bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of secondary myelodysplastic syndrome and acute myeloid leukemia in patients with ovarian and breast cancer in real-world setting in the U.S.
Authors: Fulcher Nicole , Shenolikar Rahul A. , Durden Emily , Moore Kathleen N. 
Published: September 2018

5574 Background: Limited real-world data are available on cancer patients withsecondary malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) caused by use of certain chemotherapeutic agents that interfere with DNA. This study assessedthe incidence of secondary MDS and AML in patients (pts) with ovarian cancer (OC) or breast cancer (BC), including subcohorts tested for BRCA mutations and those exposed to DNA damaging therapy. Methods: Adult females with OC or BC between 1/1/2000 and 6/30/2014 (first observed diagnosis of OC or BC = index date) were identified from the MarketScan Commercial and Medicare claims databases. Patients had ≥12 months of pre- and ≥1 month of post-index continuous health plan enrollment. The incidence of MDS and AML (per 1000 person-years [PY]) was assessed using ICD-9 codes over a variable-length post-index period for each cancer cohort and separately for pts with BRCA testing and those exposed to DNA damaging therapy. Results: The study identified 23,862 OC pts (mean [SD] follow-up: 35.8 [31.4] months), and 281,473 BC pts (mean [SD] follow-up: 46.0 [37.2] months). Among OC pts, 10.9% had BRCA testing (OC- BRCA) and 56.6% had exposure to DNA damaging therapy (OC-DNA); 12.9% of BC pts were BRCA tested (BC- BRCA) and 28.1% had exposure to DNA damaging therapy (BC-DNA). The incidence of MDS and AML expressed as cases per 1,000 PY in the OC cohort was 0.51 (0.2%) and 0.39 (0.1%); in OC- BRCA pts, 0.62 and 0.25; and in OC-DNA pts, 0.68 and 0.41. In the BC cohort, the incidence of MDS and AML was 0.33 (0.1%) and 0.19 (0.1%); in BC- BRCA pts, 0.07 and 0.15; and in BC-DNA pts, 0.60 and 0.50. Conclusions: In addition to providing background rates in OC and BC pts, these data suggest that the incidence of MDS and AML in OC and BC pts was higher in patient subcohorts exposed to DNA damaging agents than in the overall cohort.
Impact of beta blocker medication on survival outcome of ovarian cancer: A nationwide population-based cohort study.
Authors: Park Jeong-Yeol , Baek Min-Hyun , Park Young-Han , Kim Dae-Yeon , Suh Dae-Shik , Kim Jong-Hyeok , Kim Yong-Man , Kim Young-Tak , Nam Joo-Hyun 
Published: September 2018

5578 Background: In experimental studies, adrenergic hormones are involved in tumorigenesis of ovarian cancer and its progression. We investigated the impact of beta adrenergic blocker on survival outcome of ovarian cancer since few studies have investigated its relevance. Methods: Data of Korean National Health Insurance Service was analyzed (n = 866). We analyzed the impact of beta blocker on survival outcome of ovarian cancer according to the duration on medication and age groups of patients. Cox proportional hazards regression was used to analyze hazard ratios (HR) for all-cause mortality with 95% confidence intervals (CI) adjusting for confounding factors. Results: Median years of follow-up was 5.98 and 6.71 for non-users and users, respectively. Among the 866 patients, 206 (23.8%) were users and 660 (76.2%) were non-users. In total, there was no survival difference between the 2 groups. But, when patietns were grouped according to the duration of medication, patients with longer duration of medication (≥1 year) showed better survival outcome (adjusted HR 0.305 [95% CI: 0.187-0.500], P < 0.001). Also, beta blocker use in patients with > 60 years showed better survival compared to younger patients (adjusted HR 0.579 [95% CI: 0.408-0.822], P = 0.002). In patients with > 60 years, medication longer than 720 days was associated with better survival outcome (adjusted HR 0.267 [95% CI: 0.140-0.511], P < 0.001). Both selective and non-selective beta blocker showed identical survival benefit in these settings without difference between each other. Conclusions: Beta blocker medication was associated with favorable survival outcome in ovarian cancer, especially when used in older patients and in long term duration.
