Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis of randomized clinical trials.

BACKGROUND: The comparison of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) for locally advanced esophageal squamous cell carcinoma (ESCC) remains inconclusive, and the optimal regimen is still under investigation. METHODS: Prospective randomized clinical trials were systematically searched in electronic databases from inception to Oct 2023. A graphical reconstructive algorithm was employed to extract time-to-event outcomes from Kaplan-Meier curves presented in the original studies. Using reconstructed individual patient data, summary overall survival (OS) and disease progression-free survival (DFS) for nCRT versus nCT, primarily doublet chemotherapy were recalculated. Hazard Ratios (HRs) of OS and DFS reported were also pooled by the fixed-effects model. RESULTS: A total of 6 randomized clinical trials comprising 1162 patients were included in our analysis. In the individual patient data (IPD) pooled analysis, a significant OS benefit was found for nCRT in ESCC (HR=0.81, 95 %CI:0.67-0.98, p=0.029), compared with the treatment of nCT. The median overall survival time were 53 months (95 %CI:41.9-67.7 m) and 66 months(95 %CI:57.2-NA) respectively in the nCT and nCRT groups. Additionally, a significant improvement in PFS for nCRT compared to nCT in the IPD pooled analysis (HR=0.79,95 %CI:0.64-0.98; p=0.027). Consistent with above results, the pooled HRs of OS and DFS for nCRT versus nCT were 0.78 (95 % CI 0.65-0.92, p=0.004) and 0.79 (95 % CI: 0.65-0.97, p=0.02), respectively. Notably, no substantial heterogeneity across studies was observed. CONCLUSIONS: Our findings indicate that nCRT offers better survival outcomes for ESCC, at least when compared to neoadjuvant doublet chemotherapy.This evidence continues to support the clinical practice of employing nCRT in locally advanced resectable ESCC.

Efficacy and safety analysis of anlotinib in combination with immune checkpoint inhibitors for second-line and subsequent extensive-stage small-cell lung cancer.

Currently, there is a lack of effective second-line and subsequent treatments for patients with extensive-stage small-cell lung cancer (ES-SCLC), and the establishment of a standardized treatment protocol is still underway. Considering the potential synergistic therapeutic effects of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs), combination therapy could be a viable option for treating lung cancer. This research concentrates on assessing the efficacy and safety of anlotinib in combination with ICIs for the treatment of ES-SCLC. We undertook a retrospective analysis of patients with extensive-stage SCLC who received anlotinib in combination with ICIs as second-line and subsequent treatment at Zhejiang Cancer Hospital between April 2020 and April 2023. Survival rates were analyzed using the Kaplan-Meier method. Among the 43 patients who received combination therapy, there were no cases of complete response (CR), 16 patients who achieved partial response (PR), 21 patients who had stable disease (SD), and 6 patients who experienced disease progression (PD). This resulted in an overall response rate (ORR) of 37.2% (16/43) and a disease control rate (DCR) of 86.0% (34/43). The median progression-free survival (PFS) was 4.0 months (95% CI: 2.74-5.26), and the median overall survival (OS) time was 10 months (95% CI: 4.8-15.2). Cox multifactorial regression analysis disclosed that the performance score (PS) and the number of metastatic organs were independent factors influencing PFS in ES-SCLC (p<0.001). The combination therapy demonstrated acceptable toxicity, with a total grade 3/4 toxicity rate of 30.2%. The combination therapy showed a notable association with several adverse events, including hand-foot syndrome, hypertension, and fatigue, which were the most significant. Combining anlotinib with immune checkpoint inhibitors has demonstrated favorable efficacy and safety in the treatment of second-line and subsequent extensive-stage small-cell lung cancer.

The analysis of the efficacy and safety of stereotactic body radiotherapy with sequential immune checkpoint inhibitors in the management of oligoprogressive advanced non-small cell lung cancer.

