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.

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.

Ablative Radiotherapy as a Strategy to Overcome TKI Resistance in EGFR-Mutated NSCLC.

Tyrosine kinase inhibitor (TKI) therapy is the recommended first-line treatment for metastatic non-small-cell lung cancer (NSCLC) positive for epidermal growth factor receptor (EGFR) gene mutation. However, most individuals treated with TKI therapy for EGFR-mutant NSCLC will develop tumor resistance to TKI therapy. Therapeutic strategies to overcome TKI resistance are the topic of several ongoing clinical trials. One potential strategy, which has been explored in numerous trials, is the treatment of progressive sites of disease with stereotactic body radiation treatment (SBRT) or stereotactic radiosurgery (SRS). We sought to review the literature pertaining to the use of local ablative radiation therapy in the setting of acquired resistance to TKI therapy and to discuss stereotactic radiation therapy as a strategy to overcome TKI resistance.

Cancer Survivors, Oncology, and Primary Care Perspectives on Survivorship Care: An Integrative Review.

PURPOSE: Evidence-based models of cancer survivorship care are lacking. Such models should take into account the perspectives of all stakeholders. The purpose of this integrative review is to examine the current state of the literature on cancer survivorship care from the cancer survivor, the oncology care team, and the primary care team perspectives. METHODS: Using defined inclusion and exclusion criteria, we conducted a literature search of PubMed, PsycINFO, CINAHL, and Scopus databases to identify relevant articles on the stakeholders' perspectives on cancer survivorship care published between 2010 and 2021. We reviewed and abstracted eligible articles to synthesize findings. RESULTS: A total of 21 studies were included in the review. Barriers to the receipt and provision of cancer survivorship care quality included challenges with communication, cancer care delivery, and knowledge. CONCLUSION: Persistent stakeholder-identified barriers continue to hinder the provision of quality cancer survivorship care. Improved communication, delivery of care, knowledge/information, and resources are needed to improve the quality of survivorship care. Novel models of cancer survivorship care that address the needs of survivors, oncology teams, and PCPs are needed.

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.

Patterns of Care in Maintenance Therapy in US Patients Undergoing Definitive Chemoradiation for Stage 3 Non-Small Cell Lung Cancer (NSCLC).

OBJECTIVE: The recommended treatment for patients with unresectable stage 3 non-small cell lung cancer (NSCLC) is definitive chemoradiation followed by 1 year of maintenance durvalumab. Our objective was to assess the rate of maintenance durvalumab use after chemoradiation. METHODS: Analyses were conducted in both open claims (IQVIA pharmacy and medical claims data) and adjudicated closed claims (IQVIA PharMetrics Plus Health Plan Claims Database). Patients with a lung cancer diagnosis between November 2017 and November 2020 who received definitive chemoradiation were included. RESULTS: Of the 5802 NSCLC patients included in the open claims source, 1794 (31%) received durvalumab, 1403 (24%) received maintenance chemotherapy, and 2605 (45%) did not receive any maintenance therapy. Of the 239 NSCLC patients included in the closed claims source, 127 (53%) received durvalumab, 40 (17%) received maintenance chemotherapy, and 72 (30%) did not receive any maintenance therapy. The most common maintenance chemotherapy agents patients received were carboplatin, pemetrexed, and paclitaxel. CONCLUSIONS: The rate of durvalumab utilization was overall low in both the open and closed claims data sources (31% and 53%, respectively). It remains unknown what percent of eligible patients end up receiving durvalumab, as our analysis was unable to filter out patients who were unfit for durvalumab or if they had progression after chemoradiation. Future efforts are needed to increase maintenance durvalumab utilization and to determine how best to manage patients who are unfit for durvalumab.

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.

Histologic Transformation in EGFR-Mutant Lung Adenocarcinomas: Mechanisms and Therapeutic Implications.

With the advent of potent EGFR tyrosine kinase inhibitors (TKIs), the treatment landscape of EGFR-mutant lung adenocarcinomas has changed drastically in recent years. However, the development of resistance to EGFR TKIs remains a critical barrier to improving survival in these patients. Histologic transformations to small cell lung carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, and the sarcomatoid phenotype have been increasingly recognized as important mechanisms of resistance. In this article, we summarize the known biological bases for such phenotypic switches in regard to EGFR TKIs and describe novel pathways that might be harnessed to develop effective novel therapies for patients with EGFR-mutant non-small cell lung cancers.

