bluuebunny/crossref_metadata_2025_split huggingface dataset:
Financial burdens (FB), quality of life, and psychological distress among advanced cancer patients (ACP) in phase I trials and their spousal caregivers (SC).
Authors: Hlubocky Fay J. , Cella David , Sher Tamara G. , Ratain Mark J. , Daugherty Christopher 
Published: March 2020

6117 Background: FBs have been identified as a significant predictor of stress for cancer patients and their caregivers/partners. FBs may indirectly affect the quality of life and psychological distress of clinical trial subjects, particularly those with advanced disease on Phase I trials. Methods: A convenience sample of ACP enrolling in phase I trials was assessed at baseline (T1) and one month (T2) using several measures including: depression (CES-D), state-trait anxiety (STAI-S/T), quality of life/qol (FACIT-Pal), and global health (SF-36). Data on FB were obtained via the questions of Ell (2008), querying subjects on: employment status, unexpected medical costs, concerns regarding wages (e.g. termination, use of sick time), and financial stress. Results: 104 subjects (52 Phase I ACPs and 52 SC) were separately interviewed at T1 and T2. For the total population: median age 61 (28-78y); 50% male; 100% married; 87% Ca; 67%> HS educ; 55% GI dx; 53% income <$65,000 yr, with45% ACPs employed full/part-time; 55% retired; 66% SC employed full/part-time with 34% retired. At T1, 82% of ACP reported medical cost concerns and 79% reported financial stress. For SC at T1, 69% reported medical costs concerns; 83% employed SC reported wage concerns; and 81% reported financial stress. For both ACP and SC, rates remained consistent with the exception of increased self-report re medical cost concerns at 85% and 72% respectively at T2. At T2, ACP who reported unexpected medical costs had higher STAI-S (31 ± 10 v 29 ±12, p=0.02) and CES-D scores (12 ± 11 v 10 ± 9, p=0.04). SC with self-reported financial stress had higher STAI-S anxiety (39 ± 17 v 35 ± 13, p=0.03) at T2. In regression analyses, ACP with medical costs concerns had poorer FACIT-Pal QOL over time. Also, SC with medical cost concerns at T2 was negatively associated with SF-36 scores. ACP and SC qualitative responses re FBs revealed salient themes: insurance coverage, unexpected costs associated with research study participation, Medicare, bankruptcy, and worry re financial stability after ACP death. Conclusions: FBs are negatively associated with quality of life among clinical trial subjects and SC in phase I trials.
Variation in health-related quality of life (HRQOL) by ECOG performance status (PS) and fatigue among patients with chronic lymphocytic leukemia (CLL).
Authors: Flowers Christopher , Pashos Chris L , Weiss Mark Adam , Lamanna Nicole , Farber Charles Michael , Kipps Thomas J. , Lerner Susan , Kay Neil E , Sharman Jeff Porter , Grinblatt David L. , Flinn Ian W. , Kozloff Mark , Swern Arlene S , Khan Zeba M. , Street Thomas , Sullivan Kristen , Keating Michael J. , Yu Ren 
Published: March 2020

6122 Background: Clinicians and investigators commonly use ECOG PS and clinician-reported patient (pt) fatigue as surrogates for HRQOL, a multi-faceted construct that comprehensively looks at the pt perspective on disease and well-being. Because limited data exist on the relationships between PS, fatigue, and HRQOL for CLL pts, we examined the associations between these measures, and 3 validated HRQOL instruments: the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), EQ-5D, and Brief Fatigue Inventory (BFI). Methods: Data were collected in CONNECT CLL, a prospective US observational registry initiated in 2010. Patient demographics and clinical characteristics were provided by clinicians. Patient HRQOL was self-reported at enrollment using the FACT-Leu, EQ-5D, and BFI. Scores were analyzed by ECOG PS (0, 1, 2-4) and clinician-reported fatigue (yes, no). Differences in HRQOL scores were assessed by ANOVA. Results: HRQOL data were reported by 899 pts from 148 community, 10 academic, and 3 government centers. ECOG PS was available on 711 pts. Overall HRQOL, measured by mean FACT-Leu, FACT-G and EQ-5D Visual Analogue Scale (VAS), worsened with ECOG PS severity and was worse in pts with fatigue (all p<0.0001). All FACT-Leu domains except social/family were worse in pts with fatigue and those with higher ECOG PS. Mean EQ-5D pain/discomfort, mobility, self care and usual activities domain scores worsened in severity as ECOG worsened and for pts with fatigue (all p<0.011). BFI data indicated that global fatigue, fatigue severity and fatigue-related interference worsened by ECOG severity and were associated with clinician-reported fatigue (all p<0.0001). Conclusions: Initial CONNECT CLL results confirm that HRQOL worsens with worsening ECOG PS and was worse among pts with fatigue, especially in physical/functioning domains, pain/discomfort, and mobility. These results indicate that baseline ECOG PS and physician-rated fatigue are rapid assessments that predict robust measures of HRQOL. Future analyses are planned to examine how HRQOL, ECOG PS and fatigue change over time with changes in treatment and CLL disease status.
Relationship of MRI tests and referral of malignant adnexal masses to gynecologic oncologists for surgery.
Authors: Kupets Rachel , Miroshnichenko Gennady , Paszat Lawrence Frank 
Published: March 2020

