bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lorlatinib for advanced ALK and ROS1+ non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort.
Authors: Baldacci Simon , Avrillon Virginie , Besse Benjamin , Mennecier Bertrand , Duruisseaux Michael , Mazieres Julien , Descourt Renaud , Doubre Helene , Dubray-Longeras Pascale , Cadranel Jacques , Moro-Sibilot Denis , Ricordel Charles , Galland-Girodet Sigolène , Monnet Isabelle , Otto Josiane , Schneider Sophie , Missy Pascale , Morin Franck , Westeel Virginie , Girard Nicolas 
Published: May 2020

9615 Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival. Results: 200 patients were included: 143 (71.5%) ALK+, 57 (28.5%) ROS1+, 87 (44%) men, 127 (66%) never-smokers, and 167 (85%) stage IV disease. Mean age was 59 years. At the time of initiation of lorlatinib, 146 (74%) patients had Central Nervous System (CNS) disease (78 % for ALK+, 63% for ROS1+), 131 (76%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 3%/17%/27%/53%of ALK+ patients and in 30%/30%/16%/24%of ROS1+ patients, respectively. 150 (75%), 185 (93%), 138 (69%), and 80 (40%) patients had received prior chemotherapy, crizotinib, 2nd generation TKIs, and brain radiotherapy, respectively. Median PFS and OS from the initiation of lorlatinib were 11.8 (95% CI 7.3-14.6) months and NR (95% CI 18.6-NR) months, respectively for ALK+ patients and 7.6 (95% CI 6.2-10.2) months and 20.9 (95% CI 10.0-NR) months, respectively for ROS1+ patients. ORR and DCR were 46.2% (95% CI 37.6-54.7) and 86.2% (95% CI 80.2-92.1), respectively for ALK+ patients and 47.1% (95% CI 33.4-60.8) and 88.2% (95% CI 79.4-97.1), respectively for ROS1+ patients. CNS ORR was 41.7% (95% CI 33.3-50.1) and 37.7% (95% CI 24.7-50.8), respectively. With a median follow-up of 15.6 (95% CI 14.0-17.6) months, progression under lorlatinib treatment was observed in 71 (50%) ALK+ patients and 35 (61%) ROS1+ patients, and CNS progression in 24 (34%) and 8 (23%) patients, respectively. The safety profile of lorlatinib was consistent with published data. Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC.
Breast cancer recurrence rate in patients treated for early breast cancer.
Authors: Munguti Cecilia , Mutebi Miriam Claire , Ng'ang'a Mukuhi , Wasike Ronald 
Published: May 2020

e12508 Background: Recurrence rates for early breast cancer vary in different studies from 7% to 18%. Recurrent breast cancer is associated with poorer outcome and higher mortality rates. The recurrence rate in the Kenyan population remains unknown despite high prevalence of known risk factors. Methods: Single institution retrospective study of all women (18 -75 years) treated for early breast cancer at a single center private tertiary unit from 2009 to 2017. Results: 239 patient records were reviewed. The mean age at diagnosis was 51 (SD13.1). 98% of women presented with a palpable breast lesion. The molecular sub-type’s prevalence was: ER/PR+ (76%), triple negative (12.1%), HER2+ (2.9%). The overall recurrence rate was 7.2%, 66% recurrences were loco-regional, while 27% were metastatic disease, with 61% of the recurrences being detected initially on clinical/ self-breast examination. 77% of the recurrences were in women with ER/PR+ molecular sub-types. Recurrences in women with DCIS (2/27) were invasive breast cancers. There were no identified risk factors on uni-variate and multivariate regression analysis which conferred a risk of breast cancer recurrence. Discussion: The mean age at diagnosis in this group is younger than the western average (65 - 75 years). Majority of the women presented with symptoms – a presentation that differs from that of countries with a national breast cancer screening program. The molecular distribution of breast cancers is comparable to western populations. Conclusions: Recurrence rate for early breast cancer in this series is 7.2%, which is comparable with documented western data, with majority of the recurrences being detected initially on clinical/self-breast examination.
Efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor in the prevention of chemotherapy-induced neutropenia in patients with breast cancer.
Authors: Chong Xiaoyu , Zhu Xiaoli , Li Xuejuan , Gao Lingna , Ma Hongfang , Chong Baogui 
Published: May 2020

