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Social distancing has been recommended by the Centers for Disease Control and Prevention to avoid exposure to SARS-CoV-2 ( Epidemiol Prev 2020;44:353-362).Cancer patients on or after active therapy seem to be more prone to COVID being symptomatic and life-threatening. When evaluating cancer patients' risk of acquiring COVID, it is essential to know the behavior of cancer patients that will affect their risk of exposure. However, it is not known to what degree social distancing is practiced by cancer patients compared with noncancer patients and what factors lead to the decision to distance oneself.After a pilot phase using patients' MyChart messaging, links to the electronic questionnaires were texted to patients using Twillio. Responses were stored on REDCap (Vanderbilt University, Nashville, TN). Six questions about their social distancing behavior and mask wearing were posed and responses were compared between cancer and noncancer patients. Demographics, comorbidities, and a questionnaire about anxiety (Generalized Anxiety Disorder 7-item scale) were recorded. To assess differences between cancer and noncancer groups, Bonferroni-corrected χ 2 tests and proportions confidence intervals were used.The pilot survey was sent in mid-2020 and the full survey followed in January 2021 during a high community COVID incidence. Three hundred eighty-seven cancer patients (32.4% responded) and 503 noncancer patients (22.9% responded) completed the survey. Questions about leaving their houses, driving, shopping, friends, and family indicated that patients with cancer are more cautious ( P0.001). Cancer patients were up to 20% more likely to distance themselves. No difference was seen in wearing a mask-both groups wore approximately 90% of the time. Most respondents were female (63% versus 71%). Cancer patients were older (60 y, 69% versus 45%) and less likely to work (52% versus 31%) or less likely to be White collar workers (21% versus 38%). In both groups, 54% marked "not at all anxious."Cancer patients' responses revealed a distancing behavior that would likely lower the risk exposure to SARS-CoV-2. It is unclear which of the demographic differences would account for this behavior, although remarkably anxiety was not a clear motivating factor. The high acceptance of masks is encouraging. Early publications during the pandemic and patient education suggesting a higher COVID risk for cancer patients may have reduced risk prone behavior. Considering COVID's impact on the vulnerable cancer population and uncertainty in immunosuppressed patients about clearing the virus or adequately responding to a vaccine, further studies about health behavior and health promotion during the pandemic are needed.

Promoting health-related quality of life (HRQOL) is a primary goal of lung cancer treatment. Trauma history and distress can negatively impact HRQOL.A cross-sectional design examined the associations of trauma history, cancer-specific distress, and HRQOL.Sixty lung cancer patients completed questionnaires on trauma history including the number and severity of traumatic events experienced. Cancer-specific distress, HRQOL, and depression were also reported.As hypothesized, trauma history and cancer-specific distress were negatively associated with HRQOL (allRetrospectively-reported trauma was linked with poorer HRQOL in lung cancer patients.Interventions aimed at improving lung cancer patients' HRQOL should consider the possible role of trauma history (both frequency and distress).

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage–mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti–PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non–small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound β-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy.

Small cell lung cancer (SCLC) is an aggressive disease treated as soon as possible given its rapid doubling time. Evidence for the appropriate time to chemotherapy initiation (TCI) for SCLC is lacking. This study evaluated TCI in SCLC on a national level.The National Cancer Database identified 64,491 SCLC patients treated with chemotherapy from 2010 to 2014. Factors associated with TCI were identified with multiple linear regression analyses. TCI was categorized into 4 groups using cutoff points of 7, 14, and 28 days. Using these categories, median overall survival and log-rank test was used for univariate analysis of the survival outcome and the Cox model was used for multivariate analysis.Median TCI was 18 days with 21% treated ≤7 days, 21% in 8 to 14 days, 30% 15 to 28 days, and 28%28 days from diagnosis. Younger age, white race, no insurance, more comorbidities, and higher stage were associated with shorter TCI. Median overall survival for TCI within 7 days was 8.2 months, 8 to 14 days was 9.2 months, 15 to 28 days was 10.3 months, and28 days was 10.8 months (P0.001). In the multivariate analysis, increased TCI was associated with improved survival across all stages. Among stage IV patients, compared with TCI≤7 days, the hazard ratio (HR) is 0.92 (P0.001) for 8 to 14 days, HR 0.82 (P0.001) for 15 to 28 days, and HR 0.77 (P0.001) for28 days of TCI. Results were similar for stage III and for stages I+II.Our results show worse survival with shorter TCI. This provides evidence to inform a discussion regarding appropriate treatment timing and individualizing treatment.

