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AIM: Chronic diseases often occur simultaneously and tend to be associated with adverse health outcomes, but limited research has been undertaken to understand their role in lung cancer mortality. Therefore, this study aims to describe the prevalence and patterns of having one (comorbidity) or ≥ 2 chronic diseases (multimorbidity) among lung cancer patients in Spain, and to examine the association between comorbidity or multimorbidity and short-term mortality risk at six months after cancer diagnosis. METHODS: In this population-based cohort study, data were drawn from two Spanish population-based cancer registries, Girona and Granada, and electronic health records. We identified 1259 adult lung cancer patients, diagnosed from 1st January 2011 to 31st December 2012. We identified the most common patterns of individual comorbidities and their pairwise correlations. We used a flexible parametric modelling approach to assess the overall short-term mortality risk 6 months after cancer diagnosis by levels of comorbidity after adjusting for age, sex, smoking status, province of residence, surgery, cancer stage, histology, and body mass index. RESULTS: We found high prevalence of comorbidity in lung cancer patients, especially among the elderly, men, those diagnosed with advanced-stage tumours, smokers, and obese patients. The most frequent comorbidities were chronic obstructive pulmonary disease (36.6%), diabetes (20.7%) and heart failure (16.8%). The strongest pairwise correlation was the combination of heart failure with renal disease (r = 0.20, p < 0.01), and heart failure with diabetes (r = 0.16, p < 0.01). Patients with either one or two or more comorbidities had 40% higher overall mortality risk than those without comorbidities (aHR for comorbidity: 1.4, 95%CI: 1.1-1.7; aHR for multimorbidity: 1.4, 95%CI: 1.1-1.8), when relevant confounding factors were considered. CONCLUSIONS: The presence of comorbid diseases, rather than the number of comorbidities, was associated with increasing the risk of short-term lung cancer mortality in Spain. Comorbidity was a consistent and independent predictor of mortality among lung cancer patients, six months after diagnosis. The most common comorbid conditions were age-, obesity- and tobacco-related diseases. Our findings highlight the need to develop targeted preventive interventions and more personalised clinical guidelines to address the needs of lung cancer patients with one or more comorbidities in Spain.
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Neoplasias Pulmonares/mortalidade , Multimorbidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/epidemiologia , Estudos de Coortes , Comorbidade , Diabetes Mellitus/epidemiologia , Registros Eletrônicos de Saúde , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Nefropatias/epidemiologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistema de Registros , Fatores Sexuais , Espanha/epidemiologia , Fatores de Tempo , Tabagismo/epidemiologiaRESUMO
BACKGROUND: Despite newer therapies, advanced or metastatic non-small-cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths worldwide. Deficits in the design and methods of randomized controlled trials (RCTs) may contribute to reducing the clinical benefit of therapies in oncology. To prioritize treatments based on efficacy results and toxicity data, the European Society for Medical Oncology (ESMO) has developed the Magnitude of Clinical Benefit Scale (MCBS). The objective of this study was to apply the ESMO-MCBS v1.1 to a cohort of RCTs on therapies for advanced or metastatic NSCLC. MATERIAL AND METHODS: Phase III and pivotal phase II trials, published between 2013 and 2018, investigating drug therapies for advanced NSCLC were included. PubMed was specifically searched for efficacy/toxicity updates. Treatments were graded 5 to 1 on the ESMO-MCBS v1.1, using the lower limit of the 95% confidence interval of the hazard ratio (HR), where scores 5 and 4 represent a substantial clinical benefit. Additionally, scores using the point estimate HR were generated, for comparison. Discrepancies between our grade estimations and the ones published on the ESMO website, as scorecards, were identified. RESULTS: ESMO-MCBS scores were calculated for 42 positive clinical trials. 54.8% met the ESMO-MCBS thresholds for clinically meaningful benefit (final grade of 4 or 5). That percentage decreased to 40.5% when considering the point estimate of the HR. 50.0% of the trials had no published scorecard on the ESMO website and discrepancies affected 11 (26.2%) studies. CONCLUSION: Almost half of the RCTs showing a statistically significant result favoring the experimental arm, failed to demonstrate a substantial clinical benefit according to the ESMO framework.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , OncologiaRESUMO
