Effects of a change in recall period on reporting severe symptoms: an analysis of a pragmatic multisite trial.

BACKGROUND: Optimal methods for deploying electronic patient-reported outcomes to manage symptoms in routine oncologic practice remain uncertain. The electronic symptom management (eSyM) program asks chemotherapy and surgery patients to self-report 12 common symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7 days to the past 24 hours. METHODS: Using questionnaires submitted during the 16 weeks surrounding the recall period change, we assessed the likelihood of reporting severe or moderate and severe symptoms across 12 common symptoms and separately for the 5 most prevalent symptoms. Interrupted time-series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method. RESULTS: In total, 1692 patients from 6 institutions submitted 7823 eSyM assessments during the 16 weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (odds ratio = 0.65, 95% confidence interval = 0.46 to 0.93; P = .02) and lower odds of moderate and severe symptom reporting in the chemotherapy cohort (odds ratio = 0.83, 95% confidence interval = 0.71 to 0.97; P = .02). Among the most prevalent symptoms, 24-hour recall was associated with a lower rate of reporting postoperative constipation but no differences in reporting rates for other symptoms. CONCLUSION: A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether electronic patient-reported outcomes are collected for active symptom management, as a clinical trial endpoint, or another purpose. ClinicalTrials.gov ID NCT03850912.

Strategies for Implementing an Electronic Patient-Reported Outcomes-Based Symptom Management Program Across Six Cancer Centers.

Background: Electronic patient-reported outcome (ePRO)-based symptom management improves cancer patients' outcomes. However, implementation of ePROs is challenging, requiring technical resources for integration into clinical systems, substantial buy-in from clinicians and patients, novel workflows to support between-visit symptom management, and institutional investment. Methods: The SIMPRO Research Consortium developed eSyM, an electronic health record-integrated, ePRO-based symptom management program for medical oncology and surgery patients and deployed it at six cancer centers between August 2019 and April 2022 in a type II hybrid effectiveness-implementation cluster randomized stepped-wedge study. Sites documented implementation strategies monthly using REDCap, itemized them using the Expert Recommendations for Implementation Change (ERIC) list and mapped their target barriers using the Consolidated Framework for Implementation Research (CFIR) to inform eSyM program enhancement, facilitate inter-consortium knowledge sharing and guide future deployment efforts. Results: We documented 226 implementation strategies: 35 'foundational' strategies were applied consortium-wide by the coordinating center and 191 other strategies were developed by individual sites. We consolidated these 191 site-developed strategies into 64 unique strategies (i.e., removed duplicates) and classified the remainder as either 'universal', consistently used by multiple sites (N=29), or 'adaptive', used only by individual sites (N=35). Universal strategies were perceived as having the highest impact; they addressed eSyM clinical preparation, training, engagement of patients/clinicians, and program evaluation. Across all documented SIMPRO strategies, 44 of the 73 ERIC strategies were addressed and all 5 CFIR barriers were addressed. Conclusion: Methodical collection of theory-based implementation strategies fostered the identification of universal, high-impact strategies that facilitated adoption of a novel care-delivery intervention by patients, clinicians, and institutions. Attention to the high-impact strategies identified in this project could support implementation of ePROs as a component of routine cancer care at other institutions.

Assessing Patient Readiness for an Electronic Patient-Reported Outcome-Based Symptom Management Intervention in a Multisite Study.

PURPOSE: While the use of electronic patient-reported outcomes (ePROs) in routine clinical practice is increasing, barriers to patient engagement limit adoption. Studies have focused on technology access as a key barrier, yet other characteristics may also confound readiness to use ePROs including patients' confidence in using technology and confidence in asking clinicians questions. METHODS: To assess readiness to use ePROs, adult patients from six US-based health systems who started a new oncology treatment or underwent a cancer-directed surgery were invited to complete a survey that assessed access to and confidence in the use of technology, ease of asking clinicians questions about health, and symptom management self-efficacy. Multivariable ordinal logistic regression models were fit to assess the association between technology confidence, ease of asking questions, and symptom management self-efficacy. RESULTS: We contacted 3,212 individuals, and 1,043 (33%) responded. The median age was 63 years, 68% were female, and 75% reported having access to patient portals. Over 80% had two or more electronic devices. Most patients reported high technology confidence, higher ease of asking clinicians questions, and high symptom management self-efficacy (n = 692; 66%). Patients with high technology confidence also reported higher ease of asking nurses about their health (adjusted odds ratio [AOR], 4.58 [95% CI, 2.36 to 8.87]; P ≤ .001). Those who reported higher ease of asking nurses questions were more likely to report higher confidence in managing symptoms (AOR, 30.54 [95% CI, 12.91 to 72.30]; P ≤ .001). CONCLUSION: Patient readiness to use ePROs likely depends on multiple factors, including technology and communication confidence, and symptom management self-efficacy. Future studies should assess interventions to address these factors.

Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline.

