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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adenocarcinoma/diagnóstico , Guías de Práctica Clínica como Asunto/normasRESUMEN
BACKGROUND: The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. PATIENTS AND METHODS: The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. RESULTS: With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P = 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P = 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P = 0.033). The safety profile remained unchanged since the previous analysis. CONCLUSIONS: Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.
RESUMEN
BACKGROUND: After surgical resection of pancreatic ductal adenocarcinoma (PDAC), patients are predominantly treated with adjuvant chemotherapy, commonly consisting of gemcitabine (GEM)-based regimens or the modified FOLFIRINOX (mFFX) regimen. While mFFX regimen has been shown to be more effective than GEM-based regimens, it is also associated with higher toxicity. Current treatment decisions are based on patient performance status rather than on the molecular characteristics of the tumor. To address this gap, the goal of this study was to develop drug-specific transcriptomic signatures for personalized chemotherapy treatment. PATIENTS AND METHODS: We used PDAC datasets from preclinical models, encompassing chemotherapy response profiles for the mFFX regimen components. From them we identified specific gene transcripts associated with chemotherapy response. Three transcriptomic artificial intelligence signatures were obtained by combining independent component analysis and the least absolute shrinkage and selection operator-random forest approach. We integrated a previously developed GEM signature with three newly developed ones. The machine learning strategy employed to enhance these signatures incorporates transcriptomic features from the tumor microenvironment, leading to the development of the 'Pancreas-View' tool ultimately clinically validated in a cohort of 343 patients from the PRODIGE-24/CCTG PA6 trial. RESULTS: Patients who were predicted to be sensitive to the administered drugs (n = 164; 47.8%) had longer disease-free survival (DFS) than the other patients. The median DFS in the mFFX-sensitive group treated with mFFX was 50.0 months [stratified hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.21-0.44, P < 0.001] and 33.7 months (stratified HR 0.40, 95% CI 0.17-0.59, P < 0.001) in the GEM-sensitive group when treated with GEM. Comparatively patients with signature predictions unmatched with the treatments (n = 86; 25.1%) or those resistant to all drugs (n = 93; 27.1%) had shorter DFS (10.6 and 10.8 months, respectively). CONCLUSIONS: This study presents a transcriptome-based tool that was developed using preclinical models and machine learning to accurately predict sensitivity to mFFX and GEM.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Leucovorina , Terapia Neoadyuvante , Compuestos Organoplatinos , Neoplasias del Recto , Humanos , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Cancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients' functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank. METHODS: In a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration. RESULTS: Item assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs ≥ 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format). CONCLUSION: Two well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making.
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Neoplasias , Calidad de Vida , Humanos , Calidad de Vida/psicología , Psicometría/métodos , Encuestas y Cuestionarios , Reino Unido , Francia , Neoplasias/terapia , Neoplasias/psicologíaRESUMEN
The opportunity to detect pancreatic cancer (PC) when potentially curable depends on early diagnosis and an ability to identify and screen high-risk populations before symptoms arise. Identification of a high-risk population is challenging and optimal screening tools remain unclear.1 Older age is the strongest risk factor; incidence peaks at 65-69 years in males and 75-79 years in females.2 A pooled analysis of 117 meta-analyses assigned a relative risk to a number of common risk factors (Supplementary Table S1, available at https://doi.org/10.1016/j.annonc.2023.08.009).3 The vast majority (>80%) of PCs arise due to sporadically occurring somatic mutations. Only a small proportion are due to inherited deleterious germline mutations.1 Familial PC, defined as at least two first-degree relatives with PC, accounts for only 4%-10% of all cases. Variants in BRCA2 are the most common genetic abnormalities seen in familial PC. Other familial syndromes linked to PC are listed in Supplementary Table S2, available at https://doi.org/10.1016/j.annonc.2023.08.009. Individuals from families at risk should receive genetic counselling and be considered for enrolment in investigational screening registries. Currently, in high-risk individuals, annual endoscopic ultrasound (EUS) and/or pancreatic magnetic resonance imaging (MRI) are the procedures of choice for surveillance.4 Surveillance programmes usually begin at age 50 years (or 10 years earlier than the age of the youngest affected relative). Prospective surveillance data in high-risk individuals demonstrated high rates of resectability and encouraging observations of long-term survival.5, 6, 7, 8, 9 In sporadic PC, the major risk factors are tobacco, Helicobacter pylori infection and factors related to dietary habits (high red meat, high alcohol intake, low fruit and vegetable intake, overweight/obesity and type 2 diabetes mellitus).2,3,10 Chronic pancreatitis, irrespective of the cause (alcohol abuse, smoking, genetic mutations), is a risk factor for PC. A proportion of the risk factors associated with PC are potentially modifiable, affording a unique opportunity for primary prevention that is yet to be realised.
