Racial and socioeconomic disparities in lung cancer screening in the United States: A systematic review.

Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer deaths. Lung cancer screening (LCS) reduces NSCLC mortality; however, a lack of diversity in LCS studies may limit the generalizability of the results to marginalized groups who face higher risk for and worse outcomes from NSCLC. Identifying sources of inequity in the LCS pipeline is essential to reduce disparities in NSCLC outcomes. The authors searched 3 major databases for studies published from January 1, 2010 to February 27, 2020 that met the following criteria: 1) included screenees between ages 45 and 80 years who were current or former smokers, 2) written in English, 3) conducted in the United States, and 4) discussed socioeconomic and race-based LCS outcomes. Eligible studies were assessed for risk of bias. Of 3721 studies screened, 21 were eligible. Eligible studies were evaluated, and their findings were categorized into 3 themes related to LCS disparities faced by Black and socioeconomically disadvantaged individuals: 1) eligibility; 2) utilization, perception, and utility; and 3) postscreening behavior and care. Disparities in LCS exist along racial and socioeconomic lines. There are several steps along the LCS pipeline in which Black and socioeconomically disadvantaged individuals miss the potential benefits of LCS, resulting in increased mortality. This study identified potential sources of inequity that require further investigation. The authors recommend the implementation of prospective trials that evaluate eligibility criteria for underserved groups and the creation of interventions focused on improving utilization and follow-up care to decrease LCS disparities.

Pilot study of a telehealth intervention for personalized self-management for eating symptoms after gastroesophageal cancer surgery.

BACKGROUND AND OBJECTIVES: Following gastric and esophageal cancer surgery, patients often experience significant, prolonged eating-related symptoms. One promising approach to help patients improve their eating-related quality of life (QOL) is through self-management coaching to aid in diet modification. We performed a randomized pilot study of a nutritionist-led telehealth intervention for the self-management of eating after gastroesophageal cancer surgery. METHODS: Patients who were within 30 days of resuming oral intake after undergoing surgery for gastric and/or esophageal cancer were consented and then randomized to the intervention or usual care. The intervention was performed by a nutritionist trained in self-management coaching and delivered in four telehealth sessions over 4 months. The following outcomes were measured at baseline and at 6 months after baseline: QOL (EORTC QLQC30), weight, body mass index, and sarcopenia. RESULTS: Fifty-three patients were enrolled. 22/27 usual care and 21/26 intervention patients completed the study for a retention rate of 81%. Differences between the intervention and control groups were not statistically significant, but the intervention group had indications of greater improvements in overall QOL as measured by EORTC QLQC30 Summary Score (8.7 vs. 2.3, p = 0.17) as well as greater improvements in 4/5 functional domains (p > 0.3). The intervention group also had slightly more weight gain (6 kg vs. 3 kg, p = 0.3) and less sarcopenia (3/16 vs. 9/18, p = 0.07). CONCLUSIONS: This pilot study demonstrated the feasibility and acceptability of a telehealth intervention for self-management of eating symptoms after gastroesophageal cancer surgery. There were trends toward improved overall QOL in the intervention group. A larger study is needed to validate the results.

The impact of the COVID-19 pandemic on care delivery and quality of life in lung cancer surgery.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) pandemic and associated restrictions have altered the delivery of surgical care. The purpose of this study was to explore the impact of COVID-19 on care delivery and quality of life (QOL) from the perspectives of lung cancer surgery patients, family caregivers (FCGs), and thoracic surgery teams. METHODS: Patients/FCGs enrolled in a randomized trial of a self-management intervention for lung cancer surgery preparation/recovery were invited to participate in this qualitative study. Patients/FCGs data were collected separately 1-month postdischarge. Interviews were also conducted with thoracic surgery team members. Content analysis approaches were used to develop themes. RESULTS: Forty-one respondents including 19 patients, 18 FCGs, three thoracic surgeons, and one nurse practitioner participated in the study. Patient themes included isolation, psychological distress, delayed/impacted care, and financial impact. FCGs themes included caregiving challenges, worry about COVID-19, financial hardship, isolation, and physical activity limitations. Surgical team themes included witnessing patient/FCG's distress, challenges with telehealth, communication/educational challenges, and delays in treatment. CONCLUSIONS: COVID-19 had a varied impact on care delivery and QOL for lung cancer surgery dyads. Some dyads reported minimal impact, while others experienced added psychological distress, isolation, and caregiving challenges. Surgical teams also experienced challenges in the approach used to provide care.