6134 Background: To evaluate the patterns of radiologic imaging by family physicians and gynecologists in the work up of women found to have an adnexal mass on pelvic ultrasound. To evaluate whether advanced imaging tests are associated with improved referral of high risk adnexal masses to gynecologic oncologists. Methods: Centralized provincial databases of healthcare utilization were used to identify women aged 45 and older who received a pelvic ultrasound between 2006-2008. Subsequent imaging tests ordered by physician specialty were identified. Of those women who proceeded to laparotomy, logistic regression was performed to determine which imaging tests were associated with referral of high risk adnexal tumors to a gynecologic oncologist. Results: 193, 261 women had a pelvic ultrasound; 19, 949 (10.3%) had a laparotomy. 2223 and 627 women were categorized with benign and malignant adnexal masses respectively. Up to 12% of women had a pelvic MRI and 58% of women had a CT scan after a pelvic ultrasound.Family physicians referred 58% and gynecologists referred 47% of high risk ovarian masses to a gynecologic oncologist respectively after imaging.Gynecologic Oncologists operated on only 55% of women with malignant adnexal masses. On multivariate analysis factors significant for surgery by a gynecologic oncologist include a preoperative CT Scan OR 3.58 (p<.001) and CT Scan and MRI OR 7.78 (p<.001). Preoperative MRI alone had an OR of 1.86 (p=0.09) and was not significant. Mean time to surgery significantly increased when further imaging tests were performed after a pelvic ultrasound (100 days), CT (131 days), MRI (170 days), CT and MRI (179 days),P 0.002. Conclusions: The addition of a pelvic MRI to a pelvic ultrasound does not improve the referral of high risk adnexal masses to a gynecologic oncologist. A consensus on appropriate imaging and triage is needed when an adnexal mass is identified on ultrasound.
Long-term follow-up (FU) of patients with durable complete response (DCR) after chemotherapy (CT) and trastuzumab (T) for HER2-altered (HER2+) metastatic breast cancer (MBC).
Authors: Gullo Giuseppe , Zuradelli Monica , Sclafani Francesco , Ballot Josephine , Defrein Anne Marie , Santoro Armando , Crown John 
Published: March 2020

615 Background: Durable CT-induced complete response (DCR) of MBC is reported only anecdotally. The addition of monoclonal antibody T to conventional CT results in significant increase in response rates and prolonged survival for patients (pts) with HER2+ MBC. Though CRs are reported in most phase II and III clinical trials of CT+T, there is lack of data about clinical features and long-term outcome of these pts. Methods: We retrospectively reviewed all pts with HER2+ MBC treated at our Institutions with any CT+T and identified cases who achieved DCR. HER2 positivity was defined as 3+score at immunohistochemistry and/or amplification at FISH test. DCR was defined as a CR according to RECIST 1.0 criteria lasting >36 months. Results: We identified 13 pts with HER2+ MBC who met criteria for DCR following CT+T. Their characteristics are: median age: 56yrs (range 30-65), stage at diagnosis: M0 54%/M1 46%, histology: ductal 84%/mixed ductal-lobular 8%/unknown 8%, tumour grade: G3 54%/G2 23%/unknown 23%, oestrogen receptors (ER): neg 62%/pos 38%, sites of metastatic disease: liver only 54%/other visceral 15%/bone and soft tissues only 31%, chemotherapy regimen: taxane+carboplatin 54%/single-agent taxane 23%/docetaxel+lapatinib 15%, capecitabine 8%. Metastatic disease was biopsy-proven in 54% of pts. All pts received maintenance T. Median follow-up (FU) is 6.5 yrs (range 3.0-11.6). Median duration of T was 59 months (17-121). At database cut-off date 12 pts (92%) are alive. Five pts (38%) had disease relapse (3 on maintenance T, 2 after T discontinuation), 2 of whom had radical surgery. In 8 pts (62%) disease has not relapsed (characteristics: all 1st-line therapy, ER negative 75%, liver only distant disease 75%). Conclusions: This is the largest series to our knowledge analyzing long-term FU of HER2+ MBC pts with DCR following CT+T. DCR pts appear to have prolonged survival and a substantial subgroup of them have no further disease relapse. These pts are usually treated in the 1st-line setting, have more frequently ER-negative disease and liver-only metastases. We are currently investigating the molecular profile of this subset of pts.
Impact of PIK3CA mutations and p95HER2 expression on the outcome of HER2-positive metastatic breast cancer patients treated with a trastuzumab-based therapy.
Authors: Fontana Andrea , Allegrini Giacomo , al Zoubi Mazhar , Collecchi Paola , Mazzanti Chiara , Stasi Irene , Lucchesi Sara , Bona Eleonora , Ferrarini Ilaria , Salvadori Barbara , Arrighi Giada , Marcucci Lorenzo , Filidei Mario , Orlandini Cinzia , Falcone Alfredo , Bevilacqua Generoso , Zavaglia Katia 
Published: March 2020

