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Trimodality therapy for stage IIIA non-small cell lung cancer: Benchmarking multi-disciplinary team decision-making and function.

NSCLC3OBJECTIVES: Although the standard treatment for patients with stage IIIA non-small cell lung cancer (NSCLC) is chemoradiotherapy, some patients are considered for trimodality therapy [TT]. We analyzed outcomes for stage IIIA NSCLC, treated with TT and compared them with concurrent chemoradiotherapy [con-CRT].

MATERIALS AND METHODS: Patients treated between January 2007 and December 2011 were retrospectively analyzed. Not included were patients with sulcus superior tumors, unknown T/N-status, or recurrent disease after con-CRT followed by surgery. All patients were discussed at our multidisciplinary thoracic tumor board (MTB).

RESULTS: Mean Charlson Comorbidity Index was 2 for TT and con-CRT patients. TT patients were younger (median TT=56 years vs. con-CRT=62 years; p=0.001) and had less advanced cN-stage (TT cN2=41% vs. 83% for CRT; p<0.001). 44% of TT patients had T4-stage vs. 12% of con-CRT patients. Median RT dose was lower for TT (50Gy vs. 66Gy; p=0.001) and median RT planning target volume (PTV) in TT and con-CRT patients was 525cm(3) and 655cm(3) (p=0.010), respectively. The majority of TT patients had a lobectomy (23/32). Median follow-up was 30.3 months (95% CI=18.7-41.9) for TT and 51 months (95% CI=24.9-77.4) for con-CRT. Median overall survival was not reached for TT and was 18.6 months (95% CI=12.8-24.4) for con-CRT (p=0.001). For PTV</≥500cm(3), median OS for TT was not reached/33.9 months and 29.1/17.1 months for con-CRT. TT patients with cN0/1 had better survival than those receiving con-CRT (p=0.015), but those with cN2 did not (p=0.158). The 90-day mortality from start of RT was 0% (0/32) for TT and 1.7% (1/58) for con-CRT. 90-day post-operative mortality for TT was 3.1% (1/32, event unrelated to TT).

CONCLUSIONS: Selected patients with IIIA NSCLC treated with TT had favorable long-term survival with acceptable short-term mortality. These outcomes support the decision-making and function of our MTB/treatment team. The role of TT in cN2 disease and large tumors merits further evaluation.

Long-term home noninvasive mechanical ventilation increases systemic inflammatory response in chronic obstructive pulmonary disease: a prospective observational study.

Long-term home noninvasive mechanical ventilation (NIV) is beneficial in COPD but its impact on inflammation is unknown.

We assessed the hypothesis that NIV modulates systemic and pulmonary inflammatory biomarkers in stable COPD. Methods. Among 610 patients referred for NIV, we shortlisted those undergoing NIV versus oxygen therapy alone, excluding subjects with comorbidities or non-COPD conditions. Sputum and blood samples were collected after 3 months of clinical stability and analyzed for levels of human neutrophil peptides (HNP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha). Patients underwent a two-year follow-up. Unadjusted, propensity-matched, and pH-stratified analyses were performed.

Results. Ninety-three patients were included (48 NIV, 45 oxygen), with analogous baseline features. Sputum analysis showed similar HNP, IL-6, IL-10, and TNF-alpha levels (P > 0.5). Conversely, NIV group exhibited higher HNP and IL-6 systemic levels (P < 0.001) and lower IL-10 concentrations (P < 0.001). Subjects undergoing NIV had a significant reduction of rehospitalizations during follow-up compared to oxygen group (P = 0.005). These findings were confirmed after propensity matching and pH stratification.

Conclusions. These findings challenge prior paradigms based on the assumption that pulmonary inflammation is per se detrimental. NIV beneficial impact on lung mechanics may overcome the potential unfavorable effects of an increased inflammatory state.

Pathway Reconstruction of Airway Remodeling in Chronic Lung Diseases: A Systems Biology Approach.

airway-in-asthmaAirway remodeling is a pathophysiologic process at the clinical, cellular, and molecular level relating to chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma and mustard lung. These diseases are associated with the dysregulation of multiple molecular pathways in the airway cells.

