Increase Response Rates Research Articles

Pre-incentive Efficacy in Survey Response Rates in a Large Prospective Military Cohort

Declining survey response rates concern researchers aiming to ensure study validity. This article tested the effectiveness of multiple pre-incentives on increasing survey response to the Millennium Cohort Study. Participants consisted of U.S. military service members and veterans, and were randomly assigned to receive a $2 bill, $5 gift card, magnet, Apple iPad® lottery entry, or no pre-incentive. Participants who received the gift card or cash pre-incentive had the highest response rates and were significantly more likely to respond to the survey than those who did not receive a pre-incentive. There was no significant difference in survey response among the magnet or lottery entry groups compared to the no pre-incentive group. This study found that giving participants a monetary pre-incentive was an effective way to increase response rates, and thereby participant retention, in a hard-to-reach, highly mobile population, and re-engage participants who did not respond to a previous follow-up survey.

Pharmacogenomic Profiling to Tailor Antidepressant Therapy: Improving Treatment Outcomes and Reducing Adverse Drug Reactions in Major Depressive Disorder

Major Depressive Disorder (MDD) presents a significant challenge in clinical practice due to the variability in patient responses to antidepressants and the high incidence of adverse drug reactions (ADRs). The traditional trial-and-error approach to prescribing antidepressants often results in prolonged treatment periods, increased patient suffering, and higher healthcare costs. This study investigates the benefits of pharmacogenomic profiling to tailor antidepressant therapy, aiming to improve treatment outcomes and reduce ADRs. The primary objectives of this study were to evaluate the efficacy of personalized medication selection based on genetic profiles, reduce the time to achieve therapeutic efficacy, and enhance patient safety by minimizing ADRs. Pharmacogenomic testing methodologies, including genotyping and whole genome sequencing, were employed to identify genetic polymorphisms affecting drug metabolism and response. Key findings indicate that personalized antidepressant therapy increases response rates by 20-30% and reduces the time to symptom relief by 50%. The incidence of ADRs was decreased by 40-50% through tailored dosing and medication selection. Additionally, pharmacogenomic profiling identified 90% of high-risk patients before treatment, enabling preventive measures and personalized interventions. Dosage accuracy improved by 25-35%, contributing to better treatment outcomes. Economic analysis revealed substantial cost savings, with average annual savings of $2,000-$4,000 per patient and potential healthcare system savings of $100 million annually. The adoption of pharmacogenomic testing has increased from 5% to 25% of clinics over the past five years, demonstrating growing recognition of its clinical utility. This study underscores the transformative potential of pharmacogenomic profiling in optimizing antidepressant therapy, enhancing patient care, and reducing healthcare costs. Future research should focus on expanding genetic panels, increasing population diversity, and developing strategies for broader clinical integration.

