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1.
Scand J Gastroenterol ; 59(9): 1097-1104, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38994854

RESUMO

OBJECTIVES: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. |This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. MATERIALS AND METHODS: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. RESULTS: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. CONCLUSION: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.


Assuntos
Neoplasias Pancreáticas , Guias de Prática Clínica como Assunto , Humanos , Neoplasias Pancreáticas/cirurgia , Países Escandinavos e Nórdicos , Recidiva Local de Neoplasia , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/normas , Inquéritos e Questionários , Pancreatectomia , Vigilância da População
2.
AJR Am J Roentgenol ; 221(1): 117-123, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36629303

RESUMO

Incidental imaging findings are common and analogous to the results of screening tests when screening is performed of unselected, low-risk patients. Approximately 15-30% of all diagnostic imaging and 20-40% of CT examinations contain at least one incidental finding. Patients with incidental findings but low risk for disease are likely to experience length bias, lead-time bias, overdiagnosis, and overtreatment that create an illusion of benefit while conferring harm. This includes incidental detection of many types of cancers that, although malignant, would have been unlikely to affect a patient's health had the cancer not been detected. Detection of some incidental findings can improve health, but most do not. Greater patient- and disease-related risk increase the likelihood an incidental finding is important. Clinical guidelines for incidental findings should more deeply integrate patient risk factors and disease aggressiveness to inform management. Lack of outcome and cost-effectiveness data has led to reflexive management strategies for incidental findings that promote low-value and sometimes harmful care.


Assuntos
Achados Incidentais , Neoplasias , Humanos , Cuidados de Baixo Valor , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fatores de Risco
3.
Breast Cancer Res ; 24(1): 15, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35197123

RESUMO

BACKGROUND: An increasingly popular measure for summarising cancer prognosis is the loss in life expectancy (LLE), i.e. the reduction in life expectancy following a cancer diagnosis. The proportion of life lost (PLL) can also be derived, improving comparability across age groups as LLE is highly age-dependent. LLE and PLL are often used to assess the impact of cancer over the remaining lifespan and across groups (e.g. socioeconomic groups). However, in the presence of screening, it is unclear whether part of the differences across population groups could be attributed to lead time bias. Lead time is the extra time added due to early diagnosis, that is, the time from tumour detection through screening to the time that cancer would have been diagnosed symptomatically. It leads to artificially inflated survival estimates even when there are no real survival improvements. METHODS: In this paper, we used a simulation-based approach to assess the impact of lead time due to mammography screening on the estimation of LLE and PLL in breast cancer patients. A natural history model developed in a Swedish setting was used to simulate the growth of breast cancer tumours and age at symptomatic detection. Then, a screening programme similar to current guidelines in Sweden was imposed, with individuals aged 40-74 invited to participate every second year; different scenarios were considered for screening sensitivity and attendance. To isolate the lead time bias of screening, we assumed that screening does not affect the actual time of death. Finally, estimates of LLE and PLL were obtained in the absence and presence of screening, and their difference was used to derive the lead time bias. RESULTS: The largest absolute bias for LLE was 0.61 years for a high screening sensitivity scenario and assuming perfect screening attendance. The absolute bias was reduced to 0.46 years when the perfect attendance assumption was relaxed to allow for imperfect attendance across screening visits. Bias was also present for the PLL estimates. CONCLUSIONS: The results of the analysis suggested that lead time bias influences LLE and PLL metrics, thus requiring special consideration when interpreting comparisons across calendar time or population groups.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Expectativa de Vida , Mamografia/métodos , Programas de Rastreamento
4.
Cancer ; 128 Suppl 4: 883-891, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35133658

RESUMO

Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.


