bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the Prosigna (PAM50) assay on adjuvant clinical decision making in patients with early stage breast cancer: Results of a prospective multicenter public program.
Authors: Rodriguez Cesar Augusto , Garcia-Muñoz Maria , Sancho Magdalena , Garcia-Gonzalez Maria , Delgado Carlota , Soto de Prado Diego , Álvarez José V. , Bayona Cristina , Alés-Martínez José E. , Gallegos Isabel , Puertas Álvarez Javier , García-Palomo Andres , Arevalo Estefania , Condori Eliza , Gómez Asunción , Lozano Rebeca , de la Fuente Natalia , Cruz Juan J. 
Published: September 2018

e12062 Background: Prosigna is a standardized test based on the PAM50 gene signature which provides information on intrinsic subtype and risk of recurrence (ROR) score predicting 10y recurrence probability (NanoString Technologies, Inc., Seattle, WA). We evaluated Prosigna’s impact on adjuvant treatment decision beyond immunohistochemistry (IHC) testing. Methods: 125 pre- and postmenopausal EBC patients with ER+, HER2-, pT1-T2 pN0/pN1mi were enrolled (12 centers; 8/2015-11/2016). FFPE specimens were centrally analyzed using Prosigna to classify patients according to the intrinsic tumor subtype and ROR score. The primary endpoint was the impact of the Prosigna test on adjuvant treatment decision. Results: 64% of tumors were classified by PAM50 as Lum A, 35% as Lum B, 0% Basal, 1% HER2-E. The intrinsic subtype concordance between immunohistochemistry (IHC) and Prosigna (n = 119) was 61.3%. In Lum B tumors by IHC the discordance rate was the highest (48% were reclassified as Lum A by Prosigna) as shown in the Table. ROR risk groups were as follows: ROR low (54; 43%), ROR interm. (38; 30%), and ROR high (33; 27%). Prosigna results led to a treatment recommendation change in 49 (39%) patients. In the 76 (61%) cases with the initial recommendation of Hormonal Therapy (HT) alone the final decision changed to chemotherapy (CT)+HT (CHT) in 24 (32%) patients. In the 49 (39%) cases in which the initial recommendation was CHT the final decision changed to HT in 25 (51%) patients. Among the 38 patients with Prosigna intermediate risk, 21 (55%) were allocated to HT. Conclusions: In this prospective decision impact study, Prosigna results led to a 39% change in adjuvant therapy indication. Patients with initial indication of CHT were changed to HT alone in > 50% of cases. Thus, Prosigna results influenced the treatment decisions and reinforced its clinical utility in real-world settings. The intrinsic subtype classification based on IHC didn’t show to be an adequate surrogate for the genomic subtypes as determined by Prosigna. [Table: see text]
Negative predictive value of ipsilateral axillary ultrasound in the pre-operative assessment of invasive breast cancer.
Authors: Ameri Bita , Kanesa-Thasan Riti , Abu-Khalaf Maysa M. , Berger Adam C. , Eisenberg Tara , Lazar Melissa A. , Sevrukov Alexander , Tsangaris Theodore N. , Wasti Nylah , Wilkes Annina , Willis Alliric Isaac , Zorn Lisa , Hsu Elizabeth 
Published: September 2018

e12080 Objective: To determine if a negative preoperative axillary ultrasound predicts a negative sentinel lymph node biopsy at surgery. Background: Axillary lymph node involvement is an important prognostic indicator in patients with breast cancer. Sentinel lymph node biopsy (SLNB) is currently the gold standard for determining the presence or absence of axillary metastases. Pre-operative axillary ultrasound is often used to evaluate axillary lymph node status prior to surgery and SLNB. Although there are no established guidelines on when preoperative axillary ultrasound is performed, at our institution we evaluate the axilla when invasive breast cancer is suspected. This study evaluated the negative predictive value (NPV) of axillary ultrasound compared to the pathology results of SLNB. Methods: In this single-center IRB-approved retrospective study, 3 years of breast imaging data (2014-2016) were reviewed. 137 patients had pathology verified invasive breast cancer with negative preoperative axillary ultrasound and subsequent SLNB. All patients had clinically negative axillae. Based upon the pathology results of SLNB, the negative predictive value of preoperative axillary ultrasound was calculated. Negative axillary ultrasound is defined as the absence of morphologically abnormal lymph nodes on imaging. A lymph node is considered morphologically normal when there is preserved fatty hilum and a uniform cortex measuring 3 mm or less. Results: Out of 137 patients with invasive breast cancer who had negative preoperative axillary ultrasound, 122 had negative SLNB results and 15 had positive SLNB results. Preoperative axillary ultrasound demonstrated a NPV of 89.1% for the detection of axillary metastatic disease at the time of SLNB. Conclusions: Negative axillary ultrasound excluded axillary metastatic disease in 89.1% of patients. This data suggests that negative axillary ultrasound may have a role in the setting of failed SLNB (no lymph nodes found at the time of surgery) in deciding whether to pursue axillary dissection.
Dedicated breast PET to improve clinical diagnosis of breast cancer: Initial evaluation.
Authors: Masumoto Norio , Kadoya Takayuki , Fujiwara Makoto , Murakami Chika , Yoshikawa Toru , Handa Yoshinori , Amioka Ai , Gohda Noriko , Kono Miho , Sasada Shinsuke , Kajitani Keiko , Emi Akiko , Haruta Rumi , Kataoka Tsuyoshi , Okada Morihito 
Published: September 2018

