Atezolizumab Before and After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: A Phase II Nonrandomized Controlled Trial.

Importance: Outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy. Objective: To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC. Design, Setting, and Participants: This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023. Interventions: Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m2, followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m2, for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy. Main Outcomes and Measures: The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points. Results: A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events. Conclusions and Relevance: These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03102242.

Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria.

Horizontal gene transfer (HGT) and gene duplication are often considered as separate mechanisms driving the evolution of new functions. However, the mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could drive gene duplications. Here, we use a combination of modeling and experimental evolution to examine this hypothesis and use long-read genome sequences of tens of thousands of bacterial isolates to examine its generality in nature. Modeling and experiments show that antibiotic selection can drive the evolution of duplicated antibiotic resistance genes (ARGs) through MGE transposition. A key implication is that duplicated ARGs should be enriched in environments associated with antibiotic use. To test this, we examined the distribution of duplicated ARGs in 18,938 complete bacterial genomes with ecological metadata. Duplicated ARGs are highly enriched in bacteria isolated from humans and livestock. Duplicated ARGs are further enriched in an independent set of 321 antibiotic-resistant clinical isolates. Our findings indicate that duplicated genes often encode functions undergoing positive selection and horizontal gene transfer in microbial communities.

Seedless wet synthesis of copper-twinned nanocrystals.

The wet synthesis of copper (Cu)-twinned nanostructures often requires the addition of noble metal seeds, as twinned Cu seeds are prone to oxidative etching, which inevitably introduces other metal species. In this study, a universal and seedless wet method is proposed for the synthesis of various Cu-twinned nanostructures, such as large Cu decahedrons (with sizes up to 300 nm), singly twinned Cu right bipyramids, and Cu nanorods. The amount of chloride ions (Cl-) and oleylamine and an optimal heating rate at the initial stage were proven to be crucial in this synthesis. Theoretical results revealed that the amount of Cl- could adjust the Gibbs free energy of Cu seeds by promoting the dissociation of oleylamine, which, in turn, determined the structure of thermodynamically favorable seeds based on the thermodynamic model. To the best of our knowledge, this is the first report on large Cu decahedrons and singly twinned Cu right bipyramids. Moreover, they both showed strong localized surface plasmon resonance in the near-infrared region. The photothermal conversion efficiency of large Cu decahedrons increased up to 52.9% upon 808 nm laser irradiation, which is the highest value ever reported for Cu nanocrystals.

Multi-Scale Microstructural Tailoring and Associated Properties of Press-Hardened Steels: A Review.

High-strength press-hardened steels (PHS) are highly desired in the automotive industry to meet the requirement of carbon neutrality. This review aims to provide a systematic study of the relationship between multi-scale microstructural tailoring and the mechanical behavior and other service performance of PHS. It begins with a brief introduction to the background of PHS, followed by an in-depth description of the strategies used to enhance their properties. These strategies are categorized into traditional Mn-B steels and novel PHS. For traditional Mn-B steels, extensive research has verified that the addition of microalloying elements can refine the microstructure of PHS, resulting in improved mechanical properties, hydrogen embrittlement resistance, and other service performance. In the case of novel PHS, recent progress has principally demonstrated that the novel composition of steels coupling with innovative thermomechanical processing can obtain multi-phase structure and superior mechanical properties compared with traditional Mn-B steels, and their effect on oxidation resistance is highlighted. Finally, the review offers an outlook on the future development of PHS from the perspective of academic research and industrial applications.

Regional anesthesia is associated with improved metastasis free survival after surgical resection of bone sarcomas.