Background: No standardized treatment strategy exists for managing oligoprogression during maintenance therapy in driver-negative advanced non-small cell lung cancer (NSCLC). Similarly, a uniform response to oligoprogression during maintenance therapy using immune checkpoint inhibitors (ICIs) has not been established. Consequently, our investigation focused on assessing the efficacy and safety of employing stereotactic total body radiotherapy in conjunction with ICIs to address oligoprogression in advanced NSCLC. Methods: We conducted a retrospective analysis of patients diagnosed with driver-negative advanced NSCLC who received stereotactic body radiotherapy (SBRT) in combination with ICIs to manage oligoprogressive lesions within the period from October 2018 to October 2023 at our institution. Oligoprogression, defined as progression occurring in three or fewer disease sites, was the focus of our investigation. Our assessment encompassed various parameters including the local control rate (LCR), progression-free survival post-oligoprogression (PFS-P), overall survival post-oligoprogression (OS-P), progression-free survival (PFS), overall survival (OS), and the safety profile associated with SBRT followed by sequential ICIs after oligoprogression. Results: A total of 15 patients were enrolled in this study, all at stage IV, with 12 (80%) receiving a diagnosis of adenocarcinoma. Before oligoprogression, 11 (73.3%) patients had undergone immunotherapy. Following the treatment of oligoprogressed lung cancer with SBRT sequential ICIs, the median PFS-P and OS-P were 8 months (95% CI: 2.7-13.3) and 12 months (95% CI: 7.3-16.7), respectively. Additionally, the median PFS and OS were 26 months (95% CI: 8.0-44.0) and 30 months (not reached), respectively. The median local control (LC) of 15 oligoprogressed lesions was 13 months (95% CI: 5.3-20.2), with a 1-year LCR of 77.9%. Notably, patients with a performance status (PS) score of less than 2 demonstrated a more favorable survival benefit. Conclusions: Stereotactic systemic radiation therapy, combined with sequential ICIs, enhances both LC and survival in advanced NSCLC characterized by oligoprogression and negative driver gene mutations. This approach also exhibits the potential to postpone the transition between systemic chemotherapy regimens. Manageable adverse reactions were observed, with the absence of grade 4 reactions.

High-fidelity multi-channel optical information transmission through scattering media.

High-fidelity optical information transmission through strongly scattering media is challenging, but is crucial for the applications such as the free-space optical communication in a haze or fog. Binarizing optical information can somehow suppress the disruptions caused by light scattering. However, this method gives a compromised communication throughput. Here, we propose high-fidelity multiplexing anti-scattering transmission (MAST). MAST encodes multiple bits into a complex-valued pattern, loads the complex-valued pattern to an optical field through modulation, and finally employs a scattering matrix-assisted retrieval technique to reconstruct the original information from the speckle patterns. In our demonstration, we multiplexed three channels and MAST achieved a high-fidelity transmission of 3072 (= 1024× 3) bits data per transmission and average transmission error as small as 0.06%.

Erratum: Wavefront shaping improves the transparency of the scattering media: a review (Publisher's Note).

[This corrects the article DOI: 10.1117/1.JBO.29.S1.S11507.].

Wavefront shaping improves the transparency of the scattering media: a review.

Significance: Wavefront shaping (WFS) can compensate for distortions by optimizing the wavefront of the input light or reversing the transmission matrix of the media. It is a promising field of research. A thorough understanding of principles and developments of WFS is important for optical research. Aim: To provide insight into WFS for researchers who deal with scattering in biomedicine, imaging, and optical communication, our study summarizes the basic principles and methods of WFS and reviews recent progress. Approach: The basic principles, methods of WFS, and the latest applications of WFS in focusing, imaging, and multimode fiber (MMF) endoscopy are described. The practical challenges and prospects of future development are also discussed. Results: Data-driven learning-based methods are opening up new possibilities for WFS. High-resolution imaging through MMFs can support small-diameter endoscopy in the future. Conclusion: The rapid development of WFS over the past decade has shown that the best solution is not to avoid scattering but to find ways to correct it or even use it. WFS with faster speed, more optical modes, and more modulation degrees of freedom will continue to drive exciting developments in various fields.

