Background
Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast ...cancer (BC) and to test the ability of scalp cooling in prevention.
Patients and methods
BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed.
Results
In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m
2
presented a significantly higher prevalence of grades 1 PA (33–52%) and 2 PA (5–12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m
2
was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36–13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m
2
, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m
2
) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse.
Conclusion
Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m
2
) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.
Counter-mapping is a useful tool to counteract the hegemonic forms of creating maps and overcoming territorial logics of domination. The purpose of counter-mapping projects is mapping and visualizing ...information to be monitored in real time and generate collaborative creation processes for the creation of alternative learning networks and interactive community cartography that works as a territorial appropriation tool. In Colombia, the counter-mapping platform AgroEcoBogotá is inspired by the social, environmental and agroecological movements that create new ways of doing and being in this world through agroecological initiatives, allowing the emergence of transformative pathways of the agrifood system in the metropolitan area of Bogotá, the capital of the country. The platform is a tool to promote and give visibility to the movement of agroecology in Bogotá, through the mapping of huertas urbanas (urban farms and gardens) and other urban agriculture projects. The aim is to create solidarity links between different urban and peri-urban food initiatives of Bogotá and its neighborhoods and to connect the existing networks of urban agriculture with the rural sphere. The motivation to create the platform was the observation and acknowledgment of the lack of a network of networks that could encourage the interaction and strengthening of agroecological initiatives. With the example of one mapping-point, Casa Taller Las Moyas in the Eastern Hills of Bogotá (Cerros Orientales) we want to illustrate the importance of huertas urbanas as spaces of local community empowerment. In this context, counter-mapping also serves as a resource for resistance and grassroots appropriation of space. As a conclusion, we will reflect about the challenges that AgroEcoBogotá is facing in the effort to make visible the agroecological movement of Bogotá, as well as, to strengthen the existing networks in Bogotá and their rural food supply connections in different parts of the region of Cundinamarca.
In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.
Spatial reasoning is critical for mathematics learning and achievement, and its comprising skills are necessary in science, technology, engineering, and mathematics careers. To support young children ...in learning to reason spatially, clear definitions of the construct and supports for early childhood educators to teach the skills are needed. This study defines spatial reasoning as a comprehensive, comprehensible framework of skills. Using problem-driven content analysis, 835 text units from 103 sources, plus definitions from two reputable dictionary sources, were used to adopt, adapt, and infer the definitions for 40 terms that collectively represent spatial reasoning. Findings provide both the definitions and evidence of the extent to which various spatial reasoning skills have been investigated empirically. Directions for future research are discussed, including the need to refine the framework to ensure its utility for teachers and researchers.
Abstract
Background: No specific targeted therapies are available for Triple Negative Breast Cancers (TNBC), an aggressive and diverse subgroup. The basal TNBC sub-group share some phenotypic and ...molecular similarities with germline BRCA (gBRCA) tumours. In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow drugs called PARP inhibitors (Olaparib) to work more effectively. Aims: To establish if the addition of olaparib to neoadjuvant platinum based chemotherapy for basal TNBC and/or gBRCA breast cancer is safe and improves efficacy (pathological complete response (pCR)).
Methods: Trial design: 3-stage open label randomised phase II/III trial of neoadjuvant paclitaxel and carboplatin +/- olaparib, followed by clinicians' choice of anthracycline regimen. Stage 1 and 2: Randomisation (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 for 4 cycles) or one of two research arms with the same chemotherapy regimen but with two different schedules of olaparib 150mg BD for 12 days. Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. End-points: Stage 1: Safety; Stage 2: Schedule selection using pCR rate and completion rate of olaparib using a “pick-the-winner” design. Stage 3: pCR rate. Enrichment design is applied with an overall significance level 0.05(α) and 80% power. A total of 527 patients will be included to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to platinum based chemotherapy.
Trial Progress: PARTNER has been recruiting in UK since 27th May 2016. IDSMC recommended to continue the trial without change after reviewing the Stage 1 safety data. The recruitment of stage 2 was completed in April 2018 and results to be reviewed by the IDSMC in early 2019. The trial is open and enrolling patients to national and international sites.
Citation Format: Abraham J, Vallier A-L, Qian W, Machin A, Grybowicz L, Thomas S, Weiss M, Harvey C, McAdam K, Hughes-Davies L, Roberts A, Roylance R, Copson E, Pinilla K, Armstrong A, Provenzano E, Tischkowitz M, McMurty E, Earl H. PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients abstract. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-03-03.
Abstract
Pathological evaluation of response after NAC is a controversial issue. M&P has been for years the most widely employed score. Recently RCB index, a new system including axillary evaluation, ...seems to improve prognostic discrimination.
