ABSTRACT
The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
Subject(s)
Melanoma , Skin Neoplasms , Consensus , Humans , Medical Oncology , Melanoma/therapy , Netherlands , Skin Neoplasms/therapyABSTRACT
The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment for brain metastases. The expert panel was divided into five working groups to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of metastatic melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
Subject(s)
Medical Oncology , Melanoma , Consensus , Humans , Melanoma/therapy , NetherlandsABSTRACT
OBJECTIVE: To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university hospital. METHODS: This was a retrospective analysis of the activity of our HFCU in its first 5 years of existence. RESULTS: Between July 2010 and July 2015, 1,518 patients from 1,318 families attended our HFCU. Genetic testing was offered to 862 patients. Of those, 833 (96.6%) accepted testing, with available results for 636 (76.4%). Pathogenic mutations in BRCA1 and BRCA2 were found in 175 patients. Lynch syndrome and adenomatous polyposis were the most frequent syndromes diagnosed (151/175, 86.3%) among 17 different syndromes studied. Of the 404 patients without a previous genetic diagnosis in the family, 62 (15.3%) were found to have mutations in disease-causing genes. Prophylactic surgery and follow-up (33.7%) or follow-up only (66.3%) was proposed for mutation carriers according to international guidelines and patients' preferences. CONCLUSION: We have a high mutation detection rate, genetic test acceptance, and compliance with risk reduction strategies. However, there is room for improvement, especially in genetic testing timing, considering that an increase in the indications for genetic testing is expected.
Subject(s)
Hospitals, University/organization & administration , Neoplastic Syndromes, Hereditary/therapy , Female , Genetic Predisposition to Disease , Genetic Testing , Humans , Male , Neoplastic Syndromes, Hereditary/classification , Neoplastic Syndromes, Hereditary/genetics , Retrospective Studies , SpainABSTRACT
BACKGROUND: The introduction of anti-programmed cell death protein 1 (PD-1) immunotherapy has revolutionized the treatment landscape for melanoma, enhancing both response rates and survival outcomes in patients with advanced stages of the disease. Despite these remarkable advances, a noteworthy subset of patients (40%-60%) does not derive advantage from this therapeutic approach. This study aims to identify key predictive factors and create a user-friendly predictive nomogram for stage IV melanoma patients receiving first-line anti-PD-1-based immunotherapy, improving treatment decisions. MATERIALS AND METHODS: In this retrospective study, we included patients with unresectable stage IV melanoma who received first-line treatment with either anti-PD-1 monotherapy or anti-PD-1 plus anti-cytotoxic T-lymphocyte associated protein 4 between 2014 and 2018. We documented clinicopathological features and blood markers upon therapy initiation. By employing the random survival forest model and backward variable selection of the Cox model, we identified variables associated with progression-free survival (PFS) after the first-line anti-PD-1-based treatment. We developed and validated a predictive nomogram for PFS utilizing the identified variables. We assessed calibration and discrimination performance metrics as part of the evaluation process. RESULTS: The study involved 719 patients, divided into a training cohort of 405 (56%) patients and a validation cohort of 314 (44%) patients. We combined findings from the random survival forest and the Cox model to create a nomogram that incorporates the following factors: lactate dehydrogenase (LDH), S100, melanoma subtype, neutrophil-to-lymphocyte ratio (NLR), body mass index, type of immune checkpoint inhibitor, and presence of liver or brain metastasis. The resultant model had a C-index of 0.67 in the training cohort and 0.66 in the validation cohort. Performance remained in different patient subgroups. Calibration analysis revealed a favorable correlation between predicted and actual PFS rates. CONCLUSIONS: We developed and validated a predictive nomogram for long-term PFS in patients with unresectable stage IV melanoma undergoing first-line anti-PD-1-based immunotherapy.