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.

Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions.

Immune checkpoint inhibitors have revolutionized the treatment landscape for patients with non-small cell lung cancers. Existing treatment paradigms for brain metastases in lung cancer patients leave patients with adverse neurocognitive function, poor quality of life, and dismal prognosis, thus highlighting the need to develop more effective systemic therapies. Although data are limited, emerging knowledge suggests promising activity and safety of immune checkpoint inhibitors in brain metastases in non-small cell lung cancer patients. This review aims to summarize the current data, highlight the challenges of incorporating immune checkpoint inhibitors in treating these patients, and identify areas for future research.

Efficacy and Safety of Direct Oral Anticoagulants in Venous Thromboembolism Compared to Traditional Anticoagulants in Morbidly Obese Patients: A Systematic Review and Meta-Analysis.

Background Randomized clinical trials comparing the efficacy and safety of direct oral anticoagulants (DOAC) with vitamin K antagonist (VKA) or low molecular weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) generally exclude patients who are morbidly obese (body mass index ≥ 40 kg/m2 or weight ≥ 120 kg). Recently, smaller studies have compared DOACs with warfarin or low molecular weight heparin (LMWH) in morbidly obese patients with VTE. We aim to systematically review and do a meta-analysis of the studies that directly compared DOACs with VKAs or LMWH in morbidly obese patients. Methods Studies comparing DOAC with warfarin or LMWH in patients with acute VTE were identified through electronic literature searches of MEDLINE, EMBASE, Scopus, clinicaltrials.gov, and the Cochrane Library up to March 2020. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) guidelines. Study-specific odds ratios (OR) were calculated and combined using a random-effects model meta-analysis. Result Five studies were identified. Recurrent VTE occurred in 95 of 3207 (2.96%) patients in the DOAC group and 81 of 3181 (2.54%) patients in the VKA and LMWH group (OR: 1.17; 95% CI 0.87 to 1.59, p=.30). Major bleeding occurred in 63 of 3316 (1.89%) patients in the DOAC group, and 83 of 3259(2.54%) patients in the VKA or LMWH group (OR: 0.74; 95% CI: 0.53 to 1.03, p=.08). Sensitivity analysis comparing factor Xa inhibitors apixaban and rivaroxaban to warfarin also yielded consistent findings. Conclusion DOACs showed similar efficacy and safety in the prevention of recurrent VTE risk and major bleeding events in morbidly obese patients when compared to warfarin/LMWH. Our study underscores the need for further modifications of therapy to reduce the high VTE recurrence rate irrespective of whether the patient is on a DOAC or VKA. This might be possible through a very large multi-institutional randomized clinical trial.

Chemoradiation as a nonsurgical treatment option for early-stage esophageal cancers: a retrospective cohort study.

BACKGROUND: Complete tumor removal via esophagectomy or endoscopic excision has been associated with the greatest survival in early-stage esophageal cancer. However, patient health, anatomy, or goals of care may render patients ineligible for excision or resection. In this setting, chemoradiation (CRT) may be considered as a nonsurgical approach, however the outcomes associated with CRT in early-stage esophageal cancer are incompletely understood. METHODS: The National Cancer Database was queried for treatment-naïve cT1/T2, N0, M0 esophageal cancer patients managed with concurrent multi-agent CRT (≥50 Gy) between 2004 and 2015. Medically inoperable patients were excluded. Kaplan-Meier curves were generated to estimate 5-year overall survival (OS) from diagnosis in both stages. RESULTS: Of the 828 patients identified, 279 were cT1 and 549 were cT2. For cases after 2010, cT1 (N=124) was further stratified in cT1a (N=32, 25.8%) and cT1b (N=46, 37.1%). Kaplan-Meier estimates demonstrated a 5-year survival of 21.7% for cT1 and 25.9% for cT2. Sensitivity analyses were performed to mitigate competing survival risk from poor health. Among 589 comorbidity-free patients (i.e., Charlson = score zero), the 5-year survival with CRT was 23.4% for cT1 and 27.8% for cT2. Finally, a subset of patients who refused a recommended surgery were evaluated with 5-year survival cT1 =33.5% and cT2 =33.4%). CONCLUSIONS: Up to a third of selected patients with early-stage esophageal cancer may be cured after CRT as definitive non-surgical treatment. However, cure rates may be underestimated in this setting, secondary to persistent health-related bias.