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Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Pancreaticoduodenectomía/normas , Neoplasias Pancreáticas/cirugía , Tomografía Computarizada por Rayos X , Factores de RiesgoRESUMEN
BACKGROUND: The Generic Adherence for Chronic Diseases Profile is a French generic scale (GACID-P) developed to measure adherence in several disease areas such as cardiology, rheumatology, diabetes, cancer and infectiology. METHOD: We aimed to study the measurement invariance of the Generic Adherence for Chronic Diseases Profile by an item response model, optimize the new instrument version from item response model and qualitative content analyses results, and validate the instrument. The metric properties of the optimized version were studied according to classical test theory and item response model analysis. RESULTS: A sample of 397 patients consulting at two French hospitals (in diabetes, cardiology, rheumatology, cancerology and infectiology) and in four private practices was recruited; 314 (79%) patients also completed the questionnaire 15 days later. Factor analyses revealed four dimensions: "Forgetting to take medication", "Intention to comply with treatment", "Limitation of risk-related consumer habits" and "Healthy lifestyle". The item response model and content analyses optimized these four dimensions, regrouping 32 items in four dimensions of 25 items, including one item conditioned on tobacco use. The psychometric properties and scale calibration were satisfactory. One score per dimension was calculated as the sum of the items for the dimensions "Forgetting to take medication" and "Intention to comply with treatment" and as a weighted score according to the item response model analysis for the two other dimensions because of differential item functioning found for two items. CONCLUSION: Four adherence profile scores were obtained. The instrument validity was documented by a theoretical approach and content analysis. The Generic Adherence for Chronic Diseases Profile is now available for research targeting adherence in a broad perspective.
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Estilo de Vida Saludable , Calidad de Vida , Humanos , Calibración , Enfermedad Crónica , Análisis FactorialRESUMEN
KNOWLEDGE TRANSFER STATEMENT: This commentary highlights that effective implementation of best-practice oral health care in acute geriatric units is built on the time and relationship building invested in the preimplementation phase.
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Atención a la Salud , ConocimientoRESUMEN
BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.
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COVID-19 , Neoplasias/complicaciones , COVID-19/complicaciones , Femenino , Francia , Humanos , Masculino , SARS-CoV-2RESUMEN
BACKGROUND: Health-related quality of life (HRQoL) has become a major endpoint to assess the clinical benefit of new therapeutic strategies in oncology clinical trials. Typically, HRQoL outcomes are analyzed using linear mixed models (LMMs). However, longitudinal analysis of HRQoL in the presence of missing data remains complex and unstandardized. Our objective was to compare the modeling alternatives that account for informative dropout. METHODS: We investigated three alternative methods-the selection model (SM), pattern-mixture model (PMM), and shared-parameters model (SPM)-in relation to the LMM. We first compared them on the basis of methodological arguments highlighting their advantages and drawbacks. Then, we applied them to data from a randomized clinical trial that included 267 patients with advanced esophageal cancer for the analysis of four HRQoL dimensions evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. RESULTS: We highlighted differences in terms of outputs, interpretation, and underlying modeling assumptions; this methodological comparison could guide the choice of method according to the context. In the application, none of the four models detected a significant difference between the two treatment arms. The estimated effect of time on HRQoL varied according to the method: for all analyzed dimensions, the PMM estimated an effect that contrasted with those estimated by the SM and SPM; the LMM estimated effects were confirmed by the SM (on two of four HRQoL dimensions) and SPM (on three of four HRQoL dimensions). CONCLUSIONS: The PMM, SM, or SPM should be used to confirm or invalidate the results of LMM analysis when informative dropout is suspected. Of these three alternative methods, the SPM appears to be the most interesting from both theoretical and practical viewpoints. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov , number NCT00861094 .
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Neoplasias Esofágicas , Calidad de Vida , Neoplasias Esofágicas/tratamiento farmacológico , Humanos , Estudios Longitudinales , Oncología Médica , Encuestas y CuestionariosRESUMEN
BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire. PATIENTS AND METHODS: The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items. RESULTS: The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale. CONCLUSION: Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module.
