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Objective: Esophageal cancers that invade the submucosa (T1b) have increased risk for occult lymph node metastases. To avoid the morbidity and recovery from esophagectomy, patients with cT1bN0 tumors have been increasingly managed endoscopically. We hypothesized that tumor attributes could predict upstaging and outcome associated with surgical and endoscopic treatment. Our objective was to evaluate the comparative effectiveness of esophagectomy across different cT1bN0 tumor attributes., Methods: Treatment-naïve patients who underwent endoscopic management or esophagectomy for a clinical stage cT1bN0 esophageal cancer diagnosed between 2010 and 2018 in the National Cancer Database were identified. Factors associated with upstaging were assessed by logistic regression. Adjusted survival was assessed by Kaplan-Meier analysis of 528 propensity-matched pairs and accelerated time failure models, stratified across tumor attributes., Results: Overall, 1469 patients classified as cT1bN0 were identified; 926 underwent esophagectomy and 543 were managed endoscopically. In general, patients who were managed endoscopically were older (median, 71; interquartile range, 63-78; vs 66; interquartile range, 60-72; P < .0001) with smaller tumors compared with the patients who were managed with esophagectomy. Nodal upstaging was associated with lymphovascular invasion (odds ratio [OR], 6.88; confidence interval [CI], 4.39-10.77; P < .0001), poor tumor differentiation (OR, 2.77; CI, 1.30-5.88; P = .0081), and tumor size >1 cm (OR, 3.19; CI, 1.49-6.83, P = .0028). Overall survival was better among propensity-matched patients who underwent esophagectomy (5-year 68.4% vs 59.7% endoscopic, P < .001). However, accelerated time failure models suggested similar outcomes among patients with well-differentiated tumors managed surgically or endoscopically., Conclusions: Esophagectomy was associated with improved survival for cT1bN0 esophageal cancer; however, endoscopic treatment may achieve similar survival in patients with favorable tumor attributes. Further study is warranted., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: For patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) who progress on first-line osimertinib, the optimal second-line treatment regimen after progression is not known. We sought to assess practice patterns and evaluate the association between different therapies and survival in patients with EGFR-mutated NSCLC following progression on first-line osimertinib., Methods: Retrospective cohort study of patients who received first-line treatment with osimertinib using a population-based, multicenter nationwide electronic health record-derived deidentified database., Results: We identified 2373 patients who received first-line osimertinib. The majority (n = 2279) received osimertinib monotherapy. A total of 538 patients received first-line osimertinib and had second-line treatment data available. Second-line treatment regimens were varied: 65% (n = 348) included chemotherapy, 37% (n = 197) included an immune checkpoint inhibitor (ICI), and 44% (n = 234) included an EGFR tyrosine kinase inhibitor (TKI). We then analyzed the 333 patients with performance status 0-2 who received chemotherapy with osimertinib (n = 107, 32%) versus chemotherapy without osimertinib (n = 226, 68%). The continuation of osimertinib with chemotherapy was associated with superior progression-free survival (PFS; median: 10.1 versus 5.9 months, Hazard Ratio [HR]: 0.48, 95% Confidence Interval [CI]: [0.34, 0.68], P < .001) and overall survival (OS; median: 17.0 versus 12.8 months, HR: 0.64, 95% CI: [0.44, 0.93], P = .018) compared to other chemotherapy approaches without osimertinib. This effect was most pronounced in patients with an EGFR exon 19 deletion., Conclusions: Following progression on osimertinib, a wide variety of treatment regimens were used. The continuation of osimertinib with chemotherapy in the second line was associated with increased PFS and OS., Competing Interests: Disclosure The authors report the following potential conflicts of interest and additional funding sources, none of which are related to the currently presented manuscript: Dr Boffa has received experimental services without charge from Epic Sciences, and was paid to attend a panel discussion in May of 2022 by Iovance. Dr Goldberg has received research funding from AstraZeneca, Boehringer Ingelheim, and Mirati. She is a consulting/advisory board member for AstraZeneca, Boehringer Ingelheim, Bristol–Myers–Squibb, Genentech, Amgen, Blueprint Medicine, Sanofi Genzyme, Daiichi-Sankyo, Takeda, Janssen, Summit Therapeutics, Merck, Regeneron, and Eli Lilly. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Defects in the DNA mismatch repair (MMR) pathway can predispose individuals to colorectal cancer (CRC), with germline mutations in this pathway leading to Lynch syndrome. Consequently, universal MMR testing is recommended for all newly diagnosed CRC patients to detect mismatch repair deficient (MMR-D) tumors, enabling informed treatment decisions. Given the increased potential for metachronous disease in patients with Lynch syndrome, the current guidelines for surgical management of Lynch-associated colon cancer recommend extended resection in patients under age 60., Methods: A retrospective analysis of nonmetastatic CRC was performed from the National Cancer Database to evaluate the current trends and practice patterns in the surgical management of MMR-D colon cancer, as well as assess the factors influencing choice of surgical procedure., Results: From 2018 to 2020, 98,112 nonmetastatic CRC patients were identified, with 19.93% being MMR-D. MMR-D colon cancer patients were more likely to undergo extended resection than those with mismatch repair proficient tumors (9.4% versus 4.2%, P < 0.001). When accounting for approximately one-fourth of MMR-D colon cancers being attributable to Lynch syndrome, the frequency of extended resection was less than expected (9.4% versus 25%, P < 0.001). MMR-D patients under age 60 were more likely to undergo extended resection than those over age 60 (9% versus 3%) (odds ratio [OR] 3.57, 95% confidence interval [CI] 3.06-4.15). Several factors were associated with decreased rate of extended resection: uninsured (OR 0.42, 95% CI 0.21-0.84), Black race (OR 0.54, 95% CI 0.35-0.82), treatment at nonacademic centers (OR 0.74, 95% CI 0.56-0.97), and crowfly distance >25 miles (OR 1.98, 95% CI 1.14-3.45)., Conclusions: These findings provide valuable insight into the current surgical practice patterns in the management of MMR-D colon cancers and possibly colon cancers associated with Lynch syndrome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Palliative treatment has been associated with improved quality of life and survival for a wide variety of metastatic cancers. However, it is unclear whether the benefits of palliative treatment are uniformly experienced across the US cancer population. We evaluated patterns and outcomes of palliative treatment based on socioeconomic, sociodemographic and treating facility characteristics., Methods: Patients diagnosed between 2008 and 2019 with Stage IV primary cancer of nine organ sites were analyzed in the National Cancer Database. The association between identified variables, and outcomes concerning the administration of palliative treatment were analyzed with multivariable logistic regression and Cox proportional hazard models., Results: Overall 238,995 (23.6%) of Stage IV patients received palliative treatment, which increased over time for all cancers (from 20.7% in 2008 to 25.6% in 2019). Palliative treatment utilization differed significantly by region (West less than Northeast, OR: 0.55 [0.54-0.56], p < 0.001) and insurance payer status (uninsured greater than private insurance, OR: 1.35 [1.32-1.39], p < 0.001). Black race and Hispanic ethnicity were also associated with lower rates of palliative treatment compared to White and non-Hispanics respectively (OR for Blacks: 0.91 [0.90-0.93], p < 0.001 and OR for Hispanics: 0.79 [0.77-0.81] p < 0.001)., Conclusions: There are important differences in the utilization of palliative treatment across different populations in the United States. A better understanding of variability in palliative treatment use and outcomes may identify opportunities to improve informed decision making and optimize quality of care at the end-of-life., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Patients with non-small cell lung cancer treated with immunotherapy and modern chemoradiation regimens show improved progression-free and overall survival. However, patients with limited oligo-progression represent a potential population in which local therapy such as surgery may have a potential role as salvage treatment. The objectives of our study were to evaluate the feasibility and safety of salvage lung resection after immunotherapy in patients with non-small cell lung cancer., Methods: The National Cancer Database was queried for patients diagnosed and treated for non-small cell lung cancer stage I to IV, from 2013 to 2020. Patients who underwent surgery as salvage after immunotherapy were defined as undergoing surgery >5 months from