Assuntos
Detecção Precoce de Câncer , Neoplasias , Humanos , Programas de Rastreamento , Neoplasias/diagnóstico
5.
BMC Cancer ; 20(1): 1124, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33218313

RESUMO

BACKGROUND: Lead time, the interval between screen detection and when a disease would have become clinically evident, has been cited to explain longer survival times in mammography detected breast cancer cases (BC). METHODS: An institutional retrospective cohort study of BC outcomes related to detection method (mammography (MamD) vs. patient (PtD)). Cases were first primary invasive stage I-III BC, age 40-74 years (n = 6603), 1999-2016. Survival time was divided into 1) distant disease-free interval (DDFI) and 2) distant disease-specific survival (DDSS) as two separate time interval outcomes. We measured statistical association between detection method and diagnostic, treatment and outcome variables using bivariate comparisons, Cox proportional hazards analyses and mean comparisons. Outcomes were distant recurrence (n = 422), DDFI and DDSS. RESULTS: 39% of cases were PtD (n = 2566) and 61% were MamD (n = 4037). MamD cases had a higher percentage of Stage I tumors [MamD 69% stage I vs. PtD 31%, p < .001]. Rate of distant recurrence was 11% among PtD BC cases (n = 289) vs. 3% of MamD (n = 133) (p < .001). Order of factor entry into the distant recurrence time interval (DDFI) model was 1) TNM stage (p < .001), 2) HR/HER2 status (p < .001), 3) histologic grade (p = .005) and 4) detection method (p < .001). Unadjusted PtD DDFI mean time was 4.34 years and MamD 5.52 years (p < .001), however when stratified by stage, the most significant factor relative to distant recurrence, there was no significant difference between PtD and MamD BC. Distant disease specific survival time did not differ by detection method. CONCLUSION: We observed breast cancer distant disease-free interval to be primarily associated with stage at diagnosis and tumor characteristics with less contribution of detection method to the full model. Patient and mammography detected breast cancer mean lead time to distant recurrence differed significantly by detection method for all stages but not significantly within stage with no difference in time from distant recurrence to death. Lead time difference related to detection method appears to be present but may be less influential than other factors in distant disease-free and disease specific survival.


Assuntos
Neoplasias da Mama/diagnóstico , Adulto , Idoso , Neoplasias da Mama/patologia , Estudos de Coortes , Diagnóstico Precoce , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos
6.
Chin J Cancer Res ; 32(4): 467-475, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963459

RESUMO

OBJECTIVE: To investigate what extent lead-time bias is likely to affect endoscopic screening effectiveness for esophageal cancer in the high-risk area in China. METHODS: A screening model based on the epidemiological cancer registry data, yielding a population-level incidence and mortality rates, was carried out to simulate study participants in the high-risk area in China, and investigate the effect of lead-time bias on endoscopic screening with control for length bias. RESULTS: Of 100,000 participants, 6,150 (6.15%) were diagnosed with esophageal squamous dysplasia during the 20-year follow-up period. The estimated lead time ranged from 1.67 to 5.78 years, with a median time of 4.62 years [interquartile range (IQR): 4.07-5.11 years] in the high-risk area in China. Lead-time bias exaggerated screening effectiveness severely, causing more than a 10% overestimation in 5-year cause-specific survival rate and around a 43% reduction in cause-specific hazard ratio. The magnitude of lead-time bias on endoscopic screening for esophageal cancer varied depending on the screening strategies, in which an inverted U-shaped and U-shaped effects were observed in the 5-year cause-specific survival rate and cause-specific hazard ratio respectively concerning a range of ages for primary screening. CONCLUSIONS: Lead-time bias, usually causing an overestimation of screening effectiveness, is an elementary and fundamental issue in cancer screening. Quantification and correction of lead-time bias are essential when evaluating the effectiveness of endoscopic screening in the high-risk area in China.

