ung cancer is the leading cause of cancer mortality in the United States among both men and women and is estimated to account for over one-quarter of all cancer deaths in 2018 (Fig 1) (1). Although the 5-year survival rate is 56% when patients present with localized disease, 57% of patients have distant disease at diagnosis, which carries a 5-year survival rate of only 4.7% (1). In 2011, National Lung Screening Trial (NLST) investigators reported that, compared with chest radiography, screening for lung cancer in high-risk current and former smokers with three rounds of annual low-dose CT reduced lung cancer mortality by 20% (2). At the end of 2013, the U.S. Preventive Services Task Force (USP-STF) issued a grade B recommendation for lung cancer screening (LCS) with annual low-dose CT for eligible individuals (3). Consequently, provisions of the Patient Protection and Affordable Care Act have required private insurers to cover LCS without cost sharing since January 2015 (4). In February 2015, the Centers for Medicare and Medicaid Services (CMS) added the LCS counseling and shared decision-making visit and lowdose CT screening for eligible beneficiaries to the list of covered preventive services (5).Analysis of 2015 National Health Interview Survey data estimated that 3.9% of 6.8 million eligible smokers in the United States underwent low-dose CT screening over the previous 12 months (6). In 2016, 1.9% of 7.6 million eligible individuals were screened based on analysis of the American College of Radiology (ACR) Lung Cancer Screening Registry (Fig 2) (7). In 2017, this registry indicated that 254 127 screening low-dose CT examinations were performed, an increase from 159 673 in 2016, which equals a growth rate of 59% (8). These data show that the fraction of eligible smokers who have undergone screening is small, though potentially increasing.Radiologists are essential to every LCS program. Increased awareness of challenges faced by patients and referring providers (Fig 3) will empower radiologists to continue to collaboratively guide nationwide multidisciplinary efforts to implement LCS. For radiology practices participating in efforts to initiate or improve implementation, better understanding of these challenges may help refine current initiatives, develop new interventions, and foster interdisciplinary collaboration. Recommendations and practice guidelines for implementation have been

Immune checkpoint inhibitors are a new class of cancer therapeutics that have demonstrated striking successes in a rapid series of clinical trials. Consequently, these drugs have dramatically increased in clinical use since being first approved for advanced melanoma in 2011. Current indications in addition to melanoma are non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, and classical Hodgkin lymphoma. A small subset of patients treated with immune checkpoint inhibitors undergoes an atypical treatment response pattern termed pseudoprogression: New or enlarging lesions appear after initiation of therapy, thereby mimicking tumor progression, followed by an eventual decrease in total tumor burden. Traditional response standards applied at the time of initial increase in tumor burden can falsely designate this as treatment failure and could lead to inappropriate termination of therapy. Currently, when new or enlarging lesions are observed with immune checkpoint inhibitors, only follow-up imaging can help distinguish patients with pseudoprogression from the large majority in whom this observation represents true treatment failure. Furthermore, the unique mechanism of immune checkpoint inhibitors can cause a distinct set of adverse events related to autoimmunity, which can be severe or life threatening. Given the central role of imaging in cancer care, radiologists must be knowledgeable about immune checkpoint inhibitors to correctly assess treatment response and expeditiously diagnose treatment-related complications. The authors review the molecular mechanisms and clinical applications of immune checkpoint inhibitors, the current strategy to distinguish pseudoprogression from progression, and the imaging appearances of common immune-related adverse events. RSNA, 2017.

Summary The BCL-2 family proteins are central regulators of apoptosis. However, cells deficient for BAX and BAK or overexpressing BCL-2 still succumb to oxidative stress upon DNA damage or matrix detachment. Here, we show that ΔNp63α overexpression protects cells from oxidative stress induced by oxidants, DNA damage, anoikis, or ferroptosis-inducing agents. Conversely, ΔNp63α deficiency increases oxidative stress. Mechanistically, ΔNp63α orchestrates redox homeostasis through transcriptional control of glutathione biogenesis, utilization, and regeneration. Analysis of The Cancer Genome Atlas (TCGA) lung squamous cell carcinoma dataset reveals that TP63 amplification/overexpression upregulates the glutathione metabolism pathway in primary human tumors. Strikingly, overexpression of ΔNp63α promotes clonogenic survival of p53-/-Bax-/-Bak-/- cells against DNA damage. Furthermore, co-expression of BCL-2 and ΔNp63α confers clonogenic survival against matrix detachment, disrupts the luminal clearance of mammary acini, and promotes cancer metastasis. Our findings highlight the need for a simultaneous blockade of apoptosis and oxidative stress to promote long-term cellular wellbeing.