Objectives Lung cancer screening with low dose computed-tomography (LDCT) is currently recommended for high-risk populations based on mortality benefit shown in the National Lung Screening Trial (NLST). This study evaluated performance of a community-based lung cancer screening program in a Histoplasma endemic region. Materials and Methods Demographic and clinical information was collected through retrospective review of patients in the Lung Cancer Screening program of a Kentucky (Histoplasma endemic region) health system from 2016 and 2017. A positive LDCT screen is defined as Lung-RADS version 1.0 assessment categories 3 or 4. Patients characteristics, initial screening results and follow up were analyzed and compared to NLST results. Results A total of 4500 LDCT screens were performed in 2016 (39%) and 2017 (61%) with 43% adherence rate to repeat annual screen in 2017. Mean age of patients was 64 years, with majority being females (54%) and current smokers (69%) with average 52-pack year smoking history. The rate of positive LDCT was 13.3% (600) varying based on baseline (14.6%) and annual (9.5%) screen. A total of 70 lung cancers were diagnosed among all positive LDCT screens (11.7%) with a false positive rate of 12%. Conclusions Baseline positive screens in our study are similar to NLST data with Lung-RADS criteria implementation (14.6% vs 13.6%, p = 0.15) despite being a Histoplasma endemic region. Our study shows a successful performance of a community-based lung cancer screening program in a Histoplasma endemic region.

Background Since 2013, the United States Preventive Services Task Force has recommended annual screening for lung cancer in high-risk patients with low-dose computed tomography (LDCT). Current literature has provided estimates of the lung cancer screening rate and only prior to appropriate insurance coverage for LDCTs. The aim of this study was to use newly established registry data to assess the lung cancer screening rate across the United States. Materials and Methods Using data from the Lung Cancer Screening Registry provided by the American College of Radiology in 2016, we collected the total number of LDCT screens performed from all 1962 accredited radiographic screening sites. The 2015 National Health Interview Survey was used to estimate screening eligible smokers per United States Preventive Services Task Force criteria. These data were compared to calculate screening rate. Results In 2016, 2.0% of 7.6 million eligible smokers were screened. Rates varied by region from 1.1% in the West to 3.9% in the Northeast. The South consisted of 40.4% of eligible smokers and the most accredited screening sites (37%); however, their screening rate was among the lowest (1.7%) in the nation. Smoking cessation counseling was offered to 84% of screened current smokers prior to receiving LDCTs. Conclusions Lung cancer screening remains heavily underutilized despite guideline recommendation since 2013, insurance coverage, and its potential to prevent thousands of lung cancer deaths annually.

Small-cell lung cancer (SCLC) is an aggressive disease with poor survival and rapid doubling time. Current practice is to treat SCLC as soon as possible but evidence on appropriate timing of treatment from diagnosis (TTD) is lacking. This is a retrospective analysis of SCLC patients from the 2012 to 2015 Kentucky Cancer Registry. Data collected included age at diagnosis, stage, gender, race, insurance and treatment. Factors and survival associated with TTD were identified with logistic regression analyses and Cox proportional hazards models. Among the 2992 SCLC patients, 2371 (79%) of SCLC patients were treated with one or more treatment modalities. Among treated patients, 93% received chemotherapy ± radiation with the mean TTD of 18 days. Most patients (80%) have TTD of ≤ 4 weeks with 33% treated within 1 week, 20% 1-2 weeks, and 27% 2-4 weeks from diagnosis. Delay in treatment (TTD 4 weeks) was less in stage III and IV disease (odds ratio: 0.33 and 0.27 respectively, p 0.01) but not significantly associated with age, race, gender, and insurance. One and two-year survival of patients with TTD ≤ 4 weeks was significantly worse when compared to 4 weeks (hazard ratio = 1.43, 95% CI 1.2-1.6, p 0.01; HR = 1.45, 95% CI 1.3-1.6, p 0.01 respectively). These results show a trend toward better survival with late treatment of SCLC. Therefore, a general urgency to treat SCLC needs to be re-evaluated with consideration of patients needing more optimization before treatment. Further studies are needed to better clarify the appropriate timing of treatment from diagnosis in SCLC and who will benefit from early versus late treatment.