the initiation of immunotherapy. As a sensitivity analysis, patients who underwent surgery as salvage after chemoradiation were also analyzed in a similar fashion. Surgical outcomes such as type of surgery, complete resection (R0) rates, and complete pathologic response rates were determined for feasibility. Length of stay, 30-day readmission rates, and 30-day mortality rates were determined and overall survivals were estimated with Kaplan-Meier analysis to evaluate for safety., Results: Of the 934,093 patients diagnosed with non-small cell lung cancer stage I to IV from 2013 to 2020, 164 patients received immunotherapy and after 5 months underwent surgery. Lobectomy was the most commonly performed operation (74%) and pneumonectomy was required in 9% (n = 15). R0 resection was achieved in 89% (n = 146) and of these patients, 23% (n = 37) had complete pathologic response. Median length of stay was 4 days, 30-day readmission was 5%, and 30-day mortality was 0.6%. In our sensitivity analysis of chemoradiation patients (n = 445), the above data were similar to previously reported cohort studies of patients undergoing chemoradiation and subsequently salvage surgery., Conclusions: Lung resection after immunotherapy appears to be a feasible salvage treatment option, with lobectomy being most common and with high R0 resection rates. Low patient morbidity and mortality rates also suggest the safety of this approach. Salvage surgery may be considered in patients who have oligo-progression after immunotherapy within the context of a comprehensive multidisciplinary treatment plan., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Objective: To evaluate trends in the utilization of stereotactic body radiotherapy (SBRT) and to compare overall survival (OS) of patients with early-stage non-small cell lung cancer (NSCLC) undergoing SBRT versus those undergoing surgery., Methods: The National Cancer Database was queried for patients without documented comorbidities who underwent surgical resection (lobectomy, segmentectomy, or wedge resection) or SBRT for clinical stage I NSCLC between 2012 and 2018. Peritreatment mortality and 5-year OS were compared among propensity score-matched cohorts., Results: A total of 30,658 patients were identified, including 24,729 (80.7%) who underwent surgery and 5929 (19.3%) treated with SBRT. Between 2012 and 2018, the proportion of patients receiving SBRT increased from 15.9% to 26.0% (P < .001). The 30-day mortality and 90-day mortality were higher among patients undergoing surgical resection versus those receiving SBRT (1.7% vs 0.3%, P < .001; 2.8% vs 1.7%, P < .001). In propensity score-matched patients, OS favored SBRT for the first several months, but this was reversed before 1 year and significantly favored surgical management in the long term (5-year OS, 71.0% vs 41.8%; P < .001). The propensity score-matched analysis was repeated to include only SBRT patients who had documented refusal of a recommended surgery, which again demonstrated superior 5-year OS with surgical management (71.4% vs 55.9%; P < .001)., Conclusions: SBRT is being increasingly used to treat early-stage lung cancer in low-comorbidity patients. However, for patients who may be candidates for either treatment, the long-term OS favors surgical management., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Non-intubated thoracoscopic surgery with spontaneous breathing is rarely utilized, but may have several advantages over standard intubation, especially in those with significant cardiopulmonary comorbidities. In this study we evaluate the safety, feasibility, and 3-year survival of thoracoscopic surgery without endotracheal intubation for oncologic and non-oncologic indications., Methods: All consecutive patients [2018-2022] selected for lung resection or other pleural space intervention under local anesthesia and sedation were compared to a cohort undergoing elective thoracoscopic procedures with endotracheal intubation. A propensity-score matched cohort was used to compare perioperative outcomes and 3-year overall survival., Results: A total of 72 patients underwent thoracoscopic surgery without intubation compared to 1,741 who were intubated. Non-intubated procedures included 19 lobectomies (26.4%), 9 segmentectomies (12.5%), 25 wedge resections (34.7%), and 19 pleural or mediastinal resections (26.4%). Non-intubated patients had a lower average body mass index (BMI; 24.6 vs. 27.1 kg/m 2 , P<0.001) and a higher comorbidity burden. Primary lung cancer was the indication in 30 (41.7%) non-intubated patients. The non-intubated cohort had no operative or 30-day mortality. After