e12097 Background: Unlike whole body (WB) 18F-fluorodeoxyglucose (FDG) PET, dedicated breast PET (DBPET) enables detailed high-resolution images within the breast and quantitative assessment using SUV. We aimed to determine whether DBPET can detect ductal carcinoma in situ (DCIS) and predict the malignancy and neoplastic progress of invasive breast cancer. Methods: We investigated 155 consecutive patients with breast cancer who underwent concurrent DB– and WB– PET (Elmammo®) between January and November 2016. All DB– and WB– PET images were quantified based on standard uptake values (SUV). We also assessed 12 patients with ring-like uptake (RU) without central FDG accumulation in invasive breast cancers on DBPET images. Results: The SUV (means ± SD) determined from DB– and WB– PET images of breast cancer were 8.2 ± 7.7 and 3.1 ± 3.3 respectively. We detected DCIS in DB- and WB– PET images from 22 (84.7%) and 15 (57.6%) of 26 among the 155 patients, respectively (p = 0.003). The SUV on WB– PET images was significantly higher for NG3 than for NG1-2 (p = 0.004), and for high (≥ 20%) than low ( < 20%) Ki67 (p = 0.003), and significantly lower for Luminal A than Luminal B, HER2 and triple-negative cancer (p < 0.05 for all three). The SUV for NG (p = 0.002), Ki67 (p = 0.001) and the luminal (p < 0.05) type also significantly differed in DBPET images. RU without central FDG accumulation was evident in DbPET images of 12 patients, all of whom had Ki67 ≥ 20 (p = 0.0001), two had NG1-2 and 10 had NG3 (p = 0.005), one had clinical T1, 11 had T2 (p = 0.0004), five had clinical N0 and seven had N1 (p = 0.03). RU was associated with high-grade malignancy and neoplastic progress. Conclusions: The detection rate of DBPET was excellent for DCIS. The RU on DBPET offers predictive value for high-grade malignancy and the neoplastic progress of invasive breast cancer. Thus, DBPET might help to determine therapeutic strategies.
64Cu-DOTA-trastuzumab PET/CT to predict response to ado-trastuzumab emtansine (TDM1) in HER2-positive metastatic breast cancer.
Authors: Mortimer Joanne E. , Bading James R. , Frankel Paul Henry , Gidwaney Rita , Park John , Tumyan Lusine , Parayno Maria , Poku Kofi , Colcher David 
Published: September 2018