BACKGROUND: The use of circulating tumor cells (CTCs) as indicators of treatment response in metastatic colorectal cancer (mCRC) needs to be clarified. The objective of this study is to compare the Response Evaluation Criteria in Solid Tumors (RECIST) with the Cytologic Criteria Assessing Response (CyCAR), based on the presence and phenotypic characterization of CTCs, as indicators of FOLFOX-bevacizumab treatment response. METHODS: 77 mCRC blood samples from FOLFOX-bevacizumab treated patients were analyzed to isolate CTCs before and after (12 and 24 weeks) treatment, using an immunomagnetic separation method. VEGFR expression was identified by double immunostaining. RESULTS: We observed a decrease of CTCs (42.8 vs. 18.2%) and VEGFR positivity (69.7% vs. 41.7%) after treatment. According to RECIST, 6.45% of the patients did not show any clinical benefit, whereas 93.55% patients showed a favorable response at 12 weeks. According to CyCAR, 29% had a non-favorable response and 71% patients did not. No significant differences were found between the response assessment by RECIST and CyCAR at 12 or 24 weeks. However, in the multivariate analysis, RECIST at 12 weeks and CyCAR at 24 weeks were independent prognostic factors for OS (HR: 0.1, 95% CI 0.02-0.58 and HR: 0.35, 95% CI 0.12-0.99 respectively). CONCLUSIONS: CyCAR results were comparable to RECIST in evaluating the response in mCRC and can be used as an alternative when the limitation of RECIST requires additional response analysis techniques.
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Neoplasias Colorretais/patologia , Células Neoplásicas Circulantes/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Padrões de Referência , Resultado do TratamentoRESUMO
BACKGROUND: Brain metastases occur when cancer cells spread from their original site to the brain and are a frequent cause of morbidity and death in people with cancer. They occur in 20% to 40% of people during the course of their disease. Brain metastases are also the most frequent type of brain malignancy. Single and solitary brain metastasis is infrequent and choosing the most appropriate treatment is a clinical challenge. Surgery and stereotactic radiotherapy are two options. For surgery, tumour resection is performed using microsurgical techniques, while in stereotactic radiotherapy, external ionising radiation beams are precisely focused on the brain metastasis. Stereotactic radiotherapy may be given as a single dose, also known as single dose radiosurgery, or in a number of fractions, also known as fractionated stereotactic radiotherapy. There is uncertainty regarding which treatment (surgery or stereotactic radiotherapy) is more effective for people with single or solitary brain metastasis. OBJECTIVES: To assess the effectiveness and safety of surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2018), MEDLINE and Embase up to 25 March 2018 for relevant studies. We also searched trials databases, grey literature and handsearched relevant literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing surgery versus stereotactic radiotherapy, either a single fraction (stereotactic radiosurgery) or multiple fractions (fractionated stereotactic radiotherapy) for treatment of single or solitary brain metastasis. DATA COLLECTION AND ANALYSIS: Two review authors screened all references, evaluated the quality of the included studies using the Cochrane tool for assessing risk of bias, and performed data extraction. The primary outcomes were overall survival and adverse events. Secondary outcomes included progression-free survival and quality of life . We analysed overall survival and progression-free survival as hazard ratios (HRs) with 95% confidence intervals (CIs), and analysed adverse events as risk ratios (RRs). For quality of life we used mean difference (MD). MAIN RESULTS: Two RCTs including 85 participants met our inclusion criteria. One study included people with single untreated brain metastasis (n = 64), and the other included people with solitary brain metastasis (22 consented to randomisation and 21 were analysed). We identified a third trial reported as completed and pending results this may be included in future updates of this review. The two included studies were prematurely closed due to poor participant accrual. One study compared surgery plus whole brain radiotherapy (WBRT) versus stereotactic radiosurgery alone, and the second study compared surgery plus WBRT versus stereotactic radiosurgery plus