propensity-score matching, there was no significant difference in pre-operative factors. In propensity-score matched analysis, non-intubated patients had shorter median total operating room time (109 vs. 159 min, P<0.001) and procedure time (69 vs. 119 min, P<0.001). Peri-operative morbidity was rare and did not differ between intubated and non-intubated patients. There was no significant difference in 3-year survival associated with non-intubation in the propensity-score matched cohorts (95% vs. 89%, P=0.10) or in a Cox proportional hazard model [hazard ratio (HR), 1.15; 95% confidence interval (CI): 0.36-3.67; P=0.81]., Conclusions: Non-intubated thoracoscopic surgery is safe and feasible in carefully selected patients for both benign and oncologic indications., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-591/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Purpose: This study aims to clarify the association between metastatic pattern and prognosis in stage IV gastric cancer, with a focus on patients presenting with metastases limited to nonregional lymph nodes., Methods: In this retrospective cohort study, the National Cancer Database was used to identify patients ≥ 18 years of age diagnosed with stage IV gastric cancer between 2016 and 2019. Patients were stratified according to pattern of metastatic disease at diagnosis: nonregional lymph nodes only ("stage IV-nodal"), single systemic organ ("stage IV-single organ"), or multiple organs ("stage IV-multi-organ"). Survival was assessed by Kaplan-Meier curves and multivariable Cox models in unadjusted and propensity score-matched samples., Results: Overall, 15,050 patients were identified, including 1,349 (8.7%) stage IV-nodal patients. Most patients in each group received chemotherapy [68.6% of stage IV-nodal patients, 65.2% of stage IV-single organ patients, and 63.5% of stage IV-multi-organ patients (p = 0.003)]. Stage IV-nodal patients exhibited better median survival (10.5 months, 95% CI 9.7-11.9, p < 0.001) than single organ (8.0, 95% CI 7.6-8.2) and multi-organ (5.7, 95% CI 5.4-6.0) patients. In the multivariable Cox model, stage IV-nodal patients also exhibited better survival (HR 0.79, 95% CI 0.73-0.85, p < 0.001) than single organ (reference) and multi-organ (HR 1.27, 95% CI 1.22-1.33, p < 0.001) patients., Conclusions: Nearly 9% of clinical stage IV gastric cancer patients have their distant disease confined to nonregional lymph nodes. These patients were managed similarly to other stage IV patients but experienced a better prognosis, suggesting opportunities to introduce M1 staging subclassifications., (© 2023. Society of Surgical Oncology.)

Introduction: For patients with stage IV esophageal cancer, esophageal radiation may be used selectively for local control and palliation. We aimed to understand patterns of radiation administration among patients with stage IV esophageal cancer and any potential survival associations., Methods: In this retrospective cohort study, the National Cancer Database was queried for patients with metastatic stage IV esophageal cancer diagnosed between 2016 and 2019. Patterns of radiation use were identified. Survival was determined through Kaplan-Meier analysis of propensity score-matched pairs of patients who did and did not receive radiotherapy and time-to-event models., Results: Overall, 12,088 patients with stage IV esophageal cancer were identified, including 32.7% who received esophageal radiation. The median age was 65 (interquartile range [IQR]: 58-73) years, and 82.6% were male. Among the irradiated patients, the median total radiation dose was 35 (IQR: 30-50) Gy administered in a median of 14 (IQR: 10-25) fractions given in 22 (IQR: 14-39) days. Overall, esophageal radiation was not associated with better survival (log-rank p  = 0.41). When stratified by radiation dose, a survival advantage (over no radiation) was found in the 1144 patients (29% of the irradiated patients) who received 45 to 59.9 Gy (time ratio = 1.28, 95% confidence interval: 1.20-1.37, p < 0.001) and the 88 patients (2.2%) who received 60 to 80 Gy (time ratio = 1.37, 95% confidence interval: 1.11-1.69, p  = 0.003)., Conclusions: One-third of the patients with metastatic stage IV esophageal cancer in the National Cancer Database received esophageal radiation. Most received a radiation dose that, although consistent with palliative regimens, was not associated with a survival advantage. Further study is warranted to understand the indications for radiation in stage IV esophageal cancer and potentially reevaluate the most appropriate radiation dose for palliation., (© 2022 The Authors.)