7.
Gastroenterology ; 154(8): 2068-2086.e5, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29458154

RESUMO

BACKGROUND & AIMS: Guidelines recommend endoscopic surveillance of patients with Barrett's esophagus (BE) to identify those with dysplasia (a precursor of carcinoma) or early-stage esophageal adenocarcinoma (EAC) who can be treated endoscopically. However, it is unclear whether surveillance increases survival times of patients with BE. We performed a systematic review and meta-analysis to qualitatively and quantitatively examine evidence for the association of endoscopic surveillance in patients with BE with survival and other outcomes. METHODS: We searched publication databases for studies reporting the effects of endoscopic surveillance on mortality and other EAC-related outcomes. We reviewed randomized controlled trials, case-control studies, studies comparing patients with BE who received regular surveillance with those who did not receive regular surveillance, and studies comparing outcomes of patients with surveillance-detected EAC vs symptom-detected EACs. We performed a meta-analysis of surveillance studies to generate summary estimates using a random effects model. The primary aim was to examine the association of BE surveillance on EAC-related mortality. Secondary aims were to examine the association of BE surveillance with all-cause mortality and EAC stage at time of diagnosis. RESULTS: A single case-control study did not show any association between surveillance and EAC-related mortality. A meta-analysis of 4 cohort studies found that lower EAC-related and all-cause mortality were associated with regular surveillance (relative risk, 0.60; 95% CI, 0.50-0.71; hazard ratio, 0.75; 95% CI, 0.59-0.94). Meta-analysis of 12 cohort studies showed lower EAC-related and all-cause mortality among patients with surveillance-detected EAC vs symptom-detected EAC (relative risk, 0.73; 95% CI, 0.57-0.94; hazard ratio, 0.59; 95% CI, 0.45-0.76). Lead- and length-time bias adjustment substantially attenuated/eliminated the observed benefits. Surveillance was associated with detection of EAC at earlier stages. A randomized trial is underway to evaluate the effects of endoscopic surveillance on mortality in patients with BE. CONCLUSIONS: In a systematic review and meta-analysis of the effects of surveillance in patients with BE, surveillance as currently performed was associated with detection of earlier-stage EAC and may provide a small survival benefit. However, the effects of confounding biases on these estimates are not fully defined and may completely or partially explain the observed differences between surveyed and unsurveyed patients.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/epidemiologia , Esôfago de Barrett/diagnóstico por imagem , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/epidemiologia , Esofagoscopia/estatística & dados numéricos , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Esôfago de Barrett/patologia , Esôfago de Barrett/cirurgia , Progressão da Doença , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/estatística & dados numéricos , Esofagoscopia/normas , Esôfago/diagnóstico por imagem , Esôfago/patologia , Esôfago/cirurgia , Humanos , Incidência , Guias de Prática Clínica como Assunto , Medição de Risco
8.
Colorectal Dis ; 21(7): 775-781, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30848537

RESUMO

AIM: Studies addressing the benefit of early intervention are prone to lead-time bias, which results in an artificial improvement in cancer-specific mortality. We have previously compared the age at death for patients with colorectal cancer presenting on an emergency or elective basis. In this study, we aimed to repeat the analysis with a minimum follow-up of 10 years. METHOD: A nonscreen-detected cohort of patients presenting with colorectal cancer to three Lanarkshire Hospitals between 2000 and 2006 were entered into a prospective database, with analysis performed on 28 November 2016. The following data were collected: age at death, presentation type (emergency/elective), operative intent (palliative/curative) and Dukes stage. Results are presented as [mean (95% confidence intervals)]. Statistical analysis was undertaken using Student's t-test and multivariate analysis performed using Cox proportional hazard models. RESULTS: One thousand six hundred and thirty-six patients were identified. Elective patients presented younger than emergency patients [67.9 (67.3-68.5) vs 70.9 (69.6-72.2) years; P < 0.0001]. Overall mortality was 71.1% at time of analysis; no difference was seen in the mean age at death between emergency and elective presentation [73.5 (72.4-74.8) vs 73.6 (72.3-74.9) years; P = 0.841]. CONCLUSION: Current early detection strategies to diagnose colorectal cancer may improve cancer-specific survival by increasing lead-time bias. However, in our cohort of symptomatic patients, treatment on an elective or emergency basis does not influence overall survival. These data suggest that in selected patients, particularly where there is comorbidity, it may be reasonable to adopt a more expectant approach to investigate and treat colorectal symptoms.


Assuntos
Fatores Etários , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos Eletivos/mortalidade , Tratamento de Emergência/mortalidade , Fatores de Tempo , Idoso , Viés , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Prospectivos
9.
Dig Dis Sci ; 64(9): 2622-2630, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30835027

