bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical impact and prognostic value of 18F-fluorodeoxyglucose PET/CT in the initial staging non-small cell lung cancer at MD Anderson Cancer Center.
Authors: Takeuchi Satoshi , Khiewvan Benjapa , Swisher Stephen , Rohren Eric , Macapinlac Homer A. 
Published: March 2020

11079 Background: 18F-fluorodeoxyglucosePositron Emission Tomography/Computed Tomography (FDG-PET/CT) has an important role for Non-Small Cell lung cancer (NSCLC) management, especially in staging. Our objective was to assess stage migration, the clinical impact, and prognostic value of PET/CT in patients with NSCLC at MD Anderson Cancer Center (MDACC). Methods: We retrospectively reviewed the database from MDACC, and identified 729 NSCLC patients referred for staging between 2006 and 2011. Stage was classified using TNM classification. FDG-PET/CT and conventional imaging staging were compared with all-cause mortality and the survival rates of the respective clinical stage. The management impact of FDG-PET/CT was determined based on conventional imaging and PET/CT management plans. A change in stage was confirmed by histopathology and/or further imaging. Results: We identified 598 NSCLC patients with FDG-PET/CT and conventional imaging performed. FDG-PET/CT changed stage in 28.1 % (16.4 % upstaged, 11.7 % downstaged). Based on FDG-PET/CT, treatment plans were modified in 38 % of patients. Median progression free survival (PFS) and overall survival (OS) was significantly worse in patients with management impact of FDG-PET/CT than patients without impact (PFS, 24.9 v 60.6 months, P < 0.001; OS, 66.7 v 115.9 months, P < 0.001). Multivariate analysis showed that the impact of FDG-PET/CT impact on management was an independent prognostic factor for DFS (hazard ratio [HR] = 2.08; 95 % CI, 1.63 to 2.65; P < 0.001) and OS (HR = 2.16; 95 % CI, 1.56 to 2.99; P < 0.001). Stage migration from stage I (40/249 patients) showed worse outcome than those without change (PFS, 21.0 v 60.0 months, P < 0.001; OS, 64.7 v 115.9 months, P = 0.003). Conclusions: FDG-PET/CT has major role in NSCLC management. The added staging information provided by FDG-PET/CT as compared to conventional imaging resulted in a change in management in more than one third NSCLC patients. FDG-PET/CT is also a powerful tool for outcome prediction. Even in patients diagnosed as stage I by conventional method, FDG-PET/CT at initial diagnosis may have an impact on survival.
Prognostic significance of the maximal value of the baseline standardized uptake value on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for predicting pathologic malignancy of operable breast cancer.
Authors: Kadoya Takayuki , Aogi Kenjiro , Kiyoto Sachiko , Kanno Emiko , Akimoto Etsushi , Emi Akiko , Shigematsu Hideo , Masumoto Norio , Sugawara Yoshifumi , Okada Morihito 
Published: March 2020

11111 Background: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is potentially useful in predicting prognosis of breast cancer patients. Methods: 344 breast cancer patients (mean age: 58.0 ± 12.5) with clinical stage IxIII between January 2006 and December 2011, were prospectively evaluated (median follow-up period: 52.0 months). Patients underwent a whole-body FDG PET/CT before operation. The maximal value of the baseline standardized uptake values (SUVmax) were assessed for predicting disease free survival (DFS). For the evaluation of relationship between SUVmax values and prognostic factors such as hormone receptors, human epidermal growth factor receptor 2 (HER2), nuclear grade, lymph node metastasis and tumor size, statistical analyses were performed using Student t test and log-rank test, and p values of less than 0.05 were considered to indicate statistically significant differences. Results: Clinical stage included were I (n =194), II (n=134) and III (n=16). Tumors with estrogen receptor (ER) positive were 292 (84.9%) and negative were 52 (15.1%). Patients were divided into two groups according to cut-off SUVmax established on the basis of receiver operating characteristic analysis (≤3.0 vs >3.0, AUC=0.713). There was a significant difference in DFS between two groups (p=0.001) and, hormone receptor, HER2, nuclear grade, lymph node metastasis were found strong relation to SUVmax values. SUVmax and ER status were predictive factors with multivariable analysis using cox proportional hazard regression model (p=0.033 and p=0.004, respectively). Conclusions: SUVmax on FDG PET/CT before operation has a predictive value for high-grade malignancy and prognosis in operable breast cancer. [Table: see text]
Targeting radiation resistance in p53 mutant tumors with AKT inhibitors.
Authors: Abraham Aswin George , Hamilton Garth , O'Neill Eric 
Published: March 2020

