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BACKGROUND: The objective of the present analysis was to assess whether small bowel gastrointestinal stromal tumor (GIST) is associated with worse cancer-specific survival (CSS) and overall survival (OS) compared with gastric GIST on a population-based level. PATIENTS AND METHODS: Data on patients aged 18 years or older with histologically proven GIST was extracted from the SEER database from 1998 to 2011. OS and CSS for small bowel GIST were compared with OS and CSS for gastric GIST by application of adjusted and unadjusted Cox regression analyses and propensity score analyses. RESULTS: GIST were located in the stomach (n = 3011, 59 %), duodenum (n = 313, 6 %), jejunum/ileum (n = 1288, 25 %), colon (n = 139, 3 %), rectum (n = 172, 3 %), and extraviscerally (n = 173, 3 %). OS and CSS of patients with GIST in the duodenum [OS, HR 0.95, 95 % confidence interval (CI) 0.76-1.19; CSS, HR 0.99, 95 % CI 0.76-1.29] and in the jejunum/ileum (OS, HR 0.97, 95 % CI 0.85-1.10; CSS, HR = 0.95, 95 % CI 0.81-1.10) were similar to those of patients with gastric GIST in multivariate analyses. Conversely, OS and CSS of patients with GIST in the colon (OS, HR 1.40; 95 % CI 1.07-1.83; CSS, HR 1.89, 95 % CI 1.41-2.54) and in an extravisceral location (OS, HR 1.42, 95 % CI 1.14-1.77; CSS, HR = 1.43, 95 % CI 1.11-1.84) were significantly worse than those of patients with gastric GIST. CONCLUSIONS: Contrary to common belief, OS and CSS of patients with small bowel GIST are not statistically different from those of patients with gastric GIST when adjustment is made for confounding variables on a population-based level. The prognosis of patients with nongastric GIST is worse because of a colonic and extravisceral GIST location. These findings have implications regarding adjuvant treatment of GIST patients. Hence, the dogma that small bowel GIST patients have worse prognosis than gastric GIST patients and therefore should receive adjuvant treatment to a greater extent must be revisited.
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Adenocarcinoma/mortalidad , Tumores del Estroma Gastrointestinal/mortalidad , Neoplasias Intestinales/mortalidad , Intestino Delgado/patología , Puntaje de Propensión , Neoplasias Gástricas/mortalidad , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Neoplasias Intestinales/epidemiología , Neoplasias Intestinales/patología , Neoplasias Intestinales/cirugía , Intestino Delgado/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Programa de VERF , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tasa de Supervivencia , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: There is an ongoing debate about the relationship between breast implants and secondary malignancies. METHODS: Breast cancer patients undergoing surgical reconstruction after mastectomy by either implants or autologous flap were identified in the Surveillance, Epidemiology and End Results registry between 1998 and 2002. The occurrence of secondary malignancies at least 1 year after diagnosis was compared between breast reconstruction with implants vs autologous flap. RESULTS: Of 7955 women, 3727 underwent reconstruction using implants and 4228 using autologous flap. The incidence of secondary tumours was similar in both the groups (hazards ratio (HR)=1.02, 95% confidence interval (CI): 0.82-1.26, P=0.880). For lung cancer, a significantly increased risk for implants (HR=2.51, 95% CI: 1.28-4.95, P=0.005) was observed. CONCLUSIONS: Except for lung cancer, no association between implants and secondary malignancies including lymphomas was observed.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Mamoplastia/efectos adversos , Adulto , Anciano , Implantes de Mama/efectos adversos , Neoplasias de la Mama/etiología , Femenino , Humanos , Incidencia , Mastectomía/efectos adversos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Colgajos Quirúrgicos/patología , Colgajos Quirúrgicos/cirugíaRESUMEN