Pilot study of a telehealth perioperative physical activity intervention for older adults with cancer and their caregivers.

BACKGROUND: Older adults undergoing cancer surgery are at greater risk for poor postoperative outcomes. Caregivers also endure significant burden. Participation in perioperative physical activity may improve physical functioning and enhance overall well-being for both patients and caregivers. In this study, we assessed the feasibility of a personalized telehealth intervention to enhance physical activity for older (≥ 65 years) gastrointestinal (GI) and lung cancer surgery patients/caregivers. METHODS: Participants completed four telehealth sessions with physical therapy/occupational therapy (PT/OT) before surgery and up to 2 weeks post-discharge. Outcomes included preop geriatric assessment, functional measures, and validated measures for symptoms and psychological distress. Pre/post-intervention trends/trajectories for outcomes were explored. RESULTS: Thirty-four patient/caregiver dyads (16, GI; 18, lung) were included. Accrual rate was 76% over 8 months; retention rate was 88% over 2 months. Median for postop of a 6-min walk test, timed up and go, and short physical performance battery test scores improved from baseline to postop. Participant satisfaction scores were high. CONCLUSION: Our conceptually based, personalized, multimodal, telehealth perioperative physical activity intervention for older patient/caregiver dyads is feasible and acceptable. It offers an opportunity to improve postoperative outcomes by promoting functional recovery through telehealth, behavior change, and self-monitoring approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03267524.

Generation of a selectable marker free, highly expressed single copy locus as landing pad for transgene stacking in sugarcane.

KEY MESSAGE: A selectable marker free, highly expressed single copy locus flanked by insulators was created as landing pad for transgene stacking in sugarcane. These events displayed superior transgene expression compared to single-copy transgenic lines lacking insulators. Excision of the selectable marker gene from transgenic sugarcane lines was supported by FLPe/FRT site-specific recombination. Sugarcane, a tropical C4 grass in the genus Saccharum (Poaceae), accounts for nearly 80% of sugar produced worldwide and is also an important feedstock for biofuel production. Generating transgenic sugarcane with predictable and stable transgene expression is critical for crop improvement. In this study, we generated a highly expressed single copy locus as landing pad for transgene stacking. Transgenic sugarcane lines with stable integration of a single copy nptII expression cassette flanked by insulators supported higher transgene expression along with reduced line to line variation when compared to single copy events without insulators by NPTII ELISA analysis. Subsequently, the nptII selectable marker gene was efficiently excised from the sugarcane genome by the FLPe/FRT site-specific recombination system to create selectable marker free plants. This study provides valuable resources for future gene stacking using site-specific recombination or genome editing tools.

Overexpression of Flap Endonuclease 1 Correlates with Enhanced Proliferation and Poor Prognosis of Non-Small-Cell Lung Cancer.

