An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy.

Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

What is the predictive value of RECIST criteria following stereotactic lung radiation?

PURPOSE: Response EvaluationCriteriain Solid Tumors (RECIST) is commonly used to assess response to anti-cancer therapies. However, its application after lung stereotactic ablative radiotherapy (SABR) is complicated by radiation-induced lung changes. This study assesses the frequency of progressive disease (PD) by RECIST following lung SABR and correlates this with actual treatment outcomes as determined by longitudinal follow-up. METHODS AND MATERIALS: We reviewed patients treated with lung SABR for primary lung tumors or oligometastases between 2010 and 2015. Patients were treated with SABR doses of 54-60 Gy in 3-8 fractions. All follow-up scans were assessed and the treated lesion was serially measured over time, with the maximum diameter on axial CT slices used for RECIST calculations. Lesions demonstrating PD by RECIST criteria were identified and subsequently followed for long-term outcomes. The final 'gold-standard' assessment of response was based on size changes after PD and, as available, positron emission tomography scan and/or biopsy. RESULTS: Eighty-eight lesions met inclusion criteria. Seventy-five were lung primaries and thirteen were lung metastases. Median follow-up was 52 months (interquartile range: 33-68). Two-thirds (66 %, 58/88) of treated lesions met RECIST criteria for PD; however, local recurrence was only confirmed in 16 % (9/58) of cases. Most lesions that triggered PD by RECIST (47/58, 81 %) were ultimately found not to represent recurrence, while a minority (2/58, 3 %) had an uncertain response. The positive predictive value [PPV] of a RECIST defined PD event was 0.16. If PD was triggered within 12-months post-treatment, PPV was 0.08, compared to 0.21 for lesions triggering PD after 12-months. CONCLUSION: Using RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, only a minority had recurrence, leading to a poor PPV of RECIST. This highlights the limitations of RECIST in this setting and provides context for physicians when interpreting post-lung SABR imaging.

Preoperative mediastinal staging in early-stage lung cancer: Targeted nodal sampling is not inferior to systematic nodal sampling.

OBJECTIVE: To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non-small cell lung cancer (NSCLC). METHODS: Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P < .05. RESULTS: Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, -0.003% to 4.1%; P = .13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS. CONCLUSIONS: In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients.

SOHO State of the Art Updates and Next Questions | Immunotherapeutic Options for Patients With Mantle Cell Lymphoma Who Progress on BTK Inhibitors.

Mantle cell lymphoma is a challenging subtype of B-cell non-Hodgkin lymphoma treat characterized by its aggressive nature and propensity for relapse or refractory (R/R) disease for many patients. The introduction of Bruton's tyrosine kinase inhibitors has significantly improved the outcomes for patients with R/R MCL, but a considerable proportion of patients eventually experience disease progression or develop resistance to these agents. In recent years, immunotherapeutic approaches have emerged as promising treatment options. The treatment landscape is quickly progressing with the FDA approval of CAR-T cell therapy as well as several promising bispecific antibody therapies and antibody-drug conjugates in clinical development. This review article aims to provide a comprehensive overview of the current state of immunotherapeutic options available for patients with R/R MCL.

340B-Where Do We Go From Here?

This Viewpoint summarizes inefficiencies in the 340B program and provides suggestions for equitable reform that will potentially benefit patients.

The Inflation Reduction Act: How Will Medicare Negotiating Drug Prices Impact Patients with Heart Disease?

PURPOSE OF REVIEW: Cardiovascular medications improve health and prevent early death. However, high drug prices reduce the use of these medications and strain the health system. The Inflation Reduction Act (IRA) of 2022 allows Medicare to negotiate drug prices with manufacturers and reduces out-of-pocket drug costs for Medicare beneficiaries. This article explores the potential impact that the IRA will have on the treatment of cardiovascular disease. RECENT FINDINGS: Cardiovascular disease medications are likely to be selected for price negotiations under the IRA, leading to savings for patients and for Medicare. Recent work suggests that the IRA's reforms to the Medicare Part D drug benefit will meaningfully reduce out-of-pocket costs for important cardiovascular medications. The IRA is expected to impact cardiovascular disease treatments via price negotiations and through the broader access to medications afforded by improvements to Part D coverage design.

Estimation of Out-of-Pocket Costs for Guideline-Directed Medical Therapy for Heart Failure Under Medicare Part D and the Inflation Reduction Act.

