National enrollment of lung cancer clinical trials is disproportionate based on race and health care access.

OBJECTIVE: Despite declining lung cancer mortality in the United States, survival differences remain among racial and ethnic minorities in addition to those with limited health care access. Improvements in lung cancer treatment can be obtained through clinical trials, yet there are disparities in clinical trial enrollment of other cancer types. This study aims to evaluate disparities in lung cancer clinical trial enrollment to inform future enrollment initiatives. METHODS: We analyzed patients with non-small cell lung cancer from the National Cancer Database (2004-2018), categorizing them as enrolled or not enrolled in clinical trials based on "rx_summ_other" data element. Clinical, demographic, and institutional factors associated with trial enrollment were assessed using bivariate and multivariate analysis, adjusting for institutional-level clustering. RESULTS: A total of 1924 (0.12%) patients with lung cancer were enrolled in clinical trials. Enrolled patients were predominantly non-Hispanic White (82%), with greater socioeconomic status, treated at academic programs (67%), and had private insurance (42%) or Medicare (44%). They also traveled further for treatment compared with unenrolled patients (56 vs 27 miles, P < .001). After adjusting for demographic and clinical factors, lung cancer trial enrollment was significantly less likely among Black (odds ratio, 0.55; 95% confidence interval, 0.5-0.7, P < .001) and Hispanic (0.66; 95% confidence interval, 0.5-0.9, P = .01) patients. Patients with Medicaid or uninsured, in the lowest socioeconomic status group, and those treated at community-based cancer programs were the least likely to enroll. CONCLUSIONS: Enrollment in lung cancer trials disproportionally excludes minority patients, those in the lowest socioeconomic status, community cancer programs, and the underinsured. These disparities in demographic and access for trial participation show a need for improved enrollment strategies.

Evaluating the Optimal Time Between Diagnosis and Surgical Intervention for Early-Stage Lung Cancer.

INTRODUCTION: There is no consensus on the optimal timing for lung cancer surgery. We aim to evaluate the impact of timing of surgical intervention. We hypothesize delay in intervention is associated with worse overall survival and higher pathologic upstaging in early-stage lung cancer. METHODS: We identified patients with cT1/2N0M0 nonsmall cell lung cancer in the National Cancer Database from 2004 to 2018. Patients were categorized by time to surgery groups: early (<26 d), average (26-60 d), and delayed (61-365 d). Primary outcome was overall survival and secondary outcome was pathologic upstaging. Multivariate models and survival analyses were used to determine factors associated with time from diagnosis to surgery, pathologic upstaging, and overall survival. RESULTS: In multivariate model, advanced age, non-Hispanic Black patients, nonprivate insurance, low median income and education, and treatment at low-volume facilities were less likely to undergo early intervention and compared to the average group were more likely to receive delayed intervention. Pathologic upstaging was more likely in the delayed group (odds ratio 1.11, 1.07-1.14) compared to early group (odds ratio 0.96, 0.93-0.99). Early intervention was associated with improved overall survival (hazard ratio 0.93, 0.91-0.95), while delayed intervention was associated with inferior survival (hazard ratio 1.11, 1.09-1.14). CONCLUSIONS: Expeditious surgical intervention is associated with lower rates of pathologic upstaging and improved overall survival in early-stage lung cancer. Delays in surgery are associated with social and economic factors, suggesting disparities in access to surgery. Lung cancer surgery should be performed as quickly as possible to maximize oncologic outcomes.

Methodological considerations for the determination of VO2max in healthy men.

