Extension of stable longitudinal coherence from vacuum ultraviolet to x rays is highly sought after in the free-electron laser (FEL) community, but it is often prevented by bandwidth broadening ...originated in the electron beam microbunching instability. We demonstrate that a proper tuning of the linear optics before the beam enters the undulator mitigates the microbunching-induced sideband instability. The experiment was conducted at the Fermi FEL operated in echo-enabled harmonic generation mode, where the spectral brightness at 7 nm wavelength was doubled. The FEL performance is compared to nonoptimized optics solutions and characterized in terms of peak intensity and spectral bandwidth shot-to-shot stability. The technique has straightforward implementation, because it uses quadrupole magnets routinely adopted for beam transport, and it applies to any FEL architecture, so paving the way to the production of high-intensity Fourier-transform limited x-ray pulses in existing and planned FEL facilities.
Background: Despite several randomised trials comparing radiotherapy alone with concomitant radio-chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC), it is not clear ...whether the addition of chemotherapy improves survival. Patients and methods: This meta-analysis was based on individual patient data from published and unpublished randomised trials which compared radiotherapy alone with the same radiotherapy combined with concomitant cisplatin- or carboplatin-based chemotherapy. Trials with accrual completed after 2000 were excluded. Trials were sought in electronic databases, clinical trial registries and by additional manual searches. The primary endpoint was overall survival analysed using the log-rank test stratified by trials. Results: There were twelve eligible trials that included a total of 1921 patients. The data from 3 trials were not available. Therefore, the analysis was based on 9 trials including 1764 patients. Median follow-up was 7.2 years. The hazard ratio of death among patients treated with radio-chemotherapy compared to radiotherapy alone was 0.89 (95% confidence interval, 0.81–0.98; P = 0.02) corresponding to an absolute benefit of chemotherapy of 4% at 2 years. There was some evidence of heterogeneity among trials and sensitivity analyses did not lead to consistent results. The combination of platin with etoposide seemed more effective than platin alone. Conclusions: Concomitant platin-based radio-chemotherapy may improve survival of patients with locally advanced NSCLC. However, the available data are insufficient to accurately define the size of such a potential treatment benefit and the optimal schedule of chemotherapy.
Artificial Intelligence (AI) methods are being increasingly investigated as a means to generate predictive models applicable in the clinical practice. In this study, we developed a model to predict ...the efficacy of immunotherapy (IO) in patients with advanced non-small cell lung cancer (NSCLC) using eXplainable AI (XAI) Machine Learning (ML) methods.
We prospectively collected real-world data from patients with an advanced NSCLC condition receiving immune-checkpoint inhibitors (ICIs) either as a single agent or in combination with chemotherapy. With regards to six different outcomes - Disease Control Rate (DCR), Objective Response Rate (ORR), 6 and 24-month Overall Survival (OS6 and OS24), 3-months Progression-Free Survival (PFS3) and Time to Treatment Failure (TTF3) - we evaluated five different classification ML models: CatBoost (CB), Logistic Regression (LR), Neural Network (NN), Random Forest (RF) and Support Vector Machine (SVM). We used the Shapley Additive Explanation (SHAP) values to explain model predictions.
Of 480 patients included in the study 407 received immunotherapy and 73 chemo- and immunotherapy. From all the ML models, CB performed the best for OS6 and TTF3, (accuracy 0.83 and 0.81, respectively). CB and LR reached accuracy of 0.75 and 0.73 for the outcome DCR. SHAP for CB demonstrated that the feature that strongly influences models' prediction for all three outcomes was Neutrophil to Lymphocyte Ratio (NLR). Performance Status (ECOG-PS) was an important feature for the outcomes OS6 and TTF3, while PD-L1, Line of IO and chemo-immunotherapy appeared to be more important in predicting DCR.
In this study we developed a ML algorithm based on real-world data, explained by SHAP techniques, and able to accurately predict the efficacy of immunotherapy in sets of NSCLC patients.