e12525 Background: Having demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent for HER2 positive (HER2+) breast cancer, we now evaluate the methodology for prediction of response and benefit from TDM1 in women with metastatic disease. Methods: Patients eligible to receive TDM1 as therapy were chosen on the basis of biopsy confirmed HER2+ disease, and at least 1 site of metastasis ≥ 2.0 cm outside the biopsy site. Pretreatment staging included 18F-FDG PET/CT. Prior to injection of 64Cu-DOTA-trastuzumab, patients received 45 mg of cold trastuzumab to reduce liver uptake. PET-CT scans were obtained at 16-28 h (Day1) and 39-49 h (Day 2) over fields of view chosen in reference to the 18F-FDG scans. TDM1 (3.6 mg/kg) was administered every 3 weeks. Restaging 18F-FDG PET/CT was performed every 2 cycles, and response to therapy was determined by PERCIST (solid tumor) criteria. Radiolabel uptake was measured in terms of maximum voxel, standardized uptake value (SUVmax). Results: Ten women between the ages of 48-83 years old (median 55 years) qualified for study, and have been evaluated for response; 4 continue on TDM1 with treatment durations of 3-27 months.Three were trastuzumab-naïve, while 7 had received trastuzumab-containing chemotherapy 3 wks to 55 mo prior to study entry. HER2 was positive by ImmunoHistoChemistry, IHC (3+) in 5 patients, and by FISH testing in the other 5 (3 were 2+ by IHC; 1 was 1+, and 1 was indeterminate). Complete or partial metabolic response was observed in 5 patients. Median Day 2 SUVmax for 64Cu-DOTA trastuzumab was 9.3 g/ml in responding patients, and 4.6 g/ml in non-responders ( P= 0.03). Progression-free survival was longer for patients with higher SUVmax, with a hazard ratio of 0.73 (95% confidence interval 0.46-1.16) for each 1 unit increase in SUVmax. This was not statistically significant, although we can select a threshold SUVmaxfor which the effect is significant even for this small study. Further data is required to confirm such a threshold effect. Conclusions: 64Cu-DOTA-trastuzumab PET imaging predicts benefit from TDM1 in women with biopsy-confirmed HER2+ metastatic disease. Supported by NCI Clinical trial information: NCT02827877.
Real-world dosing patterns of everolimus-based lines of therapy among post-menopausal women with hormone receptor-positive and human epidermal growth factor receptor-negative (HR+/HER2-) metastatic breast cancer (mBC).
Authors: Princic Nicole , Brouillette Matthew , Tang Derek , Lin Chinjune , Lanoue Brad , Barghout Victoria E. 
Published: September 2018

e12528 Background: This study sought to describe dosing patterns of post-menopausal women with HR+/HER2- mBC treated with everolimus during a second or later lines of therapy in the US. Methods: MarketScan Commercial and Medicare Supplemental administrative claims databases were used to select post-menopausal HR+/HER2- mBC females who initiated an everolimus-based line of therapy during 1/1/2013- 7/31/2016. The first secondary malignancy diagnosis was the index date. Patients had 6 months of continuous enrollment in their health plans pre- and post- index, and were followed until the earliest date of disenrollment, inpatient death, or end of study. A line of therapy ended at discontinuation (gap >60 days in all treatment) or switch to a new treatment. Dose modification during 2L, 3L, or 4L was defined by a change in daily dose of >2.5 mg compared to the prior prescription and treatment interruption was defined as a gap >60 days of everolimus followed by a restart of therapy during follow-up. Results: There were 645 mBC patients with everolimus-based line(s) of therapy eligible for analysis (mean age = 61.1 [SD 11.7], mean days to treatment initiation = 33.4 [SD 65.1]). Across all lines, the majority (72.5%-80.8%) of patients were on a combination regimen with endocrine therapy and <10% were on a combination regimen with chemotherapy. Among patients with valid dose data (96.2%), mean initial dose in mg was 8.6 (SD 2.6) in 2L, 8.3 (SD 2.8) in 3L and 9.1 (SD 5.9) in 4L, the majority (71.4%-79%) did not have a dose modification, and <5% had a treatment interruption (Table). Conclusions: Results from this analysis of real-world data suggest that 71%-79% of patients did not experience any modification to the initial dose during an everolimus-based 2L, 3L, or 4L of therapy and less than 4% experienced a treatment interruption. [Table: see text]
Median progression free survival (PFS) for patients treated with everolimus (EVE) + exemestane (EXE) for HR+ mBC in routine clinical practice: Results of the 3rd interim analysis of the non-interventional trial BRAWO.
Authors: Jackisch Christian , Fasching Peter A. , Grischke Eva-Maria , Schuetz Florian , Decker Thomas , Uleer Christoph , Salat Christoph , Foerster Frank , Schmidt Marcus , Mundhenke Christoph , Tesch Hans , Wimberger Pauline , Aktas Bahriye , Zahn Mark-Oliver , Tome Oliver , Bloch Wilhelm , Hanson Sven , Schubert Joerg , Lueftner Diana 
Published: September 2018