Little progress has so far been made in discovering the molecular causes of complex disease in a holistic systems manner. Therefore, pathway and network reconstruction is an essential part of a systems biology approach to solve this challenging problem.

In this paper, multiple data sources were used to construct the molecular process of airway remodeling pathway in mustard lung as a model of airway disease. We first compiled a master list of genes that change with airway remodeling in the mustard lung disease and then reconstructed the pathway by generating and merging the protein-protein interaction and the gene regulatory networks. Experimental observations and literature mining were used to identify and validate the master list.

The outcome of this paper can provide valuable information about closely related chronic obstructive airway diseases which are of great importance for biologists and their future research.

Reconstructing the airway remodeling interactome provides a starting point and reference for the future experimental study of mustard lung, and further analysis and development of these maps will be critical to understanding airway diseases in patients.

Noninvasive ventilation as a palliative measure.

VNIDyspnea is a distressing consequence of many unremitting diseases. This review discusses the therapeutic use of noninvasive ventilation (NIV) in advanced illness.

RECENT FINDINGS: NIV continues to be investigated most rigorously in patients with progressive neuromuscular weakness and the combination of emphysema and lung cancer. Data are quite limited on the palliative role of NIV in bronchiectasis and interstitial lung diseases. It remains difficult to identify the subsets of patients with acute-on-chronic respiratory failure who are most likely to benefit from ICU admission, but NIV may particularly help those with hypercapnia. The question of whether general or disease-specific instruments should be used to evaluate the effects of NIV on quality of life is unanswered. Computerized decision aids have been developed to assist providers, patients, and their families with advance care planning.

SUMMARY: NIV is an important adjunct to medications for patients with intractable dyspnea. Future research should attempt to clarify the effectiveness of NIV at controlling dyspnea within and outside the hospital. Barriers to its domiciliary application are largely unknown. Processes should be developed to optimize communication among clinicians, patients, and their caregivers around the issues of when to start NIV and how to withdraw it at the end of life.

Increasing nontuberculous mycobacteria infection in cystic fibrosis.

Related Articles

NTMBINontuberculous mycobacteria (NTM) are emerging infections in the CF population.

AIMS: To assess NTM infection prevalence and associated features in our CF clinic population.
METHODS: Patient records, 2002-2011, were reviewed for NTM infection. FEV1, pancreatic function, sputum microbiology, and serum cytokines were compared in patients with and without NTM infection.

RESULTS: Incidence rate of NTM infection increased from 0 in 2002 to 8.7% in 2011 (p<0.001). NTM infection prevalence increased 3-fold from 5% (4/79) in 2003 to 14.5% (16/110) in 2011 (p=0.05). Prevalence of chronic NTM lung disease has decreased somewhat since a peak in 2009, with institution of aggressive triple therapy. Of NTM-infected compared to uninfected patients, 88.2% vs. 60.3% had a known 'severe' CFTR genotype (p=0.04), 88.2% vs. 58.9% were pancreatic insufficient (p=0.02); 70.6% vs. 43.8% had chronic Pseudomonas aeruginosa (p=0.06); 75% vs. 32% had Aspergillus infection (p=0.007) and 23.5% vs 2.7% had allergic bronchopulmonary aspergillosis (p=0.01). Patients infected with Mycobacterium abscessus had increased TGF-β, TNF-α, IL-1β, IL-2, IL-4 and IL-5 levels (p<0.05). There was no difference in cytokine levels for all NTM infected compared to uninfected patients. M. abscessus comprised 46% of all NTM infections. Comparing M. abscessus versus other NTM, duration was 10.5 (1-118) months versus 1 (1-70) month, median (range) (p=0.004); lung disease occurred in 69% versus 17% (p=0.0004), with sputum conversion in 4/11 versus 5/6, respectively (NS).

CONCLUSIONS: NTM incidence and prevalence have increased dramatically in our CF clinic, associated with a severe CF genotype and phenotype. M. abscessus, the most prevalent NTM, caused prolonged infection despite therapy. There has been some decrease in the prevalence of NTM lung disease since 2009.

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