(1) Background: In advanced non-small cell lung cancer (aNSCLC), programmed death ligand 1 (PD-L1) remains the only biomarker for candidate patients to immunotherapy (IO). This study aimed at using ...artificial intelligence (AI) and machine learning (ML) tools to improve response and efficacy predictions in aNSCLC patients treated with IO. (2) Methods: Real world data and the blood microRNA signature classifier (MSC) were used. Patients were divided into responders (R) and non-responders (NR) to determine if the overall survival of the patients was likely to be shorter or longer than 24 months from baseline IO. (3) Results: One-hundred sixty-four out of 200 patients (i.e., only those ones with PD-L1 data available) were considered in the model, 73 (44.5%) were R and 91 (55.5%) NR. Overall, the best model was the linear regression (RL) and included 5 features. The model predicting R/NR of patients achieved accuracy ACC = 0.756, F1 score F1 = 0.722, and area under the ROC curve AUC = 0.82. LR was also the best-performing model in predicting patients with long survival (24 months OS), achieving ACC = 0.839, F1 = 0.908, and AUC = 0.87. (4) Conclusions: The results suggest that the integration of multifactorial data provided by ML techniques is a useful tool to select NSCLC patients as candidates for IO.
Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the ...observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.
Synopsis When an electron is ejected from an atom after absorption of a photon, the photoelectron wave packet has an extremely short group delay between the photon absorption and the electron ...emission. This interval, called the Eisenbud-Wigner-Smith delay, is on the order of a few attoseconds. Here, we present a new method to measure the photoemission delay, using coherent-controlled free-electron laser pulses.
Extreme ultraviolet and X-ray free-electron lasers (FELs) produce short-wavelength pulses with high intensity, ultrashort duration, well-defined polarization and transverse coherence, and have been ...utilized for many experiments previously possible only at long wavelengths: multiphoton ionization, pumping an atomic laser and four-wave mixing spectroscopy. However one important optical technique, coherent control, has not yet been demonstrated, because self-amplified spontaneous emission FELs have limited longitudinal coherence. Single-colour pulses from the FERMI seeded FEL are longitudinally coherent, and two-colour emission is predicted to be coherent. Here, we demonstrate the phase correlation of two colours, and manipulate it to control an experiment. Light of wavelengths 63.0 and 31.5 nm ionized neon, and we controlled the asymmetry of the photoelectron angular distribution by adjusting the phase, with a temporal resolution of 3 as. This opens the door to new short-wavelength coherent control experiments with ultrahigh time resolution and chemical sensitivity.
To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were ...previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity.
The analysis was conducted in 17 patients with "in-field" recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test.
The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05).
Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.
Abstract Purpose To derive Normal Tissue Complication Probability (NTCP) models for severe patterns of early radiological radiation-induced lung injury (RRLI) in patients treated with radiotherapy ...(RT) for lung tumors. Second, derive threshold doses and optimal doses for prediction of RRLI to be used in differential diagnosis of tumor recurrence from RRLI during follow-up. Methods and materials Lyman-EUD (LEUD), Logit-EUD (LogEUD), relative seriality (RS) and critical volume (CV) NTCP models, with DVH corrected for fraction size, were used to model the presence of severe early RRLI in follow-up CTs. The models parameters, including α/β, were determined by fitting data from forty-five patients treated with IMRT for lung cancer. Models were assessed using Akaike information criterion (AIC) and area under receiver operating characteristic curve (AUC). Threshold doses for risk of RRLI and doses corresponding to the optimal point of the receiver operating characteristic (ROC) curve were determined. Results The α/βs obtained with different models were 2.7–3.2 Gy. The thresholds and optimal doses curves were EUDs of 3.2–7.8 Gy and 15.2–18.1 Gy with LEUD, LogEUD and RS models, and μd of 0.013 and 0.071 with the CV model. NTCP models had AUCs significantly higher than 0.5. Occurrence and severity of RRLI were correlated with patients’ values of EUD and μd. Conclusions The models and dose levels derived can be used in differential diagnosis of tumor recurrence from RRLI in patients treated with RT. Cross validation is needed to prove prediction performance of the model outside the dataset from which it was derived.
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