BACKGROUND: There is ongoing debate about nonpalliative primary tumor surgery in metastatic breast cancer patients. This issue has become even more relevant with the introduction of increasingly sensitive imaging modalities. METHODS: Metastatic breast cancer patients were identified in the SEER registry between 1998 and 2009. The effect of primary tumor surgery on overall and cancer-specific mortality using risk-adjusted Cox proportional hazard regression modeling and stratified propensity score matching was assessed. RESULTS: Overall, 16,247 women with metastatic breast cancer were included. Of those 7600 women underwent primary tumor surgery although 8647 did not have any surgery at all. Primary tumor surgery decreased from 62.0% in 1998 to 39.1% in 2009 (P < 0.001). Primary tumor surgery was associated with decreased overall mortality (hazard ratio (HR) = 0.53, 95% CI 0.50-0.55, P < 0.001) and cancer-specific mortality (HR = 0.51, 95% CI 0.48-0.54, P < 0.001) in the propensity score-matched model. The benefit of primary tumor surgery increased from 1998 to 2009 for overall mortality (1998: HR = 0.72, 95% CI 0.59-0.89, 2009: HR = 0.42, 95% CI 0.35-0.50) and cancer-specific mortality (1998: HR = 0.72, 95% CI 0.58-0.89, 2009: HR = 0.40, 95% CI 0.33-0.48). CONCLUSIONS: The present study-the first population-based analysis using propensity score methods-provides evidence of a favorable impact of primary tumor surgery on mortality in metastatic breast cancer patients. Most importantly, the benefit of primary tumor surgery increased over time from 1998 to 2009. Although the final results of ongoing randomized studies are awaited, currently available evidence should be discussed with metastatic breast cancer patients.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Programa de VERF , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The distinction between right-sided and left-sided colon cancer has recently received considerable attention due to differences regarding underlying genetic mutations. There is an ongoing debate if right- versus left-sided tumor location itself represents an independent prognostic factor. We aimed to investigate this question by using propensity score matching. METHODS: Patients with resected, stage I - III colon cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2012). Both univariable and multivariable Cox regression as well as propensity score matching were used. RESULTS: Overall, 91,416 patients (51,937 [56.8 %] with right-sided, 39,479 [43.2 %] with left-sided colon cancer; median follow-up 38 months) were eligible. In univariable analysis, patients with right-sided cancer had worse overall (hazard ratio [HR] = 1.32, 95 % CI:1.29-1.36, P < 0.001) and cancer-specific survival (HR = 1.26, 95 % CI:1.21-1.30, P < 0.001) compared to patients with left-sided cancer. After propensity score matching, the prognosis of right-sided carcinomas was better regarding overall (HR = 0.92, 95 % CI: 0.89 - 0.94, P < 0.001) and cancer-specific survival (HR = 0.90, 95 % CI:0.87 - 0.93, P < 0.001). In stage I and II, the prognosis of right-sided cancer was better for overall (HR = 0.89, 95 % CI:0.84-0.94 and HR = 0.85, 95 % CI:0.81-0.89) and cancer-specific survival (HR = 0.71, 95 % CI:0.64 - 0.79 and HR = 0.75, 95 % CI:0.70-0.80). Right- and left-sided colon cancer had a similar prognosis for stage III (overall: HR = 0.99, 95 % CI:0.95-1.03 and cancer-specific: HR = 1.04, 95 % CI:0.99-1.09). CONCLUSIONS: This population-based analysis on stage I - III colon cancer provides evidence that the prognosis of localized right-sided colon cancer is better compared to left-sided colon cancer. This questions the paradigm from previous research claiming a worse survival in right-sided colon cancer patients.
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Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Programa de VERFRESUMEN
OBJECTIVE: To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND: There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS: Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS: Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS: On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.