There is increasing evidence that perioperative factors, including type of anesthesia, may be an important consideration regarding oncological disease progression. Previous studies have suggested that regional anesthesia can improve oncological outcomes by reducing the surgical stress response that occurs during tumor resection surgery and that may promote metastatic progression. The purpose of this study is to provide the first robust investigation of the impact of adding regional anesthesia to general anesthesia on oncological outcomes following sarcoma resection. One hundred patients with bone sarcoma were retrospectively analyzed in this study. After adjusting for confounding variables such as age and grade of the tumor, patients with bone sarcoma receiving regional anesthesia in addition to general anesthesia during resection had improved metastasis free survival (multivariate hazard ratio of 0.47 and p = 0.034). Future studies are needed to confer the beneficial effect of regional anesthesia, and to further investigate the potential mechanism. Clinical significance: The results from this study provide evidence that regional anesthesia may be advantageous in the setting of bone sarcoma resection surgery, reducing pain while also improving oncological outcomes and should be considered when clinically appropriate.

The Characteristic Microstructures and Properties of Steel-Based Alloy via Additive Manufacturing.

Differing from metal alloys produced by conventional techniques, metallic products prepared by additive manufacturing experience distinct solidification thermal histories and solid-state phase transformation processes, resulting in unique microstructures and superior performance. This review starts with commonly used additive manufacturing techniques in steel-based alloy and then some typical microstructures produced by metal additive manufacturing technologies with different components and processes are summarized, including porosity, dislocation cells, dendrite structures, residual stress, element segregation, etc. The characteristic microstructures may exert a significant influence on the properties of additively manufactured products, and thus it is important to tune the components and additive manufacturing process parameters to achieve the desired microstructures. Finally, the future development and prospects of additive manufacturing technology in steel are discussed.

Study on Corrosion Behavior and Mechanism of Ultrahigh-Strength Hot-Stamping Steel Based on Traditional and Compact Strip-Production Processes.

Hot-stamping steel is a type of high-strength steel that is mainly used in key safety components such as the front and rear bumpers, A-pillars, and B-pillars of vehicles. There are two methods of producing hot-stamping steel, i.e., the traditional process and the near net shape of compact strip production (CSP) process. To assess the potential risks of producing hot-stamping steel using CSP, the microstructure and mechanical properties, and especially the corrosion behavior were focused on between the traditional and CSP processes. The original microstructure of hot-stamping steel produced by the traditional process and the CSP process is different. After quenching, the microstructures transform into full martensite, and their mechanical properties meet the 1500 MPa grade. Corrosion tests showed that the faster the quenching speeds, the smaller the corrosion rate of the steel. The corrosion current density changes from 15 to 8.6 µA·cm-2. The corrosion resistance of hot-stamping steel produced by the CSP process is slightly better than that of traditional processes, mainly since the inclusion size and distribution density of CSP-produced steel were both smaller than those of the traditional process. The reduction of inclusions reduces the number of corrosion sites and improves the corrosion resistance of steel.

Phase Transformation Behaviors of Medium Carbon Steels Produced by Twin Roll Casting and Compact Strip Production Processes.

Medium carbon steels have been widely used in the fields of tool and die manufacturing due to their outstanding hardness and wear resistance. In this study, microstructures of 50# steel strips fabricated by twin roll casting (TRC) and compact strip production (CSP) processes were analyzed to investigate the influences of solidification cooling rate, rolling reduction, and coiling temperature on composition segregation, decarburization, and pearlitic phase transformation. The results show that a partial decarburization layer with a thickness of 13.3 µm and banded C-Mn segregation were observed in the 50# steel produced by CSP, leading to the banded distributions of ferrite and pearlite in the C-Mn poor regions and C-Mn rich regions, respectively. For the steel fabricated by TRC, owing to the sub-rapid solidification cooling rate and short processing time at high temperatures, neither apparent C-Mn segregation nor decarburization was observed. In addition, the steel strip fabricated by TRC has higher pearlite volume fractions, larger pearlite nodule sizes, smaller pearlite colony sizes and interlamellar spacings due to the co-influence of larger prior austenite grain size and lower coiling temperatures. The alleviated segregation, eliminated decarburization and large volume fraction of pearlite render TRC a promising process for medium carbon steel production.