This cross-sectional study estimates out-of-pocket costs of heart failure with reduced ejection fraction medication regimens in Medicare Part D under current law and the Inflation Reduction Act.

Rapid Response EEG: Current State and Future Directions.

PURPOSE OF REVIEW: To critically appraise the literature on the application, methods, and advances in emergency electroencephalography (EEG). RECENT FINDINGS: The development of rapid EEG (rEEG) technologies and other reduced montage approaches, along with advances in machine learning over the past decade, has increased the rate and access to EEG acquisition. These achievements have made EEG in the emergency setting a practical diagnostic technique for detecting seizures, suspected nonconvulsive status epilepticus (NCSE), altered mental status, stroke, and in the setting of sedation. Growing evidence supports using EEG to expedite medical decision-making in the setting of suspected acute neurological injury. This review covers approaches to acquiring EEG in the emergency setting in the adult and pediatric populations. We also cover the clinical impact of this data, the time associated with emergency EEG, and the costs of acquiring EEG in these settings. Finally, we discuss the advances in artificial intelligence for rapid electrophysiological interpretation.

Predicting recurrence risks in lung cancer patients using multimodal radiomics and random survival forests.

Purpose: We developed a model integrating multimodal quantitative imaging features from tumor and nontumor regions, qualitative features, and clinical data to improve the risk stratification of patients with resectable non-small cell lung cancer (NSCLC). Approach: We retrospectively analyzed 135 patients [mean age, 69 years (43 to 87, range); 100 male patients and 35 female patients] with NSCLC who underwent upfront surgical resection between 2008 and 2012. The tumor and peritumoral regions on both preoperative CT and FDG PET-CT and the vertebral bodies L3 to L5 on FDG PET were segmented to assess the tumor and bone marrow uptake, respectively. Radiomic features were extracted and combined with clinical and CT qualitative features. A random survival forest model was developed using the top-performing features to predict the time to recurrence/progression in the training cohort ( n = 101 ), validated in the testing cohort ( n = 34 ) using the concordance, and compared with a stage-only model. Patients were stratified into high- and low-risks of recurrence/progression using Kaplan-Meier analysis. Results: The model, consisting of stage, three wavelet texture features, and three wavelet first-order features, achieved a concordance of 0.78 and 0.76 in the training and testing cohorts, respectively, significantly outperforming the baseline stage-only model results of 0.67 ( p < 0.005 ) and 0.60 ( p = 0.008 ), respectively. Patients at high- and low-risks of recurrence/progression were significantly stratified in both the training ( p < 0.005 ) and the testing ( p = 0.03 ) cohorts. Conclusions: Our radiomic model, consisting of stage and tumor, peritumoral, and bone marrow features from CT and FDG PET-CT significantly stratified patients into low- and high-risk of recurrence/progression.

Maintenance therapy for AML after allogeneic HCT.

Allogeneic hematopoietic cell transplant (allo-HCT) for eligible patients with acute myeloid leukemia (AML) in first complete remission is a central treatment paradigm to achieve durable remission. However, disease relapse after allo-HCT remains a significant concern and generally portends a poor prognosis. There is significant interest regarding the role for maintenance therapy after allo-HCT for patients with high risk of relapse, regardless of the presence of measurable residual disease. While there are currently no therapies approved for maintenance therapy for AML after allo-HCT, there are a number of ongoing investigations examining the role of maintenance therapies that include targeted agents against FLT3-ITD or IDH mutations, hypomethylating agents, immunomodulatory therapies and cellular therapies. In this review, we examine the current landscape and future strategies for maintenance therapy for AML after allo-HCT.

Robotic vs Thoracoscopic Anatomic Lung Resection in Obese Patients: A Propensity-Adjusted Analysis.

