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PURPOSE: Health literacy is a current Public Health priority in Portugal. The participation of well-informed patients in their care and shared decision making are essential, especially in chronic aggressive and debilitating pathologies such as recurrent or metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC). AIMS: This study aimed to characterize R/M HNSCC patients' and caregivers' information needs identified by healthcare professionals (HCPs). METHODS: Two online Focus Groups, one with only medical doctors and the other with other HCPs involved in the treatment of R/M HNSCC patients, were conducted, using a modified Metaplan, Lean or adapted PDCA methodology. The discussions were audio recorded in full and content analysis was performed using ATLAS.ti qualitative data analysis software. RESULTS: Topics addressed were diagnosis, treatment, quality of life, and global evaluation. In general, all experts agreed that only essential information should be cautiously given, according to patients' and caregivers' wishes. It was consensual that patients are given the necessary information to adhere to treatment. Two main barriers were identified: one barrier was associated with verbal communication due to the lack of health literacy of these patients, and the other barrier regarded healthcare access. It was also considered important to remind patients of the daily and social activities that they could and should maintain, as well as providing sufficient social resources and problem-solving training to caregivers. CONCLUSIONS: This qualitative study highlights the complexity of R/M HNSCC patients' care. Immediate availability of psychologists and psychiatrists should be implemented in all centers that treat HNSCC patients. The differences found between the physicians' Focus Group and other HCPs' Focus Group in some of the addressed topics emphasize the importance of a multidisciplinary and holistic approach, in a biomedical model integrated with a biopsychosocial model.
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Neoplasias de Cabeça e Pescoço , Letramento em Saúde , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Letramento em Saúde/métodos , Qualidade de Vida/psicologia , Recidiva Local de Neoplasia , Neoplasias de Cabeça e Pescoço/terapia , Equipe de Assistência ao PacienteRESUMO
BACKGROUND: Aromatase inhibitors (AI) are frequently used to treat hormone-receptor-positive breast cancer, but they have multiple adverse effects (e.g., osteoporosis, arthralgia), resulting in premature therapy discontinuation/switch. Physical activity (PA) can attenuate these negative effects and improve quality of life (QoL). However, most cancer survivors fail to perform/sustain adequate PA levels, especially in the long-term. Theory-based interventions, using evidence-based behavior change techniques, aimed at promoting long-term behavior change in breast cancer survivors are effective, but remain scarce and fail to promote self-regulatory skills and better-quality motivations associated with sustained PA adoption. This paper describes the design of the PAC-WOMAN trial, which will test the long-term effectiveness and cost-effectiveness of two state of the art, group-based interventions encouraging sustained changes in PA, sedentary behavior, and QoL. Additional aims include examining the impact of both interventions on secondary outcomes (e.g., body composition, physical function), and key moderators/mediators of short and long-term changes in primary outcomes. METHODS: A 3-arm pragmatic randomized controlled trial, involving a 4-month intervention and a 12-month follow-up, will be implemented, in a real exercise setting, to compare: 1) brief PA counseling/motivational intervention; 2) structured exercise program vs. waiting-list control group. Study recruitment goal is 122 hormone-receptor-positive breast cancer survivors (stage I-III), on AI therapy (post-primary treatment completion) ≥ 1 month, ECOG 0-1. Outcome measures will be obtained at baseline, 4 months (i.e., post-intervention), 10 and 16 months. Process evaluation, analyzing implementation determinants, will also be conducted. DISCUSSION: PAC-WOMAN is expected to have a relevant impact on participants PA and QoL and provide insights for the improvement of interventions designed to promote sustained adherence to active lifestyle behaviors, facilitating its translation to community settings. TRIAL REGISTRATION: April 20, 2023 - NCT05860621. April 21, 2023 - https://doi.org/10.17605/OSF.IO/ZAQ9N April 27, 2023 - UMIN000050945.