Introduction: Metastatic involvement of at least one nonregional lymph node currently renders patients with esophageal cancer as having stage IV disease. However, the management and outcomes of patients whose sole determinant of stage IV status is nonregional lymph nodes (abbreviated as "stage IV-nodal" disease) have not been fully characterized., Methods: In this retrospective cohort study, the National Cancer Database was queried to identify patients 18 years of age or older who were diagnosed with stage IV esophageal cancer between 2016 and 2019. Survival was assessed by Kaplan-Meier analysis and Cox models in the overall sample and a propensity-matched sample. Patients with "stage IV-nodal" disease were compared with patients with systemic metastases involving a single organ or multiple organs., Results: Overall, 11,589 patients with clinical stage IV esophageal cancer were identified, including 1331 (11.5%) patients with stage IV-nodal disease. Patients with stage IV-nodal disease were more likely to receive chemotherapy (77%) than those with single systemic organ metastases (64%) and multiorgan metastases (63%) ( p < 0.0001); patients with stage IV-nodal disease were also more likely to receive radiation (49%) than those with single systemic organ metastases (40%) and multiorgan metastases (39%) ( p < 0.0001). Squamous cell carcinoma (OR = 1.58, 95% confidence interval [CI]: 1.34-1.86, p < 0.0001) and academic facility type (OR = 1.24, 95% CI: 1.09-1.4, p  = 0.0009) were associated with higher likelihood of the stage IV-nodal presentation. Patients with stage IV-nodal disease experienced superior survival (hazard ratio = 0.72, 95% CI: 0.66-0.78, p < 0.0001) than those with stage IV-single systemic metastases (reference group) and stage IV-multiorgan disease (hazard ratio = 1.30, 95% CI: 1.24-1.37)., Conclusions: Approximately 12% of patients with stage IV esophageal cancer lack systemic metastases at presentation. These patients with stage IV-nodal disease are more likely to receive treatment and experience superior survival. Further study of the stage IV-nodal population and consideration of a potential stage IV subclassification system is justified., (© 2022 The Authors.)

Importance: The 2017 international PACIFIC trial established a role for immunotherapy after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC). However, in the US, patients with NSCLC commonly differ from clinical trial populations in terms of age, health, access to care, and treatment course, which may all factor into the efficacy of immunotherapy., Objective: To determine the outcomes of immunotherapy use in unresectable stage III NSCLC in the general US population., Design, Setting, and Participants: This cohort study analyzed the National Cancer Database for patients diagnosed with clinical stage III NSCLC between 2015 and 2017 with follow-up through the end of 2018 who were treated with chemotherapy and radiation. Data were analyzed January 2022., Main Outcomes and Measures: Mortality hazard in a multivariable Cox proportional hazards model and survival among a propensity-matched sample treated with chemotherapy and radiation, with and without immunotherapy., Results: A total of 23 811 patients with clinical stage III NSCLC with median (IQR) age 66 (59-72) years met inclusion criteria (10 454 [43.9%] women; 564 [2.4%] Asian, 2930 [12.3%] Black, 20 077 [84.3%] White patients), including 209 (16.1%) patients with multiple comorbidities and 1297 (5.4%) immunotherapy recipients. Immunotherapy after chemotherapy and radiation was associated with reduced mortality (hazard ratio [HR], 0.74; 95% CI, 0.67-0.82; P < .001). Among a propensity-matched sample, immunotherapy was associated with superior 3-year survival (52% [1297 patients at 0 months, 56 patients at 36 months] vs 44% [2594 patients at 0 months, 173 patients at 36 months]; P < .001). The treatment of 833 patients who received immunotherapy (64.2%) differed from the PACIFIC trial protocol, including 221 patients (17.0%) who received radiation doses outside of the protocol range and 731 patients (56.4%) who started immunotherapy more than 6 weeks after radiation was completed. The survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75; 95% CI, 0.61-0.92). Among patients who received radiation outside the PACIFIC protocol range, the survival advantage of immunotherapy was not significant (HR, 0.87; 95% CI, 0.69-1.01)., Conclusions and Relevance: In this cohort study, immunotherapy after chemotherapy and radiation for stage III NSCLC was associated with a survival advantage in the general US population despite two-thirds of patients treated differently than the PACIFIC protocol. The findings suggest there may be flexibility in the timing of immunotherapy initiation after radiation; further study is warranted to clarify the clinical benefits of immunotherapy.

