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Rafael M Grochot,1,2 Janaína Brollo,2 Floriano Riva Neto,2,3 Aline C Tregnago,2,3 Cassiano Scholze,3 Rui Norris,3 Sargeele Silva,2 Débora C Weschenfelder,2 André B Reiriz,1,2 Lessandra Michelin,1 Fábio F Pasqualotto11Department of Health Sciences, School of Medicine, University of Caxias do Sul, Caxias do Sul, RS, Brazil; 2UNACON Cancer Center, Caxias do Sul General Hospital, Caxias do Sul, RS, Brazil; 3CPM Laboratory, Caxias do Sul, RS, BrazilBackground: The PD-1/PD-L1 signaling axis is currently the most elucidated mechanism for tumor evasion of T-cell-mediated immunity. Nevertheless, few data are available regarding its impact on cervical cancer and the relationship with lymphocytic infiltrates.Methods: A retrospective assessment of all cases of cervical neoplasia treated in Caxias do Sul General Hospital, Brazil, between 2012 and 2016 was performed. Clinical and pathological data were collected from electronic records and analyzed. Original slides were independently reviewed by three pathologists to confirm diagnoses and to assess the immunohistochemical expression of PD-L1 and FoxP3 in tumor cells and lymphocytic infiltrates.Results: PD-L1 staining was present in 32.2% of the 59 cervical samples. Median overall survival time of the PD-L1-negative group was 47.8 months, a time point not yet reached by the PD-L1-positive group (p=0.968). Median progression-free survival was 24.3 months for PD-L1-negative and 11.5 months for PD-L1-positive patients (p=0.263). PD-L1 staining was found in 27.1% of the lymphocytic infiltrates, and survival analysis revealed no difference between PD-L1-positive and PD-L1-negative samples. There was no impact on survival related to FoxP3 staining in neither tumor samples nor lymphocytic infiltrates.Conclusion: Although the median progression-free survival times differed, the difference was not statistically significant. Our study corroborates the rationale that PD-L1 expression in cervical neoplasms has no impact on survival. PD-L1 expression in peritumoral lymphocytes revealed no impact on infiltration volume nor survival.Keywords: uterine cervical neoplasms, tumor-infiltrating lymphocytes, cancer, tumor microenvironment, survival

Al/Al2O3-composites as an example of light weight materials are very interesting for many industrial applications because of a favourable combination of low density and improved mechanical properties. The prediction of the macroscopic mechanical behaviour of these materials related to their microstructure requires the knowledge of damage initiation and crack development under external loading conditions and, if present, residual stresses have to be taken into consideration. Different types of material degradation like particle/matrix-debonding, particle failure and matrix cracking can be observed in these types of metal matrix composites. The aim of the present work is to introduce damage criteria into a FE-microstructural model in order to foresee the degradation process in an Al2O3-particle reinforced Al(6061) composite during mechanical loading. Presently, the conventional fabrication route of the Al/Al2O3-composite is a metallurgical method with extrusion for homogenisation of the microstructure and final heat treatment to achieve a defined precipitation state. The influence of thermal residual stresses due to cooling down from annealing temperature on the deformation and damage initiation of Al(6061)/10vol%Al2O3-composites is investigated through finite element analyses using the experimentally mapped real microstructure as binary data. Especially, the stresses in the ceramic particles which are responsible for particle cracking and the hydrostatic stresses in the Al-matrix making the particle–matrix interface prone to debonding were analysed. The results show the importance of the thermal residual stresses with respect to damage criteria as obtained by micromechanical FE-calculations. [Copyright &y& Elsevier]

Akinetopsia is a rare neurological syndrome characterized by an impaired perception of movement, often resulting from brain damage due to ischemia, epilepsy, or medication. It is also known as visual motion blindness, and patients with this condition are unable to perceive motion normally even with perfect visual acuity. This report aims to present a case of a patient in their late 40 s who developed akinetopsia and also an impairment in movement perception of objects without emitting sounds, after experiencing a late relapse of breast cancer with the occurrence of multiple brain metastases. The patient also experienced visual hallucinations, night terrors, and difficulty forming anterograde memory. Neuroimaging with MRI revealed severe brain damage, especially in the middle temporal area of the visual cortex. Akinetopsia is a rare phenomenon, and this is the first known case of its association with brain metastases., (© 2024. Fondazione Società Italiana di Neurologia.)

