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Background Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies; however, there is a lack of understanding of the characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade. Patients and methods We retrospectively analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations. Results Compared with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar for EGFRL858R lung tumors. EGFRT790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFRΔ19 alterations harbored a lower tumor mutation burden compared with EGFRL858R lung tumors despite similar smoking history. Conclusions EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease. [ABSTRACT FROM AUTHOR]

Background: Androgen deprivation therapy (ADT) is a common treatment modality for men with prostate cancer. Increases in adipose tissue mass and decreases in skeletal muscle mass are known on-target adverse effects of standard ADT. The effects of newer agents such as abiraterone acetate (ABI) and enzalutamide (ENZA) on body composition and how these compare with standard luteinizing hormone-releasing hormone agonists (aLHRHs) are unclear., Objective: To assess the effects of different forms of androgen deprivation therapy on body composition in men with prostate cancer., Design Setting and Participants: Using a retrospective design, 229 patients receiving aLHRHs alone ( n  = 120) or in combination with ABI ( n  = 53) or ENZA ( n  = 56) were studied., Outcome Measurements and Statistical Analysis: Muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at baseline, 6 mo, and 18 mo after initiating therapy using a cross-sectional densitometry analysis performed on standard of care computed tomography images. Response trajectories for all treatment groups were calculated via a two-way analysis of variance post hoc test, for both within-group and between-group differences., Results and Limitations: Treatment with aLHRHs, ABI, and ENZA was associated with a median muscle volume loss of -1.4%, -4.8%, and -5.5% at 6 mo, and -7.1%, -8.1%, and -8.3% at 18 mo, respectively. Therapy with aLHRHs was associated with minimal changes in VAT (0.3% at 6 mo and -0.1% at 18 mo). ABI therapy was associated with significant increases in VAT at 6 mo (4.9%) but not at 18 mo (0.5%), and ENZA therapy was associated with significant decreases in VAT (-4.6% at 6 mo and -5.4% at 18 mo). With respect to SAT, treatment with aLHRHs was associated with increases over time (8.6% at 6 mo and 4.7% at 18 mo), ABI was associated with decreases over time (-3.6% at 6 mo and -6.8% at 18 mo), and ENZA had no clear effects (1.7% at 6 mo and 3.3% at 18 mo)., Conclusions: ADT regimens cause significant short-term losses in muscle mass, with the most rapid effects occurring with ABI and ENZA. The three regimens have disparate effects on SAT and VAT, suggesting distinct roles of androgens in these tissues., Patient Summary: Androgen deprivation therapy alters body composition in men with prostate cancer. Abiraterone and enzalutamide are associated with losses in muscle mass compared with luteinizing hormone-releasing hormone agonists. These treatments impact subcutaneous and visceral fat mass, suggesting distinct roles of androgens in these tissues., (© 2023 The Author(s).)

Background: Compared with general anesthesia, spinal anesthesia has many benefits for patients undergoing total hip (THA) or total knee (TKA) arthroplasty, but few studies have explored rates of morbidity and mortality. We aimed to compare perioperative outcomes by anesthetic type for patients undergoing THA or TKA for osteoarthritis., Methods: We identified patients who underwent primary THA or TKA from the affiliated institute's database. We calculated inpatient, 30-day, 60-day and 90-day mortality rates, as well as 90-day perioperative complications, readmissions and length of stay (LOS). We compared outcomes between groups using logistic regression and propensity-adjusted multivariate analysis., Results: We included 6100 (52.2%) patients undergoing THA and 5580 (47.8%) undergoing TKA. We found no differences by anesthetic type in mortality rates up to 90 days after surgery. Patients under spinal anesthesia were less likely to need a blood transfusion (THA odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60 to 0.92; TKA OR 0.52, 95% CI 0.40 to 0.67) and were more likely to be discharged home among those who underwent TKA (OR 1.61, 95% CI 1.30 to 2.00). Patients who received spinal anesthesia for THA had a longer LOS (0.28 d, 95% CI 0.17 to 0.39), and patients who received spinal anesthesia for TKA had a shorter LOS than those who received general anesthesia (-0.34 d, 95% CI -0.51 to -0.18). Anesthetic type was not associated with any difference in adverse events., Conclusion: These findings may inform decisions on anesthetic type for total joint arthroplasty, especially for rapid discharge protocols. Further research is needed to understand postoperative pain and functional outcomes between anesthetic types., Competing Interests: Competing interest: Rajrishi Sharma reports consulting fees from Depuy Synthes, Zimmer Biomet, Stryker and OSI. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Breast cancer brain metastases (BCBM) are a common and devastating complication of metastatic breast cancer with conventional systemic therapies demonstrating limited effectiveness. Consequently, radiotherapy (RT) ± surgery remains the cornerstone of BCBM management. Because preclinical and clinical evidence indicate that immune checkpoint blockade (ICB) may synergize with RT to promote systemic tumor regression, we explored the safety and efficacy of RT and concurrent tremelimumab-mediated cytotoxic T-lymphocyte associated protein 4 (CTLA-4) ICB with tremelimumab ± HER2-directed therapy with trastuzumab for BCBM. Eligible patients had BCBM indicated for brain RT. A Simon two-stage design was adopted to evaluate the efficacy of tremelimumab and RT in 20 patients with human epidermal growth factor receptor normal (HER2-) BCBM. The safety of concurrent RT, tremelimumab, and trastuzumab was evaluated in a cohort of 6 HER2+ patients. The primary endpoint was 12-week non-central nervous system (CNS) disease control rate (DCR). Secondary endpoints included safety, survival, and CNS response. Exploratory correlatives included characterization of peripheral blood immune responses among exceptional responders. Tremelimumab plus RT ± trastuzumab was tolerated with no treatment-related grade 4 adverse events reported. The 12-week non-CNS DCR was 10% (2/20) in the HER2- cohort and 33% (2/6) in the HER2+ cohort. One patient with HER2+ disease experienced a durable partial response with evidence of peripheral T-cell activation. Thus, tremelimumab and RT ± trastuzumab was tolerated. Although modest clinical activity was observed in the HER2- efficacy cohort, encouraging responses were observed in the HER2+ safety cohort. Consequently, a trial to determine efficacy in HER2+ BCBM is planned.Clinical Trial Registration Number: NCT02563925., (© 2022. The Author(s).)