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Neoplasias da Mama , Sobreviventes de Câncer , Feminino , Humanos , Qualidade de Vida , Neoplasias da Mama/tratamento farmacológico , Inibidores da Aromatase/efeitos adversos , Motivação , Exercício Físico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Precision oncology is the ultimate goal of cancer treatment, i.e., to treat cancer and only cancer, leaving all the remaining cells and tissues as intact as possible. Classical chemotherapy and radiotherapy, however, are still effective in many patients with cancer by effectively inducing apoptosis of cancer cells. Cancer cells might resist apoptosis via the anti-apoptotic effects of the inhibitor of apoptosis proteins. Recently, the inhibitors of those proteins have been developed with the goal of enhancing the cytotoxic effects of chemotherapy and radiotherapy, and one of them, xevinapant, has already demonstrated effectiveness in a phase II clinical trial. This class of drugs represents an example of synergism between classical cytotoxic chemo- and radiotherapy and new targeted therapy.
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Neoplasias , Radioterapia (Especialidade) , Humanos , Neoplasias/tratamento farmacológico , Medicina de Precisão , Apoptose , Proteínas Inibidoras de ApoptoseRESUMO
Dermatomyositis (DM) is a systemic autoimmune disorder characterized by proximal myopathy and dermatological findings. Approximately 15-30% of DM cases emerge as a paraneoplastic syndrome caused by a concomitant malignancy. Although more rare, in cancer patients DM has also been reported as a possible result of toxicity of some antineoplastic agents, such as taxanes and monoclonal antibodies. Herein, we report a 35-year-old woman with metastatic breast cancer who presented with skin lesions after initiation of paclitaxel and anti-HER2 agents. Clinical, laboratory, and histological findings were consistent with the diagnosis of DM.
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Neoplasias da Mama , Dermatomiosite , Feminino , Humanos , Adulto , Anticorpos Monoclonais , Autoanticorpos , PaclitaxelRESUMO
AIM: Evaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy. BACKGROUND: Anemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes. MATERIALS AND METHODS: Retrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5 g/dL or <12.5 g/dL) at the beginning of cCRT with overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: A total of 108 patients were identified. With a median follow-up of 16.10 months median OS was 59.70 months for Hb ≥12.5 g/dL vs. 14.13 months for Hb <12.5 g/dL (p = 0.004). PFS was 12.29 months for Hb ≥12.5 g/dL and 1.68 months for Hb <12.5 g/dL (p = 0.016). CONCLUSIONS: In this analysis, Hb ≥12.5 g/dL correlated with significantly better OS and PFS. Further studies are needed to validate these findings.
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Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50-69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.
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Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Masculino , Feminino , Portugal , Pessoa de Meia-Idade , Idoso , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Estudos Retrospectivos , Metástase Neoplásica , Recursos em Saúde/estatística & dados numéricosRESUMO
Breast cancer (BC) is the most prevalent malignancy affecting women worldwide, including Portugal. While the majority of BC cases are sporadic, hereditary forms account for 5-10% of cases. The most common inherited mutations associated with BC are germline mutations in the BReast CAncer (BRCA) 1/2 gene (gBRCA1/2). They are found in approximately 5-6% of BC patients and are inherited in an autosomal dominant manner, primarily affecting younger women. Pathogenic variants within BRCA1/2 genes elevate the risk of both breast and ovarian cancers and give rise to distinct clinical phenotypes. BRCA proteins play a key role in maintaining genome integrity by facilitating the repair of double-strand breaks through the homologous recombination (HR) pathway. Therefore, any mutation that impairs the function of BRCA proteins can result in the accumulation of DNA damage, genomic instability, and potentially contribute to cancer development and progression. Testing for gBRCA1/2 status is relevant for treatment planning, as it can provide insights into the likely response to therapy involving platinum-based chemotherapy and poly[adenosine diphosphate (ADP)-ribose] polymerase inhibitors (PARPi). The aim of this review was to investigate the impact of HR deficiency in BC, focusing on BRCA mutations and their impact on the modulation of responses to platinum and PARPi therapy, and to share the experience of Unidade Local de Saúde Santa Maria in the management of metastatic BC patients with DNA damage targeted therapy, including those with the Portuguese c.156_157insAlu BRCA2 founder mutation.
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The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell's subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2- mBC.