11115 Background: Increasing our understanding of how resistance to radiation occurs, helps us develop more efficient and personalised radiotherapy treatments for cancer patients. Through molecular dissection of events that drive tumour initiation and progression, we have uncovered a functional connection between the most frequent oncogenic mutations that are likely to contribute to therapeutic resistance in 30% of all human tumours. Mutations activating the "AKT" signalling pathway and inactivation of the “TP53” tumour suppressor gene are common mechanisms that cancer cells require to proliferate and escape pre-programmed cell death. We find that in combination these events lead to therapeutic resistance that is reversible by the AKT clinical candidate, MK-2206 and the PI3K inhibitor PI-103. Methods: Using a combination of in vivo and in vitro techniques we have tracked the molecular mechanism for AKT mediated resistance to treatment in solid tumours. This has helped us to simultaneously derive potential biomarkers that could highlight where the greatest efficacy may be achieved in clinical practise. Results: Tumours employ many strategies to inactivate p53; however sequence mutations that result in mutant p53 protein (p53mut) are most often observed. p53mut tumours not only fail to respond to DNA damaging therapy, but are also described to promote therapeutic resistance by dominant negative suppression of p53 dependent promoter activity. We demonstrate that AKT inhibitors- and as proof of concept, the clinical candidate AKT inhibitor, MK-2206, and PI3K inhibitor, PI-103, are effective in treatment of mice with therapeutically resistant tumours with elevated AKT and carrying p53mut. AKT inhibition promotes reduced cellular levels of p53mut via a novel mechanism and promoted re-engagement of cell cycle arrest, senescence and increased sensitivity to ionising radiation in both in vivo and in vitro systems. Conclusions: We show that AKT inhibitors sensitise xenografts carrying p53 mutations to DNA damaging therapy. We have also been identifying potential molecular markers to select the cohort of patient most likely to benefit from this treatment.
Long-term quality of life in patients with breast cancer according to sentinel lymph node biopsy or axillary lymph node dissection: A multicenter cohort study with 6 years follow-up.
Authors: Dabakuyo Tienhan Sandrine , De Gournay Emmanuel , Guyomard Aurelie , Boulet Stephanie , Arveux Patrick , Causeret Sylvain , Gouy Sebastien , Padeano Marie-Martine , Loustalot Catherine , Smail Marc , Sauzedde Jean-Marc , Combier Jean-Philibert , Chevillote Patrick , Rosburger Christian , Bonnetain Franck , Coutant Charles , Fraisse Jean 
Published: March 2020

1114 Background: the aim of this study was to assess long term quality of life (QoL) over a period of 6 years in women with a breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), or SLNB followed by ALND. Methods: The EORTC-QLQ-C30 and the EORTC-QLQ-BR-23 questionnaires were used to assess QoL before surgery, just after surgery, 6, 12 and 72 months later. The Kruskal Wallis test with the Bonferroni correction was used to compare scores. A mixed model analysis of variance for repeated measurements was then applied to assess the longitudinal effect of surgical modalities on QoL. Results: Five hundred and eighteen BC patients were initially included. The median follow-up was 6 years. During the follow-up, 61 patients died. None of the patients of the SLNB group has developed lymphedema during follow-up and the relapse rate was not different between the different groups (p=0.62). Before surgery, global health (GHS) (P = 0.5226) and arm symptoms (BRAS) (P = 0.9902) QoL scores were similar whatever the surgical procedure. BRAS score (p=0.0001) was better in the SNLB group 72 months after surgery. Moreover, compared to ALND patients, patients treated with SLNB had fewer arm symptoms with the follow-up. In addition, body image (P = 0.0005), upset by hair loss (P = 0.0045), systemic therapy side effects (P = 0.0097) and future perspective (P = 0.0375) QoL dimensions remained better 5 to 6 years after diagnosis in patients treated by SLNB. Conclusions: Long term follow-up showed that, SLNB is a safe and acceptable accurate method associated with less morbidity than ALND.
Incidence and characteristics of breast cancer following a diagnosis of ductal carcinoma in situ.
Authors: Lei Xiudong , Dawood Shaheenah S. , Albarracin Constance T. , Dent Rebecca , Gupta Sudeep , Cortes Javier , Mittendorf Elizabeth Ann , Buchholz Thomas A. , Gonzalez-Angulo Ana M. 
Published: March 2020