ABSTRACT
BACKGROUND: Hereditary breast cancer comprises 5-10% of all breast cancers. Mutations in two high-risk susceptibility genes, BRCA1 and BRCA2, along with rare intermediate-risk genes and common low-penetrance alleles identified, altogether explain no more than 45% of the high-risk breast cancer families, although the majority of cases are unaccounted for and are designated as BRCAX tumours. Micro RNAs have called great attention for classification of different cancer types and have been implicated in a range of important biological processes and are deregulated in cancer pathogenesis. METHODS: Here we have performed an exploratory hypothesis-generating study of miRNA expression profiles in a large series of 66 primary hereditary breast tumours by microarray analysis. RESULTS: Unsupervised clustering analysis of miRNA molecular profiles revealed distinct subgroups of BRCAX tumours, 'normal-like' BRCAX-A, 'proliferative' BRCAX-B, 'BRCA1/2-like' BRCAX-C and 'undefined' BRCAX-D subgroup. These findings introduce a new insight in the biology of hereditary breast cancer, defining specific BRCAX subgroups, which could help in the search for novel susceptibility pathways in hereditary breast cancer. CONCLUSION: Our data demonstrate that BRCAX hereditary breast tumours can be sub-classified into four previously unknown homogenous groups characterised by specific miRNA expression signatures and histopathological features.
Subject(s)
Breast Neoplasms/congenital , MicroRNAs/genetics , Transcriptome , Adult , Aged , Aged, 80 and over , Algorithms , Breast Neoplasms/classification , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cluster Analysis , Female , Gene Expression Regulation, Neoplastic , Genes, BRCA1 , Genes, BRCA2 , Humans , Microarray Analysis , Middle AgedABSTRACT
BACKGROUND: Germline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown. MATERIALS AND METHODS: We performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Marañón, Spain, from 2010 to 2019. RESULTS: One-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients. CONCLUSIONS: The VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.
Subject(s)
Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Neoplasms/complications , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Adult , Aged , Breast Neoplasms/complications , Breast Neoplasms/genetics , Female , Humans , Incidence , Middle Aged , Neoplasms/genetics , Ovarian Neoplasms/complications , Ovarian Neoplasms/genetics , Retrospective Studies , Young AdultABSTRACT
Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available.
Subject(s)
Melanoma/pathology , Melanoma/therapy , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Biopsy , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Chemotherapy, Adjuvant/methods , Follow-Up Studies , Humans , Immunotherapy/methods , Lymph Node Excision , Medical Oncology , Melanoma/diagnosis , Melanoma/genetics , Molecular Targeted Therapy/methods , Neoplasm Staging , Proto-Oncogene Proteins B-raf/analysis , Proto-Oncogene Proteins B-raf/genetics , Radiotherapy, Adjuvant , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Societies, Medical , SpainABSTRACT
AIM: To analyze the accuracy of the sentinel lymphatic node biopsy (SLNB) and to investigate predictive factors for sentinel node (SN) status and prognostic factors for recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with melanoma. MATERIAL AND METHODS: Between June 1997 and June 2017, 440 consecutive patients, who underwent SLNB by a single surgical team, were prospectively included. Descriptive and survival analysis were performed. RESULTS: 119 of 440 patients (26%) had positive SN. SLNB's false-negative rate was 6.3%. Breslow thickness, Clark´s level, ulceration and histological subtype were statistically significant predictive factors of SN metastases. In a multivariate analysis, positive SN (HR = 2.21, p = 0.01), deeper Breslow thickness (HR = 2.05, p = 0.013), male gender (RR = 2.05, p = 0.02), and higher Clark's level (HR = 2.30, p = 0.043) were significantly associated with decreased RFS; and positive SN (HR = 2.58, p < 0.001), deeper Breslow thickness (HR = 2.57, p = 0.006) and male gender (HR = 1.93, p = 0.006) were associated with lower DSS. CONCLUSION: SLNB is a reliable and reproducible procedure with high sensitivity (93.7%). Positive SN metastases, Breslow thickness and male gender were statistically associated with poorer outcomes. Male gender was an independent prognostic factor of tumor thickness or SN status.