High-Dose Once-Daily Thoracic Radiotherapy in Limited-Stage Small-Cell Lung Cancer: CALGB 30610 (Alliance)/RTOG 0538.

PURPOSE: Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated. METHODS: This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity analysis, and the study continued with two remaining arms. The primary end point was overall survival (OS) in the intention-to-treat population. RESULTS: Trial accrual opened on March 15, 2008, and closed on December 1, 2019. All patients randomly assigned to 45-Gy twice-daily (n = 313) or 70-Gy once-daily radiotherapy (n = 325) are included in this analysis. After a median follow-up of 4.7 years, OS was not improved on the once-daily arm (hazard ratio for death, 0.94; 95% CI, 0.76 to 1.17; P = .594). Median survival is 28.5 months for twice-daily treatment, and 30.1 months for once-daily treatment, with 5-year OS of 29% and 32%, respectively. Treatment was tolerable, and the frequency of severe adverse events, including esophageal and pulmonary toxicity, was similar on both arms. CONCLUSION: Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage small-cell lung cancer.

Survival and tumor characteristics of patients presenting with single primary versus second primary melanoma lesions.

BACKGROUND: Patients with single primary melanomas have an increased risk of developing subsequent melanomas. Secondary tumors diagnosed within and after 3 months are termed "synchronous" and "asynchronous," respectively. OBJECTIVE: To compare tumor distributions and survival characteristics between patients with second primary melanomas and those with single primary melanomas. METHODS: Retrospective cohort study. Data were collected from an institutional database from 14,029 patients with a diagnosis of a primary melanoma seen between 1970 and 2004. RESULTS: The synchronous and asynchronous cohorts demonstrated significantly improved survival probabilities compared with the single primary cohort (P = .04 and .002, respectively). Single primary lesions (2.2 ± 2.3 mm) were significantly thicker than the first-identified synchronous (2.0 ± 1.7 mm) and asynchronous (1.7 ± 1.3 mm) lesions. Synchronous lesions were more likely to be anatomically concordant compared with asynchronous lesions (55.7% vs 38.2%, P < .001). LIMITATIONS: Single-center study design and incomplete records for second primary melanoma Breslow depth and histopathology. CONCLUSION: Patients with second primary melanomas demonstrated a significant survival advantage and thinner lesions compared with those with single primary melanomas. Our reported tumor distributions support the role of full body skin examinations, with attention to the region of initial diagnosis.

Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma.

This study aims to investigate whether adding neoadjuvant radiotherapy (RT), anti-programmed cell death protein-1 (PD-1) antibody (anti-PD-1), or RT + anti-PD-1 to surgical resection improves disease-free survival for mice with soft tissue sarcomas (STS). We generated a high mutational load primary mouse model of STS by intramuscular injection of adenovirus expressing Cas9 and guide RNA targeting Trp53 and intramuscular injection of 3-methylcholanthrene (MCA) into the gastrocnemius muscle of wild-type mice (p53/MCA model). We randomized tumor-bearing mice to receive isotype control or anti-PD-1 antibody with or without radiotherapy (20 Gy), followed by hind limb amputation. We used micro-CT to detect lung metastases with high spatial resolution, which was confirmed by histology. We investigated whether sarcoma metastasis was regulated by immunosurveillance by lymphocytes or tumor cell-intrinsic mechanisms. Compared with surgery with isotype control antibody, the combination of anti-PD-1, radiotherapy, and surgery improved local recurrence-free survival (P = 0.035) and disease-free survival (P = 0.005), but not metastasis-free survival. Mice treated with radiotherapy, but not anti-PD-1, showed significantly improved local recurrence-free survival and metastasis-free survival over surgery alone (P = 0.043 and P = 0.007, respectively). The overall metastasis rate was low (∼12%) in the p53/MCA sarcoma model, which limited the power to detect further improvement in metastasis-free survival with addition of anti-PD-1 therapy. Tail vein injections of sarcoma cells into immunocompetent mice suggested that impaired metastasis was due to inability of sarcoma cells to grow in the lungs rather than a consequence of immunosurveillance. In conclusion, neoadjuvant radiotherapy improves metastasis-free survival after surgery in a primary model of STS.