Anti-scattering light focusing with full-polarization digital optical phase conjugation based on digital micromirror devices.

The high resolution of optical imaging and optogenetic stimulation in the deep tissue requires focusing light against strong scattering with high contrast. Digital optical phase conjugation (DOPC) has emerged recently as a promising solution for this requirement, because of its short latency. A digital micromirror device (DMD) in the implementation of DOPC enables a large number of modulation modes and a high speed of modulation both of which are important when dealing with a highly dynamic scattering medium. Here, we propose full-polarization DOPC (fpDOPC) in which two DMDs simultaneously modulate the two orthogonally polarized components of the optical field, respectively, to mitigate the effect of depolarization caused by strong scattering. We designed a simple system to overcome the difficulty of alignment encountered when modulating two polarized components independently. Our simulation and experiment showed that fpDOPC could generate a high-contrast focal spot, even though the polarization of light had been highly randomized by scattering. In comparison with the conventional method of modulating the polarization along a particular direction, fpDOPC can improve the peak to background ratio of the focal spot by a factor of two. This new technique has good potential in applications such as high-contrast light focusing in vivo.

Anti-scattering light focusing by fast wavefront shaping based on multi-pixel encoded digital-micromirror device.

Speed and enhancement are the two most important metrics for anti-scattering light focusing by wavefront shaping (WS), which requires a spatial light modulator with a large number of modulation modes and a fast speed of response. Among the commercial modulators, the digital-micromirror device (DMD) is the sole solution providing millions of modulation modes and a pattern rate higher than 20 kHz. Thus, it has the potential to accelerate the process of anti-scattering light focusing with a high enhancement. Nevertheless, modulating light in a binary mode by the DMD restricts both the speed and enhancement seriously. Here, we propose a multi-pixel encoded DMD-based WS method by combining multiple micromirrors into a single modulation unit to overcome the drawbacks of binary modulation. In addition, to efficiently optimize the wavefront, we adopted separable natural evolution strategies (SNES), which could carry out a global search against a noisy environment. Compared with the state-of-the-art DMD-based WS method, the proposed method increased the speed of optimization and enhancement of focus by a factor of 179 and 16, respectively. In our demonstration, we achieved 10 foci with homogeneous brightness at a high speed and formed W- and S-shape patterns against the scattering medium. The experimental results suggest that the proposed method will pave a new avenue for WS in the applications of biomedical imaging, photon therapy, optogenetics, dynamic holographic display, etc.

Dual differential confocal method for surface profile measurement with a large sensing measurement range.

To meet the requirements of the large sensing measurement range and high axial depth resolution for profile measurement, a dual differential confocal method (DDCM) is proposed in this paper. The DDCM uses the confocal signal to process separately the signal of two pinholes with axial offset, and it adds the two processed signals to obtain an axial response curve with a large slope and linear response range, thereby achieving a high-precision surface profile measurement with no axial scanning. Preliminary experiments show that the DDCM has a sensing measurement range of 0.54 µm and an axial resolution of 1 nm at the numerical aperture of 0.9. Furthermore, the sensing measurement range of the DDCM is approximately 2.9 times that of the differential confocal microscopy.

Divided-aperture subtraction-differential confocal method with nanoscale axial resolution.

In this paper, a divided-aperture subtraction-differential confocal method (DASDCM) is proposed to meet the requirements of nanoscale noncontact height measurements for precision machining, materials science, and biology. The DASDCM divides the spot on the detection focal plane into two groups of circular detection areas, which are symmetrical to the optical axis and consist of two concentric detection pinholes with different sizes in each group. Then, the DASDCM uses a subtraction of the intensity signals received from the two detection pinholes in each group to suppress the interference of the nonconjugated information on the intensity signal; it also uses the differential subtraction of two obtained circular detection signals to obtain a sensitive axial response curve. Thereby, the DASDCM greatly improves the axial resolution while considering the signal-to-noise ratio and axial dynamic range of the system and can realize surface height measurement without axial scanning by using the linear range of the axial response curve. Theoretical analysis and preliminary experiments show that DASDCM has an axial resolution of 2 nm with a laser wavelength of λ=632.8 nm and a numerical aperture of NA=0.8. It provides an effective technique for nanoscale height detection with high axial resolution.