Importance: Clinical trials and compassionate use agreements provide selected patients with access to potentially life-saving treatments before approval by the Food and Drug Administration (FDA). Approval from the FDA decreases a number of access barriers; however, it is unknown whether FDA approval is associated with increases in the equitable use of novel therapies and reductions in disparities in use among patients with cancer in the US., Objective: To assess the association between FDA drug approval and disparities in the use of immunotherapy across health, sociodemographic, and socioeconomic strata before and after approval of the first checkpoint inhibitors for the treatment of patients with cancer in the US., Design, Setting, and Participants: This cohort study used data from the National Cancer Database to examine the use of immunotherapy across health, sociodemographic, and socioeconomic strata before and after FDA approval of the first checkpoint inhibitor therapies. A total of 402 689 patients 20 years or older who were diagnosed with stage IV non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma of the skin between January 1, 2007, and December 31, 2018 (specific years varied by tumor type), were included., Exposures: Patient health (Charlson-Deyo comorbidity score and age), sociodemographic characteristics (sex, race, and ethnicity), and socioeconomic (insurance status and household income based on zip code of residence) characteristics., Main Outcomes and Measures: The association of patient characteristics with receipt of immunotherapy was evaluated in the 4 years before and the 3 years immediately after FDA approval using multivariable logistic regression modeling., Results: Among 402 689 patients (median [IQR] age, 68 [60-76 years]; 225 081 men [55.9%]), 347 233 had NSCLC, 43 714 had RCC, and 11 742 patients had melanoma. A total of 47 527 patients (11.8%) were Black, 15 763 (3.9%) were Hispanic, 375 874 (93.3%) were non-Hispanic, 335 833 (83.4%) were White, and 16 553 (4.1%) were of other races. Before FDA approval, 6271 patients (3.2%) with NSCLC, 1155 patients (4.8%) with RCC, and 504 patients (8.6%) with melanoma received immunotherapy compared with 23 908 patients (15.6%) with NSCLC, 3890 patients (19.7%) with RCC, and 1143 patients (19.3%) with melanoma after FDA approval. Before FDA approval, sociodemographic and socioeconomic characteristics were associated with variable immunotherapy administration by tumor type. For example, among those with NSCLC, Black patients were less likely to receive immunotherapy than White patients (odds ratio [OR], 0.78; 95% CI ,0.71-0.85; P < .001); among those with RCC, uninsured patients were less likely to receive immunotherapy than privately insured patients (OR, 0.31; 95% CI, 0.20-0.48; P < .001). After FDA approval, most disparities persisted, but several narrowed (eg, Black patients with NSCLC: OR, 0.87 [95% CI, 0.83-0.91; P < .001]; uninsured patients with RCC: OR, 0.60 [95% CI, 0.48-0.75; P < .001]). Although many disparities remained, some gaps across socioeconomic characteristics appeared to widen (eg, patients with NSCLC in the lowest vs highest income quartile: OR, 0.80; 95% CI, 0.76-0.83; P < .001), and new gaps emerged (eg, Black patients with RCC: OR, 0.82; 95% CI, 0.72-0.93; P = .003)., Conclusions and Relevance: In this cohort study, disparities in immunotherapy use existed across a number of sociodemographic and socioeconomic characteristics among patients with NSCLC, RCC, and melanoma before FDA approval, including during the important period when clinical trials were accruing patients. Although FDA approval was associated with a significant increase in the use of immunotherapy, gaps persisted, suggesting that FDA approval may not eliminate disparities in the use of novel therapies.

Introduction: Available guidelines are inconsistent as to whether patients with newly diagnosed clinical stage II NSCLC should receive routine brain imaging., Methods: The National Cancer Database was queried for the prevalence of isolated brain metastases among patients with newly diagnosed NSCLC in 2016 and 2017. Patients with metastases in locations other than the brain were excluded. The prevalences were then stratified by clinical T and N classifications and further stratified into a summary stage, which was calculated based on T and N classifications. The summary stage represents the clinical stage that would have been available at the time of decision for brain imaging., Results: A total of 6,949 of 149,958 patients (4.6%) with clinical stages I, II, III, or brain-limited stage IV NSCLC had dissemination limited to the brain. As T and N stages increased, prevalence of brain metastases generally increased. Among patients with node-negative (N0) NSCLC, the prevalence of brain-only metastases increased from 1.2% in patients with T1a to 3.8% among patients with T4 ( p < 0.001). Among patients with T1a, the prevalence of brain-only metastases increased from 1.2% for patients with N0 to 7.9% for patients with N3 ( p < 0.001). The prevalence of brain-limited metastases generally increased with increasing summary stage. The prevalence of brain-only metastases among patients with stage IA was 1.7% whereas that among patients with stage IIIA was 6.7% ( p < 0.001). Of note, the prevalence of brain-limited metastases was approximately 6% for both summary stages II and III., Conclusions: Considering the similarity in prevalence of isolated brain metastases and the potential hazards associated with brain imaging in early stage NSCLC, practitioners may consider a more liberal use of brain imaging when interpreting conflicting guidelines., (© 2022 The Authors.)