Purpose: Retrospective studies suggest that it may be safe to extend the maintenance flushing interval of implanted ports from once every month, as recommended by the manufacturer, to once every 3 months, but no prospective cohort studies have been done specifically assessing the safety and feasibility of this intervention. Methods: This was a phase II study in oncologic patients who retained a functional port after completion of systemic chemotherapy. Patients enrolled in the study had their port flushed once every 3 months and were observed until completion of five scheduled flushes (one on enrollment and four additional flushes, one every 3 months) or development of any port-related complication, including infections, thrombosis, and occlusions. The primary end points were frequency of port-related complications and port failure requiring removal. Results: A total of 87 patients were enrolled in the study. The median follow-up time was 308 days, accounting for a total of 24,202 catheter-days. There were 10 port-related complications (11.49%; 95% CI, 4.85% to 18.14%). No infection or symptomatic thrombosis occurred. The mean time to port-related complication was 184 days. No patients developed port failure while on protocol, but on subsequent medical record review, four patients developed a complication that required port removal or port revision within 30 days of being removed from the trial (4.6%; 95% CI, 0.4% to 8.8%; 0.17/1,000 catheter-days). Conclusion: Extending the maintenance flushes of implanted ports in adult oncologic patients to once every 3 months is safe, effective, and likely to increase patient adherence and satisfaction while decreasing the associated cost.

Introduction The purpose of this study is to provide data on the outcomes of using stereotactic body radiotherapy (SBRT) as a means of salvage for non-small cell lung cancer (NSCLC) relapses previously treated with radiation. Materials and methods The records of 128 consecutive patients treated with thoracic SBRT from 2009 through 2012 were retrospectively reviewed. Twenty-seven patients (29 lesions) treated with prior thoracic radiation for stage IIB-IIIB NSCLC with subsequent recurrences and retreated with SBRT were identified. Results The median prior radiation dose was 64.8 Gy (range, 45 to 74 Gy) with a median retreatment dose of 50 Gy (range, 30 to 54 Gy), corresponding to a biological equivalent dose of 100 Gy (range, 48 to 151 Gy), at a median time of 13.4 months from prior radiation. The mean follow-up after salvage SBRT was 22 months. Local failure following salvage was 11%, nodal failure was 37%, and distant failure was 30%. The local recurrence-free survival at 2 years was 72%. Out-of-field failure was predictive for worse local control (hazard ratio, 47.38; 95% confidence interval, 5.795-64.899). Progression-free survival at 1 year was 55% and 38% at 2 years. Overall survival at 2 years from SBRT salvage was 79%. Salvage biological equivalent dose ≥100 Gy was predictive of improved progression-free survival (48% vs. 18%, P=0.021) and overall survival (91% vs. 52%, P=0.004) at 2 years. The rate of symptomatic pneumonitis was 63% and chest wall pain reported was 26%. Conclusions We observed improved outcomes following SBRT as a means of salvage for locally advanced recurrent NSCLC over traditional radiation therapy options. The toxicities were greater than expected from naive lung irradiation, but the adverse effects remained controlled with medications.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole β-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor-bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis. On a different axis, WGP-treated M-MDSC differentiated into F4/80+CD11c+ cells in vitro that served as potent APC to induce Ag-specific CD4+ and CD8+ T cell responses in a dectin-1–dependent manner. Additionally, Erk1/2 phosphorylation was required for the acquisition of APC properties in M-MDSC. Moreover, WGP-treated M-MDSC differentiated into CD11c+ cells in vivo with high MHC class II expression and induced decreased tumor burden when inoculated s.c. with Lewis lung carcinoma cells. This effect was dependent on the dectin-1 receptor. Strikingly, patients with non–small cell lung carcinoma that had received WGP treatment for 10–14 d prior to any other treatment had a decreased frequency of CD14−HLA-DR−CD11b+CD33+ MDSC in the peripheral blood. Overall, these data indicate that WGP may be a potent immune modulator of MDSC suppressive function and differentiation in cancer.

Purpose: Every year a significant population exists of those diagnosed with nonsmall cell lung cancer (NSCLC) who do not receive initial treatment upon diagnosis and then “migrate” to additional hospital before ultimately getting treatment. Migration to different hospitals may play a role in the decision to treat or not-to-treat, and we aimed to evaluate the potential factors that lead to treatment. Methods: A retrospective review of 6212 patients with NSCLC from 29 Kentucky hospital registries from 2012 to 2014 was performed. Variables collected included hospital accreditation status, age at diagnosis, stage, overall survival (OS), and insurance status. Hospital records were matched to Kentucky Cancer Registry records to determine the number of hospitals visited for treatment. Results: Most patients were treated at their initial hospital (73%). Of the remaining patients, 36% migrated to a different hospital where most received treatment (93%). Migrating to another hospital was associated with Stage I-III disease, younger age (66.4 vs 72.2 years), and longer OS (561 vs 157 days). Notably, migration was also associated with private insurance status and missing treatment modalities at the initial hospital. Treatment after migrating was associated with Stage I-II disease, younger age (65.8 vs 72.8 years), and longer OS (595 vs 153 days). After adjusting for confounders, treated migrating patients lived longer than initially treated patients (591 vs 505 days), especially among those with stage III (563 vs 495 days) and IV (379 vs 300 days) disease. Conclusion: This analysis demonstrates a survival benefit for initially untreated patients with advanced disease who migrate to another hospital for treatment. Migration was associated with having private insurance, thus making it noteworthy of the relationship between NSCLC survival benefit and insurance status.

