Financial toxicity among people with metastatic cancer: findings from the Cancer Experience Registry.

PURPOSE: This study describes financial toxicity (FT) reported by people with metastatic cancer, characteristics associated with FT, and associations between FT and compensatory strategies to offset costs. METHODS: Cancer Support Community's Cancer Experience Registry data was used to identify respondents with a solid tumor metastatic cancer who completed the Functional Assessment of Chronic Illness Therapy COmprehensive Score for Financial Toxicity (FACIT-COST) measure. Multivariable logistic regression analyses examined associations between respondent characteristics and FT, and FT and postponing medical visits, nonadherence to medications, and postponing supportive and/or psychosocial care. RESULTS: 484 individuals were included in the analysis; the most common cancers included metastatic breast (31%), lung (13%), gynecologic (10%), and colorectal (9%). Approximately half of participants (50.2%) reported some degree of FT. Those who were non-Hispanic White, Hispanic, or multiple races (compared to non-Hispanic Black), and who reported lower income, less education, and being less than one year since their cancer diagnosis had greater odds of reporting FT. Individuals with any level of FT were also more likely to report postponing medical visits (Adjusted Odds Ratio [OR] 2.58; 95% Confidence Interval [CI] 1.45-4.58), suboptimal medication adherence (Adjusted OR 5.05; 95% CI 2.77-9.20) and postponing supportive care and/or psychosocial support services (Adjusted OR 4.16; 95% CI 2.53-6.85) compared to those without FT. CONCLUSIONS: With increases in the number of people living longer with metastatic cancer and the rising costs of therapy, there will continue to be a need to systematically screen and intervene to prevent and mitigate FT for these survivors.

Interrater Reliability of an Observational Rating Scale and Video Analysis of Yoga Poses.

CONTEXT: Yoga is increasingly popular, not only as a form of recreational exercise but also as a physician-recommended intervention for health conditions. While serious adverse effects accompanying yoga practice are rare, poses that involve upper-extremity weight-bearing have a high risk of discomfort. To better understand factors contributing to adverse effects, there is a critical need for robust instruments that objectively evaluate pose performance. The purpose of this study was to assess the interrater reliability of an observational scale developed to assess the alignment of 3 yoga poses. DESIGN: Cross-sectional experimental study. METHODS: Thirty-eight individuals were given standardized instructions and performed 3 poses (Downward Dog, Plank, and Side Plank). Lateral videos were rated by 2 raters. A rating scale evaluating the alignment of 7 regions was developed by the study team with input from yoga teachers. Descriptive statistics were used to summarize the percentage of subjects showing ideal alignment and deviations. Interrater reliability was quantified using Cohen kappa coefficient (κ). RESULTS: In Downward Dog, the prevalence of ideal alignment was 20%, 28%, and 37%, at the neck, shoulder, and back, respectively; κ ranged from .44 to .69. In Plank, the prevalence of ideal alignment was 31%, 45%, and 54% at the neck, shoulder, and back, respectively; κ ranged from .47 to .95. In Side Plank, the prevalence of ideal alignment was 16, 41%, and 24%, at the neck, shoulder, and back, respectively; κ ranged from .20 to .84. CONCLUSION: The observational scale found a high prevalence of deviations, and demonstrated fair to substantial interrater agreement.

Seeing the whole elephant - How lobstermen's local ecological knowledge can inform fisheries management.

Lobstermen in Southern New England come from a longstanding intergenerational fishing tradition. Their local ecological knowledge (LEK) on the American lobster, Homarus americanus can be an important source of information for management. This paper examines lobstermen's LEK as it relates to stock assessment and the overlap to science based ecological knowledge (SEK). Although in recent years, using vent-less trap assessments and conducting young of the year surveys, has set the stage for more cooperative research, in our opinion, lobstermen's LEK remains underutilized in fisheries management. There has been a steady decline in the lobster stocks over the years, raising concerns regarding fisheries management. For this reason, we turn to lobstermen's knowledge as an important source that could inform fisheries management. Using a semi-structured approach, the stakeholders' LEK and open discussions were recorded during three meetings where lobstermen participated with managers and scientists. LEK was transcribed and categorized and matched to the corresponding SEK described in the literature. Results generally found that the lobstermen's LEK corresponded with the best available SEK. LEK is compatible with an ecosystem view of the fishery that integrates the complexities of interacting systems. The lobstermen explained that they viewed their fishing grounds as "managed landscapes", areas used productively, maintained and protected by them. These results are a starting point to broaden the base of the knowledge used in fisheries management enabling us to see the whole picture. Topics of LEK and SEK convergence are promising common ground, while topics where lobstermen and managers' views differ, can serve as points of entry to enable research and cooperative management. Both can be the basis for cooperative hypothesis testing.