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Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Células Neoplásicas Circulantes , Inibidores de Proteínas Quinases , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/sangue , Feminino , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/metabolismo , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Idoso , Metástase Neoplásica , Adulto , Estudos ProspectivosRESUMO
INTRODUCTION: Head and neck cancers remain a significant health burden worldwide. Standardizing the care provided to these patients through the systematic measurement of established indicators is key to improve their outcomes. The aim of this study was to establish a relevant set of outcome indicators in this condition and identify measurement tools and requirements to do so. MATERIAL AND METHODS: One scientific committee and two regional working groups worked in a stepwise manner to narrow down an initial list of potential outcome indicators retrieved from an exhaustive literature review to a smaller set of outcome indicators according to their clinical practice. This was assessed by one representative of a head and neck cancer patient association until a final set of indicators was reached. RESULTS: A total of 164 outcome indicators comprising case-mix, outcomes, and adverse events dimensions were retrieved from the literature. These were reduced to a working set of 79 outcome indicators by the Scientific Committee and divided into seven categories including demographics, clinical status, tumor-related parameters, nutritional status, treatment, health and quality of life parameters and survival. Subsequently, these indicators were further reduced to a set of 50 indicators by the regional working groups and to a set of 49 indicators by the final Scientific Committee assessment. Finally, the discussed indicators were appraised by a head and neck cancer patient association, which added the 'rehabilitation' category, a key parameter to these patients. CONCLUSION: An initial set of outcome indicators for head and neck cancer was systematically developed aiming to standardize the care provided to these patients across institutions at national level and identify measurement tools and requirements to measure those indicators. This standard set should be continuously improved and consistently adopted in the different clinical and national settings.
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Neoplasias de Cabeça e Pescoço , Avaliação de Resultados da Assistência ao Paciente , Assistência Centrada no Paciente , Humanos , Técnica Delphi , Neoplasias de Cabeça e Pescoço/terapia , Avaliação de Resultados em Cuidados de Saúde , Qualidade de VidaRESUMO
Breast sarcomas (BSs), phyllodes tumors (PTs), and desmoid tumors (DTs) are rare entities that arise from connective tissue. BSs can be classified as either primary or secondary, whether they develop de novo or after radiation exposure or lymphedema. PIK3CA seems to play an important common role in different BS. Malignant PTs show similar behavior to BSs, while DTs are locally aggressive but rarely metastasize. BSs usually present as unilateral, painless, rapidly growing masses with rare nodal involvement. The diagnosis should be based on magnetic resonance imaging and a core needle biopsy. Staging should comprise a chest computed tomography (CT) scan (except for benign PT and DT), while abdominal and pelvic CT scans and bone scans should be added in certain subtypes. The mainstay of treatment for localized BS is surgery, with margin goals that vary according to subtype. Radiotherapy and chemotherapy can be used as neoadjuvant or adjuvant approaches, but their use in these settings is not standard. Advanced BS should be treated with systemic therapy, consistent with recommendations for advanced soft tissue sarcomas of other topographies. Given the rarity and heterogeneity of these entities, multidisciplinary and multi-institutional collaboration and treatment at reference centers are critical.
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Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. While surgical resection is the cornerstone of a multimodal curative approach, some tumors are deemed recurrent or metastatic (R/M) and often not suitable for curative surgery. This mainly occurs due to the extent of lesions or when surgery is expected to result in poor functional outcomes. Amongst the main non-surgical therapeutic options for oral squamous cell carcinoma are radiotherapy, chemotherapy, molecular targeted agents, and immunotherapy. Depending on the disease setting, these therapeutic approaches can be used isolated or in combination, with distinct efficacy and side effects. All these factors must be considered for treatment decisions within a multidisciplinary approach. The present article reviews the evidence regarding the treatment of patients with R/M oral squamous cell carcinoma. The main goal is to provide an overview of available treatment options and address future therapeutic perspectives.
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INTRODUCTION: Heart disease and cancer are the two leading causes of morbidity and mortality worldwide. Advances in cancer screening and management have led to longer survival and better quality of life. Despite this progress, many cancer patients experience cardiovascular complications during and after cancer treatment. This study describes the experience of a cardio-oncology program at tertiary academic hospital. METHODS: In this retrospective observational study, cancer patients referred to the CHULN cardio-oncology consultation (COC) between January 2016 and December of 2019 were included. Data collected included: patient demographics, cancer type, reason for referral, cardiovascular risk factors, cardiac and oncologic treatments and clinical outcomes. RESULTS: A total of 520 patients (mean age: 65 ± 14 years; 65% women) were referred to the COC. The main reasons for referral were suspected heart failure (26%), pre-high risk chemotherapy assessment (20%) and decreased LVEF (15%). Pre-existing cardiovascular risk factors were common (79%) and 309 (59%) were taking cardiac medications. The most common type of malignancy was breast cancer (216, 41%) followed by gastrointestinal (139, 27%). More than half received anthracycline-based regimens (303, 58%). Most patients (401; 77%) successfully completed cancer therapy. At the time of last data collection, the majority of patients were alive (430, 83%). Cardiac-related mortality was observed in 16%. CONCLUSIONS: The close collaboration between cardiology and oncology teams and timely cardiac monitoring was the key to the majority of patients to completing their prescribed cancer therapy.