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Neoplasias Colorrectales/cirugía , Cuidados Paliativos/tendencias , Anciano , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/secundario , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Programa de VERF , Análisis de Supervivencia , Estados UnidosRESUMEN
BACKGROUND: The objective of the present population-based analysis was to assess survival patterns in patients with resected and metastatic GIST. METHODS: Patients with histologically proven GIST were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 1998 through 2011. Survival was determined applying Kaplan-Meier-estimates and multivariable Cox-regression analyses. The impact of size and mitotic count on survival was assessed with a generalized receiver-operating characteristic-analysis. RESULTS: Overall, 5138 patients were included. Median age was 62 years (range: 18-101 years), 47.3% were female, 68.8% Caucasians. GIST location was in the stomach in 58.7% and small bowel in 31.2%. Lymph node and distant metastases were found in 5.1 and 18.0%, respectively. For non-metastatic GIST, three-year overall survival increased from 68.5% (95 % CI: 58.8-79.8%) in 1998 to 88.6% (95 % CI: 85.3-92.0%) in 2008, cancer-specific survival from 75.3% (95 % CI: 66.1-85.9%) in 1998 to 92.2% (95 % CI: 89.4-95.1%) in 2008. For metastatic GIST, three-year overall survival increased from 15.0% (95 % CI: 5.3-42.6%) in 1998 to 54.7% (95 % CI: 44.4-67.3%) in 2008, cancer-specific survival from 15.0% (95 % CI: 5.3-42.6%) in 1998 to 61.9% (95 % CI: 51.4-74.5%) in 2008 (all PTrend < 0.05). CONCLUSIONS: This is the first SEER trend analysis assessing outcomes in a large cohort of GIST patients over a 11-year time period. The analysis provides compelling evidence of a statistically significant and clinically relevant increase in overall and cancer-specific survival from 1998 to 2008, both for resected as well as metastatic GIST.
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Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Programa de VERF , Análisis de Supervivencia , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Adulto JovenRESUMEN
Mantle cell lymphoma (MCL) is a rare non-Hodgkin's lymphoma entity with a heterogeneous clinical presentation. Various therapeutic considerations in MCL for younger and elderly patients were used over the past decade. We retrospectively analyzed all 44 patients consecutively treated in a tertiary hospital between 2000 and 2010 with newly diagnosed MCL. Patient characteristics, treatment regimens and biological markers were evaluated with regard to overall survival (OS). Treatment regimens were categorized into internationally accepted intensive standard therapies and less intensive alternative treatment regimens given with palliative intent. Biological markers were correlated with clinical outcome by univariate analysis. The median age of the entire study group was 66 years (range: 42-88), with 23 (52%) patients ≥65 years. Thirty-one (70%) patients received standard regimens, the remaining 13 (30%) patients were treated with other, less intensive regimens with palliative intent. With a median follow-up of 5.25 years, the three-year OS rate was 60% [95% confidence interval (CI) 0.47-0.77]. Patients treated with standard regimens had a three-year survival rate of 77% (range: 64-94%). Of these, patients younger than 65 years were observed to have better OS (83% at 3 years; 95% CI 68-100%) than those older than 65 years (69% at 3 years; 95% CI 48-99%). In univariate analysis, the only parameters with a statistically significant prognostic impact on OS were absolute monocyte count as a continuous variable, lactate dehydrogenase and absolute lymphocyte count (>0.5 × 10(9) /l) at diagnosis. In conclusion, our data of an unselected group of patients with newly diagnosed MCL treated at a single centre tertiary hospital are in line with results from larger randomized trials demonstrating an improved OS rate of younger as well as elderly MCL patients within the last decade.
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Linfoma de Células del Manto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Células , Quimioterapia/métodos , Femenino , Humanos , Inmunoterapia/métodos , L-Lactato Deshidrogenasa/metabolismo , Linfocitos/citología , Masculino , Persona de Mediana Edad , Monocitos/citología , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Age-period-cohort (APC) models are the state of art in cancer projections, assessing past and recent trends and extrapolating mortality or incidence data into the future. Nordpred is a well-established software, assuming a Poisson distribution for the counts and a log-link or power-link function with fixed power; however, its predictive performance is poor for sparse data. Bayesian models with log-link function have been applied, but they can lead to extreme estimates. In this paper, we address criticisms of the aforementioned models by providing Bayesian formulations based on a power-link and develop a generalized APC power-link model, which assumes a random rather than fixed power parameter. In addition, a power model with a fixed power parameter of five was formulated in the Bayesian framework. The predictive performance of the new models was evaluated on Swiss lung cancer mortality data using model-based estimates of observed periods. Results indicated that the generalized APC power-link model provides best estimates for male and female lung cancer mortality. The gender-specific models were further applied to project lung cancer mortality in Switzerland during the periods 2009-2013 and 2014-2018.
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Teorema de Bayes , Estudios de Cohortes , Modelos Estadísticos , Adulto , Anciano , Anciano de 80 o más Años , Simulación por Computador , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Cadenas de Markov , Persona de Mediana Edad , Valor Predictivo de las Pruebas , SuizaRESUMEN
A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (PTEN) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775 N-linked glycoproteins from sera and prostate tissue of wild-type and Pten-null mice. Using label-free quantitative proteomics, we showed that Pten inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue PTEN status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling.