Chloride-ion-directed synthesis of plate-like Cu2O mesocrystals for effective nitrogen fixation.

Cuprous oxide (Cu2O) mesocrystals, which are composed of numerous nanocrystals with a common crystallographic orientation, are supposed to possess superior photocatalytic abilities than the normal constructions, but very few of them have been reported to date. In this work, plate-like Cu2O mesocrystals were successfully fabricated via a facile one-pot wet chemical strategy. Unlike the commonly used polymers or small molecules, chloride ions (Cl-) were employed as structure-directing agents and played the main role in the Cu2O mesocrystal formation. The formation mechanism was interpreted as follows: the presence of Cl- inhibited the formation of CuO and Cu by forming the intermediate product CuCl, which was further hydrolyzed to Cu2O nanocrystals. Cl- tended to adsorb on the (111) facets of the formed Cu2O nanocrystals and stabilize them. Then the Cu2O nanocrystals were aligned side by side through the unabsorbed side faces, leading to mutual nanocrystals orientation and crystallographic lock-in, facilitating the formation of plate-like Cu2O mesocrystals. The polymer, polyacrylamide (PAM), also promoted the mesocrystals formation by serving as a stabilizer and fixed the crystallographic orientation of the Cu2O nanocrystals during their orderly stacking process. The plate-like Cu2O mesocrystals showed a long decay time and pronounced performance toward the visible-light-driven photocatalytic reduction of N2 into NH3. This research may stimulate in-depth investigations into the exploration of new synthetic methods for the design and construction of novel mesocrystals.

Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration.

In orthopedic oncology, the implant of a megaprosthetic device is standard of care after large-scale tumor resection involving segmental removal of bone. Infection remains the leading cause of implant failure, often resulting in major morbidity. Perioperative antibiotic practices for megaprosthetic reconstructions are not standardized and are based on guidelines for conventional joint arthroplasties. This study aims to evaluate the efficacy of current prophylactic strategies for megaprosthetic reconstructions. We conducted a retrospective review of megaprosthetic reconstructions performed at Duke University from 2001 to 2021. Logistic regression with GEE was used to assess whether a prolonged course of postoperative antibiotics is associated with infection risk. We assessed the microbial profile and corresponding susceptibilities of megaprosthetic infections through record review. Additionally, we designed a pharmacokinetic subgroup analysis using liquid chromatography-tandem mass spectrometry to quantify antibiotic concentrations in surgical tissue. Wilcoxon rank-sum tests were used to correlate tissue concentrations with infection risk. Out of 184 cases, 23 (12.5%) developed infection within 1 year. Extended postoperative antibiotics were not significantly associated with infection risk (P = 0.23). Among 18 culture-positive cases, 4 (22.2%) were caused by cefazolin-susceptible organisms. Median bone and muscle concentrations of cefazolin among cases that developed postoperative infection (0.065 ng/mL and 0.2 ng/mL, respectively) were significantly lower than those of cases that did not (0.42 ng/mL and 1.95 ng/mL, P < 0.01 and P = 0.03). This study is the first to comprehensively assess aspects of perioperative prophylaxis for megaprosthetic reconstructions. Extending postoperative antibiotics did not reduce infection risk. We detected a high frequency of cefazolin nonsusceptible organisms among postoperative infections. Additionally, intraoperative antibiotic tissue concentrations may be predictive of later infection. Future studies ought to examine optimal drug choices and dosing strategies.

Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma.