Abstract P4-06-10: Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting

Abstract Background: Breast cancer is the second most commonly diagnosed cancer in North American women. The administration of neoadjuvant chemotherapy (NAC) is the mainstay of treatment for individuals with high risk disease in an effort to reduce the extent of surgery, evaluate the role of additional adjuvant therapies (based on pathologic response to NAC), and improve disease-free and overall survival (OS). Anthracyclines have been shown to increase response rates leading to a greater likelihood of pathologic complete response compared to non-anthracycline regimens. However, for some individuals anthracyclines are omitted from the NAC regimen due to toxicities including greater immunosuppression, cardiac toxicity and risk of acute leukemia. We established a population-based cohort of individuals treated with NAC for breast cancer. We report the outcomes of women selected for treatment with non-anthracycline NAC compared to those treated with anthracyclines. Methods: This is a retrospective population-based cohort study using linked health administrative data held at the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada. We identified adult women diagnosed with stage I-III breast cancer (ICD-10 C50^) between 2012 and 2020 who received NAC. Administration of at least 50% of the planned chemotherapy regimen was required. We excluded patients with bilateral breast cancer, previous malignancy and male sex. NAC regimens were classified as anthracycline and non-anthracycline-containing regimens. To address confounding between those receiving anthracycline and other regimens, we built a propensity score model including patient and disease characteristics. The association with OS was calculated using Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using cause-specific Cox proportional hazards models. Models were adjusted for the propensity score, radiation treatment as a time-varying covariate, age, socioeconomic status, breast cancer stage and receptor sub-type, as well as Charlson comorbidity index. Results: A total of 4,180 women were identified with a median follow up of 62 months (IQR 44 – 85). Of these, 279 (6.7%) were treated with non-anthracycline regimens compared to 3,901 treated with anthracycline. Patients who received non-anthracyclines were older (median 62 years vs. 50 years; p < 0.001), and less likely to have stage III disease (33.0% vs. 48.7%; p < 0.001), and harbor triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p < 0.001). They were more likely to have no recorded comorbidities (89.2% vs. 96.5%; p < 0.001), undergo mastectomy (82.1% vs. 71.9%; p < 0.001), and sentinel lymph node biopsy (44.4% vs. 32.3%; p < 0.001). After propensity score and multivariable adjustment, women selected for treatment with non-anthracycline regimens had similar OS (HR 0.85, 95% CI 0.60-1.21) and BCSS (cause-specific HR 0.76, 95% CI 0.46-1.25) compared to those treated with anthracyclines. When stratified by stage, women treated with non-anthracycline regimens did not have significantly higher incidences of breast cancer death or death from any cause (stages I, II, and III Gray’s Test p-value all > 0.1). The mean OS was 7.2 years for women who received non-anthracycline regimens (95% CI 7.0 – 7.4) compared to 7.9 years for those who received anthracycline (95% CI 7.9 – 8.0) (log-rank p = 0.100). Conclusions: Women with stage I-III breast cancer treated with non-anthracycline NAC regimens are a highly selected population. These patients were older and healthier, with earlier stage disease and more favorable subtype (i.e. non-TNBC) when compared to those treated with anthracycline NAC. Our results demonstrate that women were well selected to omit anthracyclines and did not have worse survival outcomes. Further research is needed to better understand in whom anthracycline can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Matthew Castelo, Rinku Sutradhar, Lena Nguyen, Neil Faught, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-10.

Abstract P2-24-02: Analyzing susceptibility to macrophage-activating immunotherapy bexmarilimab in breast cancer by using patient-derived tumor explants

Abstract The immunosuppressive tumor microenvironment governed by tumor-associated macrophages (TAMs) remains a major obstacle to effective cancer immunotherapy. A novel humanized antibody bexmarilimab, targeting the scavenger receptor Clever-1 on TAMs, has shown clinical benefit in ~40% of patients with late-stage ER+ breast cancer (MATINS; NCT03733990). To increase response rates, a comprehensive understanding on how TAM phenotype and the tumor immune landscape affect bexmarilimab-induced immune activation is needed. Single-cell RNA sequencing analysis of breast tumor macrophages shows high phenotypic variation across pathological subtypes and Clever-1 mRNA (STAB1) expression on various immunosuppressive IL4I1+ and TREM2+ monocyte-derived TAMs. STAB1 expressing macrophages were located in both lymphocyte rich and excluded areas in the tumor stroma based on digital spatial profiling with GeoMx. Due to this diversity, we studied bexmarilimab mode-of-action in breast cancer patient-derived tumor explant cultures (PDEC) by RNA sequencing and cytokine profiling. Our results show that bexmarilimab induced TNFα and CXCL10 secretion in 30-40% of the treated explants. In depth analysis of the responsive PDECs revealed a lower baseline expression of interferon responsive genes in their tumor microenvironment. Correspondingly, in vitro assays with primary human macrophages showed that chronic IFNγ priming abolished bexmarilimab-induced immune activation, suggesting potential use of bexmarilimab in patients with immunologically cold breast tumors. Citation Format: Jenna H. Rannikko, Reetta Virtakoivu, Akira Takeda, Pia Boström, Ilkka Koskivuo, Petri Bono, Maija Hollmén. Analyzing susceptibility to macrophage-activating immunotherapy bexmarilimab in breast cancer by using patient-derived tumor explants [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-24-02.