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Biomarcadores de Tumor/sangre , Neoplasias de la Próstata/diagnóstico , Proteómica/métodos , Animales , Biología Computacional , Silenciador del Gen , Glicoproteínas/sangre , Humanos , Masculino , Métodos , Ratones , Fosfohidrolasa PTEN/análisis , Fosfohidrolasa PTEN/genéticaRESUMEN
BACKGROUND: The objective of the present investigation is to assess the baseline mortality-adjusted 10-year survival of rectal cancer patients. METHODS: Ten-year survival was analyzed in 771 consecutive American Joint Committee on Cancer (AJCC) stage I-IV rectal cancer patients undergoing open resection between 1991 and 2008 using risk-adjusted Cox proportional hazard regression models adjusting for population-based baseline mortality. RESULTS: The median follow-up of patients alive was 8.8 years. The 10-year relative, overall, and cancer-specific survival were 66.5% [95% confidence interval (CI) 61.3-72.1], 48.7% (95% CI 44.9-52.8), and 66.4% (95% CI 62.5-70.5), respectively. In the entire patient sample (stage I-IV) 47.3% and in patients with stage I-III 33.6 % of all deaths were related to rectal cancer during the 10-year period. For patients with AJCC stage I rectal cancer, the 10-year overall survival was 96% and did not significantly differ from an average population after matching for gender, age, and calendar year (p = 0.151). For the more advanced tumor stages, however, survival was significantly impaired (p < 0.001). CONCLUSIONS: Retrospective investigations of survival after rectal cancer resection should adjust for baseline mortality because a large fraction of deaths is not cancer related. Stage I rectal cancer patients, compared to patients with more advanced disease stages, have a relative survival close to 100% and can thus be considered cured. Using this relative-survival approach, the real public health burden caused by rectal cancer can reliably be analyzed and reported.
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Neoplasias del Recto/mortalidad , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Cancer survivors are a heterogeneous group with complex health problems. Data concerning its total number and growing dynamics for Switzerland are scarce and outdated. METHODS: Population and mortality data were retrieved from the Swiss Federal Statistical Office (FSO). Incidence and relative survival for invasive cancers were computed using data from the cancer registries Geneva (1970-2009), St. Gallen - Appenzell (1980-2010), Grisons & Glarus (1989-2010), and Valais (1989-2010). We estimated prevalence for 1990-2010 using the Prevalence, Incidence Approach MODel (PIAMOD) method. We calculated trends in prevalence estimates by Joinpoint analysis. Projections were extrapolated using the above models and based on time trends of the period 2007-2010. RESULTS: The estimated number of cancer survivors increased from 139'717 in 1990 (2.08% of the population) to 289'797 persons in 2010 (3.70%). The growth rate shows an exponential shape and was 3.3% per year in the period 2008 to 2010. Almost half of the survivors have a history of breast, prostate or colorectal cancer. Among cancer survivors, 55% are women but the increases have been more marked in men (p < 0.01, 3.9% annual increase in men vs. 2.7% in women since 2008). By the end of 2020 372'000 cancer survivors are expected to live in Switzerland. CONCLUSIONS: There is a rapidly growing population of cancer survivors in Switzerland whose needs and concerns are largely unknown.