Outcomes of multidisciplinary treatment planning in US cancer care settings.

Multidisciplinary treatment planning (MTP) is a process of engaging multiple disciplines to develop or refine the disease management plan. It is widely implemented in US cancer treatment settings and is considered to have favorable effects on both care quality and other outcomes. However, evidence reviews to date regarding MTP effectiveness have based their conclusions on studies conducted predominantly outside the United States. The authors conducted a systematic review of US-based studies to synthesize and critically appraise evidence of the effects of MTP on cancer care quality, health services outcomes, and survival. Database searches identified studies of MTP outcomes conducted in US cancer care settings from 2000 to 2017. Forty-five studies met criteria for inclusion. MTP was associated with favorable effects on several indicators of cancer care quality, including delivery of guideline-concordant treatment and improvements in diagnostic accuracy, staging completeness, surgical technique, and timeliness. Effects on survival and clinical trials enrollment were mixed. Delivery formats for MTP were generally not well described, and study designs were nonrandomized, limiting the ability to identify mediators of intervention effects. Continued study is warranted to clarify effective components of MTP interventions, and to understand the mechanism(s) through which MTP produces favorable effects on outcomes.

Ontogenetic allometry conservatism across five teleost orders.

Geometric morphometrics were used to analyse ontogenetic trajectories in representatives of the Characiformes, Cichliformes, Cyprinodontiformes, Siluriformes, and Tetraodontiformes. It was not possible to differentiate any allometric growth patterns across groups, indicating that a phylogenetically conserved developmental pattern is widespread throughout Teleostei.

The National Cancer Institute Community Cancer Centers Program (NCCCP): Sustaining Quality and Reducing Disparities in Guideline-Concordant Breast and Colon Cancer Care.

BACKGROUND: The National Cancer Institute Community Cancer Centers Program (NCCCP) pilot was designed to improve quality of cancer care and reduce disparities at community hospitals. The NCCCP's primary intervention was the implementation of the Commission on Cancer Rapid Quality Reporting System (RQRS). The RQRS is a hospital-based data collection and evaluation system allowing near real-time assessment of selected breast and colon cancer quality of care measures. Building on previous NCCCP analyses, this study examined whether improvements in quality cancer care within NCCCP hospitals early in the program were sustained and whether improvements were notable for minority or underserved populations. METHODS: We compared changes in concordance with three breast and two colon cancer quality measures approved by the National Quality Forum for patients diagnosed at NCCCP hospitals from 2006 to 2007 (pre-RQRS), 2008 to 2010 (early-RQRS), and 2011 to 2013 (later-RQRS). Data were obtained from NCCCP sites participating in the Commission on Cancer Rapid Quality Reporting System. Logistic regression analyses were performed to identify predictors of concordance with breast and colon cancer quality measures. RESULTS: The sample included 13,893 breast and 5,546 colon cancer patients. After RQRS initiation, all five quality measures improved significantly and improvements were sustained through 2013. Quality of care measures showed sustained improvements for both breast and colon cancer patients and for vulnerable patient subgroups including black, uninsured, and Medicaid-covered patients. CONCLUSIONS: Quality improvements in NCCCP hospitals were sustained throughout the duration of the program, both overall and among minority and underserved patients. Because many individuals receive cancer treatment at community hospitals, facilitating high-quality care in these environments must be a priority. IMPLICATIONS FOR PRACTICE: Quality improvement programs often improve practice, but the methods are not maintained over time. The implementation of a real-time quality reporting system and a network focused on improving quality of care sustained quality improvement at select community cancer centers. The NCCCP pilot increased numbers of patients receiving guideline-concordant care for breast and colon cancer in community settings, and initial improvements noted in earlier years of RQRS were sustained into later years, both overall and among minority and underserved patients. National initiatives that improve care for diverse patient groups are important for reducing and eliminating barriers to care.

