Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO) RAPIDO collaborative investigators; Bahadoer

BACKGROUND Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.)

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BackgroundElderly colorectal cancer patients have worse prognosis than younger patients. Age-related survival differences may be cancer or treatment related, but also due to death from other causes. This study aims to compare population-based survival data for young (<65 years), aged (65–74 years), and elderly (≥75 years) colorectal cancer patients.MethodsAll patients operated for stage I–III colorectal cancer between 1991 and 2005 in the western region of The Netherlands were included. Crude survival, relative survival, and conditional relative survival curves, under the condition of surviving 1 year, were made for colon and rectal cancer patients separately. Furthermore, 30-day, 1-year, and 1-year excess mortality data were compared.ResultsA total of 9,397 stage I–III colorectal cancer patients were included in this study. Crude survival curves showed clear survival differences between the age groups. These age-related differences were less prominent in relative survival and disappeared in conditional relative survival (CRS). Only in stage III disease did elderly patients have worse CRS than young patients. Furthermore, significant age-related differences in 30-day and 1-year excess mortality were found. Thirty-day mortality vastly underestimated 1-year mortality for all age groups.ConclusionsElderly colorectal cancer patients who survive the first year have the same cancer-related survival as younger patients. Therefore, decreased survival in the elderly is mainly due to differences in early mortality. Treatment of elderly colorectal cancer patients should focus on perioperative care and the first postoperative year.

BackgroundNeoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer.MethodsThis is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4–6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6–8 weeks after CRE-I. CRE-II will include 18F–FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy.DiscussionIf active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

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BackgroundThirty-day mortality after surgery for colorectal cancer may vastly underestimate 1-year mortality. This study aimed to quantify the excess mortality in the first postoperative year of stage I–III colorectal cancer patients and to identify risk factors for excess mortality.MethodsAll 2,131 patients who were operated with curative intent for stage I–III colorectal cancer in the western region of the Netherlands between January 1, 2006, and December 31, 2008, were analyzed. Thirty-day mortality and relative survival were calculated. In addition, relative excess risk (RER) of death was estimated by a multivariable model.ResultsThirty-day mortality was 4.9%. One-year mortality was 12.4%. Risk factors for excess mortality in the first postoperative year for colon cancer patients were emergency surgery (excess mortality 29.7%, RER 2.5, 95% confidence interval 2.5–5.0), a Charlson score of >1 (excess mortality 12.6%, RER 2.3, 95% confidence interval 1.5–3.7), stage II or III disease (excess mortality 14.9%, RER 3.9, 95% confidence interval 1.9–8.1), and postoperative adverse events (excess mortality 22.6%, RER 2.1, 95% confidence interval 1.4–3.2).ConclusionsThe 30-day mortality rate highly underestimates the risk of dying in the first year after surgery, with excess 1-year mortality rates varying from 15 to 30%. This excess mortality was especially prominent in patients with comorbidities, higher stages of disease, emergency surgery, and postoperative surgical complications.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-012-2294-6) contains supplementary material, which is available to authorized users.

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