e12515 Background: To explore the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, brand name: Jinyouli) in the prevention of neutropenia in breast cancer patients receiving adjuvant chemotherapy with EC regimen (epirubicin combined with cyclophosphamide). Methods: Retrospective analysis was conducted on breast cancer patients receiving adjuvant chemotherapy with EC regimen in Hengshui People's Hospital between January 2018 to October 2019. In cycle 1, all patients developed grade 3/4 neutropenia and PEG-rhG-CSF was used prophylactically in the subsequent cycles. The incidence of grade 3/4 neutropenia, febrile neutropenia (FN), chemotherapy delay and dose adjustment were observed as well as relative dose intensity (RDI), antibiotics application and adverse events. Results: 96 breast cancer patients were enrolled and all of them developed grade 3/4 neutropenia (100%) in cycle 1. After secondary prophylactic use of PEG-rhG-CSF, the incidence of grade 3/4 neutropenia decreased to 26.32% (25/95), 12.50% (10/80) and 13.63% (9/66) in cycle 2-4, respectively, with a statistically significant difference with cycle 1 ( P<0.001); The incidence of FN decreased from 2.08% (2/96) in cycle 1 to 0% (0/95), 1.25% (1/80) and 0% (0/66) in the subsequent cycles ( P>0.05). The incidence of chemotherapy delay was 2.08% (2/96), 2.50% (2/80) and 1.52% (1/66) in cycle 2-4, respectively, and the incidence of dose adjustment was 9.38% (9/96) in cycle 2. There was no dose adjustment in cycle 3-4. The average RDI was 92%, 92% and 94% in cycle 2-4, respectively. The most common treatment-related adverse events were fever (2.08%), muscle pain (1.04%) and fatigue (1.04%). Conclusions: PEG-rhG-CSF secondary prevention can effectively reduce the incidence of neutropenia in breast cancer patients receiving adjuvant chemotherapy with EC regimen, which ensures the implementation of standard-dose chemotherapy with good safety.
The adjuvant radiotherapy benefits on pure mucinous breast carcinoma patients in different age stages: A SEER-based study.
Authors: Wei Xiaoqing , Dian Li ping , Tang Fan , Zhao Huijun , Situ Honglin , Xu Rui , Ren Liping , Zhang Yuzhu , Chen Qianjun 
Published: May 2020

e12519 Background: The aim of this analysis is to study the prognostic impacts of adjuvant radiotherapy on pure mucinous breast carcinoma patients in different age stages. Methods: Patients diagnosed pure mucinous breast carcinoma between 1998 and 2015 were identified from the Serveillance,Epidemiology,and Results End database. Chi-square, Kaplan-Meier method, Multivariate Cox proportional hazards models were used for statistical analysis. Results: We enrolled 10656 patients, including 5758 (54.0%) and 4898 (46.0%) in the with radiotherapy and without radiotherapy cohorts, respectively.The K-M method shows age is an independent prognostic factor in pure mucinous breast carcinoma patients with radiotherapy( p= 0.000 ). Compared with the younger groups (<45y and 46-54y),the older groups (55-64y, 65-75y and >75y) show a greater benefits with radiotherapy. The multivariate Cox proportional hazards model shows significant difference (all p= 0.000), the group 55-64y((HR = 0.58, 95%CI:0.453–0.742),the group 65-75y(HR = 0.709, 95% CI: 0.610–0.825),the group>75y (HR = 0.613, 95% CI: 0.543–0.691), which indicates a better radiotherapy benefits in older groups(especially in 65-75y). Conclusions: This study shows a better benefits of postoperative adjuvant radiotherapy in pure mucinous breast carcinoma older patients. Owing to the common incompleteness of systematic basic treatments in older breast cancer patients,our real world analysis results may be helpful for the clinical decision-making.
Safety and clinical evaluation of dual inhibition with pertuzumab and trastuzumab in HER-2-positive breast cancer patients.
Authors: Suppan Christoph , Steiner Daniel , Klocker Valentina Eva , Posch Florian , Henzinger Elisabeth Christina , Stoeger Herbert , Dandachi Nadia , Balic Marija 
Published: May 2020

