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Impact of tumor size on outcomes after anatomic lung resection for stage 1A non-small cell lung cancer based on the current staging system.

OBJECTIVE: Anatomic segmentectomy may achieve results comparable to lobectomy for early-stage non-small cell lung cancer. The 7th edition of the AJCC Cancer Staging Handbook stratified the previous T1 tumor designation into T1a and T1b subsets, which still define stage 1A node-negative non-small cell lung cancer. We are left to hypothesize whether this classification may aid in directing the extent of surgical resection. We retrospectively reviewed our anatomic segmentectomy and lobectomy management of stage 1A non-small cell lung cancer to determine differences in survival and local recurrence rates based on the new stratification.

METHODS: We performed a retrospective review of 429 patients undergoing resection of pathologically confirmed stage 1A non-small cell lung cancer via lobectomy or anatomic segmentectomy. Primary outcome variables included mortality, recurrence, and survival. Recurrence-free and cancer-specific survivals were estimated using the Kaplan-Meier method.

RESULTS: Patients undergoing segmentectomy were older than patients undergoing lobectomy (mean age 69.2 vs 66.8 years, P < .006). The mean preoperative forced expiratory volume in 1 second was significantly lower in the segmentectomy group than in the lobectomy group (71.8% vs 81.1%, P = .02). Mortality was similar after segmentectomy (1.1%) and lobectomy (1.2%). There was no difference in mortality, recurrence rates (14.0% vs 14.7%, P = 1.00), or 5-year cancer-specific survival (T1a: 90% vs 91%, P = .984; T1b: 82% vs 78%, P = .892) when comparing segmentectomy and lobectomy for pathologic stage 1A non-small cell lung cancer, when stratified by T stage.

CONCLUSIONS: Anatomic segmentectomy may achieve equivalent recurrence and survival compared with lobectomy for patients with stage 1A non-small cell lung cancer. Prospective studies will be necessary to delineate the potential merits of anatomic segmentectomy in this setting.

Adenocarcinomas with prominent lepidic spread: retrospective review applying new classification of the American Thoracic Society.

BACKGROUND: Recently, a new classification of lung adenocarcinomas has been proposed for tumors with lepidic spread. The greatest diameter of the invasive component determines minimally invasive cancers, and the term bronchioloalveolar carcinoma is no longer used.

METHODS: We retrospectively reviewed 87 resected adenocarcinomas of the lung; 30 tumors with lepidic growth and without high-grade invasive areas were identified, and the invasive component was measured morphometrically and categorized. A dimension of 5 mm was the cutoff for invasion. Regional lymph node involvement and short-term follow-up were compared among subtypes of these well-differentiated and moderately differentiated adenocarcinomas.

RESULTS: There were 11 well-differentiated adenocarcinomas with lepidic growth: 3 adenocarcinomas in situ (nonmucinous) and 8 minimally invasive adenocarcinomas (MIAs) (4 mucinous and 4 nonmucinous). There were 19 invasive moderately differentiated adenocarcinomas with a prominent lepidic growth pattern (LPAs). The mean size of the 3 adenocarcinomas in situ cases was 0.9±0.7 mm; the total size of the 8 MIA cases was 1.4±1.8 cm and that of the 19 LPA cases was 3.2±2.1 cm. The invasive size of the MIA was 0.3±0.6 and that of the LPA was 2.2±0.3. The invasive pattern of the LPAs was papillary and acinar without desmoplasia (n=3) and acinar with desmoplasia (n=16). Seven of the invasive desmoplastic tumors showed complex single-cell invasion or lymphatic invasion. Identification of the transition from lepidic to invasive acinar was straightforward because of the presence of elastotic desmoplasia. The transition between complex acinar papillary invasion and lepidic growth was often difficult to discern. Lymph node metastases were present in 5 cases (26%), all in tumors with an acinar, desmoplastic invasive component of >1 cm, with areas of single-cell invasion. With follow-up, progressive nodal involvement or distant metastases occurred in 4 patients, all with complex invasive patterns; 3 with invasion >1 cm and 1 with lymphatic invasion in smaller invasive tumors. Recurrent lung nodules occurred in 5 patients, including 1 patient with MIA, 1 with nondesmoplastic invasion, 2 with desmoplastic invasion, and 1 with complex desmoplastic invasion.