Purpose: To compare global health-related quality of life (HRQoL) and overall survival (OS) in patients with head and neck cancer treated with intensity modulated radiation therapy (IMRT), conformal radiation therapy (3DCRT) or conventional radiation therapy (2DRT)., Methods and Materials: In this real-world, multi-institutional and prospective study, HRQoL outcomes were assessed using the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Head and Neck 43 (H&N43) questionnaires. Item response theory was used to generate a global HRQoL score, based on the 71 questions from both forms. The effect of treatment modality on HRQoL was studied using multivariate regression analyses. Survival was estimated using the Kaplan-Meyer method, and groups were compared by the log-rank test., Results: Five hundred and seventy patients from 13 institutions were included. Median follow-up was 12.2 months. Concerning the radiation technique, 29.5% of the patients were treated with 2DRT, 43.7% received 3DCRT, and 26.8% were treated with IMRT. A higher proportion of patients receiving 2DRT had a treatment interruption of more than 5 days (69% vs 50.2% for 3DCRT and 42.5% for IMRT). IMRT had a statistically significant positive effect on HRQoL compared with 3DCRT (β= 2.627, standard error = 0.804, P = .001) and 2DRT had a statistically significant negative effect compared with 3DCRT (β= -5.075, standard error = 0.926, P < .001). Patients receiving 2DRT presented a worse OS (P = .01). There were no differences in OS when IMRT was compared with 3DCRT., Conclusions: IMRT provided better HRQoL than 3DCRT, which provided better HRQoL than 2DRT. Patients receiving 2DRT presented a worse OS, which might be related to more frequent treatment interruptions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Trastuzumab, in combination with chemotherapy, is the gold standard in the adjuvant treatment of patients with HER2 positive breast cancer. Limited data are available on the role of adjuvant trastuzumab in the elderly population. We performed a systematic review of prospective randomized trials with available data on the use of adjuvant trastuzumab in patients older than 60years, focusing on both the efficacy and the cardiac safety. Data extrapolated from two prospective trials were included for efficacy and cardiac safety. A significant 47% relative risk reduction was observed in elderly patients receiving trastuzumab compared to chemotherapy alone (pooled Hazard Ratio: 0.53; 95% CI, 0.36-0.77). The pooled proportion of cardiac events in elderly patients treated with trastuzumab was 5% (95% CI, 4-7%). The use of trastuzumab should be considered as a standard of care in the adjuvant therapy of elderly patients with HER-2 positive breast cancer. Acute and chronic medical conditions, nutritional status and level of daily activities should be considered. Uncertainty about cardiac safety in the elderly is a major concern., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Our purpose was to evaluate the locoregional recurrence (LRR) of patients with false-negative, frozen-section or close margins of retroareolar specimen in nipple-sparing mastectomy (NSM) procedure., Methods: From 2002-2008, we recruited patients who had atypia or presence of cancer cells in definitive histology of retroareolar tissue despite of absence of tumor cell in intraoperative retroareolar frozen section. We also included the close margin cases defined as the presence of tumor cells at the first frozen section, but after deeper core out of retroareolar tissue were revealed free of malignancy. The incidence of LRR and NAC recurrence were reported, and the factors associated were analyzed., Results: Of 948 NSM procedures, there were 88 false-negative, frozen-sections and 10 close margin cases. The 5-year cumulative incidence of LRR and NAC recurrence was 11.2 % (10/98 patients) and 2.4 % (2/98 patients), respectively. Analyzing the definitive results of retroareolar tissue, the 5-year cumulative incidence of LRR was 42.9 % (n = 4) for atypia, 10 % (n = 2) for lobular carcinoma in situ (LCIS), 10 % (n = 1) for close margins, 8.7 % (n = 3) for ductal carcinoma in situ (DCIS), and 0 % for invasive carcinoma. In situ carcinoma as a primary tumor was a significant predictor of NAC recurrence (P < 0.01)., Conclusions: Despite a high reliability of frozen section, there is still a minority of false-negative results. Nevertheless, the LRR is considerably low. This fact suggests the possibility of preservation of the NAC after discussion with the patient.

Background: Biopsy of metastatic site of disease can influence treatment decisions, but its impact on survival remains uncertain., Patients and Methods: One-hundred patients with first metachronous liver metastases (LM) from breast cancer (BC) who underwent liver biopsy between 1999 and 2009 were identified. One-hundred matched control patients with LM from BC and no biopsy were selected., Results: Liver biopsy had no statistically significant impact on survival when comparing biopsied patients to controls [HR 0.82 (95% CI 0.58-1.16)]. Patients with early metastasis (within 3 years) undergoing liver biopsy had a better survival [HR 0.60 (95% CI 0.38-0.97)] compared to those who did not. Liver biopsy had no statistically significant impact on survival in patients with late LM (after 3 years) [HR 1.09 (95% CI 0.69-1.74)]. We observed that 18 out of 100 biopsied patients (18.0%) had a conversion of predictive factors which allowed adjusting for therapy, specifically new expression of ER (n=5), overexpression of HER2 (n=12) or both (n=1). Fourteen out of 18 (77.8%) received anti-HER2 treatment for the first time at the time of metastasis and 3 others (16.7%) received hormone therapy. Those 18 patients showed a better survival compared to the other 82 biopsied patients [HR 0.55 (95% CI 0.28-1.10)] and compared to the 13 biopsied patients with disappearance of features which predicted responsiveness to a given treatment [HR 0.19 (95% CI 0.06-0.62)]., Conclusions: Liver biopsy can impact survival of patients with early metastases from BC. Discordance between primary and distant lesions can offer the patients new treatment options., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The choice of adjuvant treatments for women with breast cancer is based on several features that take into account the heterogeneity of the disease. Questions raised during the decision process include the following: i) What leads to the use of endocrine therapy? ii) What leads to the use of anti-HER2 therapy? iii) What justifies the use of chemotherapy?, Areas Covered: Choices of adjuvant treatment are based on parameters defined by molecular characterization of breast cancer subtypes or by approximations to this classification using traditional clinical-pathological features. Clinicians should consider cases within the various distinct subpopulation in order to properly select the most 'personalized' adjuvant therapeutic approach. Sensitivity to chemotherapy and/or targeted agents in subtypes of breast cancers are predictable based on gene pathway alterations and associated gene products. This review covers several clinical data on several investigational agents for early-stage breast cancer molecular subtypes. We selected from literature data prospective Phase I, II and III clinical trials of chemotherapy (weekly or daily schedules), including indicators of activity and toxicity and data on survival/mortality., Expert Opinion: The future of many investigational therapeutics in breast cancer is linked to our ability to identify the most druggable target in each subtype.