e12520 Background: The addition of Herceptin to standard chemotherapy improved survival in patients with Her-2-positive breast cancer in neoadjuvant, adjuvant and metastatic setting. In higher tumor stage, the addition of pertuzumab is now standard of care and associated with a favorable toxicity profile. The purpose of this study was to evaluate the safety and efficacy of the biosimilar trastuzumab-dttb in combination with pertuzumab in Her-2-positive breast cancer patients. Methods: Thirty-five female patients with Her-2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz between September 2018 and August 2019 were included. Summary measures are reported as medians 25th– 75thpercentile for continuous variables and as absolute frequencies (%) for count data. Results: Thirty-five patients received a median of four [3-7] cycles of trastuzumab-dttb plus pertuzumab. The median cumulative trastuzumab-dttb dose was 1904mg [1560-2640] and the median cumulative pertuzumab dose was 2100mg [1680-3360]. All patients had a normal baseline LVEF (> 50%) prior to the initiation of trastuzumab-dttb plus pertuzumab treatment with a median LVEF of 60% [60-65]. At completion of trastuzumab-dttb plus pertuzumab treatment (or in case of ongoing therapy the last EF assessment), the median LVEF was 60.0 % [58-62]. 21 patients had a median absolute LVEF decline of 1% -5-0], corresponding to a median percent change of 1.7 percent points [-7.7-0]. Two patients (5.7%) had a LVEF reduction ≤50%. None of the patients had a decline in LVEF of ≥ 10 %. In 8 patients, a switch from Herceptin to trastuzumab-dttb was tolerated well and these were also included in the analyses. In only two palliative patients, pertuzumab was either interrupted or stopped due to diarrhea and appetite loss, while trastuzumab-dttb was ongoing. 24 of 35 patients (69%) were treated with trastuzumab-dttb plus pertuzumab in the neoadjuvant setting. Two of these patients were treated for local relapse and were excluded for efficacy assessment. Of the remaining 22 patients, 11 patients achieved a pCR (ypT0/ypTis and ypN0). Conclusions: In these series of Her-2-positive breast cancer patients, the combination of trastuzumab-dttb/pertuzumab was consistent with the known safety and efficacy profile of Herceptin/pertuzumab.
Chemotherapy-induced neutropenia among breast cancer patients presenting to a tertiary hospital in Nigeria.
Authors: Salako Omolola , Okunade Kehinde Sharafadeen , Adeniji Adeoluwa Akeem , Fagbenro Gabriel , Afolaranmi Oluwasegun 
Published: May 2020

e12523 Background: Neutropenia and febrile neutropenia are major dose-limiting adverse effects of systemic cancer chemotherapy. It has been associated with significant morbidity and mortality, and high costs of management, and treatment breaks in cancer patients especially in resource-limited environments leading to poorer outcomes. Chemotherapy-induced neutropenia is an established complication of breast cancer treatment, however, there is paucity of information on the exact magnitude of the condition. This study assessed the prevalence of neutropenia and febrile neutropenia, while identifying their associated factors. Methods: A cross-sectional study was conducted among 113 female chemotherapy-naïve breast cancer patients over a two-year period. Sociodemographic, clinical and haematological data was obtained via semi-structured interviews and from medical case files. Blood samples for complete blood count parameters were collected after each course of chemotherapy. The National Cancer Institute Common Terminology CTCAE version 4.03 was used to assess febrile neutropenia, neutropenia and its severity. Results: The prevalence of neutropenia and febrile neutropenia among the patients was 31.9% and 5.3% respectively. Throughout all courses of chemotherapy, there were neutropenic episodes 11.4% (57/502) with mild neutropenia 6.6%, moderate 3.4% and severe 1.4%. Prevalence of neutropenia decreased with increasing chemotherapy courses, with prevalence after first course being 14.2% and last course 4.9%. Associated risk factors for developing neutropenia include increasing age ( p = 0.014), ECOG performance score > 1 at presentation (p = 0.033) and presence of bone metastasis (p = 0.002). Conclusions: One in three breast cancer patients developed neutropenia while on chemotherapy. The use of prophylactic G-CSF after each course of chemotherapy should be a routine practice, especially among elderly patients, unstable patients, and those with bone metastasis.
High-risk of recurrence for nodal micrometastasis with breast pathologic complete response (ypT0/Tis ypN1mi) after neoadjuvant chemotherapy.
Authors: Garcia Torralba Esmeralda , de la Morena Pilar , Garcia Gomez Marina , Ivars Rubio Alejandra , Garcia Martinez Elena , Garcia-Garre Elisa , Martinez Galvez Maria , Zafra Gema Marin , Aguilar Jimenez Jose , Navarro Manzano Esther , Ayala Francisco 
Published: May 2020

