Purpose
The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).

Patients and Methods
In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs).

Results
A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain.

Conclusion
Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

Background

We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials.

Methods

Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393.

Findings

Median follow-up in LUX-Lung 3 was 41 months (IQR 35–44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31–37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28·2 months (95% CI 24·6–33·6) in the afatinib group and 28·2 months (20·7–33·2) in the pemetrexed-cisplatin group (HR 0·88, 95% CI 0·66–1·17, p=0·39). In LUX-Lung 6, median overall survival was 23·1 months (95% CI 20·4–27·3) in the afatinib group and 23·5 months (18·0–25·6) in the gemcitabine-cisplatin group (HR 0·93, 95% CI 0·72–1·22, p=0·61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33·3 months (95% CI 26·8–41·5) in the afatinib group versus 21·1 months (16·3–30·7) in the chemotherapy group (HR 0·54, 95% CI 0·36–0·79, p=0·0015); in LUX-Lung 6, it was 31·4 months (95% CI 24·2–35·3) versus 18·4 months (14·6–25·6), respectively (HR 0·64, 95% CI 0·44–0·94, p=0·023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27·6 months (19·8–41·7) in the afatinib group versus 40·3 months (24·3–not estimable) in the chemotherapy group (HR 1·30, 95% CI 0·80–2·11, p=0·29); in LUX-Lung 6, it was 19·6 months (95% CI 17·0–22·1) versus 24·3 months (19·0–27·0), respectively (HR 1·22, 95% CI 0·81–1·83, p=0·34). In both trials, the most common afatinib-related grade 3–4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3–4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3–4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]).

Interpretation

Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials.

Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials

Molecular basis and rationale for combining immune checkpoint inhibitors with chemotherapy in non-small cell lung cancer

Studying how neural circuits orchestrate limbed behaviors requires the precise measurement of the positions of each appendage in three-dimensional (3D) space. Deep neural networks can estimate two-dimensional (2D) pose in freely behaving and tethered animals. However, the unique challenges associated with transforming these 2D measurements into reliable and precise 3D poses have not been addressed for small animals including the fly, Drosophila melanogaster. Here, we present DeepFly3D, a software that infers the 3D pose of tethered, adult Drosophila using multiple camera images. DeepFly3D does not require manual calibration, uses pictorial structures to automatically detect and correct pose estimation errors, and uses active learning to iteratively improve performance. We demonstrate more accurate unsupervised behavioral embedding using 3D joint angles rather than commonly used 2D pose data. Thus, DeepFly3D enables the automated acquisition of Drosophila behavioral measurements at an unprecedented level of detail for a variety of biological applications.

DeepFly3D, a deep learning-based approach for 3D limb and appendage tracking in tethered, adult Drosophila.

PROBLEM TO BE SOLVED: To improve the uniformity of gas flow in a process container and the uniformity of the temperature in the process container.SOLUTION: A substrate processing apparatus 1 performs processing to a wafer W and includes: a process container 10 that stores the wafer W in an airtight manner; a placement base 11 where a substrate is placed in the process container 10; and an exhaust mechanism 80 which exhausts air in the process container 10. The process container 10 includes: a body part 20 with a closed bottom which opens on an upper surface; a cylindrical part 22 including a flange 21 which closes the upper surface of the body part 20 in an airtight manner and a side wall 40 having a diameter which is smaller than that of the body part 20 and larger than an outer surface of the placement base 11; and a lid 23 which is provided on an upper surface of the flange 21 and closes an opening of the body part 20 in an airtight manner. A heater 42 is disposed at a groove part 41 on the upper surface of the flange 21. An engagement member 43 which protrudes toward a center direction of the side wall 40 is provided at a lower end of the side wall 40 of the cylindrical part 22. A baffle plate 44 in which multiple openings 44a are formed is disposed on an upper surface of the engagement member 43.