Exploratory phase II evaluation of cabozantinib in recurrent/metastatic uterine carcinosarcoma (CS): A study of the Princess Margaret, Chicago, and California phase II consortia.
Authors: Mandilaras Victoria , Dhani Neesha C. , Tan Qian , Jain Angela , Johnston Carolyn , Hirte Hal W. , Tonkin Katia Sonia , Cristea Mihaela C. , Matsuo Koji , Butler Marcus O. , Lheureux Stephanie , Burnier Julia V. , Wang Lisa , Mehta Anjali , Wright John Joseph , Oza Amit M. 
Published: September 2018

5587 Background: Carcinosarcoma (CS) is a rare ( < 5%) aggressive subtype of endometrial cancer (EC). Patients (pts) with progression on platinum-based chemotherapy (CTX) have limited options, there is no standard 2ndline treatment and median progression-free survival (PFS) is < 2months (mt), 6-mt PFS less than 20%. Limited molecular data on CS aligns with epithelial EC, providing rationale for evaluating similar strategies such as targeting MET and angiogenesis. Cabozantinib (cabo) is multi-targeted tyrosine kinase inhibitor against MET, VEGFR, TIE2, RET, AXL and KIT. Methods: PHL-86 (NCI#9322/NCT01935934) is a multi-centre, non-randomized, phase II trial of cabo (60 mg oral daily dose on a 28-day cycle) in EC pts recurring within a year of adjuvant CTX or with progression after 1stline of CTX for metastatic disease. Pts with rare histology including CS, were enrolled in an exploratory cohort. Activity of interest for further evaluation was defined as 4 responses (either partial response [PR] or 12-wk PFS) out of 10 pts of a given histotype. CT scans were performed after cycle 3 and every 2 cycles thereafter. Results: From 2013 to 2016, 32 pts were treated in the exploratory cohort, 19 pts with CS. Median age was 66 years (range 25-75); prior treatment included CTX (17: 1 line, 6: 2 lines) and/or radiation (11). Fifteen pts were evaluable for response, with 1 PR (7%) and 8 pts with 12-wk PFS (53%). Median PFS was 3 mt (95% CI: 2.7 – 4.6) with estimated 6-mt PFS of 13% (2 to 33%). Toxicity evaluation is available for 19 pts. Common events were fatigue and GI upset. Most frequent > Grade3 toxicities were hypertension (5), anemia (4), diarrhea (2). Four pts had GI fistula (2) or perforation (2). Mutation profiling in archival tissue showed TP53 (73%), PIK3CA (40%), KRAS (27%), PTEN(13%) with > 1 mutation present in 14/15 pts analyzed. The 1 pt with no somatic mutations had a PR (31% decrease) on cabo (PFS 6.7mt). Conclusions: Cabo in CS cohort met the predefined endpoint for further evaluation and compares favourably with other agents in this poor prognosis disease. Larger studies are required to define depth and durability of response and identify relevant biomarkers. Clinical trial information: NCT01935934.
Contemporary breast conservation patient outcomes for ductal carcinoma in situ and margins < 2 mm.