Upregulation of Apolipoprotein L6 Improves Tumor Immunotherapy by Inducing Immunogenic Cell Death.

In the past few years, immune checkpoint blockade (ICB) therapy has emerged as a breakthrough treatment for cancers and has demonstrated inspiring effects in tumor patients with Epstein-Barr virus (EBV) infection. To allow more patients to benefit from immunotherapy, exploring novel biomarkers based on EBV-related tumors and immunotherapy cohorts was pursued in the present study. The essential biomarkers that may enhance antitumor immunity across EBV-related tumors were identified using the large-scale transcriptomic profiles of EBV-associated tumors and tumor immunotherapy cohorts. The clinical significance of vital genes was evaluated in multiple tumor immunotherapy cohorts. Moreover, the potential function of essential genes in immunotherapy was explored via bioinformatic analyses and verified by qRT-PCR, Western blot analysis, CCK8 assay and flow cytometry. Apolipoprotein L6 (APOL6) was considered the essential biomarker for enhancing antitumor immunity across EBV-positive tumors. The upregulation of APOL6 was correlated with increased response rates and prolonged survival in multiple tumor immunotherapy cohorts. Bioinformatic analyses suggested that APOL6 may enhance tumor immunotherapy by inducing immunogenic cell death. Pancreatic cancer cells transfected with APOL6 overexpression plasmid underwent apoptosis, necroptosis, and pyroptosis with immunogenic features. The biomarker upregulated in EBV-related tumors could further elucidate the drivers of immunotherapy response. The upregulation of APOL6 could improve immunotherapy by triggering immunogenic cell death, thus offering a new target to optimize cancer immunotherapy.

Efficacy of immune-checkpoint inhibitor (ICI) combination as a first-line (1L) therapy in metastatic renal cell carcinoma (mRCC) with sarcomatoid histology: A systematic review and meta-analysis.

692 Background: Sarcomatoid mRCC exhibits poor prognosis and limited response to vascular endothelial growth factor pathway inhibition. Therefore, we assessed the efficacy of ICI combination therapy in this patient population using data from contemporary trials. Methods: MEDLINE and EMBASE were searched to identify phase III randomized controlled trials (RCTs) comparing the efficacy of ICI combinations with sunitinib monotherapy in patients with sarcomatoid mRCC. Patient important outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR). Precomputed hazard ratios (HR) with 95% confidence intervals (CI) for survival outcomes and binary outcome data for response rates (expressed as relative risk [RR] were meta-analyzed using a DerSimonian-Lairds random-effects method. Mixed treatment comparisons among different ICI combinations were made using a network-meta-analysis within the Bayesian framework. The surface under the cumulative ranking curves (SUCRA) were computed to assess the relative treatment rankings. Results: Six RCTs with a total of 618 patients were considered eligible for inclusion. ICI combination therapy was significantly associated with improved OS (HR: 0.56; 95% CI: 0.43-0.72) and PFS (HR: 0.50; 0.40-0.62), increased ORR (RR: 2.42; 1.92-3.06), and CR (RR: 4.23; 2.00-8.93) when compared to sunitinib in patients with sarcomatoid mRCC (Table). The results were consistent with Hartung-Knapp adjustment. Mixed treatment comparisons using current data revealed no statistically significant differences among different ICI combinations. However, the combination of nivolumab-ipilimumab was consistently ranked higher (rank 2 for OS, ORR, and CR) and may potentially be more efficacious than other counterparts. Conclusions: Current evidence suggests improved survival, delayed disease progression and increased response rates with the use of ICI combination therapy in patients with sarcomatoid mRCC. [Table: see text]

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Oncolytic adenovirus-mediated expression of CCL5 and IL12 facilitates CA9-targeting CAR-T therapy against renal cell carcinoma