Stylosanthes species are economically important tropical and subtropical forage legumes which are generally vulnerable to chilling and frost. Fine-stem stylo ( S. guianensis var. intermedia ) has the most superior cold tolerance among all stylo species. A REVEILLE ( RVE ) gene, SgRVE6 , was cloned from fine-stem stylo. Bioinformatic analysis suggests that SgRVE6 encodes a transcription factor of 292 amino acid residues, which belongs to the LATE ELONGATED HYPOCOTYL/CIRCADIAN CLOCK ASSOCIATED 1-LIKE (LCL) subgroup of RVE family and contains a SHAQKYF-class MYB domain and a LCL domain. SgRVE6 is universally expressed in root, stem and leaf tissues of fine-stem stylo and is rapidly up-regulated in all tested tissues under cold stress. Over-expressing SgRVE6 affects expression of 21 circadian clock genes, up-regulates expression of 6 nucleotide binding domain leucine-rich repeats (NB-LRR) encoding genes associated with tobacco cold tolerance, improves physiological responses to low temperature, and endows the transgenic tobaccos with higher tolerance to cold stress. This is the first time a study investigates the biological function of RVE6 in cold responses of plant species., (Copyright © 2020 Chen, Huang, Chen, Fu, Zhan, Ke, Zhang, Zhong and Xie.)

Spinal arteriovenous malformations (AVMs) comprise a group of complex vascular lesions whose treatment with microsurgery or transarterial embolization can be challenging. Stereotactic radiosurgery is a well-established treatment for intracranial AVMs, and spinal radiosurgery and fractionated radiotherapy are common treatments for spinal tumors of both primary and metastatic origin. The use of radiosurgery and fractionated radiotherapy for the treatment of spinal arteriovenous malformations, however, has been infrequently reported. Spinal stereotactic radiosurgery is emerging as a promising option for the treatment of these lesions. We conducted a systematic review of English language articles reporting one or more cases of spinal radiosurgery or fractionated radiotherapy for the treatment of spinal arteriovenous fistulas (AVFs) or arteriovenous malformations. Eight unique studies comprising 64 patients were identified. All treated lesions consisted primarily of spinal AVMs, either intramedullary or metameric. Most were treated with CyberKnife technology. Marginal doses in the most current studies ranged from 18 to 21 Gy given over 2-4 fractions. In aggregate, good outcomes were reported in 92.2% with no instances of post-treatment hemorrhage over a mean follow-up time of 46.8 months. Angiographic follow-up showed the nidus to be obliterated in 16%, decreased in 44.6%, and unchanged in 39.3%. Stereotactic radiosurgery for spinal arteriovenous malformations holds promise as a safe and potentially effective option in the treatment of these rare but complex lesions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Methods involving the use of mathematical models of competitive ligand-receptor binding to characterize mixtures of ligands in terms of compositions and properties of the component ligands have been developed. The associated mathematical equations explicitly relate component ligand physical-chemical properties and mole fractions to measurable properties of the mixture including steady state binding activity, 1/K d,apparent or equivalently 1/EC50, and kinetic rate constants k on,apparent and k off,apparent allowing: (1) component ligand physical property determination and (2) mixture property predictions. Additionally, mathematical equations accounting for combinatorial considerations associated with ligand assembly are used to compute ligand mole fractions. The utility of the methods developed is demonstrated using published experimental ligand-receptor binding data obtained from mixtures of afucosylated antibodies that bind FcγRIIIa (CD16a) to: (1) extract component ligand physical property information that has hitherto evaded researchers, (2) predict experimental observations, and (3) provide explanations for unresolved experimental observations. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:500-510, 2017., (© 2017 American Institute of Chemical Engineers.)