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Neoplasias da Mama , Cardiopatias , Neoplasias , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Qualidade de Vida , Oncologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Antraciclinas/efeitos adversos , Cardiopatias/complicações , Neoplasias da Mama/tratamento farmacológico , Centros de Atenção Terciária , Cardiotoxicidade/etiologiaRESUMO
INTRODUCTION: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer. METHODS: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents' regions, case volumes, and practice type were explored. RESULTS: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents' region and case volume were noted. CONCLUSION: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.
This study was an online survey of Portuguese medical oncologists to determine how they managed patients with breast cancer during the COVID-19 pandemic. Forty-two questions covered topics such as how COVID testing was done, the types of cancer treatments used, and how this compared to before the pandemic. It also examined whether the geographic region, the number of patients each doctor was responsible for (caseload), and the type of medical institution influenced how patients with breast cancer were managed. One hundred and twenty-nine oncologists completed the survey, of whom 108 worked in the public health system, making this survey representative of breast cancer management during the COVID-19 pandemic across Portugal. Most (71%) said there were fewer visits for new cases of breast cancer during lockdown. The use of telemedicine increased, as did the use of pre-surgery hormone therapy or chemotherapy when access to surgery was difficult, and the use of anticancer medications taken orally or metronomically (low doses given frequently over a long time period). Chemotherapy given very frequently (dose-dense) was used less often, and fewer patients participated in clinical trials. Treatment decisions for patients with aggressive breast cancer types (e.g., triple-negative breast cancer) were largely unchanged, except for greater use of cyclin-dependent kinase 4/6 inhibitorsdrugs targeting the cell cycle and cell division control. Geographic region and caseload influenced treatment decisions. All of these changes in breast cancer treatment during the COVID-19 pandemic were logical and reasonable for the circumstances, but their long-term impact is not yet known.
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Introduction With an estimated incidence of 2%-4% per year, the development of a second primary malignancy (SPM) in patients with head and neck tumors (HNTs) is not a rare event. The present study aimed to (i) assess the frequency of SPMs in patients with HNTs treated in a university hospital over a five-year period and (ii) provide a demographic characterization of these patients. Methods Retrospective single-centre study of patients with more than one primary tumor (including at least one HNT) diagnosed between January 1, 2015, and December 31, 2019. Data were retrieved from patients' clinical records and anonymized for analysis purposes. Results A total of 53 out of 824 (6.43%) patients with multiple primary malignancies were identified, 18 of which synchronous and 35 metachronous. The median follow-up was 25 months. Thirteen patients were diagnosed with more than one HNT. Forty patients were diagnosed with at least one HNT and one non-HNT. The most frequently diagnosed non-HNT SPMs were lung cancer (n=17) and esophageal cancer (n=8). The five-year survival rate was 53% for patients with multiple HNSCCs and 47% for patients with at least one non-HNT (log-rank p=0.729). The median overall survival was 14 months for synchronous and 58 months for metachronous SPMs (log-rank p=0.002). Conclusion Findings from this study highlight the importance of long-term follow-up of HNT patients for early detection of SPMs, increasing the chance of providing treatment with curative intent and improving patient outcomes and survival.