Subject(s)
Melanoma/pathology , Neoplasm Recurrence, Local/pathology , Sentinel Lymph Node Biopsy/methods , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphatic Metastasis , Male , Melanoma/mortality , Melanoma/surgery , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Prognosis , Prospective Studies , Sentinel Lymph Node/pathology , Skin Neoplasms/mortality , Skin Neoplasms/secondary , Skin Neoplasms/surgery , Survival Analysis , Young Adult , Melanoma, Cutaneous MalignantABSTRACT
PURPOSE: There is limited evidence on the efficacy and safety of anti-programmed cell death protein 1 (PD-1)-/anti-programmed death-ligand 1 (PD-L1)-based immunotherapy in the elderly, particularly those aged over 75 years. METHODS/PATIENTS: The clinical response and toxicity profile of anti-PD-1-/anti-PD-L1-based immunotherapy in patients aged over 75 years were assessed in this retrospective observational study conducted in the Medical Oncology Service of a tertiary level hospital. The associations among clinical responses, adverse events, and geriatric syndromes were evaluated. RESULTS: In total, 20 patients aged between 75 and 94 years were evaluated. Pembrolizumab and nivolumab were the most commonly used drugs. A clinical benefit (stable disease, partial response or complete response) was documented in 13 patients (65%). This proportion was 80% in patients aged between 75 and 79 years, and 50% in those aged over 79 years (p = 0.236). The adverse events were similar to those reported in younger patients. At least one clinical adverse event (cAE) and one laboratory adverse event (lAE) was reported in 75% and 55% of patients, respectively. Polypharmacy was observed for all patients and multi-morbidity in 95%. Patients without gait disorders showed more responses to immunotherapy. The number of lAEs was significantly associated with the number of commonly prescribed drugs (slope = 0.218, p = 0.010), the Eastern Cooperative Oncology Group score, and the number of cAEs. CONCLUSIONS: The elderly can obtain benefits from anti-PD-1-/anti-PD-L1-based immunotherapy. The toxicity profile was similar to that reported in younger counterparts.
Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , Aged , Aged, 80 and over , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Male , Neoplasms/mortality , Retrospective StudiesABSTRACT
PURPOSE: To study the utility of positron emission tomography with computerized tomography (PET/CT) in patients with a stage I-III melanoma. PATIENTS AND METHODS: PET/CT findings from all patients with a stage I-III melanoma attended at our hospital from September 2011 to November 2015 were reviewed. RESULTS: Data from 83 patients with a stage I-III melanoma, 39 patients with a positive sentinel lymph node biopsy (SLNB) and 35 patients with locoregional recurrences were analyzed. Sensitivity of PET/CT in clinical stage I-III patients was 5%, with a 14% of false positives. In patients with a positive SLNB, PET/CT previous to complete lymph node dissection had a 23% of false negatives. In patients with clinical locoregional recurrences, PET/CT findings revealed asymptomatic visceral distant metastasis in 25.7%. CONCLUSIONS: PET/CT has a significant rate of false positive and negative results in patients with a stage I-III melanoma. Utility in patients with nodal locoregional recurrences seems higher than in patients with skin metastases.
Subject(s)
Melanoma/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Positron Emission Tomography Computed Tomography , Sentinel Lymph Node Biopsy , Skin Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , False Negative Reactions , False Positive Reactions , Female , Humans , Lymph Node Excision , Male , Melanoma/mortality , Melanoma/pathology , Melanoma/surgery , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Sensitivity and Specificity , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Neoplasms/surgeryABSTRACT
INTRODUCTION: The aim of this study is to evaluate the cost-effectiveness and impact of gene-expression assays (GEAs) on treatment decisions in a real-world setting of early-stage breast cancer (ESBC) patients. METHODS: This is a regional, prospective study promoted by the Council Health Authorities in Madrid. Enrolment was offered to women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, node-negative or micrometastatic, stage I or II breast cancer from 21 hospitals in Madrid. Treatment recommendations were recorded before and after knowledge of tests results. An economic model compared the cost-effectiveness of treatment, guided by GEAs or by common prognostic factors. RESULTS: 907 tests (440 Oncotype DX® and 467 MammaPrint®) were performed between February 2012 and November 2014. Treatment recommendation changed in 42.6% of patients. The shift was predominantly from chemohormonal (CHT) to hormonal therapy (HT) alone, in 30.5% of patients. GEAs increased patients' confidence in treatment decision making. Tumor grade, progesterone receptor positivity and Ki67 expression were associated with the likelihood of change from CHT to HT (P < 0.001) and from HT to CHT (P < 0.001). Compared with current clinical practice genomic testing increased quality-adjusted life years by 0.00787 per patient and was cost-saving from a national health care system (by 13.867 per patient) and from a societal perspective (by 32.678 per patient). CONCLUSION: Using GEAs to guide adjuvant therapy in ESBC is cost-effective in Spain and has a significant impact on treatment decisions.
