Increasing clinician participation in tobacco cessation by an implementation science-based tobacco cessation champion program.

BACKGROUND: We designed a process to increase tobacco cessation in an academic center and its widely distributed network community sites using clinical champions to overcome referral barriers. METHODS: In 2020 a needs assessment was performed across the City of Hope Medical Center and its 32 community treatment sites. We reviewed information science strategies to choose elements for our expanded tobacco control plan, focusing on distributed leadership with tobacco cessation champions. We analyzed smoking patterns in patients with cancer before and following program implementation. We evaluated the champion experience and measured tobacco abstinence after 6 months of follow-up. RESULTS: Cancer center leadership committed to expanding tobacco control. Funding was obtained through a Cancer Center Cessation Initiative (C3I) grant. Multi-disciplinary leaders developed a comprehensive plan. Disease-focused clinics and community sites named cessation champions (a clinician and nurse) supported by certified tobacco treatment specialists. Patient, staff, clinician, and champion training/education were developed. Roles and responsibilities of the champions were defined. Implementation in pilot sites showed increased tobacco assessment from 80.8 to 96.6%, increased tobacco cessation referral by 367%, and moderate smoking abstinence in both academic (27.2%) and community sites (22.5%). 73% of champions had positive attitudes toward the program. CONCLUSION: An efficient process to expand smoking cessation in the City of Hope network was developed using implementation science strategies and cessation champions. This well-detailed implementation process may be helpful to other cancer centers, particularly those with a tertiary care cancer center and community network.

Comparative efficacy of chemoimmunotherapy versus immunotherapy for advanced non-small cell lung cancer: A network meta-analysis of randomized trials.

BACKGROUND: To the authors' knowledge, in the absence of head-to-head trials, it is unclear whether chemoimmunotherapy provides an additional overall survival (OS) benefit compared with immunotherapy alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors conducted a systematic literature review and network meta-analysis (NMA) to compare the efficacy of chemoimmunotherapy versus ICI. METHODS: MEDLINE, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 2020. Phase 3 trials evaluating the efficacy of first-line ICI or chemoimmunotherapy and reporting efficacy outcomes (OS, progression-free survival [PFS], and the overall response rate [ORR]) stratified by programmed death-ligand 1 (PD-L1) status were included. NMA with a Bayesian random effects model was performed. RESULTS: A total of 12 eligible trials comprising 7845 patients were included. In patients who were negative for PD-L1 (tumor proportion score [TPS] <1%), NMA comparing chemoimmunotherapy with dual-agent ICI failed to demonstrate a statistically significant difference with regard to OS, PFS, or the ORR. In patients with low PD-L1 (TPS 1%-49%), there was no statistically significant difference observed between chemoimmunotherapy compared with either single-agent ICI or dual-agent ICI with regard to OS or the ORR. In patients with high PD-L1 (TPS ≥50%), chemoimmunotherapy was found to be associated with an improved PFS and ORR compared with single-agent ICI, but not with dual-agent ICI. No differences in OS were observed with chemoimmunotherapy when compared with either single-agent or dual-agent ICIs. CONCLUSIONS: Although chemoimmunotherapy appears to improve the ORR and PFS in patients with PD-L1-high tumors when compared with single-agent ICI, it does not appear to confer an OS benefit over single-agent or dual-agent ICI for patients with advanced NSCLC regardless of PD-L1 status. Prospective trials are needed to validate these findings.

Immune Checkpoint Inhibitor-Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases.

BACKGROUND: The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immune-related adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature. MATERIALS AND METHODS: Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines. RESULTS: A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICIs (38%). The most-reported symptoms were fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9,645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. Sixty percent of the patients died in hospital because of acute complications. CONCLUSION: IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition. IMPLICATIONS FOR PRACTICE: Clinicians should suspect coexisting myositis and/or myasthenia gravis in all patients with immune checkpoint inhibitor-induced myocarditis, given their propensity to occur together. Early recognition and prompt treatment with the help of a multidisciplinary team might help improve the outcomes of this life-threatening condition.

Venous Thromboembolism in COVID-19: Towards an Ideal Approach to Thromboprophylaxis, Screening, and Treatment.

PURPOSE OF REVIEW: Novel coronavirus disease 2019 (COVID-19) has been associated with an increased risk of arterial and venous thromboembolic (VTE) diseases. However, there is a limited amount of data regarding the prevention and management of VTE in severe hospitalized COVID-19 patients. RECENT FINDINGS: In this article, we review currently available clinical data, and mechanisms for COVID-associated coagulopathy, and propose algorithms for screening, prevention (including extended-duration prophylaxis), and treatment of these patients. Although these recommendations are subject to change given rapidly evolving data, we provide a framework that can guide clinicians in managing thrombotic complications in this challenging condition.