PURPOSE: To provide evidence-based recommendations to practicing clinicians on the management of patients with small-cell lung cancer. METHODS: An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2022. Outcomes of interest included response rates, overall survival, disease-free survival or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 95 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: Evidence-based recommendations were developed to address systemic therapy options, timing of therapy, treatment in patients who are older or with poor performance status, role of biomarkers, and use of myeloid-supporting agents in patients with small-cell lung cancer.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Implementation of patient-reported outcomes for symptom management in oncology practice through the SIMPRO research consortium: a protocol for a pragmatic type II hybrid effectiveness-implementation multi-center cluster-randomized stepped wedge trial.

BACKGROUND: Many cancer patients experience high symptom burden. Healthcare in the USA is reactive, not proactive, and doctor-patient communication is often suboptimal. As a result, symptomatic patients may suffer between clinic visits. In research settings, systematic assessment of electronic patient-reported outcomes (ePROs), coupled with clinical responses to severe symptoms, has eased this symptom burden, improved health-related quality of life, reduced acute care needs, and extended survival. Implementing ePRO-based symptom management programs in routine care is challenging. To study methods to overcome the implementation gap and improve symptom control for cancer patients, the National Cancer Institute created the Cancer-Moonshot funded Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium. METHODS: Symptom Management IMplementation of Patient Reported Outcomes in Oncology (SIMPRO) is one of three research centers that make up the IMPACT Consortium. SIMPRO, a multi-disciplinary team of investigators from six US health systems, seeks to develop, test, and integrate an electronic symptom management program (eSyM) for medical oncology and surgery patients into the Epic electronic health record (EHR) system and associated patient portal. eSyM supports real-time symptom tracking for patients, automated clinician alerts for severe symptoms, and specialized reports to facilitate population management. To rigorously evaluate its impact, eSyM is deployed through a pragmatic stepped wedge cluster-randomized trial. The primary study outcome is the occurrence of an emergency department treat-and-release event within 30 days of starting chemotherapy or being discharged following surgery. Secondary outcomes include hospitalization rates, chemotherapy use (time to initiation and duration of therapy), and patient quality of life and satisfaction. As a type II hybrid effectiveness-implementation study, facilitators and barriers to implementation are assessed throughout the project. DISCUSSION: Creating and deploying eSyM requires collaboration between dozens of staff across diverse health systems, dedicated engagement of patient advocates, and robust support from Epic. This trial will evaluate eSyM in routine care settings across academic and community-based healthcare systems serving patients in rural and metropolitan locations. This trial's pragmatic design will promote generalizable results about the uptake, acceptability, and impact of an EHR-integrated, ePRO-based symptom management program. TRIAL REGISTRATION: ClinicalTrials.gov NCT03850912 . Registered on February 22, 2019. Last updated on November 9, 2021.

eSyM: An Electronic Health Record-Integrated Patient-Reported Outcomes-Based Cancer Symptom Management Program Used by Six Diverse Health Systems.

PURPOSE: Collecting patient-reported outcomes (PROs) can improve symptom control and quality of life, enhance doctor-patient communication, and reduce acute care needs for patients with cancer. Digital solutions facilitate PRO collection, but without robust electronic health record (EHR) integration, effective deployment can be hampered by low patient and clinician engagement and high development and deployment costs. The important components of digital PRO platforms have been defined, but procedures for implementing integrated solutions are not readily available. METHODS: As part of the NCI's IMPACT consortium, six health care systems partnered with Epic to develop an EHR-integrated, PRO-based electronic symptom management program (eSyM) to optimize postoperative recovery and well-being during chemotherapy. The agile development process incorporated user-centered design principles that required engagement from patients, clinicians, and health care systems. Whenever possible, the system used validated content from the public domain and took advantage of existing EHR capabilities to automate processes. RESULTS: eSyM includes symptom surveys on the basis of the PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE) plus two global wellness questions; reminders and symptom self-management tip sheets for patients; alerts and symptom reports for clinicians; and population management dashboards. EHR dependencies include a secure Health Insurance Portability and Accountability Act-compliant patient portal; diagnosis, procedure and chemotherapy treatment plan data; registries that identify and track target populations; and the ability to create reminders, alerts, reports, dashboards, and charting shortcuts. CONCLUSION: eSyM incorporates validated content and leverages existing EHR capabilities. Build challenges include the innate technical limitations of the EHR, the constrained availability of site technical resources, and sites' heterogenous EHR configurations and policies. Integration of PRO-based symptom management programs into the EHR could help overcome adoption barriers, consolidate clinical workflows, and foster scalability and sustainability. We intend to make eSyM available to all Epic users.

Primary large cell neuroendocrine carcinoma of the breast, a case report with an unusual clinical course.

Large cell neuroendocrine carcinoma of the breast (NECB) is an extremely rare type of breast cancer; little is known about effective chemotherapies, and data on pathologic response to treatment are unavailable. We report the case of a 34-years-old woman with large cell NECB with initial clinical and pathologic evidence of treatment response to anthracycline-containing neo-adjuvant therapy. Histologic reassessment early during anthracycline chemotherapy revealed cell death with necrosis of 50% of the tumor cells seen in the biopsy specimen. After completing neo-adjuvant chemotherapy, the patient underwent breast-conserving surgery. Pathologic evaluation of the surgical specimen showed a partial response but margins were positive for residual carcinoma. Despite repeated neo-adjuvant chemotherapy, radiotherapy, and surgical resection, the tumor grew rapidly between surgeries and recurred systemically. Therefore, we review the literature on large cell NECB and its treatment options.