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Neoplasias de la Mama , Calidad de Vida , Neoplasias de la Mama/tratamiento farmacológico , Ensayos Clínicos como Asunto , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
PURPOSE: The role of chemotherapy has not been established in the treatment of metastatic squamous cell oesophageal cancer (mESCC). PATIENTS AND METHODS: E-DIS is a discontinuation trial, aimed at estimating efficacy, quality of life and safety of chemotherapy continuation (CT-CONT) in patients with mESCC who are free from progression after a selection phase of chemotherapy. The primary end-point was overall survival. RESULTS: Sixty-seven patients were randomised. The 9-month survival rate was 50% (85% confidence interval [CI]: 37-62%) and 48% (85% CI: 35-60%) in the CT-CONT arm and in the chemotherapy discontinuation (CT-DISC) arm, respectively. The time until definitive deterioration of the global health status (European Organisation for Research and Treatment of Cancer [EORTC] core quality of life questionnaire) was 6.6 months (95% CI: 3.3-12.4) for the CT-CONT arm and 4.2 months (95% CI: 2.9-6.3) for the CT-DISC arm, with a hazard ratio (HRCT-DISC/CT-CONT) = 1.44 (95% CI: 0.82-2.53). We observed a beneficial trend in favour of CT-CONT (HR > 1) for most dimensions, including an improvement for three dimensions (dysphagia, eating and oesophageal pain) of the EORTC Oesophageal Cancer Module QLQ-OES18. CONCLUSION: CT-CONT provides an overall survival rate that is similar to CT-DISC. E-DIS trial provides valuable data to support shared decision-making between physicians and patients regarding CT-CONT/DISC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
Advances in cancer care delivery require revision and further development of questionnaires assessing patients' perceived quality of care. This study pre-tested the revised EORTC satisfaction with cancer care core questionnaire applicable in both the cancer inpatient and outpatient settings, and its new, outpatient-specific complementary module. The process of revision, development of the extended application, and pre-testing of these questionnaires was based on phases I to III of the "EORTC Quality of Life Group Module Development Guidelines." In phase III, patients in 11 countries in four European regions, South America and Asia completed provisional versions of the questionnaires. Fifty-seven relevant issues selected from literature reviews and input from experts were operationalized into provisional items, and subsequently translated into ten languages. Assessment of understanding, acceptability, redundancy and relevance by patients (n = 151) from oncology inpatient wards, and outpatient chemotherapy, radiotherapy and consultation settings, led to retention of, deletion of and merging of 40, 14 and 6 items respectively. Cronbach's alpha coefficients for hypothesized questionnaire scales were above 0.80. Our results provide preliminary support for the 33-item EORTC Satisfaction with cancer care core questionnaire and the 7-item complementary module specific for the outpatient care setting. A large scale phase IV cross-cultural psychometric study is now underway.
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Neoplasias/terapia , Satisfacción del Paciente , Anciano , Atención Ambulatoria , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sociedades Médicas , Encuestas y CuestionariosRESUMEN
BACKGROUND: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up. PATIENTS AND METHODS: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires. RESULTS: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms. CONCLUSIONS: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Quimioradioterapia Adyuvante/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias del Recto/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: A recent prospective randomised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy (CRT) regimens for inoperable non-metastatic oesophageal cancer patients. This secondary analysis aimed to describe the impact of CRT on health-related quality of life (HRQOL), physical functioning, dysphagia, fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival. PATIENTS AND METHODS: A total of 267 patients were randomly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1. HRQOL was prospectively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 with the oesophageal cancer module (QLQ-OES18). RESULTS: Both groups showed high baseline compliance. Subsequently, compliance reduced to 41% at the 6-month follow-up. Baseline HRQOL scores showed no statistical differences between treatment arms. During treatment, both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea, although dysphagia moderately improved in the fluorouracil-cisplatin arm only (p = 0.047). During follow-up, HRQOL scores revealed no significant differences between chemotherapy regimens. Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia (p = 0.017) with a greater decrease in dysphagia in the fluorouracil-cisplatin group. Time until definitive deterioration analysis showed no significant differences in global HRQOL, functional or main symptom domains. However, time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss (p = 0.002), QLQ-OES-18 pain (p = 0.008), trouble swallowing saliva (p = 0.011) and trouble talking (p = 0.020). CONCLUSION: Analyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil-cisplatin regimen as part of definitive CRT.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Adenoescamoso/terapia , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Cisplatino/uso terapéutico , Neoplasias Esofágicas/terapia , Calidad de Vida , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/psicología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/patología , Carcinoma Adenoescamoso/psicología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/psicología , Quimioradioterapia/efectos adversos , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/psicología , Carcinoma de Células Escamosas de Esófago , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Francia , Humanos , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
On entering the Earth's atmosphere, micrometeoroids partially or completely ablate, leaving behind layers of metallic atoms and ions. The relative concentration of the various metal layers is not well explained by current models of ablation. Furthermore, estimates of the total flux of cosmic dust and meteoroids entering the Earth's atmosphere vary over two orders of magnitude. To better constrain these estimates and to better model the metal layers in the mesosphere, an experimental Meteoric Ablation Simulator (MASI) has been developed. Interplanetary Dust Particle (IDP) analogs are subjected to temperature profiles simulating realistic entry heating, to ascertain the differential ablation of relevant metal species. MASI is the first ablation experiment capable of simulating detailed mass, velocity, and entry angle-specific temperature profiles whilst simultaneously tracking the resulting gas-phase ablation products in a time resolved manner. This enables the determination of elemental atmospheric entry yields which consider the mass and size distribution of IDPs. The instrument has also enabled the first direct measurements of differential ablation in a laboratory setting.