PURPOSE: A square-wave verification bout to confirm maximal oxygen uptake ([Formula: see text]O2max) from a graded exercise test (GXT) has been recommended. This study ascertained if a verification bout is necessary to determine [Formula: see text]O2max in moderately trained men. METHODS: Ten men (24 ± 4 years) completed familiarization and two treadmill GXTs, followed by a submaximal verification bout to determine [Formula: see text]O2GXT and [Formula: see text]O2verification (highest [Formula: see text]O2 from each testing method). After completing the GXT, subjects rested for 5 min then performed a verification bout at 90% speed and 50% incline at termination of the GXT. The analyses included a 2-way repeated-measures ANOVA, intra-class correlation coefficients (ICC2,1), standard errors of the measurement (SEM), minimal differences (MD), and coefficients of variation (CoV). RESULTS: There was no test (test 1 vs test 2) × method (GXT vs verification) interaction (p = 0.584), or main effect for test (p = 0.320), but there was a main effect for method (p = 0.011). The [Formula: see text]O2GXT (50.9±3.0 mL·kg-1·min-1) was greater than [Formula: see text]O2verification (46.9 ± mL·kg-1·min-1). The [Formula: see text]O2GXT (ICC = 0.988, SEM = 1.0 mL·kg-1 min-1, MD = 2.9 mL kg-1 min-1, CoV = 2.03%) and [Formula: see text]O2verification (ICC = 0.976, SEM = 1.0 mL·kg-1 min-1, MD = 2.7 mL·kg-1·min-1, CoV = 2.03%) demonstrated "excellent" reliability. No subject exceeded the MD for [Formula: see text]O2GXT test-retest or for [Formula: see text]O2verification test-retest, but 50% of subjects had a [Formula: see text]O2GXT that was greater than the [Formula: see text]O2verification (> MD). CONCLUSION: While [Formula: see text]O2GXT and [Formula: see text]O2verification demonstrated excellent reliability, [Formula: see text]O2GXT from a stand-alone GXT provided higher estimates of [Formula: see text]O2 and, therefore, should be considered [Formula: see text]O2max. The lack of test-retest differences in [Formula: see text]O2GXT above the MD indicated that subjects achieved their highest [Formula: see text]O2 ([Formula: see text]O2max) from a standalone GXT. Therefore, the verification bout may not be required to confirm [Formula: see text]O2max in this population.

Regional control after precision lymph node dissection for clinically evident melanoma metastasis.

INTRODUCTION: Completion lymph node dissection (CLND) for microscopic lymph node metastases has been replaced by observation; however, CLND is standard for clinically detectable nodal metastases (cLN). CLND has high morbidity, which may be reduced by excision of only the cLN (precision lymph node dissection [PLND]). We hypothesized that same-basin recurrence risk would be low after PLND. METHODS: Retrospective review at four tertiary care hospitals identified patients who underwent PLND. The primary outcome was 3-year cumulative incidence of isolated same-basin recurrence. RESULTS: Twenty-one patients underwent PLND for cLN without synchronous distant metastases. Reasons for forgoing CLND included patient preference (n = 11), comorbidities (n = 5), imaging indeterminate for distant metastases (n = 2), partial response to checkpoint blockade (n = 1), or not reported (n = 2). A median of 2 nodes (range: 1-6) were resected at PLND, and 68% contained melanoma. Recurrence was observed in 33% overall. Only 1 patient (5%) developed an isolated same-basin recurrence. Cumulative incidences at 3 years were 5.0%, 17.3%, and 49.7% for isolated same-basin recurrence, any same-basin recurrence, and any recurrence, respectively. Complications from PLND were reported in 1 patient (5%). CONCLUSIONS: These pilot data suggest that PLND may provide adequate regional disease control with less morbidity than CLND. These data justify prospective evaluation of PLND in select patients.

Associations of immune cell homing gene signatures and infiltrates of lymphocyte subsets in human melanomas: discordance with CD163+ myeloid cell infiltrates.

BACKGROUND: Immune cells in the tumor microenvironment have prognostic value. In preclinical models, recruitment and infiltration of these cells depends on immune cell homing (ICH) genes such as chemokines, cell adhesion molecules, and integrins. We hypothesized ICH ligands CXCL9-11 and CCL2-5 would be associated with intratumoral T-cells, while CXCL13 would be more associated with B-cell infiltrates. METHODS: Samples of human melanoma were submitted for gene expression analysis and immune cells identified by immunohistochemistry. Associations between the two were evaluated with unsupervised hierarchical clustering using correlation matrices from Spearman rank tests. Univariate analysis performed Mann-Whitney tests. RESULTS: For 119 melanoma specimens, analysis of 78 ICH genes revealed association among genes with nonspecific increase of multiple immune cell subsets: CD45+, CD8+ and CD4+ T-cells, CD20+ B-cells, CD138+ plasma cells, and CD56+ NK-cells. ICH genes most associated with these infiltrates included ITGB2, ITGAL, CCL19, CXCL13, plus receptor/ligand pairs CXCL9 and CXCL10 with CXCR3; CCL4 and CCL5 with CCR5. This top ICH gene expression signature was also associated with genes representing immune-activation and effector function. In contrast, CD163+ M2-macrophages was weakly associated with a different ICH gene signature. CONCLUSION: These data do not support our hypothesis that each immune cell subset is uniquely associated with specific ICH genes. Instead, a larger set of ICH genes identifies melanomas with concordant infiltration of B-cell and T-cell lineages, while CD163+ M2-macrophage infiltration suggesting alternate mechanisms for their recruitment. Future studies should explore the extent ICH gene signature contributes to tertiary lymphoid structures or cross-talk between homing pathways.