WBRT. Meta-analysis was not possible due to clinical heterogeneity between trial interventions. The overall certainty of evidence was low or very low for all outcomes due to high risk of bias and imprecision.We found no difference in overall survival in either of the two comparisons. For the comparison of surgery plus WBRT versus stereotactic radiosurgery alone: HR 0.92, 95% CI 0.48 to 1.77; 64 participants, very low-certainty evidence. We downgraded the certainty of the evidence to very low due to risk of bias and imprecision. For the comparison of surgery plus WBRT versus stereotactic radiosurgery plus WBRT: HR 0.53, 95% CI 0.20 to 1.42; 21 participants, low-certainty evidence. We downgraded the certainty of the evidence to low due to imprecision. Adverse events were reported in both trial groups in the two studies, showing no differences for surgery plus WBRT versus stereotactic radiosurgery alone (RR 0.31, 95% CI 0.07 to 1.44; 64 participants) and for surgery plus WBRT versus stereotactic radiosurgery plus WBRT (RR 0.37, 95% CI 0.05 to 2.98; 21 participants). Most of the adverse events were related to radiation toxicities. We considered the certainty of the evidence from the two comparisons to be very low due to risk of bias and imprecision.There was no difference in progression-free survival in the study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT (HR 0.55, 95% CI 0.22 to 1.38; 21 participants, low-certainty evidence). We downgraded the evidence to low certainty due to imprecision. This outcome was not clearly reported for the other comparison. In general, there were no differences in quality of life between the two studies. The study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT found no differences after two months using the QLQ-C30 global scale (MD -10.80, 95% CI -44.67 to 23.07; 14 participants, very low-certainty evidence). We downgraded the certainty of evidence to very low due to risk of bias and imprecision. AUTHORS' CONCLUSIONS: Currently, there is no definitive evidence regarding the effectiveness and safety of surgery versus stereotactic radiotherapy on overall survival, adverse events, progression-free survival and quality of life in people with single or solitary brain metastasis, and benefits must be decided on a case-by-case basis until well powered and designed trials are available. Given the difficulties in participant accrual, an international multicentred approach should be considered for future studies.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Neoplasias Encefálicas/mortalidade , Terapia Combinada/métodos , Terapia Combinada/mortalidade , Irradiação Craniana/métodos , Irradiação Craniana/mortalidade , Humanos , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos , Radiocirurgia/mortalidade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Lung cancer (LC) remains the leading cause of cancer-related mortality globally, necessitating timely diagnosis and treatment to improve patient outcomes. This study aimed to evaluate the timeliness of care for LC patients at a public hospital in Almería, Spain, assess adherence to guidelines, and explore associations between timeliness and survival. METHODS: A retrospective cohort study was conducted, reviewing medical records of LC patients diagnosed between 2019 and 2021. Quality indicators, adapted from prevailing guidelines, facilitated the assessment of care timeliness, with a focus on diagnostic and treatment wait times. Cox regression modeling was employed to explore survival associations, adjusting for covariates including age, performance status, stage, histology, and treatment modalities. RESULTS: Of 539 patients included, most (79.84 %) had initial specialist contact within 7 days, and 82.25 % received diagnosis within 30 days. However, delays were observed in treatment initiation, with surgery experiencing the longest median wait time (78 days). Survival analysis showed no significant difference between shorter and longer diagnostic (HR: 0.87, 95 % CI: 0.62-1.24) or treatment intervals (HR: 1.14, 95 % CI: 0.83-1.58). Multivariate analysis identified age, performance status, stage, histology, and treatment as prognostic factors. CONCLUSION: This study highlights the importance of timely diagnosis and treatment in improving lung cancer outcomes. Despite achieving diagnostic targets, treatment delays were common, particularly for surgical interventions. These findings underscore the need for enhanced coordination and efficient care pathways to minimize delays, ultimately improving survival rates and quality of life for lung cancer patients. Addressing these issues is crucial for optimizing lung cancer care delivery in the future.