RESUMO

BACKGROUND: The long-term outcomes of post-colonoscopy colorectal cancer have varied in previous studies. Our nationwide cohort analysis estimated expected years of life lost to adjust for lead time bias. AIM: We recalculated the long-term outcomes for post-colonoscopy and detected colorectal cancer. METHODS: Patients with colorectal cancer registered in the Taiwan Cancer Registry between 2002 and 2009 were enrolled. The detected group included 22,169 cases of colorectal cancer confirmed within 6 months after a colonoscopy. The post-colonoscopy group included 1653 cancer patients who received a colonoscopy 6-60 months before diagnosis. Patients were followed up until 2011. We simulated age-, sex-, and calendar year-matched referents from life tables in the Taiwan National Vital Statistics using a Monte Carlo method. The life expectancy and expected years of life lost of the cancer patients were obtained from extrapolation of the logit transformation of the survival ratio between the cancer cohorts and the referent groups. RESULTS: Post-colonoscopy colorectal cancer had shorter life expectancies than detected cancer (stages 2-4: 13.6 vs. 16.1 years; 8.7 vs. 12.6 years; 2.1 vs. 4.1 years, p < 0.001). The loss-of-life expectancy did not show this trend after adjusting for lead time bias. Post-colonoscopy colorectal cancer was found at an older age, more often proximal, and was associated with previous endoscopic polypectomy procedures (p < 0.001). CONCLUSIONS: Post-colonoscopy colorectal cancer leads to a shorter life expectancy, which appears partially explained by the presence of lead time bias. Quality assurance for colonoscopy and close surveillance for high risk groups would reduce post-colonoscopy colorectal cancer.


Assuntos
Colo/patologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Expectativa de Vida , Idoso , Idoso de 80 Anos ou mais , Viés , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Sistema de Registros , Taxa de Sobrevida , Taiwan/epidemiologia , Fatores de Tempo
10.
Liver Int ; 38(12): 2260-2268, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29981527

RESUMO

BACKGROUND & AIMS: Surveillance reportedly has benefit on survival in patients with hepatocellular carcinoma (HCC), even after adjustment for lead-time bias. However, previous adjustment for lead-time bias using tumour volume doubling time (TVDT) had inherent problem in accuracy. We evaluated survival benefit of HCC surveillance with newly developed approach for adjusting lead-time bias. In addition, survival benefit was evaluated according to HCC aetiology and liver function. METHODS: A total of 3899 patients were studied. TVDT was calculated in 255 study patients with ≥2 tumour size measurements before the diagnosis of HCC. Adjusted survival time was calculated based on TVDT, as the time from when HCC was assumed to be 5 mm to death or last follow-up. Survival rates based on this adjusted survival time were compared between the surveillance and nonsurveillance groups and categorized by HCC aetiology and liver function. RESULTS: Calculated TVDT varied widely by study patients (median 141.9, IQR, 73.1-261.7 days). Survival rates based on adjusted survival time were higher in the surveillance group overall and by patients HCC aetiology. Whereas adjusted survival rates were higher in the surveillance group in Child-Pugh class A patients, the survival benefit was smaller in Child-Pugh class B patients and not statistically significant in Child-Pugh class C patients. CONCLUSIONS: The survival benefit of surveillance for patients with HCC was demonstrated after adjustment for lead-time bias with novel, more accurate methodology. However, the benefits differed based on liver function and may vary largely by patients because of wide variation in TVDT.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Carga Tumoral , Idoso , Carcinoma Hepatocelular/mortalidade , Distribuição de Qui-Quadrado , Feminino , Humanos , Japão/epidemiologia , Fígado/fisiopatologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Vigilância da População , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Eur Radiol ; 28(3): 1085-1094, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28983713

RESUMO

OBJECTIVES: Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. METHODS: A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan-Meier (K-M) survival rates, separately for baseline and annual rounds. RESULTS: Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long-term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81-89%) for adenocarcinoma, 74% (95% CI 63-85%) for squamous cell, 48% (95% CI 34-62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. CONCLUSIONS: The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. KEY POINTS: • Lung cancer aggressiveness varies considerably by cell type and nodule consistency. • Kaplan-Meier survival rates varied by cell type between 100% and 48%. • The percentages of lung cancers by cell type in screening rounds reflect screening biases. • Rank ordering by cell type survival is consistent with that by lead times. • Empirical evidence provides critical information for the regimen of screening.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/mortalidade , Idoso , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Estudos Prospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/mortalidade , Tomografia Computadorizada por Raios X/métodos
12.
Int J Colorectal Dis ; 31(5): 1039-1045, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26763006