Evaluation of different recall periods for the US National Cancer Institute's PRO-CTCAE.

AIMS: The US National Cancer Institute recently developed the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g. nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-, 2-, 3-, and 4-week recall periods, using daily reporting as the reference. METHODS: English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four US cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-, 2-, 3-, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g. maximum of daily scores over 7 days vs 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. RESULTS: A total of 127 subjects completed questionnaires (57% male; median age: 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size) was -0.20 (-0.20) for 1-week recall, -0.36 (-0.31) for 2-week recall, -0.45 (-0.39) for 3-week recall, and -0.47 (-0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54-0.82), for 2-week recall was 0.74 (range: 0.58-0.83), for 3-week recall was 0.72 (range: 0.61-0.84), and for 4-week recall was 0.72 (range: 0.64-0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. CONCLUSION: A 1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss.

The rationale for patient-reported outcomes surveillance in cancer and a reproducible method for achieving it.

Patient-reported outcomes (PROs) measure quality of life, symptoms, patient functioning, and patient perceptions of care; they are essential for gaining a full understanding of cancer care and the impact of cancer on people's lives. Repeatedly captured facility-level and/or population-level PROs (PRO surveillance) could play an important role in quality monitoring and improvement, benchmarking, advocacy, policy making, and research. This article describes the rationale for PRO surveillance and the methods of the Patient Reported Outcomes Symptoms and Side Effects Study (PROSSES), which is the first PRO study to use the American College of Surgeons Commission on Cancer's Rapid Quality Reporting System to identify patients and manage study data flow. The American Cancer Society, the National Cancer Institute, the Commission on Cancer, and RTI International collaborated on PROSSES. PROSSES was conducted at 17 cancer programs that participated in the National Cancer Institute Community Cancer Centers Program among patients diagnosed with locoregional breast or colon cancer. The methods piloted in PROSSES were successful as demonstrated by high eligibility (93%) and response (61%) rates. Differences in clinical and demographic characteristics between respondents and nonrespondents were mostly negligible, with the exception that non-white individuals were somewhat less likely to respond. These methods were consistent across cancer centers and reproducible over time. If repeated and expanded, they could provide PRO surveillance data from patients with cancer on a national scale.

Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

BACKGROUND: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. METHODS: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. RESULTS: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. CONCLUSIONS: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. TRIAL REGISTRATION: NCT Clinicaltrials.gov identifier: NCT02158637.

The development and acceptability of symptom management quality improvement reports based on patient-reported data: an overview of methods used in PROSSES.

PURPOSE: Patient experiences with symptom care need to be assessed and documented to ensure successful management of cancer-related symptoms. This paper details one method for creating symptom management quality improvement (SMQI) reports, including case-mix adjustment of patient-reported measures. Qualitative data regarding the acceptability of these reports at participating cancer centers (CCs) are also provided. METHODS: Data were collected from 2226 patients treated at 16 CCs via mailed/Web questionnaires. Twelve items assessing patient perceptions of symptom management-pain, fatigue, emotional distress-served as key quality indicators. Medico-demographic variables suitable for case-mix adjustment were selected using an index score combining predictive power and heterogeneity across CCs. SMQI reports were designed with staff feedback and produced for each CC, providing crude and adjusted CC-specific rates, along with study-wide rates for comparison purposes. RESULTS: Cancer type and participant educational level were selected for case-mix adjustment based upon high index scores. The Kendall rank correlation coefficient showed that case-mix adjustments changed the ranking of CCs on the key quality indicators (% Δ rank range: 5-22 %). The key quality indicators varied across CCs (all p < 0.02). SMQI reports were well received by CC staff, who described plans to share them with key personnel (e.g., cancer committee, navigator). CONCLUSIONS: This paper provides one method for creating hospital-level SMQI reports, including case-mix adjustment. Variation between CCs on key quality indicators, even after adjustment, suggested room for improvement. SMQI reports based on patient-reported data can inform and motivate efforts to improve care through professional/patient education and applying standards of care.

Survivorship concerns among individuals diagnosed with metastatic cancer: Findings from the Cancer Experience Registry.