CONCLUSIONS: Approximately one third of lung adenocarcinomas have significant lepidic spread, and of these nearly one third are minimally invasive. Measurement of the invasive component may be difficult without elastotic desmoplasia. In this small series, lymph node and distant metastases occurred only in those with complex invasive patterns, but lung recurrence occurred in all subtypes, including MIAs.

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

BACKGROUND: The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging.

METHODS: A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC).

FINDINGS: Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5-80·0) in low-risk, 58·3% (48·9-66·6) in intermediate-risk, and 49·2% (42·2-55·8) in high-risk patients (p(trend)=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0-80·6) in low-risk, 57·4% (48·3-65·5) in intermediate-risk, and 44·6% (40·2-48·9) in high-risk patients (p(trend)<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages.

INTERPRETATION: Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection.

Do asthmatic smokers benefit as much as non-smokers on budesonide/formoterol maintenance and reliever therapy? Results of an open label study.

Studies with inhaled corticosteroids (ICS) in smoking asthmatics have mostly shown poorer treatment responses than in non-smoking asthmatics.

METHODS: EuroSMART, an open, randomised, 6-month study, compared budesonide/formoterol (Symbicort (®) Turbuhaler(®))(h) maintenance and reliever therapy (Symbicort SMART(®)) at two maintenance doses of budesonide/formoterol (160/4.5 μg), 1 × 2 and 2 × 2, in patients with asthma who were symptomatic despite treatment with ICS ± long-acting β(2)-agonists. The 8424 randomised patients included 886 smokers (11%; aged <40 years or with a smoking history <10 pack-years if older), who were compared with a propensity-matched group of non-smokers. At baseline, smokers had lower post-bronchodilator peak expiratory flow, lower peak flow reversibility and used more reliever medication per day. Severe asthma exacerbations were counted and changes in five-item Asthma Control Questionnaire (ACQ-5) scores from baseline calculated.

RESULTS: There were 48 and 47 exacerbations in smokers and non-smokers, respectively. Mean time to first severe exacerbation was not statistically different between the two groups. The mean change in ACQ-5 score was significantly greater in non-smokers. Considering the two treatment options there was a statistically significant prolonged time to first severe exacerbation with 2 × 2 versus 1 × 2 in the smokers, but not in the non-smokers. In smokers, the reductions in ACQ-5 scores, asthma symptoms, use of as-needed medication and awakenings were also all significant in favour of 2 × 2 with similar or greater changes than in smokers treated with 1 × 2.

CONCLUSION: Asthmatic patients with a limited smoking history benefit from treatment with budesonide/formoterol maintenance and reliever therapy with dosing 2 × 2 being superior to 1 × 2.

Symptoms, lung function, and perception of asthma control: an exploration into the heterogeneity of the asthma control construct.

BACKGROUND: Asthma control is still surprisingly poor, which may be related to factors causing discrepancies between objective lung function measures and subjective symptom reports or discrepancies between objective indicators of asthma control and control perception. Identifying patients prone to such discrepancies may help to understand asthma control problems.

METHODS: Ninety-four persons with asthma participated in this study. We used cluster analysis to identify different subgroups of asthma control, based on a measure of lung function and self-report of daytime and nighttime symptoms, activity limitations, reliever medication use, and perception of asthma control. Subsequently, we explored between-cluster differences in clinical and psychological characteristics.

RESULTS: We identified two homogeneous clusters: a cluster of persons with poorly controlled asthma and a cluster of persons with well-controlled asthma. A third cluster included persons with an intermediate level of asthma control, an absence of nighttime symptoms, and a reduced impact of asthma symptoms on daily activities despite high levels of symptoms and reliever medication use. Members of the poorly controlled asthma cluster showed higher symptom levels, more catastrophic thinking, and activity avoidance beliefs compared with members of other clusters.

CONCLUSION: The clusters we identified crosscut current definitions of asthma severity and asthma control and indicate the importance of affective evaluation of symptoms in explaining poor asthma control.

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