Authors: Tadros Audree , Smith Benjamin D. , Shen Yu , Lin Heather Y. , Krishnamurthy Savitri , Lucci Anthony , Barcenas Carlos Hernando , Hwang Rosa F. , Rauch Gaiane , Santiago Lumarie , Strom Eric A , DeSnyder Sarah Marie , Yang Wei Tse , Black Dalliah MaShon , Albarracin Constance T. , Chavez-Mac Gregor Mariana , Hunt Kelly , Kuerer Henry Mark 
Published: September 2018

559 Background: Recent national consensus guidelines regarding optimal margin width for the management of DCIS have been published; however, controversy remains for managing margins <2mm. The relationship between margin width and locoregional recurrence (LRR) was determined in a contemporary cohort of patients. Methods: 1504 patients with DCIS undergoing definitive breast conserving surgery from 1996 to 2010 were analyzed for clinical and pathologic characteristics from a prospectively managed comprehensive academic cancer center database. Cox proportional hazard models were used to examine the relationship between margin width (<2mm or ≥2mm) and LRR by adjuvant radiation therapy (RT). Patients with positive margins (n=11) were excluded. Results: Overall, 3.4% of patients had a LRR at a median follow-up of 8.7 years. Univariate analysis of age, family history, grade, tumor size, comedonecrosis, RT, adjuvant hormonal therapy, ER status, and margin width found younger age (< 40 yr, p=0.02), no RT (n=299, p=0.005), and margin width <2mm(n=138, p=0.005) to be associated with LRR. The association between margin width and LRR differed by adjuvant radiation therapy status (p=0.02 for the interaction). There was no statistical significant difference in LRR for patients with margins <2mm vs ≥2 mm who received RT, (10-year LRR 6.0% vs 3.2%, respectively; HR 1.5, 95% CI 0.5-4.2, p=0.48). For patients who did not receive RT (n=299), those with margins < 2 mm were significantly more likely to develop a LRR than those with margins ≥2mm (10-year LRR 35.7% vs. 4.6%, respectively; HR 7.2, 95%CI 2.6-19.4, p=0.0001). Conclusions: In patients with <2mm margins receiving adjuvant radiation therapy, there is no difference in locoregional recurrence when compared to patients with ≥2mm margins. Additional surgery for wider margins of resection are not routinely justified in this group of patients but should be obtained for patients with <2mm margins who forego radiotherapy.
The combination of preoperative computed tomography lymphography and intraoperative fluorescence imaging navigation for sentinel lymph node biopsy of early breast cancer patients.
Authors: Abe Hajime , Teramoto Atsuko , Yamasaki Keiichi , Yoneda Kohri , Ogawa Masao , Kawasaki Masayasu , Kameyama Masao 
Published: September 2018

567 Background: This study investigated a usefulness of the combination of fluorescence imaging and computed tomography lymphography (CTLG) for sentinel lymph node biopsy (SLN) biopsy of early breast cancer patients. Methods: Between January 2013 and August 2016, 350 breast cancer patients without clinical evidence of lymph node metastasis were treated. Preoperaitve CTLG was performed using 64-row multidetector CT injected contrast agent. The contrasted lymph route and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. We established typical pattern of the lymphography: stain defect of SLN, stagnation of lymphatic route for preoperative diagnosis of metastatic SLN. Intraoperative fluorescence images were obtained using the fluorescence imaging system (pde-neo). After dye mixed indocyanine green and indigocarmin was injected, lymphatic route was observed with fluorescence images. SLN biopsy was performed referring to the point by axillary compression technique by plastic device. Results: The median age of the 350 patients was 59 (range 28 – 90) years old. CTLG could visualize lymphatic route and accurately identify SLN in 336 (96.0 %) and 343 (98.0 %) cases, respectively, whereas fluorescence imaging identified successfully lymphatic route and SLN in all patients. Lymphatic routes of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.6, p<0.01). Fifty of 350 patients had metastatic SLN pathologically, and 11 of them had micrometastases of SLNs. The accuracy for metastatic diagnosis of SLN using CTLG without micrometastasis was 84.1 %, sensitivity was 82.1 % and specificity was 84.3 %. The positive predictive value was 40.5 % and negative predictive value was 97.3 %. Conclusions: This combined navigation method of fluorescence imaging and CTLG revealed more easy and effective to detect SLN than fluorescence imaging alone. In addition, the information from CTLG would be helpful for the preoperative diagnosis of SLN metastasis.
Hypofractionated, normofractionated and intraoperative breast irradiation: Long term cosmetic outcome based on photographic evaluation.