INTRODUCTION: Individuals with metastatic cancer experience many medical, physical, and emotional challenges due to changing medical regimens, oscillating disease states, and side effects. The purpose of this study was to describe the type and prevalence of survivorship concerns reported by individuals with metastatic cancer, and their associations with cancer diagnosis, treatment, and socio-demographic variables. METHODS: This study utilized data from the Cancer Support Community's Cancer Experience Registry. Individuals were included if they self-reported a solid tumor metastatic cancer and completed CancerSupportSource, which evaluates five domains of concerns (emotional well-being, symptom burden, body image/healthy lifestyle, healthcare team communication, and relationships/intimacy). Multivariable linear regression examined associations between independent predictors of each survivorship concern domain. RESULTS: Of the 403 included participants, individuals reported a metastatic diagnosis of breast (43%), colorectal (20%), prostate (7%), lung (7%), gynecologic cancer (6%) and other. Nearly all (96%) reported at least one survivorship concern, with the most prevalent concern about cancer progression or recurrence. Survivorship concerns were higher across multiple domains for individuals unemployed due to disability. Individuals who were less than five years since diagnosis reported higher concerns related to emotional well-being, symptom burden, and healthcare communication compared to those more than five years since diagnosis. CONCLUSION: Individuals with metastatic cancer experience a variety of moderate-to-severe survivorship concerns that warrant additional investigation. IMPLICATIONS FOR CANCER SURVIVORS: As the population of individuals with metastatic cancer lives longer, future research must investigate solutions to address modifiable factors associated with survivorship concerns, such as unemployment due to disability.

Epizootic shell disease in American lobsters Homarus americanus in southern New England: past, present and future.

The emergence of epizootic shell disease in American lobsters Homarus americanus in the southern New England area, USA, has presented many new challenges to understanding the interface between disease and fisheries management. This paper examines past knowledge of shell disease, supplements this with the new knowledge generated through a special New England Lobster Shell Disease Initiative completed in 2011, and suggests how epidemiological tools can be used to elucidate the interactions between fisheries management and disease.

Thematic Analysis of Organizational Characteristics in NCI Community Oncology Research Program Cancer Care Delivery Research.

Organizational characteristics, including organizational structures and processes, are important to understanding care delivery and health outcomes. However, organizational-level constructs present measurement challenges in care delivery research. This analysis aims to understand if, when, and how organizational characteristics are examined in a National Cancer Institute (NCI) research network conducting cancer care delivery research (CCDR). The NCI Community Oncology Research Program encourages consideration of organizational variables in CCDR studies. We conducted a cross-sectional thematic analysis to identify organizational characteristics examined in this portfolio of research. Organizational characteristics targeted, related measures, and analytic approach were abstracted by 2 study investigators using a coding framework adapted from 2 existing frameworks. A total of 78.9% of eligible study protocols included organizational characteristics. Structural characteristics were the most common, collected in all 15 included protocols, 14 examined at least 1 organizational process, and 12 examined organizational-level outcomes. Most studies proposed descriptive practice-level analyses or multilevel analyses using random effects to account for clustering of patients and staff within practices. Few (n = 5) specified that organizational variables would be modeled as effects of interest (vs covaried out) or proposed analytic approaches that could more robustly examine effects of targeted organizational characteristics on primary outcomes. Inclusion of organizational variables is common in CCDR conducted through the NCI Community Oncology Research Program, NCI's national network charged with bringing cancer clinical trials to people in their communities. Nonetheless, opportunities remain to improve the use of theory to guide organizational construct selection, operationalization, measurement, and incorporation into study hypotheses and analyses.

Cost-Related Medication Nonadherence and Patient Cost Responsibility for Rural and Urban Cancer Survivors.