Subject(s)
Breast Neoplasms/drug therapy , Gene Expression Profiling/economics , Registries , Adolescent , Adult , Aged , Biomarkers, Tumor/genetics , Breast Neoplasms/economics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Clinical Decision-Making , Cost-Benefit Analysis , Female , Gene Expression Profiling/methods , Humans , Middle Aged , Prospective Studies , Quality-Adjusted Life Years , Spain/epidemiology , Young AdultABSTRACT
Drug repurposing offers advantages over traditional drug development in terms of cost, speed and improved patient outcomes. The receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) inhibitor denosumab is approved for the prevention of skeletal-related events in patients with advanced malignancies involving bone, including solid tumours and multiple myeloma. Following improved understanding of the role of RANK/RANKL in cancer biology, denosumab has already been repurposed as a treatment for giant cell tumour of bone. Here, we review the role of RANK/RANKL in tumourigenesis, including effects on tumour initiation, progression and metastasis and consider the impact of RANK/RANKL on tumour immunology and immune evasion. Finally, we look briefly at ongoing trials and future opportunities for therapeutic synergy when combining denosumab with anti-cancer agents such as immune checkpoint inhibitors.
Subject(s)
Antineoplastic Agents/therapeutic use , Drug Repositioning , Neoplasms/drug therapy , Neoplasms/metabolism , RANK Ligand/metabolism , Receptor Activator of Nuclear Factor-kappa B/metabolism , Humans , PrognosisABSTRACT
PURPOSE: To describe patient characteristics by disease stage, resectability status and current treatment management after first diagnosis of IIIB to IV1c advanced (AM)/metastatic melanoma (MM). METHODS/PATIENTS: Multicentre, retrospective study based on data from medical charts of patients > 18 years at MM first diagnosis, visited by oncologists at 4 reference centres in Spain: Hospital Universitario Gregorio Marañón (Madrid), Hospital General de Valencia (Valencia), Clínica Universidad de Navarra (Pamplona), and Hospital Clínic (Barcelona). RESULTS: Metastatic non-visceral melanoma (IIIB, IIIC, IV M1a) was reported in 139 (48.6%) patients and 40.9% (n = 117) were diagnosed with IV-M1c disease. 160 (55.9%) metastases were resectable. Available therapies under clinical practice were used in 210 patients; 74 were treated under clinical trials (CT). Intention-to-cure surgery (47.6%) was the most common treatment at time of MM diagnosis. Systemic (45.1% overall) therapy included chemo-, targeted- and immunotherapy (19.6%, 14.3%, 8.4%, respectively). At time of data collection, 26 patients were still alive and 120 had progressed to IV-M1c. Median overall survival (OS) was significantly larger in IIIB patients, 28.9 m (25.2-32.7); the shortest for IV-M1c patients, 11.0 m (8.7-13.3). CONCLUSIONS: Novel treatments are undoubtedly a major step forward in AM/MM, however these are often only available in the CT setting because early stages of development or country-specific regulations. Further prospective studies and multifactorial analysis should be performed to clearly identify possible clinical associations for outcome in Spanish patients with AM/MM.
Subject(s)
Melanoma/therapy , Adult , Age Distribution , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic/statistics & numerical data , Female , Humans , Immunotherapy/statistics & numerical data , Intention to Treat Analysis/statistics & numerical data , Male , Medical Records , Melanoma/epidemiology , Melanoma/mortality , Melanoma/secondary , Metastasectomy/statistics & numerical data , Middle Aged , Molecular Targeted Therapy/statistics & numerical data , Neoplasm Staging , Retrospective Studies , Sex Distribution , Spain/epidemiology , Treatment Outcome , Young AdultABSTRACT
All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy. Up to 10 years follow up is reasonable for melanoma patients with dermatologic examinations and physical exams.