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Neoplasias/epidemiología , Sobrevivientes/estadística & datos numéricos , Distribución por Edad , Femenino , Humanos , Incidencia , Masculino , Distribución por Sexo , Suiza/epidemiologíaRESUMEN
PURPOSE: This study investigated satisfaction with treatment decision (SWTD), decision-making preferences (DMP), and main treatment goals, as well as evaluated factors that predict SWTD, in patients receiving palliative cancer treatment at a Swiss oncology network. PATIENTS AND METHODS: Patients receiving a new line of palliative treatment completed a questionnaire 4-6 weeks after the treatment decision. Patient questionnaires were used to collect data on sociodemographics, SWTD (primary outcome measure), main treatment goal, DMP, health locus of control (HLoC), and several quality of life (QoL) domains. Predictors of SWTD (6 = worst; 30 = best) were evaluated by uni- and multivariate regression models. RESULTS: Of 480 participating patients in eight hospitals and two private practices, 445 completed all questions regarding the primary outcome measure. Forty-five percent of patients preferred shared, while 44 % preferred doctor-directed, decision-making. Median duration of consultation was 30 (range: 10-200) minutes. Overall, 73 % of patients reported high SWTD (≥24 points). In the univariate analyses, global and physical QoL, performance status, treatment goal, HLoC, prognosis, and duration of consultation were significant predictors of SWTD. In the multivariate analysis, the only significant predictor of SWTD was duration of consultation (p = 0.01). Most patients indicated hope for improvement (46 %), followed by hope for longer life (26 %) and better quality of life (23 %), as their main treatment goal. CONCLUSION: Our results indicate that high SWTD can be achieved in most patients with a 30-min consultation. Determining the patient's main treatment goal and DMP adds important information that should be considered before discussing a new line of palliative treatment.
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Neoplasias/psicología , Cuidados Paliativos/psicología , Prioridad del Paciente/psicología , Satisfacción del Paciente , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Actitud Frente a la Salud , Comunicación , Toma de Decisiones , Femenino , Objetivos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Cuidados Paliativos/métodos , Valor Predictivo de las Pruebas , Pronóstico , Calidad de VidaRESUMEN
Screening for malignant disease aims to reduce the population risk of impaired health due to the tumor in question. Screening does not only entail testing but covers all steps required to achieve the intended reduction in risk, from the appropriate information of the population to a suitable therapy. Screening tests are performed in individuals free or unaware of any symptoms associated with the tumor. An essential condition is a recognizable pathological abnormality, which occurs without symptoms and represents a pre-clinical, early stage of the tumor. Overdiagnosis and overtreatment have only recently been recognized as important problems of screening for malignant disease. Overdiagnosis is defined as a screening-detected tumor that would never have led to symptoms. In prostate-specific antigen (PSA) screening for prostate cancer 50 % - 70 % of screening-detected cancers represent such overdiagnoses. Similarly, in the case of mammography screening 20 % - 30 % of screening-detected breast cancers are overdiagnoses. The evaluation of screening interventions is often affected by biases such as healthy screenee effects or length and lead time bias. Randomized controlled trials are therefore needed to examine the efficacy and effectiveness of screening interventions and to define the rate of adverse outcomes such as unnecessary diagnostic evaluations, overdiagnosis and overtreatment. Unfortunately there is no independent Swiss body comparable to the National Screening Committee in the United Kingdom or the United States Preventive Services Task Force, which examines screening tests and programs and develops recommendations. Clearly defined goals, a central organization responsible for inviting eligible individuals, documentation and quality assurance and balanced information of the public are important attributes of successful screening programs. In Switzerland the establishment of such programs is hampered by the highly fragmented, Federal health system which allows patients to access specialists directly.
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Medicina Basada en la Evidencia , Tamizaje Masivo/métodos , Tamizaje Masivo/tendencias , Neoplasias/diagnóstico , Neoplasias/prevención & control , HumanosRESUMEN
Background: Patient preferences for treatment outcomes are important to guide decision-making in clinical practice, but little is known about the preferences of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Objective: To evaluate patient preferences regarding the attributed benefits and harms of systemic treatments for mHSPC and preference heterogeneity between individuals and specific subgroups. Design setting and participants: We conducted an online discrete choice experiment (DCE) preference survey among 77 patients with metastatic prostate cancer (mPC) and 311 men from the general population in Switzerland between November 2021 and August 2022. Outcome measurements and statistical analysis: We evaluated preferences and preference heterogeneity related to survival benefits and treatment-related adverse effects using mixed multinomial logit models and estimated the maximum survival time participants were willing to trade to avert specific adverse effects. We further assessed characteristics associated with different preference patterns via subgroup and latent class analyses. Results and limitations: Patients with mPC showed an overall stronger preference for survival benefits in comparison to men from the general population (p = 0.004), with substantial preference heterogeneity between individuals within the two samples (both p < 0.001). There was no evidence of differences in preferences for men aged 45-65 yr versus ≥65 yr, patients with mPC in different disease stages or with different adverse effect experiences, or general population participants with and without experiences with cancer. Latent class analyses suggested the presence of two groups strongly preferring either survival or the absence of adverse effects, with no specific characteristic clearly associated with belonging to either group. Potential biases due to participant selection, cognitive burden, and hypothetical choice scenarios may limit the study results. Conclusions: Given the relevant heterogeneity in participant preferences regarding the benefits and harms of treatment for mHSPC, patient preferences should be explicitly discussed during decision-making in clinical practice and reflected in clinical practice guidelines and regulatory assessment regarding treatment for mHSPC. Patient summary: We examined the preferences (values and perceptions) of patients and men from the general population regarding the benefits and harms of treatment for metastatic prostate cancer. There were large differences between men in how they balanced the expected survival benefits and potential adverse effects. While some men strongly valued survival, others more strongly valued the absence of adverse effects. Therefore, it is important to discuss patient preferences in clinical practice.