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AIM: The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112). MATERIALS AND METHODS: Patients who completed neoadjuvant P + H + chemotherapy + surgery were randomised 1:1 to three intravenous (IV) P + H cycles followed by three cycles of PH FDC SC or vice versa (crossover) and then chose subcutaneous (SC) injection or IV infusion to continue up to 18 cycles (continuation). Assessments were via patient and healthcare professional (HCP) questionnaires. RESULTS: One hundred and sixty patients were randomised (cut-off: 24 February 2020); 136 (85.0%, 95% confidence interval: 78.5-90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n = 119) and comfort during administration (n = 73). One hundred and forty-one patients (88.1%) were very satisfied/satisfied with SC injection versus 108 (67.5%) with IV infusion; 86.9% chose PH FDC SC continuation. HCP perceptions of median patient treatment room time ranged from 33.0-50.0 min with SC and 130.0-300.0 min with IV. Most adverse events (AEs) were grade 1/2 (no 4/5s); serious AE rates were low. AE rates before and after switching were similar (cycles 1-3 IV â cycles 4-6 SC: 77.5% â 72.5%; cycles 1-3 SC â cycles 4-6 IV: 77.5% â 63.8%). CONCLUSION: Most patients strongly preferred PH FDC SC over P + H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Terapia Neoadjuvante/métodos , Preferência do Paciente/estatística & dados numéricos , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/psicologia , Quimioterapia Adjuvante/estatística & dados numéricos , Estudos Cross-Over , Combinação de Medicamentos , Feminino , Humanos , Infusões Intravenosas/efeitos adversos , Infusões Intravenosas/psicologia , Injeções Subcutâneas/efeitos adversos , Injeções Subcutâneas/psicologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/psicologia , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Satisfação do Paciente , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Adulto JovemRESUMO
The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases (RTKs) are among the first layer of molecules that receive, interpret, and transduce signals leading to distinct cancer cell phenotypes. Since the discovery of the tooth-lid factor-later characterized as the epidermal growth factor (EGF)-and its high-affinity binding EGF receptor, HER kinases have emerged as one of the commonly upregulated or hyperactivated or mutated kinases in epithelial tumors, thus allowing HER1-3 family members to regulate several hallmarks of cancer development and progression. Each member of the HER family exhibits shared and unique structural features to engage multiple receptor activation modes, leading to a range of overlapping and distinct phenotypes. EGFR, the founding HER family member, provided the roadmap for the development of the cell surface RTK-directed targeted cancer therapy by serving as a prototype/precursor for the currently used HER-directed cancer drugs. We herein provide a brief account of the discoveries, defining moments, and historical context of the HER family and guidepost advances in basic, translational, and clinical research that solidified a prominent position of the HER family in cancer research and treatment. We also discuss the significance of HER3 pseudokinase in cancer biology; its unique structural features that drive transregulation among HER1-3, leading to a superior proximal signaling response; and potential role of HER3 as a shared effector of acquired therapeutic resistance against diverse oncology drugs. Finally, we also narrate some of the current drawbacks of HER-directed therapies and provide insights into postulated advances in HER biology with extensive implications of these therapies in cancer research and treatment.
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Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Terapia de Alvo Molecular , Mutação , Neoplasias/genética , Neoplasias/patologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de SinaisRESUMO
AIM: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). METHODS: Retrospective evaluation of patients with mCRPC treated with AA. RESULTS: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10-0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14-0.41; p < 0.001). CONCLUSION: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.
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We intend to present some aspects related with the coping process in a person with chronic pain. The presence of pain has implications in daily life activities, such as eating, drinking, sleeping or selfcare. Pain can unchain responses in the person, namely depression, anxiety, isolation, fear of pain and pessimistic thoughts. Thus we verify that in his/her adaptation process to the condition of chronic pain the person needs to integrate some strategies to manage his/her day by day activities. In this article we try to systematize the process where nurses based on Lazarus and Folkman's Model: Stress processing and Coping, can systematize care. In fact, nurses try to help people in the identification of their personal resources as well as the socio-ecological resources. The sense the care process has as a goal is the improvement of the quality of life through pain control and the person's adaptation of his/her condition of health, through development of his/her knowledge and capacities to use the resources, be they personal as instrumental or social.
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Adaptação Psicológica , Dor/psicologia , Doença Crônica , HumanosRESUMO
Considerable advances in cancer therapies in recent decades have reshaped the prognosis of cancer patients. There are now estimated to be over 20 million cancer survivors in the USA and Europe, numbers unimaginable a few years ago. However, this increase in survival, along with the aging of the patient population, has been accompanied by a rise in adverse cardiovascular effects, particularly when there is a previous history of heart disease. The incidence of cardiotoxicity continues to grow, which can compromise the effectiveness of cancer therapy. Cardiotoxicity associated with conventional therapies, especially anthracyclines and radiation, is well known, and usually leads to left ventricular dysfunction. However, heart failure represents only a fraction of the cardiotoxicity associated with newer therapies, which have diverse cardiovascular effects. There are few guidelines for early detection, prevention and treatment of cardiotoxicity of cancer treatments, and no well-established tools for screening these patients. Echocardiography is the method of choice for assessment of patients before, during and after cancer treatment. It therefore makes sense to adopt a multidisciplinary approach to these patients, involving cardiologists, oncologists and radiotherapists, collaborating in the development of new training modules, and performing clinical and translational research in a cardio-oncology program. Cardio-oncology is a new frontier in medicine and has emerged as a new medical subspecialty that concentrates knowledge, understanding, training and treatment of cardiovascular comorbidities, risks and complications in patients with cancer in a comprehensive approach to the patient rather than to the disease.
