cohort study designed to examine predictors of breast cancer treatment initiation and adherence, 699 women with non-metastatic stage I-III breast cancer and aged < 70 years were recruited from Kaiser Permanente Northern California during 2006-2010. Baseline interviews assessed current use of five CAM modalities (dietary supplements: vitamins/minerals, herbs/botanicals, other natural products; mind/body therapies: mind-body self-practice, mind-body practitioner-based). Based on electronic pharmacy records, hormonal therapy initiation was defined as ≥2 prescriptions of ≥30 pills of any hormonal therapy drug within 1 year after diagnosis. Multivariable logistic regression analysis examined a priori hypotheses testing whether current CAM use was associated with hormonal therapy initiation, adjusted for demographic, tumor characteristics, and cancer treatment. Results: Of the 699 participants,552 were diagnosed with HR+ breast cancer. Among the 552 women with HR+ breast cancer, 494 (89%) used at least 1 modality of CAM, 414 (76%) used dietary supplements, and 391 (71%) used mind/body therapies. Within 1 year after diagnosis, 481 (87%) participants initiated hormonal therapy. The rate of initiation was comparable between CAM users and non-users (87% vs. 86%). In multivariable analyses, baseline overall CAM use was not associated with initiation of hormonal therapy. However, vitamins/minerals users were more likely to initiate hormonal therapy compared to non-users (OR = 1.87, 95% CI: 1.04, 3.51). Conclusions: CAM use was high among early stage HR+ breast cancer patients. Overall, use of CAM was not associated with hormonal therapy initiation. Current use of vitamins/minerals was associated with higher initiation rate of hormonal chemotherapy.
Incorporation of NCCN guideline information in NGS-based cancer testing panel design.
Authors: Leamon John
Published: September 2018

e13099

Background: NGS has revolutionized medical genomics. However, challenges remain in data analysis and interpretation due to the sheer volume of sequencing data produced. As such, optimized panel design is essential to effectively reduce data analysis burden while ensuring inclusion of critical variants. Ideally a panel should target biomarkers of clinical actionability, such as inclusion an active clinical trial or in the NCCN guideline. As information constantly evolves it is difficult if not impossible for any individual laboratory to capture and reflect real-time view in their panel design. Here we present an objective process for biomarker panel design utilizing a comprehensive database to identify key variants with clinical actionability. Methods: QIAGEN has built a bioinformatics database that comprehensively captures relevant scientific and clinical literature, curated through automated and manual processes. This database covers critical information including the NCCN guideline used by laboratories to interpret their sequencing results. We used this database to design an NGS biomarker panel focused on hotspot mutations clinically associated with clear clinical evidence in breast, lung, colon, breast/ovarian, melanoma cancers. Coverage of key variants is then compared with alternative commercial panels. Results: Comparative analysis indicated the QIAGEN panel covered substantially more relevant variants than either of the other ones. Over 100 variants are unique to the QIAGEN Panel. One such example is a point mutation in ERBB2 (S301F) which occurs in Non-Small Cell Lung Cancer (NSCLC) and is referenced in the NCCN guideline. Such finding would be missed if a sample harboring this mutation is tested with alternative panels. Conclusions: This study supports the value of utilizing comprehensive mutational databases in gene panel design. Specifically, the QIAGEN gene panel designed using this approach compared favorably against alternative commercial panels, employing fewer amplicons to provide superior coverage of variants with known actionability. These results demonstrate that optimal panel design permits improves the effectiveness and efficiency of NGS biomarker testing.
Durable complete responses observed in IDH1 mutated high grade glioma at first recurrence undergoing treatment with Toca 511 and Toca FC.
Authors: Cloughesy Timothy Francis , Ostertag Derek , Landolfi Joseph C. , Walbert Tobias , Vogelbaum Michael A. , Elder J. Bradley , Bloomfield Steven , Carter Bob , Chen Clark , Kalkanis Steven N. , Kesari Santosh , Lai Albert , Lee Ian , Liau Linda M. , Mikkelsen Tom , Nghiemphu Phioanh Leia , Piccioni David Eric , Jolly Douglas J. , Gruber Harry E. , Das Asha
Published: September 2018