Authors: Ellethy Tarek , Welzel Grit , Sperk Elena , Neumaier Christian , Tuschy Benjamin , Berlit Sebastian , Ehmann Michael , Sütterlin Marc , Wenz Frederik K. , Abo-Madyan Yasser 
Published: September 2018

568 Background: Photographic documentation of breast changes after breast radiotherapy (RT) is a helpful tool to both subjectively and objectively evaluate cosmesis. The aim of this study was to evaluate cosmesis in breast cancer patients after receiving hypofractionated whole breast RT (HF-WBRT), normofractionated (NF-WBRT), intraoperative RT (IORT) or combined WBRT/IORT. Methods: After excluding cases with missing or inadequate photos from three prospective clinical trials, KOSIMA, TARGIT-A & TARGIT-E, 155 and 205 cases were included in a subjective analysis while 132 and 185 cases were included in an objective analysis postoperatively and after 2 years respectively. Subjective evaluation was done by 9 observers using the Harvard scale. Objective evaluation was done by assessing percentage breast retraction (pBRA). Based on the treatment received, patients were divided into 5 groups: 1. HF-WBRT 40/2,67 Gy ± Boost, 2. NF-WBRT 50/2 Gy ± Boost, 3. NF-WBRT 56/2 Gy, 4. IORT 20 Gy, 5. IORT 20 Gy+WBRT 46/2 Gy. Results: Subjectively, the rate of excellent-good cosmesis was 92% postoperatively and 84% after 2 years while objectively it was around 56% at both time points. At 2 years, no significant difference was observed between the 5 treatment groups with the subjective excellent-good cosmesis being 82%, 80%, 92%, 83%, 85% (p = 0.546) and objective being 56%, 61%, 52%, 53%, 50% (p = 0.883) in groups 1-5 respectively. Factors possibly affecting cosmesis at 2 years were examined. No significant difference was observed with age, smoking, BMI, chemotherapy, hormone therapy or type of axillary surgery. Significantly better cosmesis was observed with upper outer tumor location compared to other quadrants (p < 0.0001) also with a ratio of excised/total breast volume under 20% (p < 0.0294). Conclusions: Cosmetic outcome after hypofractionated and IORT was similar to normofractionated breast RT. After 2 years of treatment, cosmetic deterioration remained acceptable, overall < 10%. Tumor location and excised breast volume were the only factors significantly affecting cosmetic outcome.
A gene signature of chemo-immunization to predict outcome in patients with triple negative breast cancer treated with neoadjuvant chemotherapy.
Authors: Bayar Mohamed-Amine , Criscitiello Carmen , Curigliano Giuseppe , Symmans William Fraser , Desmedt Christine , Bonnefoi Herve R. , Sinn Bruno Valentin , Pruneri Giancarlo , Vicier Cecile , Pierga Jean-Yves , Denkert Carsten , Loibl Sibylle , Sotiriou Christos , Michiels Stefan , Andre Fabrice 
Published: September 2018

575 Background: In patients with triple-negative breast cancer (TNBC), the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease after anthracycline-based neoadjuvant chemotherapy (NACT) is associated with a better prognosis. We aimed to develop a genomic signature from pre-treatment samples to predict the extent of TILs after NACT, and then to test its prognostic value on survival. Methods: Using 99 pre-treatment samples (training set), we generated a four-gene signature that predicts post-NACT TILs using the LASSO technique. Prognostic value of the signature on survival was assessed on the training set (n=99) and then evaluated on an independent validation set including 185 patients with TNBC treated with NACT. Results: A four-gene signature, assessed on pre-treatment samples and combining the expression levels of HLF, CXCL13, SULT1E1, and GBP1 predicted the extent of lymphocytic infiltration after NACT. In a multivariate analysis performed on the training set, a one-unit increase in the signature value was associated with distant-relapse free survival (DRFS) (HR: 0.28, 95%CI: 0.13-0.63, p=0.002). For the validation set, the four-gene signature was significantly associated with DRFS in the entire set (HR: 0.26, 95%CI: 0.11-0.59, p=0.001) and in the subset of patients with residual disease (HR: 0.23, 95%CI: 0.10-0.55, p< 0·001). Conclusions: We developed a four-gene signature of chemotherapy-induced immune-activation, which predicts outcome in patients with TNBC treated with NACT. [Table: see text]
Utilization, trend and impact of neoadjuvant endocrine therapy compared to neoadjuvant chemotherapy in postmenopausal breast cancer patients: Analysis of the National Cancer Data Base.