BACKGROUND: Minimally invasive lung resections can be particularly challenging in obese patients. We hypothesized robotic surgery (RTS) is associated with less conversion to thoracotomy than video-assisted thoracoscopic surgery (VATS) in obese populations. METHODS: The Society of Thoracic Surgeons General Thoracic Surgery Database, Epithor French National Database, and McMaster University Thoracic Surgical Database were queried for obese (body mass index ≥30 kg/m2) patients who underwent VATS or RTS lobectomy or segmentectomy for clinical T1-2, N0-1 non-small cell lung cancer between 2015 and 2019. Propensity score adjusted logistic regression analysis was used to compare the rate of conversion to thoracotomy between the VATS and RTS cohorts. RESULTS: Overall, 8108 patients (The Society of Thoracic Surgeons General Thoracic Surgery Database: n = 7473; Epithor: n = 572; McMaster: n = 63) met inclusion criteria with a mean (SD) age of 66.6 (9) years and body mass index of 34.7 (4.5) kg/m2. After propensity score adjusted multivariable analysis, patients who underwent VATS were >5-times more likely to experience conversion to thoracotomy than those who underwent RTS (odds ratio, 5.33; 95% CI, 4.14-6.81; P < .001). There was a linear association between the degree of obesity and odds ratio of VATS conversion to thoracotomy compared with RTS. VATS patients had a longer mean length of stay (5.0 vs 4.3 days, P < .001), higher rate of respiratory failure (2.8% [168 of 5975] vs 1.8% [39 of 2133], P = .026), and were less likely to be discharged to their home (92.5% [5525 of 5975] vs 94.3% [2012 of 2133]; P = .013) compared with RTS patients. CONCLUSIONS: In obese patients, RTS anatomic lung resection is associated with a lower rate of conversion to thoracotomy than VATS.

Financial toxicity in cancer care: origins, impact, and solutions.

Financial toxicity describes the financial burden and distress that can arise for patients, and their family members, as a result of cancer treatment. It includes direct out-of-pocket costs for treatment and indirect costs such as travel, time, and changes to employment that can increase the burden of cancer. While high costs of cancer care have threatened the sustainability of access to care for decades, it is only in the past 10 years that the term "financial toxicity" has been popularized to recognize that the financial burdens of care can be just as important as the physical toxicities traditionally associated with cancer therapy. The past decade has seen a rapid growth in research identifying the prevalence and impact of financial toxicity. Research is now beginning to focus on innovations in screening and care delivery that can mitigate this risk. There is a need to determine the optimal strategy for clinicians and cancer centers to address costs of care in order to minimize financial toxicity, promote access to high value care, and reduce health disparities. We review the evolution of concerns over costs of cancer care, the impact of financial burdens on patients, methods to screen for financial toxicity, proposed solutions, and priorities for future research to identify and address costs that threaten the health and quality of life for many patients with cancer.

Complications of Chest Wall Resection in Conjunction with Pulmonary Resection.

Techniques for chest wall resection and reconstruction have evolved over the years. Chest wall resection in conjunction with pulmonary resection has several complications, including pulmonary and infectious. Risk factors for complications are related to the size of the defect, number of ribs resected, and the addition of a pulmonary resection. Material used for reconstruction does not impact the overall complication rate.

Cognitive Tests and Stool Frequency at Hospital Discharge Do Not Predict Outcomes in Hepatic Encephalopathy.

OBJECTIVES: Hepatic encephalopathy (HE) is associated with hospital readmissions and mortality. We sought to determine whether cognitive testing and stool frequency at discharge predicted 30-day readmission or death in cirrhotic patients admitted with overt HE. METHODS: We approached consecutive inpatients with cirrhosis and overt HE when they were within 48 hours of discharge. Patients underwent cognitive tests, including Psychometric Hepatic Encephalopathy Score (PHES), and stool frequency was documented. Chart review identified Model for End-Stage Liver Disease-sodium (MELD-Na) and the presence of non-HE extrahepatic organ failures. Cox proportional hazards models were used to evaluate predictors of time to the primary composite outcome of hospital readmission for HE or death within 30 days, censoring for liver transplantation. RESULTS: Of 51 patients consented and enrolled, 14 patients met the primary composite outcome. In unadjusted Cox models, 4 variables predicted HE readmission or death: MELD-Na (hazard ratio [HR] 1.10 [1.01-1.20], P = 0.03), respiratory failure (HR 4.26 [1.47-12.35], P = 0.008), total number of HE extrahepatic organ failures (HR 1.79 [1.12-2.88], P = 0.02), and score on a PHES subtest, Number Connection Test A (per 30 seconds; HR 1.25 [1.06-1.47], P = 0.01). PHES and 24-hour stool frequency did not predict the primary outcome. When controlling for MELD-Na, respiratory failure predicted the primary outcome (HR 3.67 [1.24-10.86], P = 0.02). CONCLUSION: Cognitive testing and stool frequency at discharge did not predict poor outcomes in patients admitted with HE, while respiratory failure appeared to be a strong predictor.