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Neoplasias Pulmonares , Sistema de Registros , Tempo para o Tratamento , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Feminino , Idoso , Tempo para o Tratamento/estatística & dados numéricos , Estudos Retrospectivos , Pessoa de Meia-Idade , Espanha/epidemiologia , Idoso de 80 Anos ou mais , Taxa de SobrevidaRESUMO
Cancer interception (CI) is a new approach to cancer prevention and treatment in a cancer-risk population that aims to detect and treat pre-tumoral stages. It has several potential advantages over traditional cancer diagnosis and monitoring methods because it is non-invasive, making it less painful and risky than conventional biopsy procedures. The circulating tumor cells (CTCs), liquid biopsy family members, are essential for the CI approach; then, the liquid biopsy (LB) is used as a CI tool. LB can be performed frequently because of its easy sampling and early pathological stages, which allow repeated non-invasive monitoring of cancer progression and response to treatment. CTCs have been found in the bloodstream of several types of cancer patients, including in early-stage cancer and premalignant lesions, suggesting a tumor development role in cancer's early stages. This chapter will present foundational scientific studies addressing CI and the clinical impact of CTC screening in a population at risk for cancer.
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Células Neoplásicas Circulantes , Humanos , Fatores de RiscoRESUMO
OBJECTIVES: To analyze the evolution of clinical outcomes derived from clinical trials on first-line therapies for advanced or metastatic non-small cell lung cancer (NSCLC) published between 2010 and 2020, focusing on how these outcomes impact survival rates and management of patients. METHODS: A systematic review of phase III and pivotal phase II clinical trials was conducted by a structured search on Medline and Embase. A comprehensive set of variables was collected to assess their influence on survival rates. We also estimated the clinical benefit by applying the ESMO-MCBS v1.1 and extracted the authors' conclusions. RESULTS: Sixty-six studies involving 34,951 patients were included. Best survival outcomes were found for nonsquamous non-small cell lung cancer (OS and progression-free survival medians: 19.4 and 10.2 mo) and for those expressing molecular targets (OS and progression-free survival medians: 23.8 and 11.0 mo). No significant influence on survival rates was observed for industry funding and disease stage (IIIB/IV vs. IV). ESMO-MCBS v1.1 was applied in 45 positive studies and resulted in a meaningful clinical benefit score in 37.8%. Quality of life (QoL) was reported in 57.6% of the original publications and showed statistical significance favoring the experimental arm in 33.3%. Positive authors' conclusions (75.7% of trials) were based on OS and/or QoL in 34% and on surrogate endpoints in 66%. CONCLUSIONS: Extended survival times and a steady improvement in QoL have been observed. However, there were more than twice as many studies reporting positive authors' conclusions as studies meeting the ESMO threshold for meaningful clinical benefit.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
OBJECTIVES: To evaluate the efficacy of treatment with linear accelerator-based stereotactic radiosurgery (LINAC) in cerebellopontine angle meningiomas. METHODS: We analyzed 80 patients diagnosed with cerebellopontine angle meningiomas between 2001 and 2014, treated with stereotactic radiosurgery (SRS), of whom 81.9% (n=68) were women, with an average age of 59.1 years (32-79). SRS was applied as primary treatment in 83.7% (n=67) and in 16.3% (n=13) as an adjuvant treatment to surgery. SRS treatment was provided using LINAC (Varian 600, 6MeV) with M3 micromultilamines (brainLab) and stereotactic frame. The average tumor volume was 3.12cm3 (0.34-10.36cm3) and the coverage dose was 14Gy (12-16Gy). We performed a retrospective descriptive analysis and survival analysis was performed with the Kaplan-Meier method and multivariate analysis to determine those factors predictive of tumor progression or clinical improvement. RESULTS: After an average follow-up period of 86.9 months (12-184), the tumor control rate was 92.8% (n=77). At the end of the study, there was an overall reduction in tumor volume of 32.8%, with an average final volume of 2.11cm3 (0-10.35cm3). The progression-free survival rate at 5, 10 and 12 years was 98%, 95% and 83.3% respectively. The higher tumor volume (p=0.047) was associated with progression. There was clinical improvement in 26.5% (n=21) of cases and clinical worsening in 16.2% (n=13). Worsening is related to the radiation dose received by the brainstem (p=0.02). Complications were 8.7% (7 cases) of hearing loss, 5% (4 cases) of brain radionecrosis, and 3.7% (3 cases) of cranial nerve V neuropathy. Hearing loss was related to initial tumor size (p=0.033) and maximum dose (p=0.037). The occurrence of radionecrosis with the maximum dose (p=0.037). CONCLUSIONS: Treatment of cerebellopontine angle meningiomas with single-dose SRS using LINAC is effective in the long term. Better tumor control rates were obtained in patients with small lesions.