Therapy-related acute myeloid leukemia following radioactive iodine treatment for thyroid cancer.

BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) associated with radioiodine treatment (RAI) is emerging as an important clinical entity with the rise in incidence of thyroid cancer. DESIGN AND METHODS: We conducted an electronic search of MEDLINE and EMBASE, and also searched reference lists of articles and abstracts from conference proceedings for case reports and review articles on t-AML following radioiodine therapy. A total of 37 patients with acute myeloid neoplasms following radioiodine treatment were analyzed. RESULTS: The median RAI dose was 324 mCi, and median age was 47.5 years with M/F ratio of 1:3. Latency period was 1-4 years, and the median time from RAI exposure to diagnosis of t-AML was 2.9 years. FAB M2 and M3 were the two most common t-AML subtypes reported. Seventy-one percent of the cases that reported cytogenetic abnormalities were classified as unfavorable. The most commonly reported abnormalities were del 5q and t(15:17). Survival outcomes were not reported due to lack of patient-level data. CONCLUSIONS: T-AML following radioiodine therapy for thyroid cancer appears to have a shorter latency period than other types of t-AML, which is an important consideration for post-therapy surveillance. Reporting of cases and outcomes will help provide data for further research. Identifying biomarkers that help risk-stratify patients prior to therapy and specific genetic-guided therapies may help improve outcomes.

RS3PE revisited: a systematic review and meta-analysis of 331 cases.

OBJECTIVES: Remitting seronegative symmetrical synovitis with pitting oedema (RS(3)PE) syndrome is a rare inflammatory arthritis, characterised by symmetrical distal synovitis, pitting oedema of the hands and feet, absence of rheumatoid factor, and favourable response to glucocorticoids. The aim of our study is to further delineate the clinical and laboratory features, and response to treatment. METHODS: We performed a systematic electronic search of Medline, PubMed, EMBASE, ACR and EULAR databases for case reports, case series, and related articles of RS(3)PE. Statistical analysis was done comparing categorical variables with Chi-square tests and frequencies of means via t-tests. Binary logistic regression analysis was performed to identify predictors of erosions, recurrence, malignancy and rheumatologic disorders. RESULTS: 331 cases of RS(3)PE were identified from 121 articles. RS(3)PE was found in older patients (71±10.42 years) predominantly in males (n= 211, 63.36%), was symmetrical (n=297/311, 95.50%) involved the hands (n=294/311, 94.53%) A concurrent rheumatologic condition was reported in 22 cases (6.65%), and malignancy in 54 cases (16.31%). Radiographic joint erosions were found in 5.5%. Most patients responded to medium-dose glucocorticoids (16.12±9.5 mg/day). Patients with concurrent malignancy requiring non-significantly higher doses of prednisone (18.12 vs. 15.76 mg, p 0.304) and higher likelihood of recurrence of disease (OR 4.04, 95% CI 1.10-14.88, p=0.03). CONCLUSIONS: The symptoms and unique findings that make up RS(3)PE appear to represent a steroid-responsive disease that may be a harbinger of an underlying malignancy. More study is needed to understand the molecular origins of RS(3)PE in order to determine whether it is a separate disease process. Patients with concurrent cancer tend to have more severe presentations and higher rates of recurrence.

Secondary acute myeloid leukemia in survivors of Hodgkin lymphoma.

BACKGROUND: This large population-based study determined the epidemiology and outcomes of secondary acute myeloid leukemia (sAML) developing in Hodgkin lymphoma survivors. METHODS: We utilized the Surveillance Epidemiology and End Results (SEER) 9 database to identify 104 cases of sAML. RESULTS: Patients with sAML (median age: 47 years; 82% <60 years) were significantly younger than de novo AML cases (66 years; p < 0.01). sAML had worse overall survival (OS) than de novo AML (p < 0.01). OS was better in younger patients and in more recent years. CONCLUSION: Older patients with sAML have a dismal OS and should be enrolled in trials of novel therapies. Younger patients have improved OS and hence may benefit from curative intent intensive therapy and allogeneic transplant.

An uncommon cause of acute pulmonary edema.

Acute cardiogenic pulmonary edema secondary to catecholamine-induced cardiomyopathy is a very uncommon and fatal initial presentation of pheochromocytoma. However, with early clinical suspicion and aggressive management, the condition is reversible. This case report describes a patient who presented with hypertension, dyspnea, and cough with bloody streaks, and who recovered within 48 hours after appropriate treatment.