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Cardiotoxicidade , Neoplasias/terapia , Desenvolvimento de Programas , Antraciclinas/efeitos adversos , Antineoplásicos , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Europa (Continente) , Coração , Humanos , Radioterapia/efeitos adversos , SobreviventesRESUMO
INTRODUCTION: Surgery is the only potentially curative treatment for patients with colorectal liver metastases, resulting in 5-year survival rates of 36 - 58. Although many studies have been performed to determine prognostic factors for tumor recurrence and survival after resection of colorectal liver metastases, there are few prognostic scoring systems stratifying patients undergoing surgery for colorectal liver metastases into risk group models. OBJECTIVES: To identify, evaluate and compare the existing prognostic scores for survival after surgery for resection of colorectal liver metastases. MATERIAL AND METHODS: Electronic search in PubMed, Cochrane and Embase from 1990 to 2013 using the terms 'hepatic resection', 'colorectal cancer', 'liver metastasis', 'hepatectomy', 'prognostic', and 'score'. Only studies proposing a prognostic model or risk stratification based on clinical and/or pathological variables were included. RESULTS: From 1996 to June 2013, 19 scoring systems were identified, including one nomogram. Thirty prognostic factors were identified although none of the factors was common to all prognostic models. The 4 factors most often included were: number of liver metastases, regional lymph node metastization of primary tumor, preoperative CEA level and maximum size of metastases. The median study sample size was 305 patients (81-1 568 patients) and median follow-up was 33 months (16-54 months). All studies were retrospective and used the Cox proportional hazards model for multi-variable analysis. CONCLUSION: Several factors have been constantly reported as having prognostic value after liver resection of colorectal livermetastases, although there is no consensus on the ideal scoring system.
Introdução: A ressecção de metástases hepáticas é o único tratamento potencialmente curativo em doentes com metástases hepáticas de cancro colo-rectal, resultando numa sobrevida global de 36-58%. Até à data foram publicados múltiplos trabalhos sobre factores de prognóstico após hepatectomia em doentes com metástases hepáticas de cancro colo-rectal. No entanto, poucos apresentaram modelos de prognóstico que permitam estratificar os doentes em grupos de risco, relacionando-os com sobrevida após metastasectomia hepática.Objectivos: Identificar, avaliar e comparar os diferentes scores de prognóstico após recessão de metástases hepáticas de cancro colo-rectal.Material e Métodos: Pesquisa na PubMed, Cochrane e Embase, de artigos publicados entre 1990 e 2013, usando os termos ârecessão hepáticaâ, âcancro colo-rectalâ, âmetástases hepáticasâ, âhepatectomiaâ, âprognósticoâ e âmodeloâ. Apenas os artigos que apresentaram modelos de prognóstico com base em variáveis clínico-patológicas foram incluídos.Resultados: De 1996 a Junho de 2013, 19 modelos de prognóstico foram identificados, incluindo um nomograma. Foram identificados 30 diferentes factores prognósticos, embora nenhum factor fosse comum a todos os modelos prognósticos. Os factores mais frequentemente incluídos foram: número de metástases hepáticas, envolvimento ganglionar regional do tumor primário, nível sérico de CEA pré-operatório e tamanho máximo das metástases. A amostra mediana foi de 305 doentes (81-1 568 doentes) e o seguimento mediano foi de 33 meses (16-54 meses). Todos os estudos foram retrospectivos e utilizaram o modelo proporcional de Cox para análise multivariada.Conclusão: Vários factores têm sido constantemente reportados como tendo valor prognostico após ressecção de metástases hepáticas de cancro colorectal, no entanto, não existe consenso sobre o modelo ideal de prognóstico.