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Perda Auditiva , Neoplasias Meníngeas , Meningioma , Neuroma Acústico , Radiocirurgia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Meningioma/radioterapia , Meningioma/cirurgia , Meningioma/complicações , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Resultado do Tratamento , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/complicações , Estudos Retrospectivos , Ângulo Cerebelopontino/patologia , Seguimentos , Perda Auditiva/complicações , Perda Auditiva/cirurgia , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is increasingly applied to treat meningiomas, attributable to their increased incidence in older individuals at greater surgical risk. To evaluate the effectiveness of treatment with linear accelerator (LINAC)-based stereotactic radiosurgery in skull base meningiomas as either primary treatment or postresection adjuvant therapy. METHODS: This study included 241 patients diagnosed with skull base meningiomas treated by single-dose SRS, with a median age of 59 years. SRS was primary treatment in 68.1% (n = 164) and adjuvant treatment in 31.9% (n = 77), using LINAC (Varian 600, 6 MeV). The median tumor volume was 3.2 cm 3 , and the median coverage dose was 14 Gy. Bivariate and multivariate analyses were performed to determine predictive factors for tumor progression, clinical deterioration, and complications. Kaplan-Meier analysis was used for survival analysis. RESULTS: After the median follow-up of 102 months, the tumor control rate was 91.2% (n = 220). Progression-free survival rates were 97.07%, 90.1%, and 85.7% at 5, 10, and 14 years, respectively. Clinical improvement was observed in 56 patients (23.2%). In multivariate analysis, previous surgery (hazard ratio 3.8 [95%CI 1.136-12.71], P = .030) and selectivity (hazard ratio .21 [95%CI 0.066-0.677], P = .009) were associated with tumor progression and increased maximum dose (odds ratio [OR] 4.19 [95% CI 1.287-13.653], P = .017) with clinical deterioration. The permanent adverse radiation effect rate was 6.2% (n = 15) and associated with maximum brainstem dose >12.5 Gy (OR 3.36 [95% CI .866-13.03], P = .08) and cerebellopontine angle localization (OR 3.93 [95% CI 1.29-11.98], P = .016). CONCLUSION: Treatment of skull base meningiomas with single-dose SRS using LINAC is effective over the long term. Superior tumor control is obtained in patients without previous surgery. Adverse effects are related to localization in the cerebellopontine angle, and maximum brainstem radiation dose was >12.5 Gy.