Role of radiation therapy in primary mediastinal large B-cell lymphoma in rituximab era: A US population-based analysis.

The use of radiation (RT) in primary mediastinal large B-cell lymphoma (PMBCL) may predispose young patients to the risk of cardiopulmonary toxicities and secondary malignancies. We used Surveillance, Epidemiology and End Results (SEER) 18 database to compare the overall survival (OS) differences among adult patients treated with and without RT after rituximab approval in the US. Multivariate analyses were performed using Cox proportional hazards regression to compare OS based on the use of RT while adjusting for age, year of diagnosis, race, stage and gender. PMBCL patients (n = 258), who received RT (48%), were similar in terms of age, gender, race, and stage at diagnosis to patients who did not receive RT. The five year OS was similar between patients treated with versus without RT (82.5% vs. 78.6%, P = 0.47). In a multivariate analysis, the use of RT did not influence OS in the rituximab era (HR 0.83; 95% CI 0.43-1.59; P = 0.56). Rituximab may reduce the benefit of RT in select patients such as those who achieve a metabolic complete remission at the end of chemotherapy.

Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States.

PURPOSE: Febrile neutropenia is a potentially life threatening complication of breast cancer chemotherapy associated with a significant amount of morbidity, mortality, and health care resource utilization. Recent data on the national estimates of mortality rate, length of stay, and health care costs among the subpopulation of febrile neutropenia admissions with breast cancer are lacking. METHODS: We used the Nationwide Inpatient Sample database to identify patients with breast cancer hospitalized for febrile neutropenia from 2009 to 2011. We derived data on inhospital mortality rate, length of stay, and mean health care costs and compared it with previous studies. RESULTS: The average inhospital mortality rate during 2009-2011 was 2.6 % (n = 685). Advanced age (≥ 65 years) was found to be significantly associated with a higher odds of mortality (4.4 vs 1.7 %, OR 2.7, 95 % CI 2.3-3.1, p < 0.01). The mean length of stay was 5.7 days (95 % CI 5.5-5.9 days), whereas the mean cost of hospitalization was $37,087 (95 % CI $34,009-$40,165). CONCLUSION: Febrile neutropenia-related hospitalizations continue to account for significant morbidity, mortality, and health care resource utilization among patients with breast cancer. Further efforts should be focused on curtailing the rising health care costs without compromising the quality of care.

Warfarin induced sublingual hematoma: a Ludwig angina mimic.

BACKGROUND: Sublingual hematoma is a rare but life-threatening complication of oral anticoagulants. It is important to differentiate this from infectious processes like Ludwig's angina. Securing the airway should be a priority and immediate reversal of anticoagulation with close monitoring is required. CASE REPORT: We present a case of sublingual hematoma secondary to warfarin therapy without airway compromise which was managed conservatively with reversal of INR with oral vitamin K. CONCLUSION: Although rare, it is crucial to differentiate sublingual hematomas from infectious processes. Reversal of anticoagulation with low threshold for artificial airway placement in the event of airway compromise is the treatment of choice.

Dual versus single antiplatelet therapy in patients undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis.

BACKGROUND: Although dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve replacement (TAVR), this approach is not evidence based. We therefore sought to systematically review the current evidence for this practice in terms of 30-day outcome looking at stroke, MI, bleeding, and death. METHODS: Relevant studies were identified through electronic literature search. Studies involving single antiplatelet therapy (SAPT) and DAPT in patients undergoing TAVR were included. Study specific risk ratios were calculated and combined using random-effects model meta-analysis. RESULTS: Analysis of data from 410 patients, stroke occurred in seven (3.16%) of SAPT and six (3.17%) of DAPT RR=1.03 (95% CI, 0.36-2.96, P=0.96). In analysis of 530 patients, MI occurred in three (1.07%) of SAPT and one (0.40%) of DAPT RR=1.97 (95% CI, 0.29-13.29, P=0.49), significant bleeding (major, life threatening and bleeding requiring transfusion) occurred in 20 (7.11%) of SAPT and 43 (17.27%) of DAPT RR=0.41 (95% CI, 0.25-0.69, P=0.0006). Number needed to harm for major or life threatening bleeding was 10. Death occurred in 15 (6.78%) of SAPT and 15 (7.94%) of DAPT (RR 0.91; 95% CI 0.46-1.79, P=0.78). CONCLUSION: Our meta-analysis suggests that at 30 days following TAVR there is no difference between post-procedural SAPT versus DAPT for the risk of stroke or MI and DAPT may have a higher bleeding risk. Adequately powered RCTs are warranted to clarify the optimal antiplatelet treatment strategy following TAVR.