1131 Background: Recent data indicate that the incidence of DCIS is rising. The purpose of this retrospective population based study was to examine incidence of and factors that contribute to the development of a subsequent breast primary. Methods: Using the SEER registry we identified female pts with a primary DCIS diagnosed between 1990 to 2005. Pts who had an invasive or in situ malignancy diagnosed prior to a diagnosis of DCIS were excluded. Cumulative incidence of a subsequent breast primary (invasive/non invasive) was estimated and compared across groups using the Chi-square test. Multivariable logistic regression models were then fitted to determine factors that could predict for the development of a subsequent breast primary. Results: 96,130 pts were identified of whom 14,573 (15.2%) had subsequent primaries. 9,037 (62%) pts had a subsequent primary in the breast of which 5,915 (65.5%) pts had an invasive breast cancer. Among pts who developed an invasive breast cancer 68% had hormone receptor positive disease, 59% had grade I/II disease and 80% had stage I/II disease. 2 and 5-year cumulative incidence of developing a subsequent breast primary was 3.2% and 5.9% respectively. 2 and 5-year cumulative incidence of developing a subsequent invasive breast primary was 1.6% and 3.4% respectively. 5-year cumulative incidence of developing a subsequent breast primary among pts who were of white, black and other race was 5.8%, 6.8% and 6.1% respectively (P<0.001). In the multivariable logistic model the probability of developing a subsequent breast primary decreased with each increasing year of diagnosis of DCIS (OR 0.91, 95%CI 0.91-0.92, p<0.001). Other factors that predicted for the development of a subsequent breast primary included younger age at diagnosis, non-white race and lack of surgical or radiation therapy for DCIS. Conclusions: Our results indicate that a significant proportion of pts with a diagnosis of DCIS go on to develop invasive breast cancer and may warrant further investigation to determine biological risk factors, appropriate screening procedures and possible interventions to decrease incidence. Target groups that may benefit include pts who are young and of non white race at the time of diagnosis of DCIS.
Immediate tissue expander breast reconstruction following mastectomy in pregnancy-associated breast cancer.
Authors: Zabicki Calvillo Katherina , Caragacianu Diana L. , Chun Yoon S. , Caterson Stephanie , Bellon Jennifer Ruth , Wong Julia S. , Troyan Susan , Rhei Esther , Dominici Laura Stewart , Economy Katherine E. , Tung Nadine M. , Schapira Lidia , Meisel Jane L. , Partridge Ann , Mayer Erica L. 
Published: March 2020

1133 Background: Management of pregnancy-associated breast cancer (PABC) requires balancing benefits of therapy with potential risks to the developing fetus. Surgical management can be influenced by gestational age of fetus and tumor stage. Minimal data describe surgical and obstetrical outcomes after mastectomy with immediate breast reconstruction (IR) in a pregnant patient (pt). Methods: Pts who underwent IR after mastectomy were identified within a multi-institutional PABC cohort. Retrospective chart review was performed for outcomes including adverse intraoperative events, immediate postoperative complications, gestational age at delivery and fetal weight. Other parameters evaluated included stage at presentation, duration of surgery, and use of delayed reconstruction in pts who did not receive IR. Results: Within a cohort of 79 PABC pts, 25 (32%) had mastectomy while pregnant, 8 (32%) of whom had IC; 17 (68%) did not undergo IR. Mean gestational age at time of IR was 16.6 weeks (range 10-30) and all IR utilized tissue expander (TE) placement followed by permanent implant placement in 7 pts. In the IR cohort, 1 (12.5%) pt was stage 0, 3 (37.5%) stage I and 4 (50%) stage IIB. There were no intraoperative or immediate postoperative surgical complications. The mean duration of surgery was 198 min with IR (7 pts) vs. 157 min without IR (available for 12 pts). All women who underwent IR delivered at, or close to, term infants of normal birthweight. One pt had pre-term labor after surgery at 29 weeks which resolved with tocolysis. Mean gestational age at delivery was 37.3 weeks in the IR cohort vs. 36.3 weeks in the non-IR cohort. No fetal abnormalities or major obstetrical complications were seen after IR. Post-mastectomy radiation (PMRT) was provided after pregnancy in 2 pts (25%) in the IR cohort and cosmetic outcome was not adversely affected. Conclusions: This report represents one of the largest series describing IR after mastectomy in PABC. Results suggest immediate tissue expander placement after mastectomy may increase duration of surgery but does not lead to adverse obstetrical or fetal outcomes. IR with tissue expanders may preserve reconstructive options when PMRT is indicated.
Preliminary analysis of risk factors associated with peritoneal carcinomatosis (PC) after prophylactic bilateral salpingoophorectomy (PBSO) in patients with a BRCA mutation.
Authors: Stjepanovic Neda , Carrasco Estela , Gadea Neus , Gil Antonio , Perez M. Assumpcio , Diaz Berta , Franco Silvia , Cabrera Silvia , Garcia Angel , Castellvi Josep , Díez Orland , Vilaro Marta , Balmaña Judith 
Published: March 2020