e13504

Background: Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to cell division requirements for virus integration into the genome and defects in innate and adaptive immune responses found in cancers that support virus replication. Toca 511 spreads through cancer cells and stably delivers the gene for an optimized yeast cytosine deaminase that converts the prodrug Toca FC (an investigational, extended-release formulation of 5-fluorocytosine) into 5-fluorouracil (5-FU). 5-FU kills infected cancer cells that are dividing, diffuses and kills surrounding cancer cells as well as myeloid derived suppressor cells and tumor associated macrophages, thus reestablishing immunity to tumor. Methods: In this phase 1 trial (NCT01470794), ascending doses of Toca 511 were injected into the resection bed of patients with recurrent high grade glioma undergoing resection, followed by oral administration of courses of Toca FC 5-7 weeks after Toca 511 injection. Additional cohorts included combination of Toca 511 & Toca FC with bevacizumab or lomustine. Results: Objective responses (ORs) are observed in IDH1 wildtype (wt) and mutant (mt) phenotypes, including 3 complete responses (CRs) (2 IDH1 mt and 1 IDH1 wt) and 2 partial responses (2 IDH1 wt) for patients treated with Toca 511 & Toca FC, and 1 CR (1 IDH1 mt) for a patient treated with Toca 511 & Toca FC and bevacizumab. ORs are observed 6-19 months after Toca 511 injection and are consistent with an immunologic mechanism. Median time to initial response is 9.2 months; median duration of response (mDOR) is 25.2 months. Excluding the combination cohorts, mDOR is 26.7 months. All responders are alive 21.2+ to 42.6+ months, suggesting a correlation of OR and OS. An additional radiologic CR is observed in 1 IDH1 mt patient at 1st recurrence who received intravenous Toca 511 plus injection into the resection bed. All 4 IDH1 mt patients treated at 1st recurrence had CRs. Conclusions: There may be an association between ORs and IDH1 mutation with Toca 511 & Toca FC treatment. Updated clinical benefit, molecular profiles and tumor mutational load are reported. Clinical trial information: NCT01470794.
A potential role of pemetrexed (PMTX) for the treatment (Tx) of thymidylate synthase (TS) negative primary brain tumors and systemic malignancies with CNS metastasis.
Authors: Kim Lyndon J. , Evans James J , Judy Kevin D. , Farrell Christopher , Andrews David W.
Published: September 2018

e13519

Background: Fluoropyrimidne analogue Capecitabine, a TS inhibitor, can cross blood brain barrier and has been used for the Tx of breast cancer with brain metastasis (mets). An antifolate Methotrexate (MTX), which also inhibits TS, has been used for the Tx of PCNSL secondary to it's excellent CNS penetration. MTX analogue, PMTX inhibits purine synthesis via TS and DHFR, and pyrimidine synthesis via GARFT, thus, making it a viable Tx option for CNS malignancies. Methods: We have treated 40 pts with previously heavily treated recurrent primary and systemic malignancies with CNS mets based on the molecular profiling. 26/40 pts were found to have TS negative expression (5/12 GBM, 5/5 AA, 1/1 Gr II Astrocytoma (A), 5/7 meningioma, 1/3 PCNSL, 1/2 Esthesioneuroblastoma, 1/1 chordoma, and 7/9 brain mets) and 10/26 TS negative pts were treated with PMTX. MRI was performed every 2-3 mo for tumor response. Results: Total pts: 10. M:F 6:4. Age: 48-88 yo. Median age: 61.9 yo. Tx period: 7/14–1/17. 1/1 GBM pt: stable disease (SD) x 4 mo. 1/2 AA pts: SD x 4 mo, 1/2 pts: tumor progression. 1 Gr. II A pt, SD x 7 mo. 2/2 meningioma pts: SD x 2 and 4 mo. Both pts also received concurrent cisplatin (also ERCC1 negative). 3/3 pts: squamous cell Ca of skin with skull base/brain mets responded x 24 mo, 24 mo and 3 mo respectively (1 PR and 2 SD), 2 pts: still receiving Tx. 1 pt: 26 mo reponder, died of nontumor related issue. 1/1 chordoma pt: SD x 11 mo. Toxicities: very mild except 2 pts (Gr. 3-4) who also received cisplatin. Conclusions: TS negative expression is commonly found in most of secondary malignancies with brain mets and in non-GBM primary brain tumors. PMTX appears to have a favorable efficacy for the Tx of TS negative primary and systemic malignancies with CNS mets. Albeit small cohort, overall response was 90% (PR:1, SD:8). Tx was particularly effective for squamous cell ca with brain mets and responses were durable in all spectrum. Due to favorable tolerance and response, especially in the elderly pts with squamous cell with brain mets, PMTX could be an excellent Tx option for TS negative CNS malignancies. PMTX trial for TS negative CNS malignancies should be considered.
Association of clinical phenotype and treatment history with survival in adult brainstem glioblastoma.
Authors: Nam Jooyeon , Harrison Rebecca A. , Weathers Shiao-Pei S. , Pillainayagam Clement , De Groot John Frederick , Kamiya-Matsuoka Carlos , Loghin Monica Elena , Penas-Prado Marta , Yung W. K. Alfred , Li Jing , Ferguson Sherise D. , O'Brien Barbara Jane
Published: September 2018