LIM kinase 1 deficient mice have reduced bone mass.

The cytoskeleton determines cell shape and is involved in cell motility. It also plays a role in differentiation and in modulating specialized cellular functions. LIM kinase 1 (LIMK1) participates in cytoskeletal remodeling by phosphorylating and inactivating the actin-severing protein, cofilin. Severing F-actin to release G-actin monomers is required for actin cytoskeletal remodeling. Although less well established, LIMK1 may also influence the cell cycle and modulate metalloproteinase activity. Since the role of LIMK1 in bone cell biology has not been reported, the skeletal phenotype of LIMK1(-/-) mice was examined. LIMK1(-/-) mice had significantly reduced trabecular bone mass when analyzed by microCT (p<0.01). Histomorphometric analyses demonstrated a 31% reduction in the number of osteoblasts (p=0.0003) and a 23% reduction in osteoid surface (p=0.0005). The number of osteoclasts was no different in control and knock out animals. Consistent with the in vivo findings in osteoblasts, the number of osteoblast colony forming units in LIMK1(-/-) bone marrow was reduced by nearly 50%. Further, osteoblasts isolated from LIMK1(-/-) mice showed significantly reduced rates of mineralization in vitro. Osteoclasts from LIMK1(-/-) mice evidenced more rapid cytoskeletal remodeling in response to treatment with CSF1. In keeping with this latter finding, basal levels of phospho-cofilin were reduced in LIMK1(-/-) osteoclasts. LIMK1(-/-) osteoclasts also resorbed dentine slices to a greater extent in vitro and were more active in a pit assay. These data support the hypothesis that LIMK1 is required for normal osteoblast differentiation. In addition, its absence leads to increased cytoskeletal remodeling and bone resorption in osteoclasts.

Comparison of ThinPrep and SurePath liquid-based cytology and subsequent human papillomavirus DNA testing in China.

BACKGROUND: Liquid-based cytology (LBC) has been compared with conventional cytology in numerous studies. In the current study of 2 LBC systems, the accuracy, rates of unsatisfactory cytology, and sufficiency of residual LBC specimens for Hybrid Capture 2 (HC2) HPV DNA testing were compared. METHODS: Eligible women ages 30 to 49 years were recruited for this cross-sectional population-based study in rural China. Women were assessed by visual inspection with acetic acid (VIA), LBC, and high-risk HPV HC2 DNA assay. Cervical specimens were preserved according to SurePath or ThinPrep protocols. LBC results were manually read. HC2 testing was performed on specimens with sufficient residual volume. Colposcopies and biopsies were performed on women who were VIA positive at the time of initial screening. Women with abnormal LBC or HC2 test results were called back for colposcopies and 4-quadrant cervical biopsies. RESULTS: Of 2005 eligible women, 972 were tested by SurePath and 1033 by ThinPrep. Compared with SurePath samples, ThinPrep samples had higher rates of unsatisfactory cytology (0.2% for SurePath and 1.5% for ThinPrep) and insufficient residual volume for HC2 (0.0% for SurePath and 18.2% for ThinPrep). SurePath samples yielded higher sensitivities and similar specificities for LBC and HC2 testing of residual specimens, but these differences were not determined to be significant by area-under-the-curve analysis (LBC performance: 0.89 for SurePath and 0.85 for ThinPrep; HC2 performance: 0.91 for SurePath and 0.89 for ThinPrep). CONCLUSIONS: Both methods yielded similar validity in detecting significant cervical lesions. However, SurePath samples yielded higher rates of satisfactory LBC slides and sufficient residual volume for HC2.

Osteoclasts lacking Rac2 have defective chemotaxis and resorptive activity.

The role of the small Rho GTPase Rac2 in mature osteoclasts has not been extensively studied. Rac2(-/-) mice are of normal size and have normal tooth eruption. However, femoral cortical thickness was significantly greater in Rac2(-/-) compared to wild-type mice, while percent cortical porosity was lower. As assessed by histomorphometry, trabecular bone mass was significantly higher in male Rac2(-/-) than wild-type animals, although trabecular bone mass was similar when data from male and female animals were combined. There were no significant differences in the number of osteoblasts per bone surface; however, the number of osteoclasts per total bone area tended to be higher in Rac2(-/-) mice and was significantly higher in male Rac2(-/-) mice. In the aggregate, these data suggested a defect in osteoclast function and, consistent with that, rates of bone resorption were significantly reduced in Rac2(-/-) osteoclasts. In addition, Rac2(-/-) osteoclasts had a significantly delayed spreading response to treatment with CSF1 for 15 min. Phalloidin staining showed areas of abnormal actin accumulation and impaired actin ring formation in Rac2(-/-) osteoclasts. Finally, Rac2(-/-) osteoclasts showed a marked defect in chemotaxis toward a point source of CSF1, with a dramatic reduction in migratory rate. Together, these findings indicate an important role for Rac2 in mature osteoclasts.