Flap endonuclease 1 (FEN1) plays a crucial role in both DNA replication and damage repair. In this study, FEN1 expression and its clinical-pathologic significance in non-small-cell lung cancer (NSCLC) was investigated. Quantitative RT-PCR and immunohistochemistry analysis identified that both FEN1 mRNA and protein were highly overexpressed in about 36% of 136 cancer tissues compared to adjacent tissues, in which FEN1 was generally undetectable. Notably, patients with FEN1-overexpressed cancers were prone to have poor differentiation and poor prognosis. A strong positive correlation between the levels of FEN1 and Ki-67 staining was identified in these NSCLC tissues (r = 0.485), suggesting overexpressed FEN1 conferred a proliferative advantage to NSCLC. Furthermore, knockdown of FEN1 resulted in G1/S or G2/M phase cell cycle arrest and suppressed in vitro cellular proliferation in NSCLC cancer cells. Consistently, a selective FEN1 inhibitor was shown to effectively inhibit cellular proliferation of NSCLC cells in a dose-dependent manner. Additionally, knockdown of FEN1 significantly attenuated homologous DNA repair efficiency and enhanced cytotoxic effects of cisplatin in NSCLC cells. Taken together, these findings have indicated that overexpressed FEN1 represents a prognostic biomarker and potential therapeutic target for NSCLC treatment, which warrants further study.

Targeting histone methyltransferase G9a inhibits growth and Wnt signaling pathway by epigenetically regulating HP1α and APC2 gene expression in non-small cell lung cancer.

BACKGROUND: Dysregulated histone methyltransferase G9a may represent a potential cancer therapeutic target. The roles of G9a in tumorigenesis and therapeutics are not well understood in non-small cell lung cancer (NSCLC). Here we investigated the impact of G9a on tumor growth and signaling pathways in NSCLC. METHODS: Immunohistochemistry analyzed G9a expression in NSCLC tissues. Both siRNA and selective inhibitor were used to target G9a. The impact of targeting G9a on key genes, signaling pathways and growth were investigated in NSCLC cells by RNA sequencing analysis, rescue experiments, and xenograft models. RESULTS: Overexpression of G9a (≥ 5% of cancer cells showing positive staining) was found in 43.2% of 213 NSCLC tissues. Multiple tumor-associated genes including HP1α, APC2 are differentially expressed; and signaling pathways involved in cellular growth, adhesion, angiogenesis, hypoxia, apoptosis, and canonical Wnt signaling pathways are significantly altered in A549, H1299, and H1975 cells upon G9a knockdown. Additionally, targeting G9a by siRNA-mediated knockdown or by a selective G9a inhibitor UNC0638 significantly inhibited tumor growth, and dramatically suppressed Wnt signaling pathway in vitro and in vivo. Furthermore, we showed that treatment with UNC0638 restores the expression of APC2 expression in these cells through promoter demethylation. Restoring HP1α and silencing APC2 respectively attenuated the inhibitory effects on cell proliferation and Wnt signaling pathway in cancer cells in which G9a was silenced or suppressed. CONCLUSIONS: These findings demonstrate that overexpressed G9a represents a promising therapeutic target, and targeting G9a potentially suppresses growth and Wnt signaling pathway partially through down-regulating HP1α and epigenetically restoring these tumor suppressors such as APC2 that are silenced in NSCLC.

Preparing Cancer Patients and Family Caregivers for Lung Surgery: Development of a Multimedia Self-Management Intervention.

The surgical treatment of lung malignancies often results in persistent symptoms, psychosocial distress, and decrements in quality of life (QOL) for cancer patients and their family caregivers (FCGs). The potential benefits of providing patients and FCGs with preparatory education that begins in the preoperative setting have been explored in multiple medical conditions, with positive impact observed on postoperative recovery, psychological distress, and QOL. However, few studies have explored the benefits of preparatory educational interventions to promote self-management in cancer surgery, including lung surgery. This paper describes the systematic approach used in the development of a multimedia self-management intervention to prepare cancer patients and their FCGs for lung surgery. Intervention development was informed by (1) contemporary published evidence on the impact of lung surgery on patients and FCG, (2) our previous research that explored QOL, symptoms, and caregiver burden after lung surgery, (3) the use of the chronic care self-management model (CCM) to guide intervention design, and (4) written comments and feedback from patients and FCGs that informed intervention development and refinement. Pilot-testing of the intervention is in process, and a future randomized trial will determine the efficacy of the intervention to improve patient, FCG, and system outcomes.

Loss of H2B monoubiquitination is associated with poor-differentiation and enhanced malignancy of lung adenocarcinoma.