Three-dimensional super-resolution correlation-differential confocal microscopy with nanometer axial focusing accuracy.

We present a correlation-differential confocal microscopy (CDCM), a novel method that can simultaneously improve the three-dimensional spatial resolution and axial focusing accuracy of confocal microscopy (CM). CDCM divides the CM imaging light path into two paths, where the detectors are before and after the focus with an equal axial offset in opposite directions. Then, the light intensity signals received from the two paths are processed by the correlation product and differential subtraction to improve the CM spatial resolution and axial focusing accuracy, respectively. Theoretical analyses and preliminary experiments indicate that, for the excitation wavelength of λ = 405 nm, numerical aperture of NA = 0.95, and the normalized axial offset of uM = 5.21, the CDCM resolution is improved by more than 20% and more than 30% in the lateral and axial directions, respectively, compared with that of the CM. Also, the axial focusing resolution important for the imaging of sample surface profiles is improved to 1 nm.

Bilateral fitting subtracting confocal microscopy.

This paper proposes a bilateral fitting subtracting confocal microscopy (BFSCM) based on the optical arrangement of conventional confocal microscopy (CM). BFSCM first uses the data in both sides of a confocal axial response curve, which are very sensitive to the axial position of the sample, for respective linear fitting to obtain two fitting straight lines, and then obtains a difference confocal line by subtraction of the two fitting lines. Finally, it calculates the zero position of the difference confocal line to precisely capture the focus position of the confocal system, and thereby achieving a high-precision measurement of the 3D structure of the sample. The theoretical analyses and experiments indicate that BFSCM can improve the axial resolution, and has anti-interference capability and focusing ability with bipolar absolute zero point tracking, while it does not change the structure and lateral resolution of CM. BFSCM provides a novel method for the improvement of CM axial resolution.

Large-aperture laser differential confocal ultra-long focal length measurement and its system.

A new laser differential confocal ultra-long focal length measurement (LDCFM) method is proposed with the capability to self-calibrate the reference lens (RL) focal length and the axial space between the test lens and RL. Using the property that the focus of laser differential confocal ultra-long focal length measurement system (LDCFS) precisely corresponds to the null point of the differential confocal axial intensity curve, the proposed LDCFM measures the RL focal length f(R)' by precisely identifying the positions of the focus and last surface of RL, measures the axial space d(0) between RL and test ultra-long focal length lens (UFL) by identifying the last surface of RL and the vertex of UFL last surface, and measures the variation l in focus position of LDCFS with and without test UFL, and then calculates the UFL focal length f(T)' by the above measured f(R)', d(0) and l. In addition, a LDCFS based on the proposed method is developed for a large aperture lens. The experimental results indicate that the relative uncertainty is less than 0.01% for the test UFL, which has an aperture of 610 mm and focal length of 31,000 mm. LDCFM provides a novel approach for the high-precision focal-length measurement of large-aperture UFL.

Measuring the lens focal length by laser reflection-confocal technology.

A laser reflection-confocal focal-length measurement (LRCFM) is proposed for the high-accuracy measurement of lens focal length. LRCFM uses the peak points of confocal response curves to precisely identify the lens focus and vertex of the lens last surface. LRCFM then accurately measures the distance between the two positions to determine the lens focal length. LRCFM uses conic fitting, which significantly enhances measurement accuracy by inhibiting the influence of environmental disturbance and system noise on the measurement results. The experimental results indicate that LRCFM has a relative expanded uncertainty of less than 0.0015%. Compared with existing measurement methods, LRCFM has high accuracy and a concise structure. Thus, LRCFM is a feasible method for high-accuracy focal-length measurements.