1509 Background: Women with a BRCA1 or BRCA2 mutation are at high risk of developing ovarian carcinoma (OC) and a residual risk of PC after PBSO has been reported. We aimed to analyze the incidence of PC after PBSO and the clinical, pathological and molecular risk factors associated to PC in our series. Methods: Between April 2005 and December 2012, 100 patients with BRCA1 or BRCA2 mutation (50 each) underwent PBSO and were followed in the High Risk Clinics for the development of PC. PBSO pieces were submitted to pathological examination for presence of pathological and molecular risk factors like in situ or invasive Fallopian Tube Carcinoma (isFTC, inFTC) and p53 signature. Patients’ medical charts included in the High Risk Clinics Database were revised retrospectively for clinical, pathological and molecular characteristics. We analyzed the incidence of PC and the odds ratio (OR) for PC after PBSO in univariate analysis. Results: Overall, 2 patients (2%, 1 BRCA1, 1 BRCA2) were found to have isFTC, while 5 out 34 had a positive p53 signature (15%, 1 BRCA1, 4 BRCA2). With a median follow-up of 40 months (1-90) since PBSO, 2 patients developed PC (2%, both BRCA2). They underwent PBSO at age of 63 and 64 years and developed the PC 2 and 9 years after. One had a history of isFTC with p53 signature and 5 children, while the other had a prior history of bilateral breast cancer and no children. None had a family history of OC. Performing PBSO at an age older than 50 years was associated with an OR 8.56 (3.29-22.27) of PC. Conclusions: Fifteen and 2% percent of our patients had a positive p53 signature or an occult isFTC in the PBSO piece. Our analysis suggests that delaying PBSO to women older than 50 years may be associated with a higher risk of PC. Further analysis in a larger cohort is warranted.
Breast cancer mortality among users of cholesterol-lowering drugs.
Authors: Murtola Teemu Johannes , Visvanathan Kala , Artama Miia , Vainio Harri , Pukkala Eero 
Published: March 2020

1514 Background: Breast cancer is a common malignancy and cause of cancer death. Recent studies have suggested that statins, an established cholesterol-lowering drug group used in the prevention of cardiovascular mortality, could have beneficial effects against recurrence and progression of breast cancer. We evaluated breast cancer-specific mortality among users of statins and other cholesterol-lowering drugs (fibrates and bile-acid binding resins) in a cohort of breast cancer patients. Methods: Our study cohort included all newly diagnosed breast cancer patients in Finland during 1995-2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on cholesterol-lowering medication use was obtained from a national prescription database.We used Cox proportional hazards regression method to estimate mortality among medication users. Results: A total of 4,169 participants had used statins, while 313 had used fibrates or resins. Despite similar median age, tumor and treatment characteristics, only statin use was associated with decreased breast cancer mortality (participants with localized tumors: HR 0.33, 95% CI 0.24-0.42; metastatic tumors: HR 0.52, 95% CI 0.31-0.86). Fibrate and resin use were associated with increased overall mortality (HR 1.70, 95% CI 0.96-2.99 for participants with localized disease, HR 2.65, 95% CI 1.18-5.96 for participants with metastatic disease). Conclusions: Decreased breast cancer mortality among users of statins, but not other cholesterol-lowering drugs despite similar population characteristics suggests that this drug group may have benefit in prevention of cancer progression. Clinical trials testing statins’ efficacy in breast cancer patients are warranted.
Overview of meta-analyses and pooled analyses of nutrition and breast cancer risk.
Authors: Mullie Patrick , Autier Philippe , Boyle Peter 
Published: March 2020