Introduction: The identification of anaplastic lymphoma kinase (ALK) gene rearrangements in subsets of non-small cell lung cancer patients has provided with unparalleled opportunities to hinder the progression of this disease through targeting the activity of these specific molecules. Unfortunately most patients develop disease progression in less than a year of treatment with crizotinib, the first-generation ALK-inhibitor.Areas covered: We review the resistance mechanisms to ALK inhibitors as well as an overview of the clinical activity of the alectinib, a second generation ALK inhibitor.Expert commentary: Second generation ALK inhibitors as alectinib and ceritinib can overcome crizotinib-resistant mutations and improve central nervous system control. Novel third-generation inhibitors and combination of agents give hope of achieving an even longer disease control in the next decade.

Ab therapy against surface Ags on tumor cells has demonstrated significant efficacy for some cancers. However, it is costly and patients frequently develop acquired resistance over time. In cases of Ab therapy resistance, T cell responses have been shown to be essential in controlling disease progression. Thus, vaccination that generates a sustained Ab response as well as a T cell response may be more effective and economical. Here, we have developed a vaccination strategy by targeting protein Ags to B cells via a CD19 single chain variable fragment miniAb. By using the tumor-associated Ag (TAA) her-2/neu extracellular domain (ECD), we showed that the co-engagement of CD19 and BCR induced full B cell activation to produce a high titer of Abs and enhanced CD4 Th2 response and CD8 T cell activation and differentiation. These Abs competitively inhibited humanized her-2/neu Ab binding and were capable of activating the complement and inhibiting human breast cancer growth in vitro. Therapeutic efficacy was demonstrated in vivo using murine mammary carcinomas models. Furthermore, four different ECDs of her-2/neu could be targeted to B cells to generate Abs against particular domains with different anti-tumor properties. This approach may offer a new avenue for vaccine development with significantly lower cost which may be usable not only for cancer therapy but also for infectious agents.

Tumor-associated macrophages (TAM) with an M2-like phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. Here, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized M2 macrophages or immunosuppressive TAM into an M1-like phenotype with potent immuno-stimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, krebs cycle and glutamine utilization. In addition, particulate β-glucan converts immunosuppressive TAM via the C-type lectin receptor dectin-1-induced Syk-Card9-Erk pathway. Further in vivo studies show that oral particulate β-glucan treatment significantly delays tumor growth, which is associated with in vivo TAM phenotype conversion and enhanced effector T cell activation. Mice injected with particulate β-glucan-treated TAM mixed with tumor cells have significantly reduced tumor burden with less blood vascular vessels compared to those with TAM plus tumor cell injection. In addition, macrophage depletion significantly reduced the therapeutic efficacy of particulate β-glucan in tumor-bearing mice. These findings have established a new paradigm for macrophage polarization and immunosuppressive TAM conversion and shed the light on the action mode of β-glucan treatment in cancer.

We demonstrate the rapid and label-free capture of breast cancer cells spiked in buffy coats using nanotube-antibody micro-arrays. Single wall carbon nanotube arrays were manufactured using photo-lithography, metal deposition, and etching techniques. Anti-epithelial cell adhesion molecule (EpCAM) antibodies were functionalized to the surface of the nanotube devices using 1-pyrene-butanoic acid succinimidyl ester functionalization method. Following functionalization, plain buffy coat and MCF7 cell spiked buffy coats were adsorbed on to the nanotube device and electrical signatures were recorded for differences in interaction between samples. A statistical classifier for the 'liquid biopsy' was developed to create a predictive model based on dynamic time warping to classify device electrical signals that corresponded to plain (control) or spiked buffy coats (case). In training test, the device electrical signals originating from buffy versus spiked buffy samples were classified with ∼100% sensitivity, ∼91% specificity and ∼96% accuracy. In the blinded test, the signals were classified with ∼91% sensitivity, ∼82% specificity and ∼86% accuracy. A heatmap was generated to visually capture the relationship between electrical signatures and the sample condition. Confocal microscopic analysis of devices that were classified as spiked buffy coats based on their electrical signatures confirmed the presence of cancer cells, their attachment to the device and overexpression of EpCAM receptors. The cell numbers were counted to be ∼1-17 cells per 5 μl per device suggesting single cell sensitivity in spiked buffy coats that is scalable to higher volumes using the micro-arrays.