IDO1 Expression in Melanoma Metastases Is Low and Associated With Improved Overall Survival.

Indoleamine 2-3 dioxygenase 1 (IDO1) expression may contribute to immunologic escape by melanoma metastases. However, a recent clinical trial failed to identify any clinical benefits of IDO1 inhibition in patients with unresectable metastatic melanoma, and prior characterizations of IDO1 expression have predominately studied primary lesions and local metastases, generating uncertainty regarding IDO1 expression in distant metastases. We hypothesized that IDO1 expression in such lesions would be low and correlated with decreased overall survival (OS). Metastases from patients (n=96) with stage IIIb to IV melanoma underwent tissue microarray construction and immunohistochemical staining for IDO1. Th1-related gene expression was determined quantitatively. Associations between OS and IDO1 expression were assessed with multivariate models. Of 96 metastatic lesions, 28% were IDOpos, and 85% exhibited IDO1 expression in <10% of tumor cells. IDOpos lesions were associated with improved OS (28.9 vs. 10.5 mo, P=0.02) and expression of Th1-related genes. OS was not associated with IDO1 expression in a multivariate analysis of all patients; however, IDO1 expression (hazard ratio=0.25, P=0.01) and intratumoral CD8+ T-cell density (hazard ratio=0.99, P<0.01) were correlated with OS in patients who underwent metastasectomy with curative-intent. IDOpos metastases were less likely to recur after metastasectomy (54% vs. 16%, P=0.01). IDO1 expression was low in melanoma metastases and correlated with OS after metastasectomy with curative-intent. Intratumoral CD8+ T cells and Th1-related genes were correlated with IDO1 expression, as was tumor recurrence. These suggest that IDO1 expression may be a marker of immunologic tumor control, and may inform participant selection in future trials of IDO1 inhibitors.

Gene expression analysis in formalin fixed paraffin embedded melanomas is associated with density of corresponding immune cells in those tissues.

Immune cell infiltrates in melanoma have important prognostic value. Gene expression analysis may simultaneously quantify numbers and function of multiple immune cell subtypes in formalin-fixed paraffin-embedded (FFPE) tissues. Prior studies report single gene expression can represent individual immune cell subtypes, but this has not been shown in FFPE melanomas. We hypothesized that gene expression profiling of human melanomas using a new RNA expression technology in FFPE tissue would correlate with the same immune cells identified by immunohistochemistry (IHC). This retrospective study included melanoma specimens analyzed by IHC on tumor tissue microarray (TMA) cores and by gene expression profiling with EdgeSeq Immuno-Oncology Assay using qNPA technology on the corresponding tumors. Standardized gene expression levels were analyzed relative to enumerated cells by IHC using Spearman rank test to calculate r-values. Multivariate analysis was performed by Kruskal-Wallis test. 119 melanoma specimens had both IHC and gene expression information available. There were significant associations between the level of gene expression and its quantified IHC cell marker for CD45+, CD3+, CD8+, CD4+, and CD20+ cells (all p < 0.001). There were also significant associations with exhaustion markers FoxP3+, PD-1+, and PD-L1+ (all p ≤ 0.0001). This new qNPA technology is useful to quantify intratumoral immune cells on FFPE specimens through RNA gene expression in metastatic melanoma. As previous studies have shown on other solid human tumors, we also confirm that the expression level of a single gene may be used to represent a single IHC immune cell marker in melanoma.

Bariatric surgery is associated with reduction in non-alcoholic steatohepatitis and hepatocellular carcinoma: A propensity matched analysis.