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Langerhans cell histiocytosis (LCH) is rare in adults, and only a subset of these patients suffers from central nervous system (CNS) involvement. Hence, evidence-based treatment recommendations are lacking. A case of a 20-year-old student with multisystem LCH and extensive CNS involvement is described, who showed a durable response to 2-chlorodeoxyadenosine after prior therapies with the tyrosine kinase inhibitors sorafenib and imatinib. In accordance to the experiences provided by other case series, which are reviewed herein, 2-chlorodeoxyadenosine can be considered an effective and safe option for adult LCH with CNS involvement.
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Antineoplásicos/uso terapéutico , Bencenosulfonatos/administración & dosificación , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Cladribina/uso terapéutico , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Piperazinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridinas/administración & dosificación , Pirimidinas/administración & dosificación , Adulto , Benzamidas , Enfermedades del Sistema Nervioso Central/complicaciones , Histiocitosis de Células de Langerhans/etiología , Humanos , Mesilato de Imatinib , Niacinamida/análogos & derivados , Compuestos de Fenilurea , SorafenibRESUMEN
Cancer patients with long-term venous catheter are at risk for thromboembolic complications at the catheter tip and in the adjacent venous vessels. We assessed whether local thrombogenicity could be prevented with an experimental coated (with athrombogenic layer) catheter device (CD) compared to an uncoated CD. Patients requiring a long-term venous catheter were randomly allocated to receive either a standard uncoated or experimental coated (with athrombogenic Camouflage® layer) CD. The athrombogenic layer creates a barrier against non-specific adsorption of plasma proteins. The primary endpoint was urokinase injection in cases of an unsuccessful blood aspiration from the CD. Secondary endpoints included early (haematoma, pneumothorax) and late (venous thrombosis, infection) catheter-associated complications and catheter defects. One hundred and seventy-nine patients were randomly assigned to a CD (experimental n = 89/standard n = 90). One hundred and ten (62%) patients with a total of 1,286 catheter taps were analysed for the primary endpoint. Necessity for urokinase injection was 8/680 (1.2% experimental) vs. 33/606 (5.4% standard) per catheter tap and 4/55 (7.3% experimental) vs. 18/55 (32.7% standard) per patient. A repeated measures logistic regression to assess the effect of coating yielded an odds ratio of 3.5 (95% confidence interval, 1.2-10.4; p = 0.03) for the primary endpoint. All patients allocated per protocol were analysed for the secondary endpoints. Nine (5.4%) local thrombotic complications, seven (4.1%) catheter infections, and no catheter defect were observed. Athrombogenic coating of CD in cancer patients resulted in a significant reduced necessity for urokinase injections and subsequently less inconvenience for patients and fewer costly interventions.
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Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia , Materiales Biocompatibles Revestidos , Neoplasias/tratamiento farmacológico , Tromboembolia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Cateterismo Venoso Central/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
AIM: There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. METHODS: A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. RESULTS: The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. CONCLUSIONS: A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL).