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Deterioração Clínica , Neoplasias Meníngeas , Meningioma , Radiocirurgia , Neoplasias da Base do Crânio , Humanos , Idoso , Pessoa de Meia-Idade , Meningioma/radioterapia , Meningioma/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias da Base do Crânio/radioterapia , Neoplasias da Base do Crânio/cirurgia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Base do Crânio/cirurgia , Base do Crânio/patologiaRESUMO
Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 patients with stage III NSCLC undergoing cCRT. Our findings revealed that non-responders exhibited low levels of baseline EV miR-375, miR-200c, and miR-30c. In particular, EV miR-30c showed high predictive value with an area under the curve of 87.2%. Low EV miR-30c and the presence of autophagic-activated CTCs emerged as independent predictive biomarkers for shorter relapse-free survival and overall survival. Furthermore, in experimental models simulating the effects of chemo- and radiotherapy, the administration of miR-30c, either through direct transfection or encapsulation into human EVs, led to the inhibition of autophagy in these cells. This is the first report demonstrating that EV miR-30c inhibits tumor autophagy and its quantification, together with autophagic-activated CTCs, could be used as biomarkers for the stratification and monitoring of patients with NSCLC undergoing cCRT, and they may hold promising potential for guiding subsequent consolidation treatment with immunotherapy or other novel therapies based on autophagy inhibitors.
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We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads. A direct sandwich immunoassay (with horseradish peroxidase-conjugated PSA antibody) served to quantify the cancer biomarker in serum samples. The enzymatic product was detected at -100 mV by amperometry on sputtered thin-film electrodes. Electrochemical reaction produced a current proportional to the PSA level, with a linear range from 10 pg mL-1 to 1500 pg mL-1. The sensitivity was demonstrated by a detection limit of 2 pg mL-1 and the reproducibility by a coefficient of variation of 6.16%. The clinical performance of this platform was tested in serum samples from patients with prostate cancer (PCa), observing high specificity and full correlation with gold standard determinations. In conclusion, this analytical platform is a promising tool for measuring PSA levels in patients with PCa, offering a high sensitivity and reduced variability. The small platform size and low cost of this quantitative methodology support its suitability for the fast and sensitive analysis of PSA and other circulating biomarkers in patients. Further research is warranted to verify these findings and explore its potential application at all healthcare levels.
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BACKGROUND: To describe the overall and disease-free survival at five and ten years after breast cancer diagnosis in women from a previous case-control study, and establish related prognostic factors. METHODS: We followed up 202 patients diagnosed between 1996 and 1998 in three public hospitals in Granada and Almeria provinces in Spain. Survival rates were calculated using the Kaplan and Meier method, and the Cox proportional hazards model was applied to identify the most significant variables contributing to survival. RESULTS: Mean age at diagnosis was 54.27 ± 10.4 years. Mean follow-up for overall survival was 119.91 months (95%CI 113.65-126.17); the five-year survival rate was 83.9% (95%CI: 78.13-89.66) and the ten-year rate was 71% (95% CI: 63.25-78.74). Mean follow-up for disease-free survival was 118.75 months (95%CI 111.86-125.65); the five-year disease-free survival rate was 81% (95% CI: 74.52-87.47) and the ten-year rate was 71.3% (95% CI: 63.33-79.26). The mortality rate of the study population was 33.17%. CONCLUSIONS: Disease characteristics are similar in our population to those in other Spanish and European regions, while the overall survival is higher than the mean rate during the same period in Europe (5-yr rate of 79%) and similar to that in Spain (83%).
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Neoplasias da Mama/mortalidade , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Espanha/epidemiologia , Taxa de Sobrevida , Fatores de TempoRESUMO
Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC.