BACKGROUND: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also received anti-PD-1 after lerapolturev. In preclinical models lerapolturev induces intratumoral innate inflammation that engages antitumor T cells. In the current study, prelerapolturev and postlerapolturev tumor biopsies and blood were evaluated for biomarkers of response. METHODS: The following analyses were performed on tumor tissue (n=11): (1) flow cytometric assessment of immune cell density, (2) NanoString Digital Spatial profiling of protein and the transcriptome, and (3) bulk RNA sequencing. Immune cell phenotypes and responsiveness to in vitro stimulation, including in vitro lerapolturev challenge, were measured in peripheral blood (n=12). RESULTS: Three patients who received anti-PD-1 therapy within 30 days of lerapolturev have a current median progression-free survival (PFS) of 2.3 years and had higher CD8+T cell infiltrates in prelerapolturev tumor biopsies relative to that of 7 patients with median PFS of 1.6 months and lower CD8+T cell infiltrates in prelerapolturev tumor biopsies. In peripheral blood, four patients with PFS 2.3 years (including three that received anti-PD-1 therapy within 30 days before lerapolturev and had higher pretreatment tumor CD8+T cell infiltrates) had significantly higher effector memory (CD8+, CCR7-, CD45RA-) but lower CD8+PD-1+ and CD4+PD-1+ cells compared with eight patients with median PFS 1.6 months. In addition, pretreatment blood from the four patients with median PFS 2.3 years had more potent antiviral responses to in vitro lerapolturev challenge compared with eight patients with median PFS 1.6 months. CONCLUSION: An inflamed pretreatment tumor microenvironment, possibly induced by prior anti-PD-1 therapy and a proficient peripheral blood pretreatment innate immune response (antiviral/interferon signaling) to lerapolturev was associated with long term PFS after intratumoral lerapolturev in a small cohort of patients. These findings imply a link between intratumoral T cell inflammation and peripheral immune function. TRIAL REGISTRATION NUMBER: NCT03712358.

Investigating readmission rates for patients undergoing oncologic resection and endoprosthetic reconstruction for primary sarcomas and tumors involving bone.

BACKGROUND: Little is known about the drivers of readmission in patients undergoing Orthopaedic oncologic resection. The goal of this study was to identify factors independently associated with 90-day readmission for patients undergoing oncologic resection and subsequent prosthetic reconstruction for primary tumors involving bone. METHODS: This was a retrospective comparative cohort study of patients treated from 2008 to 2019 who underwent endoprosthetic reconstruction for a primary bone tumor or soft tissue tumor involving bone, as well as those who underwent a revision endoprosthetic reconstruction if the primary endoprosthetic reconstruction was performed for an oncologic resection. The primary outcome measure was unplanned 90-day readmission. RESULTS: A total of 149 patients were identified who underwent 191 surgeries were for a primary bone or soft tissue tumor. The 90-day readmission rate was 28.3%. Female gender, depression, higher tumor grade, vascular reconstruction, longer procedure duration, longer length of stay (LOS), multiple surgeries during an admission and disposition to a Skilled Nursing Facility were associated with readmission (p < 0.05). In a multivariate analysis, female sex, higher tumor grade and longer procedure duration were independently associated with risk of readmission (p < 0.05). CONCLUSIONS: Readmission rates are high following endoprosthetic reconstruction for Orthopaedic oncologic resections. Further work is necessary to help minimize unplanned readmissions.

Nomogram Predicting Overall Survival Benefit of Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