Authors: Basnet Alina , Wang Dongliang , Sivapiragasam Abirami 
Published: September 2018

578 Background: Three small prospective trials that compared the efficacy of neoadjuvant endocrine therapy (NET) to neoadjuvant chemotherapy (NCT) showed no statistically significant difference. We report the differences in utilization of NET and NCT using National Cancer Data Base (NCDB) and their trend, response rates (RR) and breast conservation rates (BCR). Methods: A retrospective review of hormone receptor positive breast cancer patients ≥ 50 yrs without metastasis using NCDB was performed (2004-2014). Patients underwent NET or NCT prior to definitive surgery. Utilization pattern, practice trend, RR and BCR between NET and NCT was assessed using univariate and multivariate logistic analysis. Results: Out of 2,246,279 breast cancer patients reported in NCDB, 38,632 met our inclusion criteria. 9178 received NET and 29,454 received NCT. On multivariate analysis NET use was higher in academic vs community centers [Odds ratio (OR) 1.355, 95% CI 1.270-1.445], age >70 vs < 70 (OR 6.603, 95% CI 6.110-7.137) and high vs low Charlson Deyo comorbidity index (OR 1.817, 95% CI 1.548-2.133). NET use was lower in black vs white (OR 0.790, 95% CI 0.712- 0.875), tumors with higher vs lower grade (OR 0.153, 95% CI 0.138-0.169), higher vs lower T stage (OR 0.372, 95% CI 0.340-0.407), higher vs lower N stage (OR 0.274, 95% CI 0.243-0.310) and private vs no insurance (OR 0.600, 95% CI 0.509- 0.707), (all p<0.0001). A significant upward trend in utilization of NET was observed from year 2011 (25.9%) compared to before (22.2%), p<0.0001. RR was significantly higher for patients receiving NCT (90.5%) compared to NET (77.2%), with an [adjusted OR (aOR) 2.413; 95% CI 2.116-2.752], however the BCR was superior in the NET group (50.0%) compared to NCT group (31.1%) with (aOR 1.676; 95% CI 1.567-1.794). Conclusions: Our study is the first to compare NET and NCT utilization and their efficacy using NCDB database. Our results have shown striking differences in outcome among these two strategies as compared to other prospective trials. Despite high RR, more patients underwent mastectomy in the NCT group. We also see a steady upward trend in usage of NET from year 2011.
The impact of quality and quantity of visceral fat on survival outcome of early-stage breast cancer patients with prior chemotherapy.
Authors: Iwase Toshiaki , Sangai Takafumi , Sakakibara Masahiro , Nagashima Takeshi , Ohtsuka Masayuki 
Published: September 2018

584 Background: Obesity not only increases morbidity, but also chemo-resistance of breast cancer (BC). Several studies focusing on body mass index (BMI) of BC patients have been performed; however, a recent report suggested that the quality of visceral adipose tissue (VAT) plays a crucial role in fat cell function. We set out to clarify the effect of quality and quantity of VAT on survival outcome of BC patients who underwent chemotherapy. Methods: From 2,230 patients who underwent treatment for BC at our institution from January 2004 to December 2015, we included 271 patients who received chemotherapy in neo-adjuvant (NAC) or adjuvant setting. Quantification was performed using computed tomography (CT) 3-dimensional volumetric software and quality of VAT was assessed based on the CT Hounsfield Unit of VAT (VAT-HU) using electrically stocked CT images. The correlation between BMI, amount of VAT (aVAT), and VAT-HU were analyzed using Pearson’s correlation test. The effect of these factors on pathologic complete response (pCR) was evaluated using Logistic regression model with the following covariates: menopausal status, size, nodal status, and subtype. Furthermore, survival analysis for distant disease-free survival (DDFS) was performed using Kaplan Meier method and Cox proportional hazard model. Results: aVAT and VAT-HU were significantly correlated with patient BMI (p<0.05). Forty-six patients achieved pCR (24%). Logistic regression model for pCR showed that aVAT and VAT-HU did not affect pCR (p=0.60 and 0.36). After a median follow-up of 112 months, tertile stratification revealed that the third tertile of aVAT had significantly shorter DDFS in the NAC setting (p<0.05). When adjusted by covariates in the Cox proportional regression model, aVAT and VAT-HU demonstrated significant contribution to worse DDFS ([p<0.05, hazard ratio {HR} 1.39; 95% confidence interval {CI} 1.11 to 1.75] and [p<0.05, HR 1.20, 95% CI 1.01 to 1.43], respectively). Conclusions: The quantity and quality of VAT was significantly related to the survival outcome especially in the NAC setting. This new insight would enable prediction of recurrence risk in obese BC patients with prior chemotherapy.