Chimeric antigen receptor T-cell (CAR-T) is particularly prominent in hematological but not in solid tumors, mainly based on the complex tumor immune microenvironment. Oncolytic virus (OVs) is an emerging adjuvant therapy method. OVs may prime tumor lesions to induce anti-tumor immune response, thereby enhancing CAR-T cells functionality and possibly increasing response rates. Here, we combined CAR-T cells targeting carbonic anhydrase 9 (CA9) and an oncolytic adenovirus (OAV) carrying chemokine (C-C motif) ligand 5 (CCL5), cytokine interleukin-12 (IL12) to explore the anti-tumor effects of this combination strategy. The data showed that Ad5-ZD55-hCCL5-hIL12 could infect and replicate in renal cancer cell lines and induced a moderate inhibition of xenografted tumor in nude mice. IL12 mediated by Ad5-ZD55-hCCL5-hIL12 promoted the phosphorylation of Stat4 in CAR-T cells, induced CAR-T cells to secrete more IFN-γ. We also found that Ad5-ZD55-hCCL5-hIL-12 combined with CA9-CAR-T cells significantly increased the infiltration of CAR-T cells in tumor mass, prolonged the survival of the mice and restrained tumor growth in immunodeficient mice. Ad5-ZD55-mCCL5-mIL-12 could also increase CD45+CD3+T cell infiltration and prolong mice survival in immunocompetent mice. These results provided feasibility for the combination of oncolytic adenovirus and CAR-T cells, which demonstrated the sufficient potential and prospects of CAR-T for the treatment of solid tumors.

Review of outcomes of combination therapy using yttrium 90 radioembolization and sorafenib/nivolumab for HCC with hepatic vein or IVC invasion

Background A systematic review of the outcomes of combination therapy using Yttrium 90 radioembolization (Y90) and sorafenib/nivolumab for patients with hepatocellular carcinoma (HCC), with hepatic vein (HV) or inferior vena cava (IVC) invasion. The aim of this study is to summarise the results of different studies that used the combination therapy for HCC patients with tumor thrombosis involving the HV or IVC. Method A literature search was performed using keywords in Medline and Google Scholar limited to publications from 2010 to 2021. There were 173 articles identified during the initial literature search. During abstract screening, 81 articles were excluded. Another 83 did not contain information on hepatic vein or IVC invasion. Therefore, 9 articles met the eligibility criteria and were included in the synthesis. Results In total, 37 patients with hepatic vein or IVC invasion were identified. There were 31 patients who were given sorafenib, 7 were given nivolumab and 1 was given both sorafenib and nivolumab. Among the 37 patients, 21 had hepatic vein invasion, 22 had IVC invasion and 6 had both HV and IVC invasion. The median OS was 20.55 months and median PFS was 8.18 months. For the results, 23 patients were evaluated via modified RECIST (mRECIST) criteria and 14 were evaluated via RECIST 1.1. Conclusion The combination of local and systemic therapies demonstrated potential results for increased response rates, OS and PFS benefits. Further studies are required to determine the long-term outcomes of the combination therapy for this group of patients.

Choir of believers? Experimental and longitudinal evidence on survey participation, response bias, and public service motivation

Collecting data through surveys are a vital method in public administration research, but an overseen challenge for the validity of survey research is response bias, which is when response behavior correlates with study outcomes. Response bias can be particularly threatening in motivation research because motivation is an important determinant for behavior and most likely also for survey participation. Specifically, public service motivation (PSM) can increase the willingness to devote time and effort to respond to surveys for the benefit of others, whereas extrinsically motivated individuals may be less inclined to participate in surveys without prospects of economic compensation. This article examines motivation and response bias by use of a preregistered field experiment and two panel datasets. The experimental study shows that a monetary incentive increases the response rate, whereas a PSM-oriented appeal does not. Furthermore, the increased response rate of the incentive is achieved without any detectable response bias on PSM. Likewise, the panel studies offer little and mixed support for response bias related with PSM. This evidence suggests that (1) PSM is not a (strong) driver of response bias, and that (2) extrinsic motivational tools applied to PSM surveys are not necessarily associated with response bias.

Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan.

Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

Identification and development of TP53 mutation-associated Long non-coding RNAs signature for optimized prognosis assessment and treatment selection in hepatocellular carcinoma.

The TP53 gene is estimated to be mutated in over 50% of tumors, with the majority of tumors exhibiting abnormal TP53 signaling pathways. However, the exploration of TP53 mutation-related LncRNAs in Hepatocellular carcinoma (HCC) remains incomplete. This study aims to identify such LncRNAs and enhance the prognostic accuracy for Hepatoma patients. Differential gene expression was identified using the "limma" package in R. Prognosis-related LncRNAs were identified via univariate Cox regression analysis, while a prognostic model was crafted using multivariate Cox regression analysis. Survival analysis was conducted using Kaplan-Meier curves. The precision of the prognostic model was assessed through ROC analysis. Subsequently, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were executed on the TCGA dataset via the TIDE database. Fractions of 24 types of immune cell infiltration were obtained from NCI Cancer Research Data Commons using deconvolution techniques. The protein expression levels encoded by specific genes were obtained through the TPCA database. In this research, we have identified 85 LncRNAs associated with TP53 mutations and developed a corresponding signature referred to as TP53MLncSig. Kaplan-Meier analysis revealed a lower 3-year survival rate in high-risk patients (46.9%) compared to low-risk patients (74.2%). The accuracy of the prognostic TP53MLncSig was further evaluated by calculating the area under the ROC curve. The analysis yielded a 5-year ROC score of 0.793, confirming its effectiveness. Furthermore, a higher score for TP53MLncSig was found to be associated with an increased response rate to immune checkpoint blocker (ICB) therapy (p = .005). Patients possessing high-risk classification exhibited lower levels of P53 protein expression and higher levels of genomic instability. The present study aimed to identify and validate LncRNAs associated with TP53 mutations. We constructed a prognostic model that can predict chemosensitivity and response to ICB therapy in HCC patients. This novel approach sheds light on the role of LncRNAs in TP53 mutation and provides valuable resources for analyzing patient prognosis and treatment selection.

Mechanisms and Strategies to Overcome PD-1/PD-L1 Blockade Resistance in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by a high rate of systemic metastasis, insensitivity to conventional treatment and susceptibility to drug resistance, resulting in a poor patient prognosis. The immune checkpoint inhibitors (ICIs) represented by antibodies of programmed death receptor 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have provided new therapeutic options for TNBC. However, the efficacy of PD-1/PD-L1 blockade monotherapy is suboptimal immune response, which may be caused by reduced antigen presentation, immunosuppressive tumor microenvironment, interplay with other immune checkpoints and aberrant activation of oncological signaling in tumor cells. Therefore, to improve the sensitivity of TNBC to ICIs, suitable patients are selected based on reliable predictive markers and treated with a combination of ICIs with other therapies such as chemotherapy, radiotherapy, targeted therapy, oncologic virus and neoantigen-based therapies. This review discusses the current mechanisms underlying the resistance of TNBC to PD-1/PD-L1 inhibitors, the potential biomarkers for predicting the efficacy of anti-PD-1/PD-L1 immunotherapy and recent advances in the combination therapies to increase response rates, the depth of remission and the durability of the benefit of TNBC to ICIs.

Co-Targeting Luminal B Breast Cancer with S-Adenosylmethionine and Immune Checkpoint Inhibitor Reduces Primary Tumor Growth and Progression, and Metastasis to Lungs and Bone.

