BACKGROUNDPostoperative assessment of pulmonary function is important for estimating the risk of thoracic surgery and long-term disability following pulmonary resection, including predicted ...postoperative (ppo) forced expiratory volume (FEV) in one second (ppoFEV1) and percent predicted lung diffusion capacity for carbon monoxide (ppo%DLCO) estimation. The ppo values were compared using four different estimation methods between chronic obstructive pulmonary disease (COPD) and non-COPD patients and according to the resected lobe. METHODSThis prospective study included 59 eligible patients requiring single lobectomy and succeeded in performing pulmonary function tests at 3 and 12 months after lobectomy. The ppoFEV1 and ppo%DLCO were compared with poFEV1 and po%DLCO obtained at 3 and 12 months after lobectomy. The ppo values were estimated using the four usual methods: the 19-segment anatomical technique (S), perfusion scintigraphy (Q), quantitative CT (CT), and quantitative CT with low attenuation volume (CTLAV) subtraction. RESULTSFor non-COPD and COPD patients, the smallest mean difference between ppo and po values was observed by S for FEV1 and %DLCO. Based on the resected lobe, the smallest mean difference was observed by (I) Q for right upper lobectomy (RUL) excluding %DLCO at 12 months by S, (II) S for left upper lobectomy (LUL), (III) CT and CTLAV for right lower lobectomy (RLL), and (IV) CT and CTLAV for left lower lobectomy (LLL) at 12 months. The ppo values calculated by S for RUL (FEV1 at 3 and 12 months and %DLCO at 3 months) and by all four methods for LLL (FEV1 and %DLCO at 3 months) were smaller than the po values. CONCLUSIONSThe S method is adequate for calculating ppoFEV1 and ppo%DLCO when patients are classified as non-COPD and COPD. However, S sometimes overestimates the ppoFEV1 and ppo%DLCO when patients are classified according to the resected lobe. The CTLAV method may be the method of choice instead of S for calculating ppoFEV1 and ppo%DLCO in patients who undergo lung lobectomy despite the presence or absence of airflow limitation.
Pemetrexed monotherapy has come to be recognized as the standard of care for second-line therapy of non-squamous non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) expression is recognized ...as a potential predictor of the response to pemetrexed-based chemotherapy in patients with advanced NSCLC. The purpose of this study was to identify useful predictors of the response to pemetrexed other than TS expression.
The records of non-squamous NSCLC patients without driver mutations who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2009 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated.
In the 116 patients with non-squamous NSCLC, the overall response rate and progression-free survival (PFS) were 10.3% and 2.1 months, respectively. The disease control rate and PFS differed significantly among current smokers and never-smokers/former light smokers (44.9 vs. 65.8%, and 1.8 vs. 4.0 months, respectively). Furthermore, multivariate analysis identified Eastern Cooperative Oncology Group Performance Status and smoking status as independent predictors of the PFS.
The clinical data obtained in this study may provide a valuable basis for the use of smoking status as a predictor of pemetrexed monotherapy in wild-type NSCLC patients.
Postoperative assessment of pulmonary function is important for estimating the risk of thoracic surgery and long-term disability following pulmonary resection, including predicted postoperative (ppo) ...forced expiratory volume (FEV) in one second (ppoFEV
) and percent predicted lung diffusion capacity for carbon monoxide (ppo%DLCO) estimation. The ppo values were compared using four different estimation methods between chronic obstructive pulmonary disease (COPD) and non-COPD patients and according to the resected lobe.
This prospective study included 59 eligible patients requiring single lobectomy and succeeded in performing pulmonary function tests at 3 and 12 months after lobectomy. The ppoFEV
and ppo%DLCO were compared with poFEV
and po%DLCO obtained at 3 and 12 months after lobectomy. The ppo values were estimated using the four usual methods: the 19-segment anatomical technique (S), perfusion scintigraphy (Q), quantitative CT (CT), and quantitative CT with low attenuation volume (CT
) subtraction.
For non-COPD and COPD patients, the smallest mean difference between ppo and po values was observed by S for FEV
and %DLCO. Based on the resected lobe, the smallest mean difference was observed by (I) Q for right upper lobectomy (RUL) excluding %DLCO at 12 months by S, (II) S for left upper lobectomy (LUL), (III) CT and CT
for right lower lobectomy (RLL), and (IV) CT and CT
for left lower lobectomy (LLL) at 12 months. The ppo values calculated by S for RUL (FEV
at 3 and 12 months and %DLCO at 3 months) and by all four methods for LLL (FEV
and %DLCO at 3 months) were smaller than the po values.
The S method is adequate for calculating ppoFEV
and ppo%DLCO when patients are classified as non-COPD and COPD. However, S sometimes overestimates the ppoFEV
and ppo%DLCO when patients are classified according to the resected lobe. The CT
method may be the method of choice instead of S for calculating ppoFEV
and ppo%DLCO in patients who undergo lung lobectomy despite the presence or absence of airflow limitation.
A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung ...cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating
mutation, ie, exon 19 deletion or L858R point mutation.
A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major
mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of
mutation.
A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (
=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (
=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (
=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS.
Investigators should consider the proportions of sensitive
mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.
Experiments evaluated the hypothesis that angiotensin-converting enzyme (ACE) inhibition suppresses hyperglycemia-induced nitrotyrosine (NT) production in the renal cortex.