e12547 Background: BRAWO is a non-interventional study, which enrolled more than 2400 patients (pts) with advanced/metastatic, hormone-receptor-positive and HER2-negative breast cancer treated with EVE and EXE. Main objectives are a) the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis in clinical routine, and c) the sequence of therapy when EVE is used in daily clinical practice. We report updated data of the 3rd interim analysis, including PFS. Methods: This updated analysis (data cut-off 18 Oct 2016) covers data of the first 1345 documented pts with at least one follow up under therapy. Here we describe the baseline characteristics, safety and PFS as well as response rates. PFS was estimated using Kaplan-Meier estimator. Results: At the time point of this data cut-off 1289 pts (93.9%) had discontinued the documentation. The median time for pts since primary diagnosis was 7.1 yrs and 2.2 yrs, since first sign of relapse (local recurrence or metastases). At baseline, 54.1% presented with visceral metastases. 49.2% had an ECOG performance status of 0 and 74.8% of pts started with 10mg EVE, while 24.5% started with 5mg EVE. According to treatment lines we found 27% 1L (359 pts), 32% 2L (426 pts), 19% 3L (253 pts), 11% 4L (153 pts) and 11% 5L (154 pts) in our cohort Additional baseline and safety data will be presented. The Kaplan Meier estimate of the overall PFS is 6.9 months (95%CI 6.3-7.4). 2.2% (18 pts) of the pts experienced a complete and 17.8% (147 pts) a partial remission, while 57.4% (475 pts) remained stable as their best overall responses during the documentation period. 52.3% (718 pts) discontinued the treatment due to a progressive disease and 25.5% (350 pts) due to adverse events. 67.1% (902 pts) continued the antineoplastic treatment with a subsequent therapy. Conclusions: Here we report the PFS of pts treated with EVE + EXE in a real world scenario. The PFS of 6.9 months observed in our series matches somewhat perfect with the PFS of 7.8 months from the randomized Bolero-2 trial suggesting that these findings might be valid and useful for everyday routine. Clinical trial information: EUPAS9462.
Long-term disease control with capecitabine in advanced breast cancer.
Authors: Masci Giovanna , Ferraro Emanuela , Torrisi Rosalba , Giordano Laura , Zuradelli Monica , Losurdo Agnese , De Sanctis Rita , Santoro Armando 
Published: September 2018

e12566 Background: Capecitabine is an active agent in the treatment of advanced breast cancer (ABC). It is commonly administered at the approved dosage of 1250 mg/m2 twice daily for 2 weeks followed by 1 week rest period. Methods: The study population included 162 pts retrospectively analyzed with ABC treated with capecitabine between 2006 and 2015 at our Institute. Capecitabine was given 14 day on,7 day off cycle at a daily dose of 1900 mg/m2, a modified schedule used to minimize side effects. The objective were overall response rate (ORR), median duration of treatment (MDT) progression-free survival (PFS), overall survival (OS). Results: The median age was 64 years (range 33-89). Pts with hormone receptor positive ABC were 133 (82%), 6 (4%) had HER-2 positive disease and 29 (18%) a triple negative profile. One hundred and thirty eight (85%) had already received chemotherapy in adjuvant and/or metastatic setting; anthracycline and taxanes were given in 64 pts (40%), anthracycline in 60 pts (37%) and taxane in 4 pts (2%), 9 pts (6%) received other regimens of chemotherapy. Twenty-five pts (15%) were chemo-naive. One hundred and thirty-three pts (82%) received endocrine therapy. Sixty-four pts (38%) had predominantly non-visceral metastases, 26 pts (16%) exclusive visceral involvement, 72 (44%) exhibited both characteristics. ORR was 58% (CR = 2%, PR = 16% SD = 40%) and MDT was 6.9 months. The median PFS and OS were 6.9 months and 21 months, respectively. We defined as “long responders” 19 pts (12%) with disease control interval > 24 months and, among them, as “very long responders”, 9 pts (6%) who exceeded 36 months. Efficacy was unrelated to biological profiles, sites of metastasis or previous therapies. No grade 3 and 4 adverse events occurred. Conclusions: Our results show that in pts with ABC a lower dose of capecitabine has a good toxicity profile and similar overall response rate and survival data in comparison to the approved dose. In addition, we identified a subset of long and very long responders but further studies are warranted to evaluate clinical/biological predictors of a long-term response.
Early detection of oral cancer in Portugal: The experience of UMEMD.
Authors: Estevinho Fernanda , Gouveia Margarida , Costa Marta , Moura Sara , Neves João Sérgio , Paulo-Subtil Domingos , Marinho Jorge , Leite-Moreira João 
Published: September 2018

