Advancements of ALK inhibition of non-small cell lung cancer: a literature review.

Background and Objective: The therapeutic landscape for non-small cell lung cancer (NSCLC) has evolved considerably in the last few years. The targeted drugs and molecular diagnostics have been developed together at a fast pace. This narrative review explores the evolution of anaplastic lymphoma kinase (ALK) targeting therapies from discovering the ALK protein, molecular tests, present clinical trial data and future perspectives. Since the body of evidence on lung cancer is growing daily, most oncologists need time to implement data in their daily practice. Methods: We developed a narrative review to provide up-to-date help in the clinical decision-making of ALK-altered NSCLC patients. In 2022, the authors reviewed PubMed's published pivotal randomized Phase 3 trial results. Key Content and Findings: The development of ALK inhibitors was a revolution that is still ongoing; second and third-generation ALK inhibitors provided more than 30 months of progression-free survival (PFS) and impressive "brain-control". Brigatinib provided a survival benefit for patients with baseline brain metastases (HR 0.43, 95% CI: 0.21-0.89), and Lorlatinib demonstrated intracranial response rates of 82%, with 71% of complete intracranial responses. Personalized medicine is the new paradigm, from performing broad genetic panels for diagnosis to individual targeted therapy or combinations of different targeted agents. Conclusions: In the future, performing broad molecular panels should be the standard of care in the front line and after each progression to detect arising resistance mechanisms. Longer PFS will substantially convert a deadly condition into an almost chronic disease in the following decades. Treatment sequencing will be the cornerstone for patient survival, and liquid biopsies may replace tissue biopsies.

Prognostic role of 18F-FDG PET-CT in the prone position in the evaluation of invasive breast carcinoma

Introduction: The objective of this study was to correlate the features of invasive breast carcinoma in 18F-FDG positron emission tomography/computed tomography with histopathological results, findings from other imaging methods, and survival. Methods: This observational single-center study included patients who underwent staging 18F-FDG positron emission tomography/ computed tomography between September 2012 and April 2019; the results were correlated with the findings of other imaging tests and anatomopathological results. Lesions were evaluated for their maximum standardized uptake value on positron emission tomography/computed tomography performed in the prone position. Tumors were classified into three subtypes (luminal, HER2 and triple-negative) based on immunohistochemical analyses. Results: A total of 125 patients with a mean age of 52 years (24­90 years) were analyzed. The primary tumor showed an increased 18F-FDG concentration on positron emission tomography/computed tomography in 122 (97.6%) patients, with a mean maximum standardized uptake value of 7.15 (1.0­32.9 range). The mean maximum standardized uptake value was higher in the triple-negative subtype (11.4; n=24) than in the luminal (6.2; n=89) and HER2 (5.0; n=9) subtypes (p<0.01). Tumors with more aggressive histological and immunohistochemical characteristics showed higher maximum standardized uptake values. Patients with a standardized uptake value greater than 7 in the primary tumor or greater than 6.7 in the axillary lymph nodes had poor overall survival (p=0.03 and p<0.01, respectively). Conclusions: Our study suggests that the maximum standardized uptake value obtained on positron emission tomography/computed tomography in the prone position may correlate with the tumor immunophenotype and overall survival regardless of the treatments performed, and can be used as a prognostic biomarker in invasive breast carcinoma patients

The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer.

Introduction: Non-small cell lung cancer (NSCLC) is the second most common cancer globally. The mesenchymal-epithelial transition (MET) proto-oncogene can be targeted in NSCLC patients. Methods: We performed a literature search on PubMed in December 2019 for studies on MET inhibitors and NSCLC. Phase II and III clinical trials published in English between 2014 and 2019 were selected. Results: Data on MET inhibitors (tivantinib, cabozantinib, and crizotinib) and anti-MET antibodies (emibetuzumab and onartuzumab) are reported in the text. Conclusion: Emibetuzumab could be used for NSCLC cases with high MET expression. Further, studies on onartuzumab failed to prove its efficacy, while the results of tivantinib trials were clinically but not statistically significant. Additionally, cabozantinib was effective, but adverse reactions were common, and crizotinib was generally well-tolerated.