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Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Metotrexato/administración & dosificación , Algoritmos , Antimetabolitos Antineoplásicos/farmacocinética , Área Bajo la Curva , Teorema de Bayes , Neoplasias Encefálicas/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Linfoma/metabolismo , Masculino , Tasa de Depuración Metabólica , Metotrexato/farmacocinética , Resultado del TratamientoRESUMEN
Background: Patient preference studies can inform decision-making across all stages of the medical product life cycle (MPLC). The treatment landscape for advanced prostate cancer (APC) treatment has substantially changed in recent years. However, the most patient-relevant aspects of APC treatment remain unclear. This systematic review of patient preference studies in APC aimed to summarize the evidence on patient preferences and patient-relevant aspects of APC treatments, and to evaluate the potential contribution of existing studies to decision-making within the respective stages of the MPLC. Methods: We searched MEDLINE and EMBASE for studies evaluating patient preferences related to APC treatment up to October 2020. Two reviewers independently performed screening, data extraction and quality assessment in duplicate. We descriptively summarized the findings and analyzed the studies regarding their contribution within the MPLC using an analytical framework. Results: Seven quantitative preference studies were included. One study each was conducted in the marketing approval and the health technology assessment (HTA) and reimbursement stage, and five were conducted in the post-marketing stage of the MPLC. While almost all stated to inform clinical practice, the specific contributions to clinical decision-making remained unclear for almost all studies. Evaluated attributes related to benefits, harms, and other treatment-related aspects and their relative importance varied relevantly between studies. All studies were judged of high quality overall, but some methodological issues regarding sample selection and the definition of patient-relevant treatment attributes were identified. Conclusion: The most patient-relevant aspects regarding the benefits and harms of APC treatment are not yet established, and it remains unclear which APC treatments are preferred by patients. Findings from this study highlight the importance of transparent reporting and discussion of study findings according to their aims and with respect to their stage within the MPLC. Future research may benefit from using the MPLC framework for analyzing or determining the aims and design of patient preference studies.
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BACKGROUND: Information about extrapulmonary small cell carcinoma (EPSCC) is limited and the role of prophylactic cranial irradiation (PCI) is unknown. PATIENTS AND METHODS: Disease presentation and outcome of all EPSCC at our hospital between 1990 and 2009 were retrospectively analyzed. RESULTS: Of 30 EPSCC, the male:female ratio was 58%:42%; 83% had a performance status of 0-2. Median age was 71 years (32-80). Seventeen (57%) had limited stage (LS), 13 (43%) extensive stage (ES). The location of the primary tumor was gastrointestinal (n = 8), unknown (6), gynecological (6), urogenital (5), and ear nose throat (5). Four (13%) developed brain metastases (2 ES, 2 LS). In ES, first line chemotherapy (CT) was given in 85%, mostly platinum-etoposide (64%). Response rate was 90%. In LS, CT and radiotherapy (RT) ± resection resulted in persistent remissions in 67% of patients. Median survival was 16 months (1-107 months), 18 months (1-107 months), and 9 months (0.4-25 months) for LS + ES, LS, and ES, respectively. Weight loss ≥5 % and ECOG performance status 3 + 4 were associated with poorer survival (p < 0.001 and p < 0.01, respectively). CONCLUSION: The incidence of brain metastases was relatively low (13%). More studies are necessary, before routinely offering PCI to patients with EPSCC. Best survival outcomes in LS were achieved with multimodality treatment including CT and RT. Prognosis was poor in patients with ES.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundario , Irradiación Craneana , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
OBJECTIVES: Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and RET (REarranged during Transfection) signaling. The primary objective of this open-label phase I trial was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of vandetanib in combination with gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic adenocarcinoma (PAC). METHODS: Patients received vandetanib (100 or 300 mg/day) plus gemcitabine (1,000 mg/m(2) i.v. on days 1, 8 and 15 per 28-day cycle) until disease progression, unacceptable toxicity or withdrawal of patient consent. The MTD was determined by the assessment of dose-limiting toxicity (DLT) during the first 28 days of treatment. RESULTS: Fifteen patients were treated. No DLTs occurred in the first cohort of vandetanib 100 mg (n = 3) and recruitment continued at the 300-mg dose level. At the 300-mg dose, 3 out of 12 patients (including 2 in the expansion cohort) experienced DLTs (aphasia, elevated liver enzymes and neutropenia; all of them grade 3), thus exceeding the MTD. No objective responses were observed, with stable disease being the best response in 78% of evaluable patients. CONCLUSIONS: Vandetanib 100 mg/day is the RD in combination with gemcitabine in the treatment of patients with advanced PAC.