ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Advantages and challenges of using physics curricula as a model for reforming an undergraduate biology course.

We report on the development of a life sciences curriculum, targeted to undergraduate students, which was modeled after a commercially available physics curriculum and based on aspects of how people learn. Our paper describes the collaborative development process and necessary modifications required to apply a physics pedagogical model in a life sciences context. While some approaches were easily adapted, others provided significant challenges. Among these challenges were: representations of energy, introducing definitions, the placement of Scientists' Ideas, and the replicability of data. In modifying the curriculum to address these challenges, we have come to see them as speaking to deeper differences between the disciplines, namely that introductory physics--for example, Newton's laws, magnetism, light--is a science of pairwise interaction, while introductory biology--for example, photosynthesis, evolution, cycling of matter in ecosystems--is a science of linked processes, and we suggest that this is how the two disciplines are presented in introductory classes. We illustrate this tension through an analysis of our adaptations of the physics curriculum for instruction on the cycling of matter and energy; we show that modifications of the physics curriculum to address the biological framework promotes strong gains in student understanding of these topics, as evidenced by analysis of student work.

Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma.

Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4+CD25+ regulatory T (T(reg)) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25+ T(reg) cells while rituximab would deplete malignant B cells. Patients received rituximab 375 mg/m(2) weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% confidence interval (CI): 27-69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37-82%). Thirteen patients (57%) experienced grade ≥3 adverse events and one patient (4%) died. In correlative studies, soluble CD25 and the number of CD25+ T cells decreased after treatment; however, there was a compensatory increase in IL-15 and IP-10. We conclude that although the addition of denileukin diftitox to rituximab decreased the number of CD25+ T cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression.

Occlusion: an orthodontic perspective.

In recent years, orthodontists have examined their concepts of occlusion. In current literature, at professional meetings, and in continuing education courses, one hears an ongoing discussion of condylar position and mandibular border movements in relation to occlusion. There is a wide variation in opinion as to whether dental occlusion and TMJ function are interdependent. The authors have adopted a dynamic concept of dental function to replace the traditional static view of molar relationship and incisor overlap. This article discusses how occlusion has evolved in orthodontics and reviews Andrews' six keys to ideal static occlusion, the goals of ideal dynamic occlusion, and the six signs of developing malocclusions. The authors also review the literature on the relationship between orthodontics, occlusion, and TMD.

Medical device industry efforts to increase healthcare value.

Although governmental healthcare reform initiatives have come to a stop in Washington, DC, the healthcare delivery system is, nevertheless, being transformed. Change is being driven by managed care organizations, which are looking for increased cost-effectiveness, and by providers of care and suppliers of medical products, who are trying to differentiate themselves from their competitors on the basis of service and quality. The efforts of one medical device company, Medtronic, are indicative of what the medical device industry is doing to increase the value (cost and quality) of healthcare.

Using empowerment to make quality work in health care.

Is TQM dead in health care? If it is alive and well, what role does quality improvement play in managing the changes that come with health care reform? William Byham and Greg Nelson begin this article by presenting results from a recent international study on TQM, outlining factors common to successful and unsuccessful quality initiatives. The key to success? Organizations must improve how people work as much as what they do in their work, and that means empowering people to improve processes. Easier said than done, say Byham and Nelson. Empowerment requires culture change and training. People first need the right environment to work differently, then the skills, knowledge, and techniques to participate in and influence the quality process.

The impact of a preschool health curriculum on children's health knowledge.

This evaluation assessed the effect of Hale and Hardy's Helpful Health Hints preschool health education curriculum on the health knowledge of children ages three-six. The sample consisted of nine experimental preschool programs (n = 194) and three comparison preschool programs (n = 73). A picture identification test assessed children's pretest and posttest health knowledge of the five senses, safety, nutrition, dental health, personal responsibility, emotions, hygiene, and drugs/medicines. Posttest knowledge scores increased by 22% among experimental group preschool programs and 12% among comparison group preschool programs. Significant differences (p less than .01) were found between experimental and comparison group students. Findings provide direction in research efforts to define conditions in which preschool health education is optimally effective.

Establishing a system of complementary school-based surveys to annually assess HIV-related knowledge, beliefs, and behaviors among adolescents.

The Division of Adolescent and School Health, Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control has responsibility for assisting national, state, and local education agencies to provide effective HIV education for youth. In fall 1987, 14 state and 9 local education agencies that serve areas with the highest cumulative incidence of AIDS cases convened to develop a common set of data items that could provide comparable information about HIV-related knowledge, beliefs, and behaviors among adolescents in their respective jurisdictions over time. Surveys were administered during spring 1988 to representative samples of adolescents in each participating state and city. These education agencies will use the results from this complementary system of school-based surveys as a guide in planning HIV education, setting program priorities, allocating resources, and monitoring changes in HIV-related knowledge, beliefs, and behaviors among adolescents.

Health education needs in child care programs.

This article contains results from an assessment of health education needs in child care programs serving preschool children. The assessment included identification of the scope of health education activities provided in child care programs, and the program director's perception of benefits of and barriers to health education in child care settings. A mail survey assessed the health education needs in a random sample of licensed child care programs in Alabama. Survey results identified factors affecting adoption and delivery of early childhood health education programs.

Safety belt promotion: theory and practice.

The purpose of this paper is to provide practitioners a rationale and description of selected theoretically based approaches to safety belt promotion. Theory failure is a threat to the integrity and effectiveness of safety belt promotion. The absence of theory driven programs designed to promote safety belt use is a concern of this paper. Six theoretical models from the social and behavioral sciences are reviewed with suggestions for application to promoting safety belt use and include Theory of Reasoned Action, the Health Belief Model, Fear Arousal, Operant Learning, Social Learning Theory, and Diffusion of Innovations. Guidelines for the selection and utilization of theory are discussed.

Single-subject evaluation in health education.

The utilization of single-subject methodology represents a means to improve evaluation efforts in health education. This article provides a rationale for the application of the methodology in health education evaluation. Two variations of the single-subject evaluation methodology (ABAB and multiple baseline) are described. Appropriate methods of data analysis are recommended. Applications of single-subject designs in health education settings are presented. Dilemmas in health education evaluation are identified and reviewed in light of the potential contributions of single-subject methodology.