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.

Navigating by Stars: Using CMS Star Ratings to Choose Hospitals for Complex Cancer Surgery.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) developed risk-adjusted "Star Ratings," which serve as a guide for patients to compare hospital quality (1 star = lowest, 5 stars = highest). Although star ratings are not based on surgical care, for many procedures, surgical outcomes are concordant with star ratings. In an effort to address variability in hospital mortality after complex cancer surgery, the use of CMS Star Ratings to identify the safest hospitals was evaluated. METHODS: Patients older than 65 years of age who underwent complex cancer surgery (lobectomy, colectomy, gastrectomy, esophagectomy, pancreaticoduodenectomy) were evaluated in CMS Medicare Provider Analysis and Review files (2013-2016). The impact of reassignment was modeled by applying adjusted mortality rates of patients treated at 5-star hospitals to those at 1-star hospitals (Peters-Belson method). RESULTS: There were 105 823 patients who underwent surgery at 3146 hospitals. The 90-day mortality decreased with increasing star rating (1 star = 10.4%, 95% confidence interval [CI] = 9.8% to 11.1%; and 5 stars = 6.4%, 95% CI = 6.0% to 6.8%). Reassignment of patients from 1-star to 5-star hospitals (7.8% of patients) was predicted to save 84 Medicare beneficiaries each year. This impact varied by procedure (colectomy = 47 lives per year; gastrectomy = 5 lives per year). Overall, 2189 patients would have to change hospitals each year to improve outcomes (26 patients moved to save 1 life). CONCLUSIONS: Mortality after complex cancer surgery is associated with CMS Star Rating. However, the use of CMS Star Ratings by patients to identify the safest hospitals for cancer surgery would be relatively inefficient and of only modest impact.

Association of Survival With Adjuvant Chemotherapy Among Patients With Early-Stage Non-Small Cell Lung Cancer With vs Without High-Risk Clinicopathologic Features.

IMPORTANCE: Tumor size larger than 4 cm is accepted as an indication for adjuvant chemotherapy in patients with node-negative non-small cell lung cancer (NSCLC). Treatment guidelines suggest that high-risk features are also associated with the efficacy of adjuvant chemotherapy among patients with early-stage NSCLC, yet this association is understudied. OBJECTIVE: To assess the association between adjuvant chemotherapy and survival in the presence and absence of high-risk pathologic features in patients with node-negative early-stage NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study using data from the National Cancer Database included 50 814 treatment-naive patients with a completely resected node-negative NSCLC diagnosed between January 1, 2010, and December 31, 2015. The study was limited to patients who survived at least 6 weeks after surgery (ie, estimated median time to initiate adjuvant chemotherapy after surgery) to mitigate immortal time bias. Statistical analysis was performed from December 1, 2018, to February 29, 2020. EXPOSURES: Adjuvant chemotherapy use vs observation, stratified according to the presence or absence of high-risk pathologic features (visceral pleural invasion, lymphovascular invasion, and high-grade histologic findings), sublobar surgery, and tumor size. MAIN OUTCOMES AND MEASURES: The association of high-risk pathologic features with survival after adjuvant chemotherapy vs observation was evaluated using Cox proportional hazards regression models. RESULTS: Overall, 50 814 eligible patients with NSCLC (27 365 women [53.9%]; mean [SD] age, 67.4 [9.5] years]) were identified, including 4220 (8.3%) who received adjuvant chemotherapy and 46 594 (91.7%) who did not receive adjuvant chemotherapy. Among patients with tumors 3 cm or smaller, chemotherapy was not associated with improved survival (hazard ratio [HR], 1.10; 95% CI, 0.96-1.26; P = .17). For patients with tumors larger than 3 cm to 4 cm, adjuvant chemotherapy was associated with a survival benefit among patients who underwent sublobar surgery (HR, 0.72; 95% CI, 0.56-0.93; P = .004). For tumors larger than 4 cm to 5 cm, a survival benefit was associated with adjuvant chemotherapy only in patients with at least 1 high-risk pathologic feature (HR, 0.67; 95% CI, 0.56-0.80; P = .02). For tumors larger than 5 cm, adjuvant chemotherapy was associated with a survival benefit irrespective of the presence of high-risk pathologic features (HR, 0.75; 95% CI, 0.61-0.91; P = .004). CONCLUSIONS AND RELEVANCE: In this cohort study, tumor size alone was not associated with improved efficacy of adjuvant chemotherapy in patients with early-stage (node-negative) NSCLC. High-risk clinicopathologic features and tumor size should be considered simultaneously when evaluating patients with early-stage NSCLC for adjuvant chemotherapy.