e12524 Background: Nodal micrometastatic disease (ypN1mic) after neoadjuvant chemotherapy (nCT) for breast cancer (BC) is considered an indication for axillary lymph node disection. While pN1mic prognostic impact has been extensively studied, the prognostic impact of ypN1mic disease is uncertain and these patients are usually grouped together with nodal macrometastatic disease. Since outcomes may be difficult to evaluate in the setting of BC residual disease, our aim was to compare the prognostic meaning of ypN1mic with that of ypN0 when a pCR is obtained in the breast. Methods: We retrospectively analyzed a series of 454 BC consecutive patients treated between 2010 and 2018 with neoadjuvant chemotherapy (nCT) based on anthracyclines and taxanes (plus antiHER2 treatment when appropriate). Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients with pre-nCT sentinel lymph node biopsy or without post-nCT pathologic evaluation were excluded. Disease free (DFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox regression models. Results: 454 BC patients were included, with 106 (24%) pCR. Median follow-up was 39 months. 99 (21.8%) patients obtained a pCR both in breast and axilla (ypT0/Tis ypN0), with 4 recurrences (4%) while only 7 (1.5%) patients had isolated nodal micrometastatic disease (ypT0/Tis ypN1mic), with 2 recurrences (28%). Median DFS was not reached for the ypN0 group and was 28 months (95%CI: 21.6-34.4 months) for the ypN1mic group (HR: 16.55, 95%cI: 2.68-102.37; p = 0.003). No differences were observed for OS (p = 0.77), although 2/2 ypN1mi showed distant recurrence (2/4 for ypN0 patients). Baseline clinical and pathologic characteristics were comparable between both groups, with no differences in performance status (p = 0.45), clinical nodal stage (p = 0.48), HER2 (p = 0.32), estrogen receptors (p = 0.93), grade (p = 0.34), presence of carcinoma in situ (0.60) or clinical complete response (p = 0.42). Clinical characteristics of patients with recurrence were also similar (100%: clinically positive nodes, negative estrogen receptors, no clinical complete response). Conclusions: Residual nodal micrometastatic disease after nCT seems to be associated with a higher risk of recurrence. Although longer follow-up and larger series are needed to confirm our data, these results support the escalation of post-nCT treatment even in patients with ypN1mic and breast pCR.
How much is too much? Multidisciplinary management of elderly early-stage breast cancer (BC) patients.
Authors: Berger Elizabeth R. , Veeravalli Srinivasa Sevilimedu , Morrow Monica , Heerdt Alexandra S. 
Published: May 2020

e12525 Background: Optimal approach to early-stage breast cancer (BC) management in women ≥70y is unclear. Studies have demonstrated improved local control but no survival advantage with use of radiation therapy (RT) after breast-conservation therapy (BCT). The impact on survival of other management decisions, including breast procedure, axillary staging (AS), systemic treatment, and patient comorbidities is unknown. We evaluate the effect of each treatment decision on overall survival (OS), disease-free survival (DFS), and breast-cancer specific survival (BCSS). Methods: Patients age ≥70y with cT1N0/ER+/HER2- tumors undergoing surgery from 2011-2013 were identified from a prospectively maintained, single-institution database. Clinicopathologic features were evaluated. 10-year estimated mortality from comorbidity was calculated using a Suemoto index (SI). Univariate and multivariable associations were assessed using Cox modeling. Kaplan-Meier method was used to estimate OS and DFS. Results: 338 patients were identified: 312 (92%) underwent BCT; 26 (8%) had mastectomy. Median age was 75.5y (70-101); median tumor size was 1.0cm (0.1-1.9); median SI was 42.5(22-99). With a median follow-up of 60 mos, 25 patients died—1 from BC, for an OS rate of 92.8% and BCSS of 99.7%. 9 patients developed a locoregional recurrence and 1 developed distant recurrence, representing a 5-year DFS rate of 97.8%. There were no differences in DFS by age groups (≤75, 76-80, > 80; p = 0.1). On univariate analysis, DFS did not vary by age, breast procedure, or receipt of chemotherapy. It was improved in those who had AS and a lower SI (p < 0.01). OS was better in those patients who had AS, had recurrence score performed and had radiation therapy, reflecting lower SI. On multivariable analysis, lack of AS (HR 10.5, p < 0.01) and higher SI (HR 1.03, p < 0.01) were the only variables associated with worse OS. Lack of AS became non-significant in those > 80y. No treatment decision led to improved BCSS. When comparing patients with local or systemic recurrence vs those without recurrence, there was no difference in OS (p = 0.4) or BCSS (p = NS). Conclusions: Decisions in early-stage BC in the elderly are complex due to competing morbidities. While DFS and OS may vary based on treatment variables, no specific care component affected BCSS. Treatment discussions in elderly BC patients should emphasize the risks/benefits of each care component, taking into consideration the patient’s comorbidities and allowing for the patient’s understanding of outcomes and quality of life.
Analysis of the fatigue benefit, functionality, and body composition of a program of therapeutic exercise and healthy lifestyle habits in patients breast cancer operated.
Authors: Ruíz Sofía , Pajares Bella , Iglesias Campos Marcos , Roldán Jiménez Cristina , Cuesta Vargas Antonio , Alba Conejo Emilio 
Published: May 2020

