To compare overall survival in patients with esophageal adenocarcinoma who underwent transhiatal esophagectomy (THE) with limited lymphadenectomy or transthoracic esophagectomy (TTE) with extended ...lymphadenectomy with or without neoadjuvant chemoradiotherapy (nCRT).
The application of neoadjuvant therapy might change the association between the extent of lymphadenectomy and survival in patients with esophageal adenocarcinoma. This may influence the choice of surgical approach in patients treated with nCRT.
Patients with potentially curable subcarinal esophageal adenocarcinoma treated with surgery alone or nCRT followed by surgery in 7 centers were included. The effect of surgical approach on overall survival, differentiated by the addition or omission of nCRT, was analyzed using a multivariable Cox regression model that included well-known prognostic factors and factors that might have influenced the choice of surgical approach.
In total, 701 patients were included, of whom 318 had TTE with extended lymphadenectomy and 383 had THE with limited lymphadenectomy. TTE had differential effects on survival (P for interaction = 0.02), with a more favorable prognostic effect in patients who were treated with surgery alone hazard ratio (HR) = 0.77, 95% confidence interval (CI) 0.58-1.03. This association was statistically significant in a subgroup of patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 0.62, 95% CI 0.43-0.90). The favorable prognostic effect of TTE over THE was absent in the nCRT and surgery group (HR = 1.16, 95% CI 0.80-1.66) and in the subgroup of nCRT patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 1.00, 95% CI 0.61-1.68).
Compared to surgery alone, the addition of nCRT may reduce the need for TTE with extended lymphadenectomy to improve long-term survival in patients with esophageal adenocarcinoma.
Background
The value of conventional prognostic factors is unclear in the era of multimodal treatment for oesophageal cancer. This study aimed to quantify the impact of neoadjuvant chemoradiotherapy ...(nCRT) and surgery on well established prognostic factors, and to develop and validate a prognostic model.
Methods
Patients treated with nCRT plus surgery were included. Multivariable Cox modelling was used to identify prognostic factors for overall survival. A prediction model for individual survival was developed using stepwise backward selection. The model was internally validated leading to a nomogram for use in clinical practice.
Results
Some 626 patients who underwent nCRT plus surgery were included. In the multivariable model, only pretreatment cN category and ypN category were independent prognostic factors. The final prognostic model included cN, ypT and ypN categories, and had moderate discrimination (c‐index at internal validation 0·63).
Conclusion
In patients with oesophageal or oesophagogastric cancer treated with nCRT plus surgery, overall survival can best be estimated using a prediction model based on cN, ypT and ypN categories. Predicted survival according to this model showed only moderate correlation with observed survival, emphasizing the need for new prognostic factors to improve survival prediction.
Better predictor still needed
A decreased transfer coefficient of the lung for carbon monoxide (K(CO)) is associated with emphysema. We evaluated whether in heavy smokers, baseline K(CO) was associated with the progression of ...computed tomography (CT)-detected emphysema, and the progression of airflow limitation. Heavy smokers, mean ± sd 41.3 ± 18.7 pack-yrs, participating in a lung cancer screening trial underwent diffusion testing and CT scanning of the lungs. CT scanning was repeated after median (25th-75th percentile) 2.8 (2.7-3.0) yrs and emphysema was assessed by lung densitometry using the 15th percentile. The association between K(CO) at baseline with progression of emphysema and lung function decline was assessed by multiple linear regression, correcting for baseline CT-quantified emphysema severity and forced expiratory volume in 1 s (FEV₁/forced vital capacity (FVC), age, height, body mass index, pack-yrs and smoking status (current or former smoker). 522 participants aged 60.1 ± 5.4 yrs were included. Mean ± sd 15th percentile was -938 ± 19, absolute FEV₁/FVC was 71.6 ± 9% and K(CO) was 1.23 ± 0.25, which is 81.8 ± 16.5% of predicted. By interpolation, a one sd (0.25) lower K(CO) value at baseline predicted a 1.6 HU lower 15th percentile and a 0.78% lower FEV₁/FVC after follow-up (p < 0.001). A lower baseline K(CO) value is independently associated with a more rapid progression of emphysema and airflow limitation in heavy smokers.
This study examines whether couples time their work hours and how this work timing influences child care demand and the time that spouses jointly spend on leisure, household chores, and child care. ...By using an innovative matching strategy, this study identifies the timing of work hours that cannot be explained by factors other than the partners' potential to communicate about the timing of their work. The main findings are that couples with children create less overlap in their work times and this effect is more pronounced the younger the children. We find evidence for a togetherness preference of spouses, but only for childless couples. Work timing also influences the joint time that is spent on household chores, but the effect is small. Finally, work timing behaviour affects the demand for informal child care, but not the demand for formal child care.