RESUMO

BACKGROUND: Screening for colon cancer (CC) may not only reduce its occurrence but has also the potential to reduce the overall mortality. So far, there has been little evidence that detection of colon cancer by screening colonoscopy results in different survival rates compared to symptomatic patients. PATIENTS AND METHODS: Clinical, histological, diagnostic, and survival data of 1016 consecutive patients with CC from a prospectively expanded single-institutional database were analyzed for diagnostic, treatment, and prognostic factors. Findings were then stratified according to detection by screening colonoscopy vs. patients who became symptomatic prior to further diagnostic work-up. RESULTS: 7.1 % of all patients were identified by screening colonoscopy for colon cancer. Screened patients were younger (68.2 vs. 64.8 years), had smaller T stage (p = 0.032), lower tumor stage (p = 0.009), and a tendency to less lymph node metastasis. Overall survival was superior in screened patients, and stage-specific survival showed a tendency to improved survival, which was not statistically significant. Furthermore, a higher percentage of screened patients underwent adjuvant chemotherapy (84.6 vs. 55.0 %, p = 0.032). CONCLUSION: Survival outcome and enrollment in a multimodal treatment was higher in screening-detected patients compared to patients diagnosed after the onset of clinical symptoms. Besides a potential occurrence of lead time bias, these findings strongly support the need for continued improvement of screening programs and the recruitment of more patients for colorectal cancer screening.


Assuntos
Neoplasias do Colo/diagnóstico , Colonoscopia , Detecção Precoce de Câncer , Programas de Rastreamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Adulto Jovem
13.
Hepatol Res ; 46(12): 1275-1280, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26879882

RESUMO

AIM: Length time bias is a selection bias which can lead to an overestimation of survival of screening-detected cases caused by the relative excess of slower-growing tumors detected with respect to symptomatic cases. This leads to the incorrect perception that screening improves outcomes when it only selects tumors with a favorable biology. Data regarding this bias in surveillance for hepatocellular carcinoma (HCC) have never been provided. METHODS: A semi-Markov model was developed to investigate this issue. An exponential tumor growth was applied. During its growth, tumor diagnosis "at surveillance appointments" was made when tumor attained a size equal to or above the size of tumors diagnosed in surveilled patients obtained from pertinent published reports, or "in-between appointments" (due to the development of symptoms) if tumor size attained the size of symptomatic diagnosis, derived from published reports; otherwise the tumor continued to grow until the time horizon had been reached. Tumor doubling time (DT) values were recorded according to the method of diagnosis. RESULTS: In a theoretical cohort of 1000 patients submitted to semiannual surveillance, 72.5% will be diagnosed at a surveillance appointment and 18% because of symptom development, although under surveillance. Patients diagnosed with HCC at a surveillance appointment had a median tumor DT of 100 days (interquartile range, 68-143 days), whereas those diagnosed because of symptoms had a median DT of 42 days (interquartile range, 29-58 days) although under surveillance. CONCLUSION: The surveillance propensity to detect slower-growth tumors is relevant, and practical suggestions to minimize this bias in longitudinal studies are provided.

14.
Cancer ; 120(18): 2784-91, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24925345

RESUMO

Observational studies present inferential challenges. These challenges are acute in cancer screening studies, in which lead-time and length biases are ever present. These biases can make any study worthless. Moreover, a flawed study's impact on the public can be deleterious when its conclusions are publicized by a naïve media. Flawed studies can also make the public learn to be wary of any article or reports of articles claiming to be scientific. Here, the author addresses these and related issues in the context of a study published in Cancer.


Assuntos
Neoplasias da Mama/mortalidade , Detecção Precoce de Câncer/estatística & dados numéricos , Mamografia/estatística & dados numéricos , Feminino , Humanos
15.
J Hepatol ; 61(2): 333-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24717522

RESUMO

BACKGROUND & AIMS: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. METHODS: One-thousand three-hundred and eighty Child-Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. RESULTS: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p<0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5 months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen = 13), as did annual surveillance (18 patients). CONCLUSIONS: Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Neoplasias Hepáticas/diagnóstico , Idoso , Viés , Carcinoma Hepatocelular/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Fatores de Tempo
16.
Lung Cancer ; 192: 107790, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38696920