Substrate processing apparatus

This paper is aimed at calibrating the relative posture and position, i.e. extrinsic parameters, of a stationary camera against a 3D reference object which is not directly visible from the camera. We capture the reference object via a mirror under three different unknown poses, and then calibrate the extrinsic parameters from 2D appearances of reflections of the reference object in the mirrors. The key contribution of this paper is to present a new algorithm which returns a unique solution of three P3P problems from three mirrored images. While each P3P problem has up to four solutions and therefore a set of three P3P problems has up to 64 solutions, our method can select a solution based on an orthogonality constraint which should be satisfied by all families of reflections of a single reference object. In addition we propose a new scheme to compute the extrinsic parameters by solving a large system of linear equations. These two points enable us to provide a unique and robust solution. We demonstrate the advantages of the proposed method against a state-of-the-art by qualitative and quantitative evaluations using synthesized and real data.

/pdf/a-new-mirror-based-extrinsic-camera-calibration-using-an-r3sa5np5tx.pdf

A new mirror-based extrinsic camera calibration using an orthogonality constraint

This paper proposes a novel algorithm of estimating 3D human pose from multi-view videos captured by unsynchronized and uncalibrated cameras In a such configuration, the conventional vision-based approaches utilize detected 2D features of common 3D points for synchronization and camera pose estimation, however, they sometimes suffer from difficulties of feature correspondences in case of wide baselines For such cases, the proposed method focuses on that the projections of human joints can be associated each other robustly even in wide baseline videos and utilizes them as the common reference points To utilize the projections of joint as the corresponding points, they should be detected in the images, however, these 2D joint sometimes include detection errors which make the estimation unstable For dealing with such errors, the proposed method introduces two ideas The first idea is to relax the reprojection errors for avoiding optimizing to noised observations The second idea is to introduce an geometric constraint on the prior knowledge that the reference points consists of human joints We demonstrate the performance of the proposed algorithm of synchronization and pose estimation with qualitative and quantitative evaluations using synthesized and real data

/pdf/human-pose-as-calibration-pattern-3d-human-pose-estimation-1cvyb9p6b3.pdf

Human Pose as Calibration Pattern: 3D Human Pose Estimation with Multiple Unsynchronized and Uncalibrated Cameras

Background
The population of elderly patients with lung cancer is increasing worldwide. Although first-line gefitinib is one of the standard treatments for advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, few data have been reported regarding gefitinib and elderly patients.

First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901

This paper is aimed at employing mirrors to estimate relative posture and position of camera, i.e., extrinsic parameters, against a 3D reference object that is not directly visible from the camera. The key contribution of this paper is to propose a novel formulation of extrinsic camera calibration based on orthogonality constraint which should be satisfied by all families of mirror-reflections of a single reference object. This allows us to obtain a larger number of equations which contribute to make the calibration more robust. We demonstrate the advantages of the proposed method in comparison with a state-of-the-art by qualitative and quantitative evaluations using synthesized and real data.

Mirror-based Camera Pose Estimation Using an Orthogonality Constraint

This paper proposes a novel algorithm that calibrates multiple cameras scattered across a broad area. The key idea of the proposed method is “using the position of an omnidirectional camera as a reference point.” The common approach to calibrating multiple cameras assumes that the cameras capture at least some common points. This means calibration becomes quite difficult if there are no shared points in each camera’s field of view (FOV). The proposed method uses the position of an omnidirectional camera to determine point correspondence. The position of an omnidirectional camera relative to the calibrated camera is estimated by the theory of epipolar geometry, even if the omnidirectional camera is placed outside the camera’s FOV. This property makes our method applicable to multiple cameras scattered across a broad area. Qualitative and quantitative evaluations using synthesized and real data, e.g., a sports field, demonstrate the advantages of the proposed method.

/pdf/extrinsic-camera-calibration-without-visible-corresponding-1xkhmibhaf.pdf

Kosuke Takahashi

Papers

A new mirror-based extrinsic camera calibration using an orthogonality constraint

Human Pose as Calibration Pattern: 3D Human Pose Estimation with Multiple Unsynchronized and Uncalibrated Cameras

First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901

Mirror-based Camera Pose Estimation Using an Orthogonality Constraint

Extrinsic Camera Calibration Without Visible Corresponding Points Using Omnidirectional Cameras