A full-length cDNA of phytoene desaturase (PDS) gene from Andrographis paniculata was obtained through RACE-PCR. The cDNA sequence consists of 2 224 bp with an intact ORF of 1 752 bp (GeneBank: KP982892), encoding a ploypeptide of 584 amino acids. Homology analysis showed that the deduced protein has extensive sequence similarities to PDS from other plants, and contains a conserved NAD ( H) -binding domain of plant dehydrase cofactor binding-domain in N-terminal. Phylogenetic analysis demonstrated that ApPDS was more related to PDS of Sesamum indicum and Pogostemon cablin. The semi-quantitative RT-PCR analysis revealed that ApPDS expressed in whole aboveground tissues with the highest expression in leaves. Virus induced gene silencing (VIGS) was performed to characterize the functional of ApPDS in planta. Significant photobleaching was not observed in infiltrated leaves, while the PDS gene has been down-regulated significantly at the yellowish area. To the best of our knowledge, this represents the first report of PDS gene cloning and functional characterization from A. paniculata, which lays the foundation for further investigation of new genes, especially that correlative to andrographolide biosynthetic pathway.

The theory of competitive ligand-receptor binding has been used to analyze the effect of afucosylation-based antibody heterogeneity on Fc-FcγRIIIa ligand-receptor binding activity. In vitro activity is found to represent a linear combination of the component antibody activities, weighted by the relative concentrations of the different afucosylated antibody forms. An analysis of ELISA binding activity data has allowed for the dissection of the activity contributions of the different afucosylated antibodies, revealing that the heterogeneous afucosylated antibody exhibits greater activity, on a per mole basis, when compared to the homogeneous afucosylated antibody. The ratio of the afucosylated antibody equilibrium dissociation constants is computed to be KAF /KA ≈ 0.6-0.9, where KAF and KA denote the dissociation equilibrium constant of the heterogeneous and the homogeneous afucosylated antibodies, respectively. Our analysis also reveals that, in general, activity scales quadratically with the afucosylated glycan content of a sample. Linear activity-afucosylated glycan fraction correlations reported in the literature are shown to represent specific cases of this general scaling and result from oversimplifying the underlying antibody concentration distributions. The implications of our findings for drug development are also discussed., (© 2015 American Institute of Chemical Engineers.)

Objective: To study the operative methods for fracture and dislocation of lower cervical spine with articular process interlocking., Methods: From Feb. 2002 to Feb. 2008, 57 patients with fracture and dislocation of the lower cervical spine with articular process interlocking were treated by operation involving interior, posterior and combining anterior and posterior approach, of whom there were 45 males and 12 females aged from 18 to 73 years old with average of 39.5 years. There were 35 patients caused by traffic accident, 17 patients by falling injury and 5 patienst by crash injury of heavy object. Injured cervical segment: there were 4 patienst with C3-C4, 13 patients with C4-C5, 32 patientst with C5-C6 and 8 patients with C6-C7. Fracture types of cervical dislocation: there were 32 patients with unilateral articular interlocking and 25 patients with bilateral articular interlocking. According to ASIA criteria the level of nerve injury was grade A in 9 patients,grade B in 17 patients, grade C in 19 patients and grade D in 12 patients. OPERATIVE METHODS: 14 patients were selected by anterior operation, 11 by posterior operation,and 32 by combining anterior and posterior operation., Results: All patients were followed up for 3 to 26 months averaged 11 months. According to ASIA criteria, all patients improved 1 to 2 grade. Patients with cervical fracture and dislocation recovered completely with normal cervical sequence and cervical curvature. There was no patients with cervical unstability. Bony fusion were found in the patients with anterior interbody fusion at 12 weeks after operation., Conclusion: The anterior operation was selected when one segment fractures on fresh and dislocation, or the cervical fracture and dislocation were reduction with traction, or the angulation deformity was severe. The posterior operation was selected when the cervical vertebral plate of articular facet fractures and the compression were from posterior, or multi-segment of cervical injured. The combining anterior and posterior operation was selected when the compression of spinal cord was from both side.