PURPOSE: The relationship between out-of-pocket spending and cost-related medication nonadherence among older rural- and urban-dwelling cancer survivors is not well understood. METHODS: This retrospective cohort study used the Surveillance, Epidemiology, and End Results Program, Medicare claims, and the Consumer Assessment of Healthcare Providers and Systems survey linked data resource linked data (2007-2015) to investigate the relationship between cancer survivors' cost responsibility in the year before and after report of delaying or not filling a prescription medication because of cost in the past 6 months (cost-related medication nonadherence). Secondary exposures and outcomes included Medicare spending and utilization. Generalized linear models assessed bidirectional relationships between cost-related medication nonadherence, spending, and utilization. Effects of residence were assessed via interaction terms. RESULTS: Of 6,591 older cancer survivors, 13% reported cost-related medication nonadherence. Survivors were a median 8 years (interquartile range, 4.5-12.5 years) from their cancer diagnosis, 15% were dually Medicare/Medicaid-eligible, and prostate (40%) and breast (32%) cancer survivors were most prevalent. With every $500 USD increase in patient cost responsibility, risk of cost-related medication nonadherence increased by 3% (risk ratio, 1.03; 95% CI, 1.02 to 1.04). After report of cost-related medication nonadherence, patient cost responsibility was 22% higher (95% CI, 1.11 to 1.32) compared with those not reporting nonadherence, amounting to $523 USD (95% CI, $430 USD to $630 USD). Medicare spending and utilization were also higher before and after report of cost-related nonadherence versus none. For survivors residing in rural (18%) and urban (82%) areas, residence did not modify adherence or cost outcomes. CONCLUSION: A bidirectional relationship exists between patient cost responsibility and cost-related medication nonadherence. Interventions reducing urban- and rural-dwelling survivor health care costs and cost-related adherence barriers are needed.

Cancer clinical trial providers' perspectives on communicating goals of care: A key informant study.

Objectives: There has been limited research to date exploring provider communication in the context of cancer clinical trials. To elucidate multidisciplinary care providers' experiences, this qualitative study sought to understand their perspectives and communication patterns around goals of care discussions with patients enrolled in cancer clinical trials. Methods: Semi-structured key informant interviews were conducted with a purposive sample of physicians, nurse practitioners, social workers, chaplains, nurses, and administrative staff in a cancer research hospital (N=19). Data were analyzed and interpreted using thematic analysis. Results: Providers hold varied perspectives on goals of care in cancer clinical trials, highlighting the tension and potential for misalignment between scientific and clinical (patient-centered) goals. Inherent institutional hierarchies may impede some team members from initiating goal discussions. Care transitions (e.g., stopping treatment or initiating hospice) offer critical opportunities for goals of care discussions. Conclusion: Conflicting perspectives among team members, perceptions of provider roles, and communication patterns could help explain some of the communication challenges previously documented in advanced cancer and clinical trial care. Innovation: This qualitative study contributes to the literature on healthcare team communication in the clinical trial context and highlights tangible opportunities to better leverage providers' diverse experience and improve patient-centered care.

Survivorship for Individuals Living With Advanced and Metastatic Cancers: National Cancer Institute Meeting Report.

An important and often overlooked subpopulation of cancer survivors is individuals who are diagnosed with or progress to advanced or metastatic cancer. Living longer with advanced or metastatic cancer often comes with a cost of burdensome physical and psychosocial symptoms and complex care needs; however, research is limited on this population. Thus, in May 2021, the National Cancer Institute convened subject matter experts, researchers, clinicians, survivors, and advocates for a 2-day virtual meeting. The purpose of this report is to provide a summary of the evidence gaps identified by subject matter experts and attendees and key opportunities identified by the National Cancer Institute in 5 research areas: epidemiology and surveillance, symptom management, psychosocial research, health-care delivery, and health behaviors. Identified gaps and opportunities include the need to develop new strategies to estimate the number of individuals living with advanced and metastatic cancers; understand and address emerging symptom trajectories; improve prognostic understanding and communication between providers, patients, and caregivers; develop and test models of comprehensive survivorship care tailored to these populations; and assess patient and provider preferences for health behavior discussions throughout the survivorship trajectory. To best address the needs of individuals living with advanced and metastatic cancer and to deliver comprehensive evidence-based quality care, research is urgently needed to fill evidence gaps, and it is essential to incorporate the survivor perspective. Developing such an evidence base is critical to inform policy and practice.

Potent immunomodulatory and antitumor effect of anti-CD20-IL2no-alpha tri-functional immunocytokine for cancer therapy.