629 Background: Currently, no biomarkers of trastuzumab (T) clinical resistance have been validated. The aim of this pilot study was to evaluate the impact of PIK3CA mutations and p95HER2 (pHER2 truncated form) expression on the efficacy of a T based-therapy in a HER2-positive metastatic breast cancer (MBC) patients (pts). Methods: 107 HER2-positive MBC pts, treated in the last 10 years, were evaluated. Median age was 54 years (25-79); ECOG performance status was 0 in 56% of pts; all pts received several lines of treatment including T; biomarkers molecular analysis was performed in 70 tumor specimens. The IHC expression of p95HER2 was evaluated by a monoclonal antibody that specifically recognizes only the HER2 external domain; the HER2 integrity was defined by the presence of a homogeneous membrane staining (moderate or intense) in at least 30% of the cells, otherwise the HER2 was defined as p95HER2 positive. PIK3CA mutations in exons 9 and 20 were detected by automated sequencing. The molecular data were correlated to Time to progression (TTP) of the first line treatment including T and the Overall Survival (OS) by using the Kaplan-Meir method and the log-rank-test. Results: p95HER2 positive pts and PIK3CA mutations in exon 9 or 20 were detected in 42% and 22% of tumor specimens, respectively. p95HER2 positive tumors showed a shorter TTP and OS that did not reach statistical significance; PIK3CA mutations correlated with a worse TTP (median 7,6 vs 11,3 months) and OS (median 20,1 vs 41,0 months, p= 0,046). Conclusions: These preliminary results suggest a possible role of PIK3CA mutational status in predicting the outcome of MBC pts treated with T.
Lapatinib or trastuzumab? Which anti-HER2 treatment is more effective in the treatment of patients with HER2-positive breast cancer with brain metastases? An Anatolian Society of Medical Oncology Study.
Authors: Kaplan Muhammet Ali , Isikdogan Abdurrahman , Koca Dogan , Kucukoner Mehmet , Gumusay Ozge , Yildiz Ramazan , Oztop Ilhan , Demir Lutfiye , Geredeli Caglayan , Kocer Murat , Yalçintas Arslan Ülkü , Inal Ali , Coskun Ugur , Sener Nur , Inanc Mevlude , Elkiran Emin Tamer , Ozdemir Nuriye , Gok Durnali Ayse , Suner Ali , Alici Suleyman 
Published: March 2020

638 Background: In the present study, we investigate that which treatment choice is more effective in the human epidermal growth factor receptor 2 (HER2) positive breast cancer patients with brain metastases. Methods: Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 111 patients treated with lapatinib or trastuzumab after brain metastases eligible for the analyses were identified. Patients received both drugs consecutively or sequentially were excluded from the study. Results: Median age was 44 years (27-76) and 46 of the 111 patients (41.5%) had received lapatinib. Median time to development of brain metastases was 12.2 months (0-71). Sixteen patients (14.4%) had undergone surgery, 33 (29.7%) radiosurgery, and 108 (97.2%) whole brain radiation therapy (WBRT). Median overall survival (OS) after brain metastases was 15 months(95% confidence interval (CI): 12.3-17.6). Lapatinib usage was prolonged OS over trastuzumab alone (19.1 months vs 12 months, p=0.039).Other parameters affecting the survival were Karnofsky performance score (KPS, >70), number of brain metastases (>3), extracranial metastases (≥2), performed neurosurgery, and received radiosurgery. After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival [Odds ratio (OR), 0.57; p=0.02). Conclusions: Although this retrospective multi-center study had several limitations, study results suggest that the usage of lapatinib after brain metastases prolonged survival compared to the usage of trastuzumab. This result should be support with prospective studies.
Trastuzumab treatment in patients with advanced breast cancer (ABC) confined to locoregional and skeletal sites: Results from a large noninterventional study.
Authors: Jackisch Christian , Schoenegg Winfried , Selbach Johannes , Welslau Manfred , Harich Hanns-Detlev , Schroeder Jan , Schmidt Marcus , Goehler Thomas , Hinke Axel , Eustermann Heidi , Ringel Ralf 
Published: March 2020

