BackgroundMedian survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitizing properties of erlotinib and its direct effect on brain metastases and systemic activity.MethodsEighty NSCLC patients with KPS of 70 and greater and multiple brain metastases were randomly assigned to placebo (n = 40) or erlotinib (100mg, n = 40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients continued with placebo or erlotinib (150mg) until disease progression. The primary end point was neurological progression-free survival (nPFS); hazard ratios (HRs) were calculated using Cox regression. All P values were two-sided.ResultsFifteen patients (37.5%) from each arm were alive and without neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both arms; nPFS HR 0.95 (95% CI = 0.59 to1.54; P = .84). Median overall survival (OS) was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI = 0.58 to 1.55; P = .83). The frequency of epidermal growth factor receptor (EGFR) mutations was low with only 1 of 35 (2.9%) patients with available samples had activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the two groups (70.0% in each arm), except for rash 20.0% (erlotinib) vs 5.0% (placebo), and fatigue 17.5% vs 35.0%. No statistically significant quality of life differences were found.ConclusionsOur study showed no advantage in nPFS or OS for concurrent erlotinib and WBRT followed by maintenance erlotinib in patients with predominantly EGFR wild-type NSCLC and multiple brain metastases compared to placebo. Future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations.

Introduction Esophageal multiple intraluminal impedance (MII) measurement has been in used to detect gastroesophageal reflux and bolus transport. It is not clear if MII can detect changes in luminal cross sectional area (CSA) during bolus transport. Aims Intraluminal ultrasound (US) images, MII and high resolution manometry (HRM) were recorded simultaneously to determine temporal relationship between CSA and impedance during esophageal bolus transport and to define the relationship between peak distension and nadir impedance. Methods Studies were conducted in five healthy subjects. MII, HRM and US images were recorded 6 cm above LES. Esophageal distensions were studied during swallows and injections of 0.5 N saline bolus into the esophagus. Results Temporal change in esophageal CSA correlates with changes in impedance (r value: mean ± SD = −0.80 ± 0.08, range: −0.94 to −0.66). Drop in impedance during distension occurs as a two step process; initial large drop associated with onset of CSA increase, followed by a small drop during which majority of the CSA increase occurs. Peak CSA and nadir impedance occur within 1 s of each other. Increase in swallow and injection volumes increased the CSA, had no effect on large drop but increased the small drop amplitude. We observed a significant correlation between peak CSA and nadir impedance (r = − 0.90, p<0.001) and a better correlation between peak CSA and inverse impedance (r = 0.94, p<0.001). Conclusion Further studies are needed to confirm that intraluminal impedance recordings may be used to measure luminal CSA during esophageal bolus transport.

Absence of peristalsis and impaired relaxation of lower esophageal sphincter are the hallmarks of achalasia esophagus. Based on the pressurization patterns, achalasia has been subdivided into three subtypes. The goal of our study was to evaluate the esophageal contraction pattern and bolus clearance in type 3 achalasia esophagus. High-resolution manometry (HRM) recordings of all patients diagnosed with achalasia esophagus in our center between the years 2011 and 2013 were reviewed. Recordings of 36 patients with type 3 achalasia were analyzed for the characteristics of swallow-induced "simultaneous esophageal contraction." The HRM impedance recordings of 14 additional patients with type 3 achalasia were analyzed for bolus clearance from the impedance recording. Finally, the HRM impedance along with intraluminal ultrasound imaging was conducted in six patients to further characterize the simultaneous esophageal contractions. Among 187 achalasia patients, 30 were type 1, 121 type 2, and 36 type 3. A total of 434 swallows evaluated in type 3 achalasia patients revealed that 95% of the swallow-induced contractions met criteria for simultaneous esophageal contraction, based on the onset of contraction. Interestingly, the peak and termination of the majority of simultaneous esophageal contractions were sequential. The HRM impedance revealed that 94% of the "simultaneous contractions" were associated with complete bolus clearance. Ultrasound image analysis revealed that baseline muscle thickness of patients in type 3 achalasia is larger than normal but the pattern of axial shortening is similar to that in normal subjects. The majority of esophageal contractions in type 3 achalasia are not true simultaneous contractions because the peak and termination of contraction are sequential and they are associated with complete bolus clearance.