Background: While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours., Methods: Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020., Results: In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I-III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17-6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS)., Conclusions: A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Thermal ablation is a minimally invasive technique that is growing in acceptance and popularity in the management of early lung cancers. Although curative resection remains the optimal treatment strategy for stage I pulmonary malignancies, percutaneous ablative treatments may also be considered for selected patients. These techniques can additionally be used in the treatment of oligometastatic disease. Thermal ablation of early lung tumours can be achieved using several different techniques. For example, microwave ablation (MWA) and radiofrequency ablation (RFA) utilise extreme heat, whereas cryoablation uses extremely cold temperatures to cause necrosis and ultimately cell death. Typically, post-ablation imaging studies are performed within the first 1-3 months with subsequent imaging performed at regular intervals to ensure treatment response and to evaluate for signs of recurrent disease. Surveillance imaging is usually undertaken with computed tomography (CT) and integrated positron-emission tomography (PET)/CT. Typical imaging findings are usually seen on CT and PET/CT following thermal ablation of lung tumours, and it is vital that radiologists are familiar with these appearances. In addition, radiologists should be aware of the imaging findings that indicate local recurrence following ablation. The objective of this review is to provide an overview of the expected post-treatment findings on CT and PET/CT following thermal ablation of early primary lung malignancies, as well as describing the imaging appearances of local recurrence., (Published by Elsevier Ltd.)

Cancer survivors are at higher risk than the general population for development of a new primary malignancy, most commonly lung cancer. Current lung cancer screening guidelines recommend low-dose chest CT for high-risk individuals, including patients with a history of cancer and a qualifying smoking history. However, major lung cancer screening trials have inconsistently included cancer survivors, and few studies have assessed management of lung nodules in this population. This narrative review highlights relevant literature and provides expert opinion for management of pulmonary nodules detected incidentally or by screening in oncologic patients. In patients with previously treated lung cancer, a new nodule most likely represents distant metastasis from the initial lung cancer or a second primary lung cancer; CT features such as nodule size and composition should guide decisions regarding biopsy, PET/CT, and CT surveillance. In patients with extrapulmonary cancers, nodule management requires individualized risk assessment; smoking is associated with increased odds of primary lung cancer, whereas specific primary cancer types are associated with increased odds of pulmonary metastasis. Nonneoplastic causes, such as infection, medication toxicity, and postradiation or postsurgical change, should also be considered. Future prospective studies are warranted to provide evidence-based data to assist clinical decision-making in this context.

Introduction: This study assessed (i) the ability to identify the solid components of part-solid nodules (PSN) during computed tomography (CT) guided lung biopsy (CTGLB), (ii) the ability of CTGLB to assess the invasive nature of a nodule on pathology., Materials and Methods: Sixty-nine nodules were studied in 68 patients who underwent CTGLB between 1/1/2014 and 10/31/2015. Diagnostic CT images and CTGLB images were reviewed. On diagnostic CT images, nodules were classified as ground glass nodules (GGN) or PSNs. Nodule size, location, and percentage of solid component were recorded. At the time of biopsy, the ability to visualize the solid component of a PSN, depth of lesion from skin, and ability to identify the needle within the solid component were recorded., Results: There were 42 (61%) part-solid nodules and 27 (39%) GGNs. During biopsy, it was possible to differentiate the solid from the ground glass components in 35 (83%) PSNs. Fifty-nine (86%) nodules were neoplastic based on biopsy pathology (all non-small cell lung carcinoma). Thirty-nine (66%) were resected. In all cases biopsy pathology and surgical pathology agreed regarding the presence of lung carcinoma. In 6 (15%) cases biopsy pathology demonstrated purely lepidic growth but had some non-lepidic growth on surgical pathology, including 2 cases with acinar growth as a dominant pattern., Conclusion: In most patients, the solid and ground glass components of a PSN were distinguishable when performing a CTGLB. In a minority of patients, discrepancy was noted between biopsy pathology and surgical pathology regarding the invasive nature of a nodule., (Copyright © 2020. Published by Elsevier Inc.)