Rats were untreated (UNTR,
...n = 6) or received the ACE inhibitor enalapril (20 mg/kg/day; ENAL,
n = 6) for 2 weeks. Renal cortical slices were incubated for 90 min in media containing 5 (normal) or 20 mmol/L (high) glucose. Superoxide anion (O
2
·−) and nitrate + nitrite (NO
X
) levels were measured in the media. Superoxide dismutase (SOD) activity and NT content were measured in the tissue homogenate.
In the UNTR group, high glucose increased O
2
·− and NO
X
production by the renal cortex (
P < 0.05 vs. normal glucose). Likewise, NT content and SOD activity of the renal cortex augmented (
P < 0.05 vs. normal glucose). In the ENAL group, O
2
·− production and NT content were glucose-insensitive, but high glucose exerted an exaggerated impact on NO
X
production and SOD activity (
P < 0.01 vs. UNTR in high glucose).
Accelerated NT content in the renal cortex during high-glucose conditions was prevented by ACE inhibitor treatment. It was suggested that, apart from its anti-hypertensive effect, the mechanism of suppressed NT degradation in the renal cortex by the ACE inhibitor enhances both O
2
·− degradation per se and antioxidative effects including SOD activation.
Summary
Background
This study was designed to determine the recommended dose of a combination of nedaplatin (NED) and nab-paclitaxel (nab-PTX) in chemotherapy-naive patients with advanced squamous ...non-small-cell lung cancer (NSCLC).
Methods
Patients received escalating doses of NED on day 1 and nab-PTX on days 1, 8, and 15 every 4 weeks by an intravenous infusion for up to six cycles.
Results
A dose of 100 mg/m
2
NED and 100 mg/m
2
nab-PTX was determined to be the recommended dose for patients with advanced squamous NSCLC. The study had an overall response rate of 66.7% (95% confidence interval CI: 38.4–88.2) and disease control rate of 93.3% (95% CI: 68.1–99.8). The median progression-free survival time and survival time was 7.0 months (95% CI: 5.9–8.1) and 13.1 months (95% CI: 6.2–20.1), respectively. The most common adverse events were neutropenia (grade 3/4, 33%) and leukopenia (grade 3/4, 27%). Although peripheral neuropathy was observed in 5 patients (grade 1/2), non-hematological toxic effects were relatively mild. Febrile neutropenia, pneumonitis, and treatment-related death were not observed.
Conclusions
The combination of NED and nab-PTX was a tolerable and effective regimen and its recommended dose was 100 mg/m
2
and 100 mg/m
2
, respectively, in chemotherapy-naive patients with advanced squamous NSCLC (UMIN000010963).
Small cell lung cancer (SCLC) is typically categorized according to disease extent as limited or extensive, and utility of the 8th TNM classification, recommended for lung cancer staging, which ...demonstrates a strong association with non-small-cell lung cancer (NSCLC) management, remains unclear.
This retrospective study included 277 consecutive SCLC patients treated at a single institution between 2008 and 2016.
According to the currently used two-stage system, 186 (65.7%) of the patients were classified as having extensive disease (ED)-SCLC. Among the ED-SCLC patients, ten (5.3%), 38 (20.4%), 32 (17.2%), and 106 (57.0%) were categorized into stages M0, M1a, M1b, and M1c, respectively, according to the 8th TNM classification. There was a significant difference in overall survival based on the M descriptors: 15.8 (95% CI 9.4-22.2) months in the M1b group vs 7.3 (95% CI 5.7-8.9) months in the M1c group (
<0.001). Multivariate analysis showed that in addition to the known prognostic factors such as performance status, serum albumin, and lactate dehydrogenase, M descriptor was a prognostic factor (HR 1.95, 95% CI 1.38-2.77;
<0.001).
The 8th TNM classification has a prognostic value in SCLC. Similarly to NSCLC, treatment approaches should be considered on the basis of the 8th TNM classification, especially stage IVA separate from stage IVB in ED-SCLC patients.
Concurrent chemoradiotherapy (cCRT) is the standard treatment for patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, the efficacy and safety of this treatment has not been ...compared between patients who possess epidermal growth factor receptor (EGFR) mutations and patients with wild-type EGFR. The objective of the present study was to evaluate the effect of the presence of EGFR gene mutations in patients with LA-NSCLC receiving cCRT. Between January 2007 and December 2013, the records of 64 patients were reviewed retrospectively. The data were statistically analyzed to evaluate the efficacy of cCRT according to EGFR mutation status. In total, 15/64 were revealed to possess EGFR mutations, 23%, and comprised the mutant EGFR group. The progression-free survival time was significantly shorter in the mutant EGFR group compared with the patient group with tumors exhibiting wild-type EGFR, 6.3 and 9.5 months, respectively (P<0.001). The overall survival rate was longer in the mutant EGFR group compared with the wild-type EGFR group, although the difference was not statistically significant, 37.1 and 21.1 months, respectively (P=0.26). The disease recurred in all of the patients of the mutant EGFR group, whilst the recurrence rate in the wild-type EGFR group was 89%. The frequency of distant metastasis was significantly higher in the mutant EGFR group compared with the wild-type EGFR group. In conclusion, these data suggest that additional studies are required to identify strategies for reinforcing the efficacy of cCRT, with a focus on the potential use of EGFR tyrosine kinase inhibitors for patients exhibiting an EGFR mutation.
Abstract Background Theophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid ...actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia. Study design We performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration. Results Before aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration. Conclusion Aminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.
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