PURPOSE: The aim of this study was to validate the RCB index as a method to define prognosis in a reallife cohort of EBC patients treated with NAC and compare it to M&P system.
METHODS: We performed a retrospective analysis of our database. Patients with stage I-III considered candidate for NAC between January 2003 and August 2011 were included. RCB and M&P were calculated as previously published. Hormone receptor expression (RH), and Her2 were assessed following international guidelines. The Harell c-index and Roc curves were used to compare the prognostic value of RCB and M&P. Clinical, therapeutic and pathological data were obtained from medical records. A correlation with disease-free survival (DFS) and overall survival (OS) was done using the Kaplan-Meier method and Cox regression model.
RESULTS: 333 patients were included in this study. Distribution of breast cancer subtypes was: luminal 50.9%, Her2+ 31% and triple negative 18.1%. Mean tumour size was 42.3 mm. The majority of the patients had histhological grade II-III tumours (87.3%), with N stage 0-1 (97.3%). 87.4% received anthracycline and taxane-based NAC, associated to trastuzumab in her 2+ patients. Pathological complete response was 14% for the global population, being 30% for TN and 21.3% Her2+ subtypes. With a median follow-up of 56.3 months, DFS and OS at 5 years were as follows: RCB-0 93.6% and 97.9%, RCB-I 84.2% and 98.2%, RCB-II 79.1% and 89.5%, RCB-III 38.3% and 63.6%. Harell c-index value of RCB was statistically superior to M&P in both DFS (0.80 vs 0.68, p= 0.001) and OS (0.87 vs 0.69, p<0.001 ). This superiority value of RCB was consistent among all breast cancer subtypes.
CONCLUSION: RCB index is as more accurated prognostic score to predict DFS and OS compared to M&P.
Citation Format: Pons V, BurguÉs O, PÉrez-Fidalgo JA, MartÍnez MT, Pinilla K, Bermejo B, Lluch A. Validation of residual cancer burden index (RCB) as a prognostic tool in patients with early breast cancer (EBC) treated with neoadjuvant chemotherapy (NAC): Comparison of RCB and Miller & Payne system (M&P). abstract. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-12.
Abstract
Background:
In patients with TNBC, following standard neoadjuvant chemotherapy, residual disease (RD) is correlated with poor prognosis and 50% relapse within 5 years 1. PARTNER is a ...neoadjuvant clinical trial which randomises TNBC and gBRCAm patients to carboplatin and paclitaxel +/- olaparib followed by anthracycline-based chemotherapy. Patients with RD after neoadjuvant treatment in this trial also face poorer survival outcomes, due to the paucity of treatment options. PARTNERING, develops a new strategy using novel agent combinations as an alternative pathway for patients with RD within the PARTNER trial.
Methods: PARTNERING is a phase II open label, sub-study with a two-stage Simon design with biomarker guided treatment cohorts open only to patients in the PARTNER trial. A maximum of 15 patients will be included in each cohort. Patients with RD > 10% tumour cellularity (TC) on biopsy after neoadjuvant therapy will be eligible. Patients who have no tumour cells or < 10% TC, and those with progressive disease will be excluded. Allocation of patients into the cohorts will be based on tumour infiltrating lymphocytes (TILs) expression either on diagnostic or post treatment biopsy. Patients with tumours with TILs score ≤20% are considered “non-immunogenic” They will be stratified according to HRD status and allocated to receive a cell cycle checkpoint inhibitor + olaparib. Patients with a TILs score >20% are considered “immunogenic” and will be allocated to receive an immune checkpoint inhibitor with olaparib or a cell cycle checkpoint inhibitor.
Primary outcome measure is pCR / MRD rate at surgery after the administration of 2 cycles / 8 weeks of a combination of new agents. The rate of conversion to pCR/MRD will be correlated with TC, TILs, BRCA and homologous recombination deficiency (HRD) status, Ki67% and previous olaparib treatment.
Progress: The PARTNERING pathway in the PARTNER trial will be open late 2018.
Citation Format: Abraham JE, Vallier A-L, Qian W, Machin A, Grybowicz L, Thomas S, Weiss M, Harvey C, McAdam K, Hughes-Davies L, Roberts A, Provenzano E, Pinilla K, Roylance R, Copson E, Armstrong A, McMurtry E, Tischkowitz M, Earl HM. PARTNERING / PARTNER : Phase II sub-study to establish if the addition of combinations of new agents (olaparib, cell cycle and immune checkpoint inhibitors) can improve the rate of pathological complete response (pCR) and minimal residual disease (MRD) in triple negative breast cancer (TNBC) and / or germline BRCA mutated (gBRCAm) patients with evidence of residual disease after PARTNER therapy abstract. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-01-02.
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