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Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Vesículas Extracelulares/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
BACKGROUND: The objective of this review was to investigate trends in clinical trial design, specifically, the primary outcomes used, interpretation of results, and the magnitude of the benefits described in phase III controlled clinical trials in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seventy-six trials published between 2000 and 2012 were selected from a total of 122 identified in a structured search. RESULTS: Overall survival (OS) was evaluated as the primary study endpoint in 50 (65.8%) trials, followed by progression-free survival (PFS) in 15 (19.7%), and other variables, such as toxicity, quality of life (QoL), and response rate in 11 (14.5%). Ten (66.7%) out of 15 clinical trials using PFS as the primary endpoint were published between 2010 and 2012. Median overall survival (mOS) was 9.90 months (interquartile range: 3.5) with an increase of 0.384 months per year of publication (P < 0.001). A statistically significant improvement in mOS was obtained in only 13 (18.8%) trials. A total of 41 (53.9%) studies concluded that the result was positive. Of these, only 16 (39.1%) showed a statistically significant benefit in OS. QoL was assessed in 46 trials (60.5%) and of these, 10 (21.7%) reported significant improvements. CONCLUSIONS: These findings raise important questions about how clinical benefits are measured in clinical trials in advanced NSCLC. Appropriate clinically relevant outcome variables should be established and validated, and post-marketing studies should be requested by regulatory authorities to ensure meaningful clinical benefits in OS and QoL.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Determinação de Ponto Final/tendências , Neoplasias Pulmonares/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Tamanho da Amostra , Análise de Sobrevida , Resultado do TratamentoRESUMO
Metastasis is the leading cause of cancer-related deaths and despite measurable progress in the field, underlying mechanisms are still not fully understood. Circulating tumor cells (CTCs) disseminate within the bloodstream, where most of them die due to the attack of the immune system. On the other hand, recent evidence shows active interactions between CTCs and platelets, myeloid cells, macrophages, neutrophils, and other hematopoietic cells that secrete immunosuppressive cytokines, which aid CTCs to evade the immune system and enable metastasis. Platelets, for instance, regulate inflammation, recruit neutrophils, and cause fibrin clots, which may protect CTCs from the attack of Natural Killer cells or macrophages and facilitate extravasation. Recently, a correlation between the commensal microbiota and the inflammatory/immune tone of the organism has been stablished. Thus, the microbiota may affect the development of cancer-promoting conditions. Furthermore, CTCs may suffer phenotypic changes, as those caused by the epithelial-mesenchymal transition, that also contribute to the immune escape and resistance to immunotherapy. In this review, we discuss the findings regarding the collaborative biological events among CTCs, immune cells, and microbiome associated to immune escape and metastatic progression.
Assuntos
Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Imunoterapia/métodos , Metástase Neoplásica/patologiaRESUMO
Here we describe the working method used to implement an Integrated Cancer Health Plan in Andalusia (Spain) and to set out some of the lines of work for improving quality of care and health network planning. Four main initial considerations were made: (1) work must be centred on patients and respect for their autonomy; (2) cancer requires action at every healthcare level; (3) integration of expert professionals is to be encouraged; and (4) relevant information and data should be systematically used for planning. Two operative approaches were also established: structured participation and evidence-based healthcare. This methodology was used in various planning programmes, largely in relation to healthcare resources. In this article, as examples, we describe the development of two types of programmes: one for radiotherapy equipment and another for the management of lymphoedema in breast cancer patients. Analysis of results obtained against cancer is always controversial. It is necessary to review the healthcare structure used in terms of effectiveness and excellence. Comprehensive or integrated health plans are a useful model for a wide-ranging and multi-level approach to cancer. The structured and real participation of experts and an evidence- based healthcare strategy proved very useful in this public health planning experience.
Assuntos
Protocolos Antineoplásicos , Planejamento em Saúde/métodos , Neoplasias/terapia , Planejamento em Saúde/organização & administração , Humanos , EspanhaRESUMO
BACKGROUND AND OBJECTIVE: To describe cancer mortality trends in Andalusia for cancer as a whole and for their main locations, by age and gender groups during 1975-2003. MATERIAL AND METHOD: Mortality rates age and gender-adjusted have been estimated through cancer mortality data coming from mortality and polpulation official statistics. Joinpoint regression analysis has been used in order to quantify trends and their points of change. RESULTS: Cancer as a whole has showed a descending trend among women and an ascending trend among men, for the period 1975-2003. Annual change rates were -0.45% and 0.42% for women and men respectively, and both of them, statistically significant (p < 0.05). By age, except for the elder group, a fall is noted, both among women and among men. Among women, breast cancer was the first cause of cancer death; in 1993 it appeared a statistically significant change from ascendent to descendent trend. Among men, lung cancer was the first mortality cause; in 1996 appeared a significant trend change and it began to go down. Colon and rectum cancer was the second one in magnitude, both among men and women, but far from the first one and with an ascendent trend, specially among men. CONCLUSIONS: Cancer mortality shows a descending trend among andalusian women, with a similar rate to the Spanish average. Among men, the trend is ascendent with a higher magnitude than the national average.