INTRODUCTION: Obesity is a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Bariatric surgery can provide durable weight-loss, but little is known about the later development of NASH and HCC after surgery. METHODS: Bariatric surgery (n = 3,410) and obese controls (n = 46,873) from an institutional data repository were propensity score matched 1:1 by demographics, comorbidities, BMI, and socioeconomic factors. Comparisons were made through paired univariate analysis and conditional logistic regression. RESULTS: Total of 4,112 patients were well matched with no significant baseline differences except initial BMI (49.0 vs 48.2, p = 0.04). Bariatric group demonstrated fewer new-onset NASH (6 0.0% vs 10.3%, p < 0.0001) and HCC (0.05% vs 0.34%, p = 0.03) over a median follow-up of 7.1 years. After risk-adjustment, bariatric surgery was independently associated with reduced development of NASH (OR 0.52, p < 0.0001). CONCLUSIONS: Bariatric surgery is associated with reduced incidence of NASH and HCC in this large propensity matched cohort. This further supports the use of bariatric surgery for morbidly obese patients to ameliorate NASH cirrhosis and development of HCC.

Correction to: Characteristics Associated with Pathologic Nodal Burden in Patients Presenting with Clinical Melanoma Nodal Metastasis.

In the original article, there is an error in the funding information. The correct funding information is as follows.

Characteristics Associated with Pathologic Nodal Burden in Patients Presenting with Clinical Melanoma Nodal Metastasis.

BACKGROUND: Nodal observation is safe for patients with microscopic melanoma metastasis in a sentinel lymph node (LN). Complete LN dissection (CLND) remains the standard of care for patients with clinically evident LN (cLN) metastases, even though about 40% have only one pathologic LN (pLN). We sought to identify clinical features associated with having one pLN among patients with cLNs. METHODS: Patients at three melanoma centers who underwent CLND for cLNs were identified. Clinicopathologic and imaging characteristics associated with one pLN were determined by multivariable logistic regression and classification tree analysis. RESULTS: Of 190 patients, 90 (47.4%) had one pLN and 100 (52.6%) had more than one pLN. By multivariable logistic regression, extremity versus truncal primary (odds ratio [OR] 2.15, p = 0.012), axillary versus superficial inguinal location (OR 3.89, p = 0.009), and preoperative cross-sectional imaging demonstrating more than one versus one cLN (OR 17.1, p < 0.001) were associated with more than one pLN. The negative predictive value for additional pathologic nodal disease of preoperative imaging was 70.9%, increasing to 74.4% for positron emission tomography/computed tomography. In the subgroup of patients with one cLN, the classification tree identified two groups with < 10% risk of additional pLNs: (1) Breslow thickness > 6.55 mm (n = 17); and (2) if unknown primary or Breslow thickness ≤ 6.55 mm, then LN diameter > 1.8 cm in the inguinal location (n = 22). CONCLUSION: The majority of patients with one cLN from melanoma by preoperative imaging will harbor no additional pathologic nodes on CLND. Safety of nodal observation after clinical nodal excision in these patients, particularly in an era of effective adjuvant therapies, deserves prospective evaluation.

Bariatric surgery is independently associated with a decrease in the development of colorectal lesions.

BACKGROUND: Obesity is a risk factor for colorectal cancer and possibly the formation of precancerous, colorectal polyps . Bariatric surgery is very effective for long-term weight loss; however, it is not known whether bariatric surgery decreases the risk of subsequent colonic neoplasia. We hypothesized that bariatric surgery would decrease the risk of developing colorectal lesions (new cancer and precancerous polyps). METHODS: We reviewed all patients (n = 3,676) who underwent bariatric surgery (gastric bypass, sleeve gastrectomy, or gastric banding) at the University of Virginia (Charlottesville, VA) 1985-2015. Obese, nonoperative patients (n = 46,873) from an institutional data repository were included as controls. Cases and controls were propensity score matched 1:1 by demographics, comorbidities, body mass index, and socioeconomic factors. The matched cohort was compared by univariate analysis and conditional logistic regression. RESULTS: A total of 4,462 patients (2,231 per group) with a median follow-up of 7.8 years were well-matched with no statistically significant baseline differences in initial body mass index (48 vs 49 kg/m2), sex, and age in addition to other comorbidities (all P > .05). The operative cohort had more weight loss (55.5% vs -1.4% decrease in excess body mass index, P < .0001). The operative cohort developed fewer colorectal lesions (2.4% vs 4.8%, P < .0001). We observed no differences in polyp characteristics or staging for patients who developed cancer (all P > .05). After risk adjustment, bariatric surgery was independently associated with a decrease in new colorectal lesions (OR 0.62, 95% CI 0.42-0.91, P = .016). CONCLUSION: Bariatric surgery was associated with lesser, risk-adjusted incidence of new colorectal lesions in this large population of propensity matched patients undergoing bariatric surgery compared with a control group not undergoing bariatric surgery. These results suggest the benefits of bariatric surgery may extend beyond weight loss and mitigation of comorbidities.