640 Background: In a prospective observation study routine trastuzumab (T) treatment in HER2+ ABC was evaluated in a total of 1,687 patients (pts) since 2001. This large number allows the subgroup analysis of patients with the involvement of specific sites. Methods: Information on extent of advanced disease was available in 1,674 pts (99%) with HER2 overexpressing ABC. Pts were either pre-treated (39%) or naïve to palliative chemotherapy (CT). The following subgroups and their characteristics were analysed: I: locally ABC only; II: bone metastases allowing for concomitant local tumour; III: other. Results: Locally advanced lesions were found to be the sole BC manifestation in 145 pts (8.7%), while bone metastases ± locally ABC were found in 209 pts (12.5%). This leaves a comparative population of 1320 pts with metastases to other sites, predominantly visceral metastases. The table shows the baseline and treatment characteristics, as well as the long term outcome based on progression/death observed in 79%/56% of pts. Concurrent CT (74% of total group) predominantly consisted of a taxane (46%) or vinorelbin (24%), with no major differences between the groups. Conclusions: In this HER2+ cohort, palliative pts with local lesions only show a comparatively high-risk profile with respect to grading, hormone receptor status and adjuvant CT. Nevertheless, locally ABC only is a significant favourable prognostic factor in HER2+ BC treated with T combinations, with a median survival of 4 to 5 years. [Table: see text]
Estrogen receptor in HER2-positive early breast cancer: Two different diseases?
Authors: Ciruelos Gil Eva Maria , Ghanem Ismael , Manso Luis , Hoyos Sergio , Castañeda Carlos , Lora David , Mendiola Cesar , Sancho Blanca , Pascual Tomas , Cortes-Funes Hernan 
Published: March 2020

642 Background: HER2+ breast cancer (BC) is a well characterized subtype of BC, due to the predictive value of HER2 overexpression for anti-HER2 targeted therapies. Nevertheless, around 50% of HER2+ BC are ER+ and clasiffied as luminal B/HER2+, but their biological and clinical behaviour may be different from HER2+/ER- tumors. Methods: We retrospectively reviewed 347 HER2+ (Herceptest +++ or FISH+) early BC patients (see Table) diagnosed at our institution in 1997-2007, and were divided into two study groups: HER2+/ER+ (group A) and HER2+/ER- (group B). ER+ was defined if expressed in > 10% tumor cells. Results: See table below. Mean age: 54.7 y (44.6 – 65). Mean Ki 67 was higher in B (37,2 vs 22,4%, p<0.0001). At the current FU, n¼ of events were insufficient to reach median DFS/OS. Mean DFS was 6.9 y (3.5 – 10.2); recurrent disease was higher (p 0.003) for B (54 pts, 43%) vs A (62 pts, 28%). 5-year DFS estimates: 78.4 % (95% CI 72.3 – 83.3) and 62.3 % (95% CI 53 – 70.27) for A and B, and 10-year DFS was 73.4% (95% CI 66.6 – 79) and 52.5% (95% CI 42.4 – 61.6) for A and B, respectively (p 0.0006). Most common recurrent sites were local (18) and bone (9) for HER2+/ER+ and liver (8) and lung (8) for HER2+/ER-. Mean OS was 8.03y (5.4 – 10.8); 28 (12,6%) pts died in A, vs 26 (21%) in B (p 0.043). 5-year OS estimates: 93.9 % (95% CI 89.7 – 96.4) and 87.6 % (95% CI 80.3 – 92.3) for A and B, and 10-year DFS was 84.2% (95% CI 77.5 – 89.0) and 74.1% (95% CI 63.4 – 82.2) for A and B, respectively (p 0.01). Conclusions: ER expression in HER2+ early BC defines two clinically distinct diseases with different long-term prognosis. These data may help to better individualize adjuvant therapies and future clinical trial designs. [Table: see text]
Correlation of TOP2A expression in HER2-positive breast cancer with pathologic response and clinical outcomes in patients undergoing neoadjuvant treatment based on anthracycline.
Authors: Santos Elizabeth S. , Costa Felipe D'Almeida , Bezerra Stephania , Lessa Rafael Costa , Cordeiro De Lima Vladmir Claudio , Gagliato Debora De Melo , Lima Geraldine Eltz , Fanelli Marcello Ferretti , Rocha Rafael Malagoli , da Costa Alexandre Andre Balieiro , Pereira Augusto Akikubo Rodrigues , Padua Fernando Vidigal , Sousa Carlos Eduardo Pires , Freitas Paulo Henrique Aires , Pinto Flavio Augusto Ismael , Rodrigues Newton Augusto Ferreira , Benevides Carlos Frederico Lopes 
Published: March 2020