Left atrial appendage aneurysm: a systematic review of 82 cases.

BACKGROUND: Aneurysm of the left atrial appendage is rare. We sought to systematically review the published literature on left atrial appendage aneurysm (LAAA) to address its demographic features, clinical characteristics, treatment, complications, and outcomes. METHODOLOGY: A systematic electronic search of Medline, PubMed, and EMBASE for case reports, case series, and related articles of LAAA published from 1962 until July 2013 was carried out. Statistical analysis was done using SPSS version 20.0. Logistic Regression Analysis was used to identify the independent predictors of LAAA-related thrombus formation and embolism. RESULTS: Eighty-two cases of LAAA were identified. There was a slight female preponderance and most of the patients presented in their third decades. Palpitation, dyspnea or both were most common clinical symptoms associated with LAAA. Echocardiography was the main diagnostic modality used and the mean size of aneurysm was 7.08 ± 3.03 × 5.75 ± 2.36 cm. Surgical resection of the aneurysm was performed in most patients with favorable results. Systemic embolism and atrial tachyarrhythmias were the two common complications associated with untreated LAAA. Presence of atrial fibrillation/flutter was the only significant predictor of thrombus formation/embolic events. CONCLUSION: Aneurysm of left atrial appendage is rare and often an incidental diagnosis during echocardiography. It is important to recognize this entity since it is associated with cardiovascular morbidity and mortality by predisposing to atrial tachyarrhythmia and thromboembolism. Surgical resection is the standard of treatment in the current literature. Medical management is directed toward the treatment of thromboembolism and atrial tachyarrhythmia.

Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non-Small-Cell Lung Cancer After Progression on Osimertinib.

INTRODUCTION: For patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) who progress on first-line osimertinib, the optimal second-line treatment regimen after progression is not known. We sought to assess practice patterns and evaluate the association between different therapies and survival in patients with EGFR-mutated NSCLC following progression on first-line osimertinib. METHODS: Retrospective cohort study of patients who received first-line treatment with osimertinib using a population-based, multicenter nationwide electronic health record-derived deidentified database. RESULTS: We identified 2373 patients who received first-line osimertinib. The majority (n = 2279) received osimertinib monotherapy. A total of 538 patients received first-line osimertinib and had second-line treatment data available. Second-line treatment regimens were varied: 65% (n = 348) included chemotherapy, 37% (n = 197) included an immune checkpoint inhibitor (ICI), and 44% (n = 234) included an EGFR tyrosine kinase inhibitor (TKI). We then analyzed the 333 patients with performance status 0-2 who received chemotherapy with osimertinib (n = 107, 32%) versus chemotherapy without osimertinib (n = 226, 68%). The continuation of osimertinib with chemotherapy was associated with superior progression-free survival (PFS; median: 10.1 versus 5.9 months, Hazard Ratio [HR]: 0.48, 95% Confidence Interval [CI]: [0.34, 0.68], P < .001) and overall survival (OS; median: 17.0 versus 12.8 months, HR: 0.64, 95% CI: [0.44, 0.93], P = .018) compared to other chemotherapy approaches without osimertinib. This effect was most pronounced in patients with an EGFR exon 19 deletion. CONCLUSIONS: Following progression on osimertinib, a wide variety of treatment regimens were used. The continuation of osimertinib with chemotherapy in the second line was associated with increased PFS and OS.

Overcoming Barriers to Tobacco Cessation and Lung Cancer Screening among Racial and Ethnic Minority Groups and Underserved Patients in Academic Centers and Community Network Sites: The City of Hope Experience.

BACKGROUND: Tobacco control is important for cancer patient health, but delivering effective low-dose CT (LDCT) screening and tobacco cessation is more difficult in underserved and patients from racial and ethnic minority groups. At City of Hope (COH), we have developed strategies to overcome barriers to the delivery of LDCT and tobacco cessation. METHODS: We performed a needs assessment. New tobacco control program services were implemented focusing on patients from racial and ethnic minority groups. Innovations included Whole Person Care with motivational counseling, placing clinician and nurse champions at points of care, training module and leadership newsletters, and a patient-centric personalized medicine Personalized Pathways to Success (PPS) program. RESULTS: Emphasis on patients from racial and ethnic minority groups was implemented by training cessation personnel and lung cancer control champions. LDCT increased. Tobacco use assessment increased and abstinence was 27.2%. The PPS pilot program achieved 47% engagement in cessation, with self-reported abstinence at 3 months of 38%, with both results slightly higher in patients from racial and ethnic minority groups than in Caucasian patients. CONCLUSIONS: Tobacco cessation barrier-focused innovations can result in increased lung cancer screening and tobacco cessation reach and effectiveness, especially among patients from racial and ethnic minority groups. The PPS program is promising as a personalized medicine patient-centric approach to cessation and lung cancer screening.