OBJECTIVES: To develop and validate a nomogram that predicts overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) vs. observation. MATERIALS AND METHODS: Adults with biopsy-proven T1-T2N0 NCSLC treated with SABR (30-70 Gy in 1-10 fractions with biologically effective dose ≥100 Gy10) or observation between 2004 and 2015 in the National Cancer Database (NCDB) were identified. Propensity score was used to match SABR and observation cohorts on prognostic demographic and clinicopathologic factors identified by logistic regression. Using backward selection, a multivariable Cox proportional hazard was identified predicting 2- and 5-year OS via a nomogram. Model prediction accuracy was assessed by time-dependent receiver operating characteristic (ROC) curves and integrated area under the ROC curve (AUC) analysis. RESULTS: A total of 22,073 adults met inclusion criteria and 4418 matched pairs (total n = 8836) were identified for nomogram development. The factors most strongly associated with improved OS on multivariable analysis included younger age (HR 0.82 by decade, P < .001), female sex (HR 0.81, P < .001), lower comorbidity index (HR 0.65 for 0 vs. ≥3, P < .001), smaller tumor size (HR 0.60 for ≤3 cm vs. 5.1-7 cm, P < .001), adenocarcinoma histology (P < .001), and receipt of SABR (P < .001). Interaction between SABR and histology was significantly associated with OS (P = .017). Relative to adenocarcinoma, patients with squamous cell carcinoma who were observed (HR 1.44, 95% CI 1.33-1.56) or treated with SABR (HR 1.24, 95% CI 1.14-1.35) had significantly worse OS. The nomogram demonstrated fair accuracy for predicting OS, with an integrated time-dependent AUC of 0.694 over the entire follow-up period. CONCLUSION: This nomogram estimates OS at 2 and 5 years based on whether medically inoperable early-stage NSCLC patients receive SABR or elect for observation. Incorporation of other variables not captured within the NCDB may improve the model accuracy.

Lung Cancer Screening Eligibility and Use: A Population Health Perspective of One Community.

BACKGROUND Low-dose chest CT (LDCT) is the only effective screening test for lung cancer. Annual lung cancer screening (LCS) is recommended by the US Preventive Services Task Force (USPSTF) for individuals at high risk for primary lung neoplasm.METHODS We retrospectively identified patients receiving LCS from January 2016 through March 2018 whose residential addresses were within our health center's county. We estimated driving distance from the patient's address to our health center and obtained sociodemographic characteristics from the electronic health record (EHR). The census-tract-level LCS-eligible population size was estimated, and their population characteristics determined via US Census Bureau, Centers for Disease Control and Prevention (CDC), and Behavioral Risk Factor Surveillance System (BRFSS) data. The Cochran-Mantel-Haenszel test was used to determine differences amongst the LCS-eligible and LCS-enrolled populations. Multivariable regression was used to determine the effects of sociodemographic characteristics on LCS eligibility.RESULTS There was modest correlation between census-tract-level LCS-eligible population size and LCS enrollment (r = 0.68, P < .001). 5.9% (364/6185) of the estimated LCS-eligible population in our county received LCS, with census-tract LCS rates ranging from 1.5% to 12.5%. Nonwhite race status (Hispanic and African American) was associated with decreased likelihood of LCS enrollment compared to White race (OR = 95% CI, 0.765 [0.61, 0.95] and 0.031 [0.008, 0.124], respectively). Older age, Medicaid, and uninsured statuses were positively correlated with LCS eligibility (P ≤ .01).LIMITATIONS This analysis comprises a single county. Other LCS facilities within our health system in neighboring counties, as well as individuals receiving LCS outside of our health system, are not captured.CONCLUSIONS The uptake of LCS remains low, with disproportionately lower screening rates amongst Hispanic and African American populations. Medicaid and uninsured patients in our community are also more likely to be LCS-eligible. These populations may be targets for interventions aimed at increasing LCS awareness and uptake.

Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences of Pembrolizumab and Standard Platinum-Based Chemotherapy in Patients With Metastatic NSCLC.