e13539

Background: Brainstem gliomas are rare, comprising 1-2% of malignant primary brain tumors. Brainstem glioblastoma (bGBM) often poses a therapeutic challenge due to scarcity of evidence guiding treatment, and the high rate of neurologic morbidity. We examined bGBM cases at MD Anderson Cancer Center (MDACC) to characterize the salient clinical features of bGBM, and the impact of therapy on patient survival. Methods: Adult patients with pathologically-confirmed bGBM (N = 34) treated at MDACC between June 2005 and June 2015 were identified from the neurosurgical database. Patients’ clinical, radiographic, and treatment data were extracted from the medical record. Descriptive statistics and Kaplan-Meier analyses were performed. Results: Mean age was 52.5 years (SD = 12.1) and median KPS was 80 (SD = 14.2) at time of diagnosis. Initial surgical intervention included biopsy (82.4%) and resection (17.6%). Most patients were treated with concurrent chemoradiation (N = 18, 52.9%) or sequential radiation followed by chemotherapy (N = 8, 23.5%), and the remainder had no documented post-operative anti-tumor therapy. At the time of this analysis, 82.4% of the cohort had died. Median progression free survival (PFS) was 5.8 months (SD = 6.7) and overall survival (OS) was 8.9 months (SD = 19.6). On univariate analysis, gait abnormality (p = .02), incoordination (p = .002), dysphagia (p = .04), or facial numbness (p = .01) at presentation was associated with shorter OS. KPS of ≥70 at diagnosis was significantly associated with better OS (15.6 vs 3 months, p = .001), and the patients with good functional status were more likely to receive concurrent chemoradiation. Bevacizumab was given as concurrent or adjuvant treatment in 2 and 3 cases, respectively, and did not affect OS (p = .82). Conclusions: This retrospective analysis demonstrates a significant and complex relationship between presenting clinical features, functional status and variable treatments in bGBM and survival outcomes. This evidence contributes to our understanding of bGBM, and highlights areas for further study in this malignant condition.
Tako-tsubo syndrome and use of paclitaxel.
Authors: Ionescu Dana , Stone Danielle , Stone James , Durand Jean-Bernard , Iliescu Gloria , Karimzad Kaveh , Lopez-Mattei Juan , Iliescu Cezar
Published: September 2018

e14012

Background: Vasospasm and arrhythmias are the main cardiac toxic effects of cancer treatment with Paclitaxel. Chemotherapy induced stress cardiomyopathy (SC) (Tako-tsubo syndrome) has been linked to antineoplastic agents associated with abnormal vasoreactivity. We aimed to identify if there is a causal relationship between SC and Paclitaxel administration. Methods: All cancer patients who fulfilled the diagnostic criteria for SC at MD Anderson Cancer Center over a 6–year period were included in the study. We selected and retrospectively reviewed the medical records of all the patients who had chemotherapy induced SC. Clinical presentation, ECG, laboratory data, transthoracic echocardiogram and coronary angiography results were reviewed. Results: Out of30 patients who fulfilled the diagnostic criteria for SC, 5 patients (16.6%) had SC triggered by chemotherapy. Three patients (2 females, 1 male, mean age 71.3 yo) had Paclitaxel induced SC (60%); two patients received a combination of Paclitaxel and Carboplatin for ovarian cancer, and one patient had combination of Paclitaxel and Cyclophosphamide for prostate cancer. Two patients had cardiac manifestations in the first day of Paclitaxel administration. All three patients presented with chest pain; T wave inversion was the main finding on the electrocardiography. All patients had changes in the cardiac biomarkers (BNP mean 1459.7 pg/dl, TN I mean 1.36 ng/dl, CK-MB mean 8.6 ng/dl) and significant LV dysfunction (LVEF < 50%). Characteristic apical ballooning pattern was identified in all cases from left ventriculogram. Chemotherapy was interrupted ; aspirin and beta blockers were initiated in all patients. Two patients were rechallenged with chemotherapy after 10 days, respectively 20 days after SC. None of the patients experienced recurrence of SC, nor arrhythmias while on aspirin and beta blockers. Conclusions: To our knowledge there are no published data on the association of Paclitaxel administration and SC. In cancer patients who develop acute chest pain after administration of Paclitaxel, evaluation for SC is important to exclude NSTEMI diagnosis, which can impact further cancer therapy. Cancer patients with SC whom have complete recovery may early resume cancer therapy.