Introduction: The anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs. Methods: To improve the efficacy of RTX therapy, we fused a murine (mIgG2a) or a human (hIgG1) version of RTX to a mutated IL-2 (no-alpha mutein), which has a disrupted affinity for the high affinity IL-2 receptor (IL-2R) to prevent the stimulation of Tregs and reduce the binding to endothelial cells expressing CD25, the α chain of high affinity IL-2R. Characterization of anti-CD20-IL2no-alpha ICKs was performed by SDS-PAGE, Western-blotting and SEC-HPLC and also by several functional in vitro techniques like T-cell proliferation assays, apoptosis, CDC and ADCC assays. The in vivo activity was assessed by using murine tumor cells expressing huCD20 in C57/Bl6 mice. Results: Both ICKs exhibited similar in vitro specific activity of their IL2no-alpha mutein moieties and kept CD20-binding capacity. Anti-CD20-IL2no-alpha (hIgG1) retained antibody effector functions as complement-dependent cytotoxicity and enhanced direct apoptosis, NK cell activation and antibody-dependent cellular cytotoxicity relative to RTX. In addition, both ICKs demonstrated a higher antitumor efficacy than parental molecules or their combination in an EL4-huCD20 tumor model in immunocompetent mice. Anti-CD20-IL2no-alpha (hIgG1) strongly expanded NK and CD8+ T cells but not Tregs in tumor-bearing mice. Discussion: These findings suggest that anti-CD20-IL2no-alpha could represent an alternative treatment for B cell lymphoma patients, mainly those refractory to RTX therapy.

Water constraints drive allometric patterns in the body shape of tree frogs.

The origin of morphological diversity is a critical question in evolutionary biology. Interactions between the environment and developmental processes have determining roles in morphological diversity, creating patterns through space and over time. Also, the shape of organisms tends to vary with increasing size as a result of those developmental processes, known as allometry. Several studies have demonstrated that the body sizes of anurans are associated with hydric conditions in their environments and that localities with high water stress tend to select for larger individuals. However, how environmental conditions alter those patterns of covariance between size and shape is still elusive. We used 3D geometric morphometric analyses, associated with phylogenetic comparative methods, to determine if the morphological variations and allometric patterns found in Arboranae (Anura) is linked to water conservation mechanisms. We found effects of the hydric stress on the shape of Arboranae species, favouring globular shapes. Also, the allometric patterns varied in intensity according to the water stress gradient, being particularly relevant for smaller frogs, and more intense in environments with higher water deficits. Our study provides empirical evidence that more spherical body shapes, especially among smaller species, reflect an important adaptation of anurans to water conservation in water-constrained environments.

National Cancer Institute: Restructuring to Support the Clinical Trials of the Future.

OBJECTIVES: To describe the evolution and structure of the National Cancer Institute clinical trials programs, their notable accomplishments, nurses' roles in these accomplishments, and the essential role of nursing today and in the future. DATA SOURCES: Manuscripts, government publications, websites, and professional communications. CONCLUSION: Change is inevitable and a constant factor in the world of advancing science and clinical research. Nurses' contribution to research and evidence-based practice will continue to grow and is vital as the scientific landscape evolves. IMPLICATIONS FOR NURSING PRACTICE: As the understanding of cancer biology increases and clinical trials evolve, nurses will need to remain key team members and leaders in National Cancer Institute Community Oncology Research Program and National Cancer Trials Network trials and their associated infrastructure.

Evolution of Cancer Care Delivery Research in the NCI Community Oncology Research Program.

Research seeking to improve patient engagement with decision-making, use of evidence-based guidelines, and coordination of multi-specialty care has made important contributions to the decades-long effort to improve cancer care. The National Cancer Institute expanded support for these efforts by including cancer care delivery research in the 2014 formation of the National Cancer Institute Community Oncology Research Program (NCORP). Cancer care delivery research is a multi-disciplinary effort to generate evidence-based practice change that improves clinical outcomes and patient well-being. NCORP scientists and community-based clinicians and organizations rapidly embraced the addition of this type of research into the network, resulting in a robust portfolio of observational studies and intervention studies within the first 5 years of funding. This commentary describes the initial considerations in conducting this type of research in a network previously focused on cancer prevention, control, and treatment studies; characterizes the protocols developed to date; and outlines future directions for cancer care delivery research in the second round of NCORP funding.