1519 Background: Twenty years ago, recommendations for prevention of breast cancer by dietary modification were based on decreased fat consumption, and increased consumption of dietary fibre, fruits, vegetables and vitamins. Subsequent literature is replete with reports of studies of diet and nutrition often containing widely varying advice for women regarding reducing their breast cancer risk. Methods: A systematic search in PubMed of the published literature was conducted to identify meta-analyses and pooled analyses relating breast cancer risk to a wide variety of nutritional components including intake of coffee, dairy, dietary fibre, eggs, fat components, fruits and vegetables, glycaemic index and load, meat components, minerals, seafood, soy, tea, and a variety of vitamins. Inclusion criteria were: published in English, time period 2000-2011, and restricted to studies with a prospective design. All published relative risks and confidence intervals were abstracted. Results: The search retrieved 2 pooled analyses and22 meta-analyses concerning alcohol (1), coffee (2), dairy (3), dietary fibre (2), eggs (1), fat components (3), fruits and vegetables (2), glycaemic index and load (3), meat (3), minerals (1), seafood (1), soyfood (1), tea (3), and vitamins (5). In total 256 relative risks were computed by meta- and pooled analyses, with 195 (76%) statistically not significant, 16 (6%) showing an increased risk and 45 (18%) showing a decreased risk of breast cancer. 18 relative risks were less than 0.90 and 5 were greater than 1.25. Of the 5 estimates for alcohol, 2 (40%) showed statistically significant increased risk for breast cancer. For other food items, proportions associated with non-significant risk were for dairy (85%), total fat consumption (83%), dietary fibre (56%), fruits and vegetables (96%), glycaemic index/load (77%), meat (95%) and vitamins (78%). Conclusions: Other than accepted dietary risk factors alcohol, obesity and physical activity, no individual nutritional item has been consistently related to breast cancer risk. Energy balance seems to be an essential element in breast cancer prevention.
Can microsatellite status of colorectal cancer (CRC) be reliably assessed after neoadjuvant therapy?
Authors: Vilar Sanchez Eduardo , Wu William , Bhatia Gita , Cuddy Amanda , Mork Maureen M. , Bannon Sarah A. , Lynch Patrick M. , Rodriguez-Bigas Miguel A. , Taggart Melissa W. , You Y. Nancy 
Published: March 2020

1525 Background: Universal testing of resected CRC for Microsatellite Instability (MSI) status has been widely advocated. While PCR-based MSI analysis is the current gold standard test, immunohistochemistry (IHC) of mismatch repair (MMR) proteins is more commonly performed. At present, it remains un-established whether PCR-based MSI analysis remains reliable when performed on post-neoadjuvant treated specimens. Our goal was to examine the effect of neoadjuvant therapy on MSI analysis using both in vitro and clinical data. Methods: MSI analysis was performed using the standard panel of 7 markers. In vitro, MMR deficient (HCT116) and proficient (HCT116+Ch3) isogenic cell lines were exposed to 3 cycles of single agent 5-Fluorouracil, Oxaliplatin and Irinotecan and MSI analysis was tested after each cycle. To evaluate the induction of genomic instability, 3 additional coding microsatellite tracts in ATR, BLM and CHK1 were assessed by fragment analysis. In parallel, clinical data from 238 CRCs that were resected after neoadjuvant chemoradiation (n=191) or chemotherapy (n=47) between 9/2009 and 8/2011 were queried for MSI results. MSI analysis performed on paired pre-treatment and post-treatment resection tissues was compared. Results: No changes in MSI status were detected and there was no increase in genomic instability post-treatment in cell line models. In the clinical setting, pre-neoadjuvant MSI testing was limited by the availability of pre-treatment biopsy tissue. 3 patients found to be MMR proficient based on MSI analysis performed on pre-treatment biopsy remained microsatellite stable when analyzed on post-treatment resection tissue. 7 patients were MMR deficient based on MSI analysis performed on post-treatment resection tissue but most had strong clinical evidence to expect MMR deficiency. Conclusions: Based on both preclinical in vitro and clinical data, results of the MSI analysis does not appear to be affected by neoadjuvant therapy for both MMR proficient and deficient cases. In addition, preclinical results do not suggest that neoadjuvant chemoradiation induces an increase in genomic instability. Therefore, MSI analysis remains a reliable gold standard test on post-treatment specimens.