Breast cancer (BCa) is the most prevalent cancer in females and has a high rate of mortality, especially due to increased metastasis to skeletal and non-skeletal sites. Despite the marked clinical accomplishment of immune checkpoint inhibitor (CPI) therapy in patients with several cancers, it has had limited success in luminal subtypes of BCa. Accordingly, recent efforts have focused on combination therapy with CPI, including epigenetic modulators, to increase response rates of CPI in luminal BCa. We have previously shown that S-adenosylmethionine (SAM), the ubiquitous methyl donor, has strong anti-cancer effects in various cancers, including all subtypes of BCa. In the current study, we took a novel approach and examined the effect of CPI alone and in combination with SAM on tumor growth and metastasis in a syngeneic mouse model of luminal B BCa. We showed that SAM decreases cell proliferation, colony-formation (survival), and invasion of luminal B BCa cell lines (Eo771, R221A) in vitro. In in vivo studies, in Eo771 tumor-bearing mice, either SAM or anti-PD-1 antibody treatment alone significantly reduced tumor growth and progression, while the SAM+anti-PD-1 combination treatment had the highest anti-cancer efficacy of all groups. The SAM+anti-PD-1 combination reduced the percentage of animals with lung metastasis, as well as total metastatic lesion area, compared to control. Additionally, the SAM+anti-PD-1 combination significantly reduced the skeletal lesion area and protected tibial integrity to a greater extent than the monotherapies in an Eo771 bone metastasis model. Transcriptome analysis of Eo771 primary tumors revealed significant downregulation of pro-metastatic genes, including Matrix metalloproteinases (MMPs) and related pathways. On the other hand, CD8+ T cell infiltration, CD8+ T cell cytotoxicity (elevated granzymes), and immunostimulatory genes and pathways were significantly upregulated by the combination treatment. The results presented point to a combination of SAM with CPI as a possible treatment for luminal B BCa that should be tested in clinical studies.

WHAT IS THE DIGITAL MATURITY OF LONG-TERM CARE HOMES IN ONTARIO? A SURVEY PROTOCOL

Abstract Ramtin Hakimjavadi will discuss the barriers and facilitators of implementing a health information technology (HIT) maturity survey in the Canadian context. Alongside Dr. Liddy’s team, he is supporting the adaptation of the survey into a Canadian context, followed by a pilot study to distribute the survey to select nursing homes. Drawing from this work, Mr. Hakimjavadi will highlight the barriers and facilitators associated with the process of implementing the HIT maturity survey. Expected challenges include adjusting the survey format for respondents with limited resources, identifying a central contact within each nursing home, optimizing the survey user interface to limit response burden, and developing recruitment strategies to increase response rate. These challenges and the strategies to overcome them, impressions of the current state of HIT in Ontario nursing homes, and proposed action items to trend digital maturity in these settings over time will be discussed.

Insights for the Drop-off/Pick-up Method to Improve Data Collection

Mail and telephone surveys are becoming increasingly expensive and unreliable, while internet-based surveys raise issues of geographic representation and other matters of authenticity. The Drop-Off/Pick-Up (DOPU) method is an alternative which can elicit higher response rates and reduce non-response bias issues. DOPU involves dropping off and picking up surveys in person and can yield high participation because personal interactions have been shown to stimulate norms of reciprocity. We share insights from our 2019 DOPU study of hydrocarbon energy export impacts in four communities that have experienced oil-by-rail transportation and related disasters, with surveys collected in two metropolitan and two rural communities in the U.S. Midwest and Pacific Northwest. We organize and present a suite of novel and established recommendations suitable for both scholarly and community-based researchers and practitioners to strengthen community support, improve fieldwork efficiency, increase response rates, and reduce costs in future DOPU studies.