LUX-head and neck 2: Randomized, double-blind, placebo-controlled, phase III trial of afatinib as adjuvant therapy after chemoradiation (CRT) in primary unresected, high/intermediate-risk, squamous cell cancer of the head and neck (HNSCC) patients (pts).
Authors: Burtness Barbara , Haddad Robert I. , Dinis José , Trigo Perez Jose Manuel , Yokota Tomoya , Viana Luciano De Souza , Romanov Ilya , Vermorken Jan Baptist , Bourhis Jean , Tahara Makoto , Segalla J.G.M. , Psyrri Amanda , Vasilevskaya Irina , Nangia Chaitali Singh , Chaves-Conde Manuel , Wang Bushi , Gibson Neil , Ehrnrooth Eva , Harrington Kevin , Cohen Ezra E.W. ,   On Behalf of the LUX-Head and Neck 2 Investigators
Published: September 2018

6001 Background: Locally advanced HNSCC is treated curatively, but recurrence is common. In HNSCC, EGFR is richly expressed and EGFR inhibition is validated treatment (tx); the ErbB family blocker afatinib (A) showed efficacy in recurrent/metastatic disease. This Phase III trial assessed if A after definitive CRT improves disease-free survival (DFS). Methods: Eligible pts had complete response after CRT ≥66 Gy (or equivalent) with concurrent cisplatin or carboplatin but not prior EGFR inhibition, for HNSCC of oral cavity, hypopharynx, larynx, or oropharynx with >10 pack years (pk yrs) tobacco use. Pts were stratified by ECOG PS (0/1) and nodal stage (N0–2a/N2b–3), and randomized 2:1 to A 40 mg/d or placebo (P); tx continued for 18 m if tolerated, or until disease recurrence. The primary endpoint was DFS. Results: Of 669 pts planned, 617 were randomized; A 411, P 206. Median age was 58 yrs; 86% were male; 65% ECOG PS 0; most had smoked (A/P ex-smoker: 66/72%; current: 28/22%). Subsites (A/P) were: oropharynx 53/54%; hypopharynx 21/23%; larynx 18/12%; oral cavity 9/10%. The majority had T3 or 4 (A/P 70/68%) and N2 disease (67/63%). Accrual was halted for futility on independent DMC recommendation: at a pre-planned interim analysis (40% of DFS events), median DFS was A 43.4 m vs P not reached (NR; HR 1.13 [95% CI 0.81–1.57], p=0.48); the Table shows key subgroups. Median treatment duration was A 300.0 d, P 455.5 d. Recurrence was A 23%, P 23%. Dose reduction of A was required in 53% (mostly due to diarrhea, stomatitis). Tx was discontinued due to AEs in A 15%, P 4%. Conclusions: A after CRT did not improve DFS vs P. Subgroup analyses were underpowered to provide definitive conclusions. Harrington and Cohen contributed equally. Clinical trial information: NCT01345669. [Table: see text]