INTRODUCTION: The sequence of chemotherapy and pembrolizumab may affect antitumor immune response and efficacy of immunotherapy. METHODS: This multicenter, randomized, phase 2 trial was designed to evaluate the efficacy of two sequences of chemotherapy and pembrolizumab in patients with stage 4 NSCLC. Both arms were considered investigational, and the study used a "pick a winner" design. The primary end point was objective response rate by independent radiologic review after eight cycles (24 wk). Patients were randomized 1:1 to arm A (chemotherapy for four cycles followed by pembrolizumab for four cycles) or arm B (pembrolizumab for four cycles followed by chemotherapy for four cycles). Patients in both arms without disease progression after the initial eight cycles continued pembrolizumab until disease progression, unacceptable toxicity, or a maximum of 2 years. RESULTS: From March 2016 to July 2018, a total of 90 eligible patients were randomized (43 patients to arm A and 47 patients to arm B). The objective response rate at 24 weeks in arms A and B was 39.5 % (95 % confidence interval [CI]: 24.9%-54.1 %) and 40.4 % (95 % CI: 26.4%-54.5 %), respectively (p = 0.93). The progression-free survival in arms A and B was as follows: hazard ratio of B versus A equals to 1.06, 95 % CI: 0.68-1.66, p value equals to 0.84, and median progression-free survival of 5.8 months and 4 months, respectively. The overall survival was as follows: hazard ratio of B versus A equals to 1.04, 95 % CI: 0.63-1.74, p value equals to 0.85, and median overall survival of 15.5 months and 14 months, respectively. CONCLUSIONS: Additional evaluation of either sequence in a phase 3 trial is not warranted.

Effect of cryomilling time on microstructure evolution and hardness of cryomilled AZ31 powders.

The synthesis of nanostructured AZ31 powder by cryomilling was studied in this paper. The microstructural evolution during cryomilling, including the changes of particle morphology and internal grain size, was characterized via optical microscopy, SEM, TEM and XRD. Observations during the cryomilling produced four main findings. Firstly, cryomilling can refine the grains of AZ31 particles down to 100 nm after around 1 h milling and the minimum average grain size of about 30 nm was reached when the cryomilling time was extended to 6 h or longer. Secondly, cold welding played a dominant role in the early stage of cryomilling, while fracture took place in the late stage and surpassed cold welding. The former led to a particle size increase while the latter decreased the particle size. The minimum average particle size after 6 h cryomilling was approximately 26 µm. Thirdly, a few particles were agglomerated with other particles and could not be processed by cryomilling due to cold welding. Finally, after cryomilling 6 h and longer times, the hardness reached 162 HV which was much higher than other values reported in AZ31 alloy studies.

Radiogenomic Analysis of Locally Advanced Lung Cancer Based on CT Imaging and Intratreatment Changes in Cell-Free DNA.

The radiologic appearance of locally advanced lung cancer may be linked to molecular changes of the disease during treatment, but characteristics of this phenomenon are poorly understood. Radiomics, liquid biopsy of cell-free DNA (cfDNA), and next-generation sequencing of circulating tumor DNA (ctDNA) encode tumor-specific radiogenomic expression patterns that can be probed to study this problem. Preliminary findings are reported from a radiogenomic analysis of CT imaging, cfDNA, and ctDNA in 24 patients (median age, 64 years; range, 49-74 years) with stage III lung cancer undergoing chemoradiation on a prospective pilot study (NCT00921739) between September 2009 and September 2014. Unsupervised clustering of radiomic signatures resulted in two clusters that were associated with ctDNA TP53 mutations (P = .03) and changes in cfDNA concentration after 2 weeks of chemoradiation (P = .02). The radiomic features dissimilarity (hazard ratio [HR] = 0.56; P = .05), joint entropy (HR = 0.56; P = .04), sum entropy (HR = 0.53; P = .02), and normalized inverse difference (HR = 1.77; P = .05) were associated with overall survival. These results suggest heterogeneous and low-attenuating disease without a detectable ctDNA TP53 mutation was associated with early surges of cfDNA concentration in response to therapy and a generally better prognosis. Keywords: CT-Quantitative, Radiation Therapy, Lung, Computer Applications-3D, Oncology, Tumor Response, Outcomes Analysis Clinical trial registration no. NCT00921739 Supplemental material is available for this article. © RSNA, 2021.