Efficacy and safety of frontline regimens for older transplant-ineligible patients with multiple myeloma: A systematic review and meta-analysis.

INTRODUCTION: Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic cell transplantation (tiMM). We aimed to identify treatment options that provide the best balance in terms of efficacy and safety. METHODS: We searched bibliographic databases and meeting libraries for search terms reflecting newly diagnosed and older and/or transplant-ineligible patients from inception to October 21, 2018. Phase II/III randomized trials comparing at least two first line treatment regimens for newly diagnosed tiMM were included. We extracted data on efficacy (progression free survival, PFS, overall survival and overall response rate) and safety (grade ¾ toxicities) and conducted network meta-analysis using Bayesian methods and random effects models. Relative ranking of treatment regimens was assessed using Surface under the cumulative ranking (SUCRA) probabilities. RESULTS: We identified 27 trials involving 12,194 patients. For PFS, the four most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara_RD, SUCRA 0.847), Bortezomib, melphalan, prednisone, thalidomide maintenance with bortezomib-thalidomide (SUCRA 0.834) and Bortezomib, Lenalidomide and Dexamethasone (SUCRA 0.739). Among these four most efficacious regimens, toxicity profile was most favorable for Dara_RD (median additional AEs per patient vs dexamethasone = 0.74; 95% CrI 0.51-1.17; SUCRA 0.430). CONCLUSION: Among first line tiMM regimens, increasing efficacy is associated with increased toxicity. We provide relative ranking of these regimens for both efficacy and safety. Future studies should incorporate geriatric assessments and frailty biomarkers to refine treatment decision-making for each individual patient.

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.

Surgically Managed Signet Ring Cell Esophageal Carcinomas in the National Cancer Database.

BACKGROUND: Signet ring cell adenocarcinoma (SRC) is a less common histologic variant of esophageal adenocarcinoma (ACA). The low frequency of SRC limits the ability to make data-driven clinical recommendations for these patients. METHODS: The National Cancer Database was queried for adult patients with clinical stage I, II, or III adenocarcinoma of the noncervical esophagus diagnosed between 2004 and 2015 and stratified by SRC versus all other ACA variants. Cox proportional hazard regression models were adjusted for patient, tumor, and treatment characteristics. The role of surgery in SRC was evaluated among patients treated with chemoradiation alone versus chemoradiation with esophagectomy. RESULTS: Of the 681 SRC and 13,543 ACA patients who underwent esophagectomy, no significant differences in age, sex, race, or comorbidities were identified. Patients with SRC were more likely to have high-grade tumors (84% vs 41%, P < .001) and stage III tumors (47% vs 39%, P < .001) compared with patients with ACA. Complete (R0) resection was less common in SRC (81% vs 90%, P < .001). Adjusted 5-year mortality risk from surgery was higher for SRC patients compared with ACA patients (hazard ratio, 1.242; 95% confidence interval, 1.126-1.369; P < .001). Among SRC tumors, chemoradiation with esophagectomy was associated with superior survival (hazard ratio, 0.429; 95% confidence interval, 0.339-0.546; P < .001) compared with chemoradiation alone. CONCLUSIONS: Among surgically managed patients SRC appears to have a worse prognosis than ACA, which may reflect the tendency of SRC tumors to be higher grade and more locally advanced. However SRC histology does not appear to diminish the role of esophagectomy in the management of locoregionally confined esophageal cancer.