Small-cell lung cancer (SCLC) is an aggressive disease with poor survival and rapid doubling time. Current practice is to treat SCLC as soon as possible but evidence on appropriate timing of treatment from diagnosis (TTD) is lacking. This is a retrospective analysis of SCLC patients from the 2012 to 2015 Kentucky Cancer Registry. Data collected included age at diagnosis, stage, gender, race, insurance and treatment. Factors and survival associated with TTD were identified with logistic regression analyses and Cox proportional hazards models. Among the 2992 SCLC patients, 2371 (79%) of SCLC patients were treated with one or more treatment modalities. Among treated patients, 93% received chemotherapy ± radiation with the mean TTD of 18 days. Most patients (80%) have TTD of ≤ 4 weeks with 33% treated within 1 week, 20% 1–2 weeks, and 27% 2–4 weeks from diagnosis. Delay in treatment (TTD > 4 weeks) was less in stage III and IV disease (odds ratio: 0.33 and 0.27 respectively, p 4 weeks (hazard ratio = 1.43, 95% CI 1.2–1.6, p

Ab therapy against surface Ags on tumor cells has demonstrated significant efficacy for some cancers. However, it is costly and patients frequently develop acquired resistance over time. In cases of Ab therapy resistance, T cell responses have been shown to be essential in controlling disease progression. Thus, vaccination that generates a sustained Ab response as well as a T cell response may be more effective and economical. In this article, we have developed a vaccination strategy by targeting protein Ags to B cells via a CD19 single-chain variable fragment miniAb. Using the tumor-associated Ag her-2/neu extracellular domain, we showed that the coengagement of CD19 and BCR induced full B cell activation to produce a high titer of Abs and enhanced CD4 Th2 response and CD8 T cell activation and differentiation. These Abs competitively inhibited humanized her-2/neu Ab binding and were capable of activating the complement and inhibiting human breast cancer growth in vitro. Therapeutic efficacy was demonstrated in vivo using murine mammary carcinoma models. Furthermore, four different extracellular domains of her-2/neu could be targeted to B cells to generate Abs against particular domains with different antitumor properties. This approach may offer a new avenue for vaccine development with significantly lower cost, which may be of use not only for cancer therapy but also for infectious agents.

We demonstrate the rapid and label-free capture of breast cancer cells spiked in blood using nanotube-antibody micro-arrays. 76-element single wall carbon nanotube arrays were manufactured using photo-lithography, metal deposition, and etching techniques. Anti-epithelial cell adhesion molecule (anti-EpCAM), Anti-human epithelial growth factor receptor 2 (anti-Her2) and non-specific IgG antibodies were functionalized to the surface of the nanotube devices using 1-pyrene-butanoic acid succinimidyl ester. Following device functionalization, blood spiked with SKBR3, MCF7 and MCF10A cells (100/1000 cells per 5 μl per device, 170 elements totaling 0.85 ml of whole blood) were adsorbed on to the nanotube device arrays. Electrical signatures were recorded from each device to screen the samples for differences in interaction (specific or non-specific) between samples and devices. A zone classification scheme enabled the classification of all 170 elements in a single map. A kernel-based statistical classifier for the 'liquid biopsy' was developed to create a predictive model based on dynamic time warping series to classify device electrical signals that corresponded to plain blood (control) or SKBR3 spiked blood (case) on anti-Her2 functionalized devices with ∼90% sensitivity, and 90% specificity in capture of 1000 SKBR3 breast cancer cells in blood using anti-Her2 functionalized devices. Screened devices that gave positive electrical signatures were confirmed using optical/confocal microscopy to hold spiked cancer cells. Confocal microscopic analysis of devices that were classified to hold spiked blood based on their electrical signatures confirmed the presence of cancer cells through staining for DAPI (nuclei), cytokeratin (cancer cells) and CD45 (hematologic cells) with single cell sensitivity. We report 55%-100% cancer cell capture yield depending on the active device area for blood adsorption with mean of 62% (∼12 500 captured off 20 000 spiked cells in 0.1 ml blood) in this first nanotube-CTC chip study.