Vaccine Strategy in Melanoma.

The incidence of melanoma continues to increase even as advances in immunotherapy have led to survival benefits in advanced stages. Vaccines are capable of inducing strong, antitumor immune responses with limited toxicity. Some vaccines have demonstrated clinical benefit in clinical trials alone; however, others have not despite inducing strong immune responses. Recent advancements have improved vaccine design, and combining vaccines with other immunotherapies offers promise. This review highlights the underlying principles of vaccine development, common components of vaccines, and the remaining challenges and future directions of vaccine therapy in melanoma.

Updates in adjuvant systemic therapy for melanoma.

There has been a rapid increase in adjuvant therapies approved for treatment following surgical resection of stages III/IV melanoma. We review current indications for adjuvant therapy, which currently includes a heterogenous group of stages III and IV patients with melanoma. We describe several pivotal clinical trials of systemic immune therapies, targeted immune therapies, and adjuvant vaccine strategies. Finally, we discuss the evidence for selecting the most appropriate treatment regimen(s) for the individual patient.

First Descents, an adventure program for young adults with cancer: who benefits?

BACKGROUND: Participation in camps, adventure programs, retreats, and other social events offers experiences that can promote self-efficacy and quality of life. PURPOSE: The purpose of the study was to examine whether participation in a 1-week outdoor adventure program resulted in improvements in psychological distress, self-efficacy, and/or social support for young adult cancer patients (AYAs) aged 18-40 years. The study examined the differential effect of participation for AYAs who indicated moderate to severe symptoms of psychological distress prior to their trip. METHODS: Standardized measures of distress, self-efficacy, and social support were administered pre-trip, post-trip, and 1 month after program completion (follow-up). Univariate and multivariate models examined baseline scores for non-distressed participants compared to distressed participants, changes in outcomes from pre-trip to post-trip and follow-up for the entire sample, and the extent to which change rates for each outcome differed for distressed versus non-distressed participants. RESULTS: All participants demonstrated significant improvement in self-efficacy over time. Distressed participants reported a significantly greater decrease in distress symptoms and greater increase in self-efficacy and social support at post-trip and 1 month later when compared to non-distressed participants. CONCLUSIONS: Findings suggest that participation in an outdoor recreational activity designed specifically for AYAs with cancer contributes to significant reductions in distress and improvements in self-efficacy and social support, and particularly for AYAs reporting clinically significant distress symptoms prior to the initiation of their activity.

The relationship between posttraumatic stress and posttraumatic growth among adolescent and young adult (AYA) cancer patients.

OBJECTIVE: Theories of posttraumatic growth suggest that some degree of distress is necessary to stimulate growth; yet, investigations of the relationship between stress and growth following trauma are mixed. This study aims to understand the relationship between posttraumatic stress symptoms and posttraumatic growth in adolescent and young adult (AYA) cancer patients. METHOD: 165 AYA patients aged 14-39 years at diagnosis completed standardized measures of posttraumatic stress and posttraumatic growth at 12 months following diagnosis. Locally weighted scatterplot smoothing and regression were used to examine linear and curvilinear relationships between posttraumatic stress and posttraumatic growth. RESULTS: No significant relationships between overall posttraumatic stress severity and posttraumatic growth were observed at 12-month follow-up. However, curvilinear relationships between re-experiencing (a posttraumatic stress symptom) and two of five posttraumatic growth indicators (New Possibilities, Personal Strengths) were observed. CONCLUSION: Findings suggest that re-experiencing is associated with some aspects of posttraumatic growth but not others. Although re-experiencing is considered a symptom of posttraumatic stress disorder, it also may represent a cognitive process necessary to achieve personal growth for AYAs. Findings call into question the supposed psychopathological nature of re-experiencing and suggest that re-experiencing, as a cognitive process, may be psychologically adaptive. Opportunities to engage family, friends, cancer survivors, or health care professionals in frank discussions about fears, worries, or concerns may help AYAs re-experience cancer in a way that enhances their understanding of what happened to them and contributes to positive adaptation to life after cancer.