e13039 Background: Oral and pharyngeal cancer is the 11th most common malignancy worldwide. Although the oral cavity is a potentially accessible site for examination, up to 50% of oral cancers are detected at advanced stage. The Mobile Unit of Stomatology and Dental Medicine (UMEMD) of the Portuguese League Against Cancer (LPCC) and of the Portuguese Association of Hospital Dental Medicine (APMDH) has developed oral cancer early diagnosis consultations. This consultations were performed by a team of 50 doctors specialized in oral cancer diagnosis. Once a month the team of UMEMD went to a different region of the North of Portugal. Early oral cancer diagnosis consultations were also performed twice a week at the Portuguese League Against Cancer at Oporto.We present the experience of UMEMD in the early diagnosis consultation of oral cancer, since its foundation in August 2012 until the end of 2016. Methods: We performed a retrospective evaluation of medical records of patients observed in the early diagnosis consultation of oral cancer of UMEMD between August 2012 and December 2016. We assessed the demographic characteristics, risk factors, cancer history, likely diagnosis and the referral of patients. Results: 6,231 new patients were observed; median age of patients was 63 years-old [1;102], 93 patients were younger than 18 years-old. There was information about smoking habits of the majority of patients n = 4,521(72.6%): 597(9.6%) were smokers and 653(10.5%) former smokers. 228 (3.6%) patients had previous cancer. We detected: 963 lesions (15.5%); the majority of the lesions were at the tongue n = 263 (4.2%).The patients with suspicious lesions (n = 638; 10.2%) were referred to: Portuguese Institute of Oncology of Oporto: n = 146 (2.3%); Faculty of Dental Medicine of the University of Oporto: n = 353 (5.7%); Physicians at other hospitals: n = 139 (2.2%). Conclusions: Consultations for oral cancer early diagnosis performed by an experienced team has enabled the detection of suspicious lesions in 10.2% of the patients. Cooperation with other institutions, through protocols, allowed the referral and early treatment of these patients.
Low grade b-cell non-Hodgkin lymphomas (NHL) involving the central nervous system (CNS): An analysis from the National Cancer Database (NCDB).
Authors: Pophali Priyanka Avinash , Thanarajasingam Gita , Pulido Jose , Johnston Patrick B. , Go Ronald S. 
Published: September 2018

e13083 Background: CNS involvement from low grade B-cell NHL is rare and has only been reported as case series. The distribution, demographics and outcomes of patients with low grade B-cell CNS NHLs have not been well characterized. Methods: The NCDB represents ~70% of cancer cases in the United States. Using the 2004-2013 NCDB extranodal NHL database, we identified all CNS B-cell NHLs based on ICD-O-3 site and histology codes. Primary or secondary CNS involvement could not be determined. Results: Out of 9435 CNS NHL cases, 475 [5.03%] had low grade histologies. In this group, the median age at diagnosis was 58 years [range 19-89]. Majority of the cases were female [56%], White, non-Hispanic [72%], privately insured [53%], with no comorbidities [74%] and treated in academic/research programs [38%]. Site of CNS disease was not specified in 22%. HIV status was known in 318 cases (6.3% positive). The brain [44%] was the most common site of involvement followed by spinal cord [19%] and meninges [15%]. Follicular lymphoma (FL) [48%] was the most common histology overall followed by marginal zone (MZL) [37%], small lymphocytic (SLL) [8%] and lymphoplasmacytic lymphomas (LPL) [7%]. MZL was the most common histology in the brain [44%] and meninges [61%] while FL was most common in the spinal cord [77%] and nervous system, NOS [69%]. Cranial nerves and eye (retina/optic nerve) involvement was very rare [2 and 1 case each- both MZL]. The overall survival (OS) of CNS B-cell NHL was significantly better if histology was low grade vs other [5-year OS 74% vs 32%, P < 0.0001]. Among CNS low grade B-cell NHLs, 5-year OS varied by histology [MZL 83%, FL 75%, LPL 56% and SLL 50%, P = 0.0003] and site of disease [spinal cord 89%, meninges 78% and brain 63%, P = 0.03] in addition to age at diagnosis and co-morbidities on both uni- and multivariate analysis. Survival was not influenced by sex, race, insurance, year of diagnosis, facility type or location. Conclusions: CNS involvement with low grade B-cell NHL is rare but has a relatively good outcome with most patients surviving beyond 5 years. FL and MZL are the more common low grade histologies. Both histology and disease site are important factors affecting survival.