Subject(s)
Melanoma/therapy , Combined Modality Therapy/methods , HumansABSTRACT
BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. RESULTS: Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. CONCLUSION: Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Melanoma/drug therapy , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Melanoma/mortality , Middle Aged , Proportional Hazards Models , Retrospective Studies , Salvage Therapy/methods , Spain , Treatment OutcomeABSTRACT
Calcitonin gene related peptide (CGRP), a 37 amino acid neuropeptide, is the most potent vasodilator known. Participation of CGRP in hypertension and related diseases, such as preeclampsia or vasospasm after subarachnoid haemorrage, is one of the most studied topics. In this review we summarize the published roles of CGRP in pathophysiology of hypertension in humans and in experimental models. We also discuss the effects of direct administration of CGRP in the treatment of hypertension and of anti-hypertensive drugs that enhance the release or response of endogenous calcitonin gene-related peptide: angiotensin converting enzyme inhibitors, selective antagonists for the angiotensin II receptor, beta-blockers, magnesium sulphate for preeclampsia and rutaecarpine, as well as the possibilities using CGRP in gene therapy for prevention of vasospasm after subarachnoid haemorrage.
Subject(s)
Calcitonin Gene-Related Peptide/physiology , Hypertension/drug therapy , Hypertension/physiopathology , Animals , Calcitonin Gene-Related Peptide/genetics , Calcitonin Gene-Related Peptide/therapeutic use , Female , Genetic Therapy , Humans , Pre-Eclampsia/drug therapy , Pre-Eclampsia/physiopathology , Pregnancy , Receptors, Calcitonin Gene-Related Peptide/physiology , Vasospasm, Intracranial/genetics , Vasospasm, Intracranial/therapyABSTRACT
The primary cause of tumor-related death in breast cancer is still represented by distant metastasization. The dissemination of tumor cells from the primary tumor to distant sites through bloodstream cannot be early detected by standard imaging methods. Circulating tumor cells (CTCs) play a major role in the metastatic spread of breast cancer. Different analytical systems for CTCs isolation and detection have been developed and novel areas of research are directed towards developing assays for CTCs molecular characterization. This review describes the current state of art on CTCs detection techniques and the present and future clinical implications of CTCs enumeration and characterization.
Subject(s)
Biomarkers, Tumor/isolation & purification , Breast Neoplasms/pathology , Neoplastic Cells, Circulating/pathology , Animals , Breast Neoplasms/blood , Female , HumansABSTRACT
The number of breast cancer survivors increases every year, thanks to the development of new treatments and screening techniques. However, patients present with numerous side effects that may affect their quality of life. Exercise has been demonstrated to reduce some of these side effects, but in spite of this, few breast cancer patients know and follow the exercise recommendations needed to remain healthy. In this review, we describe the different breast cancer treatments and the related side effects and implications of exercise in relation to these. We propose that exercise could be an integrative complementary intervention to improve physiological, physical and psychological factors that affect survival and quality of life of these patients. For that reason, the main objective of this review is to provide a general overview of exercise benefits in breast cancer patients and recommendations of how to design exercise interventions in patients with different side effects.
Subject(s)
Breast Neoplasms/therapy , Complementary Therapies/methods , Exercise Therapy/methods , Biomarkers, Tumor/blood , Exercise Therapy/economics , Female , Humans , Quality of Life/psychologyABSTRACT
BACKGROUND: The incidence of malignant melanoma has increased over recent decades all over the world; however, we are not aware if this also occurs in Madrid. Our objective was to analyze epidemiological changes in cutaneous malignant melanomas diagnosed over a 15-year period. PATIENTS AND METHODS: Retrospective analysis of data of patients with primary cutaneous melanomas attended at Hospital Gregorio Marañón, Madrid, Spain, between 1996 and 2010, divided into three periods: 1996-2000; 2001-2005; 2006-2010, was obtained. RESULTS: In total, 969 melanomas were histologically diagnosed. The mean age at the moment of diagnosis was 58.5 years old. The mean tumor thickness was 1.61 mm. The most common histological type was surface-spreading melanoma and the most common site was the trunk. There were statistically significant differences (P < .05) between the three periods of the study: older age at diagnoses (P < .001); larger number of head and neck melanomas (P < .001); more melanomas on trunk in women (P < .001); increase of lentigo maligna melanoma (P < .001); thinner mean tumor thickness (Breslow index) (P < .001); larger number of melanomas in situ (P < .001). However, thick melanomas (tumor thickness over 2 mm) ratio was still over 20% in all periods, especially in males and in those over 65 years old. CONCLUSIONS: Diagnosis of cutaneous melanoma in Spain is made increasingly with a thinner mean tumor thickness, although thick melanomas are still diagnosed in men and in individuals over 65 years.