Magnetic resonance imaging of the breast: role in the evaluation of ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a precursor mammary lesion whose malignant cells do not extend beyond the basement membrane and presents a risk of progression to malignant disease. Its early detection increased with screening mammography. The objective of this study was to review the literature on the main presentations of DCIS on magnetic resonance imaging (MRI), through searches of the Medline/PubMed, Latin-American and Caribbean Center on Health Sciences Information (Lilacs), and Scientific Electronic Library Online (SciELO) databases. DCIS can occur in its pure form or in conjunction with invasive disease, in the same lesion, in different foci, or in the contralateral breast. MRI has a high sensitivity for the detection of pure DCIS, being able to identify the non-calcified component, and its accuracy increases with the nuclear grade of the lesion. The most common pattern of presentation is non-nodular enhancement; heterogeneous internal structures; a kinetic curve showing washout or plateau enhancement; segmental distribution; and restricted diffusion. MRI plays an important role in the detection of DCIS, especially in the evaluation of its extent, contributing to more reliable surgical excision and reducing local recurrence.

O carcinoma ductal in situ (CDIS) é uma lesão mamária precursora cujas células malignas não ultrapassam a membrana basal e possui risco de evolução para doença maligna. Sua detecção precoce aumentou com a mamografia de rastreamento. O objetivo deste estudo foi realizar uma revisão da literatura sobre as principais apresentações do CDIS na ressonância magnética (RM), utilizando mecanismos de busca na base de dados Medline/PubMed, Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde (Lilacs) e Scientific Electronic Library Online (SciELO). O CDIS pode ocorrer de forma pura ou associado a doença invasiva, na mesma lesão, em focos diferentes e na mama contralateral. A RM possui alta sensibilidade para a detecção do CDIS puro, sendo capaz de identificar o componente não calcificado da doença e sua precisão aumenta com o seu grau nuclear. O padrão de apresentação mais comum é o realce não nodular com padrão interno heterogêneo, curva cinética de lavagem rápida (washout) ou platô, de distribuição segmentar e com restrição na difusão. A RM tem importante papel na detecção do CDIS e, principalmente, na avaliação da sua extensão, contribuindo para uma exérese cirúrgica mais confiável e reduzindo as recidivas locais.

Magnetic resonance imaging of the breast: role in the evaluation of ductal carcinoma in situ / Papel da ressonância magnética das mamas na avaliação do carcinoma ductal in situ

Abstract Ductal carcinoma in situ (DCIS) is a precursor mammary lesion whose malignant cells do not extend beyond the basement membrane and presents a risk of progression to malignant disease. Its early detection increased with screening mammography. The objective of this study was to review the literature on the main presentations of DCIS on magnetic resonance imaging (MRI), through searches of the Medline/PubMed, Latin-American and Caribbean Center on Health Sciences Information (Lilacs), and Scientific Electronic Library Online (SciELO) databases. DCIS can occur in its pure form or in conjunction with invasive disease, in the same lesion, in different foci, or in the contralateral breast. MRI has a high sensitivity for the detection of pure DCIS, being able to identify the non-calcified component, and its accuracy increases with the nuclear grade of the lesion. The most common pattern of presentation is non-nodular enhancement; heterogeneous internal structures; a kinetic curve showing washout or plateau enhancement; segmental distribution; and restricted diffusion. MRI plays an important role in the detection of DCIS, especially in the evaluation of its extent, contributing to more reliable surgical excision and reducing local recurrence.

Resumo O carcinoma ductal in situ (CDIS) é uma lesão mamária precursora cujas células malignas não ultrapassam a membrana basal e possui risco de evolução para doença maligna. Sua detecção precoce aumentou com a mamografia de rastreamento. O objetivo deste estudo foi realizar uma revisão da literatura sobre as principais apresentações do CDIS na ressonância magnética (RM), utilizando mecanismos de busca na base de dados Medline/PubMed, Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde (Lilacs) e Scientific Electronic Library Online (SciELO). O CDIS pode ocorrer de forma pura ou associado a doença invasiva, na mesma lesão, em focos diferentes e na mama contralateral. A RM possui alta sensibilidade para a detecção do CDIS puro, sendo capaz de identificar o componente não calcificado da doença e sua precisão aumenta com o seu grau nuclear. O padrão de apresentação mais comum é o realce não nodular com padrão interno heterogêneo, curva cinética de lavagem rápida (washout) ou platô, de distribuição segmentar e com restrição na difusão. A RM tem importante papel na detecção do CDIS e, principalmente, na avaliação da sua extensão, contribuindo para uma exérese cirúrgica mais confiável e reduzindo as recidivas locais.