643 Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. TOP2A (a target of anthracyclines) and HER2 genes are both amplified in 40% of breast cancers. Data from literature are conflicting regarding the potential of TOP2A as a predictor of response to anthracyclines. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy and evaluated nuclear TOP2A protein expression in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2011, data from 82 patients was reviewed. Forty nine patients had the paraffin blocks corresponding to the pre-treatment biopsy. All biopsies had some degree of TOP2A IHC expression. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 10%. This was found in 77.6% of cases. Forty percent of the patients achieved pathologic complete response in pos-treatment surgical specimens. Correlation was observed between TOP2A IHC expression and tumor pathological response (p0.02). It was observed a difference in pathological complete response in favour of the group positive for TOP2A (47.4% vs. 22.7%), although not significant (p=0.09). No difference in PFS and OS was observed between patients with complete response after median follow-up of 34 months. Conclusions: The expression of TOP2A seems to be a promising marker to predict pathological response to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer; however these findings would be better evaluated in prospective trials.
Relationship between changes in left ventricular ejection and use of angiotensin-converting enzyme inhibitors and/or betablockers during adjuvant trastuzumab chemotherapy in early breast cancer: Data from the real world.
Authors: Giotta Francesco , Oliva Stefano , Boccardi Lidia , Frattini Silvia , Fioretti Agnese Maria , Simoncini Edda , Pulignano Giovanni , Cioffi Gianni , Lestuzzi Chiara , Maurea Nicola , Tarantini Luigi 
Published: March 2020

645 Background: Adjuvant trastuzumab chemotherapy (aTrastC) improves DFS of pts with breast cancer and overexpression of HER-2. However, cardiovascular complication (CV) such as heart failure (HF) or significant left ventricular ejection fraction (LVEF) reduction may appear especially in those pts at increased CV risk. Methods: 253 women treated with aTrastC for EBC in 7 italian oncologic centers during the period 2008-2009 entered in a multicenter registry and were retrospectively studied in 4 subgroups according to the treatment with ACEi and/or BB. Occurrence of symptoms of HF and/or decrease in 10 points % of LVEF were recorded during the follow up. LVEF was measured at baseline and 3-6-9-12 months. Results: Symptoms of HF occurred in 2% of pts who did not take either ACEi/ARB or BB. HF event-rate was similarly increased in pts receiving one or both medications, partially justified by the increased CV risk in these subgroups. Prevalence of decrease in LVEF > 10 points% was similar in all study subgroups. Trends in LVEF were characteristics for each study subgroup: at 3-month evaluation a significant decrease in LVEF was detected in ACEi/ARB and ACEi/ARB + BB group. Multiple logistic regression analysis showed that combined ACEi/ARB + BB therapy depended on history of hypertension (OR 36.7, CI 4.3-315.5) and reduction of LVEF from baseline to 3-month evaluation (OR 0.88, CI 0.78-0.97) (best prediction – 3.5 points %, AUC 0.78, IC 0.65-0.91). Conversely, no association was found between changes in LVEF and ACEi/ARB or BB therapy alone. LVEF recovery from 3 to 12-month evaluation was inversely related to the changes in LVEF from baseline to 3-month evaluation and did not depend on any pharmacological treatment. Conclusions: In clinical practice, a history of hypertension and changes in LVEF during the first 3 months of aTrastC for early breast cancer influence the use of ACEi/ARB and BB. This behaviour may explain the characteristic trend in LVEF showed in the subgroups of patient receiving or receiving not ACEi/ARB or BB. Subsequent recovery of LVEF does not seem to be related to any medical treatment.