Background Fear of spiders, or Arachnophobia, is one of the most common specific phobias. The gold standard treatment, in vivo exposure therapy, is effective, but comes with significant limitations, ...including restricted availability, high costs, and high refusal rates. Novel technologies, such as augmented reality, may help to overcome these limitations and make Exposure Therapy more accessible by using mobile devices. Objective This study will use a Randomized Controlled Trial design to investigate whether ZeroPhobia: Arachnophobia, a 6-week Augmented Reality Exposure Therapy smartphone self-help application, can effectively reduce spider phobia symptoms. Additionally, we will examine user-friendliness of the application and the effect of usage intensity and presence on treatment outcome. Methods This study is registered in the Netherlands Trial Registry under NL70238.029.19 (Trial NL9221). Ethical approval was received on October 11, 2019. One-hundred-twelve participants (age 18–64, score ≥ 59) on the Fear of Spiders Questionnaire FSQ will be recruited from the general Dutch population and randomly assigned to a treatment or waitlist control group. The ZeroPhobia application can be accessed on users’ smartphone. Baseline, post-test (i.e., at six weeks), 3- and 12-month follow-up assessments will be done, each including the Fear of Spiders Questionnaire as the main outcome measure as well as additional measures of anxiety, depression, user-friendliness, and presence as secondary measures and covariates. Results The study was funded on September 25, 2018. Data collection started in September 2021 and the study is expected to run until September 2022. Conclusions Our study will improve our understanding of the efficacy and feasibility of providing Exposure Therapy for spider phobia using an Augmented Reality self-help application, with the intention of making mental health care more accessible.
Heterogeneity of treatment effect (HTE) refers to the nonrandom variation in the magnitude or direction of a treatment effect across levels of a covariate, as measured on a selected scale, against a ...clinical outcome. In randomized controlled trials (RCTs), HTE is typically examined through a subgroup analysis that contrasts effects in groups of patients defined "1 variable at a time" (for example, male vs. female or old vs. young). The authors of this statement present guidance on an alternative approach to HTE analysis, "predictive HTE analysis." The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risks with versus without the intervention, taking into account all relevant patient attributes simultaneously. The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed using a multidisciplinary technical expert panel, targeted literature reviews, simulations to characterize potential problems with predictive approaches, and a deliberative process engaging the expert panel. The authors distinguish 2 categories of predictive HTE approaches: a "risk-modeling" approach, wherein a multivariable model predicts the risk for an outcome and is applied to disaggregate patients within RCTs to define risk-based variation in benefit, and an "effect-modeling" approach, wherein a model is developed on RCT data by incorporating a term for treatment assignment and interactions between treatment and baseline covariates. Both approaches can be used to predict differential absolute treatment effects, the most relevant scale for clinical decision making. The authors developed 4 sets of guidance: criteria to determine when risk-modeling approaches are likely to identify clinically important HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. The PATH Statement, together with its explanation and elaboration document, may guide future analyses and reporting of RCTs.
Background Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious ...screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be eliminated, the cost-effectiveness of a screening program could be enhanced and the potential harms of bronchoscopy avoided. Methods All consecutive participants with a positive result on a CT scan lung cancer screening between April 2004 and December 2008 were enrolled. The diagnostic sensitivity and negative predictive value were calculated at the level of the suspicious nodules. In 95% of the nodules, the gold standard for the outcome of the bronchoscopy was based on surgical resection specimens. Results A total of 318 suspicious lesions were evaluated by bronchoscopy in 308 participants. The mean ± SD diameter of the nodules was 14.6 ± 8.7 mm, whereas only 2.8% of nodules were > 30 mm in diameter. The sensitivity of bronchoscopy was 13.5% (95% CI, 9.0%-19.6%); the specificity, 100%; the positive predictive value, 100%; and the negative predictive value, 47.6% (95% CI, 41.8%-53.5%). Of all cancers detected, 1% were detected by bronchoscopy only and were retrospectively invisible on both low-dose CT scan and CT scan with IV contrast. Conclusion Conventional white-light bronchoscopy should not be routinely recommended for patients with positive test results in a lung cancer screening program. Trial registration Nederlands Trial Register; No.: ISRCTN63545820; URL: www.trialregister.nl.
PDF