Deregulated monoubiquitination of histone H2B (H2Bub1), mainly catalyzed by E3 ubiquitin-protein ligase RNF20/RNF40 complex, may play an important role in cancer. Here we investigate potential roles of H2Bub1 and the underlying mechanisms through which it contributes to cancer development and progression in lung adenocarcinoma. We show that downregulation of H2Bub1 through RNF20 knockdown dramatically decreases H3K79 and H3K4 trimethylation in both normal and malignant lung epithelial cell lines. Concurrently, global transcriptional profiling analysis reveals that multiple tumor-associated genes such as CCND3, E2F1/2, HOXA1, Bcl2 modifying factor (BMF), Met, and Myc; and signaling pathways of cellular dedifferentiation, proliferation, adhesion, survival including p53, cadherin, Myc, and anti-apoptotic pathways are differentially expressed or significantly altered in these lung epithelial cells upon downregulation of H2Bub1. Moreover, RNF20 knockdown dramatically suppresses terminal squamous differentiation of cultured bronchial epithelial cells, and significantly enhances proliferation, migration, invasion, and cisplatin resistance of lung cancer cells. Furthermore, immunohistochemistry analysis shows that H2Bub1 is extremely low or undetectable in >70% of 170 lung adenocarcinoma samples. Notably, statistical analysis demonstrates that loss of H2Bub1 is significantly correlated with poor differentiation in lung adenocarcinoma (p = 0.0134). In addition, patients with H2Bub1-negative cancers had a trend towards shorter survival compared with patients with H2Bub1-positive cancers. Taken together, our findings suggest that loss of H2Bub1 may enhance malignancy and promote disease progression in lung adenocarcinoma probably through modulating multiple cancer signaling pathways.

The triptolide derivative MRx102 inhibits Wnt pathway activation and has potent anti-tumor effects in lung cancer.

BACKGROUND: The natural compound triptolide has been shown to decrease cell proliferation and induce apoptosis and cellular senescence. We previously demonstrated that triptolide decreases tumor formation and metastasis of human non-small cell lung cancer cells (NSCLC). Due to the toxicity of triptolide, derivatives of the natural compound have been developed that show more favorable toxicity profiles and pharmacokinetics in animal models. The purpose of this study was to evaluate MRx102 as a novel therapeutic for lung cancer. METHODS: Mice injected subcutaneously with H460 lung cancer cells were treated with MRx102 or carboplatin to determine the effect of MRx102 on tumor formation in comparison to standard treatment. Patient-derived xenografts (PDX) with different WIF1 expression levels were treated with MRx102 or cisplatin. We tested the effects of MRx102 treatment on migration and invasion of lung cancer cells using Transwell filters coated with fibronectin and Matrigel, respectively. Tail vein injections using H460 and A549 cells were performed. RESULTS: Here we report that the triptolide derivative MRx102 significantly decreases NSCLC proliferation and stimulates apoptosis. Further, MRx102 potently inhibits NSCLC haptotactic migration and invasion through Matrigel. In vivo, NSCLC tumor formation and metastasis were greatly decreased by MRx102 treatment. The decrease in tumor formation by MRx102 in the patient-derived xenograft model was WIF1-dependent, demonstrating that MRx102 is a potent inhibitor of the Wnt pathway in low WIF1 expressing NSCLC patient tumors. CONCLUSIONS: These results indicate that MRx102 has potent antitumor effects both in vitro and in vivo, and is a potential novel therapy for the treatment of NSCLC.

Rates of lymph node metastasis and survival in T1a gastric adenocarcinoma in Western populations.