RESUMO

OBJECTIVES: Immune-related adverse events (irAEs) are known to be associated with clinical efficacy and better prognoses in patients receiving immune checkpoint inhibitors. In particular, endocrine irAE (e-irAE) is related to better prognoses. Since the incidence of irAEs increase as treatment duration becomes longer, we should consider lead-time bias not to overvalue the result. We evaluated the impact of e-irAE on the outcome before and after 6-, 9-, and 12-week landmark analyses. MATERIALS AND METHODS: We evaluated 222 patients with advanced or recurrent non-small cell lung cancer who received anti-PD-1 antibodies such as nivolumab or pembrolizumab from January 2016 to April 2021. Treatment efficacy and outcomes of patients with or without e-irAE (e-irAE group or no e-irAE group) were retrospectively evaluated. In addition, we performed 6-, 9-, and 12-week landmark analyses to exclude the effect of lead-time bias. RESULTS: Median progression free survival (PFS) was significantly longer in the e-irAE group than in the no e-irAE group (overall: 15.3 vs 3.9 months, p < 0.0001; 6-week: 15.3 vs 4.9 months, p < 0.0002; 9-week: 19.8 vs 6.1 months, p = 0.0012, 12-week: 19.8 vs 8.4 months, p = 0.017). Overall survival (OS) was significantly longer in the e-irAE group (overall: not reached (NR) vs 15.4 months, p = 0.0003; 6-week: NR vs 19.1 months, p = 0.0049, 9-week: NR vs 22.2 months, p = 0.006; 12-week: NR vs 23.3 months, p = 0.04). We used the multivariate cox proportional hazard model to adjust for confounding factors and found that e-irAE had better impact on both PFS and OS (PFS: overall: hazard ratio 0.37 [95% confidence interval 0.23-0.56], 6-week: 0.41 [0.26-0.63], 9-week: 0.43 [0.24-0.63], 12-week: 0.52 [0.31-0.84]; OS: overall: 0.40 [0.22-0.68], 6-week: 0.46 [0.25-0.79], 9-week: 0.47 [0.24-0.84], 12-week: 0.58 [0.29-1.08]). CONCLUSION: The occurrence of endocrine irAE was associated with better efficacy and prognoses regardless of the lead-time bias.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Biomarcadores , Prognóstico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Incidência , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Taxa de Sobrevida
17.
Schizophr Res ; 252: 287-293, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36706472

RESUMO

OBJECTIVE: The association between duration of untreated psychosis (DUP) and later outcome is not fully understood. Jonas et al. in their 20-year follow-up found that the association could be explained by lead-time bias. In this study we aimed to analyze the relationship between DUP, time since onset of psychosis and functional outcome using a similar statistical approach as the Jonas study. METHOD: Using data from 496 participants with first-episode schizophrenia, DUP was assessed using the IRAOS and functioning at the baseline assessment and the subsequent follow-ups (1, 2, 5 and 10 years) was assessed using the GAF-F. For premorbid functioning, the Premorbid Assessment of Functioning Scale was used and rescaled to correspond to the GAF. RESULTS: The model with the best fit of data included both a slope and a level change. This model of level of function over time had the inflection point at the time of first treatment. This model indicated a slow decline per year until first treatment, at which point there was a sharp decrease in functioning, and after which functioning gradually improved again. Both in this model and in models accounting for potential lead-time bias, however, longer DUP was associated with a decrease in function for each additional week of DUP. This is in contrast with the Jonas et al. study. CONCLUSION: In this study, we did not find evidence of a lead-time bias, but rather found that onset of treatment occurs at the time when participants level of functioning was most impaired, and consequently was not at random.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Psicologia do Esquizofrênico , Fatores de Tempo , Viés
18.
Neurooncol Pract ; 10(2): 113-125, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36970177