Assuntos
Neoplasias/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Programática de Saúde , Criança , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Espanha/epidemiologiaRESUMO
BACKGROUND: The improvement of care quality depends on the education and skills of the professional team as well as on an adequate work method, which uses the right instruments of clinical management such as medical history, registers or protocols. OBJECTIVES: Defining standardized criteria related to the oncology care quality and applying them to a group of hospitals within the framework of continuous improvement establishing comparisons among them. MATERIAL AND METHODS: Information taken from 14 Andalusian public hospitals, in 2003 and first semester of 2004. A total of 35 variables were collected from official sources, validated studies and surveys as a starting point, grouped in four main issues (medical history, protocols, central commission and tumour sub-commissions), delays (diagnostic, treatment and early diagnostic), variability (cytostatics and radiotherapy), research (clinical trials and financed projects) and work loads. OUTCOMES: In 3 out of 14 centers medical histories are unique for each patient. In average, 3 of the 6 most frequent tumor locations have joint protocols. The delays for the diagnostic test vary from 1 to 23 days and from 11 to 29 days for treatments. The consumption increase of 12 cytostatics was of 71.8% (average of 602,413 euro per hospital). The average rate of patients undergoing irradiation was of 34 %. 109 clinical trials were approved (a centre performes 26) and 20 projects were financed (Health Department, Consejería de Salud). The attendance pressure was of 140 patients per specialist in MO and RO (maximum of 241 and 214 respectively and minimum of 85 and 69). COMMENTS: The information gathered in this study shows a diverse nature, and meets items not always taken into consideration, in a global way, but with a clearly complementary nature. No doubt, they offer a scenery that deepens into the complexity of which today means the improvement of the quality of the non-monographic hospital centres that attend patients suffering from cancer. It finally offers instruments for the improvement of the clinical management which we understand it is of certain usefulness.
Assuntos
Neoplasias/terapia , Planejamento de Assistência ao Paciente/normas , Qualidade da Assistência à Saúde/normas , HumanosRESUMO
The objective of this review was to analyze trends in outcomes and in the quality of phase III randomized controlled trials on advanced NSCLC published between 2000 and 2012, selecting 76 trials from a total of 122 retrieved in a structured search. Over the study period, the number of randomized patients per trial increased by 14 per year (P = 0.178). The sample size significantly increased between 2000 and 2012 in trials of targeted agents (460.1 vs. 740.8 patients, P = 0.009), trials of >1 drug (360.4 vs. 584.8, P = 0.014), and those including patients with good performance status (675.3 vs. 425.6; P = 0.003). Quality of life was assessed in 46 trials (60.5%), and significant improvements were reported in 10 of these (21.7%). Platinum-based regimens were the most frequently investigated (86.8% of trials). Molecular-targeted agents were studied in 25.0% of chemotherapy arms, and the percentage of trials including these agents increased each year. The median (interquartile range) overall survival (MOS) was 9.90 (3.5) months with an increase of 0.384 months per year of publication (P < 0.001). A statistically significant improvement in MOS was obtained in only 13 (18.8%) trials. The median progression-free survival was 4.9 (1.9) months, with a nonsignificant increase of 0.026 months per year (P > 0.05). There has been a continuous but modest improvement in the survival of patients with advanced NSCLC over the past 12 years. Nevertheless, the quality of clinical trials and the benefit in outcomes should be carefully considered before the incorporation of novel approaches into clinical practice.