IMMUNOTHERAPY AS NOVEL TREATMENT OF LUNG CANCER: A SYSTEMATIC REVIEW

Lung cancer is the top cause of cancer-related fatalities in both men and women around the world, and the second most commonly diagnosed cancer in both men and women. For many patients, traditional chemotherapy (CT) fails to give long-term benefit. Moreover, newer medicines targeting activating mutations in EGFR or ALK have shown increased response rates over CT in the minority of patients with these mutations; however, the majority of patients do not have actionable mutations and will not benefit from targeted therapies. In addition, several combinations of chemotherapeutic medicines with the angiogenesis inhibitor bevacizumab have provided only minor additional benefits. However, immunotherapy using checkpoint inhibitors has shown to have a lot of potential in the treatment of advanced non-SCLC (NSCLC) in recent trials. These new medications encourage the host immune system to recognize tumor cells as foreign invaders and halting their growth. They help alleviate immune system suppression, which allows tumor development to be tolerated. In checkpoint immunotherapy, humanized monoclonal antibodies targeting checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand are employed (PD-L1). The immune system can be triggered to fight the tumor by inhibiting these receptors and signals. Immunotherapy for advanced lung cancer has created a new paradigm of therapeutic options, with increased survival and response rates and a less severe but distinct side profile when compared to CT. The PD-1 inhibitors nivolumab and pembrolizumab, as well as the PD-L1 inhibitor atezolizumab, have been approved by regulatory authorities for the treatment of advanced NSCLC. Hence, the current review article focuses on the role of immunotherapy, newer agents used for checkpoint inhibitors in lung cancer, their epidemiology, risk factors, side-effect profiles, therapeutic indications, and their mechanism of action for the successful treatment of lung cancer.

The Visible Cash Effect with Prepaid Incentives: Evidence for Data Quality, Response Rates, Generalizability, and Cost

Abstract A prior study found that mailing prepaid incentives with $5 cash visible from outside the envelope increased the response rate to a mail survey by 4 percentage points compared to cash that was not externally visible. This “visible cash effect” suggests opportunities to improve survey response at little or no cost, but many unknowns remain. Among them: Does the visible cash effect generalize to different survey modes, respondent burdens, and cash amounts? Does it differ between fresh samples and reinterview samples? Does it affect data quality or survey costs? This article examines these questions using two linked studies where incentive visibility was randomized in a large probability sample for the American National Election Studies. The first study used $10 incentives with invitations to a long web questionnaire (median 71 minutes, n = 17,849). Visible cash increased response rates in a fresh sample for both screener and extended interview response (by 6.7 and 4.8 percentage points, respectively). Visible cash did not increase the response rate in a reinterview sample where the baseline reinterview response rate was very high (72 percent). The second study used $5 incentives with invitations to a mail-back paper questionnaire (n = 8,000). Visible cash increased the response rate in a sample of prior nonrespondents by 4.0 percentage points (from 31.5 to 35.5), but it did not increase the response rate in a reinterview sample where the baseline reinterview rate was very high (84 percent). In the two studies, several aspects of data quality were investigated, including speeding, non-differentiation, item nonresponse, nonserious responses, noncredible responses, sample composition, and predictive validity; no adverse effects of visible cash were detected, and sample composition improved marginally. Effects on survey costs were either negligible or resulted in net savings. Accumulated evidence now shows that visible cash can increase incentives’ effectiveness in several circumstances.

Increased tumor glycolysis is associated with decreased immune infiltration across human solid tumors.

Response to immunotherapy across multiple cancer types is approximately 25%, with some tumor types showing increased response rates compared to others (i.e. response rates in melanoma and non-small cell lung cancer (NSCLC) are typically 30-60%). Patients whose tumors are resistant to immunotherapy often lack high levels of pre-existing inflammation in the tumor microenvironment. Increased tumor glycolysis, acting through glucose deprivation and lactic acid accumulation, has been shown to have pleiotropic immune suppressive effects using in-vitro and in-vivo models of disease. To determine whether the immune suppressive effect of tumor glycolysis is observed across human solid tumors, we analyzed glycolytic and immune gene expression patterns in multiple solid malignancies. We found that increased expression of a glycolytic signature was associated with decreased immune infiltration and a more aggressive disease across multiple tumor types. Radiologic and pathologic analysis of untreated estrogen receptor (ER)-negative breast cancers corroborated these observations, and demonstrated that protein expression of glycolytic enzymes correlates positively with glucose uptake and negatively with infiltration of CD3+ and CD8+ lymphocytes. This study reveals an inverse relationship between tumor glycolysis and immune infiltration in a large cohort of multiple solid tumor types.

How We Treat Localized Rectal Cancer-An Institutional Paradigm for Total Neoadjuvant Therapy.

Total neoadjuvant therapy (TNT)-the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery-may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians-without any claim to general validity.