RESUMO

Background: Better overall survival (OS) reported in patients with incidental diffuse low-grade glioma (iLGG) in comparison to symptomatic LGG (sLGG) may be overestimated by lead-time and length-time. Methods: We performed a systematic review and meta-analysis of studies on adult hemispheric iLGGs according to the PRISMA statement to adjust for biases in their outcomes. Survival data were extracted from Kaplan-Meier curves. Lead-time was estimated by 2 methods: Pooled data of time to become symptomatic (LTs) and time calculated from the tumor growth model (LTg). Results: We selected articles from PubMed, Ovid Medline, and Scopus since 2000. Five compared OS between patients with iLGG (n = 287) and sLGG (n = 3117). The pooled hazard ratio (pHR) for OS of iLGG to sLGG was 0.40 (95% confidence interval [CI] {0.27-0.61}). The estimated mean LTs and LTg were 3.76 years (n = 50) and 4.16-6.12 years, respectively. The corrected pHRs were 0.64 (95% CI [0.51-0.81]) by LTs and 0.70 (95% CI [0.56-0.88]) by LTg. In patients with total removal, the advantage of OS in iLGG was lost after the correction of lead-time. Patients with iLGG were more likely to be female pooled odds ratio (pOR) 1.60 (95% CI [1.25-2.04]) and have oligodendrogliomas (pOR 1.59 [95% CI {1.05-2.39}]). Correction of the length-time bias, which increased the pHR by 0.01 to 0.03, preserved the statistically significant difference in OS. Conclusions: The reported outcome in iLGG was biased by lead-time and length-time. Although iLGG had a longer OS after correction of biases, the difference was less than previously reported.

19.
Cancer Epidemiol ; 84: 102357, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37027906

RESUMO

BACKGROUND: When solid tumors are amenable to definitive resection, clinical outcomes are generally superior to when those tumors are inoperable. However, the population-level cancer survival benefit of eligibility for surgery by cancer stage has not yet been quantified. METHODS: Using Surveillance, Epidemiology and End Results data allowing us to identify patients who were deemed eligible for and received surgical resection, we examined the stage-specific association of surgical resection with 12-year cancer-specific survival. The 12-year endpoint was selected to maximize follow-up time and thereby minimize the influence of lead time bias. RESULTS: Across a variety of solid tumor types, earlier stage at diagnosis allowed for surgical intervention at a much higher rate than later-stage diagnosis. At every stage, surgical intervention was associated with a substantially higher rate of 12-year cancer-specific survival, with absolute differences of up to 51% for stage I, 51% for stage II, and 44% for stage III cancer, and stage-specific mortality relative risks of 3.6, 2.4, and 1.7, respectively. CONCLUSIONS: Diagnosis of solid cancers in early stages often enables surgical resection, which reduces the risk of death from cancer. Receipt of surgical resection is an informative endpoint that is strongly associated with long-term cancer-specific survival at every stage.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estados Unidos/epidemiologia , Estadiamento de Neoplasias , Taxa de Sobrevida
20.
Cancer Med ; 11(4): 1160-1171, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34913599

RESUMO

BACKGROUND: Current guidelines recommend endoscopic surveillance for Barrett oesophagus (BE), but the value of surveillance is still debated. Using a combination of primary care, secondary care and cancer registry datasets, we examined the impact of a prior BE diagnosis, clinical and risk factors on survival from oesophageal cancer and adenocarcinoma. METHODS: Retrospective cohort study of patients aged 50 and above diagnosed with malignant oesophageal cancer between 1993 and 2014 using Clinical Practice Research Datalink (CPRD). All prior BE diagnoses and endoscopies were identified from CPRD and Hospital Episode Statistics. Histology information was obtained from linked cancer registry data. We used flexible parametric models to estimate excess hazard ratios (EHRs) for relative survival. We simulated the potential impact of lead-time by adding random lead-times from a variety of distributions to all those with prior BE. RESULTS: Among our oesophageal cancer (n = 7503) and adenocarcinoma (n = 1476) cohorts only small percentages, 3.4% and 5.3%, respectively, had a prior BE diagnosis. Two-year relative survival was better among patients with BE: 48.0% (95% CI 41.9-54.9) compared to 25.2% (24.3-26.2) without. Patients with BE had a better prognosis (EHR = 0.53, 0.41-0.68). Survival was higher even if patients with BE had fewer than two endoscopies (50.0%; 43.6-57.3). A survival benefit was still observed after lead-time adjustment, with a 20% absolute difference in 2-year survival using a 5 year mean sojourn time. CONCLUSIONS: Patients with a prior BE diagnosis had a survival advantage. This was not fully explained by surveillance endoscopies.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Esôfago de Barrett/diagnóstico , Estudos de Coortes , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Humanos , Estudos Retrospectivos , Reino Unido/epidemiologia
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