e12533 Background: Numerous studies support the benefit of physical exercise in breast cancer, with a lower rate of fatigue, lower risk of recurrence and greater survival. In addition, it prevents cardiovascular diseases, diabetes and obesity. The objective of this work is to analyze the effect of a program of physical exercise and habits of healthy life on fatigue, functionality and body composition in breast cancer patients of the Medical Oncology Unit of the Hospital Virgen de la Victoria, Malaga. Methods: Prospective study on 97 patients with breast cancer after completing locoregional treatment and systemic chemotherapy. Treatment with hormone therapy and trastuzumab was allowed. All patients were without disease, without cardiovascular history that contraindicated the program and have signed the relevant informed consent. The duration of the program was 3 months and the parameter measurement was performed before and after. The main objective was analyze cancer-related fatigue and secondary functional parameters, anthropometric and adherence to Mediterranean diet. Fatigue, parameters functional and adherence to Mediterranean diet were evaluated by tests specific and anthropometric by different measurements including use of Tanita TBF-300A. Results: 97 patients were recruited, with a median age of 52 years (32 and 69), 60% had received neo/adjuvant chemotherapy, 84% hormonal therapy and 12% trastuzumab. Most patients underwent conservative surgery. (76%). After 3 months of intervention, women improved significantly cancer-related fatigue (p = 0.000), levels of diet adherence Mediterranean (p = 0.000), as well as functional parameters. One was observed statistically significant improvement in limb functionality/mobility upper, lower limb and general functionality (p = 0.005, p = 0.013 and 0.000, respectively). No differences were observed in terms of mass index body, fat mass or lean mass. Conclusions: This study shows the benefit in functionality and fatigue of an exercise program therapeutic and healthy lifestyle habits in breast cancer operated patients. Despite a significant increase in adherence to the Mediterranean diet, it is not they observed differences in anthropometric parameters.
Adipophilin expression as an independent marker for poor prognosis of patients with triple-negative breast cancer.
Authors: Yoshikawa Katsuhiro , Ishida Mitsuaki , Yanai Hirotsugu , Tsuta Koji , Sekimoto Mitsugu , Sugie Tomoharu 
Published: May 2020

e12552 Background: Adipophilin (ADP) is a lipid-regulating protein of the perilipin/adipophilin/tail interacting protein of 47 kDa (PAT) family that coats the surfaces of cytoplasmic lipid droplets. Lipids are essential for cellular proliferation in tumor cells, and ADP, which increases the efficiency of lipid use, may contribute to cancer growth. Some previous studies suggest that ADP expression can act as a prognostic marker for specific cancers. The aim of this study is to investigate the clinicopathological significance of ADP expression in patients with triple-negative breast cancer (TNBC). Methods: Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of ADP, glutaminase, and glutamate dehydrogenase (key enzymes in glutamine metabolism) in 61 TNBC patients who underwent operation from January 2006–December 2018. Relapse-free survival (RFS) was compared based on ADP expression and the risk factors for RFS were analyzed. Results: Fourteen (23.0%) patients were ADP-positive. As compared to ADP-negative TNBC patients, ADP-positive TNBC patients correlated with poor RFS ( p = 0.032). Among the TNBC patients with high Ki-67 labeling index, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.049). Moreover, among the patients without adjuvant chemotherapy, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.080). ADP-positive patients correlated with a significantly higher recurrence based on multivariate analyses (hazard ratio, 4.89; 95% confidence interval, 1.04–23.0; p = 0.044). Moreover, ADP expression significantly correlated with the expression of glutaminase and glutaminate dehydrogenase ( p < 0.001 and p = 0.029, respectively). Conclusions: ADP expression is a novel marker for poor prognosis of patients with TNBC and might be superior to Ki-67 as a prognostic marker. ADP expression may be related to upregulation of glutamine metabolism in cancer cells of TNBC.