Trajectories of psychological distress in adolescent and young adult patients with cancer: a 1-year longitudinal study.

PURPOSE: To examine prevalence and changes in symptoms of psychological distress over 1 year after initial cancer diagnosis in adolescent and young adult (AYA) patients with cancer. Sociodemographic and clinical predictors of changes in distress were examined. PATIENTS AND METHODS: In this multisite, longitudinal, prospective study of an ethnically diverse sample, 215 patients age 14 to 39 years were assessed for psychological distress within the first 4 months of diagnosis and again 6 and 12 months later. Linear mixed models with random intercept and slope estimated changes in distress, as measured by the Brief Symptom Inventory-18 (BSI-18). RESULTS: Within the first 4 months of diagnosis, 60 respondents (28%) had BSI-18 scores suggesting caseness for distress. On average, distress symptoms exceeded population norms at the time of diagnosis, dipped at the 6-month follow-up, but increased to a level exceeding population norms at the 12-month follow-up. A statistically significant decline in distress over 1 year was observed; however, the gradient of change was not clinically significant. Multivariate analyses revealed that the reduction in distress over time was primarily a function of being off treatment and involved in school or work. Notably, cancer type or severity was not associated with distress. CONCLUSION: Findings emphasize the importance of early psychosocial intervention for distress in AYAs as well as the need to manage treatment-related symptoms and facilitate AYAs' involvement in work or school to the extent possible. Continued research is needed to understand how distress relates to quality of life, functional outcomes, treatment, and symptom burden throughout the continuum of care.

The couples life story approach: a dyadic intervention for dementia.

This article describes an approach for working with individuals who have dementia, along with their spouses or partners. The 5-week intervention focuses on helping couples communicate, reminisce about the story of their relationship, find photographs and mementoes from their past, and develop a book that incorporates these mementoes. This clinical approach highlights the strengths and the resilience of couples and adds to the limited repertoire of dyadic interventions for dementia care which are currently available. Preliminary findings from 24 couples are presented, including the intervention's feasibility and acceptability.

Prevalence and predictors of post-traumatic stress symptoms in adolescent and young adult cancer survivors: a 1-year follow-up study.

OBJECTIVES: Post-traumatic stress symptoms (PTSS) have been identified as a meaningful indicator of distress in cancer survivors. Distinct from young adult survivors of childhood cancer, young people diagnosed with cancer as adolescents and young adults (AYAs) face unique psychosocial issues; however, there is little published research of PTSS in the AYA population. This study examines prevalence and predictors of PTSS among AYAs with cancer. METHODS: As part of a longitudinal study of AYAs with cancer, 151 patients aged 15-39 years completed mailed surveys at 6 and 12 months post-diagnosis. Severity of PTSS was estimated at 6 and 12 months post-diagnosis. Multiple regression analyses were conducted to investigate the predictive effects of socio-demographic and clinical characteristics on changes in PTSS over time. RESULTS: At 6 and 12 months, respectively, 39% and 44% of participants reported moderate to severe levels of PTSS; 29% had PTSS levels suggestive of post-traumatic stress disorder. No significant differences in severity of PTSS between 6 and 12 months were observed. Regression analyses suggested that a greater number of side effects were associated with higher levels of PTSS at 6 months. Currently receiving treatment, having surgical treatment, diagnosis of a cancer type with a 90-100% survival rate, remaining unemployed/not in school, and greater PTSS at 6 months were associated with higher levels of PTSS at 12 months. CONCLUSIONS: Post-traumatic stress symptoms were observed as early as 6 months following diagnosis and remained stable at 12-month follow-up. The development of early interventions for reducing distress among AYA patients in treatment is recommended.