Machine learning to refine prognostic and predictive nodal burden thresholds for post-operative radiotherapy in completely resected stage III-N2 non-small cell lung cancer.

BACKGROUND: The role of post-operative radiotherapy (PORT) for completely resected N2 non-small-cell lung cancer (NSCLC) is controversial in light of recent randomized data. We sought to utilize machine learning to identify a subset of patients who may still benefit from PORT based on extent of nodal involvement. MATERIALS/METHODS: Patients with completely resected N2 NSCLC were identified in the National Cancer Database. We trained a machine-learning based model of overall survival (OS). SHapley Additive exPlanation (SHAP) values were used to identify prognostic and predictive thresholds of number of positive lymph nodes (LNs) involved and lymph node ratio (LNR). Cox proportional hazards regression was used for confirmatory analysis. RESULTS: A total of 16,789 patients with completely resected N2 NSCLC were identified. Using the SHAP values, we identified thresholds of 3+ positive LNs and a LNR of 0.34+. On multivariate analysis, PORT was not significantly associated with OS (p = 0.111). However, on subset analysis of patients with 3+ positive LNs, PORT improved OS (HR: 0.91; 95% CI: 0.86-0.97; p = 0.002). On a separate subset analysis in patients with a LNR of 0.34+, PORT improved OS (HR: 0.90; 95% CI: 0.85-0.96; p = 0.001). Patients with 3+ positive lymph nodes had a 5-year OS of 38% with PORT compared to 31% without PORT. Patient with positive lymph node ratio 0.34+ had a 5-year OS of 38% with PORT compared to 29% without PORT. CONCLUSIONS: Patients with a high lymph node burden or lymph node ratio may present a subpopulation of patients who could benefit from PORT. To our knowledge, this is the first study to use machine learning algorithms to address this question with a large national dataset. These findings address an important question in the field of thoracic oncology and warrant further investigation in prospective studies.

High quality (certainty) evidence changes less often than low-quality evidence, but the magnitude of effect size does not systematically differ between studies with low versus high-quality evidence.

RATIONALE, AIMS, AND OBJECTIVES: It is generally believed that evidence from low quality of evidence generate inaccurate estimates about treatment effects more often than evidence from high (certainty) quality evidence (CoE). As a result, we would expect that (a) estimates of effects of health interventions initially based on high CoE change less frequently than the effects estimated by lower CoE (b) the estimates of magnitude of effect size differ between high and low CoE. Empirical assessment of these foundational principles of evidence-based medicine has been lacking. METHODS: We reviewed the Cochrane Database of Systematic Reviews from January 2016 through May 2021 for pairs of original and updated reviews for change in CoE assessments based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We assessed the difference in effect sizes between the original versus updated reviews as a function of change in CoE, which we report as a ratio of odds ratio (ROR). We compared ROR generated in the studies in which CoE changed from very low/low (VL/L) to moderate/high (M/H) versus M/H to VL/L. Heterogeneity and inconsistency were assessed using the tau and I2 statistic. We also assessed the change in precision of effect estimates (by calculating the ratio of standard errors) (seR), and the absolute deviation in estimates of treatment effects (aROR). RESULTS: Four hundred and nineteen pairs of reviews were included of which 414 (207 × 2) informed the CoE appraisal and 384 (192 × 2) the assessment of effect size. We found that CoE originally appraised as VL/L had 2.1 [95% confidence interval (CI): 1.19-4.12; p = 0.0091] times higher odds to be changed in the future studies than M/H CoE. However, the effect size was not different (p = 1) when CoE changed from VL/L → M/H [ROR = 1.02 (95% CI: 0.74-1.39)] compared with M/H → VL/L (ROR = 1.02 [95% CI: 0.44-2.37]). Similar overlap in aROR between the VL/L → M/H versus M/H → VL/L subgroups was observed [median (IQR): 1.12 (1.07-1.57) vs. 1.21 (1.12-2.43)]. We observed large inconsistency across ROR estimates (I2 = 99%). There was larger imprecision in treatment effects when CoE changed from VL/L → M/H (seR = 1.46) than when it changed from M/H → VL/L (seR = 0.72). CONCLUSIONS: We found that low-quality evidence changes more often than high CoE. However, the effect size did not systematically differ between the studies with low versus high CoE. The finding that the effect size did not differ between low and high CoE indicate urgent need to refine current EBM critical appraisal methods.