Competing Interests: Disclosures of Conflicts of Interest: J.A.B.A. disclosed no relevant relationships. W.D. disclosed no relevant relationships. D.H. disclosed no relevant relationships. J.W.W. disclosed no relevant relationships.

Purpose: Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab., Patients and Methods: We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis that would benefit from palliative RT and one metastasis that would not be irradiated. Nivolumab 1 mg/kg + ipilimumab 3 mg/kg and extracranial RT with a dose of 30 Gy in 10 fractions was administered in Cohort A, and then 27 Gy in 3 fractions was administered in Cohort B. The primary outcome was safety., Results: Twenty patients were treated (10 in each cohort). The rates of treatment-related grade 3-4 adverse events in Cohort A and B were 40% and 30%, respectively. There were no grade ≥3 adverse events attributed to RT. Patients responded to treatment outside of the irradiated volume (Cohort A 5/10; Cohort B 1/9). No evaluable patients had progression of irradiated metastases. Immunologic changes were seen in the peripheral blood with increases in T-cell receptor diversity in some responding patients., Conclusions: RT with nivolumab and ipilimumab was safe compared with historical data of nivolumab and ipilimumab alone. Immunologic effects were observed in the peripheral blood. Randomized studies are ongoing to assess whether RT increases the efficacy of nivolumab and ipilimumab., (©2020 American Association for Cancer Research.)

Conventional approaches to the treatment of early-stage lung cancer have focused on the use of surgical methods to remove the tumor. Recent progress in radiation therapy techniques and in the field of interventional oncology has seen the development of several novel ablative therapies that have gained widespread acceptance as alternatives to conventional surgical options in appropriately selected patients. Local control rates with stereotactic body radiation therapy for early-stage lung cancer now approach those of surgical resection, while percutaneous ablation is in widespread use for the treatment of lung cancer and oligometastatic disease for selected other malignancies. Tumors treated with targeted medical and ablative therapies can respond to treatment differently when compared with conventional therapies. For example, after stereotactic body radiation therapy, radiologic patterns of posttreatment change can mimic disease progression, and, following percutaneous ablation, the expected initial increase in the size of a treated lesion limits the utility of conventional size-based response assessment criteria. In addition, numerous treatment-related side effects have been described that are important to recognize, both to ensure appropriate treatment and to avoid misclassification as worsening tumor. Imaging plays a vital role in the assessment of patients receiving targeted ablative therapy, and it is essential that thoracic radiologists become familiar with these findings.

Thoracic tumors are a leading cause of cancer-related morbidity and mortality. In recent years, developments in oncologic treatments for these tumors have ushered in an era of targeted therapy, and, in many cases, these novel treatments have replaced conventional strategies to become standard therapeutic options, particularly in those with lung cancer. Targeted medical therapies for lung cancer now include angiogenesis inhibitors, tyrosine kinase inhibitors, and immunotherapeutic agents. Several novel ablative therapies have also gained widespread acceptance as alternatives to conventional surgical options in appropriately selected patients. Tumors treated with targeted medical therapies can respond to treatment differently when compared with conventional therapies. For example, pseudoprogression is a well-described phenomenon in patients receiving checkpoint inhibitor immunotherapy in which an initial increase in tumor burden is followed by a decrease in tumor burden and sometimes partial or complete response, while the frequent cavitating responses seen when antiangiogenic agents are used can be difficult to quantify using existing response assessment criteria. In some cases, novel response assessment criteria are needed to adequately capture response. In addition, numerous treatment-related side effects have been described, which are important to recognize, both to ensure appropriate treatment and to avoid misclassification as worsening tumor. Imaging plays a vital role in the assessment of patients receiving targeted medical therapy, and it is essential that thoracic radiologists are familiar with the rationale underpinning these treatments and the expected posttherapy findings.

A 46-year-old man with metastatic lung adenocarcinoma was treated with pembrolizumab. FDG PET/CT was performed after 3 cycles of treatment and revealed a focal region of pancreatic tail enlargement with an SUVmax value of 7. Following treatment with corticosteroids and discontinuation of pembrolizumab, radiological resolution was observed, and a diagnosis of focal immunotherapy-induced pancreatitis was made. A unique spectrum of FDG-avid adverse events can develop in patients treated with immune-checkpoint inhibitors that may mimic metastatic disease. Knowledge of the radiologic features of these potential imaging pitfalls is crucial among those interpreting FDG PET/CT to allow prompt and decisive treatment.