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are widely accepted in Asia for treatment of early gastric cancer (EGC). Few studies have examined lymph node (LN) metastasis of EGC in Western populations. We sought to examine EGC and LN metastasis in a heterogeneous Western population. METHODS: Patients with surgically resected, histologically confirmed American Joint Committee on Cancer T1a gastric adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2002 to 2012. Patients were excluded if they had stage IV disease, had multiple primary cancers, or received neoadjuvant therapy. Rates of LN metastasis were calculated, and survival analyses were performed. RESULTS: Of 923 patients in the cohort, 72 (7.8%) had at least 1 positive LN on final pathology. When stratified by race, Asian/Pacific Islanders (APIs) demonstrated the lowest rate of LN metastases (n = 17/327, 5.2%), followed by Hispanics (n = 12/171, 7.0%), whites (n = 27/278, 9.7%), and blacks (n = 16/147, 10.9%). The highest rates of stage IA disease were observed in API (93.9%) and Hispanic (92.4%) patients, followed by white (89.9%) and black (87.1%) patients (P = .04). Survival analysis of T1a gastric cancer patients by race/ethnicity showed that 5-year overall survival was highest for API patients (API, 88%; Hispanic, 81%; black, 79%; and white, 77%; P < .01). CONCLUSIONS: The rate of LN metastasis in T1a gastric cancers in the United States is higher than the rates reported in Asia. Survival outcomes in T1a gastric cancers varied significantly by race, suggesting that definitive endoscopic treatment may not be appropriate for all patients in the United States.

Palliative care and spiritual well-being in lung cancer patients and family caregivers.

BACKGROUND: Spiritual well-being is an important dimension of quality of life (QOL) and is a core component of quality oncology and palliative care. In this analysis, we aimed to describe spiritual well-being outcomes in a National Cancer Institute (NCI)-supported Program Project that tested the effectiveness of an interdisciplinary palliative care intervention in lung cancer patients and their family caregivers (FCGs). METHODS: Patients undergoing treatments for NSCLC and their FCGs were enrolled in a prospective, quasi-experimental study. Patients and FCGs in the intervention group were presented at interdisciplinary care meetings and received four educational sessions that included one session focused on spiritual well-being. Spiritual well-being for patients was measured using the FACIT-Sp-12, and FCG spiritual well-being was measured using the COH-QOL-FCG spiritual well-being subscale. Multivariate analysis of covariance was undertaken for subscale and item scores at 12 weeks, controlling for baseline, by religious affiliations (yes or no) and group assignment. RESULTS: Religiously affiliated patients reported better scores in the Faith subscale and items on finding strength and comfort in faith and spiritual beliefs compared to non-affiliated patients. Non-affiliated patients had better scores for feeling a sense of harmony within oneself. By group, patients who received the intervention had significantly better scores for the Meaning/Peace subscale. CONCLUSIONS: Our findings support the multidimensionality of spiritual well-being that includes constructs such as meaning and faith for lung cancer patients and FCGs with or without religious affiliations. Palliative care interventions should include content that targets the spiritual needs of both patients and FCGs. Copyright © 2015 John Wiley & Sons, Ltd.

A Population-Based Examination of the Surgical Outcomes for Patients with Esophageal Sarcoma.

BACKGROUND: Esophageal sarcoma (ES) is a rare malignancy. The literature is limited to small case series and reports. This study used a population data set to study the characteristics, treatments, surgical outcomes, and prognostic factors for survival among ES patients. METHODS: The study identified 178 ES cases (0.3 %) and 63,548 esophageal carcinoma (EC) cases (99.7 %) including adenocarcinoma and squamous cell carcinoma using the Surveillance, Epidemiology, and End Results (SEER) Registry (1973-2011). Characteristics and therapeutics were compared between ES and EC. Survival data were analyzed using Kaplan-Meier estimation. Uni- and multivariate Cox proportional hazard models determined predictors of 5-year overall survival (OS). RESULTS: Compared with the EC patients, the ES patients were more likely to be women, to have localized tumors, and to undergo surgery but less likely to receive radiation (p < 0.001). The most common histologies were carcinosarcoma, leiomyosarcoma, and gastrointestinal stromal tumor (GIST). The 5-year OS for the ES patients was 38 % compared with 17 % for the EC patients (p < 0.001). The median survival period for the ES and EC surgical patients with locoregional disease was respectively 50 and 24 months. The ES patients with nonmetastatic disease who received surgery had better OS than those who did not (37 vs. 14 %; p < 0.0001). In the multivariate analysis, age and advanced stage conferred worse OS, whereas GIST histology and surgery were favorable predictors for OS. CONCLUSION: The ES patients were more likely to have localized disease, to be treated with surgery, and to have better OS than the EC patients. The survival benefit of surgery suggests that surgery should be the primary treatment for ES patients with resectable disease, particularly those with GIST.

Rapid Advances in Resectable Non-Small Cell Lung Cancer: A Narrative Review.

Importance: A series of high-profile clinical trials for patients with resectable early-stage non-small cell lung cancer (NSCLC) have recently changed the standard of care in this setting. Specifically, studies have demonstrated statistically and clinically significant improvements in efficacy with the targeted therapy for adjuvant osimertinib in patients with resected NSCLC harboring an epidermal growth factor receptor (EGFR) genomic abnormality (GA), whereas trials with chemotherapy combined with nivolumab in the neoadjuvant setting and others testing atezolizumab or pembrolizumab as adjuvant therapy have all demonstrated improvements in event-free survival (EFS) (for neoadjuvant therapy) or disease-free survival (DFS) (for adjuvant therapy). These trials introduce many open questions about how to apply these findings in clinical practice. Observations: Treatment with adjuvant osimertinib for 3 years was associated with significant improvement in both DFS and overall survival (OS), but the erosion of the DFS benefit after the duration of treatment ends suggests a potential value for more longitudinal treatment. The potential value of highly effective targeted therapies as adjuvant therapy for other GAs has a compelling rationale but no data at this time. Adjuvant atezolizumab or pembrolizumab, generally administered for 1 year after postoperative chemotherapy, are appropriate considerations, but only atezolizumab for patients with tumor programmed death-ligand 1 (PD-L1) levels of 50% has demonstrated a benefit in OS. Neoadjuvant chemotherapy with nivolumab offers a strong EFS benefit, a shorter interval of treatment, and radiographic and pathologic feedback for patients with resectable stage IB to IIIA NSCLC, although very recent randomized clinical trials of perioperative immunotherapy both combined with chemotherapy preoperatively and administered postoperatively highlight the debatable value of adjuvant immunotherapy after prior chemoimmunotherapy. Improved tumor shrinkage rates with neoadjuvant chemoimmunotherapy suggest the possibility that criteria for resectability may potentially be redefined in anticipation of a good response to neoadjuvant chemoimmunotherapy. Conclusions and Relevance: Developments in resectable NSCLC have arrived so rapidly that they have also created practical challenges of identifying optimal patients and prioritizing options among these new competing standards. In some cases, practical management requires clinical judgment and discussion with the patient to cover the gaps in prospective data. Caution should be exerted when extrapolating beyond the available data.

An esophagectomy surgical Apgar score-based nomogram-a risk-based postoperative triage system: a phase II randomised trial.

Background: The esophagectomy surgical Apgar score (eSAS) has been found to be a predictor of postoperative complications in esophagectomy. In our previous study, we built a graphic nomogram based on eSAS and demonstrated that it can effectively predict the risk of major morbidity after esophagectomy. In this study, we aimed to assess the benefits of using an eSAS-based nomogram model as a postoperative risk-based triage system for patients undergoing esophagectomy. Methods: We enrolled 119 patients diagnosed with esophageal carcinoma and randomly assigned them to a nomogram group (NG) or control group (CG) from January 2019 to December 2020. Patients in the NG were assigned to a low-risk group and high-risk group based on the nomogram. Patients in the high-risk group were admitted to the intensive care unit (ICU) after esophagectomy. Risk estimation in the CG patients was based on the surgeon's clinical experience. Thirty-day major complications, postoperative hospital stay, hospital costs, and quality of life (QOL) during the follow-up were compared between the two groups. Results: Baseline clinicopathological characteristics were comparable between the NG (n=58) and CG (n=61). All patients underwent esophagectomy. Postoperative complications were significantly higher in the CG (30, 49.2%) than in the NG (14, 24.1%) (P=0.008), with pneumonia being the most common (CG: 23, 37.7%; NG: 12, 20.7%; P=0.042). There was no significant difference in anastomotic leakage (NG: 1, 1.7%; CG: 6, 9.8%; P=0.12). Postoperative median hospital stay was shorter in the NG (14 days) than in the CG (16 days) (P=0.041). Hospital costs (NG: ¥60,045.1; CG: ¥63,961.5; P=0.21) and postoperative QOL did not differ significantly between groups. Conclusions: An eSAS-based nomogram as a triage system can reduce the overall occurrence of postoperative complications and shorten postoperative hospital stay without increasing hospital costs. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900021636.

The value of perioperative physical activity in older patients undergoing surgery for lung cancer.

INTRODUCTION: With a median age at diagnosis of 70, lung cancer represents an enormous public health problem among older Americans. An estimated 19,000 people age 65 and older undergo lung cancer surgery annually in the US. Older adults undergoing lung cancer surgery are often frail with limited physiologic reserves, multi-morbidities, and functional impairments. Physical function, dyspnea, and quality of life return to baseline slower in older adults compared with younger adults after lung surgery. AREAS COVERED: In this review, we summarize available data about perioperative physical activity interventions that may improve outcomes for older adults undergoing lung cancer surgery. We also review the limitations of existing studies and discuss emerging data on the roles of telehealth and family caregiver inclusion in peri-operative physical activity interventions. EXPERT OPINION: We propose that future perioperative physical activity interventions in older adults undergoing lung cancer surgery should include a comprehensive geriatric assessment to guide personalized interventions. Interventions should be conceptually based, with a focus on enhancing self-efficacy, motivation, and adherence through classic behavior change strategies that are proven to impact outcomes. Finally, interventions should be designed with attention to feasibility and scalability. Exercise programs delivered via telehealth (telephone or tele-video) may improve access and convenience for patients.

Long-term clinical outcomes and prognosis after definitive radiotherapy for patients with cervical esophageal squamous cell carcinoma: a single-institution retrospective study.

Background: Definitive radiotherapy has become a more common treatment for cervical esophageal squamous cell carcinoma (CESCC), but data about long-term clinical outcomes is still relatively sparse. The purpose of this study was to describe long-term clinical outcomes after definitive radiotherapy for CESCC, and identify the prognostic factors influencing these outcomes. Methods: We retrospectively analyzed all patients who received definitive radiotherapy for CESCC at our institution between 2006 and 2014. The overall survival (OS) rate, locoregional failure-free survival (LRFFS) rate, and toxicities were retrospectively evaluated during long-term follow-up. Univariate and multivariate analyses were performed to identify prognostic factors. Results: A total of 120 patients were included for analysis. The median prescribed radiation dose for the gross tumor and metastatic lymph nodes was 60 Gy. Elective nodal irradiation (ENI) was performed on 99 patients (83%); 90 patients (75%) received concurrent chemotherapy. The OS rates were 22.7% at 5 years and 14.9% at 8 years. The LRFFS rates at 3, 5, and 8 years were 27.5%, 21.7%, and 15.0%, respectively. The univariate analysis suggested that N classification and non-regional lymph node metastasis (M1Lym) status were independent risk factors for overall survival (P<0.01). A dose of more than 60 Gy didn't have a statistically significant influence in the multivariate analysis, although a total dose of more than 60 Gy was associated with improved survival in the univariate analysis. Concurrent chemotherapy was not associated with OS or LRFFS time in the univariate or multivariate analysis. A total of 74 patients (61.7%) experienced locoregional treatment failure. The most commonly documented acute toxicities were grade 1 and grade 2 toxicities in 61 patients (50.8%). There were 2 patients diagnosed with hypothyroidism as a late toxicity event. Conclusions: Definitive radiotherapy is a reasonable curative treatment option with laryngopharyngeal preservation for CESCC patients. Radical treatments for lymph node metastases may improve the OS and LRFFS times. Monitoring for thyroid function may be warranted during long-term follow-up.

Social determinants of health and lung cancer surgery: a qualitative study.

Introduction: Social determinants of health (SDOH) are non-clinical factors that may affect the outcomes of cancer patients. The purpose of this study was to describe the influence of SDOH factors on quality of life (QOL)-related outcomes for lung cancer surgery patients. Methods: Thirteen patients enrolled in a randomized trial of a dyadic self-management intervention were invited and agreed to participate in semi-structured key informant interviews at study completion (3 months post-discharge). A conventional content analysis approach was used to identify codes and themes that were derived from the interviews. Independent investigators coded the qualitative data, which were subsequently confirmed by a second group of independent investigators. Themes were finalized, and discrepancies were reviewed and resolved. Results: Six themes, each with several subthemes, emerged. Overall, most participants were knowledgeable about the concept of SDOH and perceived that provider awareness of SDOH information was important for the delivery of comprehensive care in surgery. Some participants described financial challenges during treatment that were exacerbated by their cancer diagnosis and resulted in stress and poor QOL. The perceived impact of education varied and included its importance in navigating the healthcare system, decision-making on health behaviors, and more economic mobility opportunities. Some participants experienced barriers to accessing healthcare due to insurance coverage, travel burden, and the fear of losing quality insurance coverage due to retirement. Neighborhood and built environment factors such as safety, air quality, access to green space, and other environmental factors were perceived as important to QOL. Social support through families/friends and spiritual/religious communities was perceived as important to postoperative recovery. Discussion: Among lung cancer surgery patients, SDOH factors can impact QOL and the patient's survivorship journey. Importantly, SDOH should be assessed routinely to identify patients with unmet needs across the five domains. SDOH-driven interventions are needed to address these unmet needs and to improve the QOL and quality of care for lung cancer surgery patients.

Ocular pulse amplitude (OPA) in canine ADAMTS10-open-angle glaucoma (ADAMTS10-OAG).

Introduction: The role of ocular rigidity and biomechanics remains incompletely understood in glaucoma, including assessing an individual's sensitivity to intraocular pressure (IOP). In this regard, the clinical assessment of ocular biomechanics represents an important need. The purpose of this study was to determine a possible relationship between the G661R missense mutation in the ADAMTS10 gene and the ocular pulse amplitude (OPA), the difference between diastolic and systolic intraocular pressure (IOP), in a well-established canine model of open-angle glaucoma (OAG). Methods: Animals studied included 39 ADAMTS10-mutant dogs with different stages of OAG and 14 unaffected control male and female dogs between 6 months and 12 years (median: 3.2 years). Dogs were sedated intravenously with butorphanol tartrate and midazolam HCl, and their IOPs were measured with the Icare® Tonovet rebound tonometer. The Reichert Model 30™ Pneumotonometer was used to measure OPA. Central corneal thickness (CCT) was measured via Accutome® PachPen, and A-scan biometry was assessed with DGH Technology Scanmate. All outcome measures of left and right eyes were averaged for each dog. Data analysis was conducted with ANOVA, ANCOVA, and regression models. Results: ADAMTS10-OAG-affected dogs displayed a greater IOP of 23.0 ± 7.0 mmHg (mean ± SD) compared to 15.3 ± 3.6 mmHg in normal dogs (p < 0.0001). Mutant dogs had a significantly lower OPA of 4.1 ± 2.0 mmHg compared to 6.5 ± 2.8 mmHg of normal dogs (p < 0.01). There was no significant age effect, but OPA was correlated with IOP in ADAMTS10-mutant dogs. Conclusion: The lower OPA in ADAMTS10-mutant dogs corresponds to the previously documented weaker and biochemically distinct posterior sclera, but a direct relationship remains to be confirmed. The OPA may